Introduction
This topic covers the two main disorders of parathyroid hormone (PTH) secretion: hypoparathyroidism, which causes low calcium, and hyperparathyroidism, which causes high calcium. A good answer explains calcium regulation, defines and classifies both conditions, gives their causes and clinical picture, outlines laboratory diagnosis and differential diagnosis, and describes treatment, complications and prognosis.
Physiology of calcium and PTH
The four parathyroid glands secrete PTH when the ionised calcium in the serum falls. PTH restores calcium by three main actions:
- increases bone resorption, releasing calcium and phosphate
- increases renal tubular reabsorption of calcium and decreases reabsorption of phosphate
- stimulates renal conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D, which increases intestinal calcium absorption
Hypoparathyroidism
Hypoparathyroidism is deficient PTH secretion or action. It produces hypocalcaemia with hyperphosphataemia, and the PTH level is low or inappropriately normal for the calcium level.
Causes
- Postsurgical damage or devascularisation after thyroid or neck surgery, the most common cause
- Autoimmune destruction, isolated or as part of autoimmune polyglandular syndrome type 1
- Congenital causes such as DiGeorge syndrome (22q11 deletion)
- Infiltration (iron or copper overload, sarcoidosis), radiotherapy, and neck irradiation
- Severe hypomagnesaemia, which impairs PTH secretion and action; activating mutations of the calcium-sensing receptor, which cause hypocalcaemia with low PTH
Clinical picture
- Neuromuscular irritability: perioral and distal paraesthesias, muscle cramps, carpopedal spasm and tetany
- Chvostek sign (facial twitch on tapping the facial nerve) and Trousseau sign (carpal spasm after cuff inflation)
- Severe cases: laryngospasm, stridor, generalised seizures, and QT prolongation on the ECG
- Chronic cases: cataracts, basal ganglia calcification, dental enamel defects, dry skin, brittle nails and papilloedema from raised intracranial pressure
Diagnosis and treatment
- Laboratory: low total and ionised calcium, high phosphate, low or inappropriately normal PTH, low urinary calcium; check magnesium, creatinine and 25-hydroxyvitamin D
- Acute symptomatic hypocalcaemia: slow intravenous calcium gluconate with ECG monitoring, and correction of magnesium
- Chronic treatment: oral calcium with active vitamin D analogues (calcitriol or alfacalcidol); thiazides may reduce urinary calcium loss
- Aim for low-normal serum calcium to avoid hypercalciuria, nephrocalcinosis and kidney stones