Neuroimaging of central diabetes insipidus.

Central diabetes insipidus (CDI) occurs secondary to deficient synthesis or secretion of arginine vasopressin peptide from the hypothalamo-neurohypophyseal system (HNS). It is characterized by polydipsia and polyuria (urine output >30mL/kg/day in adults and >2l/m2/24h in children) of dilute urine (<250mOsm/L). It can result from any pathology affecting one or more components of the HNS including the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, and median eminence of the hypothalamus, infundibulum, stalk or the posterior pituitary gland. MRI is the imaging modality of choice for evaluation of the hypothalamic-pituitary axis (HPA), and a dedicated pituitary or sella protocol is essential. CT can provide complimentary diagnostic information and is also of value when MRI is contraindicated. The most common causes are benign or malignant neoplasia of the HPA (25%), surgery (20%), and head trauma (16%). No cause is identified in up to 30% of cases, classified as idiopathic CDI. Knowledge of the anatomy and physiology of the HNS is crucial when evaluating a patient with CDI. Establishing the etiology of CDI with MRI in combination with clinical and biochemical assessment facilitates appropriate targeted treatment. This chapter illustrates the wide variety of causes and imaging correlates of CDI on neuroimaging, discusses the optimal imaging protocols, and revises the detailed neuroanatomy required to interpret these studies.

Central diabetes insipidus induced by temozolomide: A report of two cases.

INTRODUCTION: Central diabetes insipidus is a heterogeneous condition characterized by decreased release of antidiuretic hormone by the neurohypophysis resulting in a urine concentration deficit with variable degrees of polyuria. The most common causes include idiopathic diabetes insipidus, tumors or infiltrative diseases, neurosurgery and trauma. Temozolomide is an oral DNA-alkylating agent capable of crossing the blood-brain barrier and used as chemotherapy primarily to treat glioblastoma and other brain cancers. CASES: Two men (aged 38 and 54 years) suddenly developed polyuria and polydispsia approximately four weeks after the initiation of temozolomide for a glioblastoma. Plasma and urine parameters demonstrated the presence of a urinary concentration defect. MANAGEMENT: The clinical and laboratory abnormalities completely resolved with intranasal desmopressin therapy, allowing the continuation of temozolomide. The disorder did not relapse after cessation of temozolomide and desmopressin and relapsed in one patient after rechallenge with temozolomide. DISCUSSION: Our report highlights the importance of a quick recognition of this exceptional complication, in order to initiate promptly treatment with desmopressin and to maintain therapy with temozolomide.

Endocrine Outcomes In Central Diabetes Insipidus: the Predictive Value of Neuroimaging "Mismatch Pattern".

CONTEXT: The etiology of central diabetes insipidus (CDI) in children is often unknown. Clinical and radiological features at disease onset do not allow discrimination between idiopathic forms and other conditions or to predict anterior pituitary dysfunction. OBJECTIVE: To evaluate the evolution of pituitary stalk (PS) thickening and the pattern of contrast-enhancement in relation with etiological diagnosis and pituitary function. METHODS: We enrolled 39 children with CDI, 29 idiopathic and 10 with Langerhans cell histiocytosis (LCH). Brain magnetic resonance images taken at admission and during follow-up (332 studies) were examined, focusing on PS thickness, contrast-enhancement pattern, and pituitary gland size; T2-DRIVE and postcontrast T1-weighted images were analyzed. RESULTS: Seventeen of 29 patients (58.6%) with idiopathic CDI displayed "mismatch pattern," consisting in a discrepancy between PS thickness in T2-DRIVE and postcontrast T1-weighted images; neuroimaging findings became stable after its appearance, while "mismatch" appeared in LCH patients after chemotherapy. Patients with larger PS displayed mismatch more frequently (P = 0.003); in these patients, reduction of proximal and middle PS size was documented over time (P = 0.045 and P = 0.006). The pituitary gland was smaller in patients with mismatch (P < 0.0001). Patients with mismatch presented more frequently with at least one pituitary hormone defect, more often growth hormone deficiency (P = 0.033). CONCLUSIONS: The PS mismatch pattern characterizes patients with CDI, reduced pituitary gland size, and anterior pituitary dysfunction. The association of mismatch pattern with specific underlying conditions needs further investigation. As patients with mismatch show stabilization of PS size, we assume a prognostic role of this peculiar pattern, which could be used to lead follow-up.

Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions.

CONTEXT: Association of central diabetes insipidus (CDI) and pituitary stalk thickening (PST) may have several etiologies (including malignancies) and differential diagnosis remains often difficult. OBJECTIVE: The purpose of this study was to identify which clinical, biochemical or radiological features could help clinicians to make an etiological diagnosis, especially distinguishing neoplastic from non-neoplastic pituitary stalk lesions. DESIGNS AND METHODS: We retrospectively analyzed clinical, biochemical, radiological and histological data of 38 adult patients diagnosed with CDI and PST of proven etiology. RESULTS: Of the 38 pituitary stalk lesions included, 11 (29%) were neoplastic. A histopathological diagnosis was obtained in 22/38 (58%) patients. The three most frequently observed etiologies of PST were neuroinfundibulitis (34%), germinoma (21%) and histiocytosis (18%). Pituitary stalk thickness was larger for neoplastic lesions, particularly germinomas. Male gender and a very young age were statistically associated with a risk of germinoma. At least one anterior pituitary deficit was observed in nearly 60% of patients. Patients with neoplastic PST were more affected by multiple anterior pituitary dysfunction than patients with benign PST. A high serum prolactin level was individually the best predictor of a neoplastic origin (90% sensitivity and 60% specificity for a serum prolactin level 1.27-fold above the normal upper limit (ULN)). CONCLUSION: We confirm a relatively high risk of malignancy in adult patients presenting with the association of CDI and PST. Young age, male gender, a very large thickening of the stalk, multiple anterior pituitary deficits and prolactin above 1.3× ULN increase the likelihood of a neoplastic origin.

Report: central diabetes insipidus and schwannoma in a male with X-linked congenital adrenal hypoplasia.

BACKGROUND: DAX1 mutations are related to the X-linked form of adrenal hypoplasia congenita (AHC) in infancy and to hypogonadotropic hypogonadism (HH) in puberty. We report a male patient affected by X-linked AHC who presented with central diabetes insipidus and schwannoma in adulthood, which has not been described in association with AHC. CASE PRESENTATION: A 36-day-old male infant who presented with severe dehydration was admitted to the intensive care unit. His laboratory findings showed hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis. After hormonal evaluation, he was diagnosed with adrenal insufficiency, and he recovered after treatment with hydrocortisone and a mineralocorticoid. He continued to take hydrocortisone and the mineralocorticoid after discharge. At the age of 17, he did not show any signs of puberty. On the basis of a GnRH test, a diagnosis of HH was made. At the age of 24, he was hospitalized with thirst, polydipsia and polyuria. He underwent a water deprivation test for polydipsia and was diagnosed with central diabetes insipidus. By quantitative polymerase chain reaction analysis, we identified a hemizygous frameshift mutation in DAX1 (c.543delA). CONCLUSIONS: We suggest that DAX1 mutations affect a wider variety of endocrine organs than previously known, including the posterior pituitary gland.

Magnetic resonance imaging and symptoms in patients with neurosarcoidosis and central diabetes insipidus.

