SARS-CoV-2-induced adrenal crisis in a patient with autoimmune polyglandular syndrome type 1: case report.

Autoimmune polyglandular syndromes (APS) are rare disorders characterized by the coexistence of endocrine and non-endocrine dysfunctions mediated by autoimmune mechanisms. Autoimmune polyglandular syndrome type 1 is defined as coexistence of chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. Addison's disease as the obligatory component is potentially life threatening.Herein, we demonstrate a case of a 44-year-old woman with APS-1 (hypoparathyroidism, adrenal insufficiency, hypergonadotropic hypogonadism) and SARS-CoV-2-induced adrenal crisis. The patient presented with the typical manifestations of hypotensive shock, electrolyte disturbances of hyponatremia and hyperkalemia, and hypoglycaemia.Our case report illustrates the increased risk of severe course of COVID-19 in APS-1 syndrome patients along with heightened exposure to medical complications. The case reinforced the significance of a timely diagnosis, appropriate treatment, and education of patients with such a rare condition like APS-1.

Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: the ICARO tool.

Objective: Registry data show that Cushing's syndrome (CS) and adrenal insufficiency (AI) increase mortality rates associated with infectious diseases. Little information is available on susceptibility to milder forms of infections, especially those not requiring hospitalization. This study aimed to investigate infectious diseases in patients with glucocorticoid disorders through the development of a specific tool. Methods: We developed and administered the InfeCtions in pAtients with endocRinOpathies (ICARO) questionnaire, addressing infectious events over a 12-month observation period, to 1017 outpatients referred to 4 University Hospitals. The ICARO questionnaire showed good test-retest reliability. The odds of infection (OR (95% CI)) were estimated after adjustment for confounders and collated into the ICARO score, reflecting the frequency and duration of infections. Results: In total, 780 patients met the inclusion criteria: 43 with CS, 32 with adrenal incidentaloma and mild autonomous cortisol secretion (MACS), and 135 with AI, plus 570 controls. Compared to controls, CS was associated with higher odds of urinary tract infections (UTIs) (5.1 (2.3-9.9)), mycoses (4.4 (2.1-8.8)), and flu (2.9 (1.4-5.8)). Patients with adrenal incidentaloma and MACS also showed an increased risk of UTIs (3.7 (1.7-8.0)) and flu (3.2 (1.5-6.9)). Post-dexamethasone cortisol levels correlated with the ICARO score in patients with CS. AI was associated with higher odds of UTIs (2.5 (1.6-3.9)), mycoses (2.3 (1.4-3.8)), and gastrointestinal infections (2.2 (1.5-3.3)), independently of any glucocorticoid replacement dose. Conclusions: The ICARO tool revealed a high prevalence of self-reported infections in patients with glucocorticoid disorders. ICARO is the first of its kind questionnaire, which could be a valuable tool for monitoring infections in various clinical settings.

Diagnostic strategies in adrenal insufficiency.

PURPOSE OF REVIEW: Adrenal insufficiency (AI) is the clinical manifestation of deficient production of glucocorticoids with occasionally deficiency also in mineralocorticoids and adrenal androgens and constitutes a fatal disorder if left untreated. The aim of this review is to summarize the new trends in diagnostic methods used for determining the presence of AI. RECENT FINDINGS: Novel aetiologies of AI have emerged; severe acute respiratory syndrome coronavirus 2 infection was linked to increased frequency of primary AI (PAI). A new class of drugs, the immune checkpoint inhibitors (ICIs) widely used for the treatment of several malignancies, has been implicated mostly with secondary AI, but also with PAI. Salivary cortisol is considered a noninvasive and patient-friendly tool and has shown promising results in diagnosing AI, although the normal cut-off values remain an issue of debate depending on the technique used. Liquid chromatography-mass spectrometry (LC-MS/MS) is the most reliable technique although not widely available. SUMMARY: Our research has shown that little progress has been made regarding our knowledge on AI. Coronavirus disease 2019 and ICIs use constitute new evidence on the pathogenesis of AI. The short synacthen test (SST) remains the 'gold-standard' method for confirmation of AI diagnosis, although salivary cortisol is a promising tool.

