Management and Medical Therapy of Mild Hypercortisolism.

Mild hypercortisolism (mHC) is defined as an excessive cortisol secretion, without the classical manifestations of clinically overt Cushing's syndrome. This condition increases the risk of bone fragility, neuropsychological alterations, hypertension, diabetes, cardiovascular events and mortality. At variance with Cushing's syndrome, mHC is not rare, with it estimated to be present in up to 2% of individuals older than 60 years, with higher prevalence (up to 10%) in individuals with uncontrolled hypertension and/or diabetes or with unexplainable bone fragility. Measuring cortisol after a 1 mg overnight dexamethasone suppression test is the first-line test for searching for mHC, and the degree of cortisol suppression is associated with the presence of cortisol-related consequences and mortality. Among the additional tests used for diagnosing mHC in doubtful cases, the basal morning plasma adrenocorticotroph hormone, 24-h urinary free cortisol and/or late-night salivary cortisol could be measured, particularly in patients with possible cortisol-related complications, such as hypertension and diabetes. Surgery is considered as a possible therapeutic option in patients with munilateral adrenal incidentalomas and mHC since it improves diabetes and hypertension and reduces the fracture risk. In patients with mHC and bilateral adrenal adenomas, in whom surgery would lead to persistent hypocortisolism, and in patients refusing surgery or in whom surgery is not feasible, medical therapy is needed. Currently, promising though scarce data have been provided on the possible use of pituitary-directed agents, such as the multi-ligand somatostatin analog pasireotide or the dopamine agonist cabergoline for the-nowadays-rare patients with pituitary mHC. In the more frequently adrenal mHC, encouraging data are available for metyrapone, a steroidogenesis inhibitor acting mainly against the adrenal 11-ßhydroxylase, while data on osilodrostat and levoketoconazole, other new steroidogenesis inhibitors, are still needed in patients with mHC. Finally, on the basis of promising data with mifepristone, a non-selective glucocorticoid receptor antagonist, in patients with mild cortisol hypersecretion, a randomized placebo-controlled study is ongoing for assessing the efficacy and safety of relacorilant, a selective glucocorticoid receptor antagonist, for patients with mild adrenal hypercortisolism and diabetes mellitus/impaired glucose tolerance and/or uncontrolled systolic hypertension.

Adrenal Insufficiency at the Time of COVID-19: A Retrospective Study in Patients Referring to a Tertiary Center.

CONTEXT: Coronavirus disease 2019 (COVID-19) represents a global health emergency, and infected patients with chronic diseases often present with a severe impairment. Adrenal insufficiency (AI) is supposed to be associated with an increased infection risk, which could trigger an adrenal crisis. OBJECTIVE: Our primary aim was to evaluate the incidence of COVID-19 symptoms and complications in AI patients. DESIGN AND SETTING: We conducted a retrospective case-control study. All patients were on active follow-up and lived in Lombardy, Italy, one of the most affected areas. PATIENTS: We enrolled 279 patients with primary and secondary AI and 112 controls (patients with benign pituitary lesions without hormonal alterations). All AI patients had been previously trained to modify their replacement therapy on stress doses. INTERVENTION: By administering a standardized questionnaire by phone, we collected data on COVID-19 suggestive symptoms and consequences. RESULTS: In February through April 2020, the prevalence of symptomatic patients (complaining at least 1 symptom of viral infection) was similar between the 2 groups (24% in AI and 22.3% in controls, P = 0.79). Highly suggestive COVID-19 symptoms (at least 2 including fever and/or cough) also occurred equally in AI and controls (12.5% in both groups). No patient required hospitalization and no adrenal crisis was reported. Few nasopharyngeal swabs were performed (n = 12), as indicated by sanitary regulations, limiting conclusions on the exact infection rate (2 positive results in AI and none in controls, P = 0.52). CONCLUSIONS: AI patients who are adequately treated and trained seem to display the same incidence of COVID-19-suggestive symptoms and disease severity as controls.

Case Report: Late-Onset Congenital Adrenal Hyperplasia and Acute Covid-19 Infection in a Pregnant Woman: Multidisciplinary Management.

Background: The impact of the Covid-19 infection on patients with chronic endocrine disease is not fully known. We describe here the first case of a pregnant woman with Covid-19 acute infection and non-classical congenital adrenal hyperplasia (NCAH). Case description: A woman at 36 weeks of gestation was referred to our Maternity Hospital for premature rupture of membranes (PROM). Her medical history was positive for NCAH on chronic steroid replacement till the age of 17 years (cortisone acetate and dexamethasone, both in the morning). At admission, her naso-oro-pharyngeal swab resulted positive for SARS-CoV-2. Due to hyperpyrexia and late preterm PROM, cesarean section was planned, and she was started on a 100 mg-bolus of hydrocortisone, followed by continuous infusion of 200 mg/24 h. A female neonate in good clinical condition and with a negative nasopharyngeal Covid-19 swab was delivered. On second postpartum day, the mother was in good condition and was switched to oral steroid therapy. On third postpartum day she worsened, with radiological signs of acute pulmonary embolism. Oro-tracheal intubation and mechanical ventilation were started, and she was switched back to intravenous steroid therapy. On April 30, pulmonary embolism was resolved, and on May 13th she was discharged in good condition. Conclusions: We report the first case of Covid-19 acute infection that occurred in late-pregnancy in a woman with NCAH on chronic steroid replacement. The management of the patient in a reference center with early involvement of a multidisciplinary team granted prompt care and adequate protection for all the involved sanitary operators.