Cause Of Diabetes Insipidus Research Articles

12227 The Battle Between Central And Nephrogenic Diabetes Insipidus

Abstract Disclosure: A.A. Luzuriaga Chavez: None. J.P. Hidalgo: None. A. Rao: None. N. Patel: None. Diabetes insipidus (DI) is a rare disorder characterized by excessive polyuria and polydipsia. The two main types include central diabetes insipidus (CDI), which results from antidiuretic hormone (ADH) deficiency and nephrogenic diabetes insipidus (NDI), defined by ADH resistance in the renal tubules. It can be challenging to distinguish between different types of DI in a critically ill patient. A 68-year-old female with a past medical history of hypertension, bipolar disorder came to the ER for complaints of chills and shortness of breath. She was transferred to the intensive care unit (ICU) for septic shock secondary to pneumonia and left pleural effusion. A chest tube was placed with improvement in her breathing and she was transferred out of the ICU. Four days later, the patient developed altered mental status, fevers and ICU was reconsulted due to concern for meningitis. A lumbar puncture was done with negative results but the brain MRI revealed ischemic sites involving both medial parietal cortices extending into both occipital poles, consistent with acute ischemia. Furthermore, the patient developed an increased urine output of 200ml per hour with a negative balance of 2.7L, increased sodium of 150, serum osmolality of 313 and urine osmolality of 196. The patient received desmopressin 1 mcg q 6 hrs with the persistence of hypernatremia. Upon further questioning, the patient had been on lithium therapy in the past for bipolar disorder. Amiloride 2.5mg BID was added to the treatment regimen. The patient’s hypernatremia and urine output improved and she was discharged on both amiloride and desmopressin to follow up for dose adjustments as needed. DI has a prevalence of 1 in 25000. Acquired CDI secondary to lesions in the hypophysis or hypothalamus highlights the major role of the central nervous system in regulating water homeostasis. This case report describes CDI developing after a stroke. Ischemia can cause hypoperfusion of osmoreceptors in the hypothalamus and posterior pituitary. Lithium can be frequently associated with NDI, usually seen in 20 to 40% of patients. Different mechanisms of action include lithium interference in renal collecting tubules by increasing cAMP in response to ADH and down-regulation of aquaporin-2 expression, which is accepted to be reversible with the cessation of the therapy. However, long-term treatment with lithium likely results in permanent NDI. Our patient had a history of lithium therapy which contributed to the development of symptoms of NDI and responded to a combination of desmopressin and amiloride. The successful therapy enforces the diagnosis of both a central and a peripheral pathology. Central and nephrogenic DI, despite stemming from distinct underlying causes, may concurrently manifest in critically ill patients. This case report emphasizes the need for physicians to evaluate for multiple causes of DI in a patient with water disturbances. Presentation: 6/1/2024

Erdheim Chester disease as a cause of Diabetes Insipidus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Intraoperative Central Diabetes Insipidus during Aneurysmal Clipping Surgery: An Unusual Phenomenon

AbstractCentral diabetes insipidus (DI) is a known complication associated with pituitary surgeries occurring in postoperative period. However, development of DI following aneurysmal subarachnoid hemorrhage (SAH) is rarely reported. We describe here a case of intraoperative DI in a patient undergoing aneurysmal clipping surgery that posed a challenge for both diagnosis and management. Intraoperative development of central DI was attributed to the evolving ischemic injury to the hypothalamus at the time of rebleeding that was not apparent in the preoperative scan. DI resolved postoperatively after 18 hours of medical management. A careful observation of preoperative scans and vigilant monitoring may help in early diagnosis and management of such complication in the perioperative period.

New developments and concepts in the diagnosis and management of diabetes insipidus (AVP-deficiency and resistance).

