Endocrine System
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| Hormonal regulation | |
| Rhythms | |
| Hormonal effects | |
| Pathophysiologic manifestations | |
| Receptor-associated alterations | |
| Intracellular alterations | |
| Disorders | |
| Adrenal hypofunction | |
| Congenital adrenal hyperplasia | |
| Cushing syndrome | |
| Diabetes insipidus | |
| Diabetes mellitus | |
| Gonadotropin deficiency | |
| Growth hormone deficiency | |
| Growth hormone excess | |
| Hyperparathyroidism | |
| Hypoparathyroidism | |
| Hyperthyroidism | |
| Hypopituitarism | |
| Hypothyroidism in adults | |
| Hypothyroidism in children | |
| Syndrome of inappropriate antidiuretic hormone |
T he endocrine system consists of glands, specialized cell clusters, hormones, and target tissues. The glands and cell clusters secrete hormones in response to stimulation from the nervous system and other sites. Together with the nervous system, the endocrine system regulates and integrates the body's metabolic activities and maintains internal homeostasis. Each target tissue has receptors for specific hormones. Hormones connect with the receptors, and the resulting hormone-receptor complex triggers the response of the target cell.
HORMONAL REGULATION
The hypothalamus, the main integrative center for the endocrine and nervous systems, helps control some endocrine glands by neural and hormonal pathways. Neural pathways connect the hypothalamus to the posterior pituitary gland, or neurohypophysis. Neural stimulation of the posterior pituitary causes the secretion of two effector hormones: antidiuretic hormone (ADH, also known as vasopressin) and oxytocin.
The hypothalamus also exerts hormonal control at the anterior pituitary gland, or adenohypophysis, by releasing and inhibiting hormones and factors, which arrive by a portal system. Hypothalamic hormones stimulate the pituitary gland to synthesize and release trophic hormones, such as corticotropin (ACTH, also called adrenocorticostimulating hormone), thyroid-stimulating hormone (TSH), and gonadotropins, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Secretion of trophic hormones stimulates the adrenal cortex, thyroid gland, and gonads. Hypothalamic hormones also stimulate the pituitary gland to release or inhibit the release of effector hormones, such as growth hormone (GH) and prolactin.
In a patient with a possible endocrine disorder, this complex hormonal sequence requires careful assessment to identify the dysfunction, which may result from defects in the gland; defects of releasing, trophic, or effector hormones; or defects of the target tissue. Hyperthyroidism, for example, may result from excessive thyrotropin-releasing hormone (TSH), or thyroid hormones, or excessive response of the thyroid gland.
Besides hormonal and neural controls, a feedback system regulates the endocrine system. (See Feedback mechanism of the endocrine system .) The feedback mechanism may be simple or complex. Simple feedback occurs when the level of one substance regulates secretion of a hormone. For example, a low serum calcium level stimulates the parathyroid glands to secrete parathyroid hormone (PTH), and a high serum calcium level inhibits PTH secretion.
One example of complex feedback occurs through the hypothalamic-pituitary target organ axis. Secretion of the hypothalamic corticotropin-releasing hormone releases pituitary ACTH, which in turn stimulates adrenal cortisol secretion. Subsequently, an increase in serum cortisol levels inhibits ACTH by decreasing corticotropin-releasing hormone secretion or ACTH directly. Corticosteroid therapy disrupts the hypothalamic-pituitary-adrenal axis by suppressing the hypothalamic-pituitary secretion mechanism. Because abrupt withdrawal of steroids doesn't allow time for recovery of the hypothalamic-pituitary-adrenal axis to stimulate cortisol secretion, it can induce life-threatening adrenal crisis (hypocortisolism).
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FEEDBACK MECHANISM OF THE ENDOCRINE SYSTEM
The hypothalamus receives regulatory information (feedback) from its own circulating hormones (simple loop) and also from target glands (complex loop). <center></center> |
Rhythms
The endocrine system is also controlled by rhythms, many of which last 24 hours (circadian). Circadian rhythm control of ACTH and cortisol increases levels of these hormones in the early morning hours and decreases them in the late afternoon. The menstrual cycle is an example of an infradian rhythm ― in this case, 28 days.
Hormonal effects
The posterior pituitary gland secretes oxytocin and ADH. Oxytocin stimulates contraction of the uterus and is responsible for the milk-letdown reflex in lactating women. ADH controls the concentration of body fluids by altering the permeability of the distal and collecting tubules of the kidneys to conserve water. ADH secretion depends on plasma osmolality, the characteristic of a solution determined by the ionic concentration of the dissolved substance and the solution, which is monitored by hypothalamic neurons. Hypovolemia and hypotension are the most powerful stimulators of ADH release. Other stimulators include trauma, nausea, morphine, tranquilizers, certain anesthetics, and positive-pressure breathing.
In addition to the trophic hormones, the anterior pituitary secretes prolactin, which stimulates milk secretion, and GH. GH affects most body tissues. It triggers growth by stimulating protein synthesis and fat mobilization, and by decreasing carbohydrate use by muscle and fat tissue. The thyroid gland synthesizes and secretes the iodinated hormones, thyroxine and triiodothyronine. Thyroid hormones are necessary for normal growth and development, and act on many tissues to increase metabolic activity and protein synthesis.
The parathyroid glands secrete PTH, which regulates calcium and phosphate metabolism. PTH elevates serum calcium levels by stimulating resorption of calcium and excretion of phosphate and ― by stimulating the conversion of vitamin D to its most active form ― enhances absorption of calcium from the GI tract. Calcitonin, another hormone secreted by the thyroid gland, affects calcium metabolism, although its precise role in humans is unknown.
The pancreas produces glucagon from the alpha cells and insulin from the beta cells. Glucagon, the hormone of the fasting state, releases stored glucose from the liver to increase blood glucose levels. Insulin, the hormone of the postprandial state, facilitates glucose transport into the cells, promotes glucose storage, stimulates protein synthesis, and enhances free fatty acid uptake and storage.
The adrenal cortex secretes mineralocorticoids, glucocorticoids, and sex steroid hormones (androgens). Aldosterone, a mineralocorticoid, regulates the reabsorption of sodium and the excretion of potassium by the kidneys. Although affected by ACTH, aldosterone is mainly regulated by the renin-angiotension system. Together, aldosterone, angiotensin II, and renin may be implicated in the pathogenesis of hypertension.
Cortisol, a glucocorticoid, stimulates gluconeogenesis, increases protein breakdown and free fatty acid mobilization, suppresses the immune response, and facilitates an appropriate response to stress.
The adrenal medulla is an aggregate of nervous tissue that produces the catecholamines, epinephrine and norepinephrine, which cause vasoconstriction. In addition, epinephrine stimulates the fight-or-flight response ― dilation of bronchioles and increased blood pressure, blood glucose level, and heart rate. The adrenal cortex as well as the gonads secretes androgens, which are steroid sex hormones. In males and premenopausal females, the contribution of adrenal androgens is very small, but in postmenopausal females, the adrenals are the major source of sex hormones.
The testes synthesize and secrete testosterone in response to gonadotropic hormones, especially LH, from the anterior pituitary gland; spermatogenesis occurs in response to FSH. The ovaries produce sex steroid hormones (primarily estrogen and progesterone) in response to anterior pituitary trophic hormones.
PATHOPHYSIOLOGIC MANIFESTATIONS
Alterations in hormone levels, either significantly high or low, may result from various causes. Feedback systems may fail to function properly or may respond to the wrong signals. Dysfunction of an endocrine gland may manifest as either failure to produce adequate amounts of active hormone or excessive synthesis or release. Once the hormones are released, they may be degraded at an altered rate or inactivated by antibodies before reaching the target cell. Abnormal target cell responses include receptor-associated alterations and intracellular alterations.
Receptor-associated alterations
These alterations have been associated with water-soluble hormones (peptides) and involve:
- decreased number of receptors, resulting in diminished or defective hormone-receptor binding
- impaired receptor function, resulting in insensitivity to the hormone
- presence of antibodies against specific receptors, either reducing available binding sites or mimicking hormone action and suppressing or exaggerating target cell response
- unusual expression of receptor function.
Intracellular alterations
These involve the inadequate synthesis of the second messenger needed to convert the hormonal signal into intracellular events. The two different mechanisms that may be involved are:
- faulty response of target cells for water-soluble hormones to hormone-receptor binding and failure to generate the required second messenger
- abnormal response of the target cell to the second messenger and failure to express the usual hormonal effect.
Pathophysiologic aberrations affecting target cells for lipid-soluble (steroid hormones) hormones occur less frequently or may be recognized less frequently.
DISORDERS
Common dysfunctions of the endocrine system are classified as hypofunction and hyperfunction, inflammation, and tumor.
Adrenal hypofunction
Adrenal hypofunction is classified as primary or secondary. Primary adrenal hypofunction or insufficiency (Addison's disease) originates within the adrenal gland and is characterized by the decreased secretion of mineralocorticoids, glucocorticoids, and androgens. Secondary adrenal hypofunction is due to impaired pituitary secretion of corticotropin (ACTH) and is characterized by decreased glucocorticoid secretion. The secretion of aldosterone, the major mineralocorticoid, is often unaffected.
Addison's disease is relatively uncommon and can occur at any age and in both sexes. Secondary adrenal hypofunction occurs when a patient abruptly stops long-term exogenous steroid therapy or when the pituitary is injured by a tumor or by infiltrative or autoimmune processes ― these occur when circulating antibodies react specifically against adrenal tissue, causing inflammation and infiltration of the cells by lymphocytes. With early diagnosis and adequate replacement therapy, the prognosis for adrenal hypofunction is good.
Adrenal crisis (Addisonian crisis), a critical deficiency of mineralocorticoids and glucocorticoids, generally follows acute stress, sepsis, trauma, surgery, or the omission of steroid therapy in patients who have chronic adrenal insufficiency. Adrenal crisis is a medical emergency that needs immediate, vigorous treatment.
| CULTURAL DIVERSITY Autoimmune Addison's disease is most common in white females, and a genetic predisposition is likely. It's more common in patients with a familial predisposition to autoimmune endocrine diseases. Most persons with Addison's disease are diagnosed in their third to fifth decades. |
Causes
Primary and secondary adrenal hypofunction and adrenal crisis have different causes. The most common cause of primary hypofunction is:
- Addison's disease (destruction of more than 90% of both adrenal glands, usually due to an autoimmune process in which circulating antibodies react specifically against the adrenal tissue).
