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The diagnosis of adrenal insufficiency (AI) requires a high index of suspicion, detailed clinical assessment including detailed drug history, and appropriate laboratory evaluation. The clinical characteristics of adrenal insufficiency vary according to the cause, and the presentation may be myriad, e.g. insidious onset to a catastrophic adrenal crisis presenting with circulatory shock and coma. Secondary adrenal insufficiency (SAI) often presents with only glucocorticoid deficiency because aldosterone production, which is controlled by the renin angiotensin system, is usually intact, and rarely presents with an adrenal crisis. Measurements of the basal serum cortisol at 8 am (<140 nmol/L or 5 mcg/dL) coupled with adrenocorticotrophin (ACTH) remain the initial tests of choice. The cosyntropin stimulation (short synacthen) test is used for the confirmation of the diagnosis. Newer highly specific cortisol assays have reduced the cut-off points for cortisol in the diagnosis of AI. The salivary cortisol test is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels such as pregnancy. Children and infants require lower doses of cosyntropin for testing. 21-hydoxylase antibodies are routinely evaluated to rule out autoimmunity, the absence of which would require secondary causes of adrenal insufficiency to be ruled out. Testing the hypothalamic–pituitary–adrenal (HPA) axis, imaging, and ruling out systemic causes are necessary for the diagnosis of AI. Cancer treatment with immune checkpoint inhibitors (ICI) is an emerging cause of both primary AI and SAI and requires close follow up. Several antibodies are being implicated, but more clarity is required. We update the diagnostic evaluation of AI in this evidence-based review. Full article

Preexisting diabetes mellitus (DM) should be ruled out early in pregnancy in those at risk. During screening, a significant proportion of women do not reach the threshold for overt DM but fulfill the criteria used for diagnosing conventional gestational DM (cGDM). There is no consensus on the management of pregnancies with intermediate levels of hyperglycemia thus diagnosed. We have used the term early gestational DM (eGDM) for this condition and reviewed the currently available literature. Fasting plasma glucose (FPG), oral glucose tolerance test, and glycated hemoglobin (HbA1c) are the commonly employed screening tools in early pregnancy. Observational studies suggest that early pregnancy FPG and Hba1c correlate with the risk of cGDM and adverse perinatal outcomes. However, specific cut-offs, including those proposed by the International Association of the Diabetes and Pregnancy Study Group, do not reliably predict the development of cGDM. Emerging data, though indicate that FPG ≥ 92 mg/dL (5.1 mmol/L), even in the absence of cGDM, signals the risk for perinatal complication. Elevated HbA1c, especially a level ≥ 5.9%, also correlates with the risk of cGDM and worsened outcome. HbA1c as a diagnostic test is however besieged with the usual caveats that occur in pregnancy. The studies that explored the effects of intervention present conflicting results, including a possibility of fetal malnutrition and small-for-date baby in the early treatment group. Diagnostic thresholds and glycemic targets in eGDM may differ, and large multicenter randomized controlled trials are necessary to define the appropriate strategy. Full article