Changes in the epidemiological profile of pituitary stalk thickening among pediatric population in Chile during COVID-19 pandemic (preprint)

Purpose Pituitary stalk thickening (PST) is a rare disease affecting mainly adults. Pediatric cases are infrequent. The aim of this study is to evaluate the frequency of pediatric patients with PST during the pandemic outbreak of COVID-19 in Chile and compare it with previous data. Methods A retrospective chart review was conducted in patients with PST diagnosed during COVID-19 outbreak. Patients <18 years with pituitary stalk width of 3mm or more at pituitary insertion and/or 4mm or more at optic chiasm were included. In order to characterize and compare these cases with those already published, a review of the literature was performed. Results Nine patients were diagnosed with PST. Seven were girls. Mean age at the onset of symptoms was 10.36 years (2.4-17). Germinal cell tumors (GCT) were diagnosed in 8 patients and Langerhans cell histiocytosis in one. All patients had negative tumor markers, arginine-vasopressin deficiency (AVD) and at least one anterior pituitary hormonal deficit at diagnosis. Diagnoses were confirmed histologically in all patients, and four required a second biopsy. We found a frequency of 4 patients per year with PST due to GCT which is twice the one expected in the same population in Chile. Conclusion A surprisingly high frequency of PST presented during the COVID-19 pandemic among Chilean pediatric patients, being GCT the most frequent etiology. The reasons behind this increase in reported cases are still to be elucidated.

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.

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.

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.

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.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of diabetes insipidus and hyponatraemia.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.