INTRODUCTION: In the clinical setting, the diagnosis of neurosarcoidosis in patients with central diabetes insipidus (CDI) is typically based both on symptoms (i.e. polydipsia or polyuria) and brain magnetic resonance imaging (MRI) findings (e.g. pituitary abnormality). However, inconsistent changes in the patient's symptoms and brain MRI findings may occur during the clinical course of the disease. This review was performed to summarise the relationship between symptoms and brain MRI findings in previously reported cases of neurosarcoidosis with CDI. MATERIAL AND METHODS: Case studies of patients diagnosed with neurosarcoidosis with CDI were collected via a PubMed search of studies published through 30 June 2018. RESULTS: Thirteen eligible studies were reviewed (20 patients; 12 men, 8 women; mean age 33 years). Polydipsia or polyuria was the first symptom in 13 patients. The mean duration from disease onset to diagnosis was 3.4 months. Brain MRIs showed abnormal findings in the hypothalamus and pituitary for 17 patients. Immunosuppressive drugs were used in 17 patients. For 14 patients, MRI findings improved, while symptoms did not. CONCLUSION: Patients with both neurosarcoidosis and CDI symptoms often do not improve, despite the fact that brain MRI findings often improve following treatment. More studies involving detailed pathological analyses and longer follow-up periods are necessary.

Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene.

BACKGROUND: Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone. AIM: To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus. PATIENTS AND METHODS: We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating. RESULTS: Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype-phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed the absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case. CONCLUSION: adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment.

Hydranencephaly complicated by central diabetes insipidus: report of two cases and systematic review of literature.

PURPOSE: Hydranencephaly is a congenital condition characterized by the complete or near-complete absence of the cerebral cortex and basal ganglia, while central diabetes insipidus (CDI) is a condition characterized by the inability to concentrate urine due to a deficiency in antidiuretic hormone (ADH). CDI is known to occur in midline congenital malformations such as holoprosencephaly and septo-optic dysplasia, but its association with hydranencephaly is less well-established. METHODS: We reported two cases of hydranencephaly complicated by CDI. We also performed a systematic review of the SCOPUS and PubMed databases for case reports and case series of patients with hydranencephaly and CDI, and compiled data on the clinical features and treatment options. RESULTS: Seven cases of hydranencephaly complicated by CDI were identified from the systematic review in addition to the two cases reported here, resulting in a total of nine cases. The patients' age ranged from 4 days to 4 years, and there was a female sex predilection (3.5:1). Patients most commonly presented with macrocephaly, developmental delay, and seizures, with dysmorphic features noted in 33%. In addition to CDI, other endocrinologic derangements included hypothyroidism (22%), hypocortisolemia (22%), and panhypopituitarism (22%). CDI was treated using sublingual or oral desmopressin while hypopituitarism was treated with the appropriate hormone replacement therapy. Insertion of a ventriculoperitoneal (VP) shunt was reported in 44% of cases. CONCLUSION: The case reports and systematic review suggest a previously unknown association between hydranencephaly and CDI. Clinicians managing cases of hydranencephaly are advised to have a high index of suspicion for CDI in patients presenting with the characteristic signs and symptoms.

Neuroimaging of central diabetes insipidus-when, how and findings.

Central or neurogenic diabetes insipidus (CDI) is due to deficient synthesis or secretion of antidiuretic hormone (ADH), also known as arginine vasopressin peptide (AVP). It is clinically characterised by polydipsia and polyuria (urine output > 30 mL/kg/day) of dilute urine (< 250 mOsm/L). It is the result of a defect in one of more sites involving the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei of the hypothalamus, median eminence of the hypothalamus, infundibulum or the posterior pituitary gland. A focused MRI pituitary gland or sella protocol is essential. There are several neuroimaging correlates and causes of CDI, illustrated in this review. The most common causes are benign or malignant neoplasms of the hypothalamic-pituitary axis (25%), surgery (20%), head trauma (16%) or familial causes (10%). No cause is identified in up to 30% of cases. Knowledge of the anatomy and physiology of the hypothalamo-neurohypophyseal axis is crucial when evaluating a patient with CDI. Establishing the aetiology of CDI with MRI in combination with clinical and biochemical assessment facilitates appropriate targeted treatment. The aim of the pictorial review is to illustrate the wide variety of causes of CDI on neuroimaging, highlight the optimal MRI protocol and to revise the detailed neuroanatomy and neurophysiology required to interpret these studies.

Intracranial pathologies associated with central diabetes insipidus in infants.

