Endocrine disorders can result from
Dysfunction originating in the peripheral endocrine gland itself (primary disorders)
Understimulation by the pituitary (secondary disorders)
Overstimulation by the pituitary (secondary disorders)
Rarely, because of abnormal tissue response to hormones (usually hypofunction).
The disorders can result in hormone overproduction (hyperfunction) or underproduction (hypofunction). Clinical manifestations of hypofunction disorders are often insidious and nonspecific.
(See also Overview of the Endocrine System Overview of the Endocrine System The endocrine system coordinates functioning between different organs through hormones, which are chemicals released into the bloodstream from specific types of cells within endocrine (ductless)... read more .)
Hyperfunction of endocrine glands may result from overstimulation by the pituitary but is most commonly due to hyperplasia or neoplasia of the gland itself. In some cases, cancers from other tissues can produce hormones (ectopic hormone production).
Hormone excess also can result from exogenous hormone administration. In some cases, patients take hormones without telling the physician (factitious disease).
Tissue hypersensitivity to hormones can occur. Antibodies can stimulate peripheral endocrine glands, as occurs in hyperthyroidism of Graves disease Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms are many and include tachycardia, fatigue, weight loss, nervousness, and tremor... read more . Disruption of a peripheral endocrine gland can rapidly release stored hormone (eg, thyroid hormone release in subacute thyroiditis Subacute Thyroiditis Subacute thyroiditis is an acute inflammatory disease of the thyroid probably caused by a virus. Symptoms include fever and thyroid tenderness. Initial hyperthyroidism is common, sometimes followed... read more ).
Enzyme defects in the synthesis of a peripheral endocrine hormone can result in overproduction of hormones proximal to the block. Finally, overproduction of a hormone can occur as an appropriate response to a disease state.
Hypofunction of an endocrine gland can result from understimulation by the pituitary.
Hypofunction originating within the peripheral gland itself can result from congenital or acquired disorders (including autoimmune disorders, tumors, infections, vascular disorders, and toxins).
Genetic disorders causing hypofunction can result from deletion of a gene or by production of an abnormal hormone. A decrease in hormone production by the peripheral endocrine gland with a resulting increase in production of pituitary regulating hormone can lead to peripheral endocrine gland hyperplasia. For example, if synthesis of thyroid hormone is defective, thyroid-stimulating hormone (TSH) is produced in excessive amounts, causing goiter Simple Nontoxic Goiter Simple nontoxic goiter, which may be diffuse or nodular, is noncancerous hypertrophy of the thyroid without hyperthyroidism, hypothyroidism, or inflammation. Except in severe iodine deficiency... read more .
Several hormones require conversion to an active form after secretion from the peripheral endocrine gland. Certain disorders can block this step (eg, renal disease can inhibit production of the active form of vitamin D). Antibodies to the circulating hormone or its receptor can block the ability of the hormone to bind to its receptor.
Disease or drugs can cause increased rate of clearance of hormones. Circulating substances may also block the function of hormones. Abnormalities of the receptor or elsewhere in the peripheral endocrine tissue can also cause hypofunction.
Laboratory Testing for Endocrine Disorders
Because symptoms of endocrine disorders can begin insidiously and may be nonspecific, clinical recognition is often delayed for months or years. For this reason, biochemical diagnosis is usually essential; it typically requires measuring blood levels of the peripheral endocrine hormone, the pituitary hormone, or both.
Because most hormones have circadian rhythms, measurements need to be made at a prescribed time of day. Hormones that vary over short periods (eg, luteinizing hormone) necessitate obtaining 3 or 4 values over 1 or 2 hours or using a pooled blood sample. Hormones with week-to-week variation (eg, testosterone) necessitate obtaining separate values a week apart.
Blood hormone measurements
Free or bioavailable hormone (ie, hormone not bound to a specific binding hormone) is generally believed to be the active form. Free or bioavailable hormones are measured using equilibrium dialysis, ultrafiltration, or a solvent-extraction method to separate the free and albumin-bound hormone from the binding globulin. These methods can be expensive and time-consuming. Analog and competitive free hormone assays, although often used commercially, are not always accurate and should not be used.
Blood hormone estimates
Free hormone levels can be estimated indirectly by assessing levels of the binding protein and using them to adjust levels of the total serum hormone. However, indirect methods are inaccurate if the binding capacity of the hormone-binding protein has been altered (eg, by a disorder).
