Effect of pioglitazone on adrenocorticotropic hormone and cortisol secretion in Cushing's disease

Daesman Suri, Roy E Weiss

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The lack of an effective medical therapy for patients with Cushing's disease (CD) requires the search for new modalities of treatment. Peroxisomal proliferator-activated receptors (PPAR)-γ are abundantly expressed in ACTH-secreting pituitary tumors. Treatment with PPARγ agonists inhibits ACTH-secreting pituitary tumor growth, proliferation, and ACTH secretion in vitro in human and murine models and in vivo in murine corticotroph tumors. It was hypothesized that treatment with the PPARγ agonist pioglitazone would normalize the hypothalamic-pituitary-adrenal axis of patients with CD. We evaluated the hypothalamic pituitary adrenal axis in five patients with CD in whom we measured: 1) the 24-h urine concentration of free cortisol; 2) the 24-h profile of serum cortisol and plasma ACTH; and 3) the ACTH and cortisol response to CRH stimulation. All measurements were taken at baseline and after low-dose dexamethasone treatment (0.5 mg dexamethasone every 6 h). The entire protocol was done before and after 30 d of treatment with 45 mg of daily oral pioglitazone. At baseline, before low-dose dexamethasone, all five patients had elevated 24-h urine free cortisol, elevated 24-h serum cortisol and plasma ACTH levels, and robust responses to CRH, consistent with their diagnosis of CD. There was no significant change in any of the above variables after 30 d of treatment with pioglitazone. Furthermore, there was no significant difference in the number of cortisol or ACTH spikes or in their diurnal rhythms. In summary, pioglitazone treatment (45 mg daily for 30 d) of patients with CD was not found to be effective at attenuating either ACTH or cortisol levels and does not appear to be an alternative to surgical therapy.

Original languageEnglish (US)
Pages (from-to)1340-1346
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Fingerprint

pioglitazone
Pituitary ACTH Hypersecretion
Adrenocorticotropic Hormone
Hydrocortisone
Dexamethasone
Tumors
Therapeutics
Pituitary Neoplasms
Plasmas
Urine
Corticotrophs
Circadian Rhythm

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of pioglitazone on adrenocorticotropic hormone and cortisol secretion in Cushing's disease. / Suri, Daesman; Weiss, Roy E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 3, 03.2005, p. 1340-1346.

Research output: Contribution to journalArticle

@article{493c913667d54e688a692bdca43c43e4,
title = "Effect of pioglitazone on adrenocorticotropic hormone and cortisol secretion in Cushing's disease",
abstract = "The lack of an effective medical therapy for patients with Cushing's disease (CD) requires the search for new modalities of treatment. Peroxisomal proliferator-activated receptors (PPAR)-γ are abundantly expressed in ACTH-secreting pituitary tumors. Treatment with PPARγ agonists inhibits ACTH-secreting pituitary tumor growth, proliferation, and ACTH secretion in vitro in human and murine models and in vivo in murine corticotroph tumors. It was hypothesized that treatment with the PPARγ agonist pioglitazone would normalize the hypothalamic-pituitary-adrenal axis of patients with CD. We evaluated the hypothalamic pituitary adrenal axis in five patients with CD in whom we measured: 1) the 24-h urine concentration of free cortisol; 2) the 24-h profile of serum cortisol and plasma ACTH; and 3) the ACTH and cortisol response to CRH stimulation. All measurements were taken at baseline and after low-dose dexamethasone treatment (0.5 mg dexamethasone every 6 h). The entire protocol was done before and after 30 d of treatment with 45 mg of daily oral pioglitazone. At baseline, before low-dose dexamethasone, all five patients had elevated 24-h urine free cortisol, elevated 24-h serum cortisol and plasma ACTH levels, and robust responses to CRH, consistent with their diagnosis of CD. There was no significant change in any of the above variables after 30 d of treatment with pioglitazone. Furthermore, there was no significant difference in the number of cortisol or ACTH spikes or in their diurnal rhythms. In summary, pioglitazone treatment (45 mg daily for 30 d) of patients with CD was not found to be effective at attenuating either ACTH or cortisol levels and does not appear to be an alternative to surgical therapy.",
author = "Daesman Suri and Weiss, {Roy E}",
year = "2005",
month = "3",
doi = "10.1210/jc.2004-1746",
language = "English (US)",
volume = "90",
pages = "1340--1346",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Effect of pioglitazone on adrenocorticotropic hormone and cortisol secretion in Cushing's disease

