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Introduction: Disturbances in plasma sodium levels are a major complication following recent resections of craniopharyngiomas in children. They must be properly managed to avoid neurological sequelae. We aimed to describe the variations and characteristics of postoperative natremia in children who had undergone a first craniopharyngioma resection with a particular focus on the frequency of triphasic syndrome in these patients., Methods: Paediatric patients with craniopharyngiomas who underwent a first surgical resection in the neurosurgery department of the Hôpital Femme Mère Enfant (Lyon, France) between January 2010 and September 2021 were included in the present study and the medical records were analysed retrospectively., Results: A total of 26 patients were included. Of these, 17 (65.4%) had a postoperative course characterised by the occurrence of both initial diabetes insipidus (DI) and hyponatremia a few days later. Eight patients (30.8%) presented then with isolated and persistent DI. Patients with the triphasic syndrome had a significantly higher grade of Puget classification on MRI (1 and 2), compared to the other patients., Conclusion: Dysnatremia is common after craniopharyngioma resections in children. This immediate postoperative complication is particularly difficult to manage and requires rapid diagnosis and prompt initiation of medical treatment to minimize fluctuations in sodium levels and avoid neurological sequelae., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Non-functioning pituitary adenomas (NFPAs) are often associated with hyperprolactinemia, which is known as the "stalk effect". However, the relationships between hyperprolactinemia and the radiographic characteristics of the tumor that affects the pituitary stalk have not been well characterized. We aimed to identify the differences in the clinical and radiographic characteristics of patients with NFPA, with and without hyperprolactinemia., Methods: We enrolled 107 patients with NFPA and allocated them to hyperprolactinemia and non-hyperprolactinemia groups using two different cut-off values: (1) the upper limit of the normal reference range, adjusted for sex and menopausal status, and (2) the upper quartile across the cohort, and compared their clinical and radiographic characteristics. These analyses were conducted to clarify the relationship between the "stalk effect" and the postoperative change in antidiuretic hormone secretion., Results: The specific radiographic characteristics of the patients included the presence of a cystic or hemorrhagic tumor and the presence of pituitary stalk deviation, which were more frequent in the patients with hyperprolactinemia. Interestingly, the incidence of postoperative transient diabetes insipidus was statistically significantly higher in the hyperprolactinemia group (≥40 ng/mL) and in the group with radiologic evidence of stalk deviation, which were shown to be independent risk factors on multivariate analysis., Conclusion: The presence of a "stalk effect" was associated with a higher risk of postoperative transient diabetes insipidus, reflecting perioperative pituitary stalk dysfunction following NFPA surgery, especially in patients with serum prolactin concentrations ≥40 ng/mL and radiologic evidence of stalk deviation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Traumatic neuroendocrine dysfunction may present with diabetes insipidus (DI) or with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both these pathologies involve a disturbance in the antidiuretic hormone (ADH) secretion, causing dysnatremias. Diagnosis of posttraumatic ADH dysfunction is hampered by technical difficulties in ADH assessment, and relies mostly on non-specific serum sodium, serum and urine osmolality and diuresis, often leading to misdiagnosis in the acute care setting. Research now focuses on the diagnostic role of copeptin, a peptide secreted together with ADH in an equimolar fashion, and which can be accurately evaluated. Recent studies identified cut-off values of 2.6 pmol/L for baseline copeptin and of 4.9 and 3.8 pmol/L for hypertonic saline infusion and arginine infusion stimulated copeptin, respectively, for the diagnosis of DI in patients with polyuria-polydipsia syndrome. Although SIADH is more difficult to be explored due to its heterogeneity, a ratio of copeptin to urinary sodium below 30 pmol/mmol identifies euvolemic hyponatremia. Exploring the role of copeptin assessment in patients with traumatic brain injury (TBI) in the acute phase may improve their diagnosis accuracy, management and outcome., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Central diabetes insipidus (DI) is a known complication following surgical resection of a suprasellar mass. There are limited data analyzing the outcomes of a standardized protocol for the management of postoperative DI in the pediatric population. We sought to fill this gap and hypothesized that utilizing a standardized protocol for fluid management (3-bag system) would reduce serum sodium fluctuations in the postoperative period after suprasellar surgery., Methods: A retrospective chart review was performed. Patients were identified with the following criteria: age ≤ 18 years, undergoing a surgical procedure for suprasellar mass that also had postoperative DI. The primary outcome was the variability in serum sodium during the first 48 h and between 48 and 120 h postoperatively., Results: There were 21 encounters pre-protocol and 22 encounters post-protocol for neurosurgical procedures. Use of the standardized protocol was associated with a lower range of sodium within 48 h postoperatively (p=0.065) and 83% lower odds of hypernatremia (Na>150 mmol/L) within 48 h postoperatively (CI 0.039-0.714) after controlling for age, gender, and prior DI diagnosis. History of DI conferred a lower risk of hypernatremia as well as less sodium fluctuation within 48 h postoperatively. Younger patients, those <9.7 years of age were associated with increased risk of hyponatremia and greater sodium fluctuations during the postoperative period., Conclusions: In patients with postoperative DI after suprasellar surgery, using a standardized protocol for fluid management (3-bag system) appears to reduce serum sodium variability in the first 48 h after surgery., (© 2021 Daniel Mak et al., published by De Gruyter, Berlin/Boston.)

This Review Article overviews the literature on diabetes insipidus (DI) associated with pregnancy and labor in Japan published from 1982 to 2019. The total number of patients collected was 361, however, only one-third of these cases had detailed pathophysiologic information enabling us to identify the respective etiology and subtype. Pregnancy-associated DI can be divided into 3 etiologies, central (neurogenic) DI, nephrogenic DI, and excess vasopressinase-associated DI. Neurogenic DI has various causes: for example, DI associated with tumoral lesions in the pituitary and neighboring area, DI associated with Sheehan's syndrome and/or pituitary apoplexy, and DI associated with lymphocytic infundibuloneurohypophysitis (LINH, stalkitis). Nephrogenic DI results from defective response of the kidney to normal levels of vasopressin. However, the most interesting causal factor of pregnancy-associated DI is excess vasopressinase, caused either by excess production of vasopressinase by the placenta or defective clearance of vasopressinase by the liver. Hepatic complications resulting in pregnancy-associated DI include acute fatty liver of pregnancy (AFLP) and HELLP syndrome (syndrome of hemolysis, elevated liver enzymes, low platelets), as well as pre-existing or co-incidental hepatic diseases. A possible role of glucose uptake in putative stress-induced DI and the importance of correct diagnosis and treatment of pregnancy-associated DI, including use of 1-deamino 8-D arginine vasopressin, are also discussed.

