Endocrinopathies in a Pediatric Patient Post-anatomical Hemispherectomy for Rasmussen's Encephalitis Treatment: A Case Report.

Hemispherectomy is a neurosurgical procedure that is frequently performed in pediatric patients diagnosed with Rasmussen's encephalitis. Postoperative complications include immediate complications such as hydrocephalus and hemorrhage and behavioral complications such as language impairments and contralateral weakness. However, there are limited studies or case reports that address the potential endocrinopathies associated with this and other pediatric epileptic surgeries. This case report describes the endocrinopathies following an anatomical hemispherectomy procedure. A four-year-old African-American female had a right anatomical hemispherectomy for the treatment of Rasmussen's encephalitis in 2020. The postoperative course was immediately complicated by central diabetes insipidus which was stabilized with desmopressin. The patient's labs in 2021 were consistent with central precocious puberty with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Additionally, the patient was found to have secondary adrenal insufficiency in which she failed a low-dose adrenocorticotropic hormone (ACTH) stimulation test. Oral hydrocortisone therapy was initiated for secondary adrenal insufficiency in addition to initiating leuprolide injections for central precocious puberty. Furthermore, at the age of seven years, the patient had her first menarche. This case report emphasizes the need for closer and long-term surveillance for endocrine issues in postepileptic surgical pediatric patients as well as a surveillance plan for the development of other potential endocrine abnormalities throughout the patient's life.

Antidiuretic hormone deficiency secondary to inactive hydrocephalus: a case report.

BACKGROUND: Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia. CASE PRESENTATION: Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 µmol/L), and serum uric acid (560 µmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst. CONCLUSIONS: Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus.

Persistent hypernatremia secondary to adipsic central diabetes insipidus in a patient with herpes-induced meningoencephalitis and COVID-19 infection: a case report.

Central diabetes insipidus (CDI) typically manifests as a polyuria-polydipsia syndrome, in which normonatremia is generally maintained through the polydipsia. A 53-year-old woman presented with diabetic ketosis and hyperosmolar hyperglycemic syndrome. Her medical history included herpes meningoencephalitis, which was associated with confusion and amnesia. On physical examination, she was apyretic, confused, and had signs of extracellular dehydration. Her capillary glucose concentration was high and her urine was positive for ketones. Laboratory investigations revealed severe hyperglycemia, hypernatremia (plasma hyperosmolarity of 393.6 mOsm/L), and mild acute renal failure. In addition, she had a paucisymptomatic COVID-19 infection. Intravenous rehydration with isotonic saline solution and insulin therapy were effective at controlling the ketosis and ameliorating the hyperglycemia, but failed to normalize the hypernatremia and hyperosmolarity. She was not thirsty and had a urine output of 1 L/day, with urinary hypotonicity. Desmopressin administration reduced the hypernatremia and hyperosmolarity to within their normal ranges, and the patient's urinary osmolarity increased to 743 mOsm/L. Therefore, adipsic CDI was diagnosed. Endocrine investigations revealed isolated central hypothyroidism. The results of pituitary magnetic resonance imaging were normal. Thus, patients with impaired thirst may have an atypical presentation of CDI. In addition, the diagnosis of adipsic CDI is particularly challenging.

Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus.

OBJECTIVES: The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS. CASE PRESENTATION: We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction. CONCLUSIONS: We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Correction of In-Patient Severe Hypernatremia in an 81-Year-Old Female With Hypopituitarism.

Hypernatremia has been significantly associated with in-hospital mortality and discharge to long-term care facilities. The appropriate correction of electrolyte disturbances, especially sodium, is important to consider to prevent the addition of central nervous system disturbances, such as cerebral edema and eventual brain injury. The importance of maintaining a proper correction of hypernatremia has been well studied and used in clinical practice. Choosing to use a hypotonic solution is a key principle. It is of utmost importance to adjust the rate of correction based on the patient's symptoms, underlying etiology, and associated comorbidities. This case demonstrates how a correction formula was used and adjusted accordingly in an 81-year-old female with severe hypernatremia and metabolic encephalopathy with multiple comorbidities, including hypopituitarism. It is noteworthy to examine the correction rate, how it was calculated and delivered, and how the main cause of the hypernatremia was determined. Considering all these factors can help to properly administer any additional corrective medications, such as desmopressin (DDAVP) in a patient with diabetes insipidus (DI) secondary to hypopituitarism, or adjust the correcting rate based on signs, symptoms, and laboratory findings.