Background Idiopathic central diabetes insipidus (CDI) has been associated with intracranial pathologies that do not involve the structural pituitary gland or hypothalamus. The objective was to study the association between non-structural hypothalamic/pituitary intracranial pathologies (NSHPIP) with CDI and to review etiologies that may be contributory to the development of CDI. Methods A retrospective query of our intra-institutional database from 2006 to 2015. Children admitted diagnosed with diabetes insipidus (DI) (ICD-9 253.5) between the ages of 0-1 year were included. Patient charts were reviewed to include those who have a documented diagnosis of CDI, hypernatremia (>145 mmol/L), high serum osmolality (>300 mOsm/kg), low urine osmolality (<300 mOsm/kg), and brain imaging reports. Diagnoses of nephrogenic DI were excluded. Results Twenty-three infant patients were diagnosed with CDI. Eleven subjects (48%) had NSHPIP. Of those, 18% had cerebral infarction, 27% had intracranial injury and hemorrhage due to traumatic brain injury, 18% had isolated intraventricular hemorrhage, and 27% had meningitis. Hospital prevalence for NSHPIP, age 0-1 year, ranged from 0.05% to 0.3%. Conclusions Rates of NSHPIP in those with CDI are higher than expected hospital rates (p<0.001), suggesting a possible association between CDI and NSHPIP.

Hemorrhagic fever with renal syndrome accompanied by panhypopituitarism and central diabetes insipidus: a case report.

Central diabetes insipidus (DI) was detected in a patient with hemorrhagic fever with renal syndrome (HFRS) who had been molecularly and serologically diagnosed with Hantaan virus infection. We recommend that clinicians differentiate central DI in HFRS patients with a persistent diuretic phase even when pituitary MRI findings are normal.

The central diabetes insipidus associated with septo-optic dysplasia (de Morsier syndrome).

INTRODUCTION: Septo-optic dysplasia (SOD) is a rare congenital heterogeneous malformation with postulated genetic and environmental etiology. Septo-optic dysplasia is characterized by classic triad: optic nerve hypoplasia, midline brain malformation and hypothalamic-pituitary endocrine deficiencies. The most common hormonal deficiencies affect growth hormone and gonadotropin but it can also be lower levels of the other hormones. The rarest form of hormone deficiency is the deficiency of the antidiuretic hormone. CASE REPORT: The boy was born in 39th week of pregnancy in general good condition. Weakened suction reflex and spitting resulted in substantial difficulties with breastfeeding. After transfontanelle ultrasonography central nervous system defect was suspected. In the 5th month of life MRI confirmed septo-optic dysplasia on the basis of anterior genu of corpus callosum and septum pellucidum agenesis, both optic nerves and optic chiasm hypoplasia, pachygyria and polimicrogyria of the right frontoparietal cortex. Neurological examination revealed axial laxity, psychomotor development delay, difficulties in keeping eyes fixed as well as rotary and horizontal nystagmus. At the age of 3 years he underwent the endocrinological consultation due to polydipsia and polyuria. The tests revealed lower urine specific gravity tests results, therefore diabetes insipidus was diagnosed. The boy still receives desmopressin and there are no signs of central diabetes insipidus. Currently, the boy is under a multi-disciplinary medical care. CONCLUSIONS: The attention should be focussed on early diagnosis, mutli-specialized care and treatment SOD. Hypopituitarism ranges from isolated to multiple hormone deficits, with diabetes insipidus in a minority. Although rare, SOD is an important cause of congenital hypopituitarism and should be considered in all children with midline defects and optic nerve hyploplasia.

Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

From cerebral salt wasting to diabetes insipidus with adipsia: case report of a child with craniopharyngioma.