The two main differential diagnoses of central diabetes insipidus are nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between those entities is essential as treatment differs substantially with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the indirect water deprivation test had several pitfalls, resulting in a low diagnostic accuracy. With the introduction of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of diabetes insipidus was new evaluated. While unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, a stimulation test is needed to differentiate patients with central diabetes insipidus from patients with primary polydipsia. Stimulation can either be achieved through hypertonic saline infusion or arginine infusion. While the former showed high diagnostic accuracy and superiority over the indirect water deprivation test in a recent validation study, the diagnostic accuracy for arginine-stimulated copeptin was slightly lower, but superior in test tolerance. In summary of the recent findings, a new copeptin based diagnostic algorithm is proposed for the reliable diagnosis of diabetes insipidus., Competing Interests: Declaration of Competing interest The author reports no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Diagnosis and treatment of dysnatremia is challenging and further complicated by the pitfalls of different sodium measurement methods. Routinely used sodium measurements are the indirect (plasma/serum) and direct (whole blood) ion-selective electrode (ISE) method, showing discrepant results especially in the setting of acute illness. Few clinicians are aware of the differences between the methods in clinically stable patients or healthy volunteers., Methods: Data of 140 patients and 91 healthy volunteers undergoing osmotic stimulation with hypertonic saline infusion were analyzed. Sodium levels were measured simultaneously by indirect and direct ISE method before and at different time points during osmotic stimulation up to a sodium threshold of ≥150 mmol/L. The primary outcome was the difference in sodium levels between the indirect and direct ISE method., Results: 878 sodium measurements were analyzed. Mean (s.d.) sodium levels ranged from 141 mmol/L (2.9) to 151 mmol/L (2.1) by the indirect ISE compared to 140 mmol/L (3) to 149 mmol/L (2.8) by the direct ISE method. The interclass correlation coefficient between the two methods was 0.844 (95% CI: 0.823-0.863). On average, measurements by the indirect ISE were 1.9 mmol/L (95% CI limits: -3.2 to 6.9) higher than those by the direct ISE method (P < 0.001). The tendency of the indirect ISE method resulting in higher levels increased with increasing sodium levels., Conclusion: Intra-individual sodium levels differ significantly between the indirect and direct ISE method also in the absence of acute illness. It is therefore crucial to adhere to the same method in critical situations to avoid false decisions due to measurement differences.

Context: Oxytocin (OT) and vasopressin share anatomical pathways of synthesis and secretion, and patients with central diabetes insipidus (CDI) presumably are at risk for OT deficiency. However, an OT-deficient state in hypopituitary patients has not been established., Objectives: We hypothesized that men with CDI compared to patients with similar anterior pituitary deficiencies (APD) but no CDI and healthy controls (HC) of similar age and body mass index, would have lower plasma OT levels, associated with increased psychopathology., Design: Cross-sectional., Setting: Clinical research center., Participants: Sixty-two men (20 CDI, 20 APD, 22 HC), age 18 to 60 years., Interventions: Frequent sampling of blood every 5 minutes for OT over 1 hour and validated questionnaires to assess psychopathology., Main Outcomes: Pooled plasma OT levels; depressive, anxiety, and alexithymia symptoms; and quality of life., Results: The mean 1-hour pool of fasting OT levels was lower in CDI compared with APD and HC (P = 0.02 and P = 0.009, respectively), with no differences between APD and HC (P = 0.78). Symptoms of depression, anxiety, and alexithymia were more pronounced in CDI than in HC (P = 0.001, P = 0.004, and P = 0.02, respectively). Although CDI and APD reported worse physical health compared with HC (P = 0.001 and P = 0.005) with no differences between APD and CDI, only CDI reported worse mental health compared with HC (P = 0.009)., Conclusions: We have demonstrated low plasma OT levels and increased psychopathology in hypopituitary men with CDI, suggestive of a possible OT-deficient state. Larger studies of both sexes are required to confirm these findings and clinically characterize hypopituitary patients with OT deficiency., (Copyright © 2019 Endocrine Society.)

Copeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for copeptin are similar to AVP, that is an increase in osmolality and a decrease in arterial blood volume and pressure. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation. Copeptin has, therefore, been evaluated as diagnostic biomarker in vasopressin-dependent disorders of body fluid homeostasis. Disorders of body fluid homeostasis are common and can be divided into hyper- and hypoosmolar circumstances: the classical hyperosmolar disorder is diabetes insipidus, while the most common hypoosmolar disorder is the syndrome of inappropriate antidiuresis (SIAD). Copeptin measurement has led to a "revival" of the direct test in the differential diagnosis of diabetes insipidus. Baseline copeptin levels, without prior thirsting, unequivocally identify patients with nephrogenic diabetes insipidus. In contrast, for the difficult differentiation between central diabetes insipidus and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is clearly superior to the classical water deprivation test. On the contrary, in the SIAD, copeptin measurement is of only little diagnostic value. Copeptin levels widely overlap in patients with hyponatraemia and emphasize the heterogeneity of the disease. Additionally, a variety of factors lead to unspecific copeptin elevations in the acute setting further complicating its interpretation. The broad use of copeptin as diagnostic marker in hyponatraemia and specifically to detect cancer-related disease in SIADH patients can, therefore, not be recommended., (© 2019 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.)

Purpose: Oxytocin is a hypothalamus derived, posterior pituitary stored nonapeptide which has gained recent interest as an important neuropsychiatric and metabolic hormone beyond its classic role in lactation and parturition. Hypopituitarism is a heterogenous disorder of derangement in one or more anterior or posterior pituitary hormones. Diagnosis of deficiency and hormone replacement exists to address all relevant axes except for oxytocin. Our study aims to define derangements in oxytocin in a unique population of patients with hypopituitarism and correlate levels with measures of emotional health and quality of life., Methods: A cross-sectional, single day study was completed to measure plasma oxytocin levels in a diverse population of patients with hypopituitarism compared to controls. Subjects also completed depression, quality of life and stress-related questionnaires, and emotion recognition tasks., Results: Thirty-eight subjects completed the study, 18 with hypopituitarism (9 with diabetes insipidus) and 20 controls. After controlling for differences in age, weight and gender, plasma oxytocin levels were highest in subjects with diabetes insipidus compared to control [mean, IQR: 44.3 pg/ml (29.8-78.2) vs. 20.6 (17-31.3), p = 0.032]. Amongst hypopituitary subjects, those with duration of disease greater than 1 year had higher oxytocin levels. No significant differences were observed for psychosocial measures including emotion recognition tasks., Conclusions: Plasma oxytocin levels were found higher in patients with hypopituitarism compared to controls and highest in those with diabetes insipidus. Longer duration of hypopituitarism was also associated with higher plasma levels of oxytocin. Further study is needed to better define oxytocin deficiency and investigate response to treatment.

