Primary Hyperparathyroidism: Etiology and Morphology
Primary hyperparathyroidism is caused by the pathological proliferation of parathyroid tissue. There are three main causes:
- Parathyroid adenoma (80% of cases).
Occurs with equal frequency in both sexes. Macroscopically, it presents as an encapsulated single (rarely multiple) nodule, weighing up to 10 g. The tumor has a soft consistency and a yellowish-brown color. Microscopically, it most commonly consists of chief cells (clear-cell adenoma), and occasionally transitional or oxyphil cells. The cells form trabecular, solid, and follicular structures. Secondary changes such as hemorrhage, necrosis, fibrosis, and hemosiderosis are frequently identified within the tissue.
- Primary hyperplasia (15–17%).
Characterized by diffuse, and much less frequently nodular, enlargement of the glands. Microscopic examination reveals proliferation of oxyphil or chief cells, interspersed with fat cells.
- Parathyroid carcinoma (1–5%).
Macroscopically appears as a grayish-white neoplasm confined within a single gland. It is characterized by slow growth, high hormonal activity, and progressive renal impairment. Microscopically, the tumor consists of elongated, atypical, polymorphic cells with hyperchromatic nuclei; infiltrative growth is typical. In 33% of patients, the carcinoma metastasizes to regional lymph nodes.
Secondary Hyperparathyroidism and Extraskeletal Manifestations
Unlike primary hyperparathyroidism, secondary hyperparathyroidism occurs as a compensatory response. PTH secretion increases in response to chronic hypocalcemia. The main causes of this condition include chronic kidney disease, osteomalacia, and vitamin D deficiency. The morphological appearance of the glands themselves is completely identical to primary hyperplasia.
Excess PTH leads to severe extraskeletal manifestations:
- Pancreatic involvement: stones form within the pancreatic ducts.
- Ophthalmologic changes: cataract formation and corneal calcifications.
- Neurologic disturbances: muscle weakness, dementia, memory loss, and seizures.
Hypoparathyroidism: Causes and Clinical Presentation
Decreased parathyroid function is associated with a deficiency of PTH. The causes of hypoparathyroidism can be categorized into several groups:
- Iatrogenic: surgical removal of the glands (e.g., during thyroidectomy).
- Genetic/Congenital: DiGeorge syndrome, characterized by congenital aplasia or hypoplasia of the thymus and parathyroid glands.
- Idiopathic and autoimmune: formation of autoantibodies against parathyroid tissue or PTH itself.
- Rare factors: granulomatous infiltration, hemochromatosis, aluminum toxicity, and metastatic involvement of the parathyroid glands.
The Special Role of Magnesium Deficiency Magnesium deficiency is a major cause of functional hypoparathyroidism because this ion is required for PTH to exert its full peripheral effects and for adequate hormone secretion. Magnesium deficiency occurs in chronic alcoholism, liver cirrhosis, malabsorption syndromes, prolonged vomiting, and diarrhea. Long-term use of gentamicin, cyclosporine, thiazide diuretics, and parenteral nutrition without magnesium supplementation also increase risk. Vitamin D deficiency likewise suppresses hormone secretion.
Clinical and laboratory findings include:
- Hypocalcemia and hyperphosphatemia.
- Marked increase in neuromuscular excitability, leading to laryngospasm and tetanic seizures.
- Increased calcium concentration in bone tissue.
- Development of cataracts, nail abnormalities, and dental hypoplasia.