The Luteinizing Hormone-Releasing Hormone (LHRH) Agonist [D-Trp6-Pro9-NEt]LHRH Increased rather than Lowered LH and α-Subunit Levels ina Patient with an LH- Secreting Pituitary Tumor*

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Abstract
Episodic secretion of LH [luteinizing hormone], and the responses of serum LH, .alpha.-subunit and testosterone concentrations to the acute administration of LHRH and the chronic administration of the LHRH agonist analog [D-Trp6-Pro9-NEt]LHRH (D-Trp6-Pro9) were evaluated in a 33-yr-old man previously reported to have an LH-secreting pituitary tumor unaccompanied by FSH hypersecretion. Basal serum LH and .alpha.-subunit concentrations were elevated [57 .+-. 0.7 (SEM [standard error of the mean]) mIU/ml (range, 45-71) and 26 ng/ml, respectively]. Frequent sampling revealed 6 LH secretory spikes over a 24-h period with increments above basal levels varying from 23-40% and interspike intervals ranging from 1.5-5 h. The concentrations of LH or .alpha.-subunit after i.v. administration of 150 .mu.g LHRH did not increase above these intrinsic LH secretory increments (.DELTA. LH: 23%; .DELTA. .alpha.-subunit: 21%). The low basal serum FSH concentrations (3.5 mIU/ml) and elevated basal serum testosterone levels (1480 ng/dl) were unchanged after LHRH. Administration of clomiphene citrate produced no increase in serum LH, FSH or testosterone concentrations. An attempt was made to decrease LH secretion in this patient using D-Trp6-Pro9. Administration of 200 .mu.g daily s.c. of this LHRH analog for 21 days was associated with increases in serum LH and .alpha.-subunit concentrations. Mean serum LH and .alpha.-subunit levels for the 21 days of analog administration were 110 .+-. 5.4 (SEM) mIU/ml (range, 70-170) and 64 .+-. 3 (SEM) ng/ml (range, 32-84), respectively. During the 9-day period after discontinuance of the LHRH analog, levels of both serum LH and .alpha.-subunit declined precipitously and mean serum LH and .alpha.-subunit levels were 58 .+-. 7 (SEM) mIU/ml (range, 18-90) and 22 .+-. 3 (SEM) ng/ml (range, 12-44), respectively. This patient''s pituitary tumor has diminished responsiveness to acute LHRH administration and the effect of chronic D-Trp6-Pro9 is stimulatory rather than inhibitory, as occurs after chronic administration of this analog to normal subjects. The blunted responsiveness to LHRH administration and the lack of response to clomiphene citrate suggest tumor autonomy. The presence of modest paradoxical responsiveness of serum LH and .alpha.-subunit concentrations during the course of daily D-Trp6-Pro9 administration suggests that central regulatory mechanisms, if present, are abnormal.