LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH MULTISYSTEMIC LESIONS ASSOCIATED WITH INFECTED POLIOMYELITIS AND SARS-COV-2, FEATURES OF DIAGNOSTICS. CLINICAL CASE.

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.Copyright © 2023 Institute of Physics of the Russian Academy of Sciences. All rights reserved.

AVP deficiency (central diabetes insipidus) following immunization with anti-COVID-19 BNT162b2 Comirnaty vaccine in adolescents: A case report.

Introduction: The coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case presentation: A 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. Conclusion: Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.

New developments and concepts in the diagnosis and management of diabetes insipidus (AVP-deficiency and resistance).

Diabetes insipidus (DI) is a disorder characterised by the excretion of large amounts of hypotonic urine, with a prevalence of 1 per 25,000 population. Central DI (CDI), better now referred to as arginine vasopressin (AVP)-deficiency, is the most common form of DI resulting from deficiency of the hormone AVP from the pituitary. The less common nephrogenic DI (NDI) or AVP-resistance develops secondary to AVP resistance in the kidneys. The majority of causes of DI are acquired, with CDI developing when more than 80% of AVP-secreting neurons are damaged. Inherited/familial CDI causes account for approximately 1% of cases. Although the pathogenesis of NDI is unclear, more than 280 disease-causing mutations affecting the AVP2 protein or AVP V2 receptor, as well as in aquaporin 2 (AQP2), have been described. Although the cAMP/protein kinase A pathway remains the major regulatory pathway of AVP/AQP2 action, in vitro data have also revealed additional cAMP independent pathways of NDI pathogenesis. Diagnosing partial forms of DI, and distinguishing them from primary polydipsia, can be challenging, previously necessitating the use of the water deprivation test. However, measurements of circulating copeptin levels, especially after stimulation, are increasingly replacing the classical tests in clinical practice because of their ease of use and high sensitivity and specificity. The treatment of CDI relies on desmopressin administration, whereas NDI requires the management of any underlying diseases, removal of offending drugs and, in some cases, administration of diuretics. A better understanding of the pathophysiology of DI has led to novel evolving therapeutic agents that are under clinical trial.

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.

Central diabetes insipidus following immunization with anti-COVID19 BNT162b2 Comirnaty vaccine

Introduction: The coronavirus disease 19 (COVID19) pandemic urged to develop new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case Presentation: A 16-year-old boy presented to the Paediatric Emergency Department with polyuria (9 liters per day), polydipsia and concomitant weight loss (- 6 Kg) over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after second dose of anti- COVID19 BNT162b2 Comirnaty vaccine. The patient was admitted to the Paediatric Department. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits (height -0.12 SDS, weight +0.35 SDS). Daily fluid balance monitoring confirmed polyuria and polydipsia (IN 6,250 L / OUT 7,100 L). Biochemistry laboratory analysis and urine culture were normal (Sodium levels 141 mEq/L). Serum osmolality was 297 mOsm/Kg H2O (normal values 285-305), whereas urine osmolality was 80 mOsm/Kg H2O (normal values 100-1100), suggesting diabetes insipidus. Hormonal tests showed no significant impairment of anterior pituitary function. Test with Desmopressin was performed and confirmed the diagnosis of central diabetes insipidus. Brain MRI revealed pituitary stalk enlargement (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Even in absence of pituitary enlargement, those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and detectable small posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. Conclusion(s): Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID19 vaccine and diabetes insipidus.

