Periodic ectopic Cushing's syndrome potentially evoked by glucocorticoid excess

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 163-194-Pituitary Disorders & Case Reports
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-183
Yasufumi Seki*1, Fumiko Kawakami Mori2, Masami Ono2, Michita Niiyama2, Naohiro Yoshida2, Takashi Ando2, Daisuke Watanabe2, Satoshi Morimoto2, Nobuhiro Miki2 and Atsuhiro Ichihara1
1TOKYO WOMEN'S MED UNIV, Tokyo, Japan, 2Tokyo Women's Medical University, Tokyo, Japan
Introduction: We present a case of periodic ectopic ACTH-secreting tumor likely to be induced by cortisol excess.

Clinical case: An 82 year-old woman who was complaining of appetite loss and pretibial edema on both legs, was admitted several times for investigation of serum ACTH elevation and hypokalemia since 4 years ago.

  At the previous admissions, we diagnosed ectopic ACTH-producing tumor from several endocrinological tests as follows: overnight dexamethasone (Dex) suppression test with 1 or 8 mg dose failed to suppress cortisol level. Neither CRH nor desmopressin nor metyrapone could stimulate ACTH release. Magnetic resonance imaging (MRI) did not reveal pituitary tumor, and cavernous sinus sampling showed that central versus peripheral ACTH (C/P) ratio was 2.21. However, apparent ectopic lesion could not be detected and temporal metyrapone therapy was repeated.

  Last November, she entered our hospital complaining of the same symptoms. ACTH and cortisol levels were 88.3 pg/mL and 37.2 μg/dL, respectively. A month after metyrapone therapy (250 mg per day), ACTH and cortisol were decreased in 12 pg/mL and 0.5 μg/dL, respectively. The peak level of cortisol after CRH and rapid ACTH test was 8 and 22 μg/dL, respectively, which made a diagnosis of an early phase of secondary adrenal insufficiency. Supplementation of 15 mg hydrocortisone improved her complaints, followed by stabilization of both ACTH and cortisol levels within normal to low ranges for several weeks. After discharge she took over-dose of hydrocortisone because of fatigue and anxiety, and at the first outpatient visit one month after discharge, ACTH level suddenly increased to an extremely high level of 150 pg/mL. Administration of low-dose metyrapone induced adrenal insufficiency again within a week. To examine a hypothesis that cortisol positively regulates ACTH secretion from the tumor, we loaded 1mg Dex orally for 14 days. Following Dex loading, ACTH level was elevated gradually from 10 to 70 pg/mL, supporting our hypothesis that cortisol positively feedbacks on ACTH secretion in our patient with periodic Cushing's syndrome.

  There are several reports showing that periodic ectopic Cushing's syndrome was relieved by metyrapone administration. Our present case extends their observation and demonstrates for the first time that glucocorticoid can evoke occurrence of ectopic Cushing's syndrome.

Conclusion: We experienced a case of periodic ectopic Cushing’s syndrome potentially triggered by glucocorticoid administration. The pathogenesis of this case would lead to further understanding of tumoral ACTH regulation.

Nothing to Disclose: YS, FKM, MO, MN, NY, TA, DW, SM, NM, AI

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