Endocrine hormones are synthesised in the brain, adrenal gland, pancreas, testes and ovary, and perhaps most importantly in the hypothalamus and pituitary, but they act elsewhere in the body since they are released into the circulatory system. The result is a hormonal cascade that incorporates an amplification of the amount of successive hormone released into the circulatory system, increasing from micrograms to milli grams, as well as a negative feedback that operates to control the cascade when the level of the ‘action’ hormone has reached its optimum value. Most signals originate in the central nervous system either as a result of an environmental (external) signal, such as trauma or temperature, or an internal signal. The response is a signal to the hypothalamus and the release of a hormone such as corticotropin-releasing hormone ( CRH). This travels in the bloodstream to the anterior pituitary gland, where it acts on its receptor and results in the release of a second hormone, adrenocorticotropic hormone ( ACTH). ACTH, in turn, circulates in the blood to reach its target gland, the adrenal cortex, where it acts to release the ‘action’ hormone, cortisol, known as the stress hormone. The released cortisol raises blood pressure and blood glucose and is subject to a natural diurnal variation, peaking in early morning and being lowest around midnight. It has a negative feedback effect on the pituitary and adrenal cortex. Glands linked by the action of successive hormones are referred to as an axis , e.g. the hypothalamus–pituitary–adrenal axis. These coordinated cascades regulate the growth and function of many types of cells ( Table 1). The hormones released act at specific receptors, commonly G-protein coupled receptors ( GPCRs), which trig ger the release of second messengers such as cAMP, cGMP, inositol triphosphate, Ca 2+ and protein kinases. Diseases of the endocrine system result in dysregulated hormone release, inappropriate signalling response or, in extreme cases, the destruction of the gland. Examples include diabetes mellitus, Addison’s disease, Cushing’s syndrome, hyper- and hypothyroidism and obesity. Such medical conditions are characterised by their long-term nature. Laboratory tests are commonly employed to measure hormone levels in order to assist in the diagnosis of the condition and the subsequent care of the patient.
Table1. Examples of hormones of the hypothalamus–pituitary axis
Thyroid Function Tests
Approximately 1% of the population suffers from some form of thyroid disease, although in many cases the symptoms may be non-specific. Even so, over 1 million thyroid function tests are conducted annually in the UK. As shown in Table 1, the hypothalamus releases thyrotropin-releasing hormone (TRH) which acts directly on the pituitary to produce thyroid-stimulating hormone (TSH); the latter, in turn, stimulates the thyroid gland to produce two thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3; Figure 1). The gland produces approximately 10% of the circulating T3, the remainder being produced by the metabolism of T4 mainly in the liver and kidney. The majority of T4 and T3 are bound to thyroxine-binding globulin (TBG), but only the free unbound forms (fT4, fT3) are biologically active. Although the concentration of T3 is approximately one-tenth of that of T4, T3 is ten times more active. Both hormones act on nuclear receptors to increase cell metabolism and both have a negative feedback effect on the hypothalamus to switch off the secretion of TRH and on the pituitary to switch off TSH secretion. Hyperthyroidism is a consequence of the over-production of the two hormones and common causes are thyroiditis, Grave’s disease and TSH-producing pituitary tumours. Hypothyroidism, characterised by weakness, fatigue, weight gain and joint or muscle pain, may be primary due to the under-secretion of T4 and T3, possibly due to irradiation or drugs such as lithium, autoimmune disease or secondary due to damage to the hypothalamus or pituitary. Normal laboratory tests for these conditions are based on the measurement of TSH and usually fT4 and fT3, occasionally total (bound and unbound) T4, all by immunoassay.
Fig1. Hypothalamic–pituitary thyroid axis, an example of a negative feedback system. In this case, the products of the thyroid gland, thyroxine (T4) and tri-iodothyronine (T3) feedback on the hypothalamus and pituitary to stop secretion of TRH and TSH, respectively.