Project to improve paediatric post-neurosurgical fluid management and to reduce the risks associated with Diabetes Insipidus (DI), Syndrome of Inappropriate ADH (SIADH) and Cerebral Salt Wasting (CSW)

Background. Complex fluid balance problems are well established post-neurosurgery and traumatic brain injury (TBI). The triple-phase response requires fluid management strategies reactive to urine output as patients shift between DI and SIADH. Prevalence of CSW is controversial;but ensuring sodium homeostasis is central to safe fluid management. To improve clinical care for these complex patients an audit of existing institutional guidelines was undertaken. New guidelines were developed with structured educational packages for specialist teams involved, and subsequent assessment of their impact. Method(s): Two periods were audited using set standards (table-1), before and after the quality improvements. All data was collected from the CQUIN neurosurgical database and electronic medical records;included were all paediatric patients having neurosurgical operations for posterior fossa (PFT) and supratentorial tumours (STT), plus TBI. A literature review of evidence-based practice, initial audit data and stakeholder feedback was used to develop new clinical guidelines and nursing standard operating procedures. Principles were of strict monitoring and adaptive fluid management strategies, implemented for all with active step down. Structured educational packages were designed for specialty medical and nursing teams involved to improve knowledge, consistency of approach and team working. Result(s): Audit-1 January2017-June2018, n=80;Audit-2 January2020-June2021, n=30 (reduced neurosurgical operation numbers due to COVID-19 pandemic). All patients were managed within a high dependency setting;26-33% initially in paediatric intensive care. Step-down was to a neurosurgical/neurorehabilitation ward. Results comparison (table-1) demonstrated clinical, fluid balance and biochemical monitoring improvement. The number of clear fluid management plans documented post-operatively increased, leading to early recognition and management of evolving fluid-balance abnormalities. However, the recommended adaptive fluid management strategy was not always used. The endocrine team were involved earlier and in all complex cases. Significant Na fluctuations (>12mmol in 24 hours) remained similar (5vs6patients). These represented complex pituitary-hypothalamic pathology, plus one TBI. Feedback from patients and professional teams was of increased awareness, improved consistency of approach and communication. Conclusion(s): * Clinical guidelines revised using audited data, evidence-based literature review and stakeholder consultation have been adopted with effective change. * Patient safety improved through effective post-neurosurgical fluid management and multi-professional team working. * Regular feedback and continued education will identify areas for further improvement.

Infection with SARS-CoV-2 may alter the half-life of desmopressin (DDAVP) in children with central diabetes insipidus

Background: Central diabetes insipidus (CDI) is characterised by a central deficiency of arginine vasopressin (AVP) with polyuria and polydipsia. The etiology is heterogeneous. The treatment of choice is the oral or nasal application of DDAVP (synthetic analogue of AVP). CDI in the context of coronavirus disease 2019 (COVID19) has been reported in an individual case. Case Report: We present a 9-year old male with CDI of uncertain etiology. The reason for presentation was polydipsia (5 liters/ day) and polyuria/ nocturia. MRI showed a nodular thickening of the pituitary stalk and lack of T1w hyperintensity of the neurohypophysis. As expected, the level of CT-proAVP (copeptin) in serum was very low (< 2.7 pmol/litre) despite increased osmolality in serum of 306 mosm/kg. Sodium in serum was high with a maximum of 151 mmol/l. Laboratory analysis showed no involvement of other pituitary axis. Therapy was initiated with DDAVP at 1.2 mug in the morning and 0.6 mug in the evening (nasally). Treatment showed normalisation of polyuria, polydipsia, serum sodium levels and drinking quantity (2 liters/ day). The most recent dose was 6 mug in the morning and 1.8 mug in the evening. One year later the patient complained of sore throat. The pain was gone the following morning. A PCR test was positive for SARS-CoV-2. Surprisingly, with the onset of the sore throat, the half-life of the usual dosage of DDAVP therapy was significantly prolonged. Thus, the boy received the usual 1.8 mug of desmopressin in the evening (day of onset of symptoms). The effect lasted for 17 hours. Thus, the duration of action was prolonged by approximately 6 hours. The morning dose was skipped. The evening dose of 1.8 mug was then administered again at 1 p.m. at noon. This lasted for 18 hours. Thus, the duration of action was prolonged again by approximately 5 hours. After three days, the regular dosage and timing could be reintroduced. Furthermore, there was no adjustment of the dosage and no change of the manufacturer, pharmacy, application or storage of the preparation in the temporal context. Conclusion(s): In the context of a clinically mild infection with SARS-CoV-2, the half-life of DDAVP was significantly prolonged with the onset of clinical symptoms. Our case report is of clinical relevance, as even mild COVID19 may lead to a change in DDAVP pharmacokinetics. This knowledge may reduce the risk of dilutional hyponatremia.