Primary adrenal insufficiency and myocarditis in COVID-19 disease: a case report.

BACKGROUND: COVID-19 has different manifestations from respiratory to GI problems, and some of them are more common, but some are rare. Reporting rare cases can significantly advance our understanding of the disease. CASE PRESENTATION: In this case, we report an 18-year-old teenage boy with chest pain and resistant hypotension following COVID-19 infection, finally diagnosed as primary adrenal insufficiency and COVID-19 myocarditis. CONCLUSION: Adrenal insufficiency can be life-threatening due to its adverse effects on hemodynamic and electrolyte equilibrium. In addition, COVID-19 induced myocarditis can make the situation more complicated.

New-Onset Primary Adrenal Insufficiency and Autoimmune Hypothyroidism in a Pediatric Patient Presenting with MIS-C.

INTRODUCTION: There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link is established. There are reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19. We describe the first pediatric report of adrenal insufficiency and autoimmune hypothyroidism after COVID-19. CASE PRESENTATION: A 14-year-old previously healthy girl, with vitiligo, presented in shock following 1 week of fever, lethargy, diarrhea, and vomiting. Three weeks prior, she had congestion and fatigue and known familial exposure for COVID-19. Labs were remarkable for sodium 129 mmol/L, K 4.3 mmol/L, creatinine 2.9 mg/dL, hemoglobin 8.3 g/dL, and positive COVID-19 PCR and SARS-CoV-2 IgG. She was resuscitated with normal saline and required pressor support. EKG showed abnormal repolarization presumed secondary to myocarditis. She met the criteria for multisystem inflammatory syndrome in children (MIS-C), received intravenous immune globulin and IL-1R antagonist and was admitted for intensive care. Persistent hypotension despite improved inflammatory markers and undetectable cortisol led to initiation of hydrocortisone. She was then able to rapidly wean off pressors and hydrocortisone within 48 h. Thereafter, tests undertaken for persistent bradycardia confirmed autoimmune hypothyroidism with TSH 131 µU/mL, free T4 0.85 ng/dL, and positive thyroid autoantibodies. Basal and stimulated cortisol were <1 µg/dL on a standard 250 µg cosyntropin stimulation test, with baseline ACTH >1,250 pg/mL confirming primary adrenal insufficiency. Treatment was initiated with hydrocortisone, levothyroxine, and fludrocortisone. Adrenal sonogram did not reveal any hemorrhage and anti-adrenal antibody titers were positive. The family retrospectively reported oligomenorrhea, increased salt craving in the months prior, and a family history of autoimmune thyroiditis. The cytokine panel was notably different from other cases of MIS-C. CONCLUSION: This is the first pediatric report, to our knowledge, of primary adrenal insufficiency and hypothyroidism following COVID-19, leading to a unique presentation of autoimmune polyglandular syndrome type 2. The initial presentation was attributed to MIS-C, but the subsequent clinical course suggests the possibility of adrenal crisis. It remains unknown if COVID-19 had a causal relationship in triggering the autoimmune adrenal insufficiency and hypothyroidism.

[Practical recommendations for screening and management of functional disorders of the adrenal cortex in cases of SARS-CoV-2 infections]. / Praktische Empfehlungen zum Screening und Management von Funktionsstörungen der Nebennierenrinde bei einer akuten SARS-CoV-2-Infektion.

Diseases of the adrenal cortex require particular attention during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Firstly, SARS-CoV­2 infections can give rise to extrapulmonary manifestations and cause endocrine disorders, particularly in the adrenal cortex. Furthermore, patients with pre-existing insufficiency of the adrenal cortex or hypercortisonism are particularly at risk from a severe infection such as SARS-CoV­2, to suffer from additional complications or a more severe course of a SARS-CoV­2 infection with a higher mortality. Especially in hemodynamically unstable patients with a SARS-CoV­2 infection, diseases of the adrenal glands should also be considered in the differential diagnostics and if necessary clarified, if this is not already known. Prolonged treatment of patients with a SARS-CoV­2 infection with regimens containing high doses of glucocorticoids can also result in a secondary adrenal insufficiency. In order to address these special aspects, some practical recommendations for the diagnostic and therapeutic management of functional disorders of the adrenal glands in patients with a SARS-CoV­2 infection are therefore presented.

