Thyroid Hormone Regulation

Thyroid Hormone Synthesis

• Thyroglobulin (Tg) plays a crucial role in the synthesis and storage of thyroid hormone.
• Tg is a glycoprotein containing multiple tyrosine residues, which serves as a scaffold for thyroid hormone synthesis.
• Iodine binds to carbon 3 or 5 of the tyrosine residues on Tg, resulting in the formation of monoiodinated tyrosine (MIT) and diiodinated tyrosine (DIT) residues.
• The coupling of iodinated tyrosine residues, either of 2 DIT residues or of 1 MIT and 1 DIT residue, is catalyzed by the enzyme thyroid peroxidase (TPO) to form triiodothyronine (T3) or tetraiodothyronine (T4).

Thyroid Hormone Release and Regulation

• The thyroid gland releases more T4 than T3, resulting in 40-fold higher plasma concentrations of T4.
• Most of the circulating T3 is formed peripherally by deiodination of T4, a process that involves the removal of iodine from carbon 5 on the outer ring of T4.
• T4 acts as a prohormone for T3, and its deiodination occurs predominantly in the liver, kidney, and thyroid follicular epithelial cells.
• Thyroid hormone synthesis is regulated by the hypothalamic-pituitary-thyroid axis, with TSH being the main stimulator of thyroid hormone synthesis.

Thyroid Hormone Binding and Metabolism

• Most of the plasma T4 and T3 is protein bound, mainly to thyroxine-binding globulin (TBG) and, to a lesser extent, transthyretin and albumin.
• A small fraction of each hormone (0.03% of T4 and 0.3% of T3) circulates in its free form, which is the physiologically active form.
• T4 has a lower metabolic clearance rate and a longer half-life (7 days) than T3 (1 day) due to its tighter binding to binding proteins.

Disorders of the Thyroid Gland

• Hypothyroidism is characterized by insufficient thyroid hormone action, resulting in weight gain, myopathy, menstrual disturbances, and other symptoms.
• Two main types of hypothyroidism are distinguished: primary hypothyroidism (disease of the thyroid gland) and secondary hypothyroidism (decreased TSH secretion).
• Hyperthyroidism is characterized by excessive functional activity of the thyroid gland, resulting in weight loss, tachycardia, nervousness, anxiety, and difficulty sleeping.
• The most common cause of primary hyperthyroidism in adults is Graves' disease, an autoimmune thyroid disease.

Adrenal Gland Hormones

• The adrenal gland consists of two distinct tissues: the outer cortex and the inner medulla.
• The cortex secretes glucocorticoids, mineralocorticoids, and sex steroid hormones, while the medulla secretes catecholamines, principally adrenaline.

Glucocorticoid Secretion

• Glucocorticoids have widespread metabolic effects on carbohydrate, fat, and protein metabolism.
• In the liver, cortisol stimulates gluconeogenesis, amino acid uptake and degradation, and ketogenesis.
• In adipose tissue, cortisol increases lipolysis, and in muscle, it increases proteolysis and amino acid release.

Regulation of Glucocorticoid Secretion

• The main stimulus to cortisol secretion is ACTH, which is regulated by negative feedback control, stress, and the diurnal rhythm of plasma cortisol.
• The hypothalamic-pituitary-adrenal axis is the main regulatory system controlling cortisol secretion.

Aldosterone Secretion

• The principal physiological function of aldosterone is to conserve Na+, mainly by facilitating Na+ reabsorption and reciprocal K+ or H+ secretion in the distal renal tubule.
• The renin-angiotensin system is the most important system controlling aldosterone secretion.
• Aldosterone production is stimulated by the renin-angiotensin system, which is activated in response to changes in blood volume, renal perfusion pressure, and plasma K+ levels.

Adrenocortical Hyperfunction

• Hyperfunction of the adrenal cortex can lead to overproduction of cortisol (Cushing's syndrome) or aldosterone (Conn's syndrome).
• Cushing's syndrome can be ACTH-dependent or ACTH-independent, and is caused by tumors that release either ACTH or cortisol.