Pituitary metastasis as the first manifestation of lung carcinoma.

Pituitary metastases are rare. Clinical presentation could range from asymptomatic to panhypopituitarism or local symptoms. We present a case report of a 43-year-old male patient with a new onset headache, visual disturbances, and panhypopituitarism. The investigation led to the diagnosis of pituitary metastasis as the first manifestation of underlying lung cancer.

Transient diabetes insipidus in critically ill COVID19 patients.

PURPOSE: Vasopressin has become an important vasopressor drug while treating a critically ill patient to maintain adequate mean arterial pressure. Diabetes insipidus (DI) is a rare syndrome characterized by the excretion of a large volume of diluted urine, inappropriate for water homeostasis. We noticed that several COVID19 patients developed excessive polyuria suggestive of DI, with a concomitant plasma sodium-level increase and/or low urine osmolality. We noticed a temporal relationship between vasopressin treatment cessation and polyuria periods. We reviewed those cases to better describe this phenomenon. METHODS: We retrospectively collected COVID19 ECMO patients' (from July 6, 2020, to November 30, 2021) data from the electronic medical records. By examining urine output, urine osmolality (if applicable), plasma sodium level, and plasma osmolality, we set DI diagnosis. We described the clinical course of DI episodes and compared baseline characteristics between patients who developed DI and those who did not. RESULTS: Out of 37 patients, 12 had 18 episodes of DI. These patients were 7 years younger and had lower severity scores (APACHE-II and SOFA). Mortality difference was not seen between groups. 17 episodes occurred after vasopressin discontinuation; 14 episodes were treated with vasopressin reinstitution. DI lasted for a median of 21 h, with a median increase of 14 mEq/L of sodium. CONCLUSIONS: Temporary DI prevalence after vasopressin discontinuation in COVID19 ECMO patients might be higher than previously described for vasopressin-treated patients.

Delay in desmopressin therapy: Disaster in waiting.

WHAT IS KNOWN AND OBJECTIVE: Central diabetes insipidus (DI) is a complex disease that requires firm adherence to desmopressin therapy. There is little information on the onset of hypernatremia after withdrawal of desmopressin. CASE SUMMARY: We present a case of an elderly woman with central DI whose serum sodium jumped from 141 to 171 mEq/L after 48-72 h of holding oral desmopressin. Her DI crisis resolved with intravenous desmopressin and free water administration. WHAT IS NEW AND CONCLUSION: Based on this precipitous onset of DI crisis, we recommend not withholding desmopressin for more than 24 h.

Partial Nephrogenic Diabetes Insipidus Secondary to Lithium Use

Introduction: Nephrogenic diabetes insipidus (NDI) is caused by reduced renal response to vasopressin. NDI affects up to 40% of patients on lithium. We present a case of partial NDI secondary to lithium use. Case Description: A 66 year old male with bipolar disorder on lithium presented with shortness of breath, chest tightness and cough. On exam he was cachectic, lethargic, tremulous with decreased skin turgor and dry mucous membranes found to have COVID-19 with initial unremarkable blood work. Received treatment for COVID and subsequently developed worsening encephalopathy, follow up blood work revealed elevated serum sodium of 168 mg/dl, with urine osmolality of 382 and lithium level was elevated at 1.6 mEq/L. He received adequate IV fluid hydration with hypotonic fluids and free water. Serum sodium remained elevated with polyuria. Follow up labs showed urine osmolality decrease to 94 mosml/L therefore nephrogenic diabetes insipidus was suspected. A desmopressin stimulation test was performed and hourly urine osmolality was obtained [Table 1] confirming the diagnosis of nephrogenic diabetes insipidus with a partial response to desmopressin compatible with lithium-induced partial diabetes insipidus. Treatment was started initially with chlorthalidone with inappropriate response, then dose increased to 100mg daily with further addition of amiloride 10mg twice daily with subsequent response and decrease of sodium level from 167 to 147 mEq/L. Discussion(s): Lithium-induced NDI is explained by downregulation of aquaporin 2 channel expression in the principal cells due to accumulation of toxic concentrations of lithium and reduction of the kidneys' ability to preserve water in response to vasopressin. NDI usually presents with polyuria, polydipsia, severe dehydration, and electrolyte imbalance. A less than 50% increase in urine osmolality following desmopressin administration proves NDI. Treatment options include high doses of desmopressin, low sodium diet, thiazide diuretics, amiloride, and NSAIDs. (Table Presented).

