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Diabetes insipidus is a disorder characterized by excretion of large amounts of hypotonic urine. Four entities have to be differentiated: central diabetes insipidus resulting from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, nephrogenic diabetes insipidus resulting from resistance to AVP in the kidneys, gestational diabetes insipidus resulting from an increase in placental vasopressinase and finally primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Distinguishing between the different types of diabetes insipidus can be challenging. A detailed medical history, physical examination and imaging studies are needed to detect the aetiology of diabetes insipidus. Differentiation between the various forms of hypotonic polyuria is then done by the classical water deprivation test or the more recently developed hypertonic saline or arginine stimulation together with copeptin (or AVP) measurement. In patients with idiopathic central DI, a close follow-up is needed since central DI can be the first sign of an underlying pathology. Treatment of diabetes insipidus or primary polydipsia depends on the underlying aetiology and differs in central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia. This review will discuss issues and newest developments in diagnosis, differential diagnosis and treatment, with a focus on central diabetes insipidus., (© 2021 The Association for the Publication of the Journal of Internal Medicine.)

We characterized mouse blood pressure and ion transport in the setting of commonly used rodent diets that drive K + intake to the extremes of deficiency and excess. Male 129S2/Sv mice were fed either K + -deficient, control, high-K + basic, or high-KCl diets for 10 days. Mice maintained on a K + -deficient diet exhibited no change in blood pressure, whereas K + -loaded mice developed an ~10-mmHg blood pressure increase. Following challenge with NaCl, K + -deficient mice developed a salt-sensitive 8 mmHg increase in blood pressure, whereas blood pressure was unchanged in mice fed high-K + diets. Notably, 10 days of K + depletion induced diabetes insipidus and upregulation of phosphorylated NaCl cotransporter, proximal Na + transporters, and pendrin, likely contributing to the K + -deficient NaCl sensitivity. While the anionic content with high-K + diets had distinct effects on transporter expression along the nephron, both K + basic and KCl diets had a similar increase in blood pressure. The blood pressure elevation on high-K + diets correlated with increased Na + -K + -2Cl - cotransporter and γ-epithelial Na + channel expression and increased urinary response to furosemide and amiloride. We conclude that the dietary K + maneuvers used here did not recapitulate the inverse effects of K + on blood pressure observed in human epidemiological studies. This may be due to the extreme degree of K + stress, the low-Na + -to-K + ratio, the duration of treatment, and the development of other coinciding events, such as diabetes insipidus. These factors must be taken into consideration when studying the physiological effects of dietary K + loading and depletion.

Diabetes insipidus (DI) is a disorder characterized by excretion of large amounts of hypotonic urine. Central DI results from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, whereas nephrogenic DI results from resistance to AVP in the kidneys. Central and nephrogenic DI are usually acquired, but genetic causes must be evaluated, especially if symptoms occur in early childhood. Central or nephrogenic DI must be differentiated from primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Primary polydipsia is most common in psychiatric patients and health enthusiasts but the polydipsia in a small subgroup of patients seems to be due to an abnormally low thirst threshold, a condition termed dipsogenic DI. Distinguishing between the different types of DI can be challenging and is done either by a water deprivation test or by hypertonic saline stimulation together with copeptin (or AVP) measurement. Furthermore, a detailed medical history, physical examination and imaging studies are needed to ensure an accurate DI diagnosis. Treatment of DI or primary polydipsia depends on the underlying aetiology and differs in central DI, nephrogenic DI and primary polydipsia.

Death by neurologic criteria is an irreversible sequence of events culminating in permanent cessation of cerebral functions. In this context, there are no responses arising from the brain, no cranial nerve reflexes nor motor responses to pain stimuli, and no respiratory drive. The diagnosis of death by neurologic criteria implies that there is clinical evidence of the complete and irreversible cessation of brainstem and cerebral functions. The diagnosis, confirmation, and certification of death are core skills for medical practitioners. The aim of this review is to discuss the pathophysiology and definition of death by neurological criteria, describing the clinical assessment, and the use of ancillary tests for the diagnosis of brainstem death.

