ENDOCRINE SYSTEM

I. ANATOMY OF THE ENDOCRINE SYSTEM

✔ Definition & Importance

The Endocrine System consists of ductless glands that secrete hormones directly into the bloodstream.
Works in coordination with the nervous system to regulate growth, metabolism, reproduction, homeostasis, and stress responses.

1. Hypothalamus (Master Regulator of Endocrine System)

✔ Location:

Situated in the diencephalon, just above the pituitary gland.
✔ Structure:
Composed of specialized neurosecretory cells that regulate hormone secretion from the pituitary gland.
✔ Hormones Secreted:
Corticotropin-releasing hormone (CRH) → Stimulates ACTH secretion.
Thyrotropin-releasing hormone (TRH) → Stimulates TSH secretion.
Gonadotropin-releasing hormone (GnRH) → Stimulates FSH & LH secretion.
Growth hormone-releasing hormone (GHRH) → Stimulates GH release.
Dopamine (Prolactin-inhibiting factor, PIF) → Inhibits Prolactin secretion.

2. Pituitary Gland (Master Gland of the Endocrine System)

✔ Location:

Lies within the sella turcica of the sphenoid bone.
✔ Divisions & Hormones:
Anterior Pituitary (Adenohypophysis)
- TSH → Thyroid stimulation.
- ACTH → Adrenal cortex stimulation.
- FSH & LH → Gonadal function.
- GH → Growth & metabolism.
- Prolactin → Milk secretion.
Posterior Pituitary (Neurohypophysis)
- ADH (Vasopressin) → Water retention.
- Oxytocin → Uterine contraction & lactation.

3. Thyroid Gland

✔ Location:

Anterior to the trachea, below the larynx, consisting of two lobes connected by an isthmus.
✔ Structure:
Made of follicular cells (secrete T3 & T4) and parafollicular cells (C cells) (secrete calcitonin).
✔ Hormones:
T3 (Triiodothyronine) → More active, regulates metabolism.
T4 (Thyroxine) → Less active, converted to T3 in peripheral tissues.
Calcitonin → Lowers serum calcium levels.

4. Parathyroid Glands

✔ Location:

Four small glands located behind the thyroid gland.
✔ Hormone Secreted:
Parathyroid Hormone (PTH) → Increases blood calcium by stimulating osteoclasts, increasing renal calcium reabsorption, and activating Vitamin D.

5. Adrenal Glands

✔ Location:

Situated above each kidney, consisting of cortex & medulla.
✔ Structure & Hormones:
Adrenal Cortex (Outer layer):
- Zona Glomerulosa → Secretes Aldosterone (Mineralocorticoid) for sodium retention.
- Zona Fasciculata → Secretes Cortisol (Glucocorticoid) for stress response & metabolism.
- Zona Reticularis → Produces Androgens (DHEA) for secondary sexual characteristics.
Adrenal Medulla (Inner layer):
- Produces Epinephrine & Norepinephrine (Catecholamines) for the fight-or-flight response.

6. Pancreas (Mixed Exocrine & Endocrine Gland)

✔ Location:

Lies retroperitoneally in the upper abdomen (head, body, and tail).
✔ Endocrine Function (Islets of Langerhans):
β-cells → Secrete Insulin (lowers blood glucose).
α-cells → Secrete Glucagon (raises blood glucose).
δ-cells → Secrete Somatostatin (inhibits insulin & glucagon).

7. Gonads (Testes & Ovaries)

✔ Location:

Testes (Scrotum) → Male gonads.
Ovaries (Pelvic cavity) → Female gonads.
✔ Hormones:
Testosterone → Male reproductive function.
Estrogen & Progesterone → Female reproductive function.

II. PHYSIOLOGY OF THE ENDOCRINE SYSTEM

✔ General Functions of Hormones

Maintain homeostasis (e.g., glucose, calcium levels).
Regulate growth & development (GH, IGF-1).
Modulate metabolism & energy balance (Thyroid hormones).
Control reproduction & sexual differentiation (FSH, LH, Estrogen, Testosterone).

1. Hypothalamic-Pituitary Axis (HPA System)

✔ Hypothalamus regulates pituitary secretion via releasing & inhibiting hormones.
✔ Negative feedback loops control hormone levels.