Other causes include:
- tuberculosis (once the chief cause, now responsible for less than 20% of adult cases)
- bilateral adrenalectomy
- hemorrhage into the adrenal gland
- neoplasms
- infections (histoplasmosis, cytomegalovirus [CMV])
- family history of autoimmune disease (may predispose the patient to Addison's disease and other endocrinopathies).
Causes of secondary hypofunction (glucocorticoid deficiency) include:
- hypopituitarism (causing decreased ACTH secretion)
- abrupt withdrawal of long-term corticosteroid therapy (long-term exogenous corticosteroid stimulation suppresses pituitary ACTH secretion, resulting in adrenal gland atrophy)
- removal of an ACTH-secreting tumor.
Adrenal crisis is usually caused by:
- exhausted body stores of glucocorticoids in a person with adrenal hypofunction after trauma, surgery, or other physiologic stress.
Pathophysiology
Addison's disease is a chronic condition that results from the partial or complete destruction of the adrenal cortex. It manifests as a clinical syndrome in which the symptoms are associated with deficient production of the adrenocortical hormones, cortisol, aldosterone, and androgens. High levels of ACTH and corticotropin-releasing hormone accompany the low glucocorticoid levels.
ACTH acts primarily to regulate the adrenal release of glucocorticoids (primarily cortisol); mineralocorticoids, including aldosterone; and sex steroids that supplement those produced by the gonads. ACTH secretion is controlled by corticotropin-releasing hormone from the hypothalamus and by negative feedback control by the glucocorticoids.
Addison's disease involves all zones of the cortex, causing deficiencies of the adrenocortical secretions, glucocorticoids, androgens, and mineralocorticoids.
Manifestations of adrenocortical hormone deficiency become apparent when 90% of the functional cells in both glands are lost. In most cases, cellular atrophy is limited to the cortex, although medullary involvement may occur, resulting in catecholamine deficiency. Cortisol deficiency causes decreased liver gluconeogenesis (the formation of glucose from molucules that are not carbohydrates). The resulting low blood glucose levels can become dangerously low in patients who take insulin on a routine basis.
Aldosterone deficiency causes increased renal sodium loss and enhances potassium reabsorption. Sodium excretion causes a reduction in water volume that leads to hypotension. Patients with Addison's disease may have normal blood pressure when supine, but show marked hypotension and tachycardia after standing for several minutes. Low plasma volume and arteriolar pressure stimulate renin release and a resulting increased production of angiotensin II.
Androgen deficiency may decrease hair growth in axillary and pubic areas as well as on the extremities of women. The metabolic effects of testicular androgens make such hair growth less noticeable in men.
Addison's disease is a decrease in the biosynthesis, storage, or release of adrenocortical hormones. In about 80% of the patients, an autoimmune process causes partial or complete destruction of both adrenal glands. Autoimmune antibodies can block the ACTH receptor or bind with ACTH, preventing it from stimulating adrenal cells. Infection is the second most common cause of Addison's disease, specifically tuberculosis, which causes about 20% of the cases. Other diseases that can cause Addison's disease include acquired immunodeficiency syndrome, systemic fungal infections, CMV, adrenal tumor, and metastatic cancers. Infection can impair cellular function and affect ACTH at any stage of regulation.
Signs and symptoms
Clinical features vary with the type of adrenal hypofunction. Signs and symptoms of primary hypofunction include:
- weakness
- fatigue
- weight loss
- nausea, vomiting, and anorexia
- conspicuous bronze color of the skin, especially in the creases of the hands and over the metacarpophalangeal joints (hand/finger), elbows, and knees
- darkening of scars, areas of vitiligo (absence of pigmentation), and increased pigmentation of the mucous membranes, especially the buccal mucosa, due to decreased secretion of cortisol, causing simultaneous secretion of excessive amounts of ACTH and melanocyte-stimulating hormone by the pituitary gland
- associated cardiovascular abnormalities, including orthostatic hypotension, decreased cardiac size and output, and weak, irregular pulse
- decreased tolerance for even minor stress
- fasting hypoglycemia due to decreased gluconeogenesis
- craving for salty food due to decreased mineralocorticoid secretion (which normally causes salt retention).
Signs and symptoms of secondary hypofunction are:
- similar to primary hypofunction, but without hyperpigmentation due to low ACTH and melanocyte-stimulating hormone levels
- possibly no hypotension and electrolyte abnormalities due to fairly normal aldosterone secretion
- usually normal androgen secretion.
Signs and symptoms of Addisonian crisis may include:
- profound weakness and fatigue
- nausea, vomiting, and dehydration
- hypotension
- high fever followed by hypothermia (occasionally).
Complications
Possible complications of adrenal hypofunction include:
- hyperpyrexia
- psychotic reactions
- deficient or excessive steroid treatment
- ultimate vascular collapse, renal shutdown, coma, and death (if untreated).
Diagnosis
Diagnosis of adrenal hypofunction is based on:
- plasma cortisol levels confirming adrenal insufficiency (ACTH stimulation test to differentiate between primary and secondary adrenal hypofunction)
- metyrapone test for suspicion of secondary adrenal hypofunction (oral or I.V. metyrapone blocks cortisol production and should stimulate the release of ACTH from the hypothalamic-pituitary system; in Addison's disease, the hypothalamic-pituitary system responds normally and plasma ACTH levels are high, but because the adrenal glands are destroyed, plasma concentrations of the cortisol precursor 11-deoxycortisol increase, as do urinary 17-hydroxycorticosteroids)
- rapid ACTH stimulation test by I.V. or I.M. administration of cosyntropin (Cortrosyn) after baseline sampling for cortisol and ACTH (samples drawn for cortisol 30 and 60 minutes after injection), to differentiate between primary and secondary adrenal hypofunction.
In a patient with typical Addisonian symptoms, the following laboratory findings strongly suggest acute adrenal insufficiency:
- decreased plasma cortisol level (less than10 mcg/dl in the morning; less in the evening)
- decreased serum sodium and fasting blood glucose levels
- increased serum potassium and blood urea nitrogen levels
- decreased hematocrit; increased lymphocyte and eosinophil counts
- X-rays showing adrenal calcification if the cause is infectious.
Treatment
Treatment for adrenal hypofunction may include:
- lifelong corticosteroid replacement, usually with cortisone or hydrocortisone, both of which have a mineralocorticoid effect (primary or secondary adrenal hypofunction)
- oral fludrocortisone (Florinef), a synthetic mineralocorticoid, to prevent dangerous dehydration, hypotension, hyponatremia, and hyperkalemia (Addison's disease)
- I.V. bolus of hydrocortisone, 100 mg every 6 hours for 24 hours; then, 50 to 100 mg I.M. or diluted with dextrose in saline solution and given I.V. until the patient's condition stabilizes; up to 300 mg/day of hydrocortisone and 3 to 5 L of I.V. saline and glucose solutions may be needed (adrenal crisis).
With proper treatment, adrenal crisis usually subsides quickly; blood pressure stabilizes, and water and sodium levels return to normal. After the crisis, maintenance doses of hydrocortisone preserve physiologic stability.
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) encompasses a group of genetic disorders resulting in the deficiency or absence of one of five enzymes needed for the biosynthesis of glucocorticoids and mineralocorticoids. Manifestations are usually present at birth or during early childhood, but symptoms may appear later in life in nonclassic CAH. CAH is uncommon and often has an autosomal recessive mode of inheritance. When successfully treated, sexual functioning and fertility aren't affected.
| AGE ALERT Salt-losing CAH may cause fatal adrenal crisis in newborns. |
The prevalent adrenal disorder in infants and children, simple virilizing CAH and salt-losing CAH, are the most common forms. Acquired adrenal virilism is rare and affects twice as many females as males. With successful treatment, a normal quality of life and life span are expected. In older patients, androgen excess may be part of the syndrome of polycystic ovaries or may be secondary to an adrenal carcinoma.
Causes
The cause of CAH is:
- genetic, as an autosomal recessive trait.
Pathophysiology
Cortisol levels are regulated by a negative-feedback mechanism. Corticotropin (ACTH) in the blood stimulates the release of cortisol precursors and, consequently, of cortisol, aldosterone, and androgens. In turn, cortisol suppresses ACTH secretion. With a deficiency of the enzyme 21-hydroxylase, cortical secretion of cortisol is impaired and pituitary secretion of ACTH is increased. ACTH stimulates the adrenal cortex, which in turn stimulates both aldosterone and androgen biosynthesis and release.
Signs and symptoms
Signs and symptoms of CAH may include:
- ambiguous genitalia (enlarged clitoris with urethral opening at the base and a combination of the labia and scrotum), normal genital tract and gonads (newborn females)
- pubic and axillary hair at an earlier age, a deep voice, acne, and facial hair, but no menarche (female approaching puberty)
- no apparent manifestations (newborn males)
- accentuated masculine characteristics, including a deepened voice, acne, enlarged phallus with small testes, and frequent erections (male approaching puberty)
- high androgen levels causing rapid bone and muscle growth (in children)
- short stature due to premature epiphyseal closure and high androgen levels (adults)
- more severe changes, including development of a penis in females (salt-losing CAH).
Because males have no external abnormalities, diagnosis is more difficult and commonly delayed until other symptoms occur. In the second week of life, symptoms of a salt-wasting crisis include apathy, failure to eat, diarrhea, and adrenal crisis (vomiting, dehydration from hyponatremia, and hyperkalemia). If adrenal crisis is not treated promptly, dehydration and electrolyte imbalance cause cardiovascular collapse and cardiac arrest.
Complications
Possible complications of CAH are:
- death (salt-wasting crisis)
- precocious puberty
- menstrual irregularities
- sexual dysfunction and infertility.
Diagnosis
Diagnosis of CAH may include:
- elevated urine 17-ketosteroid levels (can be suppressed by dexamethasone [Decadron])
- elevated serum 17-hydroxyprogesterone level after I.V. bolus of ACTH
- serum hyperkalemia, hyponatremia, and hypochloremia (present but not diagnostic)
- elevated 24-hour urine pregnanetriol level
- normal or decreased 24-hour urine 17-hydroxycorticosteroid levels.
Treatment
Treatment of CAH includes:
- daily cortisone (Cortone) or hydrocortisone (Cortef) to stop the excessive output of ACTH and subsequent excessive androgen production (initial and subsequent doses guided by urinary 17-ketosteroids levels) given I.M. until the infant is old enough to tolerate pills (usually about 18 months)
- I.V. sodium chloride and glucose to re-establish fluid and electrolyte balance, with desoxycorticosterone I.M. and hydrocortisone I.V. as needed (adrenal crisis); glucocorticoid (cortisone or hydrocortisone) and perhaps mineralocorticoids (desoxycorticosterone, fludrocortisone, or both after stabilization)
- sex chromatin and karyotype studies to determine genetic sex (with ambiguous external genitalia); possible reconstructive surgery for females between the ages of 1 and 3 years.
Cushing syndrome
Cushing syndrome is a cluster of clinical abnormalities caused by excessive adrenocortical hormones (particularly cortisol) or related corticosteroids and, to a lesser extent, androgens and aldosterone. Cushing's disease (pituitary corticotropin [ACTH] excess) accounts for about 70% of the cases of Cushing syndrome. Cushing's disease occurs most commonly between 20 and 40 years of age and is eight times more common in females.
| AGE ALERT Cushing syndrome caused by ectopic corticotropin secretion is more common in adult men, with the peak incidence between 40 and 60 years of age. In 30% of patients, Cushing syndrome results from a cortisol-secreting tumor. Adrenal tumors, rather than pituitary tumors, are more common in children, especially girls. |
The annual incidence of endogenous cortisol excess in the United States is 2 to 4 cases per 1 million people per year. The incidence of Cushing syndrome resulting from exogenous administration of cortisol is uncertain, but it is known to be much greater than that of endogenous types. The prognosis for endogenous Cushing syndrome is guardedly favorable with surgery, but morbidity and mortality are high without treatment. About 50% of the individuals with untreated Cushing syndrome die within 5 years of onset as a result of overwhelming infection, suicide, complications from generalized arteriosclerosis (coronary artery disease), and severe hypertensive disease.
Causes
Causes of Cushing syndrome include:
- anterior pituitary hormone (ACTH) excess
- autonomous, ectopic ACTH secretion by a tumor outside the pituitary (usually malignant, frequently oat cell carcinoma of the lung).
Pathophysiology
Cortisol excess results in anti-inflammatory effects and excessive catabolism of protein and peripheral fat to support hepatic glucose production. The mechanism may be ACTH dependent, in which elevated plasma ACTH levels stimulate the adrenal cortex to produce excess cortisol, or ACTH independent, in which excess cortisol is produced by the adrenal cortex or exogenously administered. This suppresses the hypothalamic-pituitary-adrenal axis, also present in ectopic ACTH-secreting tumors.
Signs and symptoms
Like other endocrine disorders, Cushing syndrome induces changes in many body systems. Specific clinical effects vary with the system affected, and include:
- diabetes mellitus, with decreased glucose tolerance, fasting hyperglycemia, and glucosuria due to cortisol-induced insulin resistance and increased glycogenolysis and glucogenesis in the liver (endocrine and metabolic systems)
- muscle weakness due to hypokalemia or loss of muscle mass from increased catabolism, pathologic fractures due to decreased bone mineral ionization, and skeletal growth retardation in children (musculoskeletal system)
- purple striae; facial plethora (edema and blood vessel distention); acne; fat pads above the clavicles, over the upper back (buffalo hump), on the face (moon facies), and throughout the trunk (truncal obesity), with slender arms and legs; little or no scar formation; poor wound healing due to decreased collagen and weakened tissues (skin)
- peptic ulcer due to increased gastric secretions and pepsin production and decreased gastric mucus (GI system)
- irritability and emotional lability, ranging from euphoric behavior to depression or psychosis; insomnia due to the role of cortisol in neurotransmission (central nervous system)
- hypertension due to sodium and secondary fluid retention; left ventricular hypertrophy; capillary weakness from protein loss, which leads to bleeding and ecchymosis; dyslipidemia (cardiovascular system)
- increased susceptibility to infection due to decreased lymphocyte production and suppressed antibody formation; decreased resistance to stress; suppressed inflammatory response masking even severe infection (immunologic system)
- sodium and secondary fluid retention, increased potassium excretion, ureteral calculi from increased bone demineralization with hypercalciuria (renal and urologic systems)
- increased androgen production, with clitoral hypertrophy, mild virilism, hirsutism, and amenorrhea or oligomenorrhea in women, and sexual dysfunction (reproductive system).
Complications
Complications of Cushing syndrome include:
- osteoporosis
- increased susceptibility to infections
- hirsutism
- ureteral calculi
- metastases of malignant tumors.
Diagnosis
Diagnosis is based on the following laboratory test results:
- hyperglycemia, hypernatremia, glucosuria, hypokalemia, and metabolic alkalosis
- urinary free cortisol levels more than 150 μg/24 hours
- dexamethasone suppression test to confirm the diagnosis and determine the cause, possibly an adrenal tumor or a nonendocrine, corticotropin-secreting tumor
- blood levels of corticotropin-releasing hormone, ACTH, and different glucocorticoids to diagnose and localize cause to pituitary or adrenal gland.
Treatment
Differentiation among pituitary, adrenal, and ectopic causes of hypercortisolism is essential for effective treatment, which is specific for the cause of cortisol excess and includes medication, radiation, and surgery. Possible treatments are:
- surgery for tumors of the adrenal and pituitary glands or other tissue (such as the lung)
- radiation therapy (tumor)
- drugs, such as mitotane (Lysodren) or aminoglutethimide (Cytadren), to block steroid synthesis for inoperable tumor.
Diabetes insipidus
A disorder of water metabolism, diabetes insipidus results from a deficiency of circulating vasopressin (also called antidiuretic hormone, or ADH) or from renal resistance to this hormone. Pituitary diabetes insipidus is caused by a deficiency of vasopressin, and nephrogenic diabetes insipidus is caused by the resistance of renal tubules to vasopressin. Diabetes insipidus is characterized by excessive fluid intake and hypotonic polyuria. A decrease in ADH levels leads to altered intracellular and extracellular fluid control, causing renal excretion of a large amount of urine.
The disorder may start at any age and is slightly more common in men than in women. The incidence is slightly greater today than in the past.
In uncomplicated diabetes insipidus, the prognosis is good with adequate water replacement, and patients usually lead normal lives.
Causes
The cause of diabetes insipidus may be:
- acquired, familial, idiopathic, neurogenic, or nephrogenic
- associated with stroke, hypothalamic or pituitary tumors, and cranial trauma or surgery (neurogenic diabetes insipidus)
- X-linked recessive trait or end-stage renal failure (nephrogenic diabetes insipidus, less common)
- certain drugs, such as lithium (Duralith), phenytoin (Dilantin), or alcohol (transient diabetes insipidus).
Pathophysiology
Diabetes insipidus is related to an insufficiency of ADH, leading to polyuria and polydipsia. The three forms of diabetes insipidus are neurogenic, nephrogenic, and psychogenic.
Neurogenic, or central, diabetes insipidus is an inadequate response of ADH to plasma osmolarity, which occurs when an organic lesion of the hypothalamus, infundibular stem, or posterior pituitary partially or completely blocks ADH synthesis, transport, or release. The many organic lesions that can cause diabetes insipidus include brain tumors, hypophysectomy, aneurysms, thrombosis, infections, and immunologic disorders. Neurogenic diabetes insipidus has an acute onset. A three-phase syndrome can occur, which involves:
- progressive loss of nerve tissue and increased diuresis
- normal diuresis
- polyuria and polydipsia, the manifestation of permanent loss of the ability to secrete adequate ADH.
Nephrogenic diabetes insipidus is caused by an inadequate renal response to ADH. The collecting duct permeability to water does not increase in response to ADH. Nephrogenic diabetes insipidus is generally related to disorders and drugs that damage the renal tubules or inhibit the generation of cyclic adenosine monophosphate in the tubules, preventing activation of the second messenger. Causative disorders include pyelonephritis, amyloidosis, destructive uropathies, polycystic disease, and intrinsic renal disease. Drugs include lithium carbonate (Eskalith), general anesthetics such as methoxyflurane, and demeclocycline (Declomycin). In addition, hypokalemia or hypercalcemia impairs the renal response to ADH. A rare genetic form of nephrogenic diabetes insipidus is an X-linked recessive trait.
Psychogenic diabetes insipidus is caused by an extremely large fluid intake, which may be idiopathic or related to psychosis or sarcoidosis. The polydipsia and resultant polyuria wash out ADH more quickly than it can be replaced. Chronic polyuria may overwhelm the renal medullary concentration gradient, rendering patients partially or totally unable to concentrate urine.
Regardless of the cause, insufficient ADH causes the immediate excretion of large volumes of dilute urine and consequent plasma hyperosmolality. In conscious individuals, the thirst mechanism is stimulated, usually for cold liquids. With severe ADH deficiency, urine output may be greater than 12 L/day, with a low specific gravity. Dehydration develops rapidly if fluids aren't replaced.
Signs and symptoms
Signs and symptoms of diabetes insipidus include:
- polydipsia and polyuria up to 12 L/day (cardinal symptoms)
- sleep disturbance and fatigue due to nocturia
- headache and visual disturbance due to electrolyte disturbance and dehydration
- abdominal fullness, anorexia, and weight loss due to almost continuous fluid consumption.
Complications
Possible complications of diabetes insipidus are:
- dilatation of the urinary tract
- severe dehydration
- shock and renal failure if dehydration is severe.
Diagnosis
Diagnosis is based on:
- urinalysis showing almost colorless urine of low osmolality (50 to 200 mOsm/kg, less than that of plasma) and low specific gravity (less than 1.005)
- water deprivation test to identify vasopressin deficiency, resulting in renal inability to concentrate urine
- hyponatremia.
Treatment
Until the cause of diabetes insipidus can be identified and eliminated, the administration of vasopressin (Pitressin Synthetic) can control fluid balance and prevent dehydration. Medications include:
- vasopressin aqueous preparation S.C. or I.M. several times daily, effective for only 2 to 6 hours (used as a diagnostic agent and, rarely, in acute disease)
- desmopressin acetate (DDAVP) orally (not available in the United States), by nasal spray absorbed through the mucous membranes, or S.C. or I.V. injection, effective for 8 to 20 hours depending on the dosage.
Diabetes mellitus
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia (elevated serum glucose level) resulting from lack of insulin, lack of insulin effect, or both. Three general classifications are recognized:
- type 1, absolute insulin insufficiency
- type 2, insulin resistance with varying degrees of insulin secretory defects
- gestational diabetes, which emerges during pregnancy.
