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# Secondary hyperparathyroidism and hypoparathyroidism

- Mechanism

When calcium stays low, the parathyroids grow to compensate. When they are lost, or the body ignores PTH, calcium falls.

Updated Nov 12, 2026

## Key points

- Secondary: CKD (phosphate retention, low calcitriol, low calcium) drives diffuse hyperplasia of all four glands.
- Renal osteodystrophy: osteitis fibrosa, osteomalacia, adynamic bone; vascular calcification and calciphylaxis.
- Tertiary: autonomous gland after long secondary disease; persists after kidney transplant with hypercalcaemia.
- Hypoparathyroidism: surgical (commonest), autoimmune (APS-1 with AIRE), DiGeorge 22q11.2 deletion, activating CaSR mutations, magnesium deficiency.
- Pseudohypoparathyroidism type 1a: maternal GNAS loss, end-organ resistance plus Albright hereditary osteodystrophy (short stature, short fourth and fifth metacarpals, round face).
- Pseudopseudohypoparathyroidism: paternal GNAS loss, the body shape without hormone resistance (imprinting).

## What it is

Secondary hyperparathyroidism is a compensatory response to chronic hypocalcaemia, most often from chronic kidney disease, and sometimes from vitamin D deficiency or malabsorption. All four glands become hyperplastic, and after years one or more may become autonomous (tertiary). Hypoparathyroidism is the opposite: too little PTH, most often after neck surgery. In pseudohypoparathyroidism PTH is high but the tissues cannot respond because of GNAS defects.

## Step by step

- Failing kidneys retain phosphate and make less calcitriol.
- Phosphate binds calcium, calcitriol deficiency lowers gut absorption, FGF23 rises: serum calcium falls.
- Low calcium and high phosphate stimulate all parathyroid glands to grow and secrete.
- High PTH resorbs bone (osteitis fibrosa) and calcium phosphate deposits in vessels and soft tissue.
- After years, a nodule within the hyperplastic glands may become autonomous: tertiary hyperparathyroidism.

## Parathyroid disorders by calcium and PTH

| Disorder | Calcium | Phosphate | PTH | Main cause |
| --- | --- | --- | --- | --- |
| [Primary hyperparathyroidism](https://durgical.com/en/conditions/primary-hyperparathyroidism/) | High | Low | High | Adenoma |
| [Secondary hyperparathyroidism](https://durgical.com/en/conditions/ckd-mineral-and-bone-disorder/) | Low or normal | High in CKD, low in vitamin D deficiency | High | CKD, vitamin D deficiency |
| [Tertiary hyperparathyroidism](https://durgical.com/en/conditions/ckd-mineral-and-bone-disorder/) | High | Variable | Very high | Long-standing CKD |
| [Hypoparathyroidism](https://durgical.com/en/conditions/hypoparathyroidism/) | Low | High | Low | Neck surgery, autoimmunity, 22q11.2 deletion |
| Pseudohypoparathyroidism | Low | High | High | GNAS loss, end-organ resistance |

## Clinical notes

- Hypocalcaemia: tetany, perioral numbness, Chvostek and Trousseau signs, prolonged QT, seizures, basal ganglia calcification, cataracts.
- Calciphylaxis: painful necrotic skin lesions from calcified small vessels in dialysis patients.
- Magnesium deficiency both reduces PTH secretion and causes PTH resistance.

## Memory aid

In pseudohypoparathyroidism the gland shouts PTH and nobody listens: the message is sent but the GNAS telephone line is cut.

## Test yourself

Think of the answer, then tap the question to see it.

## Why do the parathyroid glands become hyperplastic in chronic kidney disease?

Phosphate retention, low calcitriol and low calcium all stimulate PTH secretion and gland growth.

## What is tertiary hyperparathyroidism?

Autonomous PTH secretion with hypercalcaemia after long-standing secondary hyperparathyroidism, often persisting after kidney transplant.

## Why does the parent of origin matter in GNAS loss?

GNAS is imprinted in some tissues: maternal loss causes hormone resistance plus Albright osteodystrophy; paternal loss gives the physical features only.

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## Elsewhere in DurgiPedia

- [Calcium regulation: PTH, vitamin D and calcitonin](https://durgical.com/en/physiology/calcium-regulation-pth-vitamin-d-and-calcitonin/)
- [Vitamin D (calcitriol)](https://durgical.com/en/biochemistry/molecules/vitamin-d/)
- [Genomic imprinting: Prader–Willi and Angelman](https://durgical.com/en/general-pathology/genomic-imprinting-prader-willi-and-angelman/)
- [Trisomies 21, 18 and 13, and the 22q11.2 deletion](https://durgical.com/en/general-pathology/trisomies-21-18-and-13-and-the-22q11-2-deletion/)

## Connections

## Related 3

- [Primary hyperparathyroidism](https://durgical.com/en/general-pathology/primary-hyperparathyroidism/)
- [Genomic imprinting: Prader–Willi and Angelman](https://durgical.com/en/general-pathology/genomic-imprinting-prader-willi-and-angelman/)
- [Pathologic calcification: dystrophic vs metastatic](https://durgical.com/en/general-pathology/pathologic-calcification-dystrophic-vs-metastatic/)

## Related conditions 7

- [CKD-mineral and bone disorder (renal osteodystrophy)](https://durgical.com/en/conditions/ckd-mineral-and-bone-disorder/)
- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)
- [Calciphylaxis (calcific uremic arteriolopathy)](https://durgical.com/en/conditions/calciphylaxis/)
- [Rickets and osteomalacia](https://durgical.com/en/conditions/rickets-and-osteomalacia/)
- [Hypoparathyroidism (incl. post-thyroidectomy hypocalcaemia)](https://durgical.com/en/conditions/hypoparathyroidism/)
- [Hypocalcaemia](https://durgical.com/en/conditions/hypocalcaemia/)
- [Autoimmune polyendocrine syndromes (APS-1, APS-2) and IPEX](https://durgical.com/en/conditions/autoimmune-polyendocrine-syndromes-and-ipex/)

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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: [Hyperparathyroidism: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/001215.htm) (MedlinePlus, US National Library of Medicine, 2025); [Hypoparathyroidism: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000385.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/secondary-hyperparathyroidism-and-hypoparathyroidism/