Infection with SARS-CoV-2 may alter the half-life of desmopressin (DDAVP) in patients with central diabetes insipidus.

We present a 9-year-old boy with diabetes insipidus. The boy is treated with desmopressin (DDAVP) therapy. Under this therapy, the drinking quantity and the laboratory parameters were normal. No nocturia occurred any more. In the context of a clinically mild infection with SARS-CoV-2, the duration of action of DDAVP was significantly prolonged (approximately +50%). The original dosage was then reintroduced and was still sufficient until months later. A possible connection to the infection with SARS-CoV-2 can be suspected. Our case report should make physicians who care for patients with diabetes insipidus aware of such a possible prolongation of the effect of DDAVP. More frequent monitoring may be needed in such patients to assess the risk of symptomatic dilutional hyponatremia.

Socio-economic Barriers to Care and Medical Complexity Leading to a 5-year Diagnostic Delay of Untreated Chronic Diabetes Insipidus and Rapidly Progressive Puberty in a 10-year-old Venezuelan Immigrant

Introduction: Germ cell tumors, including germinomas, account for 10% of pediatric chronic Diabetes Insipidus (DI) cases. Delays in diagnosis of germinomas are generally longer than six months, however, no reported cases of suprasellar germinomas causing chronic DI and precocious puberty have been known to exceed a 5-year delay in both treatment of DI symptoms and a definitive diagnosis. Case Description: A 10-year-old Hispanic male presented with a 5-year history of polydipsia and polyuria. He underwent evaluation in Venezuela, where DI was reportedly 'ruled out';however, no head MRI was performed. After two years in the US struggling to acquire insurance, he presented to his pediatrician with worsening symptoms. A head MRI, ordered to evaluate dilute high-volume urine output, revealed a suprasellar mass. He was admitted for diagnostic evaluation and met the criteria for DI. Notably, he had an elevated Beta-Human Chorionic Gonadotropin (B-HCG) level. Biopsy confirmed the diagnosis of a Central Nervous System (CNS) germinoma. He was treated with DDAVP and proton therapy with subsequent remission of his tumor. Discussion: Throughout the patient's disease course, there were multiple delays in seeking and receiving care. These include a 5-year delay in seeking care despite worsening symptoms, a one-month delay in completing a 24-hour urine collection, a one-month delay in consulting pediatric nephrology, and another month delay before completing a retroperitoneal ultrasound. Multiple medical and socio-economic factors led to these delays. The patient did not present with symptoms more typical of CNS Germinomas like headaches, nausea, and vomiting. He had no visual disturbances despite mass effect on his optic chiasm. His increased stretched penis length and Tanner staging, which were identified later in his disease course, were contradicted by his pre-pubertal testicular volume and bone age. The patient is from a Spanishspeaking/Limited English Proficiency (SSLEP) household. While Spanish interpreters were present at each appointment, the language barrier proved to be a consistent issue. Initially, the child's mother indicated that the diagnosis of DI was 'ruled out' in Venezuela. In reality, the recommended imaging was never performed. Mychart messages left by his father further highlighted communication difficulties. Without access to an interpreter, he was forced to use broken English to relay his concerns. These frantic messages indicated misunderstandings regarding scheduling with various services and completing vital labs. Care only proceeded after significant physician intervention. Poverty in Venezuela, lack of insurance, and anxiety regarding COVID-19 also contributed to these delays. Conclusion: To our knowledge, this is the first case report of a pediatric patient presenting with a 5-year history of untreated polyuria and polydipsia due to undiagnosed DI with a B-HCG secreting CNS germinoma, without spinal metastasis. This study also illustrates the importance of supporting SSLEP families as they grapple with the complicated process of navigating our healthcare system. Sagittal T1 post gadolinium contrast image (A) and axial T2 FLAIR image (B) show an enigmatic, homogeneous, briskly enhancing mass in the suprasellar cistern (red arrow) with mass effect on the optic chiasm which is displaced upward and anteriorly (green arrow).