Background: The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin., Methods: From 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked., Results: A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test., Conclusions: The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .).

Introduction: Diabetes insipidus is characterized by hypoosmotic polyuria related to deficiency of arginine-vasopressin (AVP) secretion (central diabetes insipidus, CDI) or renal insensitivity to AVP (nephrogenic diabetes insipidus, NDI). The water deprivation test with assessment of AVP activity is currently the gold standard for differential diagnosis in patients presenting polyuria-polydipsia syndrome. Nevertheless, it can be dangerous without proper surveillance and its interpretation may be challenging. Other markers have been suggested. Direct quantification of circulating AVP is not sufficient for diagnosis: vasopressin is unstable, analysis is complex. AVP comes from prohormone preprovasopressin with concomitant release of copeptin (C-terminal moiety) in the equimolar ratio. Copeptin is stable in vitro, with easy and rapid measurement (<4h). Past studies have shown greater sensitivity and specificity of copeptin versus AVP to discriminate etiologies of polyuria in adults, but its value has not been demonstrated in infants yet., Observation: A 7-month-old infant presented polyuria-polydipsia syndrome with poor weight gain. Laboratory tests pointed out hypernatremia (170mmol/L) and blood hyperosmolarity (330mOsm/L) with inappropriate urinary hypoosmolarity (168mOsm/L). Plasmatic copeptin measurement was found at a very high level, 303pmol/L (1-14pmol/L). DdAVP administration did not improve the polyuria, confirming the final diagnosis of NDI. Hyperhydration with a hypoosmolar diet normalized the hydration status and circulating levels of copeptin within 1 week., Conclusion: Copeptin, a stable peptide reflecting AVP secretion, could be a safer and faster biomarker for etiological diagnosis of polyuria-polydipsia syndrome in children. Before regularization of hydration status, a single baseline measurement may be enough to discriminate NDI from other etiologies without the water deprivation test., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Diabetes insipidus (DI) and primary polydipsia (PP) are characterised by polyuria and polydipsia. It is crucial to differentiate between these two disorders since the treatment is different. The aim of this study was to evaluate the diagnostic value of the short and an extended variant of the water deprivation test (WDT) and of measuring urinary vasopressin (AVP) in patients with polyuria and polydipsia., Design: A retrospective, single-centre study based on WDTs performed between 2004 and 2014 including 104 consecutive patients with the polyuria-polydipsia syndrome. During a strict water deprivation, weight, urinary osmolality, urinary vasopressin and specific gravity were collected until one of the following was reached: i) >3% weight reduction, ii) Urinary specific gravity >1.020 or, urinary osmolality >800 mOsm/L, iii) Intolerable adverse symptoms such as excessive thirst., Results: Out of 104 patients (67 women, 37 men), 21 (20%) were diagnosed with DI and 83 (80%) with PP. The median (interquartile range; range) test duration was 14 hours (10-16; 3-36) in patients with DI and 18 hours (14-24; 7-48) in patients with PP (P=0.011). Of those diagnosed with PP, 22 (26%) did not reach urinary specific gravity >1.020 nor urine osmolality >800 mOsm/L. Urine AVP did not overlap between patients with PP and patients with central DI., Conclusions: The short WDT is of limited value in the diagnostic work-up of polydipsia and polyuria and a partial DI may have been missed in every fourth patient diagnosed with PP. Urinary AVP has excellent potential in discriminating PP from central DI.

Introduction: Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable., Objective: To identify clinical and radiological findings associated with response to glucocorticoids., Design and Methods: 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months)., Results: MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all., Conclusions: Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids., (© 2017 European Society of Endocrinology.)

Purpose: IgG4-related hypophysitis is a rare disease, with only 34 cases published in English (2015). Available short reviews may not present complete details of IgG4-related hypophysitis. We aimed to survey case reports of IgG4-related hypophysitis, including abstracts of scientific meetings, in English and Japanese., Methods: We searched for information about IgG4-related hypophysitis in PubMed and Igakuchuozasshi (Japan Medical Abstracts Society). Among 104 case reports found, we reviewed 84 fulfilling Leporati's diagnostic criteria., Results: The mean ±  SD age of onset was 64.2  ±  13.9, 67.5  ±  9.8, and 56.4  ±  18.6 years for all subjects, men, and women, respectively. Men:women was 2.4:1. On magnetic resonance imaging, pituitary, stalk, and pituitary-stalk mass were observed at frequencies of 14.3, 21.4, and 64.3%, respectively. Manifestations were anterior hypopituitarism in 26.2% (22 cases), central diabetes insipidus in 17.9% (15 cases), and panhypopituitarism in 52.4% (44 cases). The median level of serum IgG4 was 264.5 mg/dL for all subjects, 405 mg/dL for men, and 226 mg/dL for women. The mean number of IgG4-related systemic diseases was 2.7  ±  1.5 in all subjects, 3.0  ±  1.5 in men, and 1.8  ±  1.1 in women. Among the IgG4-related diseases, retroperitoneal fibrosis was the most frequent (26.2%), followed by salivary gland diseases (25%). Glucocorticoid therapy was generally effective, except for two cases that received replacement doses. There were significant differences between sexes in terms of age, serum IgG4 levels, and number of IgG4-related diseases., Conclusion: IgG4-related hypophysitis may have different clinical characteristics between genders. This survey may lack some information because the Japanese abstracts did not contain certain details.

Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis. Central diabetes insipidus (CDI) is the most frequent endocrine manifestation and is a known risk factor for the development of further anterior pituitary hormone deficiencies (APD). However, not all CDI patients develop APD, as observed during prolonged periods of follow-up., Aim: To find predictors of developing APD in LCH children with CDI followed in our institution., Methods: We retrospectively analysed 44 patients over a median period (quartiles) of 12.3 years (8.79-14.24). Patients were subdivided into group 1 and group 2, according to absence or presence of APD, respectively. The main variables studied were: (1) chronological age (CA) at LCH diagnosis, (2) the primary site of LCH at diagnosis: low risk (LR) and multisystemic risk organs, and (3) the presence of reactivation., Results: Multivariate Cox regression analysis showed that APD was positively associated with CA at LCH diagnosis [relative risk (RR) 1.14, p < 0.01], the LR clinical form (RR 8.6, p < 0.03), and negatively associated with the presence of reactivations (RR 0.3, p < 0.01)., Conclusions: Patients with older CA at LCH diagnosis, LR clinical forms, and fewer reactivation episodes might represent a subgroup of paediatric LCH CDI patients with a higher risk of developing APD., (© 2016 S. Karger AG, Basel.)

