438creatinine × serum calcium). The ratio is lower than 0.01 in 80% of individuals with FHH. However, approximately 20% of individuals have the ratio between 0.01 and 0.02, and in these individuals, other factors that can lower the ratio need to be considered. Possible conditions include renal insufficiency or severe calcium or vitamin D deficiency. The calcium-to-creatinine clearance ratio can also be low in individuals of African descent. 5 On the other hand, 80% of individuals with PHPT have a calcium-to-creatinine clearance ratio exceeding 0.02; an overlap of PHPT and FHH can occur in 20% of individuals and the ratio can be between 0.01 and 0.02.5 FHH should be excluded prior to confirming the diagnosis of PHPT, because hypercalcemia will persist even after parathyroid surgery, and it is important not to refer individuals with FHH for surgery because it is unnecessary and of no benefit.As the focus of the article is on diagnosis and management of PHPT, calcium homeostasis is described only briefly. The main regulator of serum calcium is PTH. The synthesis and secretion of PTH is stimulated by a decrease in extracellular calcium levels. PTH enhances renal calcium reabsorption, bone resorption, and the hydroxylation of 25-hydroxyvitamin D in the kidney, resulting in elevations in serum calcium levels into the normal reference range (FIGURES 1 and 2). Extracellular calcium binds to the calcium-sensing receptor on the chief cells in the parathyroid glands and inhibits the synthesis and secretion of PTH (FIGURE 3). Diagnosis Primary hyperparathyroidism (PHPT)is caused by a single parathyroid adenoma in approximately 85% of patients. In 15% of individuals, it can be associated with hyperplasia, and, fortunately, parathyroid carcinoma is rare. 1 PHPT is diagnosed in the presence of hypercalcemia and an elevated or inappropriately normal parathyroid hormone (PTH) levels, following exclusion of other conditions that can mimic PHPT. 1,2 The use of hydrochlorothiazide and lithium can result in elevations in serum calcium and PTH levels. Hydrochlorothiazide should be discontinued and the laboratory profile should be repeated 3 months later to confirm the diagnosis of PHPT. Hydrochlorothiazide enhances renal calcium reabsorption; it can result in elevations in serum calcium levels and must be discontinued prior to confirming the diagnosis. Lithium elevates the set point for serum calcium levels. It may be difficult to discontinue lithium and the patient may require management decisions to be made during ongoing lithium use.Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant condition that can mimic PHPT. It is caused by an inactivating mutation of the calcium-sensing receptor gene. The less common variant is FHH2, which is caused by an inactivating mutation of the G protein alpha 11 subunit.3 The FHH3 variant is caused by inactivating mutations of the adaptor protein 2 sigma subunit.4 FHH is excluded by evaluating the calcium-to-creatinine clearance ratio, which is calculated using the following formula: ...

No abstract

Background-Traditional cardiovascular risk factors lead to endothelial injury and activation of leucocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable CAD imparts a pleiotropic effect that extends beyond anti-platelet aggregation to other athero-protective processes.

No abstract

No abstract