Parathyroid Pathology
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Direct answer
Primary hyperparathyroidism is inappropriately elevated parathyroid hormone secretion — a single chief-cell adenoma in about 85 to 90 per cent — producing hypercalcaemia with low-normal phosphate, renal stones, bone resorption with osteitis fibrosa cystica and brown tumours, abdominal pain and neuropsychiatric symptoms, though modern Indian series increasingly detect asymptomatic biochemical hypercalcaemia. Secondary hyperparathyroidism is the physiological parathyroid response to chronic hypocalcaemia, classically in chronic kidney disease, and tertiary hyperparathyroidism is autonomous secretion that emerges after long-standing secondary stimulation. Hypoparathyroidism in Indian practice is most often surgical — a complication of thyroidectomy — with DiGeorge syndrome and autoimmune polyglandular failure completing the list.
What you must remember
- Causes: single adenoma 85–90 per cent, primary chief-cell hyperplasia about 10 per cent (screen for MEN1), parathyroid carcinoma under 2 per cent — suggested by a palpable mass, hoarseness from recurrent nerve invasion, and very high calcium and hormone levels.
- The clinical rhyme: stones, bones, abdominal groans and psychic moans — nephrolithiasis the commonest symptomatic presentation, with polyuria, constipation, peptic ulcer and pancreatitis.
- Brown tumour: a mass of osteoclasts, haemorrhage and fibrous tissue in hyperparathyroid bone — jaw and long bones; the discriminator from giant cell tumour of bone is the biochemistry, since calcium, parathyroid hormone and alkaline phosphatase are all deranged.
- MEN1: parathyroid hyperplasia or adenoma (the most common manifestation) with pancreatic neuroendocrine tumours such as gastrinoma and pituitary adenomas such as prolactinoma. MEN2A: medullary thyroid carcinoma, phaeochromocytoma and parathyroid disease, from RET mutation.
- Secondary hyperparathyroidism of chronic kidney disease: phosphate retention plus failing calcitriol synthesis lower ionised calcium, hormone levels rise, and the skeleton pays — renal osteodystrophy combining osteitis fibrosa, osteomalacia and brown tumours, managed with phosphate binders and active vitamin D.
- Tertiary hyperparathyroidism: autonomous nodular hyperplasia after prolonged secondary stimulation; severe hypercalcaemia in a dialysis patient warrants it, and parathyroidectomy treats it.
- Hypoparathyroidism: post-thyroidectomy surgical injury or removal the commonest cause; DiGeorge syndrome; autoimmune polyglandular syndrome type 1 (AIRE gene) with chronic mucocutaneous candidiasis and Addison disease.
- Pseudohypoparathyroidism: hormone resistance, not deficiency — low calcium, high parathyroid hormone, and Albright hereditary osteodystrophy with short fourth and fifth metacarpals (the knuckle-knuckle-dimple-dimple sign), round face and subcutaneous ossifications.
A raised calcium, worked through
A 52-year-old referred for fatigue and constipation has a serum calcium of 11.8 milligrams per decilitre with a normal albumin. The first question the numbers must answer is whether the parathyroid is driving it: an inappropriately normal or elevated parathyroid hormone level alongside hypercalcaemia confirms primary hyperparathyroidism, whereas a suppressed hormone level sends the work-up toward malignancy (PTHrP-secreting carcinoma, myeloma, bone metastases), vitamin D excess or sarcoidosis. Phosphate is low-normal in primary disease because hormone promotes phosphaturia, and this calcium-phosphate divergence is a bedside confirmation of the physiology.
Localisation then follows function: sestamibi scanning with ultrasound identifies the adenoma, and a minimally invasive parathyroidectomy cures the stones-and-bones syndrome in the overwhelming majority. Contrast the second patient on the nephrology ward — chronic kidney disease stage 5, calcium at the low end, phosphate high, parathyroid hormone ten-fold raised. This is secondary hyperparathyroidism, and the logic inverts: the gland is right and the kidney is wrong, so treatment is phosphate restriction, binders and calcitriol to quiet the stimulus rather than excision. When that same patient, years later, develops a calcium of 12.5 despite appropriate medical management, autonomy has set in — tertiary hyperparathyroidism — and surgery re-enters the conversation.
Where students slip
Every hypercalcaemia becomes "malignancy" in orals, and the parathyroid hormone level — the single test that sorts primary hyperparathyroidism from all other causes — is forgotten; the mark is for the paired interpretation, not the diagnosis. The brown tumour is biopsied as a giant cell tumour when the biochemistry would have prevented the needle. And pseudohypoparathyroidism is treated as a parathyroid deficiency and given hormone replacement, when the gland is working overtime against a resistant receptor — the short metacarpals and the high hormone level are the two findings that should stop that error.
Frequently asked questions
What is the most common cause of primary hyperparathyroidism?
A single parathyroid chief-cell adenoma in 85 to 90 per cent; primary hyperplasia suggests MEN1 screening.
What is a brown tumour and how is it distinguished from giant cell tumour of bone?
An osteoclast-rich, haemorrhagic fibrous lesion of hyperparathyroidism; the surrounding hypercalcaemia, high parathyroid hormone and raised alkaline phosphatase separate it from a true giant cell tumour.
Which syndromes include hyperparathyroidism?
MEN1 (parathyroid, pancreas, pituitary) and MEN2A (medullary thyroid carcinoma, phaeochromocytoma, parathyroid), the latter from RET mutation.
Why is parathyroid hormone high but calcium low in chronic kidney disease?
Phosphate retention and reduced calcitriol lower ionised calcium, driving physiological — secondary — parathyroid hyperplasia; the skeleton develops renal osteodystrophy.
What is the most common cause of hypoparathyroidism in India?
Surgical injury or removal during thyroidectomy, presenting with perioral tingling, carpopedal spasm and positive Chvostek and Trousseau signs.
What defines pseudohypoparathyroidism?
Target-organ resistance to parathyroid hormone — hypocalcaemia with elevated hormone levels, plus Albright hereditary osteodystrophy with short fourth and fifth metacarpals.