Principles of endocrine testing

Clinical

Principles of endocrine testing

The endocrine system is the mechanism by which information is communicated around the body using chemical messengers (hormones). These messengers are secreted by glands and may be transported through the bloodstream to a distant target organ (endocrine activity) or may act directly on local tissue (paracrine activity). Hormones are of various types including peptides, glycoproteins, steroids or amines such as catecholamines.

·        Peptide, glycoprotein and amine hormones act by binding to cell surface receptors, which initiate a cascade of intracellular signalling molecules. These hormones may be synthesised and stored as inactive precursors (prohormones).

·        Steroid hormones and thyroid hormones circulate freely and bound to plasma proteins. It is only the unbound (free) hormone that is biologically active. The bound hormone acts as a buffer against rapid changes in hormone levels. Steroid hormones act via intracellular receptors, which travel to the cell nucleus and regulate DNA transcription and hence protein synthesis.

The sensitivity of target organs to a hormone is dependent on the level of receptor expression. Prolonged exposure to a hormone often results in receptor downregulation, whereas absent or minimal hormone exposure leads to receptor upregulation.

Hormones may act on glands to cause the secretion of other hormones and may also act to downregulate their own production (negative feedback), for example the action of thyroid hormones on the anterior pituitary (see Fig. 11.1).

Endocrine dysfunction generally results in over or under functioning of a gland. Reduced function may result from a number of mechanisms. For example, hypothyroidism may result from a failure of the anterior pituitary gland or a failure of the thyroid gland. Endocrine testing is used to both identify the lack of hormone and to elucidate the underlying cause. For example,

·        measurement of thyroid hormones is used to detect hypothyroidism

·        measurement of thyroid stimulating hormone (TSH) helps to identify the cause. A low TSH signifies failure of the anterior pituitary (secondary hypothyroidism). A high TSH signifies failure of the thyroid gland (primary hypothyroidism).

Clinical features of apparent hormone deficiency may also result from a failure of response at the target organs.

Some hormones have cyclical or pulsatile secretion. In these cases a single random hormone sample will not determine whether the level is high or low. In such instances either testing at specific times of day (e.g. early morning cortisol levels) or dynamic endocrine testing is required. Dynamic endocrine testing uses techniques to stimulate or suppress hormone secretion. For example, cortisol is secreted from the adrenal glands in response to adrenocorticotrophin hormone (ACTH). Administering a synthetic ACTH (Synacthen) allows the response of the adrenal glands to be assessed.