Pathology of the parathyroid glands

1. Anatomy + Function

• 4 parathyroid glands on posterior thyroid (upper + lower poles of each lobe).
• Composed of chief cells containing secretory granules of PTH.
• Regulation: ↓ free Ca²⁺ stimulates PTH synthesis + secretion.
• PTH → ↑ bone resorption (osteoclasts), ↑ renal Ca²⁺ reabsorption + ↓ PO₄³⁻ reabsorption, ↑ renal 1α-hydroxylase → ↑ active vitamin D → ↑ intestinal Ca²⁺ absorption.

2. Primary Hyperparathyroidism

Definition

• Autonomous + spontaneous overproduction of PTH → hypercalcemia.

Causes (3 underlying lesions)

A) Adenoma (~85 %)

• Single gland involved.
• Other glands normal-sized or shrunken (suppressed by ↑ Ca²⁺ feedback).
• Well-circumscribed + encapsulated tumor.

B) Hyperplasia (~10–15 %)

• Enlargement of ALL 4 glands.
• ↓ Fat content + ↑ chief cells.
• “Water-clear cell hyperplasia” — clear cytoplasm from glycogen accumulation.

C) Carcinoma (< 1 %)

• Firm, adheres to surroundings (fibrosis + infiltration).
• Diagnosed by invasion + metastatic dissemination (not by histology alone).

Consequences of ↑ PTH → Hypercalcemia

• Recklinghausen disease (osteitis fibrosa cystica):
  • Cyst formation in diaphysis; brownish color from hemosiderin (“brown tumor”).
• Metastatic calcification: heart, stomach, nephrocalcinosis.
• Nephrolithiasis (urinary stones, Ca-containing).
• Peptic ulcers (↑ gastrin).
• Pancreatitis.

Clinical features

• Adults; F > M.
• Hypercalcemia with inappropriately ↑ PTH.
• ↑ Osteoclast activity → bone matrix erosion + Ca²⁺ mobilization.
• Classic mnemonic: “Stones, bones, abdominal groans, psychic moans”:
  • Stones (nephrolithiasis)
  • Bones (osteitis fibrosa cystica)
  • Abdominal groans (PUD, pancreatitis, constipation)
  • Psychic moans (depression, lethargy, seizures)

3. Secondary Hyperparathyroidism

Cause

• Any chronic depression of free Ca²⁺ → compensatory PTH ↑.
• #1 cause = chronic renal failure:
  • ↓ PO₄³⁻ excretion → hyperphosphatemia → binds Ca²⁺ → ↓ free Ca²⁺ → stimulates parathyroid.
  • Loss of renal tissue → ↓ 1α-hydroxylase → ↓ active vitamin D → ↓ intestinal Ca²⁺ absorption.

Morphology

• Similar to primary: gland enlargement, bone changes, metastatic calcifications.

Clinical features

• Dominated by chronic renal failure features.
• Renal osteodystrophy — less severe bone lesions than primary.
• Ca²⁺ near-normal (compensatory ↑ PTH).
• Tertiary hyperparathyroidism: parathyroid becomes autonomous → hypercalcemia despite no need → requires gland removal.

4. Hypoparathyroidism

Definition

• Less common than hyperparathyroidism.
• ↓ PTH → hypocalcemia + hyperphosphatemia.

Causes

• Surgical — inadvertent removal during thyroidectomy (#1).
• Congenital absence: DiGeorge syndrome (22q11 deletion) — with thymic aplasia.
• Autoimmune — polyglandular deficiency syndrome (autoantibodies vs multiple endocrine organs).
• Pseudohypoparathyroidism = PTH resistance (Albright hereditary osteodystrophy).

Clinical Findings (hypocalcemia)

• Neuromuscular irritability: muscle spasm, tetany, paresthesias.
  • Chvostek sign — tap facial nerve → facial muscle twitch.
  • Trousseau sign — BP cuff → carpal spasm.
• Cardiac arrhythmias (prolonged QT).
• ↑ Intracranial pressure + seizures.
• Cataracts, basal ganglia calcification.

5. Summary Table

Condition	PTH	Ca	PO₄	Cause
Primary hyperparathyroidism	↑	↑	↓	Adenoma (#1), hyperplasia, carcinoma
Secondary hyperparathyroidism	↑	↓ / nl	↑ (in CRF)	Chronic renal failure, vitamin D deficiency
Tertiary hyperparathyroidism	↑↑	↑	↑	Autonomous parathyroid from long-standing 2°
Hypoparathyroidism	↓	↓	↑	Surgical, DiGeorge, autoimmune
Pseudohypoparathyroidism	↑	↓	↑	PTH resistance (Albright)

💡 High-yield: Primary hyperparathyroidism = adenoma (#1) → hypercalcemia + ↑ PTH; stones, bones, abdominal groans, psychic moans; osteitis fibrosa cystica (brown tumors) + nephrolithiasis + PUD + pancreatitis. Secondary = chronic renal failure (↑ PO₄ + ↓ vit D → ↓ Ca → ↑ PTH); renal osteodystrophy. Tertiary = autonomous (after long-standing 2°). Hypoparathyroidism: surgical #1, DiGeorge (22q11 + thymic aplasia), autoimmune; ↓ Ca → tetany + Chvostek + Trousseau + prolonged QT + seizures.