Diabetes insipidus (DI) is a disorder characterised by the excretion of large amounts of hypotonic urine, with a prevalence of 1 per 25,000 population. Central DI (CDI), better now referred to as arginine vasopressin (AVP)-deficiency, is the most common form of DI resulting from deficiency of the hormone AVP from the pituitary. The less common nephrogenic DI (NDI) or AVP-resistance develops secondary to AVP resistance in the kidneys. The majority of causes of DI are acquired, with CDI developing when more than 80% of AVP-secreting neurons are damaged. Inherited/familial CDI causes account for approximately 1% of cases. Although the pathogenesis of NDI is unclear, more than 280 disease-causing mutations affecting the AVP2 protein or AVP V2 receptor, as well as in aquaporin 2 (AQP2), have been described. Although the cAMP/protein kinase A pathway remains the major regulatory pathway of AVP/AQP2 action, in vitro data have also revealed additional cAMP independent pathways of NDI pathogenesis. Diagnosing partial forms of DI, and distinguishing them from primary polydipsia, can be challenging, previously necessitating the use of the water deprivation test. However, measurements of circulating copeptin levels, especially after stimulation, are increasingly replacing the classical tests in clinical practice because of their ease of use and high sensitivity and specificity. The treatment of CDI relies on desmopressin administration, whereas NDI requires the management of any underlying diseases, removal of offending drugs and, in some cases, administration of diuretics. A better understanding of the pathophysiology of DI has led to novel evolving therapeutic agents that are under clinical trial.

Paediatric Diabetes Insipidus: A Review

Diabetes insipidus is a disease characterized by partial or total inability to concentrate urine due to a vasopressin secretion deficiency (central diabetes insipidus), a resistance to its action (nephrogenic diabetes insipidus) or an excessive consumption of water (primary polydipsia). The main signs and symptoms of the disease are polydipsia, polyuria, and nocturia; central diabetes insipidus has an insidious onset, whereas nephrogenic diabetes insipidus has a gradual onset. Because of the advances in clinical, laboratory, imaging techniques and molecular biology, the etiologic diagnosis of diabetes insipidus has improved, from 50% of patients with idiopathic diabetes insipidus to 10%-20% of patients; therefore, it has been achieved more timely treatments, resulting in reduction of the risk of sequelae. Accordingly, it is pivotal to rule out secondary causes of diabetes insipidus, such as drug consumption or metabolic disorders in patients with nephrogenic diabetes insipidus, brain tumors, encephalic trauma, infiltrative diseases, autoimmune disorders or central nervous system infections in case of patients suffering from central diabetes insipidus. Regarding treatment, it is recommended the use of desmopressin, an analogue of vasopressin, for the treatment of central diabetes insipidus, whereas water consumption, decrease of salt consumption and treatment with diuretic and non-steroidal anti inflammatory drugs are recommended for treatment of patients with nephrogenic diabetes insipidus.
 DS (Child) H J 2021; 37(1): 64-70

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Diabetes insipidus (DI) is a disorder characterised by the passage of excess amounts of dilute urine. In central diabetes insipidus, there is a deficiency of antidiuretic hormone (ADH) and in nephrogenic diabetes insipidus, there is decreased response of the kidneys to ADH. In addition to various congenital and acquired causes, several drugs have been implicated in the etiology of DI. Lithium and clozapine are the most common psychotropic drugs shown to induce drug-induced DI. Olanzapine-induced DI is relatively rare and has been reported to occur primarily in the context of overdose. Here, we describe the clinical manifestations and outcome of a patient who was diagnosed with alcohol-induced psychosis and later developed olanzapine-induced DI at a therapeutic dose. After initiation of olanzapine and gradual titration up to 10mg, the patient reported polyuria, polydipsia, and nocturia. Further evaluation revealed low urine osmolality and normal plasma osmolality favouring a diagnosis of diabetes insipidus. The symptoms resolved within a few days of discontinuation of olanzapine without any other specific treatment. A score of 7 was obtained on the Naranjo adverse drug reaction probability scale indicating that olanzapine was the probable cause of DI in the present patient. As evident practising psychiatrists should be aware of the possibility of drug-induced DI as a possible differential diagnosis to primary polydipsia in psychotic patients. Awareness of and familiarity with diagnostic algorithms is essential for rational investigations and identification of the underlying cause.

