Thyroid-Stimulating Hormone (TSH)

1. Overview

Thyroid-Stimulating Hormone (TSH), also known as thyrotropin, is a glycoprotein hormone that regulates the activity of the thyroid gland. It stimulates the synthesis and release of thyroid hormones—thyroxine (T4) and triiodothyronine (T3)—which control metabolism, growth, and development. TSH is part of the hypothalamic-pituitary-thyroid (HPT) axis and serves as a key component in maintaining thyroid hormone homeostasis via negative feedback mechanisms.

2. Location

TSH is secreted by the thyrotroph cells of the anterior pituitary gland (adenohypophysis), which is located at the base of the brain in the sella turcica of the sphenoid bone. Its release is regulated by:

• Thyrotropin-releasing hormone (TRH) from the hypothalamus, which stimulates TSH production.

• Negative feedback from circulating T3 and T4, which suppress TSH and TRH secretion when thyroid hormone levels are sufficient or elevated.

3. Structure

TSH is a glycoprotein hormone composed of two subunits:

• Alpha (α) subunit: Common to other pituitary glycoproteins such as LH, FSH, and hCG.

• Beta (β) subunit: Unique to TSH and confers its biological specificity by binding to the TSH receptor on thyroid follicular cells.

TSH has a molecular weight of approximately 28–30 kDa and is heavily glycosylated, which affects its stability and activity. It exerts its effects by binding to the TSH receptor (TSHR), a G protein–coupled receptor located on thyroid follicular cells.

4. Function

TSH regulates thyroid gland function through multiple mechanisms:

• Stimulates iodine uptake into thyroid cells, which is essential for thyroid hormone synthesis.

• Activates thyroglobulin production and iodination processes within thyroid follicles.

• Promotes synthesis and secretion of T3 and T4 into the bloodstream.

• Supports thyroid growth and maintenance; prolonged high TSH levels can lead to goiter formation.

5. Physiological role(s)

TSH indirectly influences a wide range of physiological systems by modulating thyroid hormone output:

• Metabolic regulation: By promoting T3/T4 secretion, TSH helps control basal metabolic rate and energy expenditure.

• Growth and development: Supports normal growth, especially of the nervous system in infancy and childhood.

• Thermoregulation: Influences heat production through metabolic activation.

• Cardiovascular health: Indirectly regulates heart rate, cardiac output, and vascular tone via thyroid hormones.

• Reproductive health: Imbalances in TSH and thyroid hormones can affect menstrual cycles and fertility.

6. Clinical Significance

TSH measurement is a cornerstone of thyroid function testing, and its levels help diagnose and monitor a variety of disorders:

• Hypothyroidism:

  • Characterized by elevated TSH and low T3/T4 (primary hypothyroidism).

  • Common causes: Hashimoto's thyroiditis, iodine deficiency, post-thyroidectomy.

  • Symptoms include fatigue, weight gain, cold intolerance, and depression.

• Hyperthyroidism:

  • Characterized by suppressed TSH and elevated T3/T4 levels (primary hyperthyroidism).

  • Common causes: Graves’ disease, toxic multinodular goiter, thyroid adenoma.

  • Symptoms include weight loss, heat intolerance, anxiety, palpitations, and tremor.

• Secondary and tertiary hypothyroidism:

  • Caused by pituitary (secondary) or hypothalamic (tertiary) dysfunction.

  • Both TSH and thyroid hormone levels are low or inappropriately normal.

• TSH-secreting pituitary adenoma:

  • Rare tumor that leads to elevated TSH despite high T3/T4 levels, causing hyperthyroidism.

• Monitoring thyroid replacement therapy:

  • TSH is routinely used to adjust levothyroxine dosing in hypothyroid patients.

• Newborn screening:

  • Elevated TSH in newborns suggests congenital hypothyroidism, which requires early treatment to prevent intellectual disability and growth retardation.