Dysregulated arousal often accompanies neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism spectrum disorder. Recently, we have found that adolescent homozygous Brattleboro (Hom) rats, which contain a mutation in the arginine vasopressin (AVP) gene, exhibit lower behavioral arousal than their heterozygous (Het) littermates in the open field test. This hypoaroused phenotype could be due to loss of AVP in magnocellular cells that supply AVP to the peripheral circulation and project to limbic structures or parvocellular cells that regulate the stress axis and other central targets. Alternatively, hypoarousal could be a side effect of diabetes insipidus - polydipsia and polyuria seen in Hom rats due to loss of AVP facilitation of water reabsorption in the kidney. We developed a viral-rescue approach to "cure" magnocellular AVP cells of their Brattleboro mutation. Infusion of a recombinant adeno-associated virus (rAAV) containing a functional Avp gene and promoter (rAAV-AVP) rescued AVP within magnocellular cells and fiber projections of the paraventricular nucleus of the hypothalamus (PVN) of male and female adolescent Hom rats. Furthermore, water intake was markedly reduced, ameliorating the symptoms of diabetes insipidus. In contrast, open field activity was unaffected. These findings indicate that the hyporaoused phenotype of adolescent Hom rats is not due to the loss of AVP function in magnocellular cells or a side effect of diabetes insipidus, but favors the hypothesis that central, parvocellular AVP mechanisms underlie the regulation of arousal during adolescence.

Aim: Different factors have been hypothesized to play a role in the cascade of events associated with the protein-induced glomerular response. However, scant data are available on the possible functional effect of vasopressin (VP) on the glomerular filtration rate (GFR) in humans with central diabetes insipidus (CDI), which was the aim of the present study., Method: Renal function was studied under fasting conditions (baseline) and after a meat meal in 16 patients with CDI before and after treatment with desmopressin (DDAVP) and in 16 control subjects. GFR was measured by the inulin method., Results: At baseline, the GFR was lower in patients with CDI. Treatment with DDAVP resulted in an insignificant increase in GFR, which was not statistically different from untreated patients. After an acute oral protein load, the GFR increased, peaking at 45 min post meal in controls, and at 135 min post meal in treated and untreated CDI patients., Conclusion: After a meat meal, the peak GFR response is delayed in CDI patients suggesting that VP might indirectly affect tubule-glomerular feedback.

The majority of women are healthy entering pregnancy and do not require measurement of renal function or serum electrolytes. Clinicians must remain alert to the possibility of renal as well as fluid and electrolyte disorders in pregnancy, as the presenting complaints are often vague and mistaken for the normal physiology of pregnancy. In this chapter, our objectives are 1) to review the renal physiology from a practical/clinical standpoint; 2) to provide the clinical obstetrician a case-based approach to fluid and electrolyte disorders commonly encountered in pregnancy; 3) to consolidate knowledge on renal physiology and fluid and electrolyte disorders in pregnancy with MCQs that are directly aligned with content; and 4) to highlight key practice points and present a research agenda., (Copyright © 2018. Published by Elsevier 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.

Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion lie at opposite ends of the spectrum of disordered renal handling of water. Whereas renal retention of water insidiously causes hypotonic hyponatremia in syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus may lead to free water loss, hypernatremia, and volume depletion. Hypernatremia and hyponatremia are associated with worse outcomes and longer intensive care stays. Moreover, pathologies causing polyuria and hyponatremia in patients in intensive care may be multiple, making diagnosis challenging. We provide an approach to the diagnosis and management of these conditions in intensive care patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although hyperemesis gravidarum (HG), an extreme form of morning sickness, is a common complication during pregnancy, HG associated simultaneous onset of rhabdomyolysis and diabetes insipidus due to electrolyte abnormalities are rare. A 34-year-old woman with severe HG at 17 weeks of gestation complicated with appetite loss, weight reduction by 17 kg, general fatigue, myalgia, weakness and polyuria was identified to have simultaneous hypophosphatemia (1.6 mg/dL) and hypokalemia (2.0 mEq/L). Appetite recovery and the improvement of the hypophosphatemia (3.2 mg/dL) were observed prior to the first visit to our department. At the admission, she presented polyuria around 7,000~8,000 mL/day with impaired concentrating activity (U-Osm 185 mOsm/L), and abnormal creatine kinase elevation (4,505 U/L). The electrolyte disturbances and physio-metabolic abnormalities in undernourished state due to HG let us diagnose this case as refeeding syndrome (RFS). In this case, abnormal loss by vomiting, insufficient intake and previous inappropriate fluid infusion as well as the development of RFS may accelerate the severity of hypokalemia due to HG. Thus, as her abnormalities were considered as results of rhabdomyolysis and diabetes insipidus due to severe HG associated hypokalemia based on RFS, oral supplementation of potassium chloride was initiated. After 6 days of potassium supplementation, her symptoms and biochemical abnormalities were completely resolved. Severe HG followed by RFS can be causes of electrolyte abnormalities and subsequent complications, including rhabdomyolysis and renal diabetes insipidus. Appropriate diagnosis and prompt interventions including adequate nutrition are necessary to prevent electrolyte imbalance induced cardiac, neuromuscular and/or renal complications.

Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: None. Further details of BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

2018 brings new insights into the differential diagnosis of patients with hypotonic polyuria syndrome. Exact localization of the antidiuretic defect in patients with hypotonic polyuria can be challenging, especially the distinction of primary polydipsia from partial pituitary or renal forms of diabetes insipidus. However, diagnostic precision is vital since therapeutic management differs substantially and false treatment may result in serious consequences.A main limitation of the indirect water deprivation test is its limited accuracy to correctly distinguish between the pathophysiologically distinct forms of hypotonic polyuria with a residual antidiuretic capacity. Direct detection of the osmotically-sensitive AVP reserve may be diagnostically superior but is technically difficult and not available for clinical routine, having left indirect diagnostic readouts the only accepted method for differentiating polyuric states, despite a diagnostic accuracy of only 70 %.New data demonstrate that selective measurement of plasma copeptin, a reliable AVP surrogate, not only captures patients with underlying renal defect, but critically improves diagnostic differentiation between primary polydipsia and pituitary forms of central diabetes insipidus.This manuscript presents the novel findings in the field and interprets their clinical consequences., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Diabetes insipidus, characterized by polyuria and polydipsia, is a rare disease during pregnancy. Nevertheless, its recognition is important to avoid complications due to dehydration and hypernatremia. Its manifestation during pregnancy ranges from exacerbation of pre-existing central or nephrogenic diabetes insipidus to transient pregnancy-induced diabetes insipidus due to the increased metabolism of the antidiuretic hormone vasopressin (AVP) by the placental vasopressinase. Diagnosis can be challenging, as urinary frequency is common during pregnancy and primary polydipsia also needs to be excluded. Also, the standard water deprivation test is not recommended during pregnancy due to the increased risk of complications. Treatment depends upon the final diagnosis, with desmopressin (DDAVP) being the medication of choice in AVP-deficient diabetes insipidus, whereas nephrogenic diabetes insipidus requires treatment of the underlying disease and supportive measures.

The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI). A lack of VP production precipitates central diabetes insipidus (CDI), which can be managed effectively by VP supplementation. A majority of cases of nephrogenic diabetes insipidus (NDI) result from V2R mutations that impair receptor sensitivity. No specific therapy is currently available for management of NDI. Evidence is evolving that (pro)renin receptor (PRR), a newly identified member of the renin-angiotensin system, is capable of regulating VP production and action. As such, PRR should be considered strongly as a therapeutic target for treating CDI and NDI. The current review will summarize recent advances in understanding the physiology of renal and central PRR as it relates to the two types of DI.

The paraventricular nucleus of the hypothalamus (PVH), located in the ventral diencephalon adjacent to the third ventricle, is a highly conserved brain region present in species from zebrafish to humans. The PVH is composed of three main types of neurons, magnocellular, parvocellular, and long-projecting neurons, which play imperative roles in the regulation of energy balance and various endocrinological activities. In this review, we focus mainly on recent findings about the early development of the hypothalamus and the PVH, the functions of the PVH in the modulation of energy homeostasis and in the hypothalamus-pituitary system, and human diseases associated with the PVH, such as obesity, short stature, hypertension, and diabetes insipidus. Thus, the investigations of the PVH will benefit not only understanding of the development of the central nervous system but also the etiology of and therapy for human diseases.

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 .).

Both microscopic and endoscopic transsphenoidal surgery are effective approaches for nonfunctioning pituitary adenomas. The issue on the comparison of their efficacy and safety remains inconsistent. A thorough search of the literatures (PubMed, EMBASE, MEDLINE) were performed up to March 2017. Studies reporting outcomes of microscopic or endoscopic transsphenoidal surgery on nonfunctioning pituitary adenomas were included. A meta-analysis was performed focusing on the early stage and long term outcomes. The final search yielded 19 eligible studies enrolling 3847 patients, 389 of them underwent microscopic approach and 3458 of them with endoscopic approach. As to the early stage outcomes, the rate of gross tumor resection was significantly higher in the endoscopic group than that in microscopic group (73% versus 60%, P < 0.001). Meanwhile, endoscopic approach showed priority over microscopy on postoperative hypopituitarism (63% versus 65%, P < 0.001) and CSF leakage (3% versus 7%, P < 0.001). For the long term outcomes, the rate of visual improvement was significant higher in the endoscopic group than that in microscopic group (77% versus 50%, P < 0.001). However, there was no significant difference between the groups regarding the rate of permanent diabetic insipidus and meningitis. The endoscopic approach may be associated with higher rate of gross tumor movement and lower risk of postoperatively complications for treating nonfunctioning pituitary adenoma, when compared with microscopic approach. However, the confidence was shorted due to limited high quality evidence (largely randomized and controlled studies)., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Gestational diabetes insipidus (GDI) is a rare endocrine complication during pregnancy that is associated with vasopressinase overproduction from the placenta. Although increased vasopressinase is associated with placental volume, the regulation of placental growth in the later stage of pregnancy is not well known., Case Presentation: A 16-year-old pregnant woman was urgently transferred to our hospital because of threatened premature labor when the Kumamoto earthquakes hit the area where she lived. During her hospitalization, she complained of gradually increasing symptoms of polyuria and polydipsia. The serum level of arginine vasopressin (AVP) was 1.7 pg/mL, which is inconsistent with central DI. The challenge of diagnostic treatment using oral 1-deamino-8-D-AVP (DDAVP) successfully controlled her urine and allowed for normal delivery. DDAVP tablets were not necessary to control her polyuria thereafter. Based on these observations, clinical diagnosis of GDI was confirmed. Pathophysiological analyses revealed that vasopressinase expression was more abundant in the GDI patient's syncytiotrophoblast in placenta compared with that in a control subject. Serum vasopressinase was also observed during gestation and disappeared soon after delivery. Vasopressinase is reportedly identical to oxytocinase or insulin regulated aminopeptidase (IRAP), which is an abundant cargo protein associated with the glucose transporter 4 (GLUT4) storage vesicle. Interestingly, the expression and subcellular localization of GLUT4 appeared to occur in a vasopressinase (IRAP)-dependent manner., Conclusion: Because placental volume may be associated with vasopressinase overproduction in GDI, vasopressinase (IRAP)/GLUT4 association appears to contribute to the growth of placenta in this case.

