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.

Frequently Asked Questions in Patients With Adrenal Insufficiency in the Time of COVID-19.

Adrenal insufficiency (AI) is a life-threatening disorder, with increased morbidity and mortality, especially in case of an acute illness that can increase the requirement of cortisol. A novel infectious disease, termed Coronavirus Disease 2019 (COVID-19), appeared in 2020. Therefore, AI patients are experiencing a novel challenge: the risk of infection. In our experience, a prompt contact to the Endocrine center (with a telemedicine consultation) and a full awareness of diseases (cortisol deficiency, COVID-19 and the self-management of an adrenal crisis) are important to motivate patients. Vaccine is an effective treatment to prevent hospitalization and aggressive course of COVID-19. Some patients manifest challenges due to inequitable access and vaccine hesitancy, resulting in a delay in the acceptance of vaccines despite the availability of vaccination services. Therefore, an effort of all physicians must be conducted in order to advise patients with AI. In this short review, we try to answer some frequently asked questions regarding the management of patients with AI.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of adrenal insufficiency.

We provide guidance on prevention of adrenal crisis during the global COVID-19 crisis, a time with frequently restricted access to the usual level of healthcare. Patients with adrenal insufficiency are at an increased risk of infection, which may be complicated by developing an adrenal crisis; however, there is currently no evidence that adrenal insufficiency patients are more likely to develop a severe course of disease. We highlight the need for education (sick day rules, stringent social distancing rules), equipment (sufficient glucocorticoid supplies, steroid emergency self-injection kit) and empowerment (steroid emergency card, COVID-19 guidelines) to prevent adrenal crises. In patients with adrenal insufficiency developing an acute COVID-19 infection, which frequently presents with continuous high fever, we suggest oral stress dose cover with 20 mg hydrocortisone every 6 h. We also comment on suggested dosing for patients who usually take modified release hydrocortisone or prednisolone. In patients with adrenal insufficiency showing clinical deterioration during an acute COVID-19 infection, we advise immediate (self-)injection of 100 mg hydrocortisone intramuscularly, followed by continuous i.v. infusion of 200 mg hydrocortisone per 24 h, or until this can be established, and administration of 50 mg hydrocortisone every 6 h. We also advise on doses for infants and children.

Presence, patterns & predictors of hypocortisolism in patients with HIV infection in India.

BACKGROUND & OBJECTIVES: : Adrenal insufficiency (AI) is rarely diagnosed in patients with HIV infection, in spite of autopsy studies showing very high rates of adrenal involvement. This study was aimed to determine the presence, patterns and predictors of AI in patients with HIV infection. METHODS: : Consecutive HIV patients, 18-70 yr age, without any severe co-morbid state, having at least one-year follow up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. RESULTS: : From initially screened 527 patients, 359 patients having good immune function were analyzed. Basal morning cortisol <6 µg/dl (<165 nmol/l; Group 1), 6-11 µg/dl (165-300 nmol/l; Group 2), 11-18 µg/dl (300-500 nmol/l; Group 3) and ≥18 µg/dl (500 nmol/l; Group 4) were observed in 13, 71, 199 and 76 patients, respectively. Adrenocorticotropic hormone (ACTH) stimulation test revealed 87 patients (24.23%) to have AI. AI in groups 1-4 was 100, 56.34, 17.09 and 0 per cent, respectively. AI patients were more likely to be females (P< 0.05), having longer disease duration (P< 0.05), immune reconstitution inflammatory syndrome, hyperkalaemia (P< 0.01), lower fasting glucose (P< 0.01), dehydroepiandrosterone sulphate (DHEAS) and vitamin D. Regression analysis revealed morning cortisol and DHEAS to be best predictors of AI (P=0.004 and 0.028, respectively). INTERPRETATION & CONCLUSIONS: : AI is a significant problem in HIV-infected individuals, observed in nearly a quarter of patients. Diagnosis warrants high index of suspicion and low threshold for screening, especially in those having low DHEAS and hyperkalaemia. Morning cortisol is a reasonable screening test, with ACTH stimulation warranted to confirm diagnosis, especially in patients with morning cortisol <11 µg/dl (300 nmol/l).