Transient Central Diabetes Insipidus (Arginine Vasopressin Deficiency) Following SARS-CoV-2 Vaccination: A Case Report and Literature Review.

INTRODUCTION: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people, causing the COVID-19 global pandemic. The use of novel technologies led to the development of different types of SARS-CoV-2 vaccines that have reduced severe disease courses and related deaths. Besides the positive impact of vaccination on the pandemic, local and systemic side effects have been reported; they are usually mild to moderate, although also serious adverse events have been described. CASE PRESENTATION: A 21-year-old female was referred to our hospital for the recent onset of severe polyuria and polydipsia, with the need for about 8 liters of daily water intake. The symptoms developed seven days after the administration of the second dose of the mRNA-based (Pfizer-BioNTech® BNT162b2) SARS-CoV-2 vaccine. In the suspicion of central diabetes insipidus (DI) development, she started treatment with desmopressin (Minirin® tablets) 60 mg/day with an improvement of symptoms and thirst. A thickening of the pituitary stalk was observed at the pituitary MRI with loss of the posterior pituitary bright spot on T1 weighted images. To confirm the diagnosis of central DI, both the water deprivation test and arginine stimulated copeptin test were performed; whilst the former gave no clear-cut indication of DI, the latter showed a reduced copeptin peak after arginine infusion consistent with the diagnosis of partial central DI. Furthermore, the development of symptoms right after the second dose of the vaccine strengthened the hypothesis that DI was related to the vaccination itself. After our evaluation, there was a progressive reduction of desmopressin dose to a complete discontinuation with the maintenance of a normal hydroelectrolytic balance. Clinical and biochemical follow-up was performed by repeating a pituitary MRI and a second arginine-stimulated copeptin test 15 months after the diagnosis. This time, copeptin levels reached a significantly higher peak after arginine stimulation that completely excluded central DI and at pituitary MRI, the thickening of the pituitary stalk previously described was no longer visible. CONCLUSION: Neurohypophysitis can have an abrupt onset independently of the etiology. Central DI is a rather exceptional event after SARS-CoV-2 vaccination but should be recalled in case of sudden polyuria and polydipsia. DI is indeed reported even after SARS-CoV-2 infection, thus, this report should not discourage the use of mRNA-based vaccines. Furthermore, our case demonstrates that full recovery of posterior pituitary function is possible after immunization with anti-Covid-19 BNT162b2 vaccine. Further studies are needed to clarify the possible mechanism relating to SARS-CoV-2 vaccination and this rare adverse event.

Clinical Factors Affecting Daily Dosage of Desmopressin Orally Disintegrating Tablets in Arginine Vasopressin Deficiency.

CONTEXT: Desmopressin orally disintegrating tablets (ODTs) are widely used to treat arginine vasopressin deficiency (AVP-D). However, limited information is available on the dosage regimen; the dosage for each patient is selected based on their response to the initiation dose. OBJECTIVE: To investigate the relationships between clinical characteristics and the daily dose of ODTs and to identify factors that affect ODT dosages. METHODS: This retrospective study included 209 adult patients with AVP-D. Patients were administered ODTs sublingually and instructed to restrict eating and drinking for 30 minutes after taking ODTs using a patient leaflet. ODT dose titration was conducted during hospitalization with close monitoring of urine output, body weight, and serum sodium levels. Multivariable linear regression models were applied to identify clinical factors associated with the daily dose of ODTs at discharge. We also evaluated the dosage at 1 year in 134 patients who were followed up in our hospital. RESULTS: The median daily dose of ODTs at discharge was 90 µg (IQR 60-120 µg). Multivariable linear regression models identified sex, age, and estimated creatinine clearance (eCCr) as significant factors associated with the daily dose of ODTs, with eCCr having the strongest effect. After excluding patients recovering from AVP-D, 71% of those followed up at our hospital took the same daily dose at 1 year after discharge. CONCLUSION: To achieve the safe and stable treatment of AVP-D, the daily dose of ODT needs to be selected based on a patient's sex, age, and eCCr under appropriate sublingual administration by patient education.

