Endocrine Physiology

🟢 Lite — Quick Review (1h–1d)

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Endocrine Physiology — Key Facts for NEET PG

• Hypothalamic-pituitary axes: HPA (adrenal), HPT (thyroid), HPG (gonadal), HPGH (somatotropic)
• Feedback loops: Most hormones regulated by negative feedback; exception: GnRH (pulsatile → no negative feedback on hypothalamus)
• G-proteins: Gs (↑ cAMP), Gq (↑ IP₃/DAG), Gi (↓ cAMP) — receptor downstream effects
• Hormone solubility: Steroids and thyroid hormones are lipophilic (need carriers); peptides are water-soluble
• ⚡ Exam tip: T3 is active hormone; T4 is prohormone (4× more potent when converted); Reverse T3 is inactive

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🟡 Standard — Regular Study (2d–2mo)

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Endocrine Physiology — NEET PG Study Guide

Hypothalamic-Pituitary Axis

Hypothalamus → Releasing/Inhibiting hormones → Anterior Pituitary → Tropic hormones → Target Glands

Hypothalamic Hormone	Pituitary Cell	Target Hormone
TRH	Thyrotrophs	TSH
CRH	Corticotrophs	ACTH
GnRH	Gonadotrophs	FSH, LH
GHRH / Somatostatin	Somatotrophs	GH
Dopamine (PIH)	Lactotrophs	Prolactin

Anterior Pituitary Hormones (mnemonic: “FLAT PEG”):

• FSH, LH, ACTH, TSH, PRL, GH

Posterior Pituitary (actually stores and releases, doesn’t synthesize):

• ADH (Vasopressin): From supraoptic nucleus
• Oxytocin: From paraventricular nucleus

⚡ Exam tip: Pineal gland secretes melatonin — regulates circadian rhythm;褪黑素 is inhibited by light (NREM promotion)

Thyroid Physiology

Thyroid Hormone Synthesis:

1. Iodide uptake: NIS (Na⁺/I⁻ cotransporter) — active transport against gradient
2. Iodination: I⁻ oxidized by thyroid peroxidase (TPO) → I₂ or I⁻
3. Organification: Iodination of tyrosine residues on thyroglobulin → MIT/DIT
4. Coupling: MIT + DIT → T₃; DIT + DIT → T₄ (on thyroglobulin)
5. Storage: Colloid (thyroglobulin)
6. Release: TSH stimulates endocytosis → proteolysis → free T₃/T₄

T₃ and T₄ Transport:

Hormone	% of Circulation	Half-life	Activity
T₄	~90%	7 days	Prohormone (weak)
T₃	~10%	1 day	Active hormone (4× more potent than T₄)

⚡ Exam tip: Pendrin (chloride-iodide transporter) — mutations → Pendred syndrome (deafness + goiter)

Adrenal Cortex

Zones and Hormones:

Zone	Hormones	Primary Function
Zona glomerulosa	Aldosterone	Mineralocorticoid (Na⁺, K⁺, BP)
Zona fasciculata	Cortisol	Glucocorticoid (glucose, stress)
Zona reticularis	DHEA, Androstenedione	Androgens

Cortisol Regulation:

• CRH (hypothalamus) → ACTH (anterior pituitary) → Cortisol (adrenal)
• Negative feedback: Cortisol inhibits CRH and ACTH
• Diurnal rhythm: Peak at 6–8 AM, nadir at midnight

Aldosterone Regulation:

• Primary: Renin-angiotensin-aldosterone system (RAAS)
• Secondary: ↑ K⁺, ↓ Na⁺ (direct)
• Tertiary: ACTH (minor role)

⚡ Exam tip: Addison disease (primary adrenal insufficiency): ↓ cortisol + ↑ ACTH; Cushing syndrome: ↑ cortisol ± ↑ ACTH; Distinguish cause by ACTH level and high-dose dexamethasone suppression

Pancreatic Hormones

Insulin (β cells):