2. Thyroid Hormones & Metabolism

✔ T3/T4 regulate basal metabolic rate (BMR) by increasing mitochondrial activity.
✔ Effects:

Increases oxygen consumption & heat production.
Stimulates protein synthesis & glucose utilization.

3. Cortisol & Stress Response

✔ Effects of Cortisol:

Increases blood glucose via gluconeogenesis.
Suppresses immune system.
Promotes lipolysis & muscle catabolism.

4. Insulin & Glucagon (Glucose Homeostasis)

✔ Insulin (Secreted after meals) → Lowers blood glucose by promoting glucose uptake & glycogenesis.
✔ Glucagon (Secreted during fasting) → Raises blood glucose by stimulating glycogenolysis & gluconeogenesis.

5. Growth Hormone (GH) & IGF-1

✔ Functions:

Stimulates bone growth & muscle anabolism.
Increases lipolysis & protein synthesis.

6. ADH & Water Regulation

✔ Effects:

Promotes water reabsorption in kidneys.
Regulates blood pressure & osmolarity.

7. Reproductive Hormones

✔ Testosterone → Promotes spermatogenesis & secondary male characteristics.
✔ Estrogen & Progesterone → Regulate ovulation & menstrual cycle.

CONCLUSION

The Endocrine System regulates growth, metabolism, reproduction, and homeostasis via hormonal feedback mechanisms.
Understanding endocrine physiology is critical for diagnosing and managing hormonal disorders.
Dysfunctions result in diseases like Diabetes, Thyroid Disorders, Cushing’s, Addison’s, and Pituitary Disorders.

PATHOLOGY OF THE ENDOCRINE SYSTEM

I. GENERAL PATHOLOGY OF THE ENDOCRINE SYSTEM

✔ Endocrine Disorders Classification

Hypofunction → Hormone deficiency due to autoimmune destruction, infection, infarction, genetic defects.
Hyperfunction → Excess hormone secretion due to tumors, autoimmune stimulation, ectopic production.
Receptor Defects → Target tissue resistance to hormones (e.g., Insulin resistance in Type 2 Diabetes).

II. PATHOLOGY OF INDIVIDUAL GLANDS

1. Hypothalamic-Pituitary Disorders

✔ Pituitary Adenomas (Most common)

Prolactinoma → Causes galactorrhea, amenorrhea, infertility.
GH-secreting adenoma → Causes Acromegaly (adults) / Gigantism (children).
ACTH-secreting adenoma → Causes Cushing’s disease.

✔ Hypopituitarism (Panhypopituitarism)

Causes: Sheehan’s Syndrome (postpartum infarction), pituitary apoplexy (hemorrhage), tumors, radiation.
Symptoms: Fatigue, infertility, cold intolerance, growth retardation.

✔ Diabetes Insipidus (ADH Deficiency)

Polyuria, polydipsia, hypernatremia, low urine osmolality.
Central DI → Lack of ADH from pituitary.
Nephrogenic DI → Renal resistance to ADH.

✔ SIADH (Syndrome of Inappropriate ADH Secretion)

Causes hyponatremia, low serum osmolality, concentrated urine.
Causes: Lung cancer (paraneoplastic), CNS disorders, drugs (carbamazepine, SSRIs).

2. Thyroid Disorders

✔ Hyperthyroidism (Thyrotoxicosis)

Graves’ Disease (Autoimmune, TSH receptor stimulation).
Toxic Multinodular Goiter.
Thyroid Storm (Life-threatening emergency).
Symptoms: Heat intolerance, weight loss, tachycardia, exophthalmos, tremors.

✔ Hypothyroidism

Hashimoto’s Thyroiditis (Autoimmune, anti-TPO antibodies).
Iodine Deficiency (Endemic goiter).
Symptoms: Cold intolerance, weight gain, bradycardia, lethargy, dry skin.

✔ Thyroid Nodules & Cancer

Papillary Carcinoma → Most common, good prognosis.
Follicular Carcinoma → Hematogenous spread.
Medullary Carcinoma → Associated with MEN 2, produces calcitonin.
Anaplastic Carcinoma → Poor prognosis, rapidly growing.

