Increased Cosecretion of Cortisol Linked to Impaired Glucose Metabolism in Primary Aldosteronism

Aldosterone hormone
Aldosterone hormone, mineralocorticoid hormone produced by adrenals, 3D illustration
Autonomous cortisol secretion is common in patients with primary aldosteronism and is associated with increased risk for type 2 diabetes.

Autonomous cortisol secretion is common in patients with primary aldosteronism and is associated with increased risk for type 2 diabetes, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

The association of cosecretion of cortisol in primary aldosteronism was previously limited to case studies or case series, but more recently, a large multicenter study reported that this cosecretion is quite frequent in patients with primary aldosteronism and may play a role in the associated metabolic risks such as impaired glucose metabolism.

In the current study, the researchers analyzed data from the German Conn Registry to identify patients with primary aldosteronism and investigate the occurrence of impaired glucose metabolism in primary aldosteronism according to cortisol cosecretion. Patients from the population-based Cooperative Health Research study were matched (3:1) for gender, age, and body mass index with patients with primary aldosteronism for comparison.

The study enrolled newly diagnosed patients with primary aldosteronism. An oral glucose tolerance test (OGTT) and Cushing screening tests were completed in all patients and included a 1-mg dexamethasone suppression test (DST) and measures of late-night salivary cortisol and 24-hour urinary free cortisol.

In 161 patients with primary aldosteronism, autonomous cortisol secretion was identified in 125 patients (78%) based on at least one of the Cushing screening tests. Of these 125 patients with autonomous cortisol secretion, type 2 diabetes was diagnosed in 6.4%, while there were no cases of diabetes in those with negative screening tests (P =.119). There was no difference in the prevalence of prediabetes (27.8% vs. 27.2%, respectively; P =.945), metabolic syndrome (19.4% vs. 16.0%, respectively; P =.626), fasting plasma glucose, 2-hour glucose levels, or homeostasis model assessment of insulin resistance scores.

In a subgroup of 35 patients with pathologic response in DST, there was a tendency toward higher 2-hour plasma glucose levels (P =.053) in OGTT, thus higher prevalence of type 2 diabetes (20% vs. 0.8%, respectively; P <.0001) compared with patients with primary aldosteronism and normal DST response. However, there was no difference in other glucose metabolism measurements.

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Patients with primary aldosteronism with negative screening tests for hypercortisolism showed no difference in fasting plasma glucose or 2-hour plasma glucose levels in OGTT compared with matched controls, however, insulin resistance scores were higher with borderline significance (P =.051), raising the possibility of hyperaldosteronism-related insulin resistance.

Compared with 102 matched patients from the Cooperative Health Research study, patients with primary aldosteronism who had pathologic response to DST (34 patients) showed significantly higher impaired glucose tolerance according to 2-hour plasma glucose levels in OGTT (P =.001).

Limitations to the study included possible distortion of the effects of glucocorticoid on glucose metabolism over time, as well as other known risk factors for glucose intolerance. Furthermore, the screening tests for hypercortisolism were not repeated following treatment, and the possibility of transient mild cortisol excess cannot be excluded.

“We describe that [type 2 diabetes] and impaired [2-hour] plasma glucose in OGTT [are] more prevalent in [patients with primary aldosteronism] with [autonomous cortisol secretion] than in controls matched for sex, age, and [body mass index]. These results give further evidence for the ‘Connshing’ syndrome and point out the relevance for further investigation of the underlying mechanisms and especially associated risks such as [type 2 diabetes],” concluded the researchers.

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Gerards J, Heinrich DA, Adolf C, et al. Impaired glucose metabolism in primary aldosteronism is associated with cortisol co-secretion [published online March 13, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00299