A Case of Hypophysitis Associated With SARS-CoV-2 Vaccination.

Background/Objective: Although SARS-CoV-2 vaccines have been developed with multiple novel technologies and rapidly disseminated worldwide, the full profile of adverse effects has not been known. Recently, there are sporadic but increasing reports of endocrinopathy in relation to SARS-CoV-2 vaccination. Here we report a rare case of hypophysitis with acute onset of diabetes insipidus, immediately after SARS-CoV-2 vaccination. Case Report: A 48-year-old female patient had been in her usual state of health until she received the first SARS-CoV-2 vaccine. Two days after vaccination, she started to have flu-like symptoms, including severe headache and myalgia as well as persistent headache, polydipsia, and polyuria. She was diagnosed with diabetes insipidus, and magnetic resonance imaging revealed thickening of the pituitary stalk. Three months after vaccination, her symptoms had somewhat improved, but she still had pituitary stalk thickening on magnetic resonance imaging. Discussion: Given the timing of the occurrence of diabetes insipidus, we believe that the patient's hypophysitis may be associated with SARS-CoV-2 vaccination. We also found 19 cases of endocrinopathy after SARS-CoV-2 vaccination by literature search. The reported endocrine organs were the thyroid, pituitary, and adrenals. Twelve cases of diabetes were also reported. Among 3 pituitary cases, diabetes insipidus was reported only in our case. Conclusion: We report a rare case of SARS-CoV-2 vaccine-triggered hypophysitis, which led to diabetes insipidus. SARS-CoV-2 vaccine-related endocrinopathy seems, indeed, possible. Endocrinopathy is associated with infrequent complications; however, it may be underestimated in the post-SARS-CoV-2-vaccinated population. Further studies are warranted to better understand SARS-CoV-2 vaccine-related endocrinopathy.

Central diabetes insipidus secondary to COVID-19 infection: a case report.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) mainly affects the lungs, but can involve several other organs. The diagnosis of acute and chronic sequelae is one of the challenges of COVID-19. The current literature proposes that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may involve the hypothalamic-pituitary axis. In this case report, we present a unique case of new-onset central diabetes insipidus secondary to the COVID-19 disease in a 54-year-old woman. CASE PRESENTATION: A 54-year-old woman presented with the history of excessive thirst, polyuria, and polydipsia, six weeks after being infected by COVID-19. Laboratory tests revealed low urine osmolarity and increased serum osmolarity, and the patient was diagnosed with central diabetes insipidus. After administration of nasal desmopressin, urinary osmolarity increased, and the patient's symptoms improved. However, to stabilize her condition, desmopressin treatment was required. CONCLUSIONS: We reported a unique case of diabetes insipidus in a COVID-19 patient. Central diabetes insipidus may be included in clinical manifestations of the COVID-19, in case of new-onset polyuria and polydipsia following COVID-19 disease. Nevertheless, a causal relationship has not been established between the symptoms of the patient and the SARS-CoV-2 infection.

