Page 3 of 10
PY8.1-7 | Endocrine Physiology — Part 2
Hypothyroidism vs. Hyperthyroidism: Physiological Basis of Clinical Features
Hypothyroidism vs Hyperthyroidism
| System | Hypothyroidism (Decreased TH) | Hyperthyroidism (Increased TH) |
|---|---|---|
| Metabolism/weight | Weight gain, decreased BMR | Weight loss despite increased appetite, increased BMR |
| Temperature | Cold intolerance | Heat intolerance, sweating |
| Cardiovascular | Bradycardia, pericardial effusion | Tachycardia, AF, wide pulse pressure |
| GIT | Constipation | Diarrhoea, increased motility |
| CNS | Lethargy, cognitive slowing, depression | Anxiety, irritability, fine tremor |
| Skin/hair | Dry skin, coarse hair, myxoedema | Warm moist skin, fine hair |
| Reflexes | Delayed relaxation of DTR | Brisk reflexes |
| TSH (primary) | Elevated | Suppressed (<0.01) |
| Free T4 | Low | High |
Hypothyroidism vs Hyperthyroidism
Figure: Hypothyroidism vs. Hyperthyroidism: Physiological Basis of Clinical Features
| System | Hypothyroidism (Decreased TH) | Hyperthyroidism (Increased TH) |
|---|---|---|
| Metabolism/weight | Weight gain, decreased BMR | Weight loss despite increased appetite, increased BMR |
| Temperature | Cold intolerance | Heat intolerance, sweating |
| Cardiovascular | Bradycardia, pericardial effusion | Tachycardia, AF, wide pulse pressure |
| GIT | Constipation | Diarrhoea, increased motility |
| CNS | Lethargy, cognitive slowing, depression | Anxiety, irritability, fine tremor |
| Skin/hair | Dry skin, coarse hair, myxoedema | Warm moist skin, fine hair |
| Reflexes | Delayed relaxation of DTR | Brisk reflexes |
| TSH (primary) | Elevated | Suppressed (<0.01) |
| Free T4 | Low | High |
Hypothyroidism vs Hyperthyroidism
| System | Hypothyroidism (Decreased TH) | Hyperthyroidism (Increased TH) |
|---|---|---|
| Metabolism/weight | Weight gain, decreased BMR | Weight loss despite increased appetite, increased BMR |
| Temperature | Cold intolerance | Heat intolerance, sweating |
| Cardiovascular | Bradycardia, pericardial effusion | Tachycardia, AF, wide pulse pressure |
| GIT | Constipation | Diarrhoea, increased motility |
| CNS | Lethargy, cognitive slowing, depression | Anxiety, irritability, fine tremor |
| Skin/hair | Dry skin, coarse hair, myxoedema | Warm moist skin, fine hair |
| Reflexes | Delayed relaxation of DTR | Brisk reflexes |
| TSH (primary) | Elevated | Suppressed (<0.01) |
| Free T4 | Low | High |
Understanding thyroid physiology lets you predict every clinical feature:
Figure: Hypothyroidism vs. Hyperthyroidism: Physiological Basis of Clinical Features
Hypothyroidism (↓ BMR, ↓ sympathetic tone, ↓ cardiac output):
- Weight gain (↓ BMR), cold intolerance (↓ thermogenesis), constipation (↓ gut motility)
- Bradycardia (↓ β1 receptor upregulation), pericardial effusion (↑ capillary permeability + ↓ lymphatic drainage)
- Dry skin, hair loss (↓ protein synthesis), periorbital/ankle myxoedema (accumulation of glycosaminoglycans)
- Lethargy, cognitive slowing, depression (↓ CNS metabolic rate)
- Delayed relaxation of deep tendon reflexes (classic sign — slowness of muscle relaxation)
- Lab: ↑ TSH, ↓ free T4
Causes: Hashimoto's thyroiditis (#1 worldwide), iodine deficiency (#1 in developing world), post-radioiodine, post-surgical.
Hyperthyroidism (↑ BMR, ↑ sympathetic-like effects — as in Kavya's case):
- Weight loss despite increased appetite, heat intolerance, sweating, diarrhoea
- Tachycardia, atrial fibrillation (especially in elderly), palpitations
- Tremor of outstretched hands, anxiety, emotional lability
- Proximal myopathy (catabolism of muscle), lid lag (Graves' specific: exophthalmos due to retroorbital inflammation)
- Lab: ↓ TSH (often undetectable), ↑ free T4 and T3
Causes of hyperthyroidism: Graves' disease (TSH receptor antibody), toxic multinodular goitre, toxic adenoma.
Treatment options: antithyroids (carbimazole), radioiodine (¹³¹I), thyroidectomy.
SELF-CHECK — : Thyroid & Pituitary
A 45-year-old woman has TSH = 18 mIU/L (high) and free T4 = 0.3 ng/dL (low). She complains of fatigue and weight gain. Which negative feedback loop is disrupted?