Adipsic diabetes insipidus (ADI) is an extremely rare complication following microsurgical clipping of anterior communicating artery aneurysm (ACoA) and left middle cerebral artery (MCA) aneurysm. It poses a significant challenge to manage due to an absent thirst response and the co-existence of cognitive impairment in our patient. Recovery from adipsic DI has hitherto been reported only once. A 52-year-old man with previous history of clipping of left posterior communicating artery aneurysm 20 years prior underwent microsurgical clipping of ACoA and left MCA aneurysms without any intraoperative complications. Shortly after surgery, he developed clear features of ADI with adipsic severe hypernatraemia and hypotonic polyuria, which was associated with cognitive impairment that was confirmed with biochemical investigations and cognitive assessments. He was treated with DDAVP along with a strict intake of oral fluids at scheduled times to maintain eunatremia. Repeat assessment at six months showed recovery of thirst and a normal water deprivation test. Management of ADI with cognitive impairment is complex and requires a multidisciplinary approach. Recovery from ADI is very rare, and this is only the second report of recovery in this particular clinical setting.

Context: Apelin and arginine vasopressin are antagonists in the regulation of body fluid and osmotic homeostasis. There are no data about apelin levels in patients with polyuria-polydipsia syndrome (PPS)., Objective: To investigate plasma apelin levels and plasma apelin to copeptin ratios in patients with PPS and healthy volunteers using copeptin as a surrogate marker for arginine vasopressin., Design, Participants, and Setting: We included 41 patients with PPS in this post hoc analysis of a prospective study performed in tertiary care hospitals in Switzerland and Germany and 113 healthy volunteers as a control group., Outcome Measures: Plasma apelin and copeptin levels were measured in 15 patients with complete central diabetes insipidus (DI), seven patients with complete nephrogenic DI, 19 patients with primary polydipsia (PP), and 113 healthy volunteers., Results: Plasma apelin levels were highest in patients with complete nephrogenic DI (413 pmol/L; interquartile range, 332-504 pmol/L; P = .01) and lower in patients with PP (190 [172-215] pmol/L; P < .001) or complete central DI (209 [174-241] pmol/L; P = .02) as compared to healthy volunteers (254 [225-311] pmol/L). Plasma apelin to copeptin ratio in patients with PP (53 [38-92] pmol/pmol; P > .9) was similar to healthy volunteers (57 [37-102] pmol/pmol). In contrast, the apelin to copeptin ratio was higher in patients with complete central DI (89 [73-135] pmol/pmol; P = .02) and lower in patients with complete nephrogenic DI (7 [6-10] pmol/pmol; P < .001) compared to healthy volunteers., Conclusion: In PP, normal plasma apelin to copeptin ratio attests a normal water homeostasis. In contrast, in patients with central or nephrogenic DI, the increased or decreased apelin to copeptin ratio, respectively, reflects a disturbed osmotic and body fluid homeostasis.

Copeptin is a 39-amino-acids containing glycosylated peptide derived from the C-terminal part of the arginine vasopressin (AVP) precursor. In the process of proteolysis the AVP precursor is processed to AVP, neurophysin II, and copeptin in equimolar amounts. In contrast to AVP, copeptin remains stable for several days at room temperature in serum or plasma. Hence, copeptin serves as a bona fide biomarker of AVP release. We briefly summarise clinical utility of copeptin in the diagnosis of diabetes insipidus. We also discuss potential applications of copeptin measurements in hyponatraemic states, assessment of an anterior pituitary function, as well as a wide range of several acute and chronic medical conditions, such as myocardial infarction, stroke or diabetes mellitus., (© Georg Thieme Verlag KG Stuttgart · New York.)

Context and Objective: Patients with cranial diabetes insipidus (CDI) are at risk of developing both hypernatraemia and hyponatraemia, due to the condition itself or secondary to treatment with vasopressin-analogues or during administration of i.v. fluids. We aimed to assess the frequency and impact of dysnatraemias in the inpatient (INPT) and outpatient (OPT) setting in desmopressin-treated CDI, comparing those with normal thirst with those with abnormal thirst., Design: The study included 192 patients with cranial diabetes, who were identified from the Beaumont Pituitary Database, a tertiary referral centre. Retrospective case note audit was performed and the clinical and biochemical information of 147 patients with CDI were available for analysis., Results: A total of 4142 plasma sodium measurements for 137 patients with normal thirst, and 385 plasma sodium measurements for ten patients with abnormal thirst were analysed. In those with normal thirst, the most common OPT abnormality was mild hyponatraemia (pNa(+) 131-134  mmol/l) in 27%, while 14.6% had more significant hyponatraemia (pNa(+) ≤130  mmol/l). Of those patients with normal thirst, 5.8% were admitted due to complications directly related to hyponatraemia. Compared with patients with normal thirst, those with abnormal thirst were more likely to develop significant OPT hypernatraemia (20% vs 1.4%, P=0.02) and significant INPT hyponatraemia (50% vs 11.1%, P 0.02)., Conclusion: OPT management of CDI is complicated by a significant incidence of hyponatraemia. In contrast, OPT hypernatraemia is almost exclusively a complication seen in adipsic CDI, who also had more frequent INPT hyponatraemia. CDI associated with thirst disorder requires increased physician attention and patient awareness of potential complications., (© 2015 European Society of Endocrinology.)

Adipsic diabetes insipidus (ADI) is a rare disorder. It can occur after transcranial surgery for craniopharyngeoma, suprasellar pituitary adenoma and anterior communicating artery aneurysm but also with head injury, toluene exposure and developmental disorders. It is often associated with significant hypothalamic dysfunction and complications like obesity, sleep apnea, thermoregulatory disorders, seizures and venous thromboembolism (VTE). Morbidity and mortality data have been reported as single case reports with only one large series suggesting increased risk for VTE in patients with ADI. Here we report a mini-series of four patients with ADI and VTE. Post-surgery immobilization, obesity, infection, with prolonged hospitalization, hemoconcentration and changes in coagulation which might be induced by inadequate hormone treatment in the postoperative period (high doses of glucocorticoids, sex steroids and DDAVP replacement) may all contribute to the pathogenesis of VTE. Thromboprophylactic treatment after pituitary surgery and during episodes of hypernatremia is therefore warranted.

