Clinical Information

Thyroid Stimulating Hormone (TSH), or thyrotropin, is a glycoprotein synthesized by the basophilic cells (thyrotropes) of the anterior pituitary. TSH stimulates the production and secretion of the metabolically active thyroid hormones thyroxine (T4) and triiodothyronine (T3) by interacting with a specific receptor on the thyroid cell surface. T3 and T4 are responsible for regulating diverse biochemical processes throughout the body which are essential for normal development and metabolic and neural activity.

The synthesis and secretion of TSH is stimulated by the hypothalamic tripeptide thyrotropin releasing hormone (TRH) in response to low levels of circulating thyroid hormones. Elevated levels of T3 and T4 suppress production of TSH via a negative feedback mechanism. Other evidence indicates that somatostatin and dopamine exert inhibitory control over TSH release, suggesting that the hypothalamus may provide both inhibitory and stimulatory influence on pituitary TSH production. Failure at any level of regulation of the hypothalamic-pituitary-thyroid axis will result in either underproduction (hypothyroidism) or overproduction (hyperthyroidism) of T4 and/or T3.

In cases of primary hypothyroidism, T3 and T4 levels are low and TSH levels are significantly elevated. In the case of pituitary dysfunction, either due to intrinsic hypothalamic or pituitary disease (central hypothyroidism, normal or marginally elevated basal TSH levels, etc.) are often seen despite significant reduction in T4 and/or T3 levels. These inappropriate TSH values are due to a reduction in TSH bioactivity frequently observed in such cases. Routine TRH stimulation is advised to confirm the diagnosis in such cases. Secondary hypothyroidism typically results in an impaired TSH response to TRH, while in tertiary hypothyroidism the TSH response to TRH may be normal, prolonged or exaggerated.

Primary hyperthyroidism (e.g., Grave’s Disease, nodular goiter) is associated with high levels of thyroid hormones and depressed or undetectable levels of TSH. The TRH stimulation test has been used in diagnosis of hyperthyroidism. Hyperthyroid patients show a subnormal response to the TRH test. In addition, large doses of glucocorticoids, somatostatin, dopamine and replacement doses of thyroid hormones reduce or totally blunt the TSH response to TRH.