3. Parathyroid Disorders

✔ Hyperparathyroidism

Primary → Parathyroid adenoma.
Secondary → Chronic kidney disease.
Symptoms: Hypercalcemia (bones, stones, abdominal groans, psychic moans).

✔ Hypoparathyroidism

Causes: Surgery, autoimmune disease.
Symptoms: Hypocalcemia (tetany, Chvostek’s & Trousseau’s signs, seizures, arrhythmias).

4. Adrenal Disorders

✔ Cushing’s Syndrome (Hypercortisolism)

Causes: Pituitary ACTH tumor, adrenal adenoma, ectopic ACTH (small cell lung cancer).
Symptoms: Moon face, buffalo hump, striae, osteoporosis, hypertension, hyperglycemia.

✔ Addison’s Disease (Adrenal Insufficiency)

Causes: Autoimmune destruction, TB, metastases.
Symptoms: Hyperpigmentation, hypotension, weight loss, hyponatremia, hyperkalemia.

✔ Pheochromocytoma (Adrenal Medulla Tumor)

Symptoms: Episodic hypertension, palpitations, sweating, headaches.
Diagnosed by elevated metanephrines & catecholamines.

5. Pancreatic Disorders (Diabetes Mellitus)

✔ Type 1 DM (Autoimmune destruction of β-cells)

Insulin deficiency → Hyperglycemia, weight loss, DKA risk.

✔ Type 2 DM (Insulin resistance)

Associated with obesity, metabolic syndrome.
Can cause hyperosmolar hyperglycemic state (HHS).

✔ Diabetic Complications

Macrovascular: Stroke, MI, PAD.
Microvascular: Retinopathy, Nephropathy, Neuropathy.

III. CLINICAL EXAMINATION OF THE ENDOCRINE SYSTEM

✔ General Inspection

Obesity (Cushing’s, Hypothyroidism), Cachexia (Addison’s, DM-1).
Skin changes: Hyperpigmentation (Addison’s), Myxedema (Hypothyroidism), Vitiligo (Autoimmune).
Hair distribution: Hirsutism (PCOS, Cushing’s), Loss of outer eyebrows (Hypothyroidism).

✔ Head & Neck Examination

Goiter (Thyroid enlargement, Graves’, Iodine deficiency).
Exophthalmos (Graves’ disease).

✔ Cardiovascular Examination

Tachycardia (Hyperthyroidism, Pheochromocytoma).
Bradycardia (Hypothyroidism, Addison’s).

✔ Neurological Examination

Tremors (Hyperthyroidism, Pheochromocytoma).
Hyporeflexia (Hypothyroidism), Hyperreflexia (Hyperthyroidism).

✔ Special Tests

Chvostek’s Sign (Facial spasm in Hypocalcemia).
Trousseau’s Sign (Carpopedal spasm in Hypocalcemia).

IV. DIFFERENTIAL DIAGNOSIS & CONFIRMATORY DIAGNOSIS

✔ Hyperthyroidism

Graves’ Disease → Diffuse goiter, exophthalmos, low TSH, high T3/T4.
Toxic Multinodular Goiter → Nodular thyroid, no eye signs.

✔ Hypothyroidism

Hashimoto’s Thyroiditis → Anti-TPO antibodies, goiter.
Iodine Deficiency → Low T3/T4, goiter.

✔ Diabetes Mellitus

Type 1 → Autoimmune, low insulin, GAD antibodies.
Type 2 → Insulin resistance, obesity, metabolic syndrome.

✔ Cushing’s Syndrome

Pituitary ACTH tumor (Cushing’s Disease) → High ACTH, suppresses with dexamethasone.
Adrenal Adenoma → Low ACTH, no suppression with dexamethasone.

✔ Pheochromocytoma

Diagnosed by 24-hour urine metanephrines, plasma catecholamines.

CONCLUSION

Endocrine disorders present with systemic manifestations due to hormone imbalances.
Clinical examination is crucial in differentiating conditions like thyroid disorders, diabetes, adrenal insufficiency, and pituitary abnormalities.
High-yield diagnostic tools include hormonal assays, imaging, and stimulation/suppression tests.
Mastering pathology, clinical examination, and diagnosis is essential for both entrance exams and clinical practice.

CLINICAL INSIGHT DIALOGUES By Dr Jayaram Krishna M

Thursday, March 20, 2025