Clinical and Functional Characterization of a Novel Mutation in AVPR2 Causing Nephrogenic Diabetes Insipidus in a Four-Generation Chinese Family.

Background: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disease that is caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2). Functional analysis of the mutated receptor is necessary to verify the impact of the mutation on receptor function and suggest some possible therapeutic strategies for specific functional defects.Methods: Family history and clinical information were collected. Whole-exome sequencing and sanger sequencing were performed to determine the potential genetic cause of diabetes insipidus. The identified variant was classified according to the American College of Medical Genetics (ACMG) criteria. Bioinformatic analysis was performed to predict the function of the identified variation. Moreover, wild-type and mutated AVPR2 vectors were constructed and transfection to HEK-293T cells. Immunofluorescence experiments were performed to investigate the expression and localization of the mutated protein and cAMP parameter assays were used to measure its activity in response to AVP.Results: The heights of the adult members affected with polyuria and polydipsia were normal, but all affected children had growth retardation. Next-generation sequencing identified a novel mutation in AVPR2 gene (c.530T > A) in this family. Bioinformatic analysis indicated that the mutation in AVPR2 changed the hydropathic characteristic of the protein and was probably deleterious. Although immunofluorescence showed that the mutated AVPR2 was normally expressed in the cell surface, the intracellular cAMP concentration stimulated by AVP was significantly lower in cells transfected with mutated AVPR2 than cells transfected with wild-type AVPR2. Based on the ACMG criteria, the novel c.530T > A variant of the AVPR2 gene was likely pathogenic and the affected family members were diagnosed as CNDI. After the confirmation of the diagnosis, the proband was treated with compound amiloride hydrochloride and rhGH, the symptoms of polyuria, polydipsia and growth retardation were all improved.Conclusion: These findings suggested that the novel mutation in AVPR2 (c.530T > A) was a true disease-causing variant with mild effects, which could be classified as a type III mutant receptor. Moreover, investigations of the function of growth hormone axis could be important for the pediatric CNDI patients with extreme short stature, and rhGH treatment might improve the final adult heights in these patients.

Sevoflurane sedation and nephrogenic diabetes insipidus in patients affected with severe acute respiratory syndrome coronavirus 2.

Sevoflurane sedation and nephrogenic diabetes insipidus in patients affected with severe acute respiratory syndrome coronavirus 2.

Central diabetes insipidus after resection of sellar-suprasellar tumors: prevalence and predictors of manifestation

Central diabetes insipidus is a neuroendocrine disorder caused by disturbances in antidiuretic hormone release. The last one is responsible for fluid and electrolyte balance regulation. The most common cause of diabetes insipidus is resection of sellar-suprasellar tumors followed by damage to hypothalamic nuclei responsible for antidiuretic hormone release, disruption of antidiuretic hormone transportation from hypothalamus or its release by neurohypophysis. According to various data, postoperative diabetes insipidus occurs in 13-30% of cases. The highest risk of diabetes insipidus is observed after resection of craniopharyngioma, Rathke's cleft cyst and ACTH-releasing pituitary microadenoma. This review is devoted to prevalence and predictors of diabetes insipidus after resection of sellar-suprasellar tumors.

