Basal Follicle-Stimulating Hormone and Peak Gonadotropin Levels after Gonadotropin-Releasing Hormone Infusion Show High Diagnostic Accuracy in Boys with Suspicion of Hypogonadotropic Hypogonadism

Context: Differential diagnosis between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty in boys is challenging. Most tests use an acute GnRH stimulus, allowing only the release of previously synthesized gonadotropins. A constant GnRH infusion, inducing de novo gonadotropin synthesis, may allow a better discrimination. Objective: We evaluated the diagnostic accuracy of basal and peak gonadotropins after GnRH infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH. Design and Setting: We conducted a validation study following Standards for Reporting of Diagnostic Accuracy criteria at a tertiary public hospital. Patients and Methods: A GnRH iv infusion test was performed in 32 boys. LH and FSH were determined by immunofluorometric assay at 0–120 min. Diagnosis Ascertainment: The following diagnoses were ascertained: complete HH (n = 19; testes < 4 ml at 18 yr), partial HH (n = 6; testes enlargement remained arrested for ≥1 yr or did not reach 15 ml), and constitutional delay of puberty (n = 7; testes ≥ 15 ml at 18 yr). Main Outcome Measures: Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were assessed. Results: Basal FSH less than 1.2 IU/liter confirmed HH with specificity of 1.00 (95% confidence interval = 0.59–1.00), rendering GnRH infusion unnecessary. In patients with basal FSH of at least 1.2 IU/liter, the coexistence of peak FSH less than 4.6 IU/liter and peak LH less than 5.8 IU/liter after GnRH infusion had high specificity (1.00; 95% confidence interval = 0.59–1.00) and diagnostic efficiency (76.9%) for HH. Conclusions: Basal FSH less than 1.2 IU/liter confirms HH, which precludes from further testing, reducing patient discomfort and healthcare system costs. In patients with basal FSH of at least 1.2 IU/liter, a GnRH infusion test has a high diagnostic efficiency.

THE INFLUENCE OF DIETARY MONENSIN ON THE LH RESPONSE TO GnRH OR ESTRADIOL AND THE OVULATORY RESPONSE TO PMSG IN GILTS

To test the effects of monensin on endocrine responsiveness, 43 gilts of Yorkshire and Landrace breeding were individually fed a 16% crude protein basal diet (CT, n = 22) or the basal diet incorporating 33 mg kg−1 monensin (M, n = 21) for 25 d. Gilt weights and feed intakes were recorded at 7-d intervals for 21 d. Monensin did not significantly affect weight gain or feed intake but feed conversion was improved (P < 0.03). At 21 d, M (n = 6) and CT (n = 7) gilts were fitted with vena caval canulae and infused with 50 μg GnRH. Blood samples were obtained at 10-min intervals from 30 min before to 60 min after GnRH infusion. After a 48-h recovery period, these gilts received an injection of estradiol-17 B (E2) and further blood samples taken at the time of injection, at 24 and 36 h then at 6-h intervals until 78 h. All serum samples were assayed for LH and FSH concentrations. The LH response to GnRH was not affected by monensin, peak values being achieved in both groups 30 min after infusion. Serum FSH was not significantly influenced by GnRH in either group. Following E2 injection, the LH surge height was greater (P < 0.09) in monensin-fed gilts and a treatment by time interaction was evident (P < 0.001). Serum FSH was elevated in both groups but was unaffected by monensin. At 21 d, non-blood sampled gilts received an injection of 750 IU PMSG and were slaughtered 10 d later. An ovarian examination indicated that monensin-fed gilts tended (P < 0.1) to have a lower ovulation rate (13.2 ± 1.0 vs. 17.4 ± 1.9 for M and CT gilts, respectively). These data suggest that the feeding of monensin to gilts alters hypothalamic/pituitary responsiveness to stimulation and may enhance growth performance. Key words: Gilts, monensin, LH, FSH

The effects of pulsatile GnRH infusion upon the diurnal variations in serum LH and testosterone in pre-pubertal and pubertal boys

