We used a new radiopharmaceutical agent, [131I]meta-iodobenzylguanidine ([131I]MIBG), to produce scintigraphic images of pheochromocytomas in eight patients. One day or more after injection, the only normal organ that displayed distinct concentrations of radioactivity was the urinary bladder. The [131I]MIBG was probably concentrated in adrenergic vesicles; in tissues where vesicles are numerous, such as pheochromocytomas, the radionuclide was retained for days. The spectrum of pheochromocytomas shown the scintigrams was broad: intra-adrenal and extraadrenal in location, benign and malignant in character, 0.2 to 65 g in weight, and with different hormone patterns in secretion. Tumors in four patients were not detected by computed tomography. In one patient, reoperation was undertaken only because the scintigram located the extra-adrenal tumors and thereby directed the surgeon's exploration. The method offers hope of safe and reliable localization of pheochromocytomas in their many guises.

Patients with isolated gonadotropin deficiency were studied to determine whether pulsatile low dose gonadotropin-releasing hormone (GnRH) could induce the hormonal changes seen during normal puberty. Four male and two female patients with immature responses to a standard GnRH test (2.5 micrograms/kg) were given GnRH (0.025 micrograms/kg) iv every 2 h for 5 days. FSH responses varied between the sexes, and FSH concentrations in males rose continuously to 17.2 +/- 4.7 mIU/ml on day 5. In the females, FSH peaked at 13.8 and 15.8 mIU/ml on days 3-4 and then declined. The males showed increasing and the females decreasing incremental FSH responses to GnRH. LH concentrations and incremental responses to GnRH rose throughout the study in both sexes. Plasma testosterone rose slightly in the males to 0.7 +/- 0.2 ng/ml (P < 0.05), but in females estradiol increased to follicular range concentrations of 128 and 102 pg/ml. Standard GnRh tests on day 6 revealed maturation of gonadotropin responses in all patients. After termination of pulsatile GnRH, four patients were given single low dose GnRH injections on two to seven occasions over a period of 2-32 days. Initial LH responses were 2- to 14-fold greater than those seen on day 5 of pulsatile GnRH, and decreased over the next 3 weeks. FSH responses showed less initial augmentation and declined more slowly. Low dose pulsatile administration of GnRH to patients with isolated gonadotropin deficiency results in changing patterns of hormone secretion similar to those seen during puberty. Exaggerated pituitary sensitivity to GnRH may be present long after a brief period of GnRH stimulation, and may indicate previous rather than current secretion of GnRH.

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SummaryFourteen children between 2.5 and 16 years of age were studied to provide a quantitative estimate of the changes in gonadotropinreleasing hormone (GnRH) pulse amplitude in hypophysial portal plasma during puberty. Responses to physiologic doses of synthetic GnRH were measured [induced luteinizing hormone (ALH) and induced follicle-stimulating hormone (AFSH)] and compared with spontaneous fluctuations in gonadotropins [spontaneous luteinizing hormone (A.LH) and spontaneous follicle-stimulating hormone (A.FSH)I. One to four lowdose (0.0125 or 0.025 &kg IV) pulses of GnRH were given every 2 hr between OSOO and 1600 or 2200 and 0400 hr. Maximal peripheral plasma concentrations of GnRH one min after pulses averaged 107 f 25 pg/ml (S.E.) (0.0125 pg/ kg dose) and 218 * 33 pg/ml (0.025 &kg dose). In early pubertal children,the maximal ALH was similar to or less than the maximal nocturnal L L H (maximum, ALH 7.0 f 0.2 versus maximum A.LH 7.0 * 1.3 mIU/ml in boys, 7.0 f 1.2 versus 16.0 f 3.0 mIU/ml in girls). Luteinizing hormone (LH) responses were low or undetectable in children whose bone ages were less than 10 years. When discernible, LH pulse frequency was similar during daytime and nighttime sampling periods in early pubertal boys. However, two hourly injections of GnRH given during the day did not simulate the initial nocturnal rise in LH. Overall mean AFSH and L F S H that luteinizing hormone (LH), but not follicle-stimulating hormone (FSH) release increases strikingly at puberty in both sexes, whereas FSH release is greater in prepubertal girls than boys.Information about GnRH secretion into the hypophysial portal system has been obtained via direct measurement in several animal species (1,3,6,18,22). Camel et al. (3) have measured portal blood GnRH in monkeys and found it to vary between 10 to 800 pg/ml. In humans, suchmeasurements are impractical, and information has been obtained via indirect techniques. We have pre-viously used responses to synthetic GnRH to istimate the hypophysial portal plasma concentration of GnRH in men and to gain information about its secretory pattern. On the basis of these studies, we concluded that the portal plasma concentration of GnRH varied between <30 and 300 pg/ml (a), an estimate similar to those obtained by direct measurement in animals. A similar study in prepubertal children would be difficult to interpret because of the shallow dose response curve for LH in these children (7,9). In this study, we have utilized the striking FSH responses of prepubertal and hypogonadal children, as well as the marked day/night difference in LH secretion characteristic of early puberty to estimate GnRH pulse amplitude. MATERIALS AND METHODSwere similar in three prepubertal female patients (3.0 * 0.2 versus 2.8 * 0.2 mIU/ml). AFSH was greater than L F S H in two patients All studies were done in the Clinical Research Center after with gonadal dysgenesis (bone ages, 2.5 m d 5 years) m d in one written informed parental These studies were approved by the Human Investigation Committee of t...