A Clinical Case of Pheochromocytoma Presenting with Decompensated Diabetes Mellitus and Paroxysmal Hypertension

Introduction: Pheochromocytoma is a rare neuroendocrine tumor that originates from the adrenal medulla, less commonly from extraadrenal chromaffin cells (paraganglioma). In about 90% of cases, the tumor produces abnormal amounts of catecholamines. Pheochromocytomas are usually benign, but in rare cases can be malignant. Typical clinical manifestations are the result of the haemodynamic and metabolic effects of catecholamines and usually include paroxysmal hypertension with the classic triad (headache, excessive sweating, palpitations), carbohydrate disorders, etc. Elevated levels of catecholamine metabolites (metanephrine and normetanephrine) tested in plasma or in 24-hour urine confirm the diagnosis. Surgical removal of the tumor is the only radical treatment. Follow-up of patients postoperatively should be lifelong and performed by a multidisciplinary team in a specialized center of expertise. Case report: A 36-year-old female patient referred to the clinic for decompensated diabetes mellitus. Detailed history revealed paroxysmal hypertension and the classic triad of pheochromocytoma. The diagnosis was confirmed by high urinary metanephrine levels and an abdominal CT scan, showing a tumor in the right adrenal gland with features typical of pheochromocytoma. Surgical removal of the pheochromocytoma and normalization of catecholamine levels led to normalization of blood pressure and reversal of diabetes mellitus. Conclusion(s): Pheochromocytoma is a difficult diagnosis in endocrinology practice as it can mimic many other diseases. Early detection and surgical removal of the tumor are crucial to avoid complications caused by elevated serum catecholamine levels.Copyright © 2022 Medical Information Center. All rights reserved.

Prevalence of reported incidental adrenal findings in chest computerized tomography scans performed during the COVID-19 pandemic in a single center in Northeast Brazil.

Objective: We investigated the prevalence of adrenal incidentalomas (AIs) in a nonselected Brazilian population in chest computed tomography (CT) performed during the COVID-19 pandemic. Materials and methods: This was a retrospective cross-sectional observational study using chest CT reports from a tertiary in- and outpatient radiology clinic from March to September 2020. AIs were defined by changes in the shape, size, or density of the gland initially identified in the released report. Individuals with multiple studies were included, and duplicates were removed. Exams with positive findings were reviewed by a single radiologist. Results: A total of 10,329 chest CTs were reviewed, and after duplicate removal, 8,207 exams were included. The median age was 45 years [IQR 35-59 years], and 4,667 (56.8%) were female. Thirty-eight lesions were identified in 36 patients (prevalence 0.44%). A higher prevalence was observed with age, with 94.4% of the findings in patients aged 40 years and over (RR 9.98 IC 2.39-41.58, p 0.002), but there was no significant difference between the sexes. Seventeen lesions (44.7%) had more than 10 HU, and five lesions (12.1%) were more than 4 cm. Conclusion: The prevalence of AIs in an unselected and unreviewed population in a Brazilian clinic is low. The impact on the health system caused by AIs discovered during the pandemic should be small regarding the need for specialized follow-up.

High prevalence of adrenal cortical adenomas in patients with cerebral meningiomas.

PURPOSE: Adrenal cortical adenomas (ACAs) represent one of the most common endocrine neoplasms. Recently, a genetic syndrome, characterized by tumor-suppressor ARMC5-gene mutations and causing primary macronodular bilateral adrenal hyperplasia with concomitant meningiomas of the central nervous system, has been described. Apart from this rare disorder and despite the well-known influence of steroid hormones on meningiomas, no data are available about the association between ACAs and meningiomas. METHODS: We investigated the prevalence of ACAs in a group of patients with cerebral meningioma undergoing unenhanced chest CT scans before attending surgical treatment. Patients with meningioma were age- and sex-matched in a 1:3 ratio with hospitalized patients for COVID-19. RESULTS: Fifty-six patients with meningioma were included and matched with 168 control patients with COVID-19. One-hundred forty-four (66.1%) were female and the median age was 63 years. Twenty ACAs were detected in the overall population (8.9% of the subjects): 10 in patients with meningioma (18%) and the remaining 10 (6%) in the control group (p = 0.007). Multivariate analysis showed that age and presence of meningioma were statistically associated with the presence of ACAs (p = 0.01, p = 0.008). CONCLUSION: We report, for the first time, a higher prevalence of ACAs in patients with meningioma as compared to age- and sex-matched controls. Larger studies are needed to confirm our data and to clarify the characteristics of the ACAs in patients with meningioma. Whether the detection of ACAs should prompt a neuroimaging evaluation to exclude the presence of meningiomas needs also to be considered.

