Prolonged Pulsatile Administration of Luteinizing Hormone-Releasing Hormone in Prepubertal Children: Diagnostic and Physiologic Aspects

In order to test gonadotropic function 30 prepubertal and 2 early pubertal girls and boys were treated with LH-releasing hormone (LRH) in a pulsatile fashion for 7 days. LRH was administered iv either in a dose of 10 µg every 90 min or in a dose of 20 µg/1-73 m² every 96 min. On days 1 and 7, just before as well as at the end of LRH treatment, a LRH test (100 µg/m² iv) was performed. In 27 patients a LRH test was repeated 4 (day 11) or 7 days (day 14) after LRH withdrawal as well. Plasma LH, FSH, and estradiol or testosterone levels were estimated during the LRH tests on days 1, 7, and 11/14. The patients were divided into 4 groups: group 1 consisted of 2 girls and 1 boy with gonadal failure, group 2 of 1 girl and 2 boys with intact pituitary and gonadal function, group 3 of 11 girls and 13 boys with various central endocrine disorders, and group 4 of 1 girl and 1 boy with pubertal arrest of unknown origin.

In group 1 LRH treatment elicited an increase of both gonadotropins into the castrate range, whereas gonadal steroids did not increase. In group 2 baseline LH as well as the response to LRH increased on day 7. In the boys FSH changed similarly. In the girl baseline FSH increased, but the high FSH response of day 1 decreased. Estradiol and testosterone levels were elevated on day 7. These changes during LRH treatment are similar to those during normal pubertal development. When the LRH test was repeated on day 11/14 basal levels had returned into the prepubertal range and a high response of LH especially was found in all 3 subjects.

Patients of group 3 were separated into two subgroups: group 3a, those with, and group 3b, those without an increase of gonadal steroids on day 7 of LRH treatment. Since an increment must be the result of increased gonadotropin stimulation, this probably indicates intact gonadotropic function. Group 3a had a pattern of gonadotropin secretion similar to group 2. In group 3b basal and peak LH levels were lower on day 7 compared to group 3a, whereas FSH levels did not differ. Four or 7 days after LRH discontinuation (day 11/14) basal gonadotropin levels were in the original low range. In the LRH test mean LH peak level of group 3a was 43.7 U/liter, of group 3b 13.1 U/liter (P < 0.01). Two of the six patients of group 3b demonstrated no response whatsoever. FSH peak levels did not differ between both groups. Based on these data we suggest that an organic defect of the gonadotrophs exists in two patients of group 3b; the absent gonadal response in the remaining four patients of group 3b is assumed to be the consequence of a delayed gonadotropic gonadal response to LRH treatment. The patients of group 4 had a distinct increase of FSH levels as well as of gonadal steroids at the end of LRH treatment, whereas basal and peak levels of LH remained in the same range. On day 11/14 LRH elicited an exaggerated LH release.

From the present study we conclude that: 1) pulsatile LRH treatment may diagnose prepubertal patients with potential gonadal failure. 2) Pulsatile LRH treatment can change the pituitary response from a prepubertal into an adult pattern within 7 days. 3) An increase of gonadal steroids during LRH stimulation indicates at least intact LH secretory potential. 4) No increase of gonadal steroids may indicate gonadotropic dysfunction, but does not rule out the possibility of a delayed response of the gonadotrophs to LRH. Therefore, 7 days of pulsatile LRH treatment may not be sufficient to distinguish intact from defective gonadotropic function in all patients. 5) Prolonged pulsatile LRH administration followed by a LRH test within 4 to 7 days after LRH withdrawal may give reliable information about gonadotropic function.