Objective: Lithium continues to be an important mood disorder treatment. Although patients exposed to higher environmental temperatures may have serum lithium level elevations due to dehydration, there is conflicting data in the literature. In addition, no study has assessed the association between temperature and other renal laboratory tests and symptoms in lithium users., Methods: This is a cross-sectional analysis of 63 current lithium users who participated in the McGill Geriatric Lithium-induced Diabetes Insipidus Clinical Study. The relationship between mean daily temperature with diabetes insipidus symptoms, glomerular filtration rate, urine osmolality, serum sodium, lithium level, and lithium dose-level ratio was assessed., Results: Although a higher temperature on the day of laboratory testing trended toward being independently associated with a lower lithium dose-level ratio (Beta = -0.17, p = 0.08), this was not found when using a dichotomous measure of temperature (T > 20°C). No association was observed between temperature and other renal parameters., Conclusions: The association of temperature with lithium levels, renal symptoms, and laboratory tests appears to be of relatively little clinical importance in lithium users in temperate climates. However, future research should re-examine patients living in climates with extreme temperatures (e.g., >40°C), who may theoretically be at higher risk., (Copyright © 2014 John Wiley & Sons, Ltd.)

Cerebral salt wasting syndrome (CSW-cerebral salt wasting) was first described in 1950 by Peters. This syndrome can occur in patients who have sustained damage to the central nervous system (e.g. patients with subarachnoid bleeding, bacterial meningitis or after neurosurgery). Patients present with excessive natriuresis and hyponatremic dehydration. Differentiating this syndrome with the syndrome of inappropriate antidiuretic hormone secretion (SIADH-syndrome of inappropriate antidiuretic hormone secretion), which may occur in the same group of patients, is necessary in order to administer the correct treatment which consists of fluid restriction and sodium replacement in SIADH and fluid and sodium replacement as well as occasional mineralocorticoid therapy in CSW.

Context: Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual., Case Presentation: This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks., Objective: The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream., Methods and Results: Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP., Conclusions: Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

Background: A 29-year-old man was referred to a multidisciplinary pituitary clinic with a 3.5-year history of central diabetes insipidus, initially presumed to be idiopathic based on a normal MRI scan of the pituitary gland. Subsequent scanning revealed a suprasellar mass, which demonstrated progressive enlargement on serial imaging. He also developed hypogonadotropic hypogonadism., Investigations: Measurement of levels of serum morning fasting cortisol, adrenocorticotropic hormone, total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, insulin-like growth factor 1, TSH and free T(4), MRI of the pituitary gland and a transsphenoidal biopsy of a pituitary mass were performed., Diagnosis: Lymphocytic hypophysitis presenting with diabetes insipidus, with development of hypogonadotropic hypogonadism and a suprasellar mass., Management: The patient was treated with intranasal desmopressin and transdermal testosterone. The underlying lymphocytic hypophysitis was initially managed conservatively with serial MRI and visual field testing. No immunosuppressant medication was given and, aside from the diagnostic transsphenoidal biopsy, no surgical intervention was required. He subsequently developed secondary hypothyroidism, secondary adrenal insufficiency and growth hormone deficiency. These disorders were managed with levothyroxine and prednisone.

Vasopressin, a peptide hormone functioning also as a neurotransmitter, neuromodulator and regulator of the stress response is considered to be one of the factors related to the development and course of depression. In the present study, we have tested the hypothesis that congenital deficit of vasopressin in Brattleboro rats leads to attenuated depression-like behavior in tests modeling different symptoms of depression. In addition, hypothalamic-pituitary-adrenocortical axis activity was investigated. Vasopressin deficient rats showed signs of attenuated depression-like behavior in forced swimming and sucrose preference tests, while their behavior on elevated plus maze was unchanged. Vasopressin deficiency had no influence on basal levels of ACTH and corticosterone and had only mild impact on hormonal activation in response to forced swimming and plus-maze exposure. However, vasopressin deficient animals showed higher level of dexamethasone induced suppression of corticosterone response to restraint stress and higher basal levels of corticotropin-releasing hormone mRNA in the hypothalamic paraventricular nucleus. In conclusion, present data obtained in vasopressin deficient rats show that vasopressin is involved in the development of depression-like behavior, in particular of the coping style and anhedonia. Moreover, behavioral and endocrine responses were found to be dissociated. We suggest that brain vasopressinergic circuits distinct from those regulating the HPA axis are involved in generating depression-like behavior.

Purpose: Gestational diabetes insipidus (GDI) is a rare endocrinopathy complicating about 4:100,000 deliveries. We present the case of a preterm parturient with GDI and severe hypernatremia (serum sodium concentration = 174 mmol.L(-1)) presenting for an urgent Cesarean section., Clinical Features: Fluid resuscitation and desmopressin supplementation partially corrected the patient's homeostasis, allowing us to carefully titrate epidural anesthesia for an urgent Cesarean section. After delivery, the patient was transferred to the intensive care unit. The serum sodium concentration of the mother and the neonate was normalized over 48 hr and three days respectively., Conclusion: The careful perioperative management of GDI led to a favourable outcome of the mother and fetus.

We report on a 19 year old patient with clinical signs of hypogonadism (small testicles, missing pollutions and diminished beard growth) despite of normal testosterone levels. Further diagnostic procedures revealed panhypopituitarism with insufficiency of the gonadotrope, somatotrope and corticotrope axis due to a beta-HCG-producing suprasellar germinoma with intracerebral metastases. Paraneoplastic production of beta-HCG resulted in sufficient stimulation of Leydig cells with normal production of testosterone, which had partly masked clinical symptoms of gonatrope insufficiency. The patient was treated by combined radiochemotherapy and is in remission since 7 years.

Objective: In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed., Design: Diabetes insipidus was determined by either standard criteria for diagnosis in the immediate postoperative period, or by water deprivation test, in all craniopharyngioma and pituitary tumour patients who underwent surgery in Beaumont Hospital between the years 1986 and 1998. Osmoregulated thirst and vasopressin release were studied during a 2-h infusion of hypertonic (5%) saline followed by a 30-min period of free access to water., Patients: Data on the incidence of postoperative diabetes insipidus was collected in 26 patients with craniopharyngioma and 154 patients with pituitary adenomata. We recruited 16 healthy control patients, 16 patients with cranial diabetes insipidus following pituitary tumour surgery and 16 patients with cranial diabetes insipidus following craniopharyngioma resection for the hypertonic saline infusion study., Results: Twenty-five patients out of 26 (96%) patients developed diabetes insipidus after surgery for craniopharyngioma, a much higher incidence than after surgery for suprasellar (26/88, 30%, P < 0.001) or intrasellar pituitary tumours (9/66, 14%, P < 0.001). Hypertonic saline infusion identified abnormal thirst responses in five of the 16 craniopharygioma patients studied; all of the pituitary tumour patients had a normal thirst response. Three of the craniopharyngioma patients had adipsic diabetes insipidus whilst two had polydipsic diabetes insipidus., Conclusion: This study demonstrates following surgery for craniopharyngioma there is a high incidence of cranial diabetes insipidus and a significant incidence of abnormal thirst responses to osmotic stimuli.

