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1/9. Tonicity balance, and not electrolyte-free water calculations, more accurately guides therapy for acute changes in natremia.

    The usual way to decide why hyponatremia or hypernatremia has developed and to plan goals for its therapy is to analyze events in electrolyte-free water (EFW) terms. We shall demonstrate that an EFW balance does not supply this information. Rather, one must calculate mass balances for water and sodium plus potassium separately (a tonicity balance) to understand the basis for the change in natremia and the proper goals for its therapy. These points are illustrated with a clinical example.
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2/9. Psychogenic diabetes insipidus in toddlers with compulsive bottle-drinking: not a rare entity.

    Psychogenic diabetes insipidus is commonly seen in adolescents but very rarely reported in toddlers. We report three toddlers who presented to our clinic with compulsive drinking behavior and polyuria. Laboratory work-up and water deprivation tests were consistent with psychogenic diabetes insipidus.
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3/9. A rare case of central post-gravid diabetes insipidus.

    Central diabetes insipidus (CDI) arising in the puerperal period has been attributed mainly to Sheehan's syndrome or to lymphocytic infundibulo-neurohypophysitis. We report the case of a 24-year-old woman who came to our observation for the appearance, 3 weeks after a normal delivery, of a polyuric-polydipsic syndrome. Measurements of urinary volumes, plasma osmolality and urinary osmolality, in conditions of free water intake, water deprivation and a water deprivation-vasopressin administration test, demonstrated CDI. brain magnetic resonance imaging showed a normal morphology of the adenohypophysis and total absence of the neurohypophysis. Assays of the pituitary hormones were found to be within normal limits. These results, incompatible with a diagnosis of Sheehan's syndrome and lymphocytic infundibulo-neurohypophysis, excluded all the other known causes of acquired CDI. Our diagnosis was therefore of post-gravid idiopathic CDI. Thus, it is possible that in the puerperal period other diseases of the posterior hypophysis may develop, of unknown etiopathogenesis but equally responsible for CDI.
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4/9. A novel mutation in the preprovasopressin gene identified in a kindred with autosomal dominant neurohypophyseal diabetes insipidus.

    Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a defect in free water conservation caused by mutations in the single gene that encodes both vasopressin (VP) and its binding protein, neurophysin II (NP II). Most of the human mutations in this gene have been in the portion encoding the NP molecule; the resultant abnormal gene products are believed to cause cellular toxicity as improperly folded precursor molecules accumulate in the endoplasmic reticulum. We identified a new American kindred with ADNDI and found a novel mutation in the VP molecule. A 78-yr-old man was noted to have hypotonic polyuria and plasma hyperosmolarity; the urinary concentration defect was reversed by administration of VP. His symptomatology dated to childhood, and his family history was consistent with autosomal transmission of the polyuric syndrome, with affected members in three generations, including several females. Affected individuals were found to be heterozygous for a 3-bp deletion in exon 1 of arginine VP (AVP)-NP II, predicting a deletion of phenylalanine 3 (known to be critical for receptor binding) in the VP nonapeptide. Neuro 2A cells stably transfected with the mutant AVP-NP construct showed increased rates of apoptosis as assessed by flow cytometric methods. These observations support the concept that cellular toxicity of abnormal AVP-NP gene products underlies the development of ADNDI, and the data further demonstrate that mutations affecting the AVP moiety can result in initiation of these pathological processes.
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5/9. Serial MR intensity changes of the posterior pituitary in patients with diabetes insipidus after transsphenoidal surgery for pituitary adenomas: report of two cases.

    This is the first report describing magnetic resonance (MR) intensity changes of the posterior pituitary gland in the patients suffering from the classical "triphasic" diabetes insipidus (DI) after transsphenoidal surgery for pituitary adenomas. A 21-year-old female and a 54-year-old female were admitted to our hospital with the diagnosis of Cushing's disease and acromegaly due to pituitary microadenomas, respectively. No evidence of DI was found, and T1-weighted MR images exhibited "bright spot" corresponding to the posterior pituitary in both cases. Both experienced the classical "triphasic" pattern of water metabolism disturbance after successful transsphenoidal resection of pituitary adenomas, that is, polyuria-oliguria-polyuria. The MR signal hyperintensity in posterior pituitary was detected during the first polyuric phase, but the hyperintensity disappeared during the second polyuric phase. In addition, "bright spot" was restored along with the recovery from DI in the chronic phase. These findings of serial MR images supported that the first DI phase of the classical triphasic course of water metabolism disturbance was caused by secretional dysfunction of stored vasopressin from the posterior gland, whereas the second DI phase was due to impairment in the functional integrity producing vasopressin-containing granules after depletion of vasopressin in the oliguric phase.
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6/9. pituitary apoplexy precipitating diabetes insipidus.

