Hydrated clearance of gadolinium-DTPA as a measurement of glomerular filtration rate.

Technetium (99mTc)-diethylene triamine pentaacetic acid (DTPA) hydrated clearance studies are accurate for determining GFR but require special facilities for handling and measuring samples. We investigated the potential of a non-radioactive paramagnetic analog, Gadolinium (Gd)-diethylene triamine pentaacetic acid (DTPA), an approved NMR contrast agent, as a glomerular filtration marker. Instead of relying on the radioactivity of technetium, this test is based on the fact that gadolinium induces alterations in the NMR T1 relaxation times in blood and urine samples. Ninety patients underwent simultaneous determinations of GFR using 1 mCi of Tc-DTPA and 0.05 mmol/kg Gd-DTPA (Berlex Labs) IV. The patients were hydrated with oral and intravenous fluid. Following a one hour equilibrium period, three or four consecutive urine collections were obtained; plasma samples were acquired at the beginning and end of each approximately 20-minute interval. 99mTc-DTPA radioactivity was determined with a scintillation counter. T1 relaxation times were measured on a 10 MHz NMR spectrometer. These were converted to Gd-DTPA concentration by comparison with standard solutions. The Gd-DTPA derived GFR closely approximated the 99mTc-DTPA derived GFR which ranged from 15 to 147 ml/min. The equation and correlation coefficient of the regression line is y = 1.04 x -2.2, r = 0.94. Thus, Gd-DTPA is a safe, non-radioactive indicator of GFR that may provide an alternative renal clearance method for clinical studies of progressive renal disease and nephrotoxicity.

A novel testis-stimulating factor in familial male precocious puberty.

BACKGROUND: Familial male precocious puberty is a gonadotropin-independent form of precocious puberty that occurs only in males. The cause of the disorder is unknown. To examine the hypothesis that the plasma of boys with familial male precocious puberty contains a novel stimulator of testicular testosterone production, we developed a bioassay using adult male cynomolgus monkeys. METHODS: We collected plasma from 12 boys with familial male precocious puberty, 7 normal prepubertal boys of similar ages and with similar plasma gonadotropin levels, and 1 boy with hypogonadotropic hypogonadism and infused it into the testicular artery of adult male cynomolgus monkeys that had been pretreated with gonadotropin-releasing-hormone antagonist to inhibit the endogenous secretion of gonadotropins. Testicular venous effluent was collected at 15-minute intervals for 3 or 5 hours for the measurement of testosterone. RESULTS: The mean (+/- SE) peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from the 12 boys with familial male precocious puberty than in the monkeys infused with plasma from the 7 normal prepubertal boys and the boy with hypogonadotropic hypogonadism (385 +/- 51 vs. 184 +/- 25 percent, P less than 0.005) in the three-hour studies. Plasma from 92 percent of the boys with familial male precocious puberty and 12.5 percent of the normal prepubertal boys stimulated a response greater than 195 percent of base-line values. In the animals studied for five hours after receiving a second dose of antagonist, the mean peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from three boys with familial male precocious puberty than in the monkeys infused with plasma from three normal prepubertal boys (363 +/- 81 vs. 115 +/- 6 percent, P less than 0.01). The mean area under the testosterone-response curve was significantly larger in the monkeys infused with plasma from the boys with familial male precocious puberty in the five-hour studies (154 +/- 34 vs. -58 +/- 10 percent, P less than 0.005), but not in the three-hour studies. CONCLUSIONS: These findings support the presence of a circulating testis-stimulating factor in the plasma of boys with familial male precocious puberty. The production of such a factor would explain the biologic nature of the disorder.