Adrenal Insufficiency as a Result of Ritonavir and Exogenous Steroid Exposure: Report of 6 Cases and Recommendation for Management.

Numerous cases of Cushing syndrome have been reported as a result of the interaction between ritonavir (RTV) and exogenous steroid medications. Another complication that frequently occurs is secondary adrenal insufficiency, which can be profound and has not been well described. Here, we report 6 cases of adrenal suppression caused by RTV and exogenous steroids, all of which required corticosteroid replacement therapy and 2 of which were severe enough to require hospitalization. These cases add to the body of literature on the dangerous interaction between RTV and corticosteroids and highlight the risk of secondary adrenal suppression. We also review the literature on this complication and make a recommendation for managing and monitoring such cases.

Transient acute adrenal insufficiency associated with adenovirus serotype 40 infection.

We present an instance of a 6-year-old boy who was admitted with adenovirus infection and developed transient acute adrenal insufficiency, which required supplementation with glucocorticoids and mineralocorticoids for 8 weeks. Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We could not find any similar reported case in medical literature. We hope our case would add to the existing knowledge of adenoviral complications in paediatric patients.

Cytomegalovirus-induced adrenal insufficiency in a renal transplant recipient.

Cytomegalovirus (CMV) is an important pathogen in organ-transplant recipients. There have been frequent reports of CMV-induced adrenal insufficiency in patients with human immunodeficiency virus infection. Herein, we report CMV-induced renal insufficiency in a renal transplant recipient. A 24-year-old woman had gradual onset of weakness, anorexia, nausea, hypotension, and skin hyperpigmentation at 5 months after renal transplantation. The immunosuppression regimen included cyclosporine, mycophenolate mofetil, and corticosteroid (prednisolone, 5 mg/d). Recent history included acute CMV infection, which was treated with ganciclovir. Basal serum cortisol concentration was 4 microg/dL, and stimulated serum cortisol concentration was less than 10 microg/dL. All clinical signs and symptoms and hypotension gradually improved after the oral prednisolone dose was increased to 10 mg/d. Clinicians must be aware of the possibility of CMV-induced adrenal insufficiency in renal transplant recipients. The condition may be symptomatic despite low-dose prednisolone therapy.

Adrenal insufficiency in severe West Nile Virus infection.

OBJECTIVE: To explore adrenal function in severe West Nile virus (WNV) infection. DESIGN AND SETTING: Prospective interventional cohort study in a medical ICU of a teaching hospital. PATIENTS: Ten consecutive patients (seven men, mean age 64+/-12years, mean SAPS II 26+/-6) with definite diagnosis of WNV related meningoencephalitis and variable proportion of organ/system failure. All patients had fever (mean body temperature 39+/-1 degrees C) and altered mental status (mean Glasgow Coma Score 11+/-2). Mean SOFA score was 9+/-2; eight patients had systemic inflammatory response syndrome, five septic shock, and six acute respiratory failure (usually from central origin) requiring mechanical ventilation. INTERVENTIONS: A short corticotropin test was performed in each patient to assess the adrenal function. MEASUREMENTS AND RESULTS: Cortisol response was defined as the difference between baseline and corticotropin-stimulated peak. Absolute adrenal insufficiency was defined by a baseline cortisol level below 15 microg/dl (415 nmol/l). Relative insufficiency was defined by a cortisol response of 9 microg/dl (250 nmol/l) or less. Relative adrenal insufficiency, defined by a corticotropin response below 9 microg/dl, was observed in seven while the remaining three had normal cortisol response; six out of these seven died in the ICU. All patients with normal adrenal function survived. CONCLUSION: Adrenal insufficiency is frequent in severe WNV infection and carries a poor outcome. In the absence of specific effective treatment, our data provide a rational to investigate a supplemental corticosteroid treatment in a controlled trial.

Infectious causes of adrenal insufficiency.