A 63-year-old African-American woman was admitted to the hospital with urosepsis and altered mental status. She had a history of schizophrenia and was treated with olanzapine 5 mg/day and lithium carbonate 300 mg 3 times/day. During her hospital stay, her sodium level and serum osmolality increased and her urine osmolality decreased, whereas her lithium levels remained within normal limits. Based on these findings, the patient was diagnosed with diabetes insipidus secondary to lithium therapy and was treated successfully with amiloride. Clinicians have been aware of lithium toxicity for many years and traditionally have administered thiazide diuretics for lithium-induced polyuria and nephrogenic diabetes insipidus. Recently, amiloride, a potassium-sparing diuretic, has been reported as a successful treatment for nephrogenic diabetes insipidus.

A 38-year-old man presented with headache, fever, and double vision associated with right abducens nerve paresis. He had neither nuchal rigidity nor visual field defect. Laboratory data revealed elevated erythrocyte sedimentation rate (ESR), eosinophilia, and lymphocytic pleocytosis in the cerebrospinal fluid (CSF). Provocation tests of pituitary hormones showed partial hypopituitarism. Magnetic resonance imaging (MRI) revealed swelling of the hypophysis and a mass lesion expanding into the right cavernous sinus. The supplement dose of dexamethasone for hypothalamic hypocortisolism manifested diabetes insipidus. Biopsy, carried out through the transsphenoidal approach, revealed giant cell granuloma. Systemic granulomatous diseases were ruled out, and the lesion was considered to be idiopathic giant cell granulomatous hypophysitis. Right abducens nerve paresis, diabetes insipidus and dysfunction of the anterior lobe were amended by the treatment with prednisolone for 4 months, and findings of the pituitary gland and stalk were normalized. The present case shows that glucocorticoid has an effect on amendment of idiopathic giant cell granulomatous hypophysitis.

Objective: To re-examine the controversial possibility that prolactin exerts renal effects, using recombinant mouse prolactin (rmP), in the presence and absence of circulating vasopressin., Design: In experiment 1, the renal effects of rmP were examined in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) lacking circulating vasopressin and normal animals of the parent Long Evans (LE) strain. In experiment 2, salt and water excretion were studied in fluid-loaded normal Sprague-Dawley (SD) rats, some of which received rmP., Methods: In experiment 1, BDI and LE rats maintained in fluid balance were infused i.v. with each of three concentrations of rmP (10, 20 and 40 microg/ml per h) or maintained on 150 mmol/l NaCl vehicle (controls). In experiment 2, the SD rats were infused with 75 mmol/l NaCl in order to induce a state of diuresis comparable to that of BDI rats, some of them then receiving the rmP i.v., Results: A profound rmP-induced dose-dependent decrease in urine excretion (P<0.005) and a lesser decrease in sodium excretion in the BDI rats was in marked contrast with the small but significant increase in urine excretion in the LE rats compared with controls (P<0.025). The rmP-infused fluid-loaded SD rats also demonstrated a significant (P<0.05) dose-related antidiuresis compared with the control animals, in addition to a decrease in sodium excretion., Conclusions: These results show that prolactin has a profound antidiuretic effect in the absence of circulating vasopressin. In contrast, when vasopressin is present in the circulation rmP has a small, but opposite, diuretic effect. Thus the use of a recombinant prolactin has provided evidence for renal effects of this hormone which are modified in the presence of the circulating neurohypophysial hormone vasopressin.

Introduction: Langerhans' cell histiocytosis is a rare disorder of unknown etiology characterized by a wide clinical spectrum and varied behavior. Diabetes insipidus is a relatively common feature in Langerhans' cell histiocytosis. The presence of both diabetes insipidus and mellitus associated with histiocytosis in an adult is rare. To our knowledge, only three previous cases have been reported., Exegesis: We report the clinical presentation, pathologic findings and clinical progress in an adult female who had disseminated Langerhans' cell histiocytosis (hypothalamic infiltration, multifocal bone involvement) associated with both diabetes insipidus and mellitus., Conclusion: The pathogenesis of diabetes mellitus in such an association will be discussed.

A 43-year-old man, with a history of central diabetes insipidus diagnosed 3 years previously, complained about reduced libido. An MRI scan showed a suprasellar lesion just below the supraoptic recess of the third ventricle. A stereotactically guided biopsy revealed fibrous glia, but no other specific tissue and no inflammatory cells. Two months later the patient presented with fatigue and muscular weakness. Tertiary adrenal failure and hypothyroidism were diagnosed by endocrine function tests and therapy with levothyroxine and hydrocortisone was started. Another 2 months later the patient was admitted with giddiness, nausea, peripheral oedema and oliguria. Radiological imaging and an open transperitoneal kidney exploration showed severe fibrosis around both ureters. Histological examination confirmed the diagnosis of idiopathic retroperitoneal fibrosis. Presumably the suprasellar tumour was the first manifestation of retroperitoneal fibrosis. Once the diagnosis 'idiopathic retroperitoneal fibrosis' is confirmed, fibrotic manifestations and complications involving extra-retroperitoneal tissues including the endocrine system, should be sought.

Pituitary apoplexy in a 38-year-old male patient with acromegaly who presented with pericardial effusion, anterior pituitary dysfunction, and diabetes insipidus is described. With corticosteroid therapy, there was good initial recovery of pituitary function and regression of pericardial effusion. On withdrawal of corticosteroids, he developed painless thyroiditis, with transient thyrotoxicosis. Subsequently, the pituitary function tests remained normal for a year, but later he gradually developed hypogonadotropic hypogonadism, hypocortisolism, growth hormone deficiency, and progressive pituitary atrophy, resulting in empty sella syndrome.

Leptin is known to regulate food intake and energy expenditure. Moreover, recent studies in rodents have shown that leptin in high doses decreases urine osmolality and increases water intake, together with renal sodium and water excretion. Since it is not clear whether leptin is involved in either the pathogenesis or in resulting metabolic abnormalities in diabetes insipidus, we measured leptin levels in 16 male patients with idiopathic central diabetes insipidus (DI) in comparison to a group of age- and BMI-matched male control subjects (no.=30). We found that plasma leptin concentration did not differ between patients with DI (4.45+/-3.24 microg/l) and healthy control group (3.69+/-2.81 microg/l; t test, p=0.41). Urine osmolality, plasma osmolality and urine volume of the patients with DI was not correlated to leptin. However, leptin was positively associated with body mass index (r=0.67; p=0.005). We conclude that leptin plasma concentrations are unchanged in diabetes insipidus. Furthermore, the lack of correlation between plasma leptin and urine osmolality, plasma osmolality or urine volume suggests that ADH deficiency does not have any impact on the plasma leptin levels.