Background: Autoimmune hypothalamitis, which is among the causes of acquired central diabetes insipidus, has seldom been described in the literature. This condition is probably provoked by the production of anti-vasopressin-secreting cell antibodies and antihypothalamus antibodies and is often associated with pituitary or polyendocrine autoimmunity. Correct diagnosis and immediate treatment are essential to avoid the progression of the pathologic process., Case Description: A woman diagnosed with central diabetes insipidus 12 years ago, who had panhypopituitarism and mild memory deficit, came to our attention. She refused radiologic studies. Magnetic resonance imaging performed in our unit showed a contrast-enhancing hypothalamic lesion. Lumbar puncture was negative for neoplastic markers. We decided to perform a biopsy of the lesion to obtain a histopathologic examination of the tissue and chose an endoscopic transventricular approach to reach the floor of the third ventricle. Autoimmune hypothalamitis was diagnosed and treatment with steroids and azathioprine was started. The lesion size decreased and was stable after 17 months of follow-up., Conclusions: The endoscopic transventricular approach has proved to be an effective and safe way to obtain tissue samples for histopathologic examination from a region that is usually difficult to reach; it also gives direct visualization of the lesion, which makes sampling easier. The lesion size decreased after treatment but no clinical improvement was detected, either on the cognitive or on the endocrinologic side., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A 38-year-old Japanese man who had undergone clipping surgery for a ruptured aneurysm of the anterior communicating artery 2 days prior, suddenly developed refractory hypernatremia (serum sodium (Na) 156 - 162 mmol/L). Symptoms included low plasma vasopressin, fluctuating urine osmolality (120 - 710 mOsm/kg) and lack of thirst, all suggesting adipsic diabetes insipidus (ADI). Hypernatremia was corrected by scheduled water intake with desmopressin administration. During 1-year follow-up after the surgery, his serum Na level normalized despite the suspension of desmopressin, but neither thirst nor osmolality-dependent vasopressin release recovered. Meanwhile, his urine osmolality shifted to a constant high level. The present case suggests that renal compensatory adaptation, apparently independent of the circulating vasopressin level, plays a major role in water handling in longitudinal ADI.
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Background and Aims: Retrospective studies of TBI have found a neuroendocrine dysfunction following traumatic brain injury in 23 to 60% of adults and 15 to 21% of children. Our aims were to determine the prevalence of hypothalamo-hypophyseal dysfunction in children following brain injury, assess its relationship to the type of injury and the course of the acute post-traumatic phase., Patients and Methods: Body development (growth, pubertal development, and skeletal maturity) were evaluated in 58 patients (21 girls) after a brain injury rated 3 to 12 on the Glasgow Coma Scale (GCS). The patients underwent standard endocrine tests - TSH, fT4, IGF-1, PRL, morning cortisol, FSH, LH, and testosterone in boys and estradiol in girls - in the early post-traumatic period (2 to 14 days; T0) and at 3, 6, and 12 months after the injury (T3, T6, and T12). Dynamic tests were carried out in patients with abnormalities in their clinical examination and/or laboratory results. An MRI was performed on all patients at T12., Results: The median age at the time of injury was 11.3 (0.5 to 18.7) years. Of the 58 patients, 23 had GCS < 8, corresponding to severe brain injury. At T0, diabetes insipidus (DI) was diagnosed in 12 patients, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in 4 patients. Frequent hormonal changes simulated central hypothyroidism (in 45% of patients) and hypogonadotropic hypogonadism (in 25% of adolescents who were already pubertal at the time of injury > Tanner II). Examination at T3 (n = 58) confirmed a combined pituitary hormone deficiency in two boys and DI in another one. At T6 (n = 49), hormonal dysfunctions were diagnosed in two boys (precocious puberty and growth hormone deficiency). At T12 (n = 39), a new endocrine dysfunction was diagnosed in five patients (growth hormone deficiency in two, hypogonadotropic hypogonadism in two, and in one patient, already diagnosed with a growth hormone deficiency, central hypothyroidism, as well). Brain MRI revealed an empty sella in two patients with growth hormone deficiency. Patients with GCS < 8 had more symptoms of SIADH or DI in the early post-traumatic period 11/23 vs. patients with GCS of 8 to 13 (4/35), and more frequent hormonal disorder (6/23) than individuals with moderate trauma (3/35), P = 0.0135. The incidence of endocrine dysfunction at T0 significantly correlated with the severity of injury (P = 0.05), but it was not an indicator for the development of a late hormonal disorder., Conclusion: Within a year after injury, a hormonal disorder was found in 17.6% of the patients. Neuroendocrine dysfunction as a late consequence of craniocerebral trauma in children and adolescents was less frequent than in adults. Risk factors for its development are the gravity of the injury, brain scan pathology, and possibly the development of DI, SIADH, or CSWS in the acute post-traumatic phase.