Assessment of quality of life in patients with craniopharyngioma and identification of risk factors for compromised overall wellness

ABSTRACT Objective: Quality of Life (QoL) has been a multifactorial concerning issue in oncology. We aimed to inspect the pre-operative QoL among patients with craniopharyngioma and to explore the potential correlations between parameters of QoL and clinical indices. Subjects and methods: We enrolled a total of 109 patients with craniopharyngioma. We utilized Short Form 36 (SF-36), Symptom Check List-90, Generalized Anxiety Disorder Questionnaire scale (GAD7), Patient Health Questionnaire Depression (PHQ9) and Pittsburgh Sleep Quality Index to prospectively evaluated their QoL. Parameters of QoL along with clinical indices were compared among sub-groups divided according to Puget classification. Correlation analyses and regression analyses were performed to detect influential determinants to self-reported wellness. Results: Patients presented impaired QoL compared with general population ( p < 0.001), as assessed by SF-36. Correlation analyses indicated the detrimental influence resulting from central diabetes insipidus (CDI). Multivariate linear regression unveiled the adverse effect of CDI on Mental Component Summary (coefficient = −13.869, p = 0.007), GAD7 total score (coefficient = 2.072, p = 0.049) as well as PHQ9 total score (coefficient = 3.721, p = 0.001). Multivariate logistic regression verified CDI as a risk factor of developing depressive symptoms (OR = 6.160, p = 0.001). Conclusion: QoL of patients with craniopharyngioma was remarkably compromised before operation. CDI exerted detrimental influences on patients' QoL and it might serve as a marker for early identification of patients at risk of depression.

Waterhouse-Friderichsen Syndrome and Central Diabetes Insipidus Due to Escherichia coli Meningitis.

Waterhouse-Friderichsen syndrome and central diabetes insipidus are uncommon but potentially fatal endocrine and metabolic diseases. Waterhouse-Friderichsen syndrome is defined as adrenal insufficiency caused by adrenal hemorrhage, which is typically bilateral and most frequently due to meningococcal infection. It is usually diagnosed by necropsy. Central diabetes insipidus in children is often caused by trauma, intracranial lesions, autoimmune diseases, and infections. In addition, it can be caused by mutations in the AVP-NPII gene, although this occurs typically later in childhood rather than in the neonatal period. This report describes a term infant who developed Escherichia coli meningitis, which resulted in septic shock and disseminated intravascular coagulation. Abdominal ultrasound led to an early diagnosis of bilateral adrenal hemorrhage and appropriate treatment with corticosteroids. Symptomatic central diabetes insipidus developed a few days after the onset of meningitis. Intravenous vasopressin was effective in resolving hemodynamic instability. In conclusion, sepsis and meningitis may have severely affected the endocrine system in this patient. Early diagnosis and appropriate treatment for both diseases may have resulted in better clinical outcomes for this patient.

Diagnosis and Treatment of Hereditary Central Diabetes Insipidus in a Swiss Family With a Mutation in the AVP Gene.

Hereditary central diabetes insipidus (CDI) is a genetic disorder characterized by polydipsia and polyuria. Most known mutations are located in the arginine-vasopressin (AVP) gene. Here, we describe a Swiss family with an autosomal dominant mutation in the AVP gene region encoding for the carrier protein neurophysin II (P55R). In addition, we discuss the algorithm for diagnosing and treating patients with hereditary CDI based on this Swiss family.

Erdheim-Chester Disease With BRAF V600E Mutation and Central Diabetes Insipidus Successfully Treated With Glucocorticoid.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by xanthoma/xanthogranuloma infiltration in various organs and a broad spectrum of clinical presentations, including bone lesions, central diabetes insipidus and renal failure. BRAF V600E mutation is seen in almost half of the cases of ECD; the BRAF inhibitor vemurafenib is recommended treatment in the United States and the European Union. However, the indication for vemurafenib in Japan is limited to unresectable malignant melanoma with BRAF mutation. Although glucocorticoids, interferon, chemotherapy, and radiation therapy are treatment options, no standard therapy for ECD has yet been established in Japan. We describe here a patient with central diabetes insipidus and retroperitoneal lesions who was successfully treated with prednisolone. Glucocorticoid therapy is therefore a plausible alternative for ECD with BRAF V600E mutation when the BRAF inhibitor vemurafenib cannot be used.

