Primary hyperparathyroidism: etiology and morphology
Primary hyperparathyroidism is caused by the pathological proliferation of parathyroid tissue. There are three main causes for its development:
- Parathyroid adenoma (80% of cases).
Develops with equal frequency in both sexes. Macroscopically, it presents as an encapsulated single (less frequently multiple) rounded node weighing up to 10 g. The tumor consistency is soft, and the color is yellowish-brown. Microscopically, it most commonly consists of chief cells (clear cell adenoma), occasionally transitional or oxyphil cells. The cells form trabecular, solid, and follicular structures. Secondary changes such as hemorrhage, necrosis, fibrosis, and hemosiderosis are frequently detected in the tissue.
- Primary hyperplasia (15–17%).
Characterized by diffuse, much less frequently nodular enlargement of the glands. Microscopic examination reveals proliferation of oxyphil or chief cells, with adipocytes interspersed between them.
- 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 characteristic. In 33% of patients, carcinoma metastasizes to regional lymph nodes.
Secondary hyperparathyroidism and extraskeletal manifestations
Unlike primary hyperparathyroidism, secondary hyperparathyroidism arises as a compensatory response. PTH secretion increases in response to chronic hypocalcemia. The main causes of this condition include renal failure, osteomalacia, and vitamin D deficiency. The morphological picture within the glands themselves is completely identical to primary hyperplasia.
Excess parathyroid hormone leads to serious extraskeletal manifestations:
- Pancreatic involvement: stone formation within the excretory ducts.
- Ophthalmological changes: development of cataracts and corneal calcifications.
- Neurological disorders: muscle weakness, dementia, memory impairment, and seizures.
Hypoparathyroidism: causes and clinical presentation
Decreased parathyroid function is associated with PTH deficiency. The causes of hypoparathyroidism can be divided into several groups:
- Iatrogenic: surgical removal of the glands (e.g., during thyroidectomy).
- Genetic/Congenital: DiGeorge syndrome (DiGeorge syndrome), characterized by congenital agenesis of the thymus and parathyroid glands.
- Idiopathic and autoimmune: formation of autoantibodies against parathyroid tissue or the hormone itself.
- Rare factors: involvement in granulomatosis, hemochromatosis, aluminum intoxication, and parathyroid metastases.
Special role of magnesium deficiency Magnesium deficiency is the most frequent cause of hypoparathyroidism, as this trace element enhances the action of parathyroid hormone. Magnesium deficiency occurs in alcoholism, liver cirrhosis, malabsorption syndrome, prolonged vomiting, and diarrhea. The risk is also increased by long-term administration of gentamicin, cyclosporine, thiazide diuretics, and parenteral nutrition without magnesium salt supplementation. Vitamin D deficiency also suppresses hormone secretion.
Clinically and laboratorily, these conditions manifest as:
- Hypocalcemia and hyperphosphatemia.
- A sharp increase in neuromuscular excitability, leading to laryngospasm and tetanic seizures.
- An increase in calcium concentration within bone tissue.
- Development of cataracts, nail abnormalities, and dental hypoplasia.
Briefly: answers to topical questions
What bone changes develop in primary hyperparathyroidism?
In primary hyperparathyroidism, processes of excessive resorption, demineralization, and generalized osteoporosis develop in bone tissue. The main bone changes include:
- Osteitis fibrosa cystica (osteitis fibrosa cystica) — Recklinghausen's disease, characterized by the replacement of bone marrow with fibrous tissue and cyst formation.
- Brown tumors — accumulations of fibroblasts, macrophages, osteoclast-like cells, and hemorrhages.
- Subperiosteal resorption — resorption of bone tissue, particularly pronounced in the phalanges of the hands.
- Intracortical resorption — linear radiolucent areas within the cortical layer.
- Chondrocalcinosis (chondrocalcinosis) — deposition of calcium pyrophosphate dihydrate crystals in articular and fibrous cartilage.
These processes lead to thinning of bone trabeculae, bone softening and deformation, as well as pathological fractures.
What pathological processes develop in the kidneys in hyperparathyroidism?
In hyperparathyroidism, pathological processes develop in the kidneys associated with hypercalcemia and increased calcium excretion. The main changes include:
- Nephrocalcinosis (nephrocalcinosis) — deposition of calcium in the renal parenchyma, including calcium phosphate and calcium oxalate. Medullary nephrocalcinosis is most common.
- Nephrolithiasis — kidney stone disease.
Nephrolithiasis frequently results in nephrosclerosis, while massive calcification in nephrocalcinosis can lead to organ failure.
In which organs do calcium salts deposit during metastatic calcification in the setting of hyperparathyroidism?
During metastatic calcification in the setting of hyperparathyroidism, calcium salts deposit in normal tissues against the background of hypercalcemia. Typical localization sites are:
- Kidneys — with the development of nephrocalcinosis.
- Stomach — in the interstitium of the mucous membrane.
- Lungs.
- Cardiovascular system — myocardium, arteries, and pulmonary veins.
Usually, non-crystalline amorphous deposits or hydroxyapatite crystals do not cause dysfunction, except for massive calcification, such as nephrocalcinosis, which can lead to organ failure.
To memorize the main groups of causes of hypoparathyroidism, use the mnemonic «YMA»: Y — Iatrogenic (surgeries), M — Magnesium deficiency, A — Agenesis (congenital, autoimmune).
Class and exam questions
What is the microscopic difference in parathyroid adenoma?
In most cases, it is a clear cell adenoma. It consists predominantly of chief cells that form solid, follicular, and trabecular structures.
What triggers the development of secondary hyperparathyroidism?
This is a compensatory process. PTH secretion increases in response to chronic hypocalcemia, frequently against the background of renal failure or vitamin D deficiency.
How is magnesium deficiency related to parathyroid function?
Magnesium is essential for parathyroid hormone to exert its full effect on tissues. Its deficiency suppresses hormone secretion and leads to pronounced hypoparathyroidism.
What else to study on this topic
- Adenohypophysis pathology: hyperpituitarism and mass effect (compression of the optic nerves, increased intracranial pressure)
- Pituitary necrosis: clinical presentation of Sheehan and Simmonds syndromes
- Granulomatous lesions of endocrine glands
- Mechanisms of action of thiazide diuretics on calcium and magnesium metabolism
- Genetics and phenotypic manifestations of DiGeorge syndrome
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