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ENDOCRINE PHYSIOLOGY - SHORT NOTES (6 Marks Each)

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1. Secondary Messenger Mechanisms

Hormone binds GPCR
        ↓
G-protein (Gs) activated
        ↓
Adenylyl cyclase activated
        ↓
ATP → cAMP
        ↓
Protein Kinase A (PKA) activated
        ↓
Phosphorylation of target proteins → Cellular Response

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2. Classification of Hormone Receptors - 4 Types (G Protein)

G-protein Coupled Receptors
        ├── Gs (stimulatory) → ↑ cAMP → PKA
        ├── Gi (inhibitory)  → ↓ cAMP
        └── Gq              → ↑ IP3 + DAG → Ca²+, PKC

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3. Acromegaly

• Facial: Prominent supraorbital ridges, prognathism (jaw protrusion), wide nose
• Hands/Feet: Spade-like hands, large feet (ring/shoe size increase)
• Skin: Oily, hyperhidrosis, skin tags
• Soft tissue: Macroglossia, organomegaly
• Metabolic: Diabetes mellitus (GH is anti-insulin), hypertension
• Local tumor effects: Bitemporal hemianopia, headache

Pituitary Adenoma
        ↓
Excess GH secretion
        ↓
↑ IGF-1 (Somatomedin C) from liver
        ↓
Soft tissue & bone growth (epiphyses fused)
        ↓
Acral enlargement + Organomegaly

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4. Dwarfism

↓ GHRH or pituitary damage
        ↓
↓ GH secretion
        ↓
↓ IGF-1 production
        ↓
↓ Bone growth (open epiphyses in child)
        ↓
Proportionate short stature

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5. Diabetes Insipidus (DI) - Central vs Nephrogenic

Pituitary lesion (Central) OR Renal resistance (Nephrogenic)
                ↓
↓ ADH action on collecting duct
                ↓
↓ Water reabsorption (aquaporin-2 not inserted)
                ↓
Large volume dilute urine (Polyuria)
                ↓
Thirst → Polydipsia (compensatory)

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6. Milk Ejection Reflex (Neurohormonal Reflex)

Infant suckles the nipple
        ↓
Sensory nerve impulses (afferent)
        ↓
Hypothalamus (Paraventricular Nucleus)
        ↓
Oxytocin released from Posterior Pituitary
        ↓
Myoepithelial cells of mammary gland contract
        ↓
Milk ejected into lactiferous sinuses → Infant feeds

• Also called "Let-down reflex"
• Can be triggered by sight/cry of baby (conditioned reflex)
• Inhibited by stress, pain, alcohol (via catecholamines suppressing oxytocin)
• Prolactin maintains milk production; Oxytocin ejects milk
• Suckling also → ↑ Prolactin (suppresses ovulation - lactational amenorrhea)

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7. Graves' Disease

Autoimmune trigger
        ↓
B cells produce TSI (IgG antibodies)
        ↓
TSI bind TSH receptors on thyroid
        ↓
Continuous stimulation (like TSH)
        ↓
↑↑ T3 and T4 synthesis and release
        ↓
Hyperthyroidism (NOT suppressed by feedback)

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8. Hypothyroidism - Myxedema, Cretinism, Hashimoto's Disease

• Weight gain, cold intolerance, bradycardia, constipation, dry skin, delayed reflexes

• Non-pitting edema due to accumulation of glycosaminoglycans (hyaluronic acid) in tissues
• Myxedema coma: Severe hypothyroidism → ↓ consciousness, hypothermia, hypoventilation (emergency)

↓ Thyroid hormone in fetus/neonate
        ↓
↓ Brain development + ↓ Bone growth
        ↓
Mental retardation (irreversible)
        ↓
Short stature, pot belly, protruding tongue
        ↓
"Cretin" appearance

• Prevention: Neonatal TSH screening + early T4 replacement
• Most common cause: Iodine deficiency globally; Thyroid dysgenesis in developed countries

• Autoimmune destruction of thyroid (CD8+ T cells + Anti-TPO, Anti-thyroglobulin antibodies)
• Most common cause of hypothyroidism in iodine-sufficient areas
• Painless goiter initially → hypothyroidism eventually
• "Hashitoxicosis" - transient hyperthyroidism early due to release of stored hormones

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9. Parathyroid Hormone (PTH) - Function and Regulation

↓ Serum Ca²+ (main stimulus)
        ↓
Chief cells of Parathyroid sense via CaSR
        ↓
↑ PTH secretion
        ↓
↑ Ca²+ (bone + kidney + gut)
        ↓
Negative feedback → ↓ PTH

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10. Cortisol - Functions

Stress / Low cortisol
        ↓
Hypothalamus → CRH
        ↓
Anterior Pituitary → ACTH
        ↓
Adrenal Cortex (Zona Fasciculata)
        ↓
Cortisol secreted
        ↓
Negative feedback to hypothalamus & pituitary