AU - Suri, Daesman

AU - Weiss, Roy E

PY - 2005/3

Y1 - 2005/3

N2 - The lack of an effective medical therapy for patients with Cushing's disease (CD) requires the search for new modalities of treatment. Peroxisomal proliferator-activated receptors (PPAR)-γ are abundantly expressed in ACTH-secreting pituitary tumors. Treatment with PPARγ agonists inhibits ACTH-secreting pituitary tumor growth, proliferation, and ACTH secretion in vitro in human and murine models and in vivo in murine corticotroph tumors. It was hypothesized that treatment with the PPARγ agonist pioglitazone would normalize the hypothalamic-pituitary-adrenal axis of patients with CD. We evaluated the hypothalamic pituitary adrenal axis in five patients with CD in whom we measured: 1) the 24-h urine concentration of free cortisol; 2) the 24-h profile of serum cortisol and plasma ACTH; and 3) the ACTH and cortisol response to CRH stimulation. All measurements were taken at baseline and after low-dose dexamethasone treatment (0.5 mg dexamethasone every 6 h). The entire protocol was done before and after 30 d of treatment with 45 mg of daily oral pioglitazone. At baseline, before low-dose dexamethasone, all five patients had elevated 24-h urine free cortisol, elevated 24-h serum cortisol and plasma ACTH levels, and robust responses to CRH, consistent with their diagnosis of CD. There was no significant change in any of the above variables after 30 d of treatment with pioglitazone. Furthermore, there was no significant difference in the number of cortisol or ACTH spikes or in their diurnal rhythms. In summary, pioglitazone treatment (45 mg daily for 30 d) of patients with CD was not found to be effective at attenuating either ACTH or cortisol levels and does not appear to be an alternative to surgical therapy.

AB - The lack of an effective medical therapy for patients with Cushing's disease (CD) requires the search for new modalities of treatment. Peroxisomal proliferator-activated receptors (PPAR)-γ are abundantly expressed in ACTH-secreting pituitary tumors. Treatment with PPARγ agonists inhibits ACTH-secreting pituitary tumor growth, proliferation, and ACTH secretion in vitro in human and murine models and in vivo in murine corticotroph tumors. It was hypothesized that treatment with the PPARγ agonist pioglitazone would normalize the hypothalamic-pituitary-adrenal axis of patients with CD. We evaluated the hypothalamic pituitary adrenal axis in five patients with CD in whom we measured: 1) the 24-h urine concentration of free cortisol; 2) the 24-h profile of serum cortisol and plasma ACTH; and 3) the ACTH and cortisol response to CRH stimulation. All measurements were taken at baseline and after low-dose dexamethasone treatment (0.5 mg dexamethasone every 6 h). The entire protocol was done before and after 30 d of treatment with 45 mg of daily oral pioglitazone. At baseline, before low-dose dexamethasone, all five patients had elevated 24-h urine free cortisol, elevated 24-h serum cortisol and plasma ACTH levels, and robust responses to CRH, consistent with their diagnosis of CD. There was no significant change in any of the above variables after 30 d of treatment with pioglitazone. Furthermore, there was no significant difference in the number of cortisol or ACTH spikes or in their diurnal rhythms. In summary, pioglitazone treatment (45 mg daily for 30 d) of patients with CD was not found to be effective at attenuating either ACTH or cortisol levels and does not appear to be an alternative to surgical therapy.

UR - http://www.scopus.com/inward/record.url?scp=15944386690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15944386690&partnerID=8YFLogxK

U2 - 10.1210/jc.2004-1746

DO - 10.1210/jc.2004-1746

M3 - Article

C2 - 15585550

AN - SCOPUS:15944386690

VL - 90

SP - 1340

EP - 1346

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -