Effect of protracted treatment with rosiglitazone, a PPARγ agonist, in patients with Cushing's disease

Francesca Pecori Giraldi, Carla Scaroni, Emanuela Arvat, Martina De Martin, Roberta Giordano, Nora Albiger, Adriana A S Leao, Andreea Picu, Franco Mantero, Francesco Cavagnini

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Objective: Cushing's disease, hypercortisolism due to a pituitary ACTH-secreting tumour, is a highly morbid illness as yet without effective medical therapy. Recent studies have demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) agonists effectively suppress ACTH secretion in a murine tumoral corticotroph cell line, but the few studies conducted so far in patients with ACTH-secreting pituitary adenomas have yielded variable results. Design: Ten patients with Cushing's disease were treated with 4-16 mg rosiglitazone p.o. daily for 1-8 months (median 3 months) and plasma ACTH and cortisol, urinary free cortisol (UFC), as well as parameters of insulin sensitivity, were recorded. An acute challenge with 8 mg rosiglitazone for 2 days preceded long-term rosiglitazone administration. Results: The acute challenge with rosiglitazone did not significantly modify plasma ACTH and cortisol levels. During protracted treatment with rosiglitazone, four patients showed a persistent reduction in UFC levels (up to 24% of pretreatment values), achieving normalization in three. In the others, UFC as well as plasma ACTH and cortisol decrements were inscribed within wide, random oscillations indicating that disease activity was substantially unchanged. Insulin sensitivity was ameliorated in most patients, without relation to ACTH or cortisol secretion. Untoward effects, such as weight gain, oedema and worsening of ecchymoses, were reported in several patients. Conclusions: Although effective in a subset of patients, protracted rosiglitazone administration did not consistently restrain ACTH and cortisol secretion in patients with Cushing's disease. Further investigations are needed to fully define the therapeutic potential of PPARγ agonists in this disorder.

Original languageEnglish
Pages (from-to)219-224
Number of pages6
JournalClinical Endocrinology
Volume64
Issue number2
DOIs
Publication statusPublished - Feb 2006

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rosiglitazone
Pituitary ACTH Hypersecretion
PPAR gamma
Hydrocortisone
Adrenocorticotropic Hormone
Therapeutics
Insulin Resistance
ACTH-Secreting Pituitary Adenoma
Corticotrophs
Ecchymosis
Cushing Syndrome

ASJC Scopus subject areas

  • Endocrinology

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Effect of protracted treatment with rosiglitazone, a PPARγ agonist, in patients with Cushing's disease. / Giraldi, Francesca Pecori; Scaroni, Carla; Arvat, Emanuela; De Martin, Martina; Giordano, Roberta; Albiger, Nora; Leao, Adriana A S; Picu, Andreea; Mantero, Franco; Cavagnini, Francesco.

In: Clinical Endocrinology, Vol. 64, No. 2, 02.2006, p. 219-224.

Research output: Contribution to journalArticle

Giraldi, FP, Scaroni, C, Arvat, E, De Martin, M, Giordano, R, Albiger, N, Leao, AAS, Picu, A, Mantero, F & Cavagnini, F 2006, 'Effect of protracted treatment with rosiglitazone, a PPARγ agonist, in patients with Cushing's disease', Clinical Endocrinology, vol. 64, no. 2, pp. 219-224. https://doi.org/10.1111/j.1365-2265.2006.02452.x
Giraldi, Francesca Pecori ; Scaroni, Carla ; Arvat, Emanuela ; De Martin, Martina ; Giordano, Roberta ; Albiger, Nora ; Leao, Adriana A S ; Picu, Andreea ; Mantero, Franco ; Cavagnini, Francesco. / Effect of protracted treatment with rosiglitazone, a PPARγ agonist, in patients with Cushing's disease. In: Clinical Endocrinology. 2006 ; Vol. 64, No. 2. pp. 219-224.
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AU - Giraldi, Francesca Pecori

AU - Scaroni, Carla

AU - Arvat, Emanuela

AU - De Martin, Martina

AU - Giordano, Roberta

AU - Albiger, Nora

AU - Leao, Adriana A S

AU - Picu, Andreea

AU - Mantero, Franco

AU - Cavagnini, Francesco

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N2 - Objective: Cushing's disease, hypercortisolism due to a pituitary ACTH-secreting tumour, is a highly morbid illness as yet without effective medical therapy. Recent studies have demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) agonists effectively suppress ACTH secretion in a murine tumoral corticotroph cell line, but the few studies conducted so far in patients with ACTH-secreting pituitary adenomas have yielded variable results. Design: Ten patients with Cushing's disease were treated with 4-16 mg rosiglitazone p.o. daily for 1-8 months (median 3 months) and plasma ACTH and cortisol, urinary free cortisol (UFC), as well as parameters of insulin sensitivity, were recorded. An acute challenge with 8 mg rosiglitazone for 2 days preceded long-term rosiglitazone administration. Results: The acute challenge with rosiglitazone did not significantly modify plasma ACTH and cortisol levels. During protracted treatment with rosiglitazone, four patients showed a persistent reduction in UFC levels (up to 24% of pretreatment values), achieving normalization in three. In the others, UFC as well as plasma ACTH and cortisol decrements were inscribed within wide, random oscillations indicating that disease activity was substantially unchanged. Insulin sensitivity was ameliorated in most patients, without relation to ACTH or cortisol secretion. Untoward effects, such as weight gain, oedema and worsening of ecchymoses, were reported in several patients. Conclusions: Although effective in a subset of patients, protracted rosiglitazone administration did not consistently restrain ACTH and cortisol secretion in patients with Cushing's disease. Further investigations are needed to fully define the therapeutic potential of PPARγ agonists in this disorder.

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