    OBJECTIVE: To describe a case of pituitary apoplexy complicated by diabetes insipidus and to review management of patients with pituitary apoplexy and water excretion disturbances associated with transsphenoidal surgery. methods: We describe clinical, laboratory, and radiologic findings in a patient with pituitary apoplexy and central diabetes insipidus. RESULTS: A 74-year-old woman presented with severe headache and sudden loss of vision for 12 hours, accompanied by thirst and frequent urination. Visual field examination demonstrated bitemporal hemianopsia. Her laboratory findings were significant for a serum sodium level of 152 mEq/L and urine specific gravity of <1.005. A magnetic resonance imaging scan of her pituitary gland identified a 3.5-cm suprasellar mass compressing the optic chiasm. She subsequently underwent transsphenoidal pituitary surgery with subtotal resection of this mass. Microscopic evaluation of tumor tissue revealed a pituitary adenoma with evidence of recent infarct and hemorrhage. Her clinical and biochemical course was consistent with the triphasic response that may occur after pituitary surgery related to damage to the hypothalamus and supraopticohypophyseal tract. CONCLUSION: pituitary apoplexy may be rarely associated with diabetes insipidus.
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7/9. Acute and fatal hyponatraemia after resection of a craniopharyngioma: a preventable tragedy.

    Central diabetes insipidus developed for the first time in a 14-year-old female during the resection of a craniopharyngioma. The water diuresis persisted until a vasopressin analogue (dDAVP) was given. Professor McCance was asked to explain why hypernatraemia developed, to anticipate dangers that might develop in the salt and water area with therapy, and to provide insights into why this patient died, due to the subsequent development of hyponatraemia that caused a lethal rise in intracranial pressure. The team specifically wanted Professor McCance's opinions as to why a PNa of 124 mmol/l was uniquely dangerous for this patient, and this was a particularly challenging conundrum. Nevertheless, with the aid of a mini-experiment, a careful chart review, and creative thinking, he was able to offer a novel solution, and to suggest ways to prevent its occurrence in other patients.
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8/9. Clinical features, diagnosis and molecular studies of familial central diabetes insipidus.

    BACKGROUND: Familial central diabetes insipidus (DI) is rare and is characterised by polydipsia and polyuria with a variable age of onset. The evaluation of arginine vasopressin (AVP) secretion in these individuals has been reported infrequently and only in adulthood. OBJECTIVE: To describe the clinical features, diagnosis and molecular investigation of children affected by familial central DI. methods: Functional studies of AVP secretion were undertaken in children from two kindreds with familial central DI. The AVP-neurophysin II (AVP-NPII) gene was also sequenced in symptomatic individuals. RESULTS: In affected individuals, the result of the water deprivation test may be inconclusive. However, the hypertonic saline test identified both the severe and partial forms of AVP deficiency. A novel mutation of the AVP-NPII gene was identified by direct gene sequencing in both families. CONCLUSIONS: This report highlights the progressive decline in AVP secretion with increasing age in this disorder and the usefulness of mutational analysis in these families. In symptomatic individuals, the hypertonic saline test may be a useful second-line investigation for functional studies of AVP secretion where molecular diagnostics are unavailable.
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9/9. Central diabetes insipidus following intracranial hemorrhage due to vitamin k deficiency in a neonate.

    A previously healthy 30-day-old girl presented with seizures, irritability and inability to sleep for three days. Vitamin K was not given just after birth. She was lethargic. A multifocal clonic seizure was evident during examination. anisocoria was diagnosed on eye examination. brain magnetic resonance imaging showed intracerebral hemorrhage, ventricular dilatation, and hematoma in the left temporofrontal region extending to the hypothalamus. Central diabetes insipidus was diagnosed by water deprivation due to dehydration and hypernatremia, and then desmopressin was added to phenobarbital. The possible mechanism of central diabetes insipidus in our patient is damage of vasopressin pathway resulting from compression of hemorrhage. An operation of ventriculoperitoneal shunt was also performed due to hydrocephalus. While she was symptom-free except for neurological sequel during routine control examinations after discharging from hospital, the parents said that she died, most probably from bronchopneumonia, at the age of 7.5 months. In conclusion, we emphasize that prophylactic vitamin K should be administrated to all babies just after birth, and infants with intracranial hemorrhage should carefully be monitored for central diabetes insipidus.
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