Weber Robert J, Kawaja Christopher, Wallerstein Robert, Kunwar Sandeep M, Liu Chienying
Department of Medicine, Division of Endocrinology, University of California, San Francisco, CA 94143, USA.
Independent Researcher, USA.
JCEM Case Rep. 2024 Sep 5;2(9):luae158. doi: 10.1210/jcemcr/luae158. eCollection 2024 Sep.
We present a patient who had surgically confirmed CD but without the full cushingoid phenotype despite markedly elevated cortisol. Nonpathologic causes of elevated ACTH and cortisol were eliminated as were pathogenic variants in the glucocorticoid receptor gene. Further studies of urine metabolites, cortisol half-life, and the ratios of cortisone to cortisol conversion revealed impaired 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. There have only been 2 prior reports of impaired 11β-HSD1 resulting in lack of classic cushingoid features in the past 2 decades. Our patient's presentation and previous reports demonstrate the key role of 11β-HSD1 in modulating intracellular cortisol concentration, therefore shielding the peripheral tissues from the effects of excess cortisol. When patients present with markedly elevated cortisol but without classic cushingoid features, impaired 11β-HSD1 should be considered in the differential diagnosis.
我们报告了一名患者，其经手术确诊为库欣病（CD），尽管皮质醇水平显著升高，但并无典型的库欣综合征表现。促肾上腺皮质激素（ACTH）和皮质醇升高的非病理性原因以及糖皮质激素受体基因的致病变异均被排除。对尿液代谢产物、皮质醇半衰期以及可的松与皮质醇转化比率的进一步研究显示，11β-羟类固醇脱氢酶1型（11β-HSD1）活性受损。在过去20年中，仅有2例先前报道称11β-HSD1活性受损导致缺乏典型的库欣综合征特征。我们患者的表现及先前的报道表明，11β-HSD1在调节细胞内皮质醇浓度方面起着关键作用，从而使外周组织免受过量皮质醇的影响。当患者出现皮质醇水平显著升高但无典型库欣综合征特征时，在鉴别诊断中应考虑11β-HSD1受损的情况。
