Endocrinology Syllabus

Contrast diabetes insipidus (DI) with SIADH.

DI = ADH deficiency (central) or resistance (nephrogenic) → dilute polyuria, hypernatremia, high plasma osmolarity. SIADH = excess ADH → water retention, dilute concentrated urine, hyponatremia, low plasma osmolarity.

What are the two main physiological actions of oxytocin?

Milk ejection (let-down) via contraction of mammary myoepithelial cells, and uterine smooth muscle contraction during labor. Both operate via positive feedback.

Outline the steps of thyroid hormone synthesis.

1) Iodide trapping via the $\ce{Na+/I-}$ symporter; 2) Oxidation of iodide by thyroid peroxidase; 3) Organification—iodination of tyrosine residues on thyroglobulin to form MIT and DIT; 4) Coupling: $DIT + DIT \to T_{4}$, $MIT + DIT \to T_{3}$; 5) Endocytosis and proteolysis of thyroglobulin to release $T_{3}$ and $T_{4}$.

What enzyme catalyzes iodide oxidation and coupling in the thyroid, and what drug inhibits it?

Thyroid peroxidase (TPO). It is inhibited by the thioamide drugs propylthiouracil (PTU) and methimazole.

Which is the more active thyroid hormone, and how is it mainly produced peripherally?

$T_{3}$ (triiodothyronine) is 3–4 times more potent than $T_{4}$. Most circulating $T_{3}$ is produced peripherally by 5'-deiodinase removing one iodine from $T_{4}$ (thyroxine).

What is the main plasma carrier protein for thyroid hormones, and which form is biologically active?

Thyroxine-binding globulin (TBG) carries most $T_{4}$/$T_{3}$. Only the small free (unbound) fraction is biologically active.

Which additional hormone does the thyroid produce, and what is its function?

Calcitonin, produced by the parafollicular (C) cells. It lowers blood calcium by inhibiting osteoclast activity (opposing PTH).

List the major physiological effects of thyroid hormone.

Increases basal metabolic rate and $\ce{O2}$ consumption (calorigenic effect), increases heat production, enhances catecholamine sensitivity (up-regulates β-adrenergic receptors), promotes normal growth and CNS maturation, and increases carbohydrate/lipid metabolism.

What is the effect of thyroid hormone on the heart, and by what mechanism?

It increases heart rate and contractility (positive chronotropic and inotropic effects), largely by up-regulating β-adrenergic receptors and increasing catecholamine sensitivity, raising cardiac output.

Compare the lab findings of primary hypothyroidism and primary hyperthyroidism.

Primary hypothyroidism: low free $T_{4}$, high TSH. Primary hyperthyroidism: high free $T_{4}$/$T_{3}$, low TSH (due to negative feedback).

What is the most common cause of hypothyroidism and of hyperthyroidism in iodine-sufficient areas?

Most common hypothyroidism: Hashimoto's (chronic autoimmune) thyroiditis. Most common hyperthyroidism: Graves' disease (TSH-receptor stimulating autoantibodies).

List classic clinical features of hyperthyroidism.

Weight loss with increased appetite, heat intolerance, tachycardia/palpitations, tremor, anxiety, sweating, diarrhea, and (in Graves') exophthalmos and goiter.

List classic clinical features of hypothyroidism.

Weight gain, cold intolerance, fatigue, bradycardia, constipation, dry skin, hair loss, depression, and in severe cases myxedema. Congenital deficiency causes cretinism.

What is the source and primary stimulus for parathyroid hormone (PTH) secretion?

PTH is secreted by the chief cells of the parathyroid glands. Its primary stimulus is a fall in serum ionized calcium ($\ce{Ca^{2+}}$), sensed by the calcium-sensing receptor.

What are the three main target actions of PTH on calcium and phosphate?

1) Bone: stimulates osteoclastic resorption → releases $\ce{Ca^{2+}}$ and phosphate; 2) Kidney: increases $\ce{Ca^{2+}}$ reabsorption and phosphate excretion; 3) Kidney: activates $1\alpha$-hydroxylase to form active vitamin D. Net effect: raises serum $\ce{Ca^{2+}}$, lowers serum phosphate.

How do PTH and calcitonin oppose each other?

PTH raises serum calcium (bone resorption, renal $\ce{Ca^{2+}}$ retention, vitamin D activation). Calcitonin lowers serum calcium (inhibits osteoclasts, promotes renal calcium excretion).

Describe the activation pathway of vitamin D to its active form.

