Shigeru Yumita

Heterogeneity of pseudohypoparathyroidism type I from the aspect of urinary excretion of calcium and serum levels of parathyroid hormone

SummaryUrinary excretion of calcium (Ca) was measured in 9 patients with pseudohypoparathyroidism (PHP) type I—3 with Albrights hereditary osteodystrophy (AHO): AHO(+) and 6 without AHO: AHO(−)—and in 13 with idiopathic hypoparathyroidism (IHP), treated with active vitamin D3 (1,25(OH)2D3 or 1αOHD3) to maintain serum Ca levels at 8.4–9.5 mg/dl. Fasting urinary excretion of Ca in PHP was significantly lower than that in IHP. Moreover, fasting urinary excretion of Ca in PHP AHO(+) was lower than that in PHP AHO(−). This difference was also seen in the urine after oral loading of Ca. Urinary excretion, of sodium (Na) was not different between PHP AHP(+) and PHP AHO(−). Serum levels of immunoreactive PTH in PHP AHO(+) were higher than those in PHP AHO(−). The difference in urinary excretion of Ca between PHP AHO(+) and PHP AHO(−) may come from the difference in the circulating levels of PTH.

Sensorineural hearing loss associated with hypoparathyroidism

The hearing loss of 21 patients with hypoparathyroidism was investigated by pure tone audiometry, short increment sensitivity index (SISI) test, Békésy audiometry, speech audiometry, and auditory brain stem response. Sensorineural hearing loss was found in 7 of 21 patients (13 of 42 ears) receiving no treatment for hypoparathyroidism or having chronic hypocalcemia. The high SISI score, presence of recruitment, and prolongation of the wave I (N1) latency suggested that the inner ear is responsible for hearing loss in these cases. Inner ear dysfunction was probably due to the low calcium level in inner ear fluid and/or the direct effect of vitamin D deficiency on the inner ear.

Response of plasma 1,25-dihydroxyvitamin D in the human PTH(1-34) infusion test: an improved index for the diagnosis of idiopathic hypoparathyroidism and pseudohypoparathyroidism.

SummarySynthetic human parathyroid hormone (1–34) (hPTH(1–34) infusion test has been utilized in the differential diagnosis of hypoparathyroidism by examining the incremental response of urinary phosphate and cyclic adenosine monophosphate (AMP). The response of plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) in parathyroid hormone (PTH) infusion test was studied as a new criterion for the differential diagnosis of idiopathic hypoparathyroidism (IHP) and pseudohypoparathyroidism (PHP). Fourteen patients with IHP, 4 patients with PHP, and five control subjects were studied. All subjects received an intravenous infusion of 30 μg hPTH(1–34) over 5 minutes. The basal levels of plasma 1,25(OH)2D in patients with IHP and PHP were significantly lower than those in control subjects, but there was no significant difference between the levels in patients with IHP and in patients with PHP. The plasma levels of 1,25(OH)2D increased after the infusion of hPTH(1–34) and reached a peak 6 to 24 hours afterward. The 1,25(OH)2D increase at 24 hours after the infusion (Δ1,25(OH)2D) in control subjects and in patients with IHP were 18.1±3.91 (mean±SEM) and 24.1±2.80 pg/ml, respectively. There was no significant increase in patients with PHP (Δ1,25(OH)2D=4.9±1.97 pg/ml). From these results, the measurement of Δ1,25(OH)2D in hPTH(1–34) infusion test is useful as a criterion for the differential diagnosis of hypoparathyroidism.

Effects of parathyroid hormone on urinary excretion of N-acetyl-β-D-glucosaminidase in idiopathic hypoparathyroidism and pseudohypoparathyroidism

SummaryN-acetyl-β-D-glucosaminidase(NAG) is a lysosomal enzyme predominantly located in renal proximal tubules. In idiopathic hypoparathyroidism(IHP), 100 Units of human PTH(1–34) increased urinary excretion of NAG from 0.029±0.027 to 0.173±0.035 U/1GF (p<0.05) in two patients before treatment and from 0.025±0.004 to 0.189±0.092U/1GF (p<0.02) in four patients during treatment with active vitamin D3 (1,25(OH)2D3 or 1αOHD3). In pseudohypoparathyroidism(PHP), PTH did not significantly increase the urinary excretion of NAG in one patient with before treatment (0.048 to 0.025 U/1GF) and four patients during treatment with active vitamin D3 (0.018±0.008 to 0.036±0.015 U/1GF). Increase in urinary excretion of NAG after injection of PTH may be a new indicator of renal effect of PTH.

Treatment of Pseudohypoparathyroidism with 1α-Hydroxyvitamin D3

A maintenance dosis of 2 microgram/day of 1 alpha-OH-D3 could keep the level of serum calcium normal in all 5 cases with pseudohypoparathyroidism, in contrast with 4.0 +/- 1.26 microgram/day needed for the 11 cases with hypoparathyroidism (8 idiopathic and 3 postoperative). The conspicuous effect of 1 alpha-OH-D3 on pseudohypoparathyroidism is likely to be attributed to the fact that the unresponsiveness of bone tissue to parathyroid hormone is corrected by the action of active vitamin D.

Suppressibility of Parathyroid Function in Primary Hyperparathyroidism as Estimated

The effects of calcium injection (3 mg/Kg/10 min) or oral calcium administration (calcium lactate 7.7 g) on plasma iPTH and Nephrogenous cyclic AMP (NcAMP) were studied in 6 normal controls and 13 patients with primary hyperparathyroidism. In the control subjects, plasma iPTH determined by a predominantly carboxyl-terminal antiserum was less than 0.3 ng/ml before and after both calcium loads, whereas 41 approximately 98% (mean 67%) of NcAMP was rapidly and uniformly suppressed to a level lower than the normal value. In 2 patients with primary hyperparathyroidism, iPTH was clearly reduced from 8.0 to 4.6 ng/ml and 1.6 to 0.96 ng/ml, respectively, by the calcium load. However, in the other 7 patients with primary hyperparathyroidism who showed only a slight elevation of iPTH: less than 0.3 approximately 0.9 ng/ml, the reductions in iPTH were not detected after the calcium load: less than 0.3 approximately 0.7 ng/ml. In contrast, 30 approximately 54% (1.02 approximately 3.85 nmol/dl GF) of NcAMP, which was greater than the diurnal variation, was suppressed after calcium injection in 5 patients with primary hyperparathyroidism (2 of 4 patients with urological, and 3 of 5 patients with chemical hyperparathyroidism). But NcAMP was not suppressed in all 4 patients with skeletal hyperparathyroidism including one with proximal renal tubular dysfunction whose basal iPTH was elevated markedly but reduced clearly by the calcium load. In general, suppression of NcAMP was followed by a decrease of phosphate excretion. On the other hand, even in a patient with primary hyperparathyroidism whose NcAMP was not suppressed at all after the calcium injection, calcium infusion (15 mg/Kg/3h) resulted in some (23%) decrease in NcAMP. Oral calcium administration resulted in responses which were almost the same as those produced by calcium injection. These results suggest that NcAMP provides a useful index in the parathyroid suppression test in patients with primary hyperparathyroidism, especially those who display a rather mild elevation of iPTH. This is not the case, however, in a few patients who show a marked elevation of iPTH and/or proximal renal tubular dysfunction.