A. High T4 is failing to suppress TSH
B. Low T4 is failing to suppress TSH — the pituitary is appropriately increasing TSH
C. The hypothalamus is over-secreting somatostatin
D. ADH feedback to the posterior pituitary is interrupted
Reveal Answer
Answer: B. Low T4 is failing to suppress TSH — the pituitary is appropriately increasing TSH
A patient with Graves' disease undergoes radioiodine (¹³¹I) therapy. Which property of the thyroid gland makes this treatment possible?
A. Thyroglobulin binds radioiodine irreversibly
B. TPO converts radioiodine faster than stable iodine
C. The Na-I symporter actively concentrates iodine in follicular cells
D. Radioiodine is secreted by parafollicular C cells
Reveal Answer
Answer: C. The Na-I symporter actively concentrates iodine in follicular cells
Adrenal Cortex: Zones and Steroids
Adrenal Cortex — Zones, Hormones, and Disorders
| Zone | Hormone | Regulation | Main Actions | Excess Disorder | Deficiency Disorder |
|---|---|---|---|---|---|
| Glomerulosa | Aldosterone | RAAS, K+ | Na+ retention, K+ excretion | Conn's syndrome (hypertension, hypokalaemia) | Addison's (hypotension, hyperkalaemia) |
| Fasciculata | Cortisol | CRH → ACTH | Gluconeogenesis, anti-inflammatory, stress | Cushing's syndrome (moon face, central obesity) | Addison's (hypoglycaemia, fatigue) |
| Reticularis | DHEA, androstenedione | ACTH | Weak androgens; converted to testosterone/oestrogen peripherally | Virilisation in females (CAH) | Decreased libido (minor in males) |
Adrenal Cortex — Zones, Hormones, and Disorders
Figure: Adrenal Cortex: Zones and Steroids
| Zone | Hormone | Regulation | Main Actions | Excess Disorder | Deficiency Disorder |
|---|---|---|---|---|---|
| Glomerulosa | Aldosterone | RAAS, K+ | Na+ retention, K+ excretion | Conn's syndrome (hypertension, hypokalaemia) | Addison's (hypotension, hyperkalaemia) |
| Fasciculata | Cortisol | CRH → ACTH | Gluconeogenesis, anti-inflammatory, stress | Cushing's syndrome (moon face, central obesity) | Addison's (hypoglycaemia, fatigue) |
| Reticularis | DHEA, androstenedione | ACTH | Weak androgens; converted to testosterone/oestrogen peripherally | Virilisation in females (CAH) | Decreased libido (minor in males) |
Adrenal Cortex — Zones, Hormones, and Disorders
| Zone | Hormone | Regulation | Main Actions | Excess Disorder | Deficiency Disorder |
|---|---|---|---|---|---|
| Glomerulosa | Aldosterone | RAAS, K+ | Na+ retention, K+ excretion | Conn's syndrome (hypertension, hypokalaemia) | Addison's (hypotension, hyperkalaemia) |
| Fasciculata | Cortisol | CRH → ACTH | Gluconeogenesis, anti-inflammatory, stress | Cushing's syndrome (moon face, central obesity) | Addison's (hypoglycaemia, fatigue) |
| Reticularis | DHEA, androstenedione | ACTH | Weak androgens; converted to testosterone/oestrogen peripherally | Virilisation in females (CAH) | Decreased libido (minor in males) |
The adrenal cortex has three concentric zones — a useful mnemonic is GFR (which also means Glomerular Filtration Rate — helps you remember it):
Figure: Adrenal Cortex: Zones and Steroids
Glomerulosa → Mineralocorticoids (aldosterone)
Fasciculata → Glucocorticoids (cortisol)
Reticularis → Androgens (DHEA, androstenedione)
All are derived from cholesterol (hence connection to BI lipid metabolism).
Aldosterone (zona glomerulosa):
Regulation: primarily by RAAS (angiotensin II → aldosterone); also by ↑ plasma K⁺ (direct stimulation); weakly by ACTH.
Actions: Na⁺ retention, K⁺ secretion in collecting duct (ENaC channels). Net effect: ↑ blood volume → ↑ BP.
Excess: Conn's syndrome (primary hyperaldosteronism) — hypertension + hypokalaemia. Often from an adrenal adenoma.
Cortisol (zona fasciculata):
Regulation: CRH → ACTH → cortisol. Diurnal rhythm: peaks at 8 AM (awakening), nadir at midnight.
Actions:
- ↑ Gluconeogenesis, ↑ glycogenolysis, ↑ lipolysis → ↑ blood glucose (anti-insulin)
- Anti-inflammatory and immunosuppressive (used pharmacologically as prednisolone/dexamethasone)
- ↑ Protein catabolism (striae, muscle wasting, thin skin in excess)
- Permissive for catecholamine effects on blood vessels
- ↑ Renal free water clearance
Excess: Cushing's syndrome — central obesity, moon face, buffalo hump, hypertension, hyperglycaemia, striae, proximal myopathy, osteoporosis, immunosuppression.
Deficiency: Addison's disease (primary adrenal insufficiency) — fatigue, hypotension, hypoglycaemia, hyponatraemia, hyperkalaemia, hyperpigmentation (↑ ACTH/MSH).
Adrenal medulla:
Adrenaline (80%) and noradrenaline (20%) — synthesised from tyrosine, catecholamines, released in response to acute stress (fight-or-flight).
Actions: ↑ HR, ↑ CO, ↑ blood glucose (glycogenolysis), bronchodilation (β2), redistribution of blood flow (skin/gut vasoconstriction, skeletal muscle vasodilation).
Phaeochromocytoma: catecholamine-secreting tumour → paroxysmal hypertension, sweating, palpitations, headache.
Insulin and Glucagon: Glucose Homeostasis
Insulin vs Glucagon — Opposing Actions
| Parameter | Insulin (Fed State) | Glucagon (Fasted State) |
|---|---|---|
| Blood glucose effect | Lowers | Raises |
| Glycogen | Promotes synthesis (glycogenesis) | Promotes breakdown (glycogenolysis) |
| Gluconeogenesis | Inhibits | Stimulates |
| Lipolysis | Inhibits | Stimulates |
| Ketogenesis | Inhibits | Stimulates |
| Protein | Promotes synthesis | Promotes catabolism (amino acids for gluconeogenesis) |
| Potassium | Drives K+ into cells (lowers serum K+) | No direct effect |
| Secretion stimulus | High glucose, amino acids, incretins | Low glucose, amino acids, sympathetic |
Insulin vs Glucagon — Opposing Actions
Figure: Insulin and Glucagon: Glucose Homeostasis
| Parameter | Insulin (Fed State) | Glucagon (Fasted State) |
|---|---|---|
| Blood glucose effect | Lowers | Raises |
| Glycogen | Promotes synthesis (glycogenesis) | Promotes breakdown (glycogenolysis) |
| Gluconeogenesis | Inhibits | Stimulates |
| Lipolysis | Inhibits | Stimulates |
| Ketogenesis | Inhibits | Stimulates |
| Protein | Promotes synthesis | Promotes catabolism (amino acids for gluconeogenesis) |
| Potassium | Drives K+ into cells (lowers serum K+) | No direct effect |
| Secretion stimulus | High glucose, amino acids, incretins | Low glucose, amino acids, sympathetic |
Insulin vs Glucagon — Opposing Actions
| Parameter | Insulin (Fed State) | Glucagon (Fasted State) |
|---|---|---|
| Blood glucose effect | Lowers | Raises |
| Glycogen | Promotes synthesis (glycogenesis) | Promotes breakdown (glycogenolysis) |
| Gluconeogenesis | Inhibits | Stimulates |
| Lipolysis | Inhibits | Stimulates |
| Ketogenesis | Inhibits | Stimulates |
| Protein | Promotes synthesis | Promotes catabolism (amino acids for gluconeogenesis) |
| Potassium | Drives K+ into cells (lowers serum K+) | No direct effect |
| Secretion stimulus | High glucose, amino acids, incretins | Low glucose, amino acids, sympathetic |
Insulin (from β cells of islets of Langerhans) and glucagon (from α cells) are the primary regulators of blood glucose. They have opposing actions and are regulated primarily by blood glucose itself.
Figure: Insulin and Glucagon: Glucose Homeostasis
Insulin release:
- Primary stimulus: ↑ blood glucose → glucose enters β cells via GLUT2 → metabolised → ↑ ATP → closes K-ATP channels → depolarisation → Ca²⁺ influx → exocytosis of insulin granules
- Also stimulated by: amino acids, GLP-1 and GIP (incretin hormones from gut), vagal nerve, glucagon
- Inhibited by: hypoglycaemia, somatostatin, sympathetic (α2), fasting
Insulin actions (anabolic — all about storing fuel):
- Glucose: ↑ GLUT4 insertion in muscle and fat → glucose uptake; ↑ glycogen synthesis; ↓ gluconeogenesis
- Protein: ↑ amino acid uptake, ↑ protein synthesis, ↓ proteolysis
- Fat: ↑ lipogenesis, ↓ lipolysis, ↓ ketogenesis
- K⁺: ↑ cellular K⁺ uptake (used clinically to treat hyperkalaemia — insulin + glucose infusion)
Glucagon actions (catabolic — all about mobilising fuel):
- ↑ Glycogenolysis and ↑ gluconeogenesis (liver) → ↑ blood glucose
- ↑ Lipolysis → ↑ fatty acids → ↑ ketogenesis (important in T1DM: no insulin → unchecked glucagon → DKA)
- Glucagon not effective on muscle (muscle lacks glucagon receptors for glycogenolysis)
Insulin:glucagon ratio determines metabolic state:
- High ratio (fed state): anabolic — store fat, build protein, replenish glycogen
- Low ratio (fasted/starved): catabolic — break down glycogen, fat, (eventually) protein