Skin: $\ce{7\text{-}dehydrocholesterol} ->[\text{UVB}] \text{cholecalciferol (D3)}$. Liver: 25-hydroxylase → 25-hydroxyvitamin D (calcidiol). Kidney: $1\alpha$-hydroxylase → 1,25-dihydroxyvitamin D (calcitriol), the active form.

What are the main actions of active vitamin D (calcitriol)?

Increases intestinal absorption of both calcium and phosphate, promotes bone mineralization, and increases renal reabsorption of calcium and phosphate—overall raising serum $\ce{Ca^{2+}}$ and phosphate.

What diseases result from vitamin D deficiency in children versus adults?

Children: rickets (defective bone mineralization, bowed legs). Adults: osteomalacia (soft, weak bones).

Compare the causes and calcium levels in hyperparathyroidism and hypoparathyroidism.

Hyperparathyroidism (often parathyroid adenoma): high PTH → hypercalcemia, hypophosphatemia. Hypoparathyroidism (often surgical): low PTH → hypocalcemia, hyperphosphatemia.

What are classic signs of hypocalcemia?

Neuromuscular excitability: tetany, perioral tingling, muscle cramps, and positive Chvostek's sign (facial twitch) and Trousseau's sign (carpal spasm with BP cuff).

List common symptoms of hypercalcemia.

'Stones, bones, groans, and psychiatric moans': kidney stones, bone pain, abdominal/GI upset (constipation), and neuropsychiatric changes (fatigue, confusion), plus polyuria and shortened QT interval.

Outline the regulation of aldosterone secretion.

Aldosterone (zona glomerulosa) is stimulated mainly by angiotensin II (via the renin–angiotensin system triggered by low blood pressure/volume or low $\ce{Na+}$) and by high plasma $\ce{K+}$; ACTH plays a minor role.

What are the main actions of aldosterone?

Acts on the renal distal tubule/collecting duct to increase $\ce{Na+}$ (and water) reabsorption and increase $\ce{K+}$ and $\ce{H+}$ excretion—raising blood volume/pressure.

What are the major metabolic actions of cortisol?

Increases blood glucose via gluconeogenesis, promotes protein catabolism and lipolysis, is anti-inflammatory/immunosuppressive, is permissive for catecholamine vascular effects, and helps the body respond to stress. Secretion follows a diurnal rhythm (peak in early morning).

Contrast Cushing's syndrome and Addison's disease.

Cushing's syndrome = cortisol excess → central obesity, moon face, striae, hyperglycemia, hypertension, muscle wasting. Addison's disease = primary adrenocortical insufficiency (cortisol + aldosterone deficiency) → fatigue, weight loss, hypotension, hyperpigmentation, hyponatremia, hyperkalemia.

Why does primary adrenal insufficiency (Addison's) cause hyperpigmentation?

Low cortisol removes negative feedback, so ACTH rises. ACTH is cleaved from POMC along with MSH, and high ACTH/MSH stimulates melanocytes, causing skin hyperpigmentation.

What is the main hormone of the adrenal medulla and what regulates its release?

Epinephrine (adrenaline), with some norepinephrine. The medulla is a modified sympathetic ganglion; release is triggered by preganglionic sympathetic (acetylcholine) stimulation during stress ('fight or flight').

What tumor arises from the adrenal medulla, and what is its classic presentation?

Pheochromocytoma—a catecholamine-secreting tumor causing episodic hypertension, headache, palpitations, sweating, and tachycardia.

Describe insulin secretion regulation and its main actions.

Insulin (β-cells of pancreatic islets) is secreted in response to high blood glucose. It lowers blood glucose by promoting cellular glucose uptake (GLUT4 in muscle/fat), glycogenesis, lipogenesis, and protein synthesis; it is the body's main anabolic hormone.

Compare the actions of insulin and glucagon.

Insulin (β-cells) lowers blood glucose: uptake, glycogenesis, lipogenesis (anabolic). Glucagon (α-cells) raises blood glucose: glycogenolysis, gluconeogenesis, lipolysis/ketogenesis (catabolic). They are antagonistic and maintain glucose homeostasis.

Contrast the pathophysiology of Type 1 and Type 2 diabetes mellitus.

Type 1: autoimmune destruction of β-cells → absolute insulin deficiency; typically young, prone to diabetic ketoacidosis, needs insulin. Type 2: peripheral insulin resistance with relative insulin deficiency; associated with obesity, adult onset, prone to hyperosmolar hyperglycemic state.