Hyperparathyroidism

Parathyroid hormone increases the release of calcium and phosphate from bone,
increases calcium reabsorption by the kidney and increases renal production of 1,25-
dihydroxyvitamin D-3 (calcitriol) which increases intestinal absorption of calcium. As well
as increasing serum calcium, parathyroid hormone also causes phosphaturia, therefore
reducing serum phosphate levels.

Epidemiology

Prevalence of primary hyperparathyroidism is approximately 4 cases in 100,000

persons.
Primary hyperparathyroidism affects women twice as frequently as men.
Prevalence increases with age, but can affect any age.
Familial cases can occur, either as part of the multiple endocrine neoplasia
syndromes (ie, type 1 or type 2a) or as familial hyperparathyroidism.

Causes of primary hyperparathyroidism

Single parathyroid adenoma (85% of cases).

Hyperplasia (14%)
Carcinoma (less than 1%)

Secondary hyperparathyroidism Parathyroid glands become hyperplastic after long-

term stimulation in response to chronic hypocalcaemia. Usually seen in renal disease
and seen in virtually all patients with dialysis-dependent chronic renal failure. It can occur
in any condition with chronic hypocalcaemia such as vitamin D deficiency or
malabsorption.
Treatment with calcitriol and calcium can either prevent or minimize secondary
hyperparathyroidism. However total parathyroidectomy and autotransplantation is
considered the treatment of choice1.

Tertiary hyperparathyroidism occurs after prolonged secondary hyperparathyroidism.

The glands become autonomous, producing excessive secretion of PTH (after the cause
of hypocalcaemia has been corrected) and results in hypercalcaemia. This occurs in
patients with chronic renal failure or after a renal transplant. Management is as for
primary hyperparathyroidism and total parathyroidectomy with auto-transplantation or
subtotal parathyroidectomy is indicated.

Presentation Clinical features are due to:

 Excessive calcium resorption from bone causing osteopenia, presenting as bone
pain and pathological fractures.
Excessive renal calcium excretion causing renal stones.
Hypercalcaemia:
o Muscle weakness, fatigue.
o Nausea and vomiting; constipation; abdominal pain; peptic ulcer disease;

pancreatitis
o Polyuria, polydipsia, dehydration
o Neuropsychiatric manifestations are particularly common and may include

depression and confusion.

o Severe cases may lead to coma and death.

Differential Diagnosis Other causes of hypercalcaemia, especially malignancy, but

other causes include thyrotoxicosis, sarcoidosis, Paget's disease and Addison's disease.

Investigations Most cases are diagnosed by demonstrating persistent hypercalcaemia

and elevated parathyroid hormone level.

Total serum calcium and albumin levels; ionized calcium levels if available.
Renal function, electrolytes, amylase.
24 hour urinary calcium excretion: to differentiate from familial hypocalciuric
hypercalcaemia in which there is a low 24 hour urine calcium excretion. May not
be necessary if the diagnosis of primary hyperparathyroidism is not in doubt.
X-rays: is occasionally helpful to determine end organ damage (but likely to be
normal in early cases). Subperiosteal resorption (especially on hand x-ray); chest
x-ray and skull x-ray (pepper-pot skull). Consider x-ray's of other joints
(chondrocalcinosis, pseudogout).
DEXA scan: osteoporosis is common.
Imaging of renal tract: x-ray, ultrasound.
If neck exploration has failed, 99mTc-sestamibi scan, Thallium or Tc subtraction
scanning, CT scan, ultrasound, and/or angiography with selective venous
sampling may be required.

Associated Diseases Multiple endocrine neoplasia type I and IIa.

Management of primary hyperparathyroidism Definitive treatment involves surgery

but surveillance may be justified in patients whose calcium levels are only mildly
elevated and whose renal and bone status are close to normal2. Such patients may
continue for long periods without deteriorating. Monitor plasma calcium, renal function,
blood pressure, regular assessments of bone mineral density and renal ultrasound.
 Avoid dehydration (advise a high fluid intake) and also avoid thiazides; patients
should have a moderate calcium intake.
Treatment hypercalcaemia with appropriate drugs (see related article).
Surgery - either by removal of an adenoma or carcinoma, or parathyroidectomy
with auto-transplantation or subtotal parathyroidectomy for hyperplasia. Surgery
is advocated because patients who are unaware of mild hyperparathyroidism may
still have an increased prevalence of mild psychiatric symptoms, bone loss, and
have increased risk of cardiovascular disease.