Incidence and severity of Coronavirus Disease 2019 (COVID-19) in children with primary and secondary adrenal insufficiency during the pandemic in Italy

Background: Adrenal insufficiency (AI) is a rare condition caused by an inadequate production of glucocorticoids. Preliminary data in adults suggest that AI could be associated with an increased susceptibility to infections;moreover, AI patients are at risk to develop a severe course of infectious diseases and to experience a life-threatening adrenal crisis. The aim of our study is to evaluate the severity and the outcome of COVID-19 in pediatric AI patients in comparison to subjects affected with other endocrinopathies not involving adrenal gland. Patients and Methods: This was a retrospective, multicenter study involving 11 Italian tertiary-centers of pediatric endocrinology. Data regarding symptoms, severity and duration of the disease, the need to increase the dose or receive parenteral administration of hydrocortisone and the outcome were collected through a telephone interview and review of patient's medical files. From March 2020 to October 2021, 80 children with a history of COVID-19 were collected: 49 subjects affected by AI (42 primary AI, 7 central AI) and 31 subjects as controls. Result(s): Mean age was comparable between patients and controls (11.4+/-4.4 years vs 10+/-3.5 years, respectively). The frequency of signs/symptoms during COVID-19 in AI patients was as follows: fever 68%, rhinorrhea 34%, headache 34%, sore-throat 30%, cough 28%, anosmia/ageusia 21%. Less common symptoms were characterized by arthralgia, abdominal pain, diarrhea and vomiting. The severity of infection was comparable between patients and controls: paucisymptomatic 40.8% vs 25.8%;mild 55.1% vs 61.3%;severe 4.1% vs 12.9%, respectively (Chi-square=0.19). Time between the first positive nasopharyngeal swab and the first negative one in patients vs controls was: <=15 days, 39% vs 56.6%;>15 days, 61% vs 43.3%, showing a tendency to longer infection in AI children, although this difference did not reach statistical significance (Chi-square=0.14). In 64% of AI patients the dose of hydrocortisone was increased during the infection and in 6.4% parenteral hydrocortisone was needed. 94% of AI subjects did not require hospitalization while only 6% were hospitalized with a complete recovery in 100% of cases. Within the entire cohort of AI subjects, 2 children (4%) experienced an adrenal crisis during infection. No fatal events occurred. Conclusion(s): Our data, suggest that children with AI adequately treated are not at increased risk of severe course of COVID-19. In comparison to controls, subjects with AI have a slightly longer duration of the disease, although this data need to be confirmed on larger sample of patients.

A rare case of intravascular diffuse large B-cell lymphoma with secondary hemophagocytic lymphohistiocytosis