Pituitary metastasis as a rare cause of diabetes insipidus

Pituitary metastasis as a rare cause of diabetes insipidus

SUN-283 Lithium Induced Partial Nephrogenic Insipidus: An Unusual Presentation

Background: Diabetes insipidus (DI) is characterized by hypotonic polyuria and polydipsia. Nephrogenic DI is the result of an inadequate response of the kidneys to arginine vasopressin (AVP), either due to hereditary causes or acquired from various drugs, most commonly lithium. Clinical case: A 30 year old male with past medical history of Hashimoto’s thyroiditis, severe mental impairment was admitted to the hospital for abdominal pain. Medical history was difficult to obtain since the patient was nonverbal. His thyroid function tests, electrolytes including sodium, potassium were all normal on admission. During the hospital course, he was made NPO for both an upper and lower GI endoscopy. He notably had a mild increase in sodium level with subsequent improvement after restitution of diet. Two days after the procedure, he was found to be drinking out of the toilet and also attempting to drink from the urine jug. Due to this odd behavior, he had to be put on physical restraints. The day after, he was found to have a serum sodium of 158 mEq/L. Hypotonic saline was started and urine output was notably ranging from 6-10 L/day with a negative balance. Desmopressin (DDAVP) test was done with a resultant urine osmolality of 170, 237, 257 and 264 mOsm/kg after 30, 60, 90 and 180 mins. Subcutaneous DDAVP was started with some improvement of serum sodium and decrease in urine output. Endocrinology service was consulted for the evaluation of hypernatremia and polyuria. Initial review of his medications did not show any potential cause of DI. Further inquiry of his prior medication history revealed that he had taken Lithium for over 10 years and stopped 4 months prior to the admission due to polyuria. After excluding other causes of polyuria, with partial improvement of urine osmolality to a level <300 mOsm/kg and a clinical history of prior Lithium therapy, a diagnosis of partial nephrogenic DI was made. Patient was started on HCTZ and given adequate water intake with subsequent improvement of his serum sodium back to normal. Conclusion: Nephrogenic DI due to Lithium use usually recovers after treatment is stopped but could be persistent for several years after. In our case, the patient compensated for his polyuria with increased water intake. When his water intake was restricted due to physical restraints, polyuria and subsequently hypernatremia became evident. A thorough medication history including past drug use is essential as it can help unravel the offending agent which was Lithium in our case. There needs to be an increased awareness that the effect of Lithium in the kidneys could be persistent even after stopping the drug for up to many years.

DIABETES INSIPIDUS: LITTLE-KNOWN FACTS

The most common causes of diabetes insipidus are neurosurgical operations on the pituitary gland due to its defeat by benign and malignant tumors, the neoplasms themselves, lymphocytic hypophysitis. Much less is known about the development of metastatic lesions of the pituitary gland by primary tumors of the lung, breast and kidneys. Even less common is diabetes insipidus caused by leukemia, lymphoma, xanthogranulomas, germinomas, HIV infection, pituitary hemorrhage, drug-induced, combined with neurofibromatosis, as well as diabetes insipidus during pregnancy. The review describes the predictors of the development of diabetes insipidus during surgical interventions, the frequency of development and prognosis in various neurosurgical operations. The article focuses doctors of various specialties on timely diagnosis, prevention and treatment of diabetes insipidus, including its atypical forms.

Metastasis - A rare cause of diabetes insipidus and pituitary insufficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Primary CNS lymphoma as a cause of diabetes insipidus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Jean Camus and Gustave Roussy: pioneering French researchers on the endocrine functions of the hypothalamus.

At the beginning of the twentieth century, the hypothalamus was known merely as an anatomical region of the brain lying beneath the thalamus. An increasing number of clinicopathological reports had shown the association of diabetes insipidus and adiposogenital dystrophy (Babinski-Fröhlich's syndrome), with pituitary tumors involving the infundibulum and tuber cinereum, two structures of the basal hypothalamus. The French physicians Jean Camus (1872-1924) and Gustave Roussy (1874-1948) were the first authors to undertake systematic, controlled observations of the effects of localized injuries to the basal hypothalamus in dogs and cats by pricking the infundibulo-tuberal region (ITR) with a heated needle. Their series of surgical procedures, performed between 1913 and 1922, allowed them to claim that both permanent polyuria and adiposogenital dystrophy were symptoms caused by damage to the ITR. Their results challenged the dominant doctrine of hypopituitarism as cause of diabetes insipidus and adiposogenital dystrophy that derived from the experiments performed by Paulescu and Cushing a decade earlier. With their pioneering research, Camus and Roussy influenced the experimental work on the hypothalamus performed by Percival Bailey and Frederic Bremer at Cushing's laboratory, confirming the hypothalamic origin of these symptoms in 1921. More importantly, they provided the foundations for the physiological paradigm of Neuroendocrinology, the hypothalamus' control over the endocrine secretions of the pituitary gland, as well as over water balance and fat metabolism. This article aims to credit Camus and Roussy for their groundbreaking, decisive contributions to postulate the hypothalamus being the brain region in control of endocrine homeostasis and energy metabolism.