A Fatal Case of Intraparenchymal Hemorrhage Masquerading as Central Diabetes Insipidus

This is 32-year-old women presented to us on postpartum day 10 with severe covid-19 pneumonia. Hercomplaints were dyspnea and headache which she described as, frontally located, 8/10 in intensity, non-radiating and not associated with any posture. She had no prior history of migraines. She was afebrile, tachycardiac and hypoxic on exam. Physical examination was unremarkable. Patient failed trial of non-invasive ventilation following which she was intubated. CT head on admission was unremarkable.For COVID 19 ARDS, she was started on dexamethasone, tocilizumab, paralysis was achieved withcisatracurium and prone protocol was followed for refractory hypoxia. Patient was placed on DVTprophylaxis with heparin. Her pneumonia and oxygenation improved. However, on hospital day 8, herlab results were suspicious of Diabetes insipidus (DI). Her serum sodium was 152mEq/L with serumosmolarity of 360 and polyuria (more than 2L of urine in one hour). A full neurological examinationcould not be obtained as she was paralyzed, however, pupils were equal in size and reactive to light. With high clinical suspicions of diabetes insipidus she received a one-time dose of 16mcg of DDAVP andMRI of pituitary gland was ordered to delineate etiology. Subsequent improvement in polyuria wasnoted. Despite DDAVP her serum sodium continued to worsen. We continued to monitor serumsodium levels every four hours. Her serum sodium levels remained labile with a precipitous drop notedfrom 174mEq/L to 152mEq/L. Review of Pituitary MRI revealed multiple intraparenchymal hemorrhageson bilateral frontal lobes along with trans tentorial and cerebellar tonsillar herniation. Subsequently, patient underwent a brain death exam and declared brain dead. We suspect the development of intracranial hemorrhage in our patient was secondary to covid-19. Onliterature review, an incidence of 0.2% in covid-19 patients with a mortality of 48% is reported. In ourpatient, inability to perform a full neurological exam due to paralysis limited early recognition andintervention. This case highlights the need for increased awareness in patients with features of central diabetesinsipidus and the urgency to obtain CT head immediately after a diagnosis has been established. Promptconsideration of neuroimaging should be made when features of central diabetes mellitus are noted with limited neurological exam.

Central Diabetes Insipidus Following Immunization With BNT162b2 mRNA COVID-19 Vaccine: A Case Report.

Introduction: Cases of central diabetes insipidus (CDI) have been reported after COVID-19 infection, with hypophysitis being the most likely cause. COVID-19 vaccines potential adverse effects may mimetize some of these complications. Case Report: Woman 37 years old, with rheumatoid arthritis under adalimumab (40 mg twice a month) since December 2018. She was in her usual state of health when she has received the second dose of BNT162b2 mRNA COVID-19 vaccine (June 2021). Seven days later, she started reporting intense thirst and polyuria and consulted her family physician. Blood Analysis: creatinine 0.7 mg/dL, glucose 95mg/dL, Na+ 141mEq/L, K+ 3.9 mEq/L, TSH 3.8 mcUI/L (0.38-5.33), FT4 0.9 ng/dL (0.6-1.1), cortisol 215.4 nmol/L (185-624), ACTH 21.9 pg/mL (6- 48), FSH 4.76 UI/L, LH5.62 UI/L, estradiol 323 pmol/L, IGF1 74.8 ng/mL (88-209), PRL 24.7mcg/L (3.3-26.7) osmolality 298.2 mOs/Kg (250- 325); Urine analysis: volume 10200 mL/24h, osmolality 75 mOs/Kg (300-900), density 1.002. On water restriction test: 0' - Serum osmolality 308.8mOsm/Kg vs. urine osmolality 61.0 mOsm/Kg; 60' - urine osmolality 102 mOsm/Kg; urine osmolality 1 h after desmopressine was 511mOsm/kg. MRI revealed no abnormal signs consistent with hypophysitis except for the loss of the posterior pituitary bright spot on T1 weighted imaging. Diagnosis of CDI was assumed, and started therapy with desmopressine. A report of potential adverse effect was addressed to national health authorities. Conclusion: In hypophysitis MRI often shows loss of posterior pituitary bright spot on T1 weighted imaging, pituitary enlargement or stalk thickening but those findings were not present in this patient. To the best of our knowledge, CDI has never been reported following administration of a COVID-19 vaccine.

