Primary hyperparathyroidism
- Lesion
One overactive parathyroid gland, usually a benign adenoma, raises blood calcium. Today most cases are found on routine blood tests.
What it is
Primary hyperparathyroidism is autonomous overproduction of parathyroid hormone, the commonest cause of hypercalcaemia in outpatients. A single adenoma causes most cases; primary hyperplasia of all glands and carcinoma cause the rest. PTH raises calcium by mobilising bone, increasing renal calcium reabsorption and stimulating vitamin D activation, so untreated disease damages bone and kidney and deposits calcium in tissues.
Structure
- Adenoma: solitary, soft, tan-brown, encapsulated; chief cells (sometimes oncocytic), scant stromal fat, rim of normal parathyroid outside the capsule.
- Primary hyperplasia: all four glands enlarged, often unequally; chief cell sheets, fat lost.
- Carcinoma: large, adherent, fibrous bands; capsular, vascular or perineural invasion.
- Bone: osteoclastic resorption (dissecting osteitis), marrow fibrosis, cysts and brown tumours.
- Metastatic calcification of kidney (nephrocalcinosis), stomach, lung, vessels.
Step by step
- A parathyroid clone loses calcium-set-point control (cyclin D1 or MEN1 change).
- It secretes PTH even when calcium is high.
- PTH activates osteoclasts through RANKL on osteoblasts, releasing calcium and phosphate.
- PTH increases distal tubular calcium reabsorption, decreases phosphate reabsorption and stimulates 1-alpha-hydroxylase.
- Hypercalcaemia and hypercalciuria: stones, nephrocalcinosis, bone loss and metastatic calcification.
Hypercalcaemia: is PTH the cause?
| Group | Examples | PTH |
|---|---|---|
| PTH-driven | Primary hyperparathyroidism, tertiary hyperparathyroidism, familial hypocalciuric hypercalcaemia | High or inappropriately normal |
| Malignancy | PTHrP from squamous carcinomas, osteolytic metastases, myeloma, calcitriol from lymphoma | Low |
| Vitamin D excess | Granulomas (sarcoidosis, TB), intoxication | Low |
| Other | Thiazides, immobilisation, milk-alkali syndrome, thyrotoxicosis | Low |
Clinical notes
- Kidney stones, polyuria, constipation, peptic ulcer, pancreatitis, depression and fatigue.
- Lab: high calcium, low phosphate, high or inappropriately normal PTH.
- Malignancy and primary hyperparathyroidism together explain most hypercalcaemia.
Test yourself
Think of the answer, then tap the question to see it.
What does the rest of the parathyroid tissue look like when there is an adenoma?
The other glands are normal or small and inactive, because high calcium suppresses them.
What is a brown tumour?
A reactive bone lesion of osteoclast-like giant cells, fibrous tissue and haemosiderin (hence brown) caused by intense PTH-driven resorption.
Which gene is linked to parathyroid carcinoma and the hyperparathyroidism-jaw tumour syndrome?
CDC73, encoding parafibromin.
Elsewhere in DurgiPedia
- Calcium regulation: PTH, vitamin D and calcitonin
- Thyroid follicles, C cells and parathyroid
- Pathologic calcification: dystrophic vs metastatic
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Primary Hyperparathyroidism (StatPearls (NCBI Bookshelf), 2025); Hyperparathyroidism: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Hypercalcemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.