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

Sheila H. Roman, M. Goldstein, I. A. Kourides, F. Comite, C. W. Bardin, D. T. Krieger

Research output: Contribution to journalArticle

Abstract

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 α-subunit concentrations were elevated [57 ± 0.7 (SEM) mIU/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 1.5-5h. The concentrations of LH or α-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 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 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) 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 α-subunit declined precipitously and mean serum LH and α-subunit levels were 58 ± 7 (SEM) mIU/ml (range, 18-90) and 22 ± (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 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 α-subunit concentrations during the course of daily D-Trp6-Pro9 administration suggests that central regulatory mechanisms, if present, are abnormal.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume58
Issue number2
StatePublished - 1984
Externally publishedYes

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Pituitary Neoplasms
Gonadotropin-Releasing Hormone
Tumors
Serum
Scanning electron microscopy
Testosterone
Clomiphene
Sampling

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Roman, Sheila H.; Goldstein, M.; Kourides, I. A.; Comite, F.; Bardin, C. W.; Krieger, D. T.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 58, No. 2, 1984, p. 313-319.

Research output: Contribution to journalArticle

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title = "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",
abstract = "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 α-subunit concentrations were elevated [57 ± 0.7 (SEM) mIU/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 1.5-5h. The concentrations of LH or α-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 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 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) 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 α-subunit declined precipitously and mean serum LH and α-subunit levels were 58 ± 7 (SEM) mIU/ml (range, 18-90) and 22 ± (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 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 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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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, M.

AU - Kourides, I. A.

AU - Comite, F.

AU - Bardin, C. W.

AU - Krieger, D. T.

PY - 1984

Y1 - 1984

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 α-subunit concentrations were elevated [57 ± 0.7 (SEM) mIU/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 1.5-5h. The concentrations of LH or α-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 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 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) 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 α-subunit declined precipitously and mean serum LH and α-subunit levels were 58 ± 7 (SEM) mIU/ml (range, 18-90) and 22 ± (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 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 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 α-subunit concentrations were elevated [57 ± 0.7 (SEM) mIU/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 1.5-5h. The concentrations of LH or α-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 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 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) 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 α-subunit declined precipitously and mean serum LH and α-subunit levels were 58 ± 7 (SEM) mIU/ml (range, 18-90) and 22 ± (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 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 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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