Onset of type 1 usually occurs before the age of 30 years (although it may occur at any age); the patient is usually thin and requires exogenous insulin and dietary management to achieve control. Conversely, type 2 usually occurs in obese adults after the age of 40 years and is treated with diet and exercise in combination with various antidiabetic drugs, although treatment may include insulin therapy.
| CULTURAL DIVERSITY More than 8% of all adults in the United States have diabetes, and 93% of these have type 2. The prevalence of type 1 diabetes is higher in white populations in the United States. Type 2 diabetes is more prevalent in persons of African, American Indian, Asian, Hispanic, and Pacific Islander descent. Although whites usually develop type 2 diabetes after the age of 40, type 2 diabetes tends to occur at an earlier age in nonwhite populations, and about 25% of the diabetes that occurs in youth in nonwhite populations is type 2. |
Medical advances permit increased longevity and improved quality of life if the patient carefully monitors blood glucose levels, uses the data to make pharmacologic and life-style changes, and uses new insulin delivery systems, such as subcutaneous insulin pumps. In addition, medications now available enhance the body's own glucose metabolism and insulin sensitivity to optimize glycemic control and prevent progression to long-term complications.
Causes
Evidence indicates that diabetes mellitus has diverse causes, including:
- heredity
- environment (infection, diet, toxins, stress)
- life-style changes in genetically susceptible persons.
Pathophysiology
In persons genetically susceptible to type 1 diabetes, a triggering event, possibly a viral infection, causes production of autoantibodies against the beta cells of the pancreas. The resultant destruction of the beta cells leads to a decline in and ultimate lack of insulin secretion. Insulin deficiency leads to hyperglycemia, enhanced lipolysis (decomposition of fat), and protein catabolism. These characteristics occur when more than 90% of the beta cells have been destroyed.
Type 2 diabetes mellitus is a chronic disease caused by one or more of the following factors: impaired insulin production, inappropriate hepatic glucose production, or peripheral insulin receptor insensitivity. Genetic factors are significant, and onset is accelerated by obesity and a sedentary lifestyle. Again, added stress can be a pivotal factor.
Gestational diabetes mellitus occurs when a woman not previously diagnosed with diabetes shows glucose intolerance during pregnancy. This may occur if placental hormones counteract insulin, causing insulin resistance. Gestational diabetes mellitus is a significant risk factor for the future occurrence of type 2 diabetes mellitus.
Signs and symptoms
Signs and symptoms of diabetes mellitus include:
- polyuria and polydipsia due to high serum osmolality caused by high serum glucose levels
- anorexia (common) or polyphagia (occasional)
- weight loss (usually 10% to 30%; persons with type 1 diabetes often have almost no body fat at time of diagnosis) due to prevention of normal metabolism of carbohydrates, fats, and proteins caused by impaired or absent insulin function
- headaches, fatigue, lethargy, reduced energy levels, and impaired school and work performance due to low intracellular glucose levels
- muscle cramps, irritability, and emotional lability due to electrolyte imbalance
- vision changes, such as blurring, due to glucose-induced swelling
- numbness and tingling due to neural tissue damage
- abdominal discomfort and pain due to autonomic neuropathy, causing gastroparesis and constipation
- nausea, diarrhea, or constipation due to dehydration and electrolyte imbalances or autonomic neuropathy.
Complications
Complications of diabetes mellitus include:
- microvascular disease, including retinopathy, nephropathy, and neuropathy
- dyslipidemia
- macrovascular disease, including coronary, peripheral, and cerebral artery disease
- hypoglycemia
- diabetic ketoacidosis
- hyperglycemic, hyperosmolar, nonketotic syndrome
- excessive weight gain
- skin ulcerations
- chronic renal failure.
Diagnosis
In adult men and nonpregnant women, diabetes mellitus is diagnosed by two of the following criteria obtained more than 24 hours apart, using the same test twice or any combination:
- fasting plasma glucose level of 126 mg/dl or more on at least two occasions
- typical symptoms of uncontrolled diabetes and random blood glucose level of 200 mg/dl or more
- blood glucose level of 200 mg/dl or more 2 hours after ingesting 75 g of oral dextrose.
Diagnosis may also be based on:
- diabetic retinopathy on ophthalmologic examination
- other diagnostic and monitoring tests, including urinalysis for acetone and glycosylated hemoglobin (reflects glycemic control over the past 2 to 3 months).
Treatment
Effective treatment for all types of diabetes optimizes blood glucose control and decreases complications. Treatment for type 1 diabetes includes:
- insulin replacement, meal planning, and exercise (current forms of insulin replacement include mixed-dose, split mixed-dose, and multiple daily injection regimens and continuous subcutaneous insulin infusions)
- pancreas transplantation (currently requires chronic immunosuppression). (See Treatment of type 1 diabetes mellitus .)
Treatment of type 2 diabetes mellitus includes:
- oral antidiabetic drugs to stimulate endogenous insulin production, increase insulin sensitivity at the cellular level, suppress hepatic gluconeogenesis, and delay GI absorption of carbohydrates (drug combinations may be used)
- exogenous insulin, alone or with oral antidiabetic drugs, to optimize glycemic control.
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TREATMENT OF TYPE 1 DIABETES MELLITUS
The following algorithm shows the pathophysiologic process of diabetes and points for treatment intervention. <center></center> Adapted with permission from Black, J.M., and Matassarin-Jacobs, E. Medical-Surgical Nursing . 5th ed. Philadelphia: W.B. Saunders Company, 1997. |
Treatment of both types of diabetes mellitus includes:
- individualized meal plan designed to meet nutritional needs, control blood glucose and lipid levels, and reach and maintain appropriate body weight (plan to be followed consistently with meals eaten at regular times)
- weight reduction (obese patient with type 2 diabetes mellitus) or high calorie allotment, depending on growth stage and activity level (type 1 diabetes mellitus).
Treatment of gestational diabetes involves:
- medical nutrition therapy and exercise
- alpha glucosidase inhibitors, injected insulin, or both (if euglycemia not achieved); postpartum counseling to address the high risk for gestational diabetes in subsequent pregnancies and type 2 diabetes later in life; regular exercise and prevention of weight gain to help prevent type 2 diabetes.
Gonadotropin deficiency
Gonadotropin deficiency is a lack of hormones (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) that stimulate the sex glands, primarily the testes and ovaries. Chronic gonadotropin deficiency, if not treated, can cause infertility and osteopenia (decreased bone mass). A decrease in testosterone results in decreased bone cell formation.
Causes
Causes of gonadotropin deficiency include:
- pituitary tumor or hemorrhage
- oversecretion of target gland hormone, such as estrogen, progesterone, or testosterone
- prolactin-secreting tumor
- hypothalamic suppression of gonadotropin-releasing hormone (GnRH) during periods of physical or emotional stress, obesity, and starvation
- genetics.
Pathophysiology
GnRH is secreted by the hypothalamus and causes the anterior pituitary to secrete the gonadotropins ― testosterone, estrogen, FSH, and LH. Estrogen, progesterone, and testosterone, produced by the gonads, function in a negative-feedback loop that regulates GnRH secretion.
Testosterone, which is responsible for masculine sex characteristics and sperm production, also functions in bone, muscle, and red blood cell formation, as well as having a role in neural signaling. Estrogen serves many functions, among them cognitive, bone, and vaginal maintenance. FSH and LH function to maintain the corpus luteum and pregnancy.
Several mechanisms can cause GnRH deficiency, including:
- pituitary tumor producing another hormone that impinges on the gonadotropin-producing cells and physically impairs GnRH biosynthesis
- medical treatments such as radiation (impairs GnRH-producing cells)
- oversecretion of estrogen, progesterone, or testosterone by dysfunctional target glands, causing GnRH inhibition through the negative-feedback loop
- prolactin (inhibits pituitary secretion of GnRH; prolactin-secreting tumors can cause GnRH deficiency)
- reduced GnRH secretion due to response of hypothalamus to physical stress, obesity, or starvation (for example, females in competitive athletics may not enter menarche or may cease menstruation for extended periods of time).
Signs and symptoms
Many symptoms are directly related to a reduction in the differentiating sexual characteristics that are caused and maintained by the gonadotropins (FSH and LH) and the hormones they stimulate, androgens and estrogen. These signs and symptoms vary with the degree and length of GnRH deficiency, and may include:
- decreased libido, strength, and body hair, and fine wrinkles around the eyes and lips (adults)
- amenorrhea; vaginal, uterine, and breast atrophy; clitoral enlargement; voice deepening; and beard growth (women)
- testicular atrophy, reduction in beard growth, and erectile dysfunction (men)
- decreased red blood cells and loss of bone and muscle mass due to low testosterone levels
- mood and behavior changes due to changes in testosterone levels
- anosmia, which is the absence of a sense of smell (genetic cases).
The age of onset of GnRH deficiency affects the presentation in children:
- inadequate sexual differentiation shown by ambiguity, pseudohermaphroditism (individual showing one or more contraindications of the morphologic sex criteria), or normal-appearing female genitalia with male genetic coding (first trimester)
- microphallus and partial or complete lack of testicular descent (second and third trimesters)
- poor secondary sex characteristics and muscle development, lack of deepening voice in males, sparse body hair, gynecomastia (enlarged breast tissue), delayed fusion of epiphyseal plates, and continued long bone growth (childhood through puberty).
Complications
A complication of gonadotropin deficiency is:
- infertility.
Diagnosis
Diagnosis of gonadotropin deficiency is based on:
- serum estrogen, testosterone, and GnRH levels to differentiate between dysfunction of the hypothalamus or of the ovaries or testicles
- low testosterone and high GnRH levels (primary testicular failure)
- low estrogen and high GnRH levels (primary ovarian failure)
- low GnRH and testosterone or estrogen levels (hypothalamic or pituitary dysfunction)
- human chorionic gonadotropin (HCG) stimulation test (HCG, 500 IU/1.7 m 2 or 100 IU/kg in children, given after measuring baseline testosterone; after 3 to 4 days, testosterone levels should increase by 50% to 200% because HCG and LH stimulate the Leydig cells to stimulate testicular function)
- clomiphene citrate test (normal response, 30% to 200% increase in FSH and 0% to 65% increase in testosterone) with impaired or absent increase in hypothalamic or pituitary disorders
- GnRH stimulation test (rapid I.V. injection of GnRH stimulates the pituitary to secrete LH and FSH), with insufficient elevation of LH or FSH levels indicating pituitary or hypothalamus dysfunction.
Treatment
Treatment of gonadotropin deficiency includes:
- surgery to remove tumors
- gonadotropin, estrogen, or testosterone replacement
- stress reduction and weight gain or loss.
Growth hormone deficiency
Growth hormone (GH) deficiency results from hypofunction of the anterior pituitary gland with a resulting decreased secretion of GH. GH deficiency includes a group of childhood disorders characterized by subnormal growth velocity, delayed bone age, and a subnormal response to at least two stimuli for release of the hormone. (See GH deficiency in children .) GH deficiency in adults is characterized by general weakness and increased mortality.