We present here a case of prominent hypercalcemia accompanied by hypothalamic tumor and Graves' disease. A 24-year-old man with hypothalamic tumor showed hypopituitarism, central diabetes inspidus (DI) and hyperthyroidism. Nausea, loss of thirst and appetite, and general fatigue were found with the unveiling of hypercalcemia and hypernatremia. Parathyroid hormone (PTH) and 1alpha-dihydroxyvitamin D levels were suppressed with a normal range of PTH-related protein values. One-desamino-(8-D-arginine)-vasopressin (DDAVP) and half-saline administration normalized hypernatremia, while hypercalcemia was still sustained. Administration of cortisone acetate and thiamazole reduced the elevated serum Ca level. In the present case, concurrent hyperthyroidism was assumed to accelerate skeletal mobilization of calcium into the circulation. Hypocortisolism and central DI was also considered to contribute, to some extent, to the hypercalcemia through renal handling of Ca.

Angiotensin produced systemically or locally in tissues such as the brain plays an important role in the regulation of blood pressure and in the development of hypertension. We have established transgenic rats [TGR(ASrAOGEN)] expressing an antisense RNA against angiotensinogen mRNA specifically in the brain. In these animals, the brain angiotensinogen level is reduced by more than 90% and the drinking response to intracerebroventricular renin infusions is decreased markedly compared with control rats. Blood pressure of transgenic rats is lowered by 8 mmHg (1 mmHg = 133 Pa) compared with control rats. Crossbreeding of TGR(ASrAOGEN) with a hypertensive transgenic rat strain exhibiting elevated angiotensin II levels in tissues results in a marked attenuation of the hypertensive phenotype. Moreover, TGR(ASrAOGEN) exhibit a diabetes insipidus-like syndrome producing an increased amount of urine with decreased osmolarity. The observed reduction in plasma vasopressin by 35% may mediate these phenotypes of TGR(ASrAOGEN). This new animal model presenting long-term and tissue-specific down-regulation of angiotensinogen corroborates the functional significance of local angiotensin production in the brain for the central regulation of blood pressure and for the pathogenesis of hypertension.

A 20-year-old Japanese man with a hypothalamic tumor (most likely germ-cell tumor) which caused secondary hypoadrenalism, hypogonadism and diabetes insipidus developed hypercalcemia and acute renal failure. The serum levels of intact PTH (iPTH), PTH-related protein (PTH-rP), 1,25-dihydroxy vitamin D (1,25- (OH)2 D), ACTH, cortisol, gonadotropins and testosterone were decreased, but his serum levels of triiodothyronine (T3) and thyroxine (T4) were within the normal range at admission, with depressed TSH and slightly increased thyroglobulin. The hypercalcemia was refractory to extensive hydration and calcitonin, but was ameliorated by pamidronate. After irradiation of the hypothalamic tumor, panhypopituitarism gradually developed. The patient has been normocalcemic for the last 2 years and is doing well under replacement therapy with glucocorticoid, L-thyroxine, methyltestosterone and 1-desamino D arginine vasopressin (dDAVP). As to the mechanism of euthyroidism at admission, transient destructive thyroiditis associated with hypopituitarism or delayed development of hypothyroidism following the hypoadrenalism was suggested. This is the first reported case of hypercalcemia in secondary hypoadrenalism due to hypothalamic tumor. Hypercalcemia was most likely induced by increased bone resorption, which was probably elicited by the combined effects of deficient glucocorticoid and sufficient thyroid hormones in addition to hypovolemia and reduced renal calcium excretion. Furthermore, severe dehydration due to diabetes insipidus and disturbance of thirst sensation caused by the hypothalamic tumor aggravated the hypercalcemia, leading to acute renal failure.

Indices of carbohydrate and lipid metabolism were investigated in male New Zealand genetically hypertensive and normotensive rats. Cross-breeding of male rats of these strains with female Brattleboro diabetes insipidus rats also provided the opportunity to examine the metabolic impact of vasopressin and its deficiency in hypertensive and normotensive rats. Hypertensive and normotensive rats, with or without diabetes insipidus, were fasted for 24 h, exsanguinated and their blood/plasma analysed for various indices of carbohydrate and lipid metabolism. Whilst each group of rats maintained fasted normoglycemia, hypertensive rats, with or without vasopressin-deficiency, were hypoinsulinaemic relative to normotensive counterparts. Moreover, hypertensive or normotensive vasopressin-deficient rats were hypoinsulinaemic relative to vasopressin-replete counterparts. In vasopressin-replete rats, the apparently improved insulin sensitivity in hypertension was associated with significant falls in plasma glucagon, triglycerides and total cholesterol. Finally, normotensive vasopressin-deficient rats were hypoglucagonaemic relative to the vasopressin-replete group. These data demonstrate that independent of vasopressin status, hypertension in the New Zealand strain and the diabetes insipidus hybrid was associated with improved insulin sensitivity. However, endogenous vasopressin exercises an influential role in carbohydrate and lipid metabolism in normotensive rats.

We encountered a pregnant woman with transient diabetes insipidus which developed during the third trimester. A hypertonic saline infusion study did not concentrate the osmolality of urine. Her laboratory data showed hypokalemia, hyperreninemia, an increased concentration of plasma aldosterone and an increased urinary excretion rate of prostaglandin E2, which resembled hyperprostaglandin E-syndrome. T1-weighted magnetic resonance imaging of the posterior pituitary gland revealed decreased intensity. Polyuria reached 4-6 L daily, and urine osmolality remained dilute despite a lapse of four days since treatment with intranasal 1-desamino-8-D-arginine vasopressin (dDAVP: 10-25 microg every 12 h). The patient was conservatively managed without medical treatment, then delivered in the 38th week of pregnancy without complication. The osmolality of the patient's urine was higher than that of the plasma when tested 3 days postpartum. The abnormality of magnetic resonance imaging of the posterior pituitary gland disappeared at 6 months after delivery. We consider that subclinical nephrogenic diabetes insipidus in our patient was exacerbated during pregnancy.

Patients with diabetes insipidus (DI) are at high risk for dehydration, hypernatremia and hemodynamic instability. Ovarian hyperstimulation syndrome (OHSS) likewise has negative effects on electrolyte balance. If ovulation induction is required in a patient with DI, there is thus a strong argument for avoiding techniques that increase the risk of OHSS. This paper reports the results of ovulation induction in a patient with anovulation of hypothalamic origin and central (vasopressin deficit) DI. Ovulation was induced with pulsatile gonadotropin-releasing hormone (GnRH), which induces single-ovule cycles and which does not increase the risk of OHSS. The patient successfully achieved pregnancy after seven ovulatory cycles.