The ISAQ Score Does Not Predict Adrenal Crisis in Patients with Primary Adrenal Insufficiency.

OBJECTIVE: This study aimed to investigate the ability of the immune system assessment questionnaire (ISAQ) to predict adrenal crisis (AC) and infectious events in patients with primary adrenal insufficiency (PAI). DESIGN: This was a prospective single-centre study over three years. METHODS: Patients answered the ISAQ at baseline and were seen every 4-6 months in the endocrine outpatient clinic. At each visit previous infectious periods which required an increase in daily glucocorticoid dosage and AC were reported and documented. Seventy-five patients with PAI (53 women; 43 patients with autoimmune PAI, 20 patients with salt-wasting congenital adrenal hyperplasia and 12 patients who underwent bilateral adrenalectomy) were analysed. Due to the COVID-19 pandemic and consecutive lockdown measures, the data were analysed separately for March 2018 to March 2020 (period 1), and March 2020 to March 2021 (period 2). RESULTS: During period 1 the ISAQ score significantly correlated with the number of reported infectious events (r=0.351; p<0.01), but not during period 2 (r=0.059, p=0.613), in which the number of infectious events per patient-year significantly decreased (1.1±0.1 vs 0.4±0.1; p<0.001). The frequency of AC decreased from 8.8 to 2.4 per 100 patient-years between the two study periods. The ISAQ score was not different between patients with or without AC. CONCLUSIONS: The ISAQ score does not identify patients prone to ACs. The COVID-19 pandemic and consecutive lockdown measures significantly diminished the frequency of infectious events and ACs.

Central adrenal insufficiency and diabetes insipidus as potential endocrine manifestations of COVID-19 infection: a case report.

SARS-CoV-2 infection, responsible for the coronavirus disease-2019 (COVID-19) has rapidly spread, causing a global pandemic. COVID-19 can affect any organ system in the body due to overwhelming dysregulated immune response and long-term effects of the disease is still unknown. Endocrine complications associated with COVID-19 is exceedingly rare. Here we present a unique case of a 44-year-old female who developed adrenal insufficiency and central diabetes insipidus following COVID-19 infection.

Adrenal insufficiency.

Adrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production. Primary AI (PAI) is rare and is caused by direct adrenal failure. Secondary AI (SAI) is more frequent and is caused by diseases affecting the pituitary, whereas in tertiary AI (TAI), the hypothalamus is affected. The most prevalent form is TAI owing to exogenous glucocorticoid use. Symptoms of AI are non-specific, often overlooked or misdiagnosed, and are related to the lack of cortisol, adrenal androgen precursors and aldosterone (especially in PAI). Diagnosis is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones and stimulation tests. The goal of therapy is to establish a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs. This Primer provides insights into the epidemiology, mechanisms and management of AI during pregnancy as well as challenges of long-term management. In addition, the importance of identifying life-threatening adrenal emergencies (acute AI and adrenal crisis) is highlighted and strategies for prevention, which include patient education, glucocorticoid emergency cards and injection kits, are described.

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.

New onset adrenal insufficiency in a patient with COVID-19.

SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host's cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.

Adrenal insufficiency in coronavirus disease 2019: a case report.

BACKGROUND: Novel coronavirus disease 2019 presents with fever, dry cough, fatigue, and shortness of breath in most cases; however, some rare manifestations in other organs have also been reported so far. CASE PRESENTATION: Here, the case of a 69-year-old Iranian man with coronavirus disease 2019 is presented who suffered from frequent episodes of vasopressor-resistant hypotension during intensive care unit admission, which was finally attributed to the occurrence of acute adrenal insufficiency. CONCLUSIONS: As this is a rare complication, adrenal insufficiency might be easily overlooked. However, early detection of this disease among critically ill patients infected with coronavirus disease 2019 could be lifesaving, especially among those unresponsive to vasopressor agents.