A case of autonomous cortisol secretion in a patient with subclinical Cushing’s syndrome, GNAS mutation, and paradoxical cortisol response to dexamethasone

BMC Endocrine Disorders

Kenichi Kohashi¹  Yoshinao Oda¹  Shohei Sakamoto²  Kenji Ashida²  Yoshihiro Ogawa²  Chihiro Sakaguchi²  Ryuichi Sakamoto²  Masatoshi Nomura²  Yayoi Matsuda²  Seiichi Yano²  Yoichi Fujii³  Kenji Ohe⁴ 

[1] Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University;Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University;Faculty of Pharmaceutical Sciences, Fukuoka University;

关键词: Cushing’s syndrome;    GNAS;    Adrenal tumor;    Cortisol;    Cyclic-AMP;    Protein kinase A;   

DOI  :  10.1186/s12902-019-0345-8

来源: DOAJ

【 摘 要 】

Abstract Background Increased urinary free cortisol in response to the oral administration of dexamethasone is a paradoxical reaction mainly reported in patients with primary pigmented nodular adrenocortical disease. Here, we describe the first case of subclinical Cushing’s syndrome represented by autonomous cortisol secretion and paradoxical response to oral dexamethasone administration, harboring an activating mutation in the α subunit of the stimulatory G protein (GNAS). Case presentation A 65-year-old woman was diagnosed with subclinical Cushing’s syndrome during an evaluation for bilateral adrenal masses. Tumors of unknown origin were found in the heart, brain, thyroid gland, colon, pancreas, and both adrenal glands. Adenocarcinoma of the sigmoid colon and systemic brown-patchy skin pigmentation were also present. Her urinary cortisol levels increased in response to oral dexamethasone, while serum dehydroepiandrosterone-sulfate was not suppressed. After right adrenalectomy, genetic analysis of the resected tumor revealed the somatic GNAS activating mutation, p.R201H. Paradoxical urinary cortisol response persisted even after unilateral adrenal resection, although serum and urinary cortisol levels were attenuated. Conclusions This patient harbored a GNAS activating mutation, and presented with a mild cortisol- and androgen-producing adrenal adenoma. Administration of oral dexamethasone paradoxically increased cortisol levels, possibly via the stimulation of the cyclic adenosine monophosphate-dependent protein kinase A signaling pathway, which is seen in patients with pigmented nodular adrenocortical disease or Carney complex. GNAS mutations may provide clues to the mechanisms of hyper-function and tumorigenesis in the adrenal cortex, especially in bilateral adrenal masses accompanied by multiple systemic tumors. Examining GNAS mutations could help physicians detect extra-adrenal malignancies, which may contribute to an improved prognosis for patients with this type of Cushing’s syndrome.

【 授权许可】

Unknown