Thyroid function tests
Approximately 1% of the population suffer 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 16.7, the hypothal-
amus releases thyrotropin-releasing hormone (TRH) which acts directly on the pituitary
to produce thyroid-stimulating hormone (TSH) which in turn stimulates the thyroid
gland to produce two thyroid hormones, thyroxine (T4) and triiodothyronine (T3).
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 overproduction 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 undersecretion of T4 and T3, possibly due to
irradiation or drugs such as lithium, or secondary due to damage to the hypothalamus
or pituitary. Normal laboratory tests for these conditions are based on the measurement
of TSH and either total (bound and unbound) T4 and total T3 or fT4 and fT3 all by
immunoassay.16.3.6 Hypothalamus–pituitary–gonad axis
In both sexes, the hypothalamus produces gonadotropin-releasing hormone (GRH) that
stimulates the pituitary to release luteinising hormone (LH) and follicle-stimulating
hormone (FSH). In males, the release of LH and FSH is fairly constant, whereas in females
the release is cyclical. In males LH stimulates Leydig cells in the testes to produce
testosterone which together with FSH causes the production of sperm. The testosterone
has a negative feedback effect on both the hypothalamus and the pituitary thereby
controlling the release of GRH. The testosterone acts on various body tissues to give male
characteristics. In females, FSH acts on the ovaries to produce both oestradiol and the
development of the follicle. The oestradiol and LH then act to stimulate ovulation.
Oestradiol has a negative feedback effect on the hypothalamus and the pituitary and acts
on body tissues to produce female characteristics.16.3.7 Diabetes mellitus
Diabetes is the most common metabolic disorder of carbohydrate, fat and protein
metabolism, and is primarily due to either a deficiency or complete lack of the secretion
of insulin by theb-cells of the islets of Langerhans in the pancreas. It affects 1–2% of
Western populations and 5–10% of the population over the age of 40. It is characterised651 16.3 Examples of biochemical aids to clinical diagnosis