Diabetes Insipidus in Severe COVID-19 Pneumonia

Coronavirus disease 2019 (COVID-19) usually presents as a respiratory infection, and may progress to multiple organ failure and eventually death. In COVID-19 patients, kidney dysfunctions reported proteinuria, elevated markers of blood urea nitrogen, plasma creatinine, uric acids, and D-dimer. We present here the case of a 49-year-old male who was admitted to the intensive care unit (ICU) with COVID-19 pneumonia and respiratory failure. Diabetes insipidus (DI) developed during intensive care follow-up without electrolyte imbalance or kidney failure. A contrast-enhanced brain and pituitary MRI was performed to identify the etiology of the central DI, but revealed no pathological findings. The drugs used to treat our patient had no polyuria side effects. No electrolyte imbalance was identified from a blood test of our patient, and there were no findings of other diseases in the differential diagnosis that could lead to nephrogenic DI. We present here a case of COVID-19 infection complicated by nephrogenic diabetes insipidus, given the lack of reports in literature indicating the occurrence of diabetes insipidus alongside COVID-19 infection.

A preterm infant with congenital disseminated herpes simplex virus following maternal COVID-19 infection

Case Report Disseminated Herpes Simplex Virus (HSV) is a feared neonatal infection typically presenting after the first week of life with sepsis-like features and encephalopathy. Congenitally acquired HSV infection represents a rare, serious variety of HSV in the neonatal period, providing a unique diagnostic challenge with significant morbidity and mortality. A female infant was delivered at 29.2 weeks gestational age via cesarean section in the setting of non-reassuring fetal heart tracings, maternal preeclampsia, gestational diabetes, and Sars- COV2 infection. Physical exam at 1 hour of life demonstrated erosive lesions of the knee, foot, and cheek. Dermatology was consulted and favored infectious source of lesions, so a sepsis evaluation including HSV, VZV, and CMV studies was performed and ampicillin, gentamicin, acyclovir, and amphotericin B were started. Given high concern for HSV vs. varicella, ophthalmology was consulted, finding bilateral, likely viral, retinitis. Laboratory evaluation revealed transaminitis, thrombocytosis, and CSF pleocytosis with elevated protein. HSV PCR was positive in blood, CSF, and cutaneous lesion, as well as HSV2 positive on surface culture, yielding the diagnosis of congenital disseminated HSV with meningoencephalitis. The remainder of infectious studies were negative. There was no known maternal HSV history, although placental pathology revealed positive immunohistochemical staining for HSV 1/2 in addition to Sars-COV2. Patient's serial CSF and blood HSV remained positive despite treatment with acyclovir. Serial HUS showed initially normal findings that progressively worsened to feature bihemispheric cystic encephalomalacia, periventricular leukomalacia with ex vacuo dilation of lateral and third ventricles. She developed central diabetes insipidus and was started on desmopressin. Ocular involvement subsequently included retinal necrosis and diffuse retinal hemorrhage. She developed severe myoclonic jerks in the absence of electrographic correlate on EEG. Levetiracetam and phenobarbital alleviated jerks, although she developed progressive hypotonia as neurologic status continued to deteriorate. Considering persistently positive HSV studies, foscarnet was added to acyclovir. However, at 3 weeks of life, she was intubated for apnea and respiratory failure, and given clinical trajectory and devastating prognosis, mother asked to compassionately withdraw support and allow natural death on day of life 25. This case of congenital, disseminated HSV is particularly unique in that it occurred in a premature infant of 29 weeks gestation and had significantly elevated copy numbers in the blood and CSF as well as skin lesions, indicating likely longstanding infection at the time of delivery. Additionally, it is unknown how concurrent placental viral infections with SARSCoV2 may have contributed to this patient's course, or if the recent maternal SARS-CoV2 infection may triggered HSV reactivation and subsequent congenital HSV.