In some cases, other indirect estimates are used. For example, because growth hormone (GH) has a short serum half-life and is difficult to detect in serum, serum insulin-like growth factor 1 (IGF-1), which is produced in response to GH, is often measured as an index of GH activity. Whether measurement of circulating hormone metabolites indicates the amount of bioavailable hormone is under investigation.
Sometimes, instead of blood levels, urine (eg, free cortisol when testing for Cushing disease Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more ) or salivary hormone levels may be used.
In many cases, a dynamic test is necessary. Thus, in the case of hypofunctioning organs, a stimulation test (eg, ACTH stimulation Provocative testing Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal crisis... read more ) can be used. In hyperfunction, a suppression test (eg, dexamethasone suppression Dexamethasone suppression test Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more ) can be used.
Treatment of Endocrine Disorders
Replacing deficient hormone
Suppressing excessive hormone production
Hypofunction disorders are usually treated by replacement of the peripheral endocrine hormone regardless of whether the defect is primary or secondary (an exception is growth hormone, a pituitary hormone replacement used for pituitary dwarfism). If resistance to the hormone exists, drugs that reduce resistance can be used (eg, metformin or thiazolidinediones for type 2 diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ). Occasionally, a hormone-stimulating drug is used.
Radiation therapy, surgery, and drugs that suppress hormone production are used to treat hyperfunction disorders. In some cases, a receptor antagonist is used.
Aging and Endocrinology
Hormones undergo many changes as a person ages.
Most hormone levels decrease.
Some hormone levels remain normal, including thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (basal), thyroxine, cortisol (basal), 1,25-dihydroxycholecalciferol, insulin (sometimes increases), and estradiol (in men).
Some hormone levels increase.
Hormones that increase, including adrenocorticotropic hormone (ACTH—increased response to corticotropin-releasing hormone), follicle-stimulating hormone, sex-hormone binding globulin, and activin (in men), gonadotropins (in women), epinephrine (in the oldest old), parathyroid hormone, norepinephrine, cholecystokinin, vasoactive intestinal peptide, vasopressin (also loss of circadian rhythm), and atrial natriuretic factor, are associated with either receptor defects or postreceptor defects, resulting in hypofunction.
Many age-related changes are similar to those in patients with hormone deficiency, leading to the hypothesis of a hormonal fountain of youth (ie, speculation that some changes associated with aging can be reversed by the replacement of one or more deficient hormones). Some evidence suggests that replacing certain hormones in the elderly can improve functional outcomes (eg, muscle strength, bone mineral density), but little evidence exists regarding effects on mortality. In some cases, replacing hormones may be harmful, as in estrogen replacement in some older women.
A competing theory is that the age-related decline in hormone levels represents a protective slowing down of cellular metabolism. This concept is based on the rate of living theory of aging (ie, the faster the metabolic rate of an organism, the quicker it dies). This concept is seemingly supported by studies on the effects of dietary restriction. Restriction decreases levels of hormones that stimulate metabolism, thereby slowing metabolic rate; restriction also prolongs life in rodents.
Specific age-related hormone decreases
Dehydroepiandrosterone (DHEA) and its sulfate levels decline dramatically with age. Despite optimism for the role of DHEA supplementation in older people, most controlled trials failed to show any major benefits.
Pregnenolone is the precursor of all known steroid hormones. As with DHEA, its levels decline with age. Studies in the 1940s showed its safety and benefits in people with arthritis, but additional studies failed to show any beneficial effects on memory and muscle strength.
Levels of growth hormone (GH) and its peripheral endocrine hormone (insulin-like growth factor 1 [IGF-1]) decline with age. GH replacement in older people sometimes increases muscle mass but does not increase muscle strength (although it may in malnourished people). Adverse effects (eg, carpal tunnel syndrome, arthralgias, water retention) are very common. GH may have a role in the short-term treatment of some undernourished older patients, but in critically ill undernourished patients, GH increases mortality. Secretagogues that stimulate GH production in a more physiologic pattern may improve benefit and decrease risk.
Levels of melatonin, a hormone produced by the pineal gland, also decline with aging. This decline may play an important role in the loss of circadian rhythms with aging.
Estrogen replacement in older women is discussed under the treatment of menopause Hormone Therapy Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more . Testosterone replacement Testosterone replacement therapy (TRT) Hypogonadism is defined as testosterone deficiency with associated symptoms or signs, deficiency of spermatozoa production, or both. It may result from a disorder of the testes (primary hypogonadism)... read more in older men is discussed elsewhere.
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