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

Background: Diabetes insipidus (DI) is a rare disease in humans and animals, which is caused by the lack of production, malfunction or dysfunction of the distal nephron to the antidiuretic effect of the antidiuretic hormone (ADH). Diagnosis requires a thorough medical history, clinical examination and further laboratory confirmation. This case report describes the appearance of DI in five Duroc boars in Switzerland., Case Presentation: Two purebred intact Duroc boars at the age of 8 months and 1.5 years, respectively, with a history of polyuric and polydipsic symptoms had been referred to the Swine Clinic in Berne. Based on the case history, the results of clinical examination and the analysis of blood and urine, a tentative diagnosis of DI was concluded. Finally, the diagnosis was confirmed by findings from a modified water deprivation test, macroscopic examinations and histopathology. Following the diagnosis, three genes known to be involved in inherited DI in humans were analyzed in order to explore a possible genetic background of the affected boars., Conclusion: The etiology of DI in pigs is supposed to be the same as in humans, although this disease has never been described in pigs before. Thus, although occurring only on rare occasions, DI should be considered as a differential diagnosis in pigs with polyuria and polydipsia. It seems that a modified water deprivation test may be a helpful tool for confirming a diagnosis in pigs. Since hereditary forms of DI have been described in humans, the occurrence of DI in pigs should be considered in breeding programs although we were not able to identify a disease associated mutation.

Background: There is limited data regarding the effect of altered serum osmolality on cardiac electrical activity. The aim of the present study is to evaluate the electrocardiographic (ECG) effects of diabetes insipidus (DI) and any related hyperosmolality in a population of young patients with DI and without any known cardiovascular disease or risk factors., Methods: Twelve-lead ECG's of 44 consecutive untreated young male patients (age: 21.8 ± 2.9 years) who had been referred to endocrinology clinic and diagnosed as DI based on water deprivation test were retrospectively evaluated. A total of 30 age-matched (21.9 ± 2.4 years) healthy males were selected as control group and ECG's of these controls were obtained for comparison with ECG's of DI patients. All ECG parameters were measured and compared., Results: Duration of QRS complex was significantly shorter in patients with DI compared with controls (85.2 ± 12.0 vs. 94.0 ± 10.6 ms, p: 0.001). P wave dispersion (PWD) of patients with DI was significantly higher compared with controls (31.9 ± 9.9 vs. 26.5 ± 10.6 ms, p: 0.03) and it was significantly correlated with serum osmolality and serum sodium level (r = - 0.36, p: 0.02 and r: - 0.35, p: 0.02, respectively)., Conclusions: DI patients without any cardiovascular disease or risk factors displayed significantly shorter QRS duration and increased p wave dispersion compared with controls.

Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal "osmoreceptors" that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance., (Copyright © 2015 by the American Society of Nephrology.)

A patient assessed by heart rate variability (HRV) methodology, beginning just after the completion of brain death (BD) diagnosis, showed remaining very low frequency (VLF) waves for approximately 10 min. A time-varying spectral analysis showed that during the first 550 s, a significant power spectral density remained in the high-frequency (HF), low-frequency (LF) and VLF bands. From 550 to 675 s, the HF oscillations totally vanished, and a marked progressive decay of the LF and VLF power density occurred. After 700 s the VLF undulations stopped and remaining small amplitude oscillations at 0.2 Hz coincided with the ventilator frequency. The VLF oscillations recorded in our case might be related to residual sympathetic vasomotor activity that progressively disappeared due to the extension of necrosis affecting the nervous centres of the lower part of the medulla and the first 2-3 cervical spine segments., (2015 BMJ Publishing Group Ltd.)

Histiocytosis is characterized by proliferation of cells from the mononuclear phagocyte system, and may be divided into Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (including Erdheim-Chester disease [ECD]). While diabetes insipidus (DI) is the most common hypothalamic-pituitary consequence, anterior pituitary deficiencies are less known. This study analyzed the frequency and progression of pituitary hormone deficiencies and the radiographic findings in 9 patients (7 with LCH and 2 with ECD) with hypothalamic-pituitary (HP) axis. Eighty-nine percent of patients had DI (62% at diagnosis), and 78% had one or more anterior pituitary deficiencies (71% at diagnosis). HP involvement is relatively common in patients diagnosed with histiocytosis and hormone deficiencies may be present at diagnosis or appear gradually during the course of disease. Regular monitoring of these patients is recommended., (Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.)

Hyponatremia is a common and potentially serious complication of transsphenoidal surgery (TSS). Since September 2009, we have implemented moderate water intake restriction (< 2500 mL/day) after TSS in an attempt to prevent this complication. The aim of this study was to investigate the efficacy of a combination of moderate restriction of water intake plus antidiuretic hormone (arginine vasopressin [AVP]) replacement therapy in patients with diabetes insipidus (DI) for reducing the incidence of delayed hyponatremia after TSS. Patients treated from September 2005 to August 2009 were allowed to drink water freely after surgery (the control group), while patients treated from September 2009 to June 2012 were restricted to less than 2500 mL water per day (the water restriction group). To reduce the occurrence of hypernatremia, AVP replacement therapy was provided immediately after the development of DI. We retrospectively analyzed the incidence of hyponatremia, DI, and hypernatremia in patients following TSS. Hyponatremia incidence was significantly lower in the water restriction group (P = 0.017); however, there were no significant differences in DI incidence and hypernatremia incidence between the 2 groups. Under DI control with AVP replacement therapy, the water restriction group showed no significant difference in the daily self-rated thirst level for the patients with and without DI. Moderate water intake restriction in addition to AVP replacement therapy significantly decreases the incidence of hyponatremia without patient discomfort (extreme thirst) and other complications. However, further studies are required to determine the most effective amount of water and the optimal duration of postoperative water restriction.

Diabetes insipidus is an uncommon disorder of water-electrolyte balance characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The disease may result from the insufficient production of vasopressin, its increased degradation, an impaired response of kidneys to vasopressin, or may be secondary to excessive water intake. Patients with severe and uncompensated symptoms may develop marked dehydration, neurologic symptoms and encephalopathy, and therefore diabetes insipidus can be a life-threatening condition if not properly diagnosed and managed. Patients with diabetes insipidus require treatment with desmopressin or drugs increasing sensitivity of the distal nephron to vasopressin, but this treatment may be confusing because of the disorder's variable pathophysiology and side-effects of pharmacotherapy. This review summarizes the current knowledge on different aspects of the pathophysiology, classification, clinical presentation, diagnosis, and management of diabetes insipidus. The reader is also provided with some practical recommendations on dealing with patients suffering from this disease.

Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: We are describing an unusual case of severe hyperglycemia and hypernatremia, resistant to treatment., Case Presentation: A thirty year old female with adenocarcinoma of rectum was admitted with increasing lethargy, headache and drowsiness. She deteriorated rapidly and had cardiac arrest, following which she remained comatose. Her initial serum glucose and sodium were normal, but after receiving dexamethasone and mannitol, the serum glucose progressively increased to 54.7 mmol/L and sodium to 175 mmol/L, despite receiving very high dose of intravenous (IV) insulin infusion. She was evaluated for diabetes insipidus because of continued polyuria even after correction of hyperglycemia. Her serum osmolality was 337 mmol/kg, and urine osmolality was 141 mmol/kg which rose to 382 mmol/kg, after receiving 4 mcg of IV Desmopressin., Conclusion: Our patient developed central diabetes insipidus post cardiac arrest and severe dehydration because of diabetes insipidus. Stress of critical illness, dehydration, dexamethasone and IV dextrose infusion were likely responsible for this degree of severe and resistant to treatment hyperglycemia.

