Pituitary, adrenal and thyroid dysfunction

Abstract

Regulation of the adrenal and thyroid glands by the hypothalamo-pituitary axis depends on feedback loops. A breakdown in this feedback system may lead to chronic stimulation or inhibition and endocrine disorders. The adrenal gland secretes steroids (mineralocorticoids, glucocorticoids and androgens) and catecholamines. Adrenal insufficiency (Addison’s disease) is an autoimmune condition that results in the destruction of the adrenal glands. Treatment is by replacement of glucocorticoids and mineralocorticoids. Primary hyperaldosteronism (Conn’s syndrome) and Cushing’s syndrome arise through mineralocorticoid and glucocorticoid secreting tumours, respectively. Both are treated by surgery where possible. Pharmacological management is by inhibitors of dehydrogenation (trilostane) and hydroxylation (metyrapone) in the steroidogenic pathway. Tumours of the adrenal medulla (phaeochromocytoma) require alpha- and beta-blocker treatment to lower blood pressure (phenoxybenzamine) and reduce tachycardia (propanolol) before surgical removal. The thyroid gland secretes triiodothyronine (T3) and thyroxine (T4). Hypothyroidism arises through iodine deficiency, autoimmunity or surgery: treatment is by replacement of T3 and T4. Hyperthyroidism is also an autoimmune disease, commonly Graves’ disease. Treatment is by selective destruction of thyroid cells by radioiodine. Alternatively thioureylenes (carbimazole) are used to inhibit iodination of thyroglobulin, thereby reducing T3 and T4 synthesis. The parathyroid gland contributes to serum calcium homeostasis by secreting parathyroid hormone. Hyperparathyroidism leads to hypercalcaemia, which is reversed by surgery or calcitonin treatment. Hypercalcaemia of malignancy is managed by bisphosphonates, which reduce bone turnover. Hypoparathyroidism and vitamin D deficiency lead to hypocalcaemia, which is treated by calcium and vitamin D metabolite replacement.