Hypoparathyroidism
Definition
Hypoparathyroidism is defined as a disorder characterised by inadequate secretion or action of PTH
Aetiology
Important causes: [Ref1][Ref2]
- Surgery – leading overall cause
- Parathyroidectomy
- Unindented injury from thyroidectomy
- Autoimmune destruction – leading non-surgical cause
- Genetic cause (e.g. DiGeorge syndrome)
- Infiltrative diseases (e.g. haemochromatosis, Wilson’s disease)
- Neck irradiation
- Hypomagnesium (causes functional hypoparathyroidism, therefore it’s important to correct any underlying hypomagnesium before correcting hypocalcaemia)
Clinical Features
Clinical features are typically secondary to hypocalcaemia [Ref]
| Early / mild hypocalcaemia features [Ref] |
|
| Features of more severe hypocalcaemia: [Ref] |
|
Hypocalcaemia increases neuromuscular excitability because ionised calcium normally stabilises voltage-gated sodium channels. When calcium levels fall, these channels open more easily, leading to spontaneous depolarisation.
Rare features typically only seen in chronic hypoparathyroidism: [Ref]
- Neuropsychiatric symptoms (e.g. confusion, depression, irritability, cognitive dysfunction)
- Basal ganglia calcification (→ secondary Parkinsonism)
- Ophthalmologic
- Cataracts
- Papilloedema
Investigation and Diagnosis
Biochemical changes: [Ref]
- ↓ PTH
- ↓ Calcium
- ↑ Phosphate
- ↓ / normal 1,25 dihydroxyvitamin D (due to lack of PTH-stimulated renal conversion)
Rationising the biochemical changes:
- Actions of PTH
- ↑ Serum calcium (via ↑ bone resorption, ↑ renal calcium reabsorption, ↑ intestinal calcium absorption)
- ↓ Serum phosphate (via ↑ renal phosphate excretion)
The initiating event is low PTH, which results in the subsequent biochemical changes (opposite of PTH’s action).
Management
Conventional therapy: [Ref1][Ref2]
- Oral calcium supplementation
- Active vitamin D (calcitriol / 1,25-hydroxyvitamin D)
- Phosphate binders for hyperphosphataemia
- Thiazide diuretic may be added in persistent hypercalciuria
If conventional therapy failed: PTH replacement therapy (e.g. teriparatide)
Therapeutic goal in hypoparathyroidism is to:
- Maintain serum calcium in the low-normal range
- Avoid hypercalcaemia and hypecalciuria
- Maintain serum phosphate in the high-normal range
Notes on various types of vitamin D and their use:
| Vitamin D type | Description | Indication |
|---|---|---|
|
Native forms of vitamin D
|
Must be hydroxylated in the liver to 25-hydroxyvitamin D (calcifediol), then in the kidney into 1,25-dihydroxyvitamin D (calcitriol) for biological activity |
|
| 25-hydroxyvitamin D (calcifediol) | Major circulating form of vitamin D (produced by 25-hydroxylation in the liver)
(If vitamin D deficiency is suspected, 25-hydroxyvitamin D is measured) |
|
Activated vitamin D metabolites (bypassing the renal activation process)
|
Both alfacalcidol / calcitriol can be given as supplements to bypass the renal activation process (thus considered activated vitamin D metabolites):
|
Impaired renal 1-alpha hydroxylase activity:
Not used for routine deficiency replacement or for general population supplementation due to increased risk of hypercalcaemia |