Context: Pituitary stalk lesions have various etiologies, often not clinically apparent. Pathological samples from these lesions are rarely obtained, because of the critical location and function of the hypophyseal stalk., Objectives: The purpose of this study was to characterize the etiological spectrum of pituitary stalk lesions seen at Mayo Clinic Rochester over 20 years and to determine whether specific magnetic resonance imaging (MRI) characteristics could provide clinician guidance with regard to the etiology of infundibular lesions., Design: A retrospective review of patients with pituitary stalk lesions seen at Mayo Clinic Rochester between 1987 and 2006 was conducted. Demographic, clinical presentation, imaging, laboratory, operative, and pathology data were reviewed and are reported using descriptive statistics., Results: Of the 152 pituitary stalk lesions included, 49 (32%) were neoplastic, 30 (20%) were inflammatory, 13 (9%) were congenital anomalies, and 60 (39%) were of unclear etiology. Diabetes insipidus was diagnosed in 43 (28%) of the 152 patients, and 49 (32%) patients had at least one anterior pituitary hormone deficit. Secondary hypogonadism was the most common endocrine deficiency. Eleven of 13 congenital lesions were round in appearance and 5 of 7 patients with neurosarcoidosis confirmed by pathology had a uniformly thickened pituitary stalk on MRI. There were no statistically significant correlations between hypopituitarism and the pattern of enhancement or size of the lesion., Conclusions: Findings on MRI remain key in guiding the diagnosis of pituitary stalk lesions, particularly when used in conjunction with other clinical clues. There are no good imaging predictors for hypopituitarism, making clinical evaluation of all patients with pituitary stalk lesions crucial.

Patients who undergo transsphenoidal pituitary tumor resection require a multidisciplinary team approach, consisting of a neurosurgeon, an endocrinologist, and nurses. Successful transsphenoidal surgery needs expert nursing care for early identification and prompt treatment of pituitary dysfunction and neurosurgical complications. Pituitary dysfunction includes adrenal insufficiency, diabetes insipidus, syndrome of inappropriate antidiuretic hormone, and cerebral salt wasting syndrome. Neurosurgical complications may include visual disturbance, cerebrospinal fluid leak, subdural hematoma, and epistaxis.

Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.

Many complications have been reported after cardiopulmonary bypass. A common physiologic change during the early postoperative period after cardiopulmonary bypass is increased diuresis. In patients whose urine output is increased, postoperative diabetes insipidus can develop, although reports of this are rare. We present the cases of 2 patients who underwent on-pump coronary artery bypass grafting (with cardiopulmonary bypass). Each was diagnosed with diabetes insipidus postoperatively: a 54-year-old man on the 3rd day, and a 66-year-old man on the 4th day. Each patient recovered from the condition after 6 hours of intranasal therapy with synthetic vasopressin (antidiuretic hormone). The diagnosis of diabetes insipidus should be considered in patients who produce excessive urine early after cardiac surgery in which cardiopulmonary bypass has been used.

The therapies of mood and anxiety disorders are not solved, because current antidepressants have delayed onset of therapeutic action and a significant number of patients are non-responsive. Research on the field was leaning towards neuropeptides as therapeutic targets. Vasopressin (VP) is a hot candidate, as beyond its peripheral actions VP is implicated in interneuronal communication and modulates the hypothalamo-pituitary-adrenal (HPA), the key stress axis, as well as behavioural functions. Affective disorders are stress related disorders and the most frequently occurring abnormality in depressed subjects is hyperactivity of the HPA. VP with nucleus paraventricularis hypothalami origin is a direct adrenocorticotrophin secretagogue through its V1b receptor. VP seems to have special importance under prolonged stress conditions, which are known to be strong predictive factor of depressive disorder and can induce depressive-like symptoms. Preclinical and clinical data summarized in this review underline the importance of VP in the development of anxiety- and depressive-like symptoms. Orally active nonpeptiderg V1b antagonists were developed and seemed to have effective anxiolytic and antidepressant profile in preclinical studies, which was not fully confirmed by clinical observations. It seems that V1a receptors on special brain areas could have same importance. Taken together current knowledge strongly implies an importance of vasopressinergic regulation in affective disorders and consider VP as endogenous anxiogenic/depressogenic substance. However, wide range of side effects could develop as a result of an intervention on the VP system; therefore there is a need for area-specific targeting of VP receptors (e.g. with modified nanoparticles).