Posttraumatic neuroendocrine pathology may be a clinically significant complication following traumatic brain injury (TBI). Metabolic abnormalities are described after TBI in two cases. A 21 year old male injured in a motor vehicle accident admitted in a minimally responsive condition presented with fluctuating high sodium levels, undetectable serum testosterone, and depressed cortisol and thyroid function. Imaging revealed near complete avulsion of the pituitary stalk leading to panhypopituitarism. A 38 year old male admitted for occipital skull fractures and brain contusions presented with hyponatremia and low serum testosterone. Both patients required hormonal replacement and correction of electrolyte abnormalities. A screening protocol adapted for selected patients at risk for endocrine problems is described. While neuroendocrine screening is not advocated in all TBI patients, physicians should be aware of the importance of neuroendocrine dysfunction following TBI.

Purpose: In the differential diagnosis of patients with polyuria-polydipsia one must distinguish usually between primary polydipsia (PP) and central diabetes insipidus (CDI). The first situation is a state of volume expansion and the second of volume contraction. We evaluate whether serum uric acid determination could help to differentiate between the two conditions., Patients and Methods: We analyzed the score of 13 consecutive patients with CDI, 7 patients with PP, and 7 patients with nephrogenic diabetes insipidus (NDI). Serum uric acid concentration was available during normonatremia without treatment with 1-desamino-8-D-arginine vasopressin (dDAVP), during mild dehydration and during treatment with dDAVP. In 8 of these patients plasma renin activity (PRA), urate, urea and creatinine clearances were also available. These data were also obtained in the patients with NDI. In 1 patient with CDI, we studied the effect on urate clearance of dDAVP, which stimulates exclusively the V2 receptors, and of triglycyl-lysine-vasopressin (TGLV), a potent V1-receptor agonist., Results: Normonatremic polydypsic patients with CDI presented an increase in uric acid concentration (7.1 +/- 2.2 mg/dL), whereas in the PP group the value was decreased (3 +/- 0.75 mg/dL; P <0.001). All the normonatremic PP presented a serum uric acid concentration lower than 5 mg/dL, whereas all the normonatremic CDI patients, exept 1, presented a value higher than 5 mg/dL. In both groups blood urea concentration was decreased as a consequence of high renal clearances. The hyperuricemia of CDI was related to low uric acid clearances. Patients with hypernatremia and NDI presented a lower increase in serum uric acid concentration than those with similar levels of hypernatremia and CDI (NDI: 5.7 +/- 0.8 mg/dL and CDI: 7.9 +/- 2.3 mg/dL; P <0.05) and the NDI patients presented an urate clearance corrected for creatinine clearance which was significantly higher than in CDI (9% +/- 3% and 4% +/- 1.1%; P <0.01). When the patients with CDI were treated with dDAVP and normalyzed their PRA (0.9 +/- 0.4 ng/mL/h) we observed still mild hyperuricemia compared to controls (5.5 +/- 1.4 mg/dL and 4.3 +/- 0.9 mg/dL; P <0.01) and a low fractional excretion of filtered uric acid (6.5% +/- 1.7% compared to 8.2% +/- 2% in controls; P <0.05). Acute administration of dDAVP, stimulating the V2 receptors, in one patient with CDI, had no effect on urate clerance, while TGLV, which stimulates the V1 receptor, increased urate clearance., Conclusion: The presence of an serum uric acid concentration higher than 5 mg/dL in polyuric polydipsic patients is highly suggestive of CDI. Even when these patients are treated with dDAVP many of them remain hyperuricemic, and this seems to be the consequence of a lack of V1 receptor stimulation.

The objective of the present study was to examine the effect of changes in plasma osmolality (pOsm) on the responses of the pituitary-adrenal axis to CRH and atrial natriuretic peptide (ANP) release in patients with central diabetes insipidus (DI). Eight normal subjects and six DI patients were subjected to human CRH (hCRH) (1 microgram/kg) stimulation alone or associated with isotonic volume loading (0.9% NaCl, 12 mL.kg.60 min) or an osmotic stimulus (5% NaCl, 0.06 mL.kg/min.120 min). The DI group showed significantly increased pOsm and undetectable or low plasma arginine vasopressin (AVP) during all tests. In the control group, pOsm and plasma AVP increased only during the osmotic stimulus. The DI group presented lower plasma ANP levels than controls during osmotic stimulus and isotonic volume loading. The lower ANP secretion in DI patients corroborates the importance of neurohypophyseal hormones in ANP regulation. Basal plasma ACTH and cortisol levels did not differ between controls and DI. The latter group presented a higher ACTH response than controls during stimulation with hCRH alone [area under the curve (AUC) 1138 +/- 99 vs. 709 +/- 62 pmol.L/min] and hCRH/5% NaCl (AUC 1602 +/- 209 vs. 1158 +/- 187 pmol.L.min). The DI cortisol AUC were higher than controls during stimulation with hCRH alone (65,471 +/- 6,070 vs. 48,062 +/- 3,476 nmol.L.min) and hCRH/5% NaCl (89,005 +/- 10,043 vs. 62,105 +/- 5,600 nmol.L.min). The highest ACTH and cortisol responses to hCRH in both groups were obtained with hCRH/5% NaCl. There was a significant correlation between mean pOsm and ACTH response to hCRH (r = 0.62). The increased responses to hCRH with increasing pOsm were present in control subjects and in patients with DI. However, at any given level of pOsm, there was no difference in ACTH response between controls and DI. These data indicate that the acute increases in pOsm augmented the ACTH and cortisol responses to hCRH that involve other factors besides magnocellular AVP.

Background: Lymphocytic adenohypophysitis is a well-known autoimmune disorder affecting the anterior pituitary gland. Posterior pituitary gland function can be impaired by a similar autoimmune disorder called lymphocytic infundibulohypophysitis. Only very few cases have been reported., Clinical Presentation: We present a patient with central diabetes insipidus in the postpartum period. On radiologic and endocrine evidence lymphocytic involvement of the pituitary stalk and infundibulum was suspected., Intervention: A diagnostic pterional craniotomy was performed. The diagnosis of lymphocytic infundibulohypophysitis was confirmed by biopsy., Conclusion: We present a case of lymphocytic infundibulohypophysitis. In view of its autoimmune pathophysiology the occurrence of this disorder in the postpartum period is not surprising, even though it has not been reported before. This rare disorder should be distinguished from the more common lymphocytic adenohypophysitis.