More than 150 years ago, Thomas Addison first described the clinical features and pathogenesis of adrenal insufficiency. At that time, tuberculosis was the most common cause of this disease. The pathway to diagnosis and treatment of Addison's disease has been well described. However, determining the cause of the disorder remains a challenge. It is important to consider recently described infectious agents in the pathogenesis of Addison's disease. Mycobacterial, bacterial, viral, and fungal infections may lead to the development of adrenal insufficiency. Skin, pulmonary, and imaging findings can aid the clinician in making a prompt diagnosis of specific infections, which is crucial because early identification of infectious causes of Addison's disease may enable recovery of adrenal function. This review describes the clinical presentations of the multiple infectious causes of adrenal insufficiency.

Adrenal function in the human immunodeficiency virus-infected patient.

Although clinical manifestations of adrenal dysfunction are uncommon in patients infected with human immunodeficiency virus (HIV), subclinical functional abnormalities of the hypothalamic-pituitary-adrenal axis are frequent. Patients infected with HIV usually have higher basal serum cortisol and lower serum dehydroepiandrosterone concentrations than HIV-seronegative individuals. This imbalance has been related to progression of the infection by inducing a shift from T(H)1 to T(H)2 immunologic responses. Although, adrenal reserve may be marginal in HIV-infected patients, clinically evident adrenal insufficiency is uncommon and, when present, it is observed in advanced stages of the infection. Hypocortisolemia should be treated regardless of the existence of associated symptoms. On the contrary, hypercortisolemia in the absence of features of Cushing syndrome is common and should not promote treatment nor specific studies. The possible influence that alterations of the adrenal function could have on the patients' immune status and the eventual effect of antiretrovirals on these alterations merit further investigation.

Adrenal insufficiency combined with gastric cardia ulcer due to herpes simplex virus type 1 infection.

Adrenal insufficiency combined with gastric ulcer due to herpes simplex virus (HSV) infection is a very unusual condition. A 75-year-old woman suffered from a 4-day history of poor appetite, constipation, dysuria, severe headache, generalized pain and malaise. Hyponatremia was noted. Escherichia coli infection was identified from urine culture. Poor pituitary-adrenal axis response to hyponatremia and infection, as well as a history of intermittent treatment with steroids, led to a diagnosis of iatrogenic tertiary adrenal insufficiency. During hospitalization, the patient passed tarry stools. In addition to an antral ulcer, panendoscopy revealed an ulcer in the gastric cardia with a clean base and irregular margins. Biopsy of the cardia demonstrated multinucleated giant cells in the stratified squamous epithelium. Polymerase chain reaction studies confirmed HSV type 1 infection. In patients suffering from gastric cardia ulcer, the possibility of herpes infection must be considered, especially when complicated by steroid treatment or misuse. Because herpes infection in the squamous epithelium is self-limiting, practitioners should be aware of it, so that overtreatment can be avoided.

Primary hypoadrenalism assessed by the 1 microg ACTH test in hospitalized patients with active pulmonary tuberculosis.

Primary hypoadrenalism, assessed by 250 microg ACTH stimulation, is uncommon in patients with active pulmonary tuberculosis (PTB). Since 1 microg ACTH produces an equivalent +30 min cortisol response to 250 microg in control subjects, the 250 microg dose is supraphysiological and may lack sensitivity for the diagnosis of hypoadrenalism. Furthermore, the impact of coexistent HIV infection on the prevalence of primary hypoadrenalism in PTB is uncertain. We thus determined the cortisol response to an intravenous bolus of 1 microg ACTH in 21 controls, 18 HIV-positive (BMI 19.5+/-0.9 kg/m(2), albumin 24+/-1.4 g/l, CD4 count 192+/-47/mm(3)) and 22 HIV-negative (BMI 19.3+/-0.8 kg/m(2), albumin 29+/-1 g/l, CD4 count 652+/-76/mm(3)) patients with active PTB. The mean basal cortisol was greater in patients than in controls (559 vs. 373 nmol/l, p=0. 0009). The mean cortisol after 1 microg ACTH stimulation did not, however, differ significantly when comparing either patients and controls or patients who were HIV-positive and -negative (p>0.05). Using the minimum +30 min cortisol derived from the 21 controls as a marker of normal adrenal function (414 nmol/l), a single patient was classified as hypoadrenal. In conclusion, primary hypoadrenalism, as assessed by the 1 microg ACTH test, is uncommon in a cohort of ill, hospitalized patients with active PTB, irrespective of HIV status.