[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Endocrine system](https://durgical.com/en/general-pathology/areas/endocrine/) › Primary hyperparathyroidism

# Primary hyperparathyroidism

- Lesion

One overactive parathyroid gland, usually a benign adenoma, raises blood calcium. Today most cases are found on routine blood tests.

Updated Nov 12, 2026

## Key points

- Causes: adenoma (most), primary hyperplasia (often MEN1, MEN2A), carcinoma (rare).
- Genes: MEN1 and CCND1 (cyclin D1) overexpression in sporadic adenomas; CDC73 (parafibromin) in carcinoma and hyperparathyroidism-jaw tumour syndrome.
- Adenoma: one enlarged gland, little fat, rim of compressed normal tissue; the other glands are small (suppressed).
- Carcinoma: diagnosis needs invasion of surrounding tissue or metastasis.
- Bone: osteitis fibrosa cystica with brown tumours (haemosiderin-laden giant-cell lesions); osteoporosis.
- Classic picture: «bones, stones, abdominal groans and psychic moans»; today usually asymptomatic hypercalcaemia.

## 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](https://durgical.com/en/conditions/primary-hyperparathyroidism/) | Primary hyperparathyroidism, tertiary hyperparathyroidism, familial hypocalciuric hypercalcaemia | High or inappropriately normal |
| [Malignancy](https://durgical.com/en/conditions/hypercalcaemia-of-malignancy/) | PTHrP from squamous carcinomas, osteolytic metastases, myeloma, calcitriol from lymphoma | Low |
| [Vitamin D excess](https://durgical.com/en/conditions/sarcoidosis/) | Granulomas (sarcoidosis, TB), intoxication | Low |
| [Other](https://durgical.com/en/conditions/hypercalcaemia/) | 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.

## Memory aid

Primary hyperparathyroidism is a thermostat stuck on high: calcium is already warm, but the gland keeps the heating running.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/primary-hyperparathyroidism/)

[More Pathology questions →](https://durgical.com/en/practice/?f=pathology)

## Elsewhere in DurgiPedia

- [Calcium regulation: PTH, vitamin D and calcitonin](https://durgical.com/en/physiology/calcium-regulation-pth-vitamin-d-and-calcitonin/)
- [Thyroid follicles, C cells and parathyroid](https://durgical.com/en/histology/thyroid-follicles-c-cells-and-parathyroid/)
- [Pathologic calcification: dystrophic vs metastatic](https://durgical.com/en/general-pathology/pathologic-calcification-dystrophic-vs-metastatic/)

## Connections

## Related 6

- [Secondary hyperparathyroidism and hypoparathyroidism](https://durgical.com/en/general-pathology/secondary-hyperparathyroidism-and-hypoparathyroidism/)
- [Multiple endocrine neoplasia (MEN) syndromes](https://durgical.com/en/general-pathology/multiple-endocrine-neoplasia-syndromes/)
- [Kidney stones](https://durgical.com/en/general-pathology/kidney-stones/)
- [Crystal nephropathies and nephrocalcinosis](https://durgical.com/en/general-pathology/crystal-nephropathies-and-nephrocalcinosis/)
- [Pathologic calcification: dystrophic vs metastatic](https://durgical.com/en/general-pathology/pathologic-calcification-dystrophic-vs-metastatic/)
- [Paraneoplastic syndromes: the table to know](https://durgical.com/en/general-pathology/paraneoplastic-syndromes-the-table-to-know/)

## Related conditions 7

- [Primary hyperparathyroidism](https://durgical.com/en/conditions/primary-hyperparathyroidism/)
- [Hypercalcaemia](https://durgical.com/en/conditions/hypercalcaemia/)
- [Hypercalcaemia of malignancy](https://durgical.com/en/conditions/hypercalcaemia-of-malignancy/)
- [Kidney stones (urolithiasis)](https://durgical.com/en/conditions/kidney-stones/)
- [Multiple endocrine neoplasia (MEN 1, 2A, 2B)](https://durgical.com/en/conditions/multiple-endocrine-neoplasia/)
- [Osteoporosis](https://durgical.com/en/conditions/osteoporosis/)
- [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/)

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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](https://www.ncbi.nlm.nih.gov/books/NBK441895/) (StatPearls (NCBI Bookshelf), 2025); [Hyperparathyroidism: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/001215.htm) (MedlinePlus, US National Library of Medicine, 2025); [Hypercalcemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000365.htm) (MedlinePlus, US National Library of Medicine, 2025).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/primary-hyperparathyroidism/