Thyroid and Adrenal Physiology
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Direct answer
The thyroid secretes mostly thyroxine — 93 per cent T4 to 7 per cent T3 — yet T3 is three to four times more potent, and about 80 per cent of circulating T3 comes from peripheral 5-prime-deiodination of T4; T4's half-life of 6-7 days versus T3's single day reflects the gland's enormous colloid store, enough for two to three months. Synthesis runs iodide trapping by the NIS symporter, oxidation and organification by thyroid peroxidase, coupling of MIT and DIT, and proteolysis — the steps thioureas block and iodide excess briefly inhibits (the Wolff-Chaikoff effect). Thyroid hormone is the only hormone that raises the basal metabolic rate, from minus 40 to minus 50 in myxoedema to plus 60 or more in thyrotoxicosis. The adrenal cortex zones follow glomerulosa, fasciculata, reticularis — mineralocorticoids, glucocorticoids, androgens: aldosterone about 100-150 micrograms daily, cortisol 15-20 mg daily peaking at 6-8 in the morning (90 per cent transcortin-bound), and the adrenal medulla secretes roughly 80 per cent adrenaline to 20 per cent noradrenaline.
What you must remember
- Thyroid transport and potency: T4 93 per cent of output, T3 7 per cent but 3-4 times more potent; TBG carries about 70 per cent; free fraction is the active fraction; T4 half-life 6-7 days, T3 about 1 day.
- Synthesis steps: NIS iodide trapping (inhibited by thiocyanate, perchlorate), peroxidase-mediated organification and coupling (blocked by carbimazole and propylthiouracil), colloid storage for 2-3 months, proteolysis for release (stimulated by TSH).
- Special effects: Wolff-Chaikoff effect — high iodide acutely blocks organification (basis of preoperative iodide); Jod-Basedow phenomenon — iodine-induced thyrotoxicosis in a nodular gland; PTU additionally blocks peripheral T4-to-T3 conversion, preferred in thyroid storm.
- Metabolic footprint: BMR minus 40 to minus 50 in hypothyroidism, plus 60 to plus 100 in thyrotoxicosis; mandatory for infant brain development — iodine deficiency in the first years causes cretinism; permissive sensitisation of beta-adrenergic receptors explains tachycardia.
- Zone map: glomerulosa — aldosterone (angiotensin II and potassium controlled); fasciculata — cortisol (ACTH controlled); reticularis — androgens; medulla — adrenaline 80 per cent, noradrenaline 20 per cent with PNMT induced by locally high cortisol.
- Cortisol numbers: 15-20 mg/day, diurnal peak 6-8 AM and trough near midnight, 90 per cent protein-bound, half-life about 60-90 minutes; the 1 mg overnight dexamethasone test screens for Cushing syndrome.
- Adrenal failure: Addison disease — cortisol and aldosterone deficiency with hyperpigmentation from ACTH-POMC melanocyte stimulation, hyponatraemia and hyperkalaemia; congenital adrenal hyperplasia is 90-95 per cent 21-hydroxylase deficiency with androgen excess and salt wasting.
Two axes, two feedback loops
Contrast the control engineering of the two glands. The thyroid axis is slow, high-gain: TRH drives TSH, TSH drives synthesis and gland growth, and thyroid hormone feeds back on both — primary hypothyroidism shows high TSH with low T4, the screening exam's most repeated endocrine pattern, and a goitre is the visible endpoint of chronic TSH stimulation. The adrenal axis runs in circadian pulses: a morning cortisol after 1 mg overnight dexamethasone failing to suppress below 1.8 micrograms/dL flags Cushing syndrome, and a lost rhythm (high midnight cortisol) is the earliest sign. Aldosterone sits outside ACTH's thumbprint, regulated by renin-angiotensin and potassium — hence Conn syndrome's low renin with high aldosterone, and hypopituitary patients keeping mineralocorticoid function. These feedback geometries generate nearly every endocrine screening question.
How the exam frames it
Expect biochemical-pattern questions rather than mechanisms: high TSH with low free T4 (primary hypothyroidism), suppressed TSH with high T4 and a diffuse uptake (Graves disease with TSH-receptor antibodies), low cortisol with high ACTH and hyperpigmentation (Addison) versus low ACTH (secondary, pale patient). The pharmacology crossover is heavy: PTU is preferred in the first trimester, beta-blockers control adrenergic symptoms while antithyroid drugs work, and levothyroxine dosing is about 1.6 micrograms/kg/day. For phaeochromocytoma, remember the rule-of-tens teaching (about 10 per cent extra-adrenal, 10 per cent bilateral or familial) and the sequence of blockade — alpha with phenoxybenzamine before any beta-blocker, or the unopposed alpha effect storms the pressure.
Frequently asked questions
Why is T3 more potent than T4 although secreted in smaller amounts?
T3 binds the nuclear receptor with much higher affinity and is the active hormone at the tissue level; about 80 per cent of T3 arises from peripheral conversion of T4, which acts largely as a prohormone.
What is the Wolff-Chaikoff effect?
Acute inhibition of thyroid hormone organification by a large iodide load, used before thyroid surgery to reduce gland vascularity, typically escaping after several days.
Which adrenal cortex zone produces aldosterone and what controls it?
The zona glomerulosa, regulated mainly by angiotensin II and potassium rather than ACTH — the reason aldosterone survives pituitary failure.
What is the diagnostic cortisol pattern in Cushing syndrome?
Loss of diurnal rhythm with elevated late-night cortisol and failure of the 1 mg overnight dexamethasone test to suppress morning cortisol below about 1.8 micrograms/dL.
Which enzyme deficiency causes most congenital adrenal hyperplasia?
21-hydroxylase deficiency, about 90-95 per cent of cases, causing cortisol and aldosterone deficiency with androgen excess and salt-wasting crises in infancy.