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11. Cushing's Syndrome

Cushing's Syndrome
        ├── ACTH-dependent (80%)
        │       ├── Cushing's DISEASE (pituitary adenoma) - most common
        │       └── Ectopic ACTH (lung small cell carcinoma)
        └── ACTH-independent (20%)
                ├── Adrenal adenoma/carcinoma
                └── Iatrogenic (exogenous steroids) - most common overall

• C - Central obesity, moon face, buffalo hump
• U - Urinary free cortisol ↑ (diagnostic)
• S - Striae (purple), Skin thinning
• H - Hypertension, Hyperglycemia
• I - Infections (immunosuppressed)
• N - aNorexia (muscle wasting), osteoporosis
• G - Gonadal dysfunction (amenorrhea, impotence)
• S - Screening: 24h UFC, overnight dexamethasone suppression test

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12. Pheochromocytoma

• 10% bilateral, 10% malignant, 10% extra-adrenal, 10% familial, 10% in children

↑↑ Catecholamine release
        ↓
        ├── Hypertension (paroxysmal/sustained) - hallmark
        ├── Headache (pounding)
        ├── Palpitations
        ├── Profuse sweating
        └── Pallor (not flushing)

• ↑ 24h urine metanephrines/VMA (vanillylmandelic acid) - most sensitive
• CT/MRI abdomen (localization)
• MIBG scan (functional imaging)

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13. Insulin - Mechanism of Action, Effects, and Somatomedin C

Insulin binds to insulin receptor (Tyrosine Kinase receptor)
        ↓
Receptor autophosphorylation (tyrosine residues)
        ↓
IRS-1 phosphorylation
        ↓
PI3K pathway → Akt activation
        ↓
GLUT-4 translocation to cell membrane
        ↓
Glucose uptake into cells (muscle, fat)

• Produced by liver in response to GH
• Mediates most anabolic/growth effects of GH
• Acts via IGF-1 receptor (tyrosine kinase, similar to insulin receptor)
• Has insulin-like effects (hence the name somatomedin C / insulin-like growth factor)
• Feedback: ↑ IGF-1 → ↓ GH from pituitary (short-loop feedback)
• Low in GH deficiency; Low in malnutrition (despite normal/high GH)

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14. Addison's Disease and Addisonian Crisis

• Autoimmune (most common in developed countries - 80%)
• TB (most common globally)
• Waterhouse-Friderichsen syndrome (meningococcal sepsis → bilateral adrenal hemorrhage)

↓ Cortisol                    ↓ Aldosterone
        ↓                             ↓
Weakness, fatigue          Na+ loss, K+ retention
Weight loss                Hypotension, dehydration
Hypoglycemia               Hyponatremia, Hyperkalemia
↑ ACTH (feedback)
        ↓
↑ MSH (same precursor POMC)
        ↓
Hyperpigmentation (buccal mucosa, skin creases)

• Precipitated by infection, surgery, trauma in Addison's patient
• Features: Severe hypotension, vomiting, abdominal pain, hypoglycemia, confusion → life-threatening
• Treatment: IV hydrocortisone 100mg stat, IV fluids (normal saline), glucose

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15. SIADH (Syndrome of Inappropriate ADH Secretion)

• CNS: Meningitis, head injury, stroke, brain tumors
• Pulmonary: TB, pneumonia, SCLC (ectopic ADH)
• Drugs: Carbamazepine, SSRIs, cyclophosphamide, vincristine
• Hypothyroidism, Addison's disease

Excess ADH (inappropriate)
        ↓
↑ Water reabsorption in collecting duct (aquaporin-2)
        ↓
↑ Total body water → Dilutional Hyponatremia
        ↓
↑ Blood volume → ↑ ANP → Na+ excretion (normovolemic state)
        ↓
Euvolemic hyponatremia (key diagnostic feature)

• Fluid restriction (800-1000 mL/day) - first line
• Hypertonic saline (3% NaCl) - for severe symptomatic hyponatremia
• Vaptans (Tolvaptan - V2 receptor antagonist) - for chronic SIADH
• Treat underlying cause

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16. Adrenal Medulla

• Epinephrine (Adrenaline): 80%
• Norepinephrine (Noradrenaline): 20%
• Small amounts of dopamine

Tyrosine → DOPA → Dopamine → Norepinephrine → Epinephrine
                                                    ↑
                              PNMT enzyme (requires cortisol from cortex)

Stress/Emergency
        ↓
Sympathetic preganglionic fibers (ACh) → Adrenal Medulla
        ↓
Mass discharge of Epinephrine + Norepinephrine
        ↓
↑ HR, ↑ BP, ↑ Blood glucose, ↑ Blood flow to muscles
Bronchodilation, ↓ GI motility, Pupil dilation
        ↓
Body prepared for fight or flight

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QUICK REVISION TABLE - All 16 Topics

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Exam Tips:

• Most commonly asked in case-based format: Cushing's, Addison's, Pheochromocytoma, SIADH
• Always mention investigations + treatment for clinical topics
• Draw the regulation flowcharts (hypothalamus-pituitary-end organ axis) for essay topics too
• ★★★★ starred topics from your question bank: Dwarfism, Graves', Hashimoto's, Acromegaly, Diabetes Insipidus - study these thoroughly