From Polyuria to Renal Mass: An Unexpected Link

From Polyuria to Renal Mass: An Unexpected Link

Evaluation of Patients with Intracranial Tumors and Central Diabetes Insipidus

The aim of the study is to evaluate the etiologic and clinical characteristics, treatment regimens, and outcome of the patients with intracranial tumors presenting with central diabetes insipidus (DI). Sixty-nine patients with intracranial tumors presenting with central DI between 1972 and 2012 were retrospectively evaluated. Fifty-three out of 69 patients were included in the analysis. Male/female ratio was 1.52, median age was 7.6 years. Of 53 patients, 37 patients (69.8%) were diagnosed with Langerhans cell histiocytosis, 14 patients (26.4%) with germinoma, 1 (1.9%) with astrocytoma, and 1 (1.9%) with optic glioma. 10-year overall survival (OS) rate and disease-free survival rate for all patients were 91.7% and 52%. 10-year OS rate according to diagnostic criteria was 91% for Langerhans cell histiocytosis (LCH) cases, 79% for intracranial germinoma, which was statistically significant (P = .0001). Central DI may be very important clinical presentation of serious underlying disease in children. Intracranial tumors are the most frequent cause of DI. Most frequent diagnosis were LCH and germ cell tumors in our series.

Diabetes insipidus: a challenging diagnosis with new drug therapies.

Diabetes Insipidus (DI) is either due to deficient secretion of arginine vasopressin (central) or to tubular unresponsiveness (nephrogenic). Drug induced DI is a well-known entity with an extensive list of medications. Polyuria is generally defined as urine output exceeding 3 liters per day in adults. It is crucial to identify the cause of diabetes insipidus and to implement therapy as early as possible to prevent the electrolyte disturbances and the associated mortality and morbidity. It is very rare to have an idiosyncratic effect after a short use of a medication, and physicians should be aware of such a complication to avoid volume depletion. The diagnosis of diabetes insipidus is very challenging because it relies on laboratory values, urine output, and the physical examination of the patient. A high clinical suspicion of diabetes insipidus should be enough to initiate treatment. The complications related to DI are mostly related to the electrolyte imbalance that can affect the normal physiology of different organ systems.

Membrane protein stability analyses by means of protein energy profiles in case of nephrogenic diabetes insipidus.

Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low incidences in an estimated one per 25,000–30,000 live births. This disease is characterized by polyuria and compensatory polydypsia. The diverse underlying causes of DI can be central defects, in which no functional arginine vasopressin (AVP) is released from the pituitary or can be a result of defects in the kidney (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to concentrate their urine despite the presence of AVP. This antidiuretic hormone regulates the process of water reabsorption from the prourine that is formed in the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP-driven cascade, which leads to the insertion of aquaporin-2 water channels into the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to NDI. We investigated a structure model of V2R in its bound and unbound state regarding protein stability using a novel protein energy profile approach. Furthermore, these techniques were applied to the wild-type and selected mutations of aquaporin-2. We show that our results correspond well to experimental water ux analysis, which confirms the applicability of our theoretical approach to equivalent problems.