Causes
Possible causes of GH deficiency are:
- autosomal recessive, autosomal dominant, or X-linked trait
- pituitary or central nervous system tumor
- pituitary hypoxic necrosis
- pituitary inflammation
- hypothalamic failure
- GH receptor insensitivity
- biologically inactive GH
- hematologic disorders
- idiopathic causes
- trauma
- pituitary irradiation.
GH DEFICIENCY IN CHILDREN
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Pathophysiology
The absence or deficiency of GH synthesis causes growth failure in children. In adults, metabolic derangements decrease GH response to stimulation.
Signs and symptoms
Signs and symptoms of GH deficiency are:
- short stature (2 standard deviations less than the predicted mean for age and gender)
- reduced muscle mass and increased subcutaneous fat due to decreased protein synthesis and insufficient muscle anabolism.
Complications
Complications of GH deficiency may include:
- short stature and possible related psychosocial difficulties (if untreated)
- fatal convulsions, especially during periods of stress, due to fasting hypoglycemia
- gonadotropin deficiency
- multiple pituitary hormone deficiencies
- increased cardiovascular mortality (adults).
Diagnosis
Diagnosis of GH deficiency is based on:
- decreased serum GH and somatomedin C levels.
Treatment
Treatment of GH deficiency includes:
- exogenous GH given S.C. up to several times weekly during puberty.
Growth hormone excess
Growth hormone (GH) excess that begins in adulthood (after epiphyseal closure) is called acromegaly. GH excess that is present before closure of the epiphyseal growth plates of the long bones causes pituitary gigantism. In both cases, the result is increased growth of bone, cartilage, and other tissues, as well as increased catabolism of carbohydrates and protein synthesis. Acromegaly is rare, with a prevalence of about 70 people per million in the United States. Most cases are diagnosed in the fourth and fifth decades, but acromegaly is usually present for years before diagnosis. GH excess is a slow but progressive disease that decreases longevity if untreated. Morbidity and mortality tend to be related to coronary artery disease and hypertension.
The earliest clinical sign of acromegaly is soft-tissue swelling of the extremities, which causes coarsening of the facial features.
In gigantism, a proportional overgrowth of all body tissues starts before epiphyseal closure. This causes remarkable height increases ― as much as 6 inches (15 cm) a year. Gigantism affects infants and children, causing them to reach as much as three times the normal height for their age. As adults, they may reach a height of more than 7.5 feet (203 cm).
Causes
GH excess is caused by:
- eosinophilic or mixed-cell adenomas of the anterior pituitary gland.
Pathophysiology
A GH-secreting tumor creates an unpredictable GH secretion pattern, which replaces the usual peaks that occur 1 to 4 hours after the onset of sleep. Elevated GH and somatomedin levels stimulate tissue growth. In pituitary gigantism, because the epiphyseal plates aren't closed, the excess GH stimulates linear growth. It also increases the bulk of bones and joints and causes enlargement of internal organs and metabolic abnormalities. In acromegaly, the excess GH increases bone density and width, and the proliferation of connective and soft tissues.
Signs and symptoms
Acromegaly develops slowly, and gigantism is characterized by rapid growth. Other signs and symptoms of acromegaly include:
- diaphoresis, oily skin, hypermetabolism, hypertrichosis (excessive hair growth), weakness, arthralgias, malocclusion of the teeth, and new skin tags (typical)
- severe headache, central nervous system impairment, bitemporal hemianopia (defective vision), loss of visual acuity, and blindness (if the intrasellar tumor compresses the optic chiasm or nerves)
- cartilaginous and connective tissue overgrowth, causing the characteristic hulking appearance, with an enlarged supraorbital ridge and thickened ears and nose
- marked prognathism (projection of the jaw) that may interfere with chewing
- laryngeal hypertrophy, paranasal sinus enlargement, and thickening of the tongue causing the voice to sound deep and hollow
- arrowhead appearance of distal phalanges on X-rays, thickened fingers
- irritability, hostility, and various psychological disturbances
- bow legs, barrel chest, arthritis, osteoporosis, kyphosis, hypertension, and arteriosclerosis (prolonged effects of excessive GH secretion)
- glucose intolerance and clinical diabetes mellitus due to action of GH as an insulin antagonist.
Signs and symptoms of gigantism include:
- backache, arthralgia, and arthritis due to rapid bone growth
- excessive height due to rapid growth before epiphyseal plate closure
- headache, vomiting, seizure activity, visual disturbances, and papilledema (edema wherein the optic nerve enters the eye chamber) due to tumor compressing nerves and tissue in surrounding structures
- deficiencies of other hormone systems (if GH-producing tumor destroys other hormone-secreting cells)
- glucose intolerance and diabetes mellitus due to insulin-antagonistic actions of GH.
Complications
Possible complications of GH excess are:
- cardiomegaly
- hypertension
- diabetes mellitus.
Diagnosis
Diagnosis of GH excess is based on:
- elevated plasma GH level measured by radioimmunoassay (results of random sampling may be misleading owing to pulsatile GH secretion)
- somatomedin-C, a metabolite of GH (a better diagnostic alternative)
- glucose suppression test (glucose normally suppresses GH secretion; if glucose infusion doesn't suppress GH to less than 2 ng/ml and the patient has characteristic clinical features, hyperpituitarism is likely)
- skull X-rays, computed tomography scan, or magnetic resonance imaging to show the presence and extent of pituitary lesion
- bone X-rays showing a thickening of the cranium (especially frontal, occipital, and parietal bones) and long bones, and osteoarthritis in the spine (support the diagnosis)
- elevated blood glucose levels.
Treatment
Treatment may involve:
- tumor removal by cranial or transsphenoidal hypophysectomy or pituitary radiation therapy
- mandatory surgery for a tumor causing blindness or other severe neurologic disturbances (acromegaly)
- replacement of thyroid, cortisone, and gonadal hormones (postoperative therapy)
- bromocriptine (Parlodel) and octreotide (Sandostatin) to inhibit GH synthesis (adjunctive treatment).
Hyperparathyroidism
Hyperparathyroidism results from excessive secretion of parathyroid hormone (PTH) from one or more of the four parathyroid glands. PTH promotes bone resorption, and hypersecretion leads to hypercalcemia and hypophosphatemia. Renal and GI absorption of calcium increase.
Primary hyperparathyroidism is commonly diagnosed based on elevated calcium levels found on laboratory test results in asymptomatic patients. It affects women two to three times more frequently than men.
Causes
Hyperparathyroidism may be primary or secondary. In primary hyperparathyroidism:
- one or more parathyroid glands enlarge and increase PTH secretion, most commonly caused by a single adenoma, but this may be a component of multiple endocrine neoplasia (all four glands usually involved).
In secondary hyperparathyroidism, a hypocalcemia-producing abnormality outside the parathyroids causes excessive compensatory production of PTH. Causes include:
- rickets, vitamin D deficiency, chronic renal failure, and osteomalacia due to phenytoin (Dilantin).
Pathophysiology
Overproduction of PTH by a tumor or hyperplastic tissue increases intestinal calcium absorption, reduces renal calcium clearance, and increases bone calcium release. Response to this excess varies for each patient for an unknown reason.
Hypophosphatemia results when excessive PTH inhibits renal tubular phosphate reabsorption. The hypophosphatemia aggravates hypercalcemia by increasing the sensitivity of the bone to PTH.
Signs and symptoms
Signs and symptoms of primary hyperparathyroidism result from hypercalcemia and are typically present in several body systems. Signs and symptoms may include:
- polyuria, nephrocalcinosis, or recurring nephrolithiasis and consequent renal insufficiency (renal system)
- chronic low back pain and easy fracturing due to bone degeneration; bone tenderness; chondrocalcinosis (decreased bone mass); osteopenia and osteoporosis, especially on the vertebrae; erosions of the juxta-articular (adjoining joint) surface; subchondral fractures; traumatic synovitis; and pseudogout (skeletal and articular systems)
- pancreatitis causing constant, severe epigastric pain that radiates to the back; peptic ulcers, causing abdominal pain, anorexia, nausea, and vomiting (GI system)
- muscle weakness and atrophy, particularly in the legs (neuromuscular system)
- psychomotor and personality disturbances, depression, overt psychosis, stupor, and possibly coma (central nervous system)
- skin necrosis, cataracts, calcium microthrombi to lungs and pancreas, anemia, and subcutaneous calcification (other systems).
Secondary hyperparathyroidism may produce the same features of calcium imbalance with skeletal deformities of the long bones (such as rickets) as well as symptoms of the underlying disease.
Complications
Complications of hyperparathyroidism include:
- pathologic fractures
- renal damage
- urinary tract infections
- hypertension.
Diagnosis
Findings differ in primary and secondary disease. In primary disease, diagnosis is based on:
- hypercalcemia and high concentrations of serum PTH on radioimmunoassay (confirms the diagnosis)
- X-rays showing diffuse demineralization of bones, bone cysts, outer cortical bone absorption, and subperiosteal erosion of the phalanges and distal clavicles
- microscopic bone examination by X-ray spectrophotometry typically showing increased bone turnover
- elevated urine and serum calcium, chloride, and alkaline phosphatase levels; decreased serum phosphorus levels
- elevated uric acid and creatinine levels, which may also increase basal gastric acid secretion and serum immunoreactive gastrin
- increased serum amylase levels (may indicate acute pancreatitis).
Diagnosis of secondary disease is based on:
- normal or slightly decreased serum calcium level, variable serum phosphorus level, especially when the cause is rickets, osteomalacia, or kidney disease
- patient history possibly showing familial kidney disease, seizure disorders, or drug ingestion.
Treatment
Effective treatment varies, depending on the cause of the disease. In primary hyperparathyroidism, surgery is the only definitive therapy. The only effective long-term medical therapy is maintaining hydration in mild hyperparathyroidism.
Treatment of primary disease includes:
- surgery to remove the adenoma or, depending on the extent of hyperplasia, all but half of one gland, to provide normal PTH levels (may relieve bone pain within 3 days, but renal damage may be irreversible)
- treatments to decrease calcium levels, such as forcing fluids, limiting dietary intake of calcium, and promoting sodium and calcium excretion through forced diuresis (using as much as 6 L of urine output in life-threatening circumstances), and use of furosemide (Lasix) or ethacrynic acid (Edecrin) (preoperatively or if surgery isn't feasible or necessary)
- oral sodium or potassium phosphate; S.C. calcitonin (Calcimar); I.V. mithramycin or biphosphonate
- I.V. magnesium and phosphate or sodium phosphate solution by mouth or retention enema (for potential postoperative magnesium and phosphate deficiencies), possibly supplemental calcium, vitamin D, or calcitriol (Calcijex) (serum calcium level decreases to low normal range during the first 4 to 5 days after surgery).