The aim of the present study was to determine the effects of exogenous GnRH pulsatile infusions on the diurnal variations of LH and testosterone secretion which occur in late pre-puberty and early puberty. GnRH infusions were administered to 12 short stature males in pre-puberty or early puberty, over 6-day periods. In 6 patients, GnRH doses of 2.5, 7.5 and 15 μg/pulse were used and 24-h profiles of serum LH and testosterone were measured before and at the end of the infusions. In the remaining 6 patients GnRH was administered at a dose of 7.5 μg/pulse and profiles between 21.00 and 06.00 h the following day were determined. Pre-infusion profiles demonstrated nocturnal LH and testosterone rises in all patients. Median pre-infusion serum LH prior to midnight was 2.2 U/l (range 1.0–5.4) rising to 3.7 U/l (range 1.9–10.7) during GnRH administration (p < 0.005). After midnight, median pre-treatment serum LH concentration was 4.3 U/l (range 2.7–7.5) which remained unaltered by GnRH administration (median 4.8 U/l, range 2.9–7.9, p > 0.05). Median pre-therapy serum testosterone before midnight was 0.8 nmol/l (range 0.1−7.1) rising significantly (p < 0.05) to 4.1 nmol/l (range 0.2–8.0). Following therapy, post-midnight median serum testosterone rose from 4.8 (range 0.4–9.4) to 7.0 nmol/l (range 0.5–13.9, p > 0.05). Diurnal variation in LH and testosterone secretion, therefore, is maintained during exogenous GnRH administration to pre-pubertal and pubertal boys. Response to exogenous GnRH pulses may be significantly influenced by endogenous GnRH.

Effects of constant infusion of gonadotrophin-releasing hormone in ovariectomized ewes with hypothalamo-pituitary disconnection: further evidence for differential control of LH and FSH secretion and the lack of a priming effect

ABSTRACT Experiments were conducted in ovariectomized ewes after hypothalamo-pituitary disconnection (HPD) (a) to examine LH and FSH secretion during constant infusion of gonadotrophin-releasing hormone (GnRH) or physiological saline and (b) to determine whether or not a constant GnRH background enhances or diminishes pituitary responsiveness to GnRH pulses. Whereas pulsatile GnRH infusions maintained LH and FSH secretion, constant infusions (125 or 250 ng/h) led to the complete cessation of LH secretion and reduced FSH secretion. The rate of decline of plasma FSH concentrations was significantly (P<0·01) greater in animals receiving 250 ng GnRH/h than in saline-treated animals, whereas that in animals receiving 125 ng/h was not significantly different. When GnRH pulses were administered during constant GnRH infusion, the plasma LH pulse amplitudes were similar to those seen without the GnRH background. These data show that, in ovariectomized-HPD ewes (a) FSH secretion does not require GnRH pulses and may merely reflect ongoing FSH synthesis and (b) a constant low background of GnRH does not affect pituitary responsiveness to GnRH pulses. J. Endocr. (1986) 111, 43–49

Pituitary LH responsiveness to GnRH in vitro as related to GnRH receptor number

The objective of this in vitro study was to determine whether the increase in the augmented phase of the biphasic luteinizing hormone (LH) response to gonadotrophin-releasing hormone (GnRH) and its enhancement by estradiol (E2) were associated with GnRH-stimulated increases in pituitary GnRH receptor concentration. Pituitary glands from 72 h ovariectomized (OVX), OVX + E2, or proestrous rats were perifused continuously with GnRH (12 ng/h). LH release was measured at 10-min intervals, and pituitary GnRH-binding capacity (GnRH-BC) was assessed at 0, 40, 80, 120, and 240 min after addition of GnRH. All treatment groups exhibited a biphasic pattern of LH release; initial (20-70 min) and augmented (120-240 min) mean rates of LH secretion (micrograms/h) were 1.78 and 3.92 (OVX), 6.40 and 16.67 (OVX + E2), and 2.79 and 18.64 (proestrus), respectively. Total LH release was significantly greater in the OVX + E2 and proestrous groups (44.0 and 45.8 micrograms) vs. the OVX group (12.4 micrograms). Throughout the GnRH infusion period, GnRH-BC did not change significantly in any of the treatment groups with the exception of the OVX group in which there was a transient small decrease at 80 min post-GnRH infusion. There were no significant differences between treatment groups in GnRH-BC at any time after infusion of GnRH. These results demonstrate that the acute and augmented phases of GnRH-stimulated LH release and the enhancement of this biphasic response by E2 occurs independent of any increase in GnRH-BC and suggest that these events are mediated by postreceptor mechanisms.