Last full review/revision April 2009 by John E. Morley, MB, BCh
Content last modified April 2009
Endocrine disorders can result from dysfunction originating in the peripheral endocrine gland itself (primary disorders) or from understimulation or overstimulation by the pituitary (secondary disorders). The disorders can result in hormone overproduction (hyperfunction) or underproduction (hypofunction). Rarely, endocrine disorders (usually hypofunction) occur because of abnormal tissue responses to hormones. Clinical presentation of hypofunction disorders is often insidious and nonspecific.
Hyperfunction: 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. Destruction of a peripheral endocrine gland can rapidly release stored hormone (eg, thyroid hormones in thyroiditis). 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: 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 conditions, tumors, infections, vascular disorders, and toxins). Genetic disorders producing 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.
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 produce hypofunction.
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 levels of the peripheral endocrine hormone, the pituitary hormone, or both in the blood.
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.
Free hormone levels can also 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).
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 h or using a pooled blood sample. Hormones with week-to-week variation (eg, testosterone) necessitate obtaining separate values a week apart.