UNLABELLED: Craniopharyngioma is associated with a wide and interesting variety of sodium states both by itself and following surgical resection. These are often challenging to diagnose, especially given their dynamic nature during the perioperative course. We present the case of a boy with craniopharyngioma who had hyponatremia due to cerebral salt wasting preoperatively, developed diabetes insipidus (DI) intraoperatively and proceeded to develop hypernatremia with adipsic DI. CONCLUSION: Cerebral salt wasting is a rare presenting feature of craniopharyngioma. Postoperative DI can be associated with thirst abnormalities including adipsia due to hypothalamic damage; careful monitoring and a high index of suspicion are required for its detection. Adipsic DI is a difficult condition to manage; hence a conservative surgical approach is suggested.

Congenital toxoplasmosis presenting as central diabetes insipidus in an infant: a case report.

BACKGROUND: Congenital toxoplasmosis has a wide range of presentation at birth varying from severe neurological features such as hydrocephalus and chorioretinitis to a well appearing baby, who may develop complications late in infancy. While neuroendocrine abnormalities associated with congenital toxoplasmosis are uncommon, isolated central diabetes insipidus is extremely rare. CASE PRESENTATION: Here, we report on a female infant who presented with fever, convulsions, and polyuria. Examination revealed weight and length below the 3rd centile along with signs of severe dehydration. Fundal examination showed bilateral chorioretinitis. This infant developed hypernatremia together with increased serum osmolality and decreased both urine osmolality and specific gravity consistent with central diabetes insipidus. Serology for toxoplasma specific immunoglobulin M was high for both the mother and the baby and polymerase chain reaction for toxoplasma deoxyribonucleic acid was positive in the infant confirming congenital toxoplasmosis. Brain computerized tomography scans demonstrated ventriculomegaly associated with cerebral and cortical calcifications. Fluid and electrolyte abnormalities responded to nasal vasopressin therapy. CONCLUSION: This report highlights central diabetes inspidus as a rare presentation of congenital toxoplasmosis.

Refractory diabetes insipidus following drainage of chronic subdural haematoma.

BACKGROUND: Post-traumatic diabetes insipidus (DI) is a relatively common complication after head injury. The authors report a fatal case of refractory DI, which developed in a patient with chronic subdural haematoma. CASE HISTORY: A 38-year-old woman presented to the emergency room with a headache for over a week. She was alert and neurological examination demonstrated no significant deficits or external wounds in her head. Brain computed tomography (CT) scans revealed a small amount of chronic subdural haematoma bilaterally. She was treated conservatively and her hospital course was uneventful until she developed a convulsive seizure and mental change on the 3rd day after admission. Immediate follow-up CT scans showed no significant change in the amount of haemorrhage except effacement of gyral marking. Bilateral trephination and drainage of the haematoma were performed immediately. Post-operatively, she developed a refractory DI and was managed in the intensive care unit. However, she died on the 6th day after the operation ultimately. CONCLUSION: The authors emphasize the importance of timely drainage of chronic subdural haematoma to prevent a fatal endocrinologic complication after head injury. This study also discusses the possible mechanism of DI after head injury, management and review of the pertinent literatures.

Primary CNS lymphoma with bilateral symmetric hypothalamic lesions presenting with panhypopituitarism and diabetes insipidus.

We present an unusual case of primary central nervous system (CNS) lymphoma presenting with bilateral symmetric hypothalamic lesions causing diabetes insipidus and hypopituitarism. A 50-year-old male presented initially with mental status changes, polyuria and polydipsia. The patient was determined to have diabetes insipidus (DI) and significant anterior pituitary deficiencies resulting in symptomatic pleural and pericardial effusions. Brain MRI with contrast demonstrated bilateral enhancement of his hypothalamus extending to the optic tract. The extensive diagnostic workup that ensued on his initial presentation was non-diagnostic as he had no obvious site of involvement that was easily accessible to biopsy. With close follow-up, the patient had rapid radiographic progression of his disease to his cerebral hemispheres. He therefore underwent brain biopsy and was diagnosed with primary CNS large B cell lymphoma. Chemotherapy has resulted in disease remission with resolution of MRI findings, but the patient has not had resolution of the hypopituitarism or DI. This case highlights the unique diagnostic challenge of patients with isolated hypothalamic lesions.