[Association between central diabetes insipidus and type 2 diabetes mellitus]. / Asociación de diabetes insípida central y diabetes mellitus tipo 2.

Central diabetes insipidus is a rare disease of the hypothalamus and neurohypophysis. It is very unusually found in the adult with type 2 diabetes mellitus. It is manifested by a polydipsic polyuric syndrome, which must be distinguished from the poorly controlled type 2 diabetes mellitus. Given the similarity of both entities and the unusual nature of their coexistence, their suspicion is difficult. The case of a 72-year-old male with type 2 diabetes mellitus with poor insulin control (fasting hyperglycemia greater than 180 mg/dl) who had a long-standing polyuric syndrome is here presented. Hypernatremia and plasma osmolality elevated together with a low urinary osmolality led to the suspicion of diabetes insipidus, which was subsequently confirmed by the dehydration test and the administration of desmopressin sc. With 61% increase in the calculated urinary osmolarity one hour post desmopressin s.c., diabetes insipidus of central type was diagnosed. Nuclear Magnetic Resonance showed a bright spot with normal neurohypophysis, contributing to the diagnosis of the idiopathic form.

Asociación de diabetes insípida central y diabetes mellitus tipo 2 / Association between central diabetes insipidus and type 2 diabetes mellitus

La diabetes insípida central es una enfermedad rara del hipotálamo y de la neurohipófisis, y muy inusualmente se halla en el adulto con diabetes mellitus 2. Se manifiesta por un síndrome poliúrico polidípsico, que debe diferenciarse de la diabetes mellitus mal controlada. Ante la similitud de ambas entidades, y lo infrecuente de su coexistencia, se dificulta su sospecha. Se presenta el caso de un hombre de 72 años de edad, con diabetes mellitus 2 y pobre control de la misma (hiperglucemias de ayuno mayores a 180 mg/dl) que cursó un síndrome poliúrico de larga data. La hipernatremia y la osmolalidad plasmática elevadas, junto a una osmolalidad urinaria baja llevaron a la sospecha de diabetes insípida, que posteriormente se confirmó con la prueba de deshidratación y la administración de desmopresina s.c. Con un aumento del 61% de la osmolalidad urinaria calculada una hora post desmopresina s.c. fue diagnosticada como diabetes insípida del tipo central. La resonancia magnética nuclear mostró una mancha brillante con neurohipófisis normal, contribuyendo al diagnóstico de la forma idiopática.

Central diabetes insipidus is a rare disease of the hypothalamus and neurohypophysis. It is very unusually found in the adult with type 2 diabetes mellitus. It is manifested by a polydipsic polyuric syndrome, which must be distinguished from the poorly controlled type 2 diabetes mellitus. Given the similarity of both entities and the unusual nature of their coexistence, their suspicion is difficult. The case of a 72-year-old male with type 2 diabetes mellitus with poor insulin control (fasting hyperglycemia greater than 180 mg/dl) who had a long-standing polyuric syndrome is here presented. Hypernatremia and plasma osmolality elevated together with a low urinary osmolality led to the suspicion of diabetes insipidus, which was subsequently confirmed by the dehydration test and the administration of desmopressin sc. With 61% increase in the calculated urinary osmolarity one hour post desmopressin s.c., diabetes insipidus of central type was diagnosed. Nuclear Magnetic Resonance showed a bright spot with normal neurohypophysis, contributing to the diagnosis of the idiopathic form.

Usefulness of anti-rabphilin-3A antibodies for diagnosing central diabetes insipidus in the third trimester of pregnancy.

We report a 27-year-old pregnant woman with polyuria, polydipsia and headache in the third trimester of pregnancy. Hypernatremia (153 mEq/L), high plasma osmolality (300 mOsm/kgH2O) and low urinary osmolality (92 mOsm/kgH2O) were observed at the admission to our hospital. Plasma arginine vasopressin (AVP) level was inappropriately low (2.2 pg/mL) compared to the high plasma osmolality. Plasma AVP responses to hypertonic-saline infusion were blunted, and her urine osmolality increased in response to desmopressin. The diagnosis of central diabetes insipidus was made from these results. Magnetic resonance imaging (MRI) of hypothalamic-pituitary region demonstrated a significant enlargement of the pituitary stalk, suggesting the presence of hypophysitis. In addition, serum anti-rabphilin-3A antibodies that have been recently reported as a biomarker of lymphocytic infundibulo-neurohypophysitis, were positive. Diabetes insipidus continued after delivery, suggesting that polyuria was not mainly due to excessive vasopressinase activity or reduced renal sensitivity to AVP by prostaglandin E2 that can cause temporal polyuria during pregnancy. We therefore clinically diagnosed central diabetes insipidus due to lymphocytic infundibulo-neurohypophysitis, without performing invasive transsphenoidal pituitary biopsy. This case suggested the usefulness of anti-rabphilin-3A antibodies for the etiological diagnosis of central diabetes insipidus during pregnancy.

Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.

Clinical characteristics of central diabetes insipidus in Taiwanese children.

BACKGROUND/PURPOSE: Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. METHODS: From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. RESULTS: The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. CONCLUSION: Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study.

Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ≤5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration.

Development of central diabetes insipidus following electroconvulsive therapy: results of a prospective pilot study.

OBJECTIVES: The objective of this study was to examine the occurrence of laboratory abnormalities and symptoms of central diabetes insipidus (CDI) in patients receiving acute electroconvulsive therapy (ECT) series. METHODS: We prospectively investigated adult psychiatric inpatients for objective and subjective evidence of CDI at baseline and after their sixth ECT. RESULTS: Although participants did not report any CDI symptoms, two thirds had clinically important decreases in urine osmolality (>200 mOsm/kg), and two thirds had serum sodium increases of 5 mmol/L following exposure to ECT. CONCLUSION: Our findings suggest that objective evidence of CDI can occur following the administration of ECT series, even in the absence of symptomatic complaints.

Desmopressin duration of antidiuretic action in patients with central diabetes insipidus.

The key question answered by this study is whether it is possible to deliver a pharmacokinetic and pharmacodynamic duration of antidiuretic action long enough to ensure adequate antidiuresis with two daily administrations of desmopressin in patients with central diabetes insipidus (CDI). We studied the efficacy and safety of desmopressin i.v. in 13 CDI patients using two 3-way crossover designs, in the doses 30, 60, 125 ng, and 125, 250 and 500 ng. Duration of action, minimum output rate, max osmolality and average osmolality during action (AUC osmolality) were measured every 30 min for the first 2 h during the infusion, and then every hour or every second hour until the urine output rate was greater than 2 ml/kg/30 min. The duration of antidiuretic action was 4, 8 and 11 h, respectively, for 125, 250, and 500 ng, increasing from 250 to 500 ng but for the remaining secondary dynamic efficacy parameters no difference could be detected based on descriptive statistics between the doses 250 and 500 ng, indicating that the upper plateau region of the dose-response curve had been reached. All treatment emergent adverse events were classified as unrelated or unlikely related to trial medication. No serious adverse events occurred. Data on duration of action indicates that it is possible to achieve antidiuretic control with 500 ng i.v. corresponding to 160 µg orodispersible tablets twice daily in CDI patients. Today, the Minirin Melt label recommends the majority of CDI patients a dose of 60 to 120 µg t.i.d.

Prenatal presentation of transient central diabetes insipidus.

INTRODUCTION: Nephrogenic diabetes insipidus (DI) in the foetus has been described as a rare presentation of severe polyhydramnios. DISCUSSION: We report a case of foetal central DI, characterised by severe polyhydramnios. Significant polyuria was noted at birth. Serum AVP level was un-measurable (<0.5 pg/ml). A dramatic response to intravenous dDAVP (desmopressin) was noted confirming central DI. Further investigations did not reveal a recognised cause for central or nephrogenic DI. The infant thrived well on a small dose of oral desmopressin until the age of 12 months. At 13 months, a water deprivation test revealed a normal ability to concentrate urine without desmopressin, and subsequently, the infant has thrived without further treatment. The transient nature of the central DI remains obscure but could be explained by a maturational delay in the tissues involved in AVP synthesis or release, during intrauterine life and infancy. CONCLUSION: Both nephrogenic and central DI should be considered as a cause of severe polyhydramnios. This may help to guide prompt intensive management and investigation, with attention to vascular access, central venous pressure, urine output monitoring and replacement.

A patient with essential hypernatremia had good response to desmopressin acetate therapy.