Treatment of secondary disease includes:
- vitamin D to correct the underlying cause of parathyroid hyperplasia; oral calcium preparation to correct hyperphosphatemia in the patient with kidney disease
- dialysis in the patient with renal failure to decrease phosphorus levels (may be lifelong)
- enlarged glands may not revert to normal size and function even after calcium levels have been controlled in the patient with chronic secondary hyperparathyroidism.
Hypoparathyroidism
Hypoparathyroidism is caused by disease, injury, or congenital malfunction of the parathyroid glands. Because the parathyroid glands primarily regulate calcium balance, hypoparathyroidism causes hypocalcemia and consequent neuromuscular symptoms ranging from paresthesia to tetany.
The clinical effects of hypoparathyroidism are usually correctable with replacement therapy. Some complications of long-term hypocalcemia, such as cataracts and basal ganglion calcifications, are irreversible.
Causes
Hypoparathyroidism may be acute or chronic and is classified as idiopathic or acquired. Possible causes include:
- autoimmune genetic disorder or congenital absence of the parathyroid glands (idiopathic)
- accidental removal of or injury to the parathyroid glands during thyroidectomy or other neck surgery or, rarely, from massive thyroid irradiation (acquired)
- ischemic infarction of the parathyroid glands during surgery, amyloidosis, neoplasms, or trauma (acquired)
- impairment of hormone synthesis and release due to hypomagnesemia, suppression of normal gland function due to hypercalcemia, and delayed maturation of parathyroid function (acquired, reversible).
Parathyroid hormone (PTH) is regulated directly by serum calcium levels, not by the pituitary or hypothalamus. It normally maintains normocalcemia by regulating bone resorption and GI absorption of calcium. It also maintains an inverse relationship between serum calcium and phosphate levels by inhibiting phosphate reabsorption in the renal tubules.
| AGE ALERT The incidence of the idiopathic and reversible forms is greatest in children; the incidence of the irreversible acquired form is greatest in adults who have undergone surgery for hyperthyroidism or other head and neck conditions. |
Pathophysiology
Underproduction of PTH causes hypocalcemia and hyperphosphatemia. Surgical manipulation of the neck may damage the parathyroid glands, possibly by causing ischemia. The degree of hypoparathyroidism can vary from decreased reserve to frank tetany. Hypomagnesemia can prevent PTH secretion in patients with chronic GI magnesium losses, nutritional deficiencies, and renal magnesium wasting.
Signs and symptoms
Mild hypoparathyroidism may be asymptomatic but usually causes:
- hypocalcemia and high serum phosphate levels affecting the central nervous system (CNS) and other systems.
Signs and symptoms of chronic hypoparathyroidism include:
- neuromuscular irritability, increased deep tendon reflexes, Chvostek's sign (spasm of the hyperirritable facial nerve when it's tapped), dysphagia, organic brain syndrome, psychosis, mental deficiency in children, and tetany
- difficulty walking and a tendency to fall (chronic tetany).
Signs and symptoms of acute hypoparathyroidism include:
- tingling in the fingertips, around the mouth, and occasionally in the feet (first symptom); spreading and becoming more severe, producing muscle tension and spasms and consequent adduction of the thumbs, wrists, and elbows; pain varying with the degree of muscle tension but seldom affecting the face, legs, and feet (acute overt tetany)
- laryngospasm, stridor, cyanosis, and seizures (CNS abnormalities); worst during hyperventilation, pregnancy, infection, withdrawal of thyroid hormone, or administration of diuretics and before menstruation (acute tetany)
- abdominal pain; dry, lusterless hair; spontaneous hair loss; brittle fingernails developing ridges or falling out; dry, scaly skin; cataracts; and weakened tooth enamel, causing teeth to stain, crack, and decay easily (effects of hypocalcemia).
Complications
Possible complications are:
- cardiac arrhythmias, heart failure
- cataracts
- basal ganglia calcifications
- stunted growth, teeth malformation, and mental retardation
- Parkinson's symptoms
- hypothyroidism.
Diagnosis
The following test results confirm the diagnosis of hypoparathyroidism:
- radioimmunoassay for PTH showing decreased PTH level
- decreased serum calcium level
- increased serum phosphorus level
- electrocardiography showing prolonged QT and ST intervals due to hypocalcemia
- inflating a blood pressure cuff on the upper arm to between diastolic and systolic blood pressure and maintaining this inflation for 3 minutes, eliciting Trousseau's sign (carpal spasm), to show clinical evidence of hypoparathyroidism.
OTHER FORMS OF HYPERTHYROIDISM
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Treatment
Treatment of hypothyroidism includes:
- immediate I.V. calcium salts, such as 10% calcium gluconate, to increase serum calcium levels (acute, life-threatening tetany)
- breathing into a paper bag and inhaling one's own carbon dioxide causes a mild respiratory acidosis that increases serum calcium levels (awake patient able to cooperate)
- sedatives and anticonvulsants to control spasms until calcium levels increase
- maintenance therapy with oral calcium and vitamin D supplements (chronic tetany)
- vitamin D and calcium supplements because of calcium absorption from the small intestine needing the presence of vitamin D (treatment of reversible disease, usually lifelong)
- calcitriol (Calcijex) if hepatic or renal problems make the patient unable to tolerate vitamin D.
Hyperthyroidism
Hyperthyroidism, or thyrotoxicosis, is a metabolic imbalance that results from the overproduction of thyroid hormone. The most common form is Graves' disease, which increases thyroxine (T 4 ) production, enlarges the thyroid gland (goiter), and causes multiple system changes. (See Other forms of hyperthyroidism .)
| AGE ALERT The incidence of Graves' disease is greatest in women between the ages of 30 and 60 years, especially those with a family history of thyroid abnormalities; only 5% of the patients are younger than 15 years. |
With treatment, most patients can lead normal lives. However, thyroid storm ― an acute, severe exacerbation of thyrotoxicosis ― is a medical emergency that may have life-threatening cardiac, hepatic, or renal consequences.
Causes
Thyrotoxicosis may result from both genetic and immunologic factors, including:
- increased incidence in monozygotic twins, pointing to an inherited factor, probably autosomal recessive gene
- occasional coexistence with other endocrine abnormalities, such as type 1 diabetes mellitus, thyroiditis, and hyperparathyroidism
- defect in suppressor T-lymphocyte function permitting production of autoantibodies (thyroid-stimulating immunoglobulin and thyroid-stimulating hormone [TSH]-binding inhibitory immunoglobulin)
- clinical thyrotoxicosis precipitated by excessive dietary intake of iodine or possibly stress (patients with latent disease)
- stress, such as surgery, infection, toxemia of pregnancy, or diabetic ketoacidosis, can precipitate thyroid storm (inadequately treated thyrotoxicosis).
Pathophysiology
The thyroid gland secretes the thyroid precursor, T 4 , thyroid hormone or triiodothyronine (T 3 ), and calcitonin. T 4 and T 3 stimulate protein, lipid, and carbohydrate metabolism primarily through catabolic pathways. Calcitonin removes calcium from the blood and incorporates it into bone.
Biosynthesis, storage, and release of thyroid hormones are controlled by the hypothalamic-pituitary axis through a negative-feedback loop. Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the release of TSH by the pituitary. Circulating T 3 levels provide negative feedback through the hypothalamus to decrease TRH levels, and through the pituitary to decrease TSH levels.
Although the exact mechanism isn't understood, hyperthyroidism has a hereditary component, and it is frequently associated with other autoimmune endocrinopathies.
Graves' disease is an autoimmune disorder characterized by the production of autoantibodies that attach to and then stimulate TSH receptors on the thyroid gland. A goiter is an enlarged thyroid gland, either the result of increased stimulation or a response to increased metabolic demand. The latter occurs in iodine-deficient areas of the world, where the incidence of goiter increases during puberty (a time of increased metabolic demand). These goiters often regress to normal size after puberty in males, but not in females. Sporadic goiter in non�iodine-deficient areas is of unknown origin. Endemic and sporadic goiters are nontoxic and may be diffuse or nodular. Toxic goiters may be uninodular or multinodular and may secrete excess thyroid hormone.
Pituitary tumors with TSH-producing cells are rare, as is hypothalamic disease causing TRH excess.
Signs and symptoms
Signs and symptoms of hyperthyroidism include:
- enlarged thyroid (goiter)
- nervousness
- heat intolerance and sweating
- weight loss despite increased appetite
- frequent bowel movements
- tremor and palpitations
- exophthalmos (characteristic, but absent in many patients with thyrotoxicosis).
Other signs and symptoms, common because thyrotoxicosis profoundly affects virtually every body system, include:
- difficulty concentrating due to accelerated cerebral function; excitability or nervousness caused by increased basal metabolic rate from T 4 ; fine tremor, shaky handwriting, and clumsiness from increased activity in the spinal cord area that controls muscle tone; emotional instability and mood swings ranging from occasional outbursts to overt psychosis (central nervous system)
- moist, smooth, warm, flushed skin (patient sleeps with minimal covers and little clothing); fine, soft hair; premature patchy graying and increased hair loss in both sexes; friable nails and onycholysis (distal nail separated from the bed); pretibial myxedema (nonpitting edema of the anterior surface of the legs, dermopathy), producing thickened skin; accentuated hair follicles; sometimes itchy or painful raised red patches of skin with occasional nodule formation; microscopic examination showing increased mucin deposits (skin, hair, and nails)
- systolic hypertension, tachycardia, full bounding pulse, wide pulse pressure, cardiomegaly, increased cardiac output and blood volume, visible point of maximal impulse, paroxysmal supraventricular tachycardia and atrial fibrillation (especially in elderly people), and occasional systolic murmur at the left sternal border (cardiovascular system)
- increased respiratory rate, dyspnea on exertion and at rest, possibly due to cardiac decompensation and increased cellular oxygen use (respiratory system)
- excessive oral intake with weight loss; nausea and vomiting due to increased GI motility and peristalsis; increased defecation; soft stools or, in severe disease, diarrhea; liver enlargement (GI system)
- weakness, fatigue, and muscle atrophy; rare coexistence with myasthenia gravis; possibly generalized or localized paralysis associated with hypokalemia; and, rarely, acropachy (soft-tissue swelling accompanied by underlying bone changes where new bone formation occurs) (musculoskeletal system)
- oligomenorrhea or amenorrhea, decreased fertility, increased incidence of spontaneous abortion (females), gynecomastia due to increased estrogen levels (males), diminished libido (both sexes) (reproductive system)
- exophthalmos due to combined effects of accumulated mucopolysaccharides and fluids in the retro-orbital tissues, forcing the eyeball outward and lid retraction, thereby producing characteristic staring gaze; occasional inflammation of conjunctivae, corneas, or eye muscles; diplopia; and increased tearing (eyes).
