Endocrine changes in SARS-CoV-2 patients and lessons from SARS-CoV.

Coronavirus infection outbreaks have occurred frequently in the last two decades and have led to significant mortality. Despite the focus on reducing mortality by preventing the spread of the virus, patients have died due to several other complications of the illness. The understanding of pathological mechanisms and their implications is continuously evolving. A number of symptoms occur in these patients due to the involvement of various endocrine glands. These clinical presentations went largely unnoticed during the first outbreak of severe acute respiratory syndrome (SARS) in 2002-2003. A few of these derangements continued during the convalescence phase and sometimes occurred after recovery. Similar pathological and biochemical changes are being reported with the novel coronavirus disease outbreak in 2020. In this review, we focus on these endocrine changes that have been reported in both SARS coronavirus and SARS coronavirus-2. As we battle the pandemic, it becomes imperative to address these underlying endocrine disturbances that are contributing towards or predicting mortality of these patients.

Disseminated cytomegalovirus infection with bilateral adrenal pseudotumors masquerading as recurrent hematologic malignancy.

BACKGROUND: Mass-like lesions are an uncommon presentation of cytomegalovirus (CMV) disease. CASE: We report on a case of disseminated CMV disease with bilateral adrenal pseudotumors in a patient with a history of acute leukemia in remission. CONCLUSION: In the settings of advanced cancer therapy and organ transplantation, a high index of suspicion for CMV should be maintained for mass-like disease.

Adrenal disorders in human immunodeficiency virus (HIV) infected patients.

Human Immunodeficiency Virus (HIV) infection is associated with adrenal disorders, which must not be underestimated. Adrenal morphologic changes are primarily related to opportunistic infections, mostly by cytomegalovirus and mycobacteria, and malignant tumours such as non-Hodgkin's lymphoma and Kaposi's sarcoma. The most frequent biological alteration reported to date is the increases in cortisol concentrations which results from a decrease in cortisol metabolism and hyperactivity of the hypothalamo-pituitary-adrenal axis commonly referred to as pseudo-Cushing's syndrome. These modifications can be a consequence of antiretroviral therapy and do not require any investigation or specific treatment. Conversely, adrenal insufficiency, either iatrogenic or secondary to glandular infiltration by neoplasms or infections, needs long-term substitution with hydrocortisone, but at present occurs more rarely and usually at late stages of disease progression. The impact of HIV infection on the other adrenocortical functions has been less reported in the literature although several studies show low levels of adrenal androgens, especially dehydroepiandrostenedione (DHEA). Impairment in mineralocorticoid function appears occasional and remains a subject of debate.

Cytomegalovirus infection of endocrine system in a patient with diffuse large B-cell lymphoma. Report of a case.

Cytomegalovirus (CMV) is an opportunistic pathogen causing different diseases in immunocompromised patients and leading to death in a high percentage of cases. CMV infection is also relatively frequent among patients with hematological malignancies, especially when treated with immunosuppressive agents. We describe the clinical history of a patient with stage IV diffuse large B-cell lymphoma (DLBCL) treated with eight courses of R-CHOP every two weeks, who presented clinical remission of the disease at the end of therapy. However, two months later he developed neurological symptoms due to cerebellar involvement and a subcutaneous dorsal lymphomatous infiltration. He had a partial response after chemotherapy and brain radiotherapy, but his clinical course was complicated by fever and hypotension. Although the fever resolved with broad-spectrum antibiotics, he presented progressive endocrine failure and died three weeks later. Autopsy confirmed disseminated multiorgan involvement by DLBCL associated with an unexpected CMV infection of the lungs and several endocrine organs including the pituitary gland, pancreatic islets and adrenals, a clinical association not previously reported in the English literature.

Disseminated herpes simplex infection with cystic fibrosis: a case report.

A 6 months old female infant presented with history of fever, cough and severe respiratory distress. There was past history of recurrent attacks of pneumonia. She succumbed to the illness after a hospital stay of 7 days. Postmortem revealed morphological evidence of cystic fibrosis along with herpes simplex infection of liver and adrenals. The co-existence of disseminated herpes simplex infection and cystic fibrosis is very rare.

Adrenal infections.

Adrenal infections are an important but under-recognized clinical entity. The adrenal gland can be infected by a myriad of pathogens including fungi, viruses, parasites, and bacteria. Infection can directly or indirectly cause tissue damage and alteration in endocrine function. Direct damage occurs via microbial replication and local production of toxic compounds, such as endotoxins. Indirect damage results from alterations in the regulation of a host's immunologic and endocrine mediators in response to damage by a microbe at a distant site. Variations in pathogen tropism, adrenal anatomy, and host immune integrity contribute to the progression of active disease and discernable adrenal dysfunction. Early recognition and intervention in the case of adrenal infection can significantly improve outcome, demonstrating the need for increased clinical suspicion in the appropriate clinical setting.

