TY - JOUR
T1 - The luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6-Pro9-net]lhrh increased rather than lowered lh and α-subunit levels in a patient with an LH-secreting pituitary tumor
AU - Roman, Sheila H.
AU - Goldstein, Mark
AU - Kourides, Ione A.
AU - Comite, Florence
AU - Bardin, C. Wayne
AU - Krieger, Dorothy T.
PY - 1984/2
Y1 - 1984/2
N2 - Episodic secretion of LH, and the responses of serum LH, α-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 a-subunit concentrations were elevated [57 ± 0.7 (SEM) mlU/ml (range, 45-71) and 26 ng/ml, respectively]. Frequent sampling revealed six 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 a-subunit after iv administration of 150 µg LHRH did not increase above these intrinsic LH secretory increments (Δ LH: 23% Δ α-subunit: 21%). The low basal serum FSH concentrations (3.5 mlU/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 µg daily sc of this LHRH analog for 21 days was associated with increases in serum LH and α-subunit concentrations. Mean serum LH and α-subunit levels for the 21 days of analog administration were 110 ± 5.4 (SEM) mlU/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 α-subunit declined precipitously and mean serum LH and α-subunit levels were 58 ± 7 (SEM) mlU/ml (range, 18–90) and 22 ± 3 (SEM) ng/ml (range, 12–44), respectively. We conclude that this patient’s pituitary tumor has diminished responsiveness to acute LHRH administration and that the effect of chronic DTrp6− 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 α-subunit concentrations during the course of daily D-Trp6-Pro9 administration suggests that central regulatory mechanisms, if present, are abnormal.
AB - Episodic secretion of LH, and the responses of serum LH, α-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 a-subunit concentrations were elevated [57 ± 0.7 (SEM) mlU/ml (range, 45-71) and 26 ng/ml, respectively]. Frequent sampling revealed six 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 a-subunit after iv administration of 150 µg LHRH did not increase above these intrinsic LH secretory increments (Δ LH: 23% Δ α-subunit: 21%). The low basal serum FSH concentrations (3.5 mlU/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 µg daily sc of this LHRH analog for 21 days was associated with increases in serum LH and α-subunit concentrations. Mean serum LH and α-subunit levels for the 21 days of analog administration were 110 ± 5.4 (SEM) mlU/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 α-subunit declined precipitously and mean serum LH and α-subunit levels were 58 ± 7 (SEM) mlU/ml (range, 18–90) and 22 ± 3 (SEM) ng/ml (range, 12–44), respectively. We conclude that this patient’s pituitary tumor has diminished responsiveness to acute LHRH administration and that the effect of chronic DTrp6− 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 α-subunit concentrations during the course of daily D-Trp6-Pro9 administration suggests that central regulatory mechanisms, if present, are abnormal.
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U2 - 10.1210/jcem-58-2-313
DO - 10.1210/jcem-58-2-313
M3 - Article
C2 - 6198331
AN - SCOPUS:0021357370
SN - 0021-972X
VL - 58
SP - 313
EP - 319
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -