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.

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.

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.

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.

Spontaneous regression of isolated neurohypophyseal langerhans cell histiocytosis with diabetes insipidus.

In pediatric and adolescent patients, the most common causes for a thickened pituitary stalk with central diabetes insipidus are germ cell tumors, lymphocytic infundibuloneurohypophysitis (LIN), and Langerhans cell histiocytosis (LCH). We describe here a 13-year-old girl who had an abrupt onset of polyuria and polydipsia. Magnetic resonance imaging of the brain revealed thickening of the pituitary stalk, and loss of the physiological hyperintense signal of the posterior pituitary gland. Based on a histopathology, she was diagnosed as having LCH. Another LCH lesion was not detected. The prognoses for LCH patients with single-system and single-site are generally good so we decided on only simple observation. The lesion spontaneously regressed 3 months later, resembling a typical self-limiting course of LIN. In conclusion, the present case suggests that 1) radiological differential diagnosis between LIN and LCH is so difficult that histological confirmation is crucial for correct diagnosis, 2) some past cases of histologically-unconfirmed LIN can include LCH, 3) solitary neurohypophyseal LCH can shrink spontaneously up to near remission level.

Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology.

Central diabetes insipidus (CDI) is a rare hypothalamus-pituitary disease due to the deficiency of arginine vasopressin (AVP) synthesis from the hypothalamus and/or secretion from the neurohypophysis. The etiology of CDI is unknown in over one third of cases, classified as idiopathic CDI. The aim of this study was 2-fold: 1) to evaluate the occurrence of circulating autoantibodies to AVP-secreting cells (AVPcAb), and 2) to correlate it to clinical (sex, age of disease onset, disease duration, and degree), immunological (clinical history of autoimmune diseases and presence of related organ-specific autoantibodies), and radiological features (neurohypophyseal bright spot, pituitary stalk thickening, and empty sella) in a large cohort of patients with apparently idiopathic CDI or CDI of known etiology. To this purpose, 150 patients with CDI were studied: 64 idiopathic, 6 familial, 12 associated to granulomatous diseases, and 68 secondary to cranial trauma, tumor, or surgery. AVPcAb were measured by an indirect immunofluorescence method. AVPcAb were found in 23.3% of CDI patients: 21 idiopathic (32.8%) and 14 nonidiopathic (16.3%; chi(2) = 13.1; P < 0.001). AVPcAb were independently associated with age less than 30 yr at disease onset (P = 0.001) in patients with idiopathic CDI and with history of autoimmune diseases (P = 0.006 and P = 0.02, respectively) and radiological evidence of pituitary stalk thickening (P = 0.02 and P = 0.003, respectively) in both idiopathic and nonidiopathic CDI. The likelihood of autoimmunity in one patient with apparently idiopathic CDI with age of disease onset less than 30 yr was 53%, it increased to 91% when history of autoimmune diseases was associated and to 99% when pituitary stalk thickening was further associated. In conclusion, autoimmunity is associated with one third of patients with apparently idiopathic CDI, which should therefore be classified as autoimmune CDI. Autoimmune CDI is highly likely in young patients with a clinical history of autoimmune diseases and radiological evidence of pituitary stalk thickening. Conversely, autoimmunity probably represents an epiphenomenon in patients with nonidiopathic CDI.