Greater adrenal gland volume seen for adults with vs. without type 2 diabetes

Ricardo Correa, MD, EsD, FACE, FACP, CMQ

Chronic physiological or psychological stress, such as experienced with chronic conditions, activates the hypothalamic-pituitary-adrenal axis. This constant activation leads to increased cortisol secretion and overwork of the adrenal glands. This adrenal gland excess can be translated to an enlargement of the adrenal cortex. Several studies have shown that people with chronic conditions have increased volume of the adrenal glands.

Type 2 diabetes is a chronic condition known to activate the hypothalamic-pituitary-adrenal axis. Patients with mild autonomous cortisol secretion have an increased prevalence of prediabetes, insulin resistance and type 2 diabetes. Prior articles have suggested that adrenal volume can indicate hypothalamic-pituitary-adrenal axis activation. However, the evidence for this is still very low, and it is not common to use this measure in clinical practice as a predictor of dysmetabolism.

MRI can help to characterize adrenal tissue and measure the volume of the gland. There have been few studies that use MRI for the volumetric measurement of the adrenal gland and correlate that with the presence of dysmetabolism. The caveat for MRI is that it is expensive imaging. Not all patients can afford this study to evaluate predisposition to prediabetes or diabetes when other techniques are cheaper and have high predictability.

The study by Askani and colleagues aimed to assess the role of adrenal gland volume as quantified by MRI and determine its position as an indirect marker of impaired glucose metabolism and dysfunction of the hypothalamic-pituitary-adrenal axis in prediabetes and type 2 diabetes in a population‐based Western cohort.

To perform a case-control study, they utilize the KORA-MRI substudy, an MRI study nested within the population‐based prospective cohort. They include 375 eligible individuals. On them, they performed a comprehensive whole‐body MRI over 15 months. For the assessment of adrenal gland volume, a two‐point T1‐weighted isotropic VIBE‐Dixon gradient‐echo sequence of the trunk was applied, and two independent blinded radiologists did the readings.

Adding the volume from the left and right adrenal, the total adrenal volume was statistically significantly higher in patients with type 2 diabetes than in prediabetes or healthy individuals, 13.9 mL,12.5 mL and 10 mL, respectively. This was true even after adjusting for age, sex, hypertension, triglyceride level and BMI. In addition, the estimated risk for type 2 diabetes increased per 1 mL increase in adrenal gland volume in all the different models performed.

This is the most extensive study to analyze adrenal volume as a marker of impaired metabolic state, including higher levels of BMI, triglycerides, hypertension and impaired glucose metabolism.

Even though there are some limitations to this study — including cross-sectional design and the specific study population, which prevent generalizability, and the lack of a gold standard to confirm the accuracy of the volumetric measurements — the findings open a new area of research. This type of research will correlate imaging and possibly artificial intelligence with metabolic predictability.

Currently, the clinical applicability of this study is very low because patients with prediabetes and diabetes do not usually get an adrenal MRI unless there are other concerns. The next step is to pursue a more detailed and standardized multicentric study to evaluate the feasibility of measuring adrenal volume by imaging as a predictor of dysmetabolism. Additionally, if we find this is a stronger predictor, cost-benefit should also be evaluated.