When thyrotoxicosis escalates to thyroid storm, these symptoms may occur:
- extreme irritability, hypertension, tachycardia, vomiting, temperature up to 106° F (41.1° C), delirium, and coma.
| AGE ALERT Consider apathetic thyrotoxicosis, a morbid condition resulting from overactive thyroid, in elderly patients with atrial fibrillation or depression. |
Complications
Possible complications include:
- muscle wasting
- visual loss or diplopia
- cardiac failure
- hypoparathyroidism after surgical removal of thyroid
- hypothyroidism after radioiodine treatment.
Diagnosis
The diagnosis of thyrotoxicosis is usually straightforward. It depends on a careful clinical history and physical examination, a high index of suspicion, and routine hormone determinations. The following tests confirm the disorder:
- radioimmunoassay showing increased serum T 4 and T 3 levels
- low TSH levels
- thyroid scan showing increased uptake of radioactive iodine 131 ( 131 I) in Graves' disease and, usually, in toxic multinodular goiter and toxic adenoma; low radioactive uptake in thyroiditis and thyrotoxic factitia (test contraindicated in pregnancy)
- ultrasonography confirming subclinical ophthalmopathy.
Treatment
The primary forms of therapy include:
- antithyroid drugs
- single oral dose of 131 I
- surgery.
Appropriate treatment depends on:
- severity of thyrotoxicosis
- causes
- patient age and parity
- how long surgery will be delayed (if patient is appropriate candidate for surgery).
Antithyroid therapy includes antithyroid drugs for children, young adults, pregnant women, and patients who refuse surgery or 131 I treatment. Antithyroid drugs are preferred in patients with new-onset Graves' disease because of spontaneous remission in many of these patients; they are also used to correct the thyrotoxic state in preparation for 131 I treatment or surgery. Treatment options include:
- thyroid hormone antagonists, including propylthiouracil (PTU) and methimazole (Tapazole), to block thyroid hormone synthesis (hypermetabolic symptoms subside within 4 to 8 weeks after therapy begins, but remission of Graves' disease requires continued therapy for 6 months to 2 years)
- propranolol (Inderal) until antithyroid drugs reach their full effect, to manage tachycardia and other peripheral effects of excessive hypersympathetic activity resulting from blocking the conversion of T 4 to the active T 3 hormone
- minimum dosage needed to keep maternal thyroid function within the high-normal range until delivery, and to minimize the risk for fetal hypothyroidism; propylthiouracil (PTU) is preferred agent (during pregnancy)
- possibly antithyroid medications and propranolol for neonates for 2 to 3 months because most infants of hyperthyroid mothers are born with mild and transient thyrotoxicosis caused by placental transfer of thyroid-stimulating immunoglobulins (neonatal thyrotoxicosis)
- continuous control of maternal thyroid function because thyrotoxicosis is sometimes exacerbated in the puerperal period; antithyroid drugs gradually tapered and thyroid function reassessed after 3 to 6 months postpartum
- periodic checks of infant's thyroid function with a breast-feeding mother on low-dose antithyroid treatment due to possible presence of small amounts of the drug in breast milk, which can rapidly lead to thyrotoxicity in the neonate
- single oral dose of 131 I (treatment of choice for patients not planning to have children; patients of reproductive age must give informed consent for this treatment, because 131 I concentrates in the gonads).
During treatment with 131 I, the thyroid gland picks up the radioactive element as it would regular iodine. The radioactivity destroys some of the cells that normally concentrate iodine and produce T 4 , thus decreasing thyroid hormone production and normalizing thyroid size and function.
In most patients, hypermetabolic symptoms diminish 6 to 8 weeks after such treatment. However, some patients may require a second dose. Almost all patients treated with 131 I eventually become hypothyroid.
Treatment with surgery includes:
- subtotal thyroidectomy to decrease the thyroid gland's capacity for hormone production (patients who refuse or aren't candidates for 131 I treatment)
- iodides (Lugol's solution or saturated solution of potassium iodide), antithyroid drugs, and propranolol to relieve hyperthyroidism preoperatively (if patient doesn't become euthyroid, surgery should be delayed, and antithyroid drugs and propranolol given to decrease the systemic effects [cardiac arrhythmias] of thyrotoxicosis)
- lifelong regular medical supervision because most patients become hypothyroid, sometimes as long as several years after surgery.
Treatment for ophthalmopathy includes:
- local application of topical medications, such as prednisone acetate suspension, but may require high doses of corticosteroids
- external-beam radiation therapy or surgical decompression (severe exophthalmos causing pressure on optic nerve and orbital contents).
Treatment for thyroid storm includes:
- antithyroid drug to stop conversion of T 4 to T 3 and to block sympathetic effect; corticosteroids to inhibit the conversion of T 4 to T 3 ; and iodide to block the release of thyroid hormone
- supportive measures, including the administration of nutrients, vitamins, fluids, and sedatives.
Hypopituitarism
Hypopituitarism, also known as panhypopituitarism, is a complex syndrome marked by metabolic dysfunction, sexual immaturity, and growth retardation (when it occurs in childhood). The cause is a deficiency of the hormones secreted by the anterior pituitary gland. Panhypopituitarism is a partial or total failure of all six of this gland's vital hormones ― corticotropin (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), human growth hormone, and prolactin. Partial and complete forms of hypopituitarism affect adults and children; in children, these diseases may cause dwarfism and delayed puberty. The prognosis may be good with adequate replacement therapy and correction of the underlying causes.
Primary hypopituitarism usually develops in a predictable pattern. It generally starts with decreased gonadotropin (FSH and LH) levels and consequent hypogonadism, reflected by cessation of menses in women and impotence in men. Growth hormone deficiency follows, causing short stature, delayed growth, and delayed puberty in children. Subsequent decreased TSH levels cause hypothyroidism, and, finally, decreased ACTH levels result in adrenal insufficiency. When hypopituitarism follows surgical ablation or trauma, the pattern of hormonal events may not necessarily follow that sequence. Damage to the hypothalamus or neurohypophysis may cause diabetes insipidus.
Causes
Hypopituitarism may be primary or secondary. Primary hypopituitarism may be caused by:
- tumor of the pituitary gland
- congenital defects (hypoplasia or aplasia of the pituitary gland)
- pituitary infarction (most often from postpartum hemorrhage)
- partial or total hypophysectomy by surgery, irradiation, or chemical agents
- granulomatous disease, such as tuberculosis
- idiopathic or autoimmune origin (occasionally).
Secondary hypopituitarism is caused by:
- deficiency of releasing hormones produced by the hypothalamus, either idiopathic or resulting from infection, trauma, or a tumor.
Pathophysiology
Hypopituitarism describes the low secretion of an anterior pituitary hormone, and panhypopituitarism describes the low secretion of all anterior pituitary hormones. Both can result from malfunction of the pituitary gland or the hypothalamus. The result is a lack of stimulation of target endocrine organs and some degree of deficiency of the target organ hormone, which may not be discovered until the body is stressed and the expected increases in secretions from the target organs don't occur.
Signs and symptoms
Signs and symptoms of hypopituitarism include:
- ACTH deficiency, causing weakness, fatigue, weight loss, fasting hypoglycemia, and altered mental function due to hypocortisolism; loss of axillary and pubic hair due to androgen deficiency in females; orthostatic hypotension and hyponatremia due to aldosterone deficiency
- TSH deficiency, causing weight gain, constipation, cold intolerance, fatigue, and coarse hair
- gonadotropin deficiency, causing sexual dysfunction and infertility
- antidiuretic hormone deficiency, causing diabetes insipidus
- prolactin deficiency, causing lactation dysfunction or gynecomastia.
Complications
Possible complications include:
- blindness
- adrenal crisis.
Diagnosis
Diagnosis of hypopituitarism includes:
- hormonal deficiency of the tropic and target organ hormone(s) affected, chosen after evaluation of clinical picture
- computed tomography or magnetic resonance imaging of pituitary and target glands, showing destruction of the anterior pituitary or atrophy of target glands (adrenal cortex, thyroid, or gonads).
Treatment
The most effective treatment for hypopituitarism is:
- replacement of hormones secreted by the target glands (cortisol, thyroxine, and androgen or cyclic estrogen); prolactin not replaced
- clomiphene or cyclic gonadotropin-releasing hormone to induce ovulation in the patient of reproductive age.
Hypothyroidism in adults
Hypothyroidism results from hypothalamic, pituitary, or thyroid insufficiency or resistance to thyroid hormone. The disorder can progress to life-threatening myxedema coma. Hypothyroidism is more prevalent in women than men; in the United States, the incidence is increasing significantly in people ages 40 to 50.
| AGE ALERT Hypothyroidism occurs primarily after the age of 40. After 65 years of age, the prevalence increases to as much as 10% in females and 3% in males. |
Pathophysiology
Hypothyroidism may reflect a malfunction of the hypothalamus, pituitary, or thyroid gland, all of which are part of the same negative-feedback mechanism. However, disorders of the hypothalamus and pituitary rarely cause hypothyroidism. Primary hypothyroidism is most common.
Chronic autoimmune thyroiditis, also called chronic lymphocytic thyroiditis, occurs when autoantibodies destroy thyroid gland tissue. Chronic autoimmune thyroiditis associated with goiter is called Hashimoto's thyroiditis. The cause of this autoimmune process is unknown, although heredity has a role, and specific human leukocyte antigen subtypes are associated with greater risk.
Outside the thyroid, antibodies can reduce the effect of thyroid hormone in two ways. First, antibodies can block the thyroid-stimulating hormone (TSH) receptor and prevent the production of TSH. Second, cytotoxic antithyroid antibodies may attack thyroid cells.
Subacute thyroiditis, painless thyroiditis, and postpartum thyroiditis are self-limited conditions that usually follow an episode of hyperthyroidism. Untreated subclinical hypothyroidism in adults is likely to become overt at a rate of 5% to 20% per year.