The development of cytomegalovirus-induced adrenal failure in a patient with AIDS while receiving corticosteroid therapy.

We report a case of Addisonian crisis due to cytomegalovirus (CMV) adrenalitis occurring in a patient with AIDS while receiving supraphysiological doses of steroids for the treatment of Pneumocystis carinii pneumonia. The case highlights the importance of considering the diagnosis of adrenal failure in AIDS, even in patients receiving supraphysiological doses of steroids.

Successful treatment with ganciclovir of a HIV endstage patient with adrenal insufficiency.

We report on a 31-year-old AIDS patient who presented with rapid progressive fatigue, weakness, weight loss and hyperpigmentation. Endoscopy showed an ulcerous CMV gastritis with the histological hallmarks of this disease. In addition, laboratory tests revealed the constellation of an adrenal insufficiency with low plasma levels of sodium and increased levels of potassium and ACTH. After initiation of ganciclovir treatment, the CMV gastritis healed and the electrolyte abnormalities were resolved within 2 weeks. We assume that a CMV adrenalitis was treated in a reversible stage. The literature on CMV adrenalitis is reviewed to support this conclusion.

[Tissue-specific expression of human endogenous retrovirus mRNA and its regulation by cytokines in vitro].

To investigate biological roles of human endogenous retroviruses (ERVs), the author examined the viral mRNA expression in the normal systemic organs in vivo and its regulation by cytokines in cultured cells. The following evidence suggesting biological activities of a human ERV, ERV3, was obtained. First, the ERV3 mRNA was demonstrated at different levels in organs, and at consistently high levels in adrenal glands from all individuals and in all adrenocortical adenomas examined, by Northern hybridization. In situ hybridization revealed that the ERV3 expression was localized in all three layers of the adrenal cortex, but not in the medulla. These results suggest that the ERV3 expression may relate to the cellular differentiation and/or steroid production of adrenocortical cells. Second, the amount of ERV3 mRNA in cultured endothelial cells from human umbilical vein was significantly increased with any of TNF-alpha, IL-1 beta or IL-1 alpha stimulation but decreased with IFN-gamma treatment, by a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with competitive PCR. The collective evidence suggests that the ERV3 expression may be upregulated at the inflammatory sites of vessels in vivo, and that the ERV3 expression may, therefore, play certain pathogenic roles in diseases, including collagen and vascular diseases in man.

Adrenalitis and the adrenocortical response of resistant and susceptible mice to acute murine cytomegalovirus infection.

Murine cytomegalovirus (MCMV) induces adrenalitis in BALB/c mice but does not compromise adrenal function, assessed by levels of circulating adrenocorticotropic hormone (ACTH) and by the response to challenge with synthetic ACTH. Levels of corticosterone increased 2 days after infection in mice of this strain, consistent with previously established interactions between mediators of acute inflammation and activation of the hypothalmus-pituitary-adrenal axis. Moreover, an adrenocortical response was critical to survival of BALB/c (but not C57BL/6) mice 3 days after infection, as pharmacologically or surgically adrenalectomized BALB/c mice died when given doses of virus up to fivefold lower, than they could normally tolerate. However, death could not be prevented by the administration of soluble cytokine receptors to inhibit the action of interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF alpha). The corticosteroid response did not mediate.MCMV-induced thymic atrophy. As the above traits were all less evident in C57BL/6 mice, a common genetic basis is discussed.

Clinico-pathological study of cytomegalovirus (CMV) in AIDS autopsies: under-recognition of CMV pneumonitis and CMV adrenalitis.

BACKGROUND: Cytomegalovirus (CMV) is a common cause of morbidity in human immunodeficiency virus (HIV) infected patients, predominantly when severe immunosuppression has occurred. Although CMV infection of the retina and gastrointestinal tract is well recognised as causing substantial morbidity, the significance of infection at other sites, in particular the lungs and adrenal glands is unclear. AIMS: To assess the extent of CMV infection in postmortem examinations performed on HIV-infected patients. To estimate the degree of concordance between clinical and postmortem findings and the effect of prior diagnosis and/or treatment of CMV infection. METHODS: The postmortem examination findings and clinical records of 25 consecutive HIV-infected patients who underwent a complete autopsy were examined. RESULTS: CMV infection was demonstrated in 19 patients (76%) at postmortem examination, with the most common sites of infection being the adrenal glands (56%) and lungs (44%). Concordance between clinical diagnosis of CMV infection and postmortem findings was low with only five of 19 patients (26%) having an antemortem diagnosis. No patient with CMV infection of the lungs or adrenal glands had a clinical diagnosis made, despite four patients having florid CMV pneumonitis at postmortem examination; in three the probable cause of death. CONCLUSION: CMV infection is a common postmortem finding in HIV-infected patients but the concordance between clinical diagnosis and autopsy findings is low. CMV appears to be a significant pathogen in HIV-related respiratory disease.