• Anabolic hormone — stores nutrients
• Receptor: Tyrosine kinase receptor
• Effects: ↑ glucose uptake (GLUT4), ↑ glycogen synthesis, ↑ lipogenesis, ↑ protein synthesis
• Stimuli: ↑ glucose, ↑ amino acids, parasympathetic stimulation
• Inhibits: Gluconeogenesis, glycogenolysis, lipolysis

Glucagon (α cells):

• Catabolic hormone — mobilizes nutrients
• Receptor: GPCR (Gs → ↑ cAMP)
• Effects: ↑ glycogenolysis, ↑ gluconeogenesis, ↑ ketogenesis
• Stimuli: ↓ glucose, ↓ insulin, sympathetic stimulation, amino acids
• Inhibits: Glycogen synthesis

⚡ Exam tip: Sulfonylureas stimulate insulin release by closing K⁺-ATP channels on β cells → depolarization → Ca²⁺ entry → insulin exocytosis; Metformin activates AMPK → ↓ hepatic gluconeogenesis, ↑ insulin sensitivity

Parathyroid Hormone and Calcium

PTH (Chief cells of parathyroid):

• Receptor: GPCR (Gs → ↑ cAMP)
• Effects on bone: ↑ osteoclastic bone resorption → ↑ Ca²⁺ release
• Effects on kidney: ↑ Ca²⁺ reabsorption (DCT), ↓ phosphate reabsorption, ↑ 1-α-hydroxylase
• Effects on intestine: ↑ Ca²⁺ absorption (via ↑ active vitamin D)

Vitamin D Metabolism:

7-dehydrocholesterol (skin, UV) → Cholecalciferol (D₃) → Liver (25-OH) → Kidney (1-α-hydroxylase) → 1,25-(OH)₂D₃ (active)

⚡ Exam tip: PTHrP (PTH-related peptide) from squamous cell lung cancer → hypercalcemia of malignancy; Shares PTH1 receptor — indistinguishable biochemically from primary hyperparathyroidism

Growth Hormone

GH (Somatotrophs):

• Release: GHRH (stimulates), Somatostatin (inhibits), GH-inhibiting hormone = somatostatin
• Effects:
  • Directly: ↑ IGF-1 (liver), lipolysis, insulin resistance
  • Via IGF-1: Growth promotion, protein synthesis
• Regulation: Primarily by GHRH and somatostatin; also affected by sleep, exercise, stress, nutrition
• Secretion pattern: Pulses every 3–4 hours; biggest pulse during deep sleep (stage N3)

⚡ Exam tip: IGF-1 (Insulin-like Growth Factor 1) — mediates most GH effects; Used as screening test for acromegaly/GH deficiency; GH itself has short half-life (pulsatile), IGF-1 is stable

Adrenal Medulla

Chromaffin cells (modified postganglionic sympathetic neurons):

• Epinephrine (80%) and Norepinephrine (20%)
• Stimulus: Pre-ganglionic sympathetic cholinergic input (ACh → nicotinic receptors)
• Enzyme: Phenylethanolamine-N-methyltransferase (PNMT) — converts NE to E (requires cortisol from adjacent zona fasciculata)

Stress Response:

System	Activation	Effects
Sympathetic	↑	↑ HR, ↑ BP, bronchodilation, glycogenolysis
HPA axis	↑	↑ cortisol → gluconeogenesis, anti-inflammatory

⚡ Exam tip: Pheochromocytoma = catecholamine-secreting tumor; Episodic hypertension, headaches, sweating, palpitations; Diagnosed by urine metanephrines and plasma free metanephrines; Treatment: α-blocker first (phenoxybenzamine), then β-blocker

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🔴 Extended — Deep Study (3mo+)

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Endocrine Physiology — Comprehensive NEET PG Notes

Hormone Classification

By Chemical Structure:

Class	Examples	Solubility	Transport	Mechanism
Peptides/Proteins	Insulin, GH, PTH, ADH, oxytocin	Water	Free in plasma	Membrane receptors (GPCR/RTK)
Steroids	Cortisol, aldosterone, estrogen, testosterone	Lipid	Bound to proteins (CBG, SHBG)	Intracellular receptors
Amines	Epinephrine, thyroid hormones	Variable	Free + bound	Membrane/intracellular

