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. 2019 Feb 11;3(3):678-686.
doi: 10.1210/js.2018-00385. eCollection 2019 Mar 1.

Cyclic Subclinical Hypercortisolism: A Previously Unidentified Hypersecretory Form of Adrenal Incidentalomas

Rafael B Giorgi  1 , Marcelo V Correa  1 , Flávia A Costa-Barbosa  1 , Claudio E Kater  1
Affiliations

Cyclic Subclinical Hypercortisolism: A Previously Unidentified Hypersecretory Form of Adrenal Incidentalomas

Rafael B Giorgi et al. J Endocr Soc. .

Abstract

Purpose: Most adrenal incidentalomas (AIs) are nonfunctioning adenomas (NFAs), but up to 30% may secrete cortisol autonomously without clinical evidence of Cushing syndrome (CS), which nevertheless may increase cardiovascular mortality. This subclinical hypercortisolism (SCH) is confirmed by cortisol resistance to a dexamethasone suppression test (DST). Cyclic cortisol secretion occurs in classic CS but was not reported in SCH.

Objective: Investigate cyclic cortisol production/autonomy in AIs using sequential DSTs.

Methods: A total of 251 patients with AI underwent 487 DSTs over 12 years; patients with at least three DSTs were selected. DSTs were validated by measuring serum dexamethasone. Cyclic SCH was defined when at least two abnormal and two normal DSTs were documented.

Results: A total of 44 patients had three or more DSTs during follow-up: 9 of 44 patients (20.4%) had all negative test results (post-DST cortisol ≤1.8 μg/dL) and were classified as NFA; another nine patients had all positive results (cortisol >1.8 μg/dL) and were classified as sustained SCH. The remaining 26 (59.2%) had discordant responses: 8 of 44 (18.3%) had at least two positive and two negative tests, matching the criterion for cyclic SCH, whereas 18 of 44 (40.9%) had only one discordant test and were classified as possibly cyclic SCH. Eleven of 20 (55%) patients initially classified as NFA did not maintain their cortisol pattern.

Conclusions: Extended follow-up with repeated DSTs uncovered an unusual subset of AIs with cyclic SCH. Recurring production of cortisol may affect determination of AI subtypes if based on just one DST. Lack of recognition of this phenomenon makes follow-up of patients with AI misleading because even cyclic SCH may result in potential cardiovascular risk.

Keywords: Cushing syndrome; cardiovascular mortality; cortisol; dexamethasone suppression; hormonal cyclicity.

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Figures

Figure 1.
Figure 1.
Changes in AI subgrouping across consecutive DST evaluations.
Figure 2.
Figure 2.
Prevalence of AI subgroups according to different post-DST cortisol cutoffs.
See this image and copyright information in PMC

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