OBJECTIVES: Essential hypernatremia is very rare in clinical practice and the pathogenesis is unclear. We performed a set of clinical tests to a patient with chronic and sustained hypernatremia as well as absence of thirst in order to investigate the clinical characteristics and make the diagnosis, yet most importantly to analyze the possible pathogenesis and explore a possible therapy regime. METHODS: Water deprivation test and acute water intravenous loading test were performed to observe the changes of urinary osmolality, plasma osmolality and plasma sodium. Free water clearance (C(H2O) was calculated. Osmolality was detected using the method of freezing point depression, and thirst grade using visual analogue scales. Desmopressin acetate (0.05-0.1 mg/d) was administered to the patient in order to observe the therapeutic effects to his disorder. RESULTS: The patient had sustained hypernatremia over a long period of time, decreased thirst, normal renal function, as well as absence of clinical hypovoluemia. The plasma sodium was 160-190 mmol/L and plasma osmolality was 330-370 mOsm/L without any thirst perception which could not be corrected by water intake. An 18-hour period of water deprivation increased the urinary osmolality from 368 mOsm/L to 420 mOsm/L with plasma osmolality increasing from 362 mOsm/L to 369 mOsm/L and rising further to 857 mOsm/L after an injection of 5 u vasopresin. With the infusion of 1 250 ml 5%-glucose during 2 hours in an acute water loading test setting, plasma osmolality decreased from 350 mOsm/L to 334 mOsm/L associated with a plasma sodium decrease from 164.7 mmol/L to 155 mmol/L urinary osmolality dropped from a maximum of 632 mOsm/L to 135 mOsm/L urinary volume from 0.25 ml/min to 2.33 ml/min and C(H2O) from -0.18 ml/min to 1.19 ml/min after acute water loading with 1 250 ml glucose dissolved in water. Our results reveal that treatment of the patient with Desmopressin acetate relieved the adypsia, hypernatremia and hyperosmolality effectively. CONCLUSIONS: The patient was considered as suffering from essential hypernatremia which was associated with partial central diabetes insipidus and adypsia. Desmopressin acetate as a common therapeutic agent of central diabetes insipidus proved to be an effective treatment for essential hypernatremia.

[Osmoregulating effect of vasopressin with prolonged action on Brattleboro rats with hypothalamic diabetes insipidus].

The particularities of urine osmotic concentration depending on hormonal background of vasopressin were studied in rats. It was found that WAG and Brattleboro lines of rats characterized respectively by normal level and absence of endogenous vasopressin, possess interline correlation of urine osmolality (p = 0.86) in various conditions between the extreme hydrating and dehydratation. Concentrating level of WAG rats varies from 747 +/- 94 to 2936 +/- 128 mOsm/kg, but that of Brattleboro rats changes more within the 160 +/- 9 being twice lower as isotonicity to 1305 +/- 142 mOcm/kg. Urine concentrating goes up to 1391 +/- 76 mOcm/kg in Brattleboro rats already on the day of the action of exogenous vasopressin secreted from ALZET minipump, however, in spite of constant work of this minipump during 4 hrs a week, further increasing of urine osmolality was not observed in Brattleboro rats.

Apoptosis of supraoptic AVP neurons is involved in the development of central diabetes insipidus after hypophysectomy in rats.

BACKGROUND: It has been reported that various types of axonal injury of hypothalamo-neurohypophyseal tract can result in degeneration of the magnocellular neurons (MCNs) in hypothalamus and development of central diabetes insipidus (CDI). However, the mechanism of the degeneration and death of MCNs after hypophysectomy in vivo is still unclear. This present study was aimed to disclose it and to figure out the dynamic change of central diabetes insipidus after hypophysectomy. RESULTS: The analysis on the dynamic change of daily water consumption (DWC), daily urine volume(DUV), specific gravity of urine(USG) and plasma vasopressin concentration showed that the change pattern of them was triphasic and neuron counting showed that the degeneration of vasopressin neurons began at 10 d, aggravated at 20 d and then stabilized at 30 d after hypophysectomy. There was marked upregulation of cleaved Caspase-3 expression of vasopressin neurons in hypophysectomy rats. A "ladder" pattern of migration of DNA internucleosomal fragments was detected and apoptotic ultrastructure was found in these neurons. There was time correlation among the occurrence of diabetes insipidus, the changes of plasma vasopressin concentration and the degeneration of vasopressin neurons after hypophysectomy. CONCLUSION: This study firstly demonstrated that apoptosis was involved in degeneration of supraoptic vasopressin neurons after hypophysectomy in vivo and development of CDI. Our study on time course and correlations among water metabolism, degeneration and apoptosis of vasopressin neurons suggested that there should be an efficient therapeutic window in which irreversible CDI might be prevented by anti-apoptosis.

Myelodysplastic syndrome with central diabetes insipidus manifesting hypodipsic hypernatremia and dehydration.