Diabetes Insipidus Secondary to Combination Atypical Antipsychotic and Lithium Use in a Bipolar Disorder Patient

To the Editor: We describe the case of 27-year-old woman with bipolar disorder who developed symptomatic and laboratory evidence of diabetes insipidus only when lithium was used in combination with risperidone or quetiapine, but not when lithium was used alone. We speculate a mechanism involving renal modulation of the antidiuretic hormone (ADH)–desensitizing effect of lithium by the antipsychotics used. This case highlights the importance of regular renal monitoring and patient inquiry for diabetes insipidus symptoms, especially in the context of combined use of lithium and antipsychotics. Case report. Ms A, a 27-year-old woman with DSM-IV bipolar disorder, type I, had been on lithium treatment for 1 month when first hospitalized and diagnosed in 2007. This was followed by risperidone 3 mg/d for 2 months and paliperidone 6 mg/d intermittently for 8 months. The medications were never taken concurrently. Polydipsia, polyuria, and nocturia had not occurred previously. Her medical history was negative for diabetes mellitus, intracranial pathology, or other potential causes of diabetes insipidus. In December 2009, after 5 months without medications, she suffered a manic episode; lithium was restarted at 1,050 mg/d and was maintained at serum levels between 0.45 and 0.90 mEq/L. Long-acting injectable risperidone 25 mg every 2 weeks was also initiated. Ten weeks after starting lithium plus long-acting injectable risperidone, she developed polydipsia and nocturia 5–6 times per night (baseline was once per night). Fasting serum glucose level was 3.2 mmol/L, serum sodium level was 143 mmol/L, and urine specific gravity was 1.010. Four weeks following onset of symptoms, long-acting injectable risperidone was discontinued, and Ms A was asked to record her liquid intake and urinary frequency. Three weeks after discontinuation of long-acting injectable risperidone, the nocturia resolved, liquid intake decreased from 3.5 to 1.5 L/d, 12-hour fasting urine osmolality was 750 mOsm/kg, urine specific gravity was 1.020, and serum lithium level was 0.88 mEq/L. Serum sodium level was 137 mmol/L; serum creatinine level was 57 μmol/L; serum prolactin, glucose, thyroid-stimulating hormone, calcium, and phosphate levels were within normal limits; and head computed tomography revealed no abnormalities. The patient agreed to a rechallenge with risperidone 0.25 mg/d. Five days later, nocturia 4–6 times per night recurred. After 4 nights of symptoms, urine osmolality was 550 mOsm/kg (< 600 mOsm/kg), urine specific gravity was 1.015, lithium level was 0.75 mEq/L, and serum osmolality was 297 mOsm/kg. Symptoms resolved within 2 days of risperidone discontinuation. A few weeks later, quetiapine 25 mg each night was started for insomnia. Within 1 week, nocturia 3 times per night recurred, but resolved with discontinuation. Three weeks after quetiapine was discontinued, urine osmolality was 845 mOsm/kg, urine specific gravity was 1.025, serum lithium level was 0.92 mEq/L, and serum sodium level was 139 mmol/L. Throughout, Ms A's bipolar I disorder remained in remission. A fine tremor was consistently observed, but there was no evidence of lithium toxicity or hypernatremia. Lithium-induced diabetes insipidus is characterized by decreased urinary concentrating ability and polyuria. Polydipsia or nocturia can also be present. In patients taking lithium long-term, the prevalences of polyuria (> 3 L/24 h), urine osmolalities less than 300 mOsm/L, and reduced renal concentrating ability (urine osmolality < 500–800 mOsm/L) are 19%, 12%, and 50%,1 respectively. Antipsychotic use has not been shown to be an independent risk factor for lithium-associated diabetes insipidus,2 despite the common coprescription of lithium and antipsychotics. In our patient, the onset of polydipsia/nocturia with lithium plus antipsychotic use, resolution of symptoms/laboratory findings outside normal limits with antipsychotic discontinuation, and recurrence with antipsychotic rechallenge are highly suggestive of diabetes insipidus induced by the combination of lithium and an antipsychotic. Serum lithium levels were lower during polyuria, so renal elimination was most likely not reduced by the antipsychotics. We speculate that the mechanism of polyuria involved modulation of the ADH-desensitizing effect of lithium by risperidone/quetiapine renally. In summary, this case emphasizes the importance of regular renal monitoring and patient inquiry for diabetes insipidus symptoms, especially in the common clinical setting when lithium and antipsychotics are coprescribed. Vigilance for potential long-term renal compromise needs to be balanced with clinically sound bipolar disorder management.