A pituitary tumor producing high molecular weight adrenocorticotropin-related peptides

Clinical and cell culture studies

P. J. Fuller, A. T W Lim, J. W. Barlow, E. L. White, B. A. Khalid, D. L. Copolov, S. Lolait, J. W. Funder, J. R. Stockigt

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Abstract

The tissue-specific processing of proopiomelanocortin (POMC), the precursor of ACTH, β-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation. Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and β-endorphin (ir-βEP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-βEP, corresponding to the elution positions of β-lipotropin and β-endorphin standards. Plasma ir-ACTH and ir-βEP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-βEP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.

Original languageEnglish
Pages (from-to)134-142
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume58
Issue number1
Publication statusPublished - 1984

Cite this

@article{afa2521727e9444f8aebd0b348ba82d9,
title = "A pituitary tumor producing high molecular weight adrenocorticotropin-related peptides: Clinical and cell culture studies",
abstract = "The tissue-specific processing of proopiomelanocortin (POMC), the precursor of ACTH, β-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation. Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and β-endorphin (ir-βEP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-βEP, corresponding to the elution positions of β-lipotropin and β-endorphin standards. Plasma ir-ACTH and ir-βEP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-βEP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.",
author = "Fuller, {P. J.} and Lim, {A. T W} and Barlow, {J. W.} and White, {E. L.} and Khalid, {B. A.} and Copolov, {D. L.} and S. Lolait and Funder, {J. W.} and Stockigt, {J. R.}",
year = "1984",
language = "English",
volume = "58",
pages = "134--142",
journal = "Journal of Clinical Endocrinology and Metablism",
issn = "0021-972X",
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A pituitary tumor producing high molecular weight adrenocorticotropin-related peptides : Clinical and cell culture studies. / Fuller, P. J.; Lim, A. T W; Barlow, J. W.; White, E. L.; Khalid, B. A.; Copolov, D. L.; Lolait, S.; Funder, J. W.; Stockigt, J. R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 58, No. 1, 1984, p. 134-142.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A pituitary tumor producing high molecular weight adrenocorticotropin-related peptides

T2 - Clinical and cell culture studies

AU - Fuller, P. J.

AU - Lim, A. T W

AU - Barlow, J. W.

AU - White, E. L.

AU - Khalid, B. A.

AU - Copolov, D. L.

AU - Lolait, S.

AU - Funder, J. W.

AU - Stockigt, J. R.

PY - 1984

Y1 - 1984

N2 - The tissue-specific processing of proopiomelanocortin (POMC), the precursor of ACTH, β-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation. Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and β-endorphin (ir-βEP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-βEP, corresponding to the elution positions of β-lipotropin and β-endorphin standards. Plasma ir-ACTH and ir-βEP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-βEP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.

AB - The tissue-specific processing of proopiomelanocortin (POMC), the precursor of ACTH, β-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation. Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and β-endorphin (ir-βEP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-βEP, corresponding to the elution positions of β-lipotropin and β-endorphin standards. Plasma ir-ACTH and ir-βEP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-βEP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.

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M3 - Article

VL - 58

SP - 134

EP - 142

JO - Journal of Clinical Endocrinology and Metablism

JF - Journal of Clinical Endocrinology and Metablism

SN - 0021-972X

IS - 1

ER -