Central diabetes insipidus (DI) is a rare but recognized complication of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) that is caused by leukemic infiltration to the hypothalamo-neurohypophyseal system. In rare patients in whom a wide region of the hypothalamus is involved, central DI results in hypodipsic hypernatremia and dehydration. Typical DI symptoms such as polydipsia, polyuria, and marked thirst are concealed in these cases, because the hypothalamic "thirst center" cannot send thirst stimuli to the cerebral cortex. Herein we describe a patient with MDS developing into AML, who presented with hypodipsic hypernatremia and dehydration. A diagnosis of central DI was made on the ground of a low level of serum anti-diuretic hormone (ADH) despite high serum osmolality. A magnetic resonance imaging study revealed attenuation of a physiological "bright spot" of the neurohypophysis. An induction course chemotherapy including regular-dose cytarabine and daunorubicin produced a rapid improvement of hypernatremia. The bone marrow aspirate after two courses of chemotherapy showed complete remission. At that point, ADH release and the "bright spot" were recovered. In order to correctly diagnose central DI in association with hematological malignancies, we should not overlook this atypical type of DI.

Oral DDAVP is a good alternative therapy for patients with central diabetes insipidus: experience of five-year treatment.

We studied the efficacy and safety of oral 1-deamino-8-D-arginine-vasopressin (DDAVP) tablets in 9 patients, aged 17-36 years, with central diabetes insipidus (DI). The tablet contained 100 microg of desmopressin acetate. Maximum plasma concentration was obtained at 90 min after a single oral administration of 100 microg DDAVP with a mean plasma level of 14.7 +/- 5.4 (range: 5.3-50.9) pg/ml. The onset of action was observed 2 h after oral administration, while the maximum effect was obtained at 4 h. Mean urine volume in patients decreased significantly from 402 +/- 52 to 26 +/- 3 ml/hr and urine osmolality increased from 91 +/- 8 to 732 +/- 21 mosm/kg at 4 h after the intake of oral DDAVP. Plasma osmolality level and serum sodium concentration remained unchanged throughout the study. Long-term treatment for 5 years with oral DDAVP resulted in control of diuresis in 8 of the 9 patients. The average oral DDAVP dose required to obtain this control was 19 +/- 2 (range: 15-30) times more than that of prior intranasal treatment. No adverse effects were observed during this follow-up period. These results indicate that oral DDAVP is a safe therapeutic agent that may be a good alternative treatment of central DI, particularly in patients who have chronic rhinitis and visual disturbances.

[Variants of the course of early noncomplicated postoperative period following excision of hypothalamo-hypophysial region tumors in children]. / Osnovnye varianty techeniia rannego neoslozhnennogo posleoperatsionnogo perioda posle udaleniia opukholei gipotalamo-gipofizarnoi oblasti u detei.

A study of non-specific and specific reactions in neurosurgical patients as conducted in the early postoperative period revealed three main variations of an early postoperative clinical course, i.e. with a normal stress-reaction, with a normal stress-reaction concomitant with diabetes insi pidus, and with a lower reactivity to surgical intervention. The treatment algorithms were appropriately amended (the preventive component was added) with due respect to the above circumstances.

Progressive decline of vasopressin secretion in familial autosomal dominant neurohypophyseal diabetes insipidus presenting a novel mutation in the vasopressin-neurophysin II gene.

OBJECTIVE: Familial autosomal dominant neurohypophyseal diabetes insipidus (FNDI) is a rare form of central diabetes insipidus (DI), which is caused by mutations in the vasopressin-neurophysin II (AVP-NPII) gene. The present study evaluated the AVP secretion over time and analysed the structure of the AVP-NPII gene in a Brazilian family with FNDI. SUBJECTS AND DESIGN: Four affected members and one nonaffected member from one Brazilian family with FNDI were studied. The diagnosis of central DI was established by fluid deprivation test and hypertonic saline infusion. Two affected members were assessed twice within a 6-year interval. For molecular analysis, genomic DNA was extracted and the AVP-NPII gene was amplified by polymerase chain reaction. RESULTS: The functional assessment of patients with FNDI over time confirmed a progressive loss in AVP secretion. Two patients were first diagnosed as partial central DI and, several years later, they developed severe central DI. Sequencing analysis revealed a heterozygous new point mutation in the nucleotide 1892 in the coding sequence for neurophysin-II of the AVP-NPII gene (1892G>C) predicting an amino acid substitution (A68P) in all affected members. CONCLUSION: Our data demonstrate a gradual vasopressinergic deficiency due to a novel mutation in the AVP-NPII gene in a Brazilian family with FNDI. The accumulation of A68P mutated precursor might have a cytotoxicity effect, leading to a gradual death of magnocellular neurones, and a progressive decline in AVP secretion.