Introduction Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and potential life-threatening syndrome characterized by excessive immune activation and cytokine release. In adults, infections, inflammatory diseases and more rarely hematological malignancies can trigger the onset of HLH. We describe a rare case of intravascular diffuse large B cell lymphoma (DLBCL) associated with HLH. Case presentation A 53-year-old woman, presenting with high fever since 3 weeks and asthenia, was admitted to the hospital. She had a negative medical and travel history. On physical examination, generalized edema and hypotension were noted. An extensive bacterial and viral work-up (including COVID-19) was negative. During admission, the patient developed progressive anasarca and an episode of epileptic convulsions. Laboratory results showed increasing cytopenia, major hyperferritinemia, hypofibrinogenemia and hypertriglyceridemia. A bone marrow examination showed prominent hemophagocytosis. Cerebrospinal fluid examination showed the presence of aberrant monocytes, indicating CNS involvement. Genetic analysis to detect hemophagocytosis-associated mutations was negative. PET-CT revealed increased FDG uptake in both adrenal glands, hypophysis, bone marrow and spleen. Biopsy of the adrenal gland was not contributive. Brain MRI showed two cerebral masses radiologically suggestive for meningioma, confirmed by histology. The patient was refractory to high-dose corticotherapy and treatment was adapted to the HLH-94 protocol. A blind skin biopsy showed the presence of a population of pathological B-lymphocytes with aberrant immunophenotype (CD20+/Pax5+/Bcl6+/Bcl2+/cMYC-) in and around the small blood vessels leading to the diagnosis of intravascular DLBCL. Treatment was adjusted to lymphoma-specific immune-chemotherapy upon which a gradual clinical improvement was noted. After four cycles R-CHOP, three cycles of high dose methotrexate and high dose Endoxan for stem cell mobilisation, treatment was intensified with two cycles R-DHAP because of laboratory signs of persistent hemophagocytosis. Thereafter, the patient received an autologous stem cell transplantation (auto-HCT) after BEAM chemotherapy. End of treatment PET-CT and skin biopsy documented complete remission of the lymphoma. Because of slow hematological recovery, repeated bone marrow examinations were done and showed hypoplasia and persistent hemophagocytosis. Dexamethasone in combination with eltrombopag led to a gradual hematological response. At 20 months after auto-HCT, the patients stay in complete remission of the DLBCL and are independent of corticotherapy, with acceptable hematological parameters and no clinical signs of HLH. Discussion In the absence of infection, HLH is a diagnostic challenge frequently leading to delayed identification of the primary trigger, if any. A characteristic image on PET-CT with increased uptake in adrenal glands and hypophysisis led us to perform a blind skin biopsy to diagnose intravascular DLBCL, a rare subtype of lymphoma. Our case also shows that 1) HLH is very difficult to manage without dealing with the primary trigger and 2) HLH can persist for prolonged periods of time after successful treatment of the primary cause and may require specific therapy for sufficient control.

ENDOCRINE DISORDERS IN THE BACKGROUND OF COVID-19 AND POSTCOVID SYNDROME

The SARS-CoV-2 virus that caused the 2019 new coronavirus infection (COVID-19) pandemic has posed an unprecedented challenge to the global health system and scientific community. As of this literature review, the infection has claimed more than 6 million lives, and more than 500 million people worldwide have already been infected with SARS-CoV-2. In addition to the basic, pulmonary manifestations of the disease, as well as the severe, life-threatening complications of acute COVID-19, the long-term changes that occur in the postcovid period also affect other systems: endocrine, cardiovascular, nervous, and musculoskeletal. In this literature review, using data from current scientific publications obtained by searching <<covid-19 endocrine disorders>>, <<postcovid endocrine disorders>> and <<postcovid syndrome endocrine disorders>> in the MEDLINE (PubMed) database and <<endocrine pathology and covid-19>>, <<postcovid and endocrine pathology>> and <<postcovid syndrome and endocrine disorders>> in the e-Library database, we focused on describing and discussing the complications and consequences that SARS-CoV-2 infection can have on the endocrine glands, including the adrenals, thyroid, pituitary, gonads and pancreas. Copyright © 2022 Russian Association of Endocrinologists. All rights reserved.

Anaesthetic management of adrenal tumours presenting with combination of rare syndromes during a pandemic: Experience from a tertiary cancer care centre in Northeast India

Background and Aims: Perioperative management of functional adrenal tumours is resource intensive. Due to the covid 19 pandemic, there has been sizeable delay in preparing and conducting these time sensitive surgeries.Quality of care andresource utilisation may worsen. This retrospective review was aimed at finding if care quality deteriorated due to covid 19 related restrictions, from anaesthetic perspective. Methods:Three cases of hormone-secreting adrenal tumours operated during a two year period in a tertiary cancer centre in India were retrospectively reviewed.Summary of the demographic profile, tumour characteristics, and the perioperative care were described using tables and analysed in the discussion. Results: Out of the three cases operated for adrenal gland tumour, pheochromocytoma tumour type with distant metastasis had prolonged hospital stay. One patient developed covid 19 infection in hospital. Cases were adequately managed during the perioperative period and the covid 19 related constraints didn't affect the quality of care. Conclusion:As in any other major surgery, adhering to a unique checklist, multidisciplinary approach, clear communication, knowledge sharing and establishing a care pathway helps to maintainquality care in high risk cases and at times of crisis.

