A Case of Cortisol Producing Adrenal Adenoma without Phenotype of Cushing's Syndrome due to Impaired 11.BETA.-Hydroxysteroid Dehydrogenase 1 Activity

Abstract

Abstract. This report concerns a case of cortisol-producing adrenocortical adenoma without the phenotype of Cushing's syndrome. A left adrenal tumor was incidentally detected in this patient. A diagnosis of adrenal Cushing's syndrome was based on the results of endocrinological and radiological examinations, although she showed none of the physical signs of Cushing's syndrome, glucose intolerance, hypertension or dyslipidermia. After a successful laparoscopic left adrenalectomy, the pathological diagnosis was adrenocortical adenoma. Slow tapering of glucocorticoids was needed to prevent adrenal insufficiency after surgery, and the plasma ACTH level remained high even though the serum cortisol level had reached the upper limit of the normal range. Further examination showed a urinary THF + allo-THF/THE ratio of 0.63, which was lower than that of control (0.90 ± 0.13, mean ± SD). Serum cortisol/cortisone ratios after the cortisone acetate administration were also decreased, and the serum half-life of cortisol was shorter than the normal range which has been reported. These findings indicated a partial defect in 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, which converts cortisone to cortisol. Our case suggests that a change in 11β-HSD1 activity results in inter-individual differences in glucocorticoid efficacy.

Overexpression of 11β-hydroxysteroid dehydrogenase 1 in visceral adipose tissue and underexpression of endothelial nitric oxide synthase in the adrenal cortex of dogs with hyperadrenocorticism

“…These authors demonstrated that the patient had a functional defect in the 11β-HSD1 enzyme that rendered it inactive, which correspondingly decreased the conversion of cortisone to cortisol at the local level. Later, the same enzymatic defect and the same clinical picture were described in a patient with HAC resulting from an adrenocortical nonhypophyseal tumour (Arai et al, 2008). Similar results were found in basic research.…”

MECHANISMS IN ENDOCRINOLOGY: Tissue-specific activation of cortisol in Cushing’s syndrome

“…Subsequent investigation revealed a functional defect in 11β-HSD1 activity, as evidenced by serum and urinary biomarkers. Similarly, Arai et al (18) described a patient with a cortisol-producing adrenocortical adenoma lacking the phenotype of Cushing's syndrome, and again a defect in 11β-HSD1 activity was identified. These clinical observations appeared to suggest that tissue intrinsic 11β-HSD1 activity is the major determinant of the adverse metabolic manifestations of circulatory GC excess.…”

“…If these rodent findings translate into clinical studies in man, then there is no doubt that this class of agent will add significantly to the repertoire of drugs available to the clinician to limit the adverse side effects experienced by patients taking prescribed GCs. Certainly, clinical studies of subjects with hypercortisolism protected from Cushingoid features, due to loss of 11β-HSD1 function are encouraging (17,18). However, there remain important issues that need to be clarified, such as the consequences of long-term 11β-HSD1 suppression, the influence of these compounds on the immunosuppressive properties of prescribed GCs, and their effects on the endogenous control of acute inflammation.…”

Glucocorticoid Excess in Bone and Muscle

“…Mutations in the GR gene, prevent the Cushingoid phenotype from developing [14]. Absence of the phenotype also occurs if the 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1), which converts inactive to active GC metabolites, is defective [13,15,16], or if there is a defect in a coenzyme, H6PDH [17,18]. 11β-HSD1 regulates the level of cortisol and its inactive precursor, cortisone, in target tissues (Figure 1C) [19].…”