ABSTRACT
Introduction: The clinical presentation of SARS-CoV-2 ranges greatly from asymptomatic disease to critical illness. The multisystemic effect of COVID-19 is becoming increasingly apparent, but its impact on the endocrine system, in particular, the hypothalamic adrenal axis has yet to be defined. Case Description: A 64-year-old woman with hypothyroidism and type 2 diabetes mellitus presented to the emergency room with a 1-week history of abdominal pain, nausea, and vomiting. The patient experienced an asymptomatic COVID-19 infection 5 months prior and reported an unintentional 30-lb weight loss since. She had been admitted several times at an outside hospital for hyponatremia where she never received exogenous steroids. Physical exam was notable for hypotension, epigastric tenderness, and hyperpigmentation of oral mucosa. Chemistry was significant for hyponatremia 117 mmol/L (135-145). Hyponatremia workup revealed a TSH of 0.33 mcIU/ml (0.35-4.00), free T4 1.4 ng/dl (0.6-1.7), serum osmoles 253 mOsm/kg (279-300), urine osmoles 324 mOsm/kg (300-900) and urine sodium 104 mmol/l consistent with hypotonic hyponatremia. Fluid restriction and salt tablets were initiated. Morning 8 AM cortisol returned low (2.6 μg/dl (ref: >18). A high-dose 250 mcg ACTH stimulation test followed;cortisol levels returned 2.3, 2.9, and 2.6 μg/dl (ref: >18) at baseline, 30, and 60 minutes, respectively. ACTH level was elevated to 1944 pg/ml (7.2-63.3), aldosterone was undetectable < 3.0 ng/dl (upright: 4.0-31.0), anti-21-hydroxylase antibody were positive (ref: neg). CT scan of the abdomen returned unremarkable for any adrenal pathologies. Fluid restriction and salt tablets were discontinued. Hypotension and hyponatremia resolved after initiation of Hydrocortisone IV 25 mg q8h. She was discharged on Hydrocortisone 30 mg daily and Fludrocortisone 0.05 mg daily. Discussion: This patient presented with hyponatremia and biochemical evidence of adrenal insufficiency confirmed by an abnormal stress cortisol response to a high-dose ACTH stimulation test. The markedly elevated ACTH level, inappropriately low aldosterone level, and the presence of anti-21-hydroxylase antibodies support the diagnosis of Addison's disease. Primary adrenal insufficiency (AI) after COVID-19 due to adrenal infarcts and hemorrhage have been documented, but the normal CT suggested that the etiology of AI, in this case, was not due to the aforementioned. This case is the first to suggest the onset of Addison’s disease in the COVID-19 sequelae.
ABSTRACT
Background: Hypercortisolism accounts for relevant morbidity and mortality and is often a diagnostic challenge for clinicians. A prompt diagnosis is necessary to treat Cushing's syndrome as early as possible. Objective: The aim of this study was to develop and validate a clinical model for the estimation of pre-test probability of hypercortisolism in an at-risk population. Design: We conducted a retrospective multicenter case-control study, involving five Italian referral centers for Endocrinology (Turin, Messina, Naples, Padua and Rome). One hundred and fifty patients affected by Cushing's syndrome and 300 patients in which hypercortisolism was excluded were enrolled. All patients were evaluated, according to current guidelines, for the suspicion of hypercortisolism. Results: The Cushing score was built by multivariable logistic regression, considering all main features associated with a clinical suspicion of hypercortisolism as possible predictors. A stepwise backward selection algorithm was used (final model AUC=0.873), then an internal validation was performed through ten-fold cross-validation. Final estimation of the model performance showed an average AUC=0.841, thus reassuring about a small overfitting effect. The retrieved score was structured on a 17.5-point scale: low-risk class (score value: ≤5.5, probability of disease=0.8%); intermediate-low-risk class (score value: 6-8.5, probability of disease=2.7%); intermediate-high-risk class (score value: 9-11.5, probability of disease=18.5%) and finally, high-risk class (score value: ≥12, probability of disease=72.5%). Conclusions: We developed and internally validated a simple tool to determine pre-test probability of hypercortisolism, the Cushing score, that showed a remarkable predictive power for the discrimination between subjects with and without a final diagnosis of Cushing's syndrome.