Adrenal Insufficiency: A Unique Presentation of Multicentric Castleman Disease with Human Herpes Virus 8 Positivity and Concomitant Kaposi Sarcoma

Introduction: Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder involving multiple lymph nodes and can be associated with human herpes 8 virus (HHV-8). Hyaline vascular (HV) MCD is rare, occurring in < 10% of cases. MCD with concomitant HIV negative Kaposi Sarcoma (KS) is also uncommon and can peculiarly present with adrenal insufficiency. Case Description: 53-year-old male with biopsy proven diagnosis of HHV-8 positive KS was transferred to our institution with persistent hypotension requiring pressor support. He described a two-week history of night sweats, 20 Ib weight & appetite loss, fatigue, muscles aches, and subjective fevers. Vitals: BP: 99/50 mmHg, HR: 90 bpm, RR: 19 and T: 103oF. Physical exam revealed multiple violaceous, non-blanching plaques on his body, tender inguinal & axillary lymphadenopathy, and bilateral lower extremity edema. Initial labs: Na: 137 mmol/L, K: 3.6 mmol/L, WBC: 5.6 k/uL, Hg: 7.1 gm/dL, Hct: 21%, Plt: 91 k/uL, AM cortisol: 12.5 mcg/dL (5.3-22.5), ACTH < 1 pg/mL, TSH: 7.5 uIU/mL, FTF: 0.63 ng/dL, PRL: 7 ng/mL, Total testosterone: 20 ng/dL, FSH: 4.2 mIU/mL, LH: 8.3 mIU/mL, IGF-1: 77 ng/mL (64-218), ESR >85 mm/hr (< 20), and CRP: 76 mg/dL (< 3). HIV and COVID-19 tests were negative. He was started on oral Levothyroxine and IV Hydrocortisone with significant improvement in his BP leading to discontinuation of pressor support. CT chest/abdomen/pelvis showed diffuse lymphadenopathy consistent with KS with normal adrenal glands. Left axillary lymph node biopsy revealed HV MCD. Additional labs;IL-6: 11.5 pg/mL (< 2), IgG4: 45 mg/dL (1-123), normal CD4 count, renin and aldosterone levels. 21 alpha hydroxylase antibody, T-spot, extensive autoimmune and infectious work-up were negative. Pituitary MRI could not be obtained due to a metal object behind his right orbit. Head CT was negative for pituitary abnormality. He failed his ACTH stimulation test with cortisol level: 13 mcg/dL at 90 minutes (baseline ACTH was not obtained). Thus, he was discharged on physiological oral Hydrocortisone upon clinical improvement. He began chemotherapy 1 week post discharge, however he succumbed to his disseminated and aggressive disease 20 days later. Discussion: MCD with concomitant KS is a rare and rapidly progressive disease which can cause death within weeks. IL-6 overproduction is thought to be associated with its symptom progression. Worse clinical outcomes are correlated with HIV or HHV-8 positivity. It can uncommonly be associated with either primary or secondary adrenal insufficiency requiring prompt evaluation and treatment with systemic steroids to prevent development of adrenal crisis.

Inherited/Genetically-Associated Pheochromocytoma/ Paraganglioma Syndromes and COVID-19.

In some subjects with inherited pheochromocytoma/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1α) stabilization/activation could lead to an increase in angiotensin converting enzymes (ACE). This would result in the stimulation of angiotensin (AT) II production and, hence, reduce the availability of ACE 2. The latter would provide decreased numbers of binding sites for the spike protein of SARS-CoV-2 and, therefore, result in less points of viral entry into cells. Thus, subjects with HIF1α-associated PPG syndromes may benefit from an inherent protective effect against COVID-19. Such an implication of HIF1α vis-à-vis COVID-19 could open ways of therapeutic interventions.

COVID-19 and the Endocrine System: A Comprehensive Review on the Theme.