Pituitary tumour apoplexy is a rare but life threatening condition. Cushing's disease usually presents with clinical features of Cushing's syndrome. We report a 30-year-old male patient with Cushing's disease who presented with severe headache and right third nerve palsy. MRI of the pituitary gland revealed a pituitary adenoma with infarction suggestive of apoplexy. After a transsphenoidal surgery he developed pan-hypopituitarism with diabetes insipidus. We also review the relevant literature., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Recent discoveries have shed new light on the understanding of water metabolism: (1.) in addition to hypothalamic osmoreceptor cells expressing a TRPV1 variant, there are peripheral TRPV4 receptors sensing tonicity in the portal vein and changing central vasopressin secretion and peripheral autonomic activity; (2.) the central osmoregulatory gain of angiotensin action participates in the non-osmotic release of vasopressin induced by hypovolaemia; (3.) prostaglandins EP2 receptors on principal cells of the collecting ducts positively regulate urine concentration mechanisms. These new developments are important clinically for the understanding of hereditary polyuric states. We recommend sequencing of the nephrogenic diabetes insipidus genes in all affected patients. This genomic information is key to the routine care of patients with congenital polyuria and, as in other genetic diseases, reduces health costs and confers psychological benefits on patients and families.

The pituitary gland is one of the most affected organs with altered anatomy and physiology during pregnancy. Acromegaly is the second most common pituitary adenoma seen in relation to gestation after prolactinomas. Acromegaly should be treated before conception to prevent potential tumor growth in patients who desire fertility. Medical therapy can be ceased safely after confirmation of pregnancy in acromegalic patients, but octreotide may be used in selected cases with compressive signs. Other hormonal and non-functional tumors are rarer and have been presented as case reports. Sheehan's syndrome, which is one of the most common causes of hypopituitarism in developing countries, and lymphocytic hypophysitis are known to be associated with pregnancy. They usually result in hypopituitarism, sometimes with delays in diagnosis and difficulties in differential diagnosis. Pregnancy is not common among patients with hypopituitarism or pituitary adenomas due to altered gonadotroph functions. Ovulation induction is essential for fertility achievement, but the replacement of other deficient pituitary hormones, including GH, seems to play an important role in the preparation of the uterus for implantation of the embryo., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Adipsic diabetes insipidus (ADI) is characterised by impaired thirst and defective AVP secretion. We have assessed the thirst response to graded osmotic stimulation using a visual analog scale (VAS) in patients with a history of ADI following surgery for a craniopharyngioma. The patients were thought to be regaining their thirst response but we wanted to confirm that this was the case objectively before relaxing their strict fluid balance regimen. Three patients with adipisa in the presence of hypernatremia following surgery for a craniopharyngioma are described. Their median age at surgery was 13 years (range 11-15 years). All patients had previously demonstrated no desire to drink despite a serum osmolality in excess of 300 mOsmol/kg. Fluid balance was maintained postoperatively with a regimen involving a fixed daily fluid intake and DDAVP dose together with daily weights and regular assessment of capillary sodium concentrations. Patients were thought to be regaining thirst sensation and so were assessed by hypertonic saline infusion (HSI) with thirst measured using a VAS. Patients underwent a HSI test 4, 6 and 9 months post surgery. All had abnormally low AVP production at raised plasma osmolalities but the visual analogue scale confirmed partial or complete thirst recovery. The intensive regimen used to maintain stable serum sodium concentrations was relaxed without the patients subsequently developing a significant hyperosmolar state. We have shown objective recovery of thirst perception in patients with adipsia within 9 months of surgery, despite persistence of cranial diabetes insipidus. These observations indicate that both osmoreceptors regulating thirst and their efferent pathways demonstrate more plasticity than those regulating AVP production. The HSI and thirst VAS are an objective way of assessing patients known to have ADI who are thought to be recovering thirst perception.

Fluid homeostasis requires adequate water intake, regulated by an intact thirst mechanism and appropriate free water excretion by the kidneys, mediated by appropriate secretion of arginine vasopressin (AVP, also known as antidiuretic hormone). AVP exerts its antidiuretic action by binding to the X chromosome-encoded V2 vasopressin receptor (V2R), a G protein coupled receptor on the basolateral membrane of renal collecting duct epithelial cells. After V2R activation, increased intracellular cyclic adenosine monophosphate mediates shuttling of the water channel aquaporin 2 to the apical membrane of collecting duct cells, resulting in increased water permeability and antidiuresis. Clinical disorders of water balance are common, and abnormalities in many steps involving AVP secretion and responsiveness have been described. This article focuses on the principal disorders of water balance, diabetes insipidus, and the syndrome of inappropriate antidiuretic hormone secretion., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a neurodegenerative disease with autosomal recessive inheritance with incomplete penetrance. DIDMOAD is a very rare disease with an estimated prevalence of 1 in 770,000 and it is believed to occur in 1 of 150 patients with juvenile-onset insulin-dependent diabetes mellitus. Additionally, WS may also present with different endocrine and metabolic abnormalities such as anterior and posterior pituitary gland dysfunction. This mini-review summarizes the variable presentation of WS and the need of screening for other metabolic and hormonal abnormalities, coexisting in this rare syndrome.