A Case of Lymphocytic Infundibulo-neurohypophysitis Exhibiting Spontaneous Regression.

Lymphocytic infundibulo-neurohypophysitis (LINH) is a rare autoimmune inflammatory process that selectively affects the neurohypophysis and the pituitary stalk, typically presenting with central diabetes insipidus (CDI). LINH is considered underdiagnosed because the definitive diagnosis requires invasive pituitary surgery with a high risk of complications. We present a case of CDI resulting from LINH, which was treated with conservative management, eschewing both glucocorticoid treatment and pituitary surgery. At presentation, the hormonal assessment indicated the presence of CDI without anterior pituitary dysfunction. Magnetic resonance imaging revealed stalk thickening without a posterior pituitary bright spot, and anti-rabphilin-3A antibodies were positive in serum. Collectively, we made a diagnosis of LINH. Considering that the patient did not exhibit any symptoms of mass effect, we chose conservative treatment with desmopressin acetate. One year later, the stalk thickening regressed spontaneously without surgical or glucocorticoid treatment, although the posterior pituitary bright spot remained absent, and CDI did not improve. The inflammatory process of LINH is mostly self-limited and recovers spontaneously, whereas life-long desmopressin treatment may be required because of pituitary stalk fibrosis and atrophy. Our case highlights the importance of noninvasive diagnosis and careful follow-up in preventing unnecessary interventions for patients with LINH.

Assessment of quality of life in patients with craniopharyngioma and identification of risk factors for compromised overall wellness.

Objective: Quality of Life (QoL) has been a multifactorial concerning issue in oncology. We aimed to inspect the pre-operative QoL among patients with craniopharyngioma and to explore the potential correlations between parameters of QoL and clinical indices. Subjects and methods: We enrolled a total of 109 patients with craniopharyngioma. We utilized Short Form 36 (SF-36), Symptom Check List-90, Generalized Anxiety Disorder Questionnaire scale (GAD7), Patient Health Questionnaire Depression (PHQ9) and Pittsburgh Sleep Quality Index to prospectively evaluated their QoL. Parameters of QoL along with clinical indices were compared among sub-groups divided according to Puget classification. Correlation analyses and regression analyses were performed to detect influential determinants to self-reported wellness. Results: Patients presented impaired QoL compared with general population (p < 0.001), as assessed by SF-36. Correlation analyses indicated the detrimental influence resulting from central diabetes insipidus (CDI). Multivariate linear regression unveiled the adverse effect of CDI on Mental Component Summary (coefficient = -13.869, p= 0.007), GAD7 total score (coefficient = 2.072, p = 0.049) as well as PHQ9 total score (coefficient = 3.721, p = 0.001). Multivariate logistic regression verified CDI as a risk factor of developing depressive symptoms (OR = 6.160, p = 0.001). Conclusion: QoL of patients with craniopharyngioma was remarkably compromised before operation. CDI exerted detrimental influences on patients' QoL and it might serve as a marker for early identification of patients at risk of depression.

A Case of Central Diabetes Insipidus in a Patient With a Pineal Mass Suspected to Be a Germinoma: A Case Report.

Central diabetes insipidus (CDI) is a rare condition characterized by excessive urination and thirst due to vasopressin deficiency. The underlying cause of CDI remains unknown in many cases. Tumors are a leading cause of CDI in young individuals, with germinoma being the most prevalent. We present a case of a 22-year-old male diagnosed with infundibuloneurohypophysitis (INH) of unknown etiology. His pituitary stalk thickening partially responded to high-dose prednisone treatment; however, one year after initial diagnosis, a new pineal region mass was noted on imaging. Further evaluation revealed the mass to be most likely a germinoma. This case emphasizes the importance of ongoing clinical and radiologic follow-up in idiopathic cases of CDI. The patient's symptoms improved with desmopressin, but the presence of the pineal mass necessitates further comprehensive neurosurgical evaluation.

Intracranial germinoma combined with parathyroid adenoma in a male pediatric patient: A case report.

