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Exp Clin Endocrinol Diabetes 2019; 127(02/03): 147-155
DOI: 10.1055/a-0664-7632
Review
© Georg Thieme Verlag KG Stuttgart · New York

“The Adrenal Gland: Central Relay in Health and Disease - Current Challenges and Perspectives 2018” – Cushing’s Disease

Günter K. Stalla
1   Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
,
Denis Ciato
1   Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
,
Christina Dimopoulou
1   Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
› Author Affiliations
Further Information

Publication History

received 14 May 2018
revised 14 July 2018

Publication Date:
21 August 2018 (online)

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Abstract

Background Despite advances in diagnostic and therapeutic approach, Cushing’s disease (CD) presents a challenging situation for the treating physician.

Aims To elucidate current challenges, present strengths and pitfalls of existing diagnostic tests, enlighten the need for new diagnostic approaches, appraise the effects of surgery and available pharmacological agents and identify future perspectives regarding CD.

Materials and methods Systematic search to PubMed and Medline databases for publications mainly over the last five years.

Results Mutations in the ubiquitin specific peptidase 8 gene have been recently identified in functional sporadic corticotroph adenomas causing CD. Since the prevalence of obesity and metabolic syndrome is rapidly increasing, new diagnostic tests are necessary to differentiate these conditions. Next to the traditional tests, a cutoff of preoperative ACTH/cortisol ratio, an ultrasensitive late night salivary cortisol assay and the desmopressin test have been suggested as valid tools for the diagnosis and differential diagnosis of CD. Transsphenoidal surgery with variable remission and recurrence rates presents the treatment of choice for CD. Medical therapy consists of adrenal-targeted drugs e. g. ketoconazole, metyrapone, etomidate and mitotane and pituitary-targeted drugs e. g. pasireotide, cabergoline and retinoic acid.

Conclusions CD is associated to a significant clinical burden, since numerous comorbidities persist after long-term biochemical control. These chronically ill patients show an increased mortality despite disease remission. Clinicians should treat comorbidities aggressively and seek for appropriate consultations. Structured consultation hours and expert excellence networks are needed in order to allow optimal, individualized care for affected patients, reverse increased morbidity and mortality and identify tumor recurrence early.

Key words

Cushing’s disease - signs and symptoms - diagnostic tests - transsphenoidal surgery - medical therapy - comorbidities
 

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