The most common cause of primary hyperparathyroidism is a sporadic, single parathyroid adenoma[6] resulting from a clonal mutation (~97%). Less common are parathyroid hyperplasia[7] (~2.5%), parathyroid carcinoma (malignant tumor), and adenomas in more than one gland (together ~0.5%).
Primary hyperparathyroidism is also a feature of several familial endocrine disorders: Multiple endocrine neoplasia type 1 and type 2A (MEN type 1 and MEN type 2A), and familial hyperparathyroidism.
Genetic associations include:
OMIM Name Gene  headingBody  145000 HRPT1 MEN1, HRPT2 145001 HRPT2 HRPT2 610071 HRPT3 unknown at 2p13.3-14[8]
In all cases, the disease is idiopathic, but is thought to involve inactivation of tumor suppressor genes (Menin gene in MEN1), or involve gain of function mutations (RET proto-oncogene MEN 2a).
Recently, it was demonstrated that liquidators of the Chernobyl power plant are faced with a substantial risk of primary hyperparathyroidism, possibly caused by radioactive strontium isotopes.[9]
Primary hyperparathyroidism can also result from pregnancy. It is apparently very rare, with only about 110 cases have so far been reported in world literature, but this is probably a considerable underestimate of its actual prevalence in pregnant women.[10]
The diagnosis of primary hyperparathyroidism is made by blood tests.
Serum calcium levels are elevated, and the parathyroid hormone level is abnormally high compared with an expected low level in response to the high calcium. A relatively elevated parathyroid hormone has been estimated to have a sensitivity of 60%-80% and a specificity of approximately 90% for primary hyperparathyroidism.[11]
A more powerful variant of comparing the balance between calcium and parathyroid hormone is to perform a 3-hour calcium infusion. After infusion, a parathyroid hormone level above a cutoff of 14 ng/l has a sensitivity of 100% and a specificity of 93% in detecting primary hyperparathyroidism, with a confidence interval of 80% to 100%.[12]
Urinary cAMP is occasionally measured; this is generally elevated.[citation needed]
Biochemical confirmation of primary hyperparathyroidism is following by investigations to localize the culprit lesion. Primary hyperparathyroidism is most commonly due to solitary parathyroid adenoma. Less commonly it may be due to double parathyroid adenomas or parathyroid hyperplasia. Tc99 sestamibi scan of head, neck and upper thorax is the most commonly used test for localizing parathyroid adenomas having a sensitivity and specificity of 70-80%. Sensitivity falls down to 30% in case of double/multiple parathyroid adenomas or in case of parathyroid hyperplasia. Ultrasonography is also a useful test in localizing suspicious parathyroid lesions.
The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are classically summarized by "stones, bones, abdominal groans, thrones and psychiatric overtones".
"Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to renal failure.&"Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.&"Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis. The peptic ulcers can be an effect of increased gastric acid secretion by hypercalcemia.[1]&"Thrones" refers to polyuria and constipation&"Psychiatric overtones" refers to effects on the central nervous system. Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma
Left ventricular hypertrophy may also be seen.[2]
Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.
When subjected to formal research, symptoms of depression, pain, and gastric dysfunction seem to correlate with mild cases of hypercalcemia.[3]