Normocalcemic primary hyperparathyroidism
The diagnosis of normocalcemic primary hyperparathyroidism (PHPT) can be made in subjects whose total and ionized serum calcium are completely normal but in whom the PTH level is persistently elevated. In order to make the diagnosis of normocalcemic PHPT, secondary causes for an elevated PTH level should be ruled out, such as vitamin D insufficiency, or renal insufficiency. Replacing the former patients with vitamin D to reach levels now considered to be normal (i.e. >30 ng/ml) often returns the PTH to normal. Occasionally, however, these patients will become hypercalcemic with vitamin D replacement thus unmasking more typical hypercalcemic PHPT. If the PTH remains elevated and the serum calcium remains normal, following vitamin D repletion, and other causes of an elevated PTH have been excluded, then the diagnosis of normocalcemic PHPT can be considered. Since there are limited data on the natural history of normocalcemic PHPT, it is unclear how these subjects should be regarded vis a vis parathyroid surgery. A large population based study of over 5000 postmenopausal women who were screened and then retested 8 years later provided evidence for the development of hypercalcemia in some of these subjects. Two observational studies of normocalcemic PHPT have followed patients longitudinally. In one study 37 patients were followed for a mean of 3 years (range 19). Typical hypercalcemic PHPT emerged in 7 (19%) individuals. However, 40% developed evidence of disease progression with development of kidney stones, fractures, marked hypercalciuria or >10% decline in BMD. Seven patients had successful parathyroidectomy, of whom three were hypercalcemic and the rest met other criteria for surgery. Clearly, normocalcemic PHPT is a newly recognized clinical phenotype of PHPT.