Circulating Parathyroid Hormone Activity: Familial Hypocalciuric Hypercalcemia Versus Typical Primary Hyperparathyroidism*

Abstract

Three indices of circulating parathyroid hormone (PTH) activity were compared between two groups: the first a group of 23 patients from three large kindreds with autosomal dominant hypercalcemia without hypercalciuria [familial hypocalciuric hypercalcemia (FHH)] and the second a group of 64 patients with typical primary hyperparathyroidism (1HPT) manifesting comparable hypercalcemia. The group with 1HPT differed from normal with respect to plasma PTH 1HPT concentration (normal, less 0.2 ng/ml), urinary cAMP excretion per 100 ml glomerular filtrate (U cAMP/GF) (normal, 2.3 x/divided by 0.6 nmol/100 ml glomerular filtrate; mean, x/divided 1 SD), and renal tubular maximum of phosphate transport corrected for glomerular filtration rate (TMP/GFR; normal, 3.4 +/- 0.4 mg/dl; mean, +/- 1 SD). The group with 1HPT also diverged significantly from the group with FHH for all three indices: for PTH, 0.37 x/divided by .48 vs. 0.25 x/divided .46 (P less than 0.05); for UcAMP/GF, 4.3 x/divided by .53 vs. 2.6 x/divided .60 (P less than 0.0005); and for TMP/GFR, 2.0 +/- 0.6 vs. 2.6 +/- 0.7 (P less than 0.01). The between-group differences for all three indices were also significant after adjustment for their variation with serum calcium. However, only the difference in TMP/GFR remained significant after adjustment for covariance attributable to serum calcium concentration, age, and creatinine clearance. The group with FHH differed from normal for TMP/GFR but not for UcAMP/GF. However, analysis of changes in UcAMP/GF and serum calcium concentration around the time of parathyroidectomy in three patients with FHH suggested that the parathyroid glands contributed to the abnormalities of mineral homeostasis in at least one. It was concluded that higher serum concentrations of PTH do not account for the lower renal clearance of calcium and magnesium in FHH calcium concentration, the group with FHH showed indices suggesting lower circulating PTH activity than the group with 1HPT.

Current Status and Treatment of Primary Hyperparathyroidism

“…BFHH can be excluded by documenting a previous normal blood calcium level or if the 24-hour urine calcium level is not low (ie, not less than 100 mg per 24 hours), with a ratio of urine calcium to creatinine clearance of >0.02 (this ratio is usually <0.01 in patients with BFHH). 20 Other laboratory derangements sometimes seen in patients with primary HPT include a low or low-normal phosphorous level, an increased chloride-to-phosphorous ratio (>33), a high or high-normal 1,25-dihydroxy vitamin D level, and an increased alkaline phosphatase level. 21,22 The latter signifies high-turnover bone disease, and these patients are at risk for developing hypocalcemia after parathyroidectomy.…”

A New Family of Boucher-Neuhauuser Syndrome: Coexistence of Holmes Type Cerebellar Atrophy, Hypogonadotropic Hypogonadism and Retinochoroidar Degeneration: Case Reports and Review of Literature.

“…Usually hypocalciuric hypercalcemia is a familial disease with autosomal dominant inheritance [33][34][35][36]. Most recently, cDNA encoding an extracellular Cat+-sensing receptor has been cloned from the bovine parathyroid gland and well characterized [37].…”

Plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism

“…Vitamin D metabolism has been explored only in a small number of FHH patients (17)(18)(19). We have recently reported on the ability of the calcium/creatinine clearance ratio (CCCR) and other variables of renal calcium excretion to discriminate between FHH and PHPT (20), as described by Marx et al and others (1,(21)(22)(23)(24)(25)(26).…”