Cases of young patients combined with intracranial germinoma and parathyroid adenoma are extremely rare. A 6.25-year-old boy was diagnosed with growth hormone deficiency at his first visit and was then treated with growth hormone substitution. Later, he was clinically diagnosed with central diabetes insipidus (CDI) and primary hyperparathyroidism, whereas no abnormal imaging evidence was identified, except for a thickened pituitary stalk. Due to persistent follow-up, parathyroid adenoma and intracranial germinoma were verified in succession. The patient had derived benefits from parathyroidectomy and chemotherapy plus radiotherapy. We concluded that children and adolescents who present with CDI and pituitary stalk thickening should undergo repeated screenings for underlying intracranial germinoma. Multiple lesions involving the parathyroid gland and pituitary should alert physicians to the possibility of multiple endocrine neoplasia or other inherited diseases; therefore, genetic screening is recommended.

Lymphocytic Infundibuloneurohypophysitis Diagnosis Owing to Positive Anti-rabphilin-3A Antibody Test Result in an 8-year-old Boy with Early-onset Central Diabetes Insipidus.

Childhood-onset lymphocytic infundibuloneurohypophysitis (LINH) has rarely been reported. Pathological evaluation via pituitary biopsy is necessary for a definitive diagnosis of LINH. However, pituitary biopsy is a highly invasive procedure. Recently, anti-rabphilin-3A antibody (RPH3A-Ab) has been reported as a promising diagnostic marker for LINH in adults; however, there are few such reports in the pediatric population. We report the case of an 8-year-old boy with central diabetes insipidus (CDI) who was clinically diagnosed with LINH based on RPH3A-Ab positivity. He was diagnosed with CDI using a water deprivation test combined with desmopressin administration. Serum and cerebrospinal fluid tumor markers were negative, and T1-weighted magnetic resonance imaging (MRI) revealed the absence of high signal intensity in the posterior pituitary gland and an enlarged pituitary stalk. Anterior pituitary function tests revealed no abnormalities. No pituitary biopsy was performed because of its invasive nature, and desmopressin treatment was initiated. Three months after CDI onset, the patient tested positive for RPH3A-Ab. MRI performed 9 months after CDI onset revealed amelioration of the pituitary stalk enlargement, and the clinical course corroborated our diagnosis of LINH. RPH3A-Ab may be useful as an early diagnostic tool for LINH in the pediatric population.

Central Diabetes Insipidus: An Acute Manifestation of COVID-19 Infection.

In recent years, there has been a rise in the number of COVID-19 cases and its complications. Central diabetes insipidus (central DI) is a rare but treatable manifestation of acute COVID-19 infection. This case reports the rapid onset of central DI in a 35-year-old male in less than two weeks post-COVID-19 infection. He made a complete recovery post-administration of desmopressin within one month. Prompt diagnosis, treatment, and periodic follow-up are hence the cornerstones of a successful recovery for a patient with central DI post-COVID-19 infection.

The therapeutic effect of oral desmopressin lyophilisate formulation in children with central diabetes insipidus.

OBJECTIVES: We aimed to assess the efficacy of oral use of oral desamino-D-arginine-8-vasopressin lyophilisate (OLD) in children with central diabetes insipidus (CDI). METHODS: Clinical, laboratory, and imaging characteristics of twenty-five children with CDI treated with OLD were evaluated. RESULTS: Fourteen boys and eleven girls with a mean age of 52.37 months were evaluated. These children (mean weight and height at admission, 26.81 ± 14.8 kg vs. 92.52 ± 30 cm) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatremia (mean sodium level, 143.12 ± 8.6 mEq/L). At the time of hypernatremia, mean serum and urine osmolality were 298.2 ± 18 mOsm/kg and 160.20 ± 8.7 mOsm/kg, respectively. ADH levels were undetectable (<0.5 pmol/L) at admission in all cases. Oral administration of desmopressin lyophilisate (120 µg/tablet) was initiated at a dose of 5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatremia. Serum sodium levels normalised in a mean duration of 15.2 ± 16.4 h with a mean decline rate of 0.12 ± 0.04 mEq/L/h. Nine children needed rehospitalization because of hypernatremia due to non-compliance. Four episode of hyponatremia was observed. Weight gain and growth were normal during the mean follow-up duration of 37.79 ± 48.2 months. CONCLUSIONS: Administration of OLD was practical and safe in the treatment of CDI in children with CNS malformations in this small retrospective series.