51. Hyperparathyroidism - classification, etiology, pathogenesis, clinical manifestations.

Hyperparathyroidism - classification, etiology, pathogenesis, and clinical manifestations

Hyperparathyroidism is a condition of excessive secretion of parathyroid hormone (PTH), leading to hypercalcemia and hypophosphatemia, with effects on bone, kidney, and other organs.

Classification

1. 1 Primary hyperparathyroidism

• Problem in the parathyroid gland itself.

1. 2 Secondary hyperparathyroidism

• Chronic hypocalcemia (external cause) → compensatory increase in PTH.

1. 3 Tertiary hyperparathyroidism

• Long-standing secondary hyperparathyroidism → autonomous PTH secretion even after correction of hypocalcemia.

Etiology

• Primary hyperparathyroidism
• Parathyroid adenoma (most common cause, ~85%).
• Parathyroid hyperplasia (e.g., in multiple endocrine neoplasia syndromes MEN 1 and MEN 2A).
• Parathyroid carcinoma (rare).
• Secondary hyperparathyroidism
• Chronic renal failure (most common cause): phosphate retention and decreased vitamin D activation → hypocalcemia → ↑ PTH.
• Vitamin D deficiency (dietary or lack of sun exposure).
• Malabsorption syndromes.
• Tertiary hyperparathyroidism
• Usually in patients with chronic renal failure after prolonged secondary hyperparathyroidism.

Pathogenesis

Primary hyperparathyroidism

1. Autonomous overproduction of PTH from adenoma or hyperplasia.
2. Increased osteoclastic bone resorption → release of calcium and phosphate.
3. Increased renal tubular calcium reabsorption, phosphate excretion → hypercalcemia, hypophosphatemia.
4. Increased conversion of vitamin D to active form → increased intestinal calcium absorption.

Secondary hyperparathyroidism

1. Chronic hypocalcemia stimulates parathyroid glands → diffuse hyperplasia.
2. Persistent stimulation → excessive PTH production.

Tertiary hyperparathyroidism

1. After long-standing secondary hyperparathyroidism, glands become autonomous.
2. Secrete PTH irrespective of calcium level → hypercalcemia.

Clinical manifestations

Due to hypercalcemia ("stones, bones, groans, and psychic moans")

• Stones: kidney stones (nephrolithiasis).
• Bones: bone pain, fractures, osteitis fibrosa cystica (bone lesions with fibrous replacement and cysts).
• Groans: gastrointestinal symptoms — nausea, vomiting, constipation, peptic ulcers, pancreatitis.
• Psychic moans: neuropsychiatric symptoms — weakness, fatigue, depression, confusion.

Other features

• Polyuria and polydipsia (nephrogenic diabetes insipidus due to hypercalcemia-induced renal concentrating defect).
• Muscle weakness.
• Hypertension (some cases).

In secondary hyperparathyroidism

• Bone changes (renal osteodystrophy): subperiosteal bone resorption, bone pain.
• Usually no hypercalcemia; patients often have low or normal calcium levels.

Summary Table