Central diabetes insipidus: a late sequela of BNT162b2 SARS-CoV-2 mRNA vaccine?

BACKGROUND: The development of an effective vaccine is a powerful tool to contain the global spread of coronavirus disease 2019 (COVID-19). Still, it raises potential safety concerns about the subsequent enhancement of associated immunopathology. Increasing evidence shows that the endocrine system, including the hypophysis, may be involved in COVID-19. Moreover, occasional but increasing reports of endocrine disorders involving the thyroid have been reported after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Among them, a few cases encompass the pituitary. Here we report a rare case of central diabetes insipidus following SARS-CoV-2 vaccination. CASE PRESENTATION: We report a 59-year-old female patient with a 25-year history of Crohn's disease in long-term remission, who presented with sudden onset of polyuria eight weeks after administration of an mRNA SARS-CoV-2 vaccination. Laboratory evaluation was consistent with isolated central diabetes insipidus. Magnetic resonance imaging displayed involvement of the infundibulum and the posterior hypophysis. Eighteen months after the vaccination, she is still under desmopressin treatment and had stable pituitary stalk thickening on magnetic resonance imaging. Although Crohn's disease-associated hypophysitis has been reported, it is scarce. In the absence of other recognizable causes of hypophysitis, we believe the involvement of the hypophysis in our patient may have been triggered by the SARS-CoV-2 vaccine. CONCLUSIONS: We report a rare case of central diabetes insipidus potentially associated with SARS-CoV-2 mRNA vaccination. Further studies are needed to understand better the mechanisms underlying autoimmune endocrinopathies development in the context of COVID-19 infection and SARS-CoV-2 vaccination.

New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection.

OBJECTIVE: Since January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients. METHODS: To review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury. RESULTS: In our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs. CONCLUSION: For clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs.

Severe hypercalcemia in a patient with chronic lymphocytic leukemia and non-small cell lung carcinoma: A case report.

RATIONALE: Hypercalcemia is a common finding in patients with advanced-stage cancers. Paraneoplastic hypercalcemia is commonly associated with dismal prognoses, with survival rates of about 3 months. In this paper, we report on a patient with advanced chronic lymphocytic leukemia and non-small cell lung carcinoma who developed severe hypercalcemia and discuss the diagnosis and treatment of this metabolic complication. PATIENT CONCERNS: A 56-year old male with a 2-year history of Rai stage IV chronic lymphocytic leukemia presented with life-threatening hypercalcemia. Positron emission tomography/computed tomography revealed a suspicious lung lesion. A transbronchial biopsy was performed from the upper left lobe. Due to the small size of the specimen, immunohistochemical markers were performed and revealed positive staining for cytokeratin 7 and negative for TTF-1, napsin A and p 40, which were consistent with non-small cell lung carcinoma. DIAGNOSIS: Humoral hypercalcemia of malignancy was diagnosed. INTERVENTION: The patient was treated with saline infusion, calcitonin, intravenous pamidronate, followed with denosumab. OUTCOMES: The hypercalcemia was successfully treated and the patient's calcium levels returned to normal. Further evaluation revealed a non-small cell lung carcinoma as a second primary malignancy. The patient was treated with venetoclax for his refractory CLL and received chemotherapy and immunotherapy for lung adenocarcinoma. Several days after starting venetoclax, he developed Legionella pneumonia and short time after the second course of chemotherapy, a severe sepsis occurred and he passed away. LESSONS: Coexistence of 2 unrelated malignancies, whichever could be a reason for hypercalcemia of malignancy is a rare event. Severe hypercalcemia, which is possible but rare feature of CLL should be a reason for further prompt evaluation.

Effects of Recommendations for Diabetes Management at Hospital Discharge on Long-Term Diabetes Control.

OBJECTIVE: To determine the impact of diabetes-specific recommendations at 1 year after hospital discharge on glycemic control and diabetes care in an outpatient setting. METHODS: A total of 139 patients with type 2 diabetes on a basal-bolus insulin regimen during hospitalization were included in the statistical analysis. We gathered data on treatment regimens after 12 to 16, 26 to 30, and 52 to 56 weeks following discharge as well as glycosylated hemoglobin (HbA1c) levels for all patients. Prescriptions for diabetes therapy were retrieved. All changes in insulin or oral/noninsulin injectable drug regimens were recorded. RESULTS: Half of the patients (n = 69) were discharged on their preadmission regimen (no change), and a change in the home treatment was recommended in the other half (n = 70). In the group of patients whose preadmission therapy was adjusted, HbA1c decreased from 9.6% (80 mmol/mol) to 8.5% (69 mmol/mol) (P = .0004) 1 year after discharge. In the group of patients discharged on their preadmission regimen, no significant changes in HbA1c levels during the study were observed. At follow-ups occurring 12 to 16 weeks after discharge, 52% (95% CI: 37.4%-66.3%) of patients in the change group had their treatment modified, compared with 18.6% (95% CI: 9.7%-30.9%) in the no-change group. In the group of patients discharged on their preadmission regimen, no significant change was observed. At the beginning of the study, patients in the change treatment group had higher HbA1c levels than patients in the no-change group (9.6 ± 2.0 vs 8.6 ± 1.7, P < .001). At the end of the study, no significant changes in terms of HbA1c levels were found between the groups (8.8 ± 1.9 vs 8.5 ± 1.9, P = .2). CONCLUSIONS: Significant improvement in diabetes control occurred 1 year after hospital discharge in patients who underwent modifications in their treatment. This supports the relevance of providing and implementing proper care recommendations at transition.

[Historical aspects and new formulations of levothyroxine sodium for hypothyroidism treatment].

At the end of the 19th century symptoms and signs of hypothyroidism were described in the medical literature. At that time myxedema was a main clinical presentation of the hypothyroid patient. Today, the diagnosis of hypothyroidism is determined mainly by laboratory evaluation with most patients exhibiting only a few clinical signs of thyroid dysfunction. The treatment of hypothyroidism has progressed from partially purified extracts of bovine thyroid gland to an oral administration of synthetic hormone. Since 1981 the only thyroid hormone replacement drug approved by the Israeli Ministry of Health was the Eltroxin brand, made by GlaxoSmithKline. Levothyroxine has a narrow therapeutic range, thus a potential variance exists in the therapeutic efficacy among different levothyroxine preparations. In 2007 the Food and Drugs Administration (FDA) announced that the difference in potency of various levothyroxine brands should not exceed ten percent. In 2007 the GSK Company moved the manufacturing of Eltroxin from Canada to Germany. This resulted in a change of the inert ingredients of the drug. It is of interest to know that since the arrival of the new thyroxine formulation in the Israeli pharmaceutical market there has been a dramatic increase in reports of adverse reactions. The media coverage of adverse effects associated with Eltroxin became widespread in television, newspapers and internet sites. This led to a burden on the healthcare system, manifesting itself by an increase in thyroid blood tests, physician follow-up visits, as well as the importing and distribution of a new brand of thyroxine.