Benign adrenal adenomas secreting excess mineralocorticoids and glucocorticoids

Abstract

Objective: To recognize that benign adrenal adenomas can co-secrete excess aldosterone and cortisol, which can change clinical management.Methods: We reviewed the clinical and histological features of an adrenal tumor co-secreting aldosterone and cortisol in a patient. Biochemical testing as well as postoperative immunohistochemistry was carried out on tissue samples for assessing enzymes involved in steroidogenesis.Results: A patient presented with hypertension, hypokalemia, and symptoms related to hypercortisolism. The case demonstrated suppressed renin concentrations with an elevated aldosterone:renin ratio, abnormal dexamethasone suppression test results, and elevated midnight salivary cortisol concentrations. The patient had a right adrenal nodule with autonomous cortisol production and interval growth. Right adrenalectomy was carried out. Postoperatively, the patient tolerated the surgery, but he was placed on a short course of steroid replacement given a subnormal postoperative serum cortisol concentration. Long-term follow-up of the patient showed that his blood pressure and glucose levels had improved. Histopathology slides showed positive staining for 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 21 hydroxylase.Conclusion: In addition to the clinical manifestations and laboratory values, the presence of these enzymes in this type of tumor provides support that the tumor in this patient was able to produce mineralocorticoids and glucocorticoids. The recognition of patients with a tumor that is co-secreting aldosterone and cortisol can affect decisions to treat with glucocorticoids perioperatively to avoid adrenal crisis.Learning points Recognition of the presence of adrenal adenomas co-secreting mineralocorticoids and glucocorticoids.Consideration for perioperative and postoperative glucocorticoid use in the treatment of co-secreting adrenal adenomas.

Impaired Glucose Metabolism in Primary Aldosteronism Is Associated With Cortisol Cosecretion

“…In the past, cortisol co-secretion in primary aldosteronism has been discussed on the basis of several case studies or case series [9][10][11][12][13][14][15] . Recently, we have investigated a large multi-center cohort of PA patients and revealed that glucocorticoid co-secretion is a phenotype frequently found in PA which might contribute to associated metabolic risks 16 , including a higher risk of cardiovascular events as shown by Nakajima et al 17 .…”

Aldosterone- and cortisol-cosecreting adrenal adenoma, ovarian hyperthecosis and breast cancer

“…Subsequently, a steroid metabolome study confirmed that glucocorticoid excess is a frequent finding in PA due to APAs and idiopathic hyperaldosteronism (IHA) and the term ‘Connshing syndrome’ was proposed for this subgroup of patients ( 9 ). These findings suggest that cortisol cosecretion is highly prevalent in patients with PA and it could be the driver for the increased metabolic alterations seen in patients with Conn syndrome ( 1 , 2 , 5 , 6 , 7 , 8 , 9 ). More recently, Gerards et al ( 10 ) performed the 1-mg dexamethasone suppression test, late-night salivary cortisol, and 24-h urinary free cortisol in 161 newly diagnosed patients with PA and found that 77.6% of them had autonomous cortisol secretion as demonstrated by a pathological response in at least one of these screening tests for Cushing’s syndrome.…”

“…The latter group, which includes 10–15% of all AAs, comprises adenomas that produce cortisol, aldosterone, or catecholamines. Although aldosterone- and cortisol-cosecreting adrenal adenomas (A/CAAs) were initially thought to be rare, a number of case reports and case series have suggested that this might not be the case ( 1 , 2 ).…”

Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism

“…These findings might provide a treatment rationale for patients suffering from PA: not only as aldosterone and salt excess increase oxidative stress by themselves but in addition because those patients frequently feature cortisol co-secretion [98,99]. The latter aggravates cardiovascular damage in scenarios with both high and low oxidative stress as glucocorticoid excess impairs the conversion of cortisol to cortisone, leading to glucocorticoid-mediated mineralocorticoid effects even in 11β-HSD2 protected epithelial tissues (▶Table 1) [100][101][102][103][104][105]. As stated previously, changes in redox state may further aggravate glucocorticoid MR agonism.…”