Giorgi Rafael B, Correa Marcelo V, Costa-Barbosa Flávia A, Kater Claudio E
Division of Endocrinology, Department of Medicine, Universidade Federal de São Paulo (UNIFESP) Medical School, São Paulo, SP, Brazil.
J Endocr Soc. 2019 Feb 11;3(3):678-686. doi: 10.1210/js.2018-00385. eCollection 2019 Mar 1.
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.
Investigate cyclic cortisol production/autonomy in AIs using sequential DSTs.
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.
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.
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.
大多数肾上腺偶发瘤（AIs）为无功能腺瘤（NFAs），但高达30%的肾上腺偶发瘤可能自主分泌皮质醇，却无库欣综合征（CS）的临床证据，不过这仍可能增加心血管疾病死亡率。这种亚临床高皮质醇血症（SCH）通过皮质醇对地塞米松抑制试验（DST）的抵抗得以证实。经典库欣综合征中会出现周期性皮质醇分泌，但亚临床高皮质醇血症中未见相关报道。
采用序贯地塞米松抑制试验研究肾上腺偶发瘤中周期性皮质醇的产生/自主性。
12年间，共有251例肾上腺偶发瘤患者接受了487次地塞米松抑制试验；选取至少接受过三次地塞米松抑制试验的患者。通过测量血清地塞米松来验证地塞米松抑制试验。当记录到至少两次异常和两次正常的地塞米松抑制试验结果时，定义为周期性亚临床高皮质醇血症。
共有44例患者在随访期间接受了三次或更多次地塞米松抑制试验：44例患者中有9例（20.4%）所有试验结果均为阴性（地塞米松抑制试验后皮质醇≤1.8μg/dL），被归类为无功能腺瘤；另外9例患者所有结果均为阳性（皮质醇>1.8μg/dL），被归类为持续性亚临床高皮质醇血症。其余26例（59.2%）反应不一致：44例中有8例（18.3%）至少有两次阳性和两次阴性试验，符合周期性亚临床高皮质醇血症的标准，而44例中有18例（40.9%）只有一次不一致试验，被归类为可能的周期性亚临床高皮质醇血症。最初被归类为无功能腺瘤的20例患者中有11例（55%）未维持其皮质醇模式。
通过重复地塞米松抑制试验进行长期随访发现了肾上腺偶发瘤中一个不寻常的周期性亚临床高皮质醇血症亚组。如果仅基于一次地塞米松抑制试验来确定肾上腺偶发瘤的亚型，皮质醇的反复产生可能会影响其判定。对这一现象缺乏认识会使肾上腺偶发瘤患者的随访产生误导，因为即使是周期性亚临床高皮质醇血症也可能导致潜在的心血管风险。