By Mechanism:

Type	Second Messenger	Examples
cAMP	Gs (Gs → AC → ↑cAMP)	Glucagon, ADH (V2), TSH, FSH, LH
IP₃/DAG	Gq (Gq → PLC → IP₃ + DAG)	Angiotensin II, TRH, GnRH
Tyrosine kinase	Receptor auto-phosphorylation	Insulin, IGF, GH
Intracellular receptor	Steroid response elements	Steroids, T3, T4

⚡ Exam tip: Gs α-subunit mutations ( constitutively active) → McCune-Albright syndrome; Gi α-subunit mutations → ↓ cAMP → Albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)

Detailed Thyroid Physiology

Thyroid Hormone Actions:

• Basal metabolic rate: ↑ Na⁺/K⁺-ATPase → ↑ O₂ consumption
• Cardiovascular: ↑ β-adrenergic receptors → ↑ HR, ↑ contractility
• CNS: Normal development (myelination); excess → irritability
• Growth: Permissive for GH; required for normal development
• Lipid: ↑ lipolysis, ↓ cholesterol
• Carbohydrate: ↑ gluconeogenesis, ↑ glycogenolysis, ↑ insulin degradation

Thyroid Pathology:

Condition	TSH	T₃/T₄	Symptoms
Primary hypothyroidism	↑	↓	Cold intolerance, weight gain, bradycardia, dry skin
Primary hyperthyroidism	↓	↑	Heat intolerance, weight loss, tachycardia, exophthalmos
Secondary hypothyroidism	↓	↓	Central (pituitary)
Secondary hyperthyroidism	↑	↑	Central (ectopic ACTH)

⚡ Exam tip: Hashimoto thyroiditis = chronic lymphocytic thyroiditis = most common cause of hypothyroidism in iodine-sufficient areas; Anti-TPO antibodies; Progresses from hyperthyroid → euthyroid → hypothyroid

Thyroid Function Tests:

Test	Elevated In	Notes
TSH	Primary hypothyroidism, TSH-secreting adenoma	Best screening test
Free T₄	Hyperthyroidism, thyroid hormone resistance	Reflects active hormone
Free T₃	T₃ toxicosis	Not elevated in T₄ toxicosis
Thyroglobulin	Thyroiditis, overproduction	Tumor marker for thyroid cancer
TRIODOTHYRONINE RESIN UPTAKE (T₃RU)	↓ TBG	Inverse relationship with TBG

Detailed Adrenal Physiology

Cortisol Actions:

System	Effect
Metabolic	↑ gluconeogenesis, ↑ proteolysis, ↑ lipolysis, insulin resistance
抗应激	Permits catecholamine effects, ↑ vasopressor sensitivity
Anti-inflammatory	↓ phospholipase A₂, ↓ NF-κB, ↓ cytokine release, stabilize lysosomes
Cardiovascular	↑ catecholamine receptors, ↑ vascular tone
CNS	Mood regulation, appetite (orexigenic)

Cushing Syndrome:

Type	Cause	ACTH	24-hr Urine Cortisol	High-dose Dexamethasone
Cushing disease	Pituitary ACTH adenoma	↑	↑	Suppressible
Ectopic ACTH	Lung cancer, carcinoid	↑	↑	Not suppressible
Adrenal adenoma	Primary adrenal tumor	↓	↑	Not applicable
Exogenous	Steroid therapy	↓	↓	Not applicable

⚡ Exam tip: Nelson syndrome = pituitary corticotroph adenoma after bilateral adrenalectomy for Cushing disease → high ACTH → hyperpigmentation; Ectopic ACTH often from small cell lung carcinoma or bronchial carcinoid

Aldosterone Actions:

• Principal cells of collecting duct
• ↑ ENaC expression → ↑ Na⁺ reabsorption
• ↑ ROMK (K⁺ channels) → ↑ K⁺ secretion
• ↑ H⁺-ATPase (α-intercalated cells) → ↑ H⁺ secretion
• Net effect: ↑ Na⁺, H₂O → ↑ blood volume; ↑ K⁺ loss; ↑ H⁺ loss