Causes
Causes of hypothyroidism in adults include:
- inadequate production of thyroid hormone, usually after thyroidectomy or radiation therapy (particularly with iodine 131 [ 131 I]), or due to inflammation, chronic autoimmune thyroiditis (Hashimoto's disease), or such conditions as amyloidosis and sarcoidosis (rare)
- pituitary failure to produce TSH, hypothalamic failure to produce thyrotropinreleasing hormone (TRH), inborn errors of thyroid hormone synthesis, iodine deficiency (usually dietary), or use of such antithyroid medications as propylthiouracil (PTU).
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CLINICAL FINDINGS IN ACQUIRED HYPOTHYROIDISM
Typical findings in acquired hypothyroidism are listed below:
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Signs and symptoms
Signs and symptoms of hypothyroidism include:
- weakness, fatigue, forgetfulness, sensitivity to cold, unexplained weight gain, and constipation (typical, vague, early clinical features) (See Clinical findings in acquired hypothyroidism .)
- characteristic myxedematous signs and symptoms of decreasing mental stability; coarse, dry, flaky, inelastic skin; puffy face, hands, and feet; hoarseness; periorbital edema; upper eyelid droop; dry, sparse hair; and thick, brittle nails (as disorder progresses)
- cardiovascular involvement, including decreased cardiac output, slow pulse rate, signs of poor peripheral circulation, and, occasionally, an enlarged heart.
Other common effects include:
- anorexia, abdominal distention, menorrhagia, decreased libido, infertility, ataxia, and nystagmus; reflexes with delayed relaxation time (especially in the Achilles' tendon)
- progression to myxedema coma, usually gradual but may develop abruptly, with stress aggravating severe or prolonged hypothyroidism, including progressive stupor, hypoventilation, hypoglycemia, hyponatremia, hypotension, and hypothermia.
Diagnosis
Diagnosis of hypothyroidism is based on:
- radioimmunoassay showing low triiodothyronine (T 3 ) and thyroxine (T 4 ) levels
- increased TSH level with cause of thyroid disorder; decreased with hypothalamic or pituitary disorder cause
- thyroid panel differentiating primary hypothyroidism (thyroid gland hypofunction), secondary hypothyroidism (pituitary hyposecretion of TSH), tertiary hypothyroidism (hypothalamic hyposecretion of TRH), and euthyroid sick syndrome (impaired peripheral conversion of thyroid hormone due to a suprathyroidal illness, such as severe infection) (See Thyroid test results in hypothyroidism .)
- elevated serum cholesterol, alkaline phosphatase, and triglyceride levels
- normocytic, normochromic anemia
- low serum sodium levels, decreased pH, and increased partial pressure of carbon dioxide, indicating respiratory acidosis (myxedema coma).
THYROID TEST RESULTS IN HYPOTHYROIDISM
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Complications
Possible complications are:
- heart failure
- myxedema coma
- infection
- megacolon
- organic psychosis
- infertility.
Treatment
Treatment includes:
- gradual thyroid hormone replacement with T 4 and, occasionally, T 3
- surgical excision, chemotherapy, or radiation for tumors.
| AGE ALERT Elderly patients should be started on a very low dose of T 4 to avoid cardiac problems; TSH levels guide gradual increases in dosage. |
Hypothyroidism in children
A deficiency of thyroid hormone secretion during fetal development and early infancy results in infantile cretinism (congenital hypothyroidism). Hypothyroidism in infants is seen as respiratory difficulties, cyanosis, persistent jaundice, lethargy, somnolence, large tongue, abdominal distention, poor feeding, and hoarse crying. Prompt treatment of hypothyroidism in infants prevents physical and mental retardation. Older children who become hypothyroid have similar symptoms to those of adults, plus poor skeletal growth and late epiphyseal maturation and dental development. Sexual maturation may be accelerated in younger children and delayed in older children.
Cretinism is three times more common in girls than boys. Early diagnosis and treatment allow the best prognosis; infants treated before the age of 3 months usually grow and develop normally. Athyroid children who remain untreated beyond the age of 3 months, and children with acquired hypothyroidism who remain untreated beyond the age of 2 years, have irreversible mental retardation; their skeletal abnormalities are reversible with treatment.
Causes
Causes include:
- defective embryonic development (most common cause), causing congenital absence or underdevelopment of the thyroid gland (cretinism in infants)
- inherited autosomal recessive defect in the synthesis of thyroxine (next most common cause)
- antithyroid drugs taken during pregnancy, causing cretinism in infants (less frequently)
- chronic autoimmune thyroiditis (cretinism after age 2 years).
Pathophysiology
Hypothyroidism in infants and children is related to decreased thyroid hormone production or secretion. Loss of functional thyroid tissue can be caused by an autoimmune process. Defective thyroid synthesis may be related to congenital defects, with thyroid dysgenesis (defective development) the most common. Iodine deficiency or antithyroid drugs used by the mother during pregnancy can also contribute. Hypothyroidism may also be related to decreased thyroid-stimulating hormone (TSH) secretion or resistance to TSH.
Signs and symptoms
Signs and symptoms include:
- infant with infantile cretinism will have normal weight and length at birth, with characteristic signs developing within 3 to 6 months; delayed onset of most symptoms until weaning from breast-feeding due to small amounts of thyroid hormone in breast milk
- typically, an infant with cretinism sleeps excessively, seldom cries (except for occasional hoarse crying), and is inactive; parents may describe a “good baby ― no trouble at all” (behavior actually due to reduced metabolism and progressive mental impairment)
- abnormal deep tendon reflexes, hypotonic abdominal muscles, protruding abdomen, and slow, awkward movements
- feeding difficulties, constipation, and jaundice because the immature liver can't conjugate bilirubin
- large, protruding tongue obstructing respiration; loud and noisy breathing through open mouth; dyspnea on exertion; anemia; abnormal facial features, such as a short forehead, puffy wide-set eyes (periorbital edema), wrinkled eyelids, a broad short and upturned nose, and a dull expression reflecting mental retardation
- cold, mottled skin due to poor circulation; and dry, brittle, and dull hair
- teeth erupting late and decaying early, below-normal body temperature, and slow pulse rate
- growth retardation shown as short stature, due to delayed epiphyseal maturation, particularly in the legs; obesity; and head appearing abnormally large due to stunted arms and legs; delayed or accelerated sexual development; mental retardation can be prevented by appropriate treatment if child acquires hypothyroidism after the age of 2 years.
Complications
Complications include:
- irreversible mental retardation (for hypothyroid infant not treated by the age of 3 months; early treatment helps prevent retardation)
- learning disabilities
- short stature
- accelerated or delayed sexual maturation.
Diagnosis
Diagnosis is based on:
- elevated TSH level associated with low T 3 and T 4 levels pointing to cretinism (because early detection and treatment can minimize the effects of cretinism, many states require measurement of infant thyroid hormone levels at birth)
- thyroid scan and 131 I uptake tests showing decreased uptake and confirming the absence of thyroid tissue in athyroid children
- increased gonadotropin levels compatible with sexual precocity in older children may coexist with hypothyroidism
- electrocardiogram showing bradycardia and flat or inverted T waves in untreated infants
- hip, knee, and thigh X-rays showing absence of the femoral or tibial epiphyseal line and markedly delayed skeletal development relative to chronological age
- low T 4 and normal TSH levels suggesting hypothyroidism secondary to hypothalamic or pituitary disease (rare).
Treatment
Early detection is mandatory to prevent irreversible mental retardation and permit normal physical development. Treatment includes:
- oral levothyroxine (Synthroid), beginning with moderate doses and gradually increasing to levels sufficient for lifelong maintenance (rapid increase in dosage may precipitate thyrotoxicity); proportionately higher doses in children than in adults because children metabolize thyroid hormone more quickly (infants younger than age 1).
Syndrome of inappropriate antidiuretic hormone
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) results when excessive ADH secretion is triggered by stimuli other than increased extracellular fluid osmolarity and decreased extracellular fluid volume, reflected by hypotension. SIADH is a relatively common complication of surgery or critical illness. The prognosis varies with the degree of disease and the speed at which it develops. SIADH usually resolves within 3 days of effective treatment.
Causes
The most common cause of SIADH is small-cell carcinoma of the lung, which secretes excessive levels of ADH or vasopressin-like substances. Other neoplastic diseases ― such as pancreatic and prostatic cancer, Hodgkin's disease, and thymoma (tumor on the thymus) ― may also trigger SIADH.
Less common causes include:
- central nervous system disorders, including brain tumor or abscess, cerebrovascular accident, head injury, and Guillain-Barré syndrome
- pulmonary disorders, including pneumonia, tuberculosis, lung abscess, and positive-pressure ventilation
- drugs, including chlorpropamide (Diabinase), vincristine (Oncovin), cyclophosphamide (Cytoxin), carbamazepine (Tegretol), clofibrate (Atromid-S), metoclopramide (Reglan), and morphine
- miscellaneous conditions, including psychosis and myxedema.
Pathophysiology
In the presence of excessive ADH, excessive water reabsorption from the distal convoluted tubule and collecting ducts causes hyponatremia and normal to slightly increased extracellular fluid volume.
Signs and symptoms
Signs and symptoms of SIADH include:
- thirst, anorexia, fatigue, and lethargy (first signs), followed by vomiting and intestinal cramping due to hyponatremia and electrolyte imbalance manifestations
- water retention and decreased urinary output due to hyponatremia
- additional neurologic symptoms, such as restlessness, confusion, anorexia, headache, irritability, decreasing reflexes, seizures, and coma, due to electrolyte imbalances, worsening with the degree of water intoxication.
Complications
Complications of SIADH include:
- cerebral edema
- brain herniation
- central pontine myelinosis.
Diagnosis
SIADH is diagnosed by the following laboratory results:
- serum osmolarity less than 280 mOsm/kg of water
- hyponatremia (serum sodium less than 135 mEq/L); lower values indicating worse condition
- elevated urinary sodium level (more than 20 mEq/day)
- elevated serum ADH level.
Treatment
Treatment of SIADH includes:
- restricted water intake (500 to 1,000 ml/day) (symptomatic treatment)
- administration of 200 to 300 ml of 3% saline solution to increase serum sodium level (severe water intoxication)
- correction of underlying cause of SIADH when possible
- surgical resection, irradiation, or chemotherapy to alleviate water retention for SIADH resulting from cancer
- demeclocycline (Declomycin) to block the renal response to ADH (if fluid restriction is ineffective)
- furosemide (Lasix) with normal or hypertonic saline to maintain urine output and block ADH secretion.
