Prediction of diabetes mellitus induced by steroid overtreatment in adrenal insufficiency

Valentina Guarnotta,Carla Giordano,Laura Tomasello

doi:10.1038/s41598-022-04904-w

Abstract

To assess the differences between patients with normal glucose tolerance (NGT) and prediabetes/diabetes mellitus (DM) in secondary adrenal insufficiency (SAI). We cross-sectionally evaluated 102, out of a total of 140, patients with SAI, who were on hydrocortisone (HC) (n = 50) and cortisone acetate (n = 52) replacement therapy. Clinical, anthropometric, and metabolic parameters were compared in patients with NGT (n = 60) and DM (n = 42). Patients with prediabetes/DM have a more marked family history of DM (p = 0.002), BMI (p < 0.001), higher waist circumference (p < 0.001), total cholesterol (p = 0.012), LDL-cholesterol (p = 0.004), triglycerides (p = 0.031), fasting glucose (p = 0.002), fasting insulin (p = 0.035), glutamate pyruvate transaminase (p = 0.018), HOMA-IR (p = 0.039), area under curves of glucose (p = 0.001) and insulin (p = 0.002), HbA1c (p < 0.001), Visceral adiposity index (VAI) (p = 0.038) and lower ISI-Matsuda (p = 0.008) and oral disposition index (p < 0.001) than patients with NGT. Multivariate analysis showed that family history of DM and VAI are independent predictive factors for DM in patients with SAI. Family history of DM and VAI can be predictors of the development of DM in patients with SAI and need to be investigated during steroid replacement therapy. Interestingly, the type and the dose of replacement steroid do not impact on diabetes mellitus.

Highlights

Secondary adrenal insufficiency (SAI) is characterized by the failure of pituitary disease to produce ACTH
Therapeutic steroid replacement management of SAI consists in cortisone acetate at the daily dose of 25–30 mg and hydrocortisone (HC) at the daily dose of 15–25 mg administered in two or three doses or, as an alternative, when cortisone acetate and/or HC are not available, prednisolone once or twice daily at the dose of 3–5 mg/day[4]
We compared patients with DM on HC and cortisone acetate therapy and observed that patients treated with HC had lower TG (p = 0.007) and Visceral Adiposity Index (VAI) (p = 0.010) and higher highdensity lipoprotein (HDL)-cholesterol (p = 0.005) than those treated with cortisone acetate (Table 2)

Summary

Introduction

Secondary adrenal insufficiency (SAI) is characterized by the failure of pituitary disease to produce ACTH It is isolated, while more frequently it is associated with other pituitary deficiencies such as hypothyroidism, hypogonadism and growth hormone deficiency (GHD). As reported in many studies, patients overtreated for a long period with conventional steroids develop frequently diabetes mellitus and dyslipidaemia, while novel formulations have no impact on metabolism[5,6,7,8,9]. Discordant reports are available between the association of high doses of cortisone replacement therapy and cardiovascular mortality, higher risk of diabetes mellitus and other c omorbidities[10,11,12]. The factors involved in the development of diabetes mellitus in patients with SAI treated with conventional steroids have not been fully investigated. The secondary aim was to identify predictive factors for the development of diabetes mellitus in order better to personalize steroid replacement treatment

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Conclusion