The Role of Isotretinoin Therapy for Cushing’s Disease: Results of a Prospective Study

Vilar, Lúcio; Albuquerque, José de Lima; Lyra, Rüy; Diniz, Erik Trovão; Filho, Frederico Rangel; Gadelha, Patrícia Calado Ferreira Pinheiro; Ibiapina, George Robson; Gomes, Bárbara; Santos, Vera; Fonseca, Maíra Melo da; Viana, K.; Lopes, Isis Gabriella; Araújo, Douglas K. Godoy de; Naves, Luciana Ansaneli

doi:10.1155/2016/8173182

Cited by 44 publications

(43 citation statements)

References 62 publications

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“…A significant UFC reduction (> 50%) in 71% of patients (5/7) with normalization in 43% of cases (3/7) was observed (126) and the drug was well tolerated. Another study with 16 CD patients showed UFC normalization in 25% of cases with isotretinoin use (20-80 mg/day) for 6-12 months (127).…”

Section: Other Medications and Perspectivesmentioning

confidence: 95%

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

Machado¹,

Fragoso²,

Moreira³

et al. 2018

Archives of Endocrinology and Metabolism

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The treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.

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Section: Other Medications and Perspectivesmentioning

confidence: 95%

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

Machado¹,

Fragoso²,

Moreira³

et al. 2018

Archives of Endocrinology and Metabolism

Self Cite

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“…In comparison with non-responders patients, the responding patients had significantly lower mean age and lower mean basal levels of UFC, nocturnal salivary cortisol and ACTH. Therefore, the authors of this study concluded that RA might be more beneficial in patients with mild hypercortisolism (60).…”

Section: Role Of Retinoic Acid In the Treatment Of Cushing's Diseasementioning

confidence: 78%

GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours

Stalla

Dimopoulou

Jung-Sievers

et al. 2020

European Journal of Endocrinology

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Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing’s disease. In view of the development of additional treatment concepts for the treatment of pituitary adenomas we speculate about the relevance of RSUME as a potential target for the development of an anti-angiogenic therapy. Moreover, the role of BMP-4 which stimulates prolactinoma development through the Smad signalling cascade is described and its role as putative drug target for the treatment of prolactinomas is discussed. Regarding the well-known resistance of a part of somatotropinomas to somatostatin analogue treatment, recently identified mechanisms responsible for the drug resistance are summarized and ways to overcome them in future treatment concepts are presented. Concerning novel therapeutic options for patients with Cushing’s disease the impact of retinoic acid, which is currently tested in clinical studies, is shown, and the action and putative therapeutic impact of silibinin to resolve glucocorticoid resistance in these patients is critically discussed.

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“…This promoted interest in the use of 13cisRA as a treatment for pituitary corticotroph tumor which is also known as Cushing Disease (CD). One study demonstrated that long-term isotretinoin treatment (60-80 mg/day for 6-12 months) led to normalization of urine free cortisol (UFC) and midnight salivary cortisol (MSC) in 6 of 16 subjects with CD (37.5%), with improved clinical symptoms and lower plasma ACTH levels [plasma ACTH (pg/mL), responders vs. non-responders, 54 ± 14 vs. 62 ± 17, p < 0.01] in responsive patients [42]. Tretinoin (also known as ATRA) has also been investigated in a pilot study of 7 patients with CD (3 males and 4 post-menopausal females) [43].…”

Section: Retinoic Acid Receptors (Rarα Rarβ Rarγ)mentioning

confidence: 99%

Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

Zhang

Heaney

2020

Cells

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The hypothalamic–pituitary–adrenal (HPA) axis plays a critical role in adaptive stress responses and maintaining organism homeostasis. The pituitary corticotroph is the central player in the HPA axis and is regulated by a plethora of hormonal and stress related factors that synergistically interact to activate and temper pro-opiomelanocortin (POMC) transcription, to either increase or decrease adrenocorticotropic hormone (ACTH) production and secretion as needed. Nuclear receptors are a family of highly conserved transcription factors that can also be induced by various physiologic signals, and they mediate their responses via multiple targets to regulate metabolism and homeostasis. In this review, we summarize the modulatory roles of nuclear receptors on pituitary corticotroph cell POMC transcription, describe the unique and complex role these factors play in hypothalamic–pituitary–adrenal axis (HPA) regulation and discuss potential therapeutic targets in disease states.

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The Role of Isotretinoin Therapy for Cushing’s Disease: Results of a Prospective Study

Cited by 44 publications

References 62 publications

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours

Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

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