Diabetes Mellitus

Type 1 DM:

• Autoimmune destruction of β cells
• Absolute insulin deficiency
• Young patients, lean, ketosis-prone
• Treatment: Insulin

Type 2 DM:

• Insulin resistance + relative insulin deficiency
• Older patients, obese, not ketosis-prone
• Treatment: Diet, oral hypoglycemics, insulin

Diabetic Complications:

Complication	Mechanism
DKA	Insulin deficiency → lipolysis → ketogenesis → metabolic acidosis
HHNK	Insulin deficiency + dehydration → hyperosmolar state
Microvascular	Hyperglycemia → AGEs → basement membrane thickening (retinopathy, nephropathy, neuropathy)
Macrovascular	Accelerated atherosclerosis (CAD, PVD, stroke)
Neuropathy	Nerve ischemia, sorbitol accumulation

⚡ Exam tip: Metabolic syndrome = central obesity + hypertension + dyslipidemia + insulin resistance; Criteria: ↑WC, ↑TG, ↓HDL, ↑BP, ↑ fasting glucose

Detailed Calcium-Phosphate Balance

Calcium Fractions:

Fraction	%	Notes
Ionized Ca²⁺	45%	Active, physiologically important
Protein-bound	40%	Mostly albumin
Complexed	15%	Bound to citrate, phosphate

⚡ Exam tip: Corrected calcium = Measured Ca + 0.8 × (4 − albumin); hypoalbuminemia → ↓ total Ca but ionized Ca normal (asymptomatic patient with low albumin-bound Ca)

Hypercalcemia ( mnemonic: “Stones, bones, groans, and psychiatric overtones”):

• Causes: Primary hyperparathyroidism, malignancy (PTHrP, bone mets), granulomas (1,25-OHvitD), thiazides, milk-alkali
• Symptoms: Constipation, nausea, polyuria, polydipsia, confusion, QT shortening
• Treatment: IV bisphosphonates, calcitonin, hydration

Hypocalcemia:

• Causes: Hypoparathyroidism (post-thyroidectomy), vitamin D deficiency, chronic kidney disease
• Symptoms: Perioral numbness, Chvostek sign (facial twitching), Trousseau sign (carpopedal spasm), QT prolongation, tetany
• Treatment: IV calcium gluconate

Parathyroid Hormone Related

PTH Actions Summary:

Target	Action	Net Effect
Bone	↑ osteoclast activity	↑ Ca²⁺, ↑ PO₄³⁻ release
Kidney	↑ Ca²⁺ reabsorption, ↓ PO₄³⁻ reabsorption, ↑ 1α-hydroxylase	↑ Ca²⁺, ↓ PO₄³⁻
Intestine	Via vitamin D activation	↑ Ca²⁺, ↑ PO₄³⁻ absorption

Growth Hormone Abnormalities

Acromegaly:

• GH excess after epiphyseal closure
• Features: Enlarged hands/feet, frontal bossing, prognathism, macroglossia, cardiomegaly, colon polyps
• Diagnosis: ↑ IGF-1, failure to suppress GH on OGTT
• Treatment: Surgery (transsphenoidal), octreotide (somatostatin analog), pegvisomant (GH receptor antagonist)

GH Deficiency:

• Short stature in children, ↑ adiposity, ↓ muscle mass
• In children: ↓ growth velocity, delayed bone age
• Diagnosis: ↓ IGF-1, GH stimulation test (insulin-induced hypoglycemia should ↑ GH)

Practice Questions for NEET PG

1. Compare the mechanisms of insulin and glucagon signaling.
2. Describe the thyroid hormone synthesis pathway step by step.
3. A patient has hypertension with hypokalemia. How do you differentiate primary aldosteronism from Cushing syndrome?
4. Explain how vitamin D and PTH work together to regulate calcium homeostasis.
5. What is the difference between Type 1 and Type 2 diabetes mellitus?
6. Describe the HPA axis and its regulation.
7. A patient with Addison disease presents with hyponatremia and hyperkalemia. Explain the electrolyte abnormalities.

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