The diagnosis of pHPT is based on the finding of normal/high serum calcium levels inadequately associated to circulating PTH values at the upper limit or higher than normal. The clinical presentation of pHPT is variable, with asymptomatic/ paucisymptomatic normocalcemic cases being now more fre­quent than classic symptomatic cases. The presence of de­pression and abdominal symptoms is often reported by these patients.

Modest increase in circulating PTH levels are a common find­ing in postmenopausal women due to widespread screening for menopausal osteoporosis. Often these PTH modifications re­veal normocalcemic asymptomatic pHPT without specific indi­cation for surgery.

Cases of pHPT with recurrent kidney stones often show serum total calcium levels in the upper limit of normal (10.0 and 10.5 mg/dl), high ionized calcium levels, modest increases of PTH, and hypercalciuria. The finding of modest increases of circulat­ing PTH in the presence of normal ionized calcium and total serum calcium level in the low-normal range is not indicative for pHPT. The presence of hypercalciuria suggests the possi­bility of idiopathic hypercalciuria (IH).

The diagnosis of pHPT relies only on clinical and laboratory da­ta, even though often pHPT patients are referred to specialized Centers with poor clinical and biochemical evaluation, but with an unnecessary and expensive imaging documentation. In­deed, imaging studies have a primary role only in the presurgi- cal detection and spatial assessment of a pathologic parathy­roid tissue.

Imaging of pathologic parathyroid nodules can be difficult due to the differences in size (from undetectable by US, CT or MR techniques to large nodules) and the variability in the location of the glands in the neck or mediastinum (due to the embryologic origin). Moreover, the presence of nodules in the neck is a common finding during routinary US examination, and the imaging techniques currently available cannot provide specific diagnostic criteria useful for the recognition of parathyroid tis­sue. The combination of US and dual phase 99mTc-MIBI, both having a high sensitivity and specificity, leads to an im­provement of sensitivity, negative predictive value, and accura­cy, with no decrease of the high specificity and positive predic­tive value with respect to each single technique. In fact, scintigraphic positivity is able to clarify the cases of lack of US characterization, while US is able to detect small glands that can be missed by scintigraphy due to small dimensions, low metabolic activity or presence of necrotic or cystic areas. It is important to emphasize that dual phase 99mTc-MIBI scintigra­phy has high accuracy in differentiating thyroid vs parathyroid nodules. However, 99mTc-MIBI scintigraphy can be considered a generic “cellular activity marker” and its positivity can be due to many pathologies such as mammary cancer, lymphomas, flogistic lymph nodes, and Hurtle cell adenoma. On the other hand US and CT provide high sensitivity in lo­cating the pathologic glands also if ectopic (neck and medi­astinum). A strong enhancement on post-contrastographic CT, indicating the presence of a high vascularity is present only in some cases of PT pathologic glands and nodules of different nature can exhibit similar enhancement ratio. Therefore the in­tensity of CT enhancement cannot be considered an unam­biguous characterization criteria for parathyroid enlarged gland. On the basis of these considerations imaging procedure, while representing a fundamental tool for the surgeon, can lead to wrong diagnostic conclusions when clinical and laboratory data are not evaluated by experienced specialists in Mineral Metab­olism.

Patient 1 is a clear example of these limitations. In fact, a histo­ry of recurrent kidney stones with hypercalciuria, high PTH lev­els, osteoporosis, depression and abdominal pain could be evocative of pHPT. However, the absence of increased serum ionized calcium levels associated to normal phosphorus and total calcium level in the low-normal range in a patient suffering from renal stones for the past 25 years has to pose the suspect of IH. In this condition PTH increase is secondary to hypercal- ciuria which causes kidney stone disease and osteoporosis. The information derived from imaging techniques did not help the primary care physician to reach a correct diagnosis. On the contrary the recognition of a mediastinal mass led to major thoracic surgery for a sarcoidotic lymph node, that could have been treated conservatively. Your life is worth living. Buy 

In patient 2 the clinical and laboratory data showed an unequiv­ocal diagnosis of symptomatic pHPT, as indicated by high cir­culating ionized calcium levels and inappropriately elevated PTH levels. In this case imaging findings guided the surgeon to the ablation of pathologic PT tissue.

In conclusion, the diagnosis of pHPT must be based on clinical and laboratory data. Imaging studies do not add useful diag­nostic information, having, however, a role in the presurgical detection of enlarged parathyroid gland(s). The use of imaging studies to clear doubts in clinical diagnosis of pHPT may in­deed lead to wrong therapeutical choices.