What is the clinical evidence from this study?

Study design: Observational. Population: Primary aldosteronism (n=644). Intervention: Autonomous cortisol secretion (pathological DST) vs. Normal DST and matched population controls. Primary outcome: Diagnosis of type 2 diabetes mellitus (p=< 0.0001).

March 13, 2019Open Access

Impaired Glucose Metabolism in Primary Aldosteronism Is Associated With Cortisol Cosecretion

Q: What are the key findings of this study?

Autonomous cortisol secretion in primary aldosteronism is associated with a higher prevalence of type 2 diabetes compared to patients with normal cortisol suppression (20% vs 0.8%, P<0.0001).

Key Result

Autonomous cortisol secretion in primary aldosteronism is associated with a higher prevalence of type 2 diabetes compared to patients with normal cortisol suppression (20% vs 0.8%, P<0.0001).

Study Design

Type

Observational (n=644)

Structured PICO

Does autonomous cortisol secretion increase the risk of impaired glucose metabolism and type 2 diabetes in patients with primary aldosteronism?

Population

161 newly diagnosed patients with primary aldosteronism (PA) from the German Conn Registry, and a population-based control sample from the KORA-F4 study matched 3:1 by sex, age, and body mass index.

Intervention

Presence of autonomous cortisol secretion (ACS) / pathological 1-mg dexamethasone suppression test (DST)

Comparator

Patients with primary aldosteronism with normal DST (no ACS) and matched population-based controls from the KORA-F4 study

Outcome

Prevalence of impaired glucose homeostasis (assessed via oral glucose tolerance tests, 2-hour plasma glucose, and type 2 diabetes mellitus diagnosis)surrogate

Autonomous cortisol secretion is common in primary aldosteronism and is significantly associated with impaired glucose metabolism and a higher risk of type 2 diabetes.

Main Result

Absolute Event Rate: 20% vs 0.8%

p-value: p=< 0.0001

Abstract

CONTEXT: Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and metabolic risks. Recent studies report glucocorticoid cosecretion as a relevant phenotype of PA, which could contribute to associated risks, including type 2 diabetes mellitus (T2DM). The relationship between autonomous cortisol secretion (ACS) and glucose metabolism in PA has not been investigated. OBJECTIVE: To evaluate the prevalence of impaired glucose homeostasis in patients with PA according to cortisol cosecretion. DESIGN: We performed oral glucose tolerance tests (OGTTs) and complete testing for hypercortisolism 1-mg dexamethasone suppression test (DST), late-night salivary cortisol, 24-hour urinary free cortisol in 161 newly diagnosed patients with PA of the German Conn Registry. Seventy-six of 161 patients were reevaluated at follow-up. We compared our results to a population-based sample from the Cooperative Health Research in the Region of Augsburg (KORA)-F4 study matched to the participants with PA (3:1) by sex, age, and body mass index. RESULTS: At the time of diagnosis, 125 patients (77.6%) had a pathological response in at least one of the Cushing screening tests; T2DM was diagnosed in 6.4% of these 125 cases. Patients with a pathological DST exhibited significantly higher 2-hour plasma glucose in OGTTs and were significantly more often diagnosed with T2DM than were patients with a normal DST (20% vs 0.8%, P < 0.0001) and matched controls from the KORA study (20.6% vs 5.9%, P = 0.022). Patients with PA without ACS tended to have higher homeostatic model assessment of insulin resistance levels than did KORA control subjects (P = 0.05). CONCLUSION: ACS appears frequently in patients with PA and is associated with impaired glucose metabolism, which could increase the risk of T2DM. PA itself seems to enhance insulin resistance.