Etiology

Eighty to 90% of hyperparathyroidism patients have single parathyroid adenomas, and up to 5% may have double adenomas. Diffuse hyperplasia of all four glands accounts for 6% cases of primary hyperparathyroidism (PHP). One to 2% of cases are due to parathyroid carcinoma.

The diffuse hyperplasia of all four glands can be sporadic or familial; occurring usually as a part of the multiple endocrine neoplasia (MEN) type 1 or 2 syndromes ( Table 7.12 ). Other familial conditions associated with all-four-gland hyperplasia include familial hyperparathyroidism–jaw tumor syndrome and familial isolated hyperparathyroidism.

Familial hypocalciuric hypercalcemia is a rare, autosomal dominant disorder that should be included in the differential diagnosis of PHP. It is caused by mutations of the calcium-sensing receptor.

Epidemiology

Primary hyperparathyroidism can occur at any age, but the great majority of cases occur over the age of 45 years. Women are affected twice as often as men.

Clinical

Primary hyperparathyroidism is most often detected incidentally by routine biochemical screening. Most patients either are asymptomatic or experience subtle and vague symptoms such as fatigue, depression, difficulty in concentration, and generalized weakness.

Patients with primary hyperparathyroidism rarely present with classic symptoms and signs of hypercalcemia, as recalled by the famed mnemonic “painful bones, renal stones, abdominal groans, and psychic moans”:

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  Bones: The classic bone disease of PHP is osteitis fibrosa cystica, which is now rare in the United States. It presents with bone pain and/or pathologic fractures. A more common skeletal manifestation of PHP is a decrease in the bone mineral density (osteopenia), preferentially at the cortical sites (forearm and hip). The cause is prolonged PTH excess.

  
  
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  Kidneys: Nephrolithiasis occurs in ~ 15 to 20% of patients with primary hyperparathyroidism. The cause is prolonged PTH excess. Hypercalciuria and chronic renal failure can also occur.

  
  
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  Gastrointestinal: Hypercalcemia-associated symptoms include anorexia, nausea, vomiting, constipation, and peptic ulcer disease.

  
  
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  Psychiatric and neurocognitive: Many patients may have depressed mood, lethargy, emotional lability, decreased cognitive function, and poor sleep. Frank psychosis is rare.

Often the presentation is much more subtle. Patients with familial hypocalciuric hypercalcemia are asymptomatic.

Parathyroid carcinomas are rare. Tumors may be large, palpable; PTH and calcium may be markedly elevated.