BACKGROUND AND AIM: The review aimed to summarize advances in the topic of endocrine diseases and coronavirus disease 2019 (COVID-19). METHODS: Scientific and institutional websites and databases were searched and data were collected and organized, when plausible, to angle the discussion toward the following clinical issues. (1) Are patients with COVID-19 at higher risk of developing acute or late-onset endocrine diseases or dysfunction? (2) May the underlying endocrine diseases or dysfunctions be considered risk factors for poor prognosis once the infection has occurred? (3) Are there defined strategies to manage endocrine diseases despite pandemic-related constraints? Herein, the authors considered only relevant and more frequently observed endocrine diseases and disorders related to the hypothalamic-pituitary region, thyroid and parathyroid glands, calcium-phosphorus homeostasis and osteoporosis, adrenal glands, and gonads. Main. Data highlight the basis of some pathophysiological mechanisms and anatomical alterations of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-induced endocrine dysfunctions. Some conditions, such as adrenal insufficiency and cortisol excess, may be risk factors of worse clinical progression once the infection has occurred. These at-risk populations may require adequate education to avoid the SARS-CoV-2 infection and adequately manage medical therapy during the pandemic, even in emergencies. Endocrine disease management underwent a palpable restraint, especially procedures requiring obligate access to healthcare facilities for diagnostic and therapeutic purposes. Strategies of clinical triage to prioritize medical consultations, laboratory, instrumental evaluations, and digital telehealth solutions should be implemented to better deal with this probably long-term situation.

Relationship between betacoronaviruses and the endocrine system: a new key to understand the COVID-19 pandemic-A comprehensive review.

BACKGROUND: A new harmful respiratory disease, called COVID-19 emerged in China in December 2019 due to the infection of a novel coronavirus, called SARS-Coronavirus 2 (SARS-CoV-2), which belongs to the betacoronavirus genus, including SARS-CoV-1 and MERS-CoV. SARS-CoV-2 shares almost 80% of the genome with SARS-CoV-1 and 50% with MERS-CoV. Moreover, SARS-CoV-2 proteins share a high degree of homology (approximately 95%) with SARS-CoV-1 proteins. Hence, the mechanisms of SARS-Cov-1 and SARS-Cov-2 infection are similar and occur via binding to ACE2 protein, which is widely distributed in the human body, with a predominant expression in endocrine tissues including testis, thyroid, adrenal and pituitary. PURPOSE: On the basis of expression pattern of the ACE2 protein among different tissues, similarity between SARS-Cov-1 and SARS-Cov-2 and the pathophysiology of COVID-19 disease, we aimed at discussing, after almost one-year pandemic, about the relationships between COVID-19 infection and the endocrine system. First, we discussed the potential effect of hormones on the susceptibility to COVID-19 infection; second, we examined the evidences regarding the effect of COVID-19 on the endocrine system. When data were available, a comparative discussion between SARS and COVID-19 effects was also performed. METHODS: A comprehensive literature search within Pubmed was performed. This review has been conducted according to the PRISMA statements. RESULTS: Among 450, 100 articles were selected. Tissue and vascular damages have been shown on thyroid, adrenal, testis and pituitary glands, with multiple alterations of endocrine function. CONCLUSION: Hormones may affect patient susceptibility to COVID-19 infection but evidences regarding therapeutic implication of these findings are still missing. SARS and COVID-19 may affect endocrine glands and their dense vascularization, impairing endocrine system function. A possible damage of endocrine system in COVID-19 patients should be investigated in both COVID-19 acute phase and recovery to identify both early and late endocrine complications that may be important for patient's prognosis and well-being after COVID-19 infection.

SARS-CoV-2 Causes a Systemically Multiple Organs Damages and Dissemination in Hamsters.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread across the world and impacted global healthcare systems. For clinical patients, COVID-19 not only induces pulmonary lesions but also affects extrapulmonary organs. An ideal animal model that mimics COVID-19 in humans in terms of the induced systematic lesions is urgently needed. Here, we report that Syrian hamster is highly permissive to SARS-CoV-2 and exhibit diffuse alveolar damage and induced extrapulmonary multi-organs damage, including spleen, lymph nodes, different segments of alimentary tract, kidney, adrenal gland, ovary, vesicular gland and prostate damage, at 3-7 days post inoculation (dpi), based on qRT-PCR, in situ hybridization and immunohistochemistry detection. Notably, the adrenal gland is a novel target organ, with abundant viral RNA and antigen expression detected, accompanied by focal to diffuse inflammation. Additionally, viral RNA was also detected in the corpus luteum of the ovary, vesicular gland and prostate. Focal lesions in liver, gallbladder, myocardium, and lymph nodes were still present at 18 dpi, suggesting potential damage after disease. Our findings illustrate systemic histological observations and the viral RNA and antigen distribution in infected hamsters during disease and convalescence to recapitulate those observed in humans with COVID-19, providing helpful data to the pathophysiologic characterization of SARS-CoV-2-induced systemic disease and the development of effective treatment strategies.