Diagnosis Of Diabetes Insipidus Research Articles

Diabetes insipidus.

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) inthe 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 bedifferentiated 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 dueto 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 toensure 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.

Visual Vignette

Case Presentation: A 30-year-old female with no prior comorbidities presented to a nephrology center with polyuria and polydipsia of 2-weeks duration. Her 24-hour urine output was more than 6 L/day, and her serum sodium was 147 mEq/L, serum osmolality 302 mOsm/L, and urine osmolality 108 mOsm/L, consistent with a diagnosis of diabetes insipidus. Her glucose, potassium, and calcium levels were normal. Her thyroid-stimulating hormone was 1.13 mIU/L, thyroxine was 8.7 µg/dL, prolactin 34.6 ng/mL, and an 8 am cortisol was 3 µg/dL. She had two normal pregnancies, with last childbirth 8 years back. Her menstrual cycles were regular. Magnetic resonance imaging (MRI) of the brain showed a thickened stalk and enlarged pituitary gland (Fig. 1). On contrast, there was thickening and abnormal enhancement of the stalk and an enlarged pituitary measuring 15 mm, with abnormal heterogeneous enhancement with a peripheral rim of enhancement and a central nonenhancing area (Fig. 1). A diagnosis of infundibulo-hypophysitis was made, and a detailed set of investigations, including antinuclear antibodies, antineutrophil cytoplasmic autoantibodies (ANCA), IgG4, angiotensin-converting enzyme levels, chest X-ray, and skin tuberculin testing was done, with nonrevealing reports. She was started on intranasal desmopressin and prednisolone 60 mg/day with good resolution of symptoms. Desmopressin was stopped after 3 months; after being on high-dose steroids for 6 months, she presented to our center with weight gain and cushingoid features. A repeat MRI was unchanged. Due to a lack of resolution of the MRI features despite prolonged steroid therapy, a whole-body computed tomography scan with a transnasal biopsy of the pituitary gland was planned. Patient's prednisone dose was reduced to 15 mg/day. Patient presented a month later to the medical emergency with acute hypoxemic respiratory failure and acute renal failure, with serum creatinine of 4.75 mg/dL. Chest X-ray showed “white out” lungs, and urine analysis showed numerous red blood cells. A clinical diagnosis of pulmonary-renal syndrome was made, and the patient was started on high-dose steroids and plasma exchange was attempted. However, the patient succumbed within 48 hours of admission. What is the diagnosis?

EJE AWARD 2019: New diagnostic approaches for patients with polyuria polydipsia syndrome.

Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since decades, the gold standard for differentiation has been the water deprivation test, which has limitations leading to an overall unsatisfying diagnostic accuracy. Furthermore, it is cumbersome for patients with a long test duration. Clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. The direct test including vasopressin (AVP) measurement upon osmotic stimulation was meant to overcome these limitations, but failed to enter clinical practice mainly due to technical constraints of the AVP assay. Copeptin is secreted in equimolar amount to AVP but can easily be measured with a sandwich immunoassay. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation and has led to a ‘revival’ of the direct test in the differential diagnosis of DI. We have shown that a baseline copeptin, without prior thirsting, unequivocally identifies patients with nephrogenic DI. In contrast, for the differentiation between central DI 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 superior to the water deprivation test. Close sodium monitoring during the test is a prerequisite. Further new test methods are currently evaluated and might provide an even simpler way of differential diagnosis in the future.

Diagnostic accuracy of copeptin in the diagnosis of diabetes insipidus after pituitary surgery

Diagnostic accuracy of copeptin in the diagnosis of diabetes insipidus after pituitary surgery

Recurrent Polyuria

Recurrent Polyuria

Twelve cases of pituitary metastasis: a case series and review of the literature.

The pituitary gland is an unusual site for metastatic spread, but as patients with metastatic malignancy are living longer, it may become more prevalent. Compression of important anatomy adjacent to the sella may produce disabling symptoms and endocrine derangement, leading to significant morbidity. An ambispective review of patient records between 2013 and 2017 from three neurosurgical centres was performed. After identifying cases, further investigation was performed to evaluate patient demographic, symptoms at presentation, radiological and histological findings, management, and outcome. Our investigation identified 12 patients with pituitary metastasis. The average age of the cases was 63.4years, with breast (n = 4) and lung (n = 4) being the most common primary cancers. In half the cases there was a history of metastatic disease, while in one-quarter of cases, pituitary symptoms were the first sign of malignancy. Adenohypophyseal dysfunction (83%), diabetes insipidus (DI) (75%), headache (67%) and visual field defects (67%) were the most common findings at presentation. Glucocorticoid replacement increased the sensitivity for diagnosis of DI. All cases were contrast enhancing on MRI and the endoscopic trans-sphenoidal approach was preferred for biopsy and debulking. The pituitary should not be overlooked as a site of metastasis and sellar symptoms may be the first presentation of neoplastic disease. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Moreover, the development of DI or ophthalmoplegia from any pituitary lesion is suggestive of metastatic disease even in patients with no known primary.

Issues of differential diagnosis and management of central diabetes insipidus / differential diagnosis and management of central diabetes insipidus

Diabetes insipidus (DI) is a syndrome characterized by the excretion of abnormally large volumes of diluted urine. It can be caused by two fundamentally different defects that must be distinguished for safe and effective management. First: central DI, due to inadequate production/secretion of vasopressin (AVP) and nephrogenic DI, due to renal insensitivity to AVP. Second: primary polydipsia, due to suppression of AVP secretion by excessive fluid intake. This review provides methods of differential diagnosis of DI. The article highlights the availability of functional tests and pituitary MRI in correct diagnosis of central DI. Common treatment algorithms of DI and management of DI in the neurosurgical patients are also discussed. The article provides comparative data of the efficacy and safety of various pharmacological forms of desmopressin in the treatment of central DI.

Lithium: one drug, five complications

BackgroundLithium poisoning could trigger multiple complications. We report the case of a lithium poisoning with five complications that are described for the first time together.Case reportA 60-year-old woman was admitted in our intensive care unit for altered consciousness. Severe lithium intoxication was diagnosed (lithium plasmatic level 8.21 mmol/l) associated with acute oliguric kidney failure. Continuous renal replacement therapy was started immediately. Orotracheal intubation was quickly required because of status epilepticus. Medullary aplasia happened 48 h after the patient was intubated. Infectious and immunological causes were ruled out and lithium poisoning was considered as the most likely etiology. Iterative blood and platelet transfusion were required. Severe polyneuropathy was diagnosed on the 5th day after admission. The patient showed a peripheral tetraparesia and cranial nerve failure while lithium plasmatic level had decreased to a therapeutic level. Conversely, urine output increased and hypernatremia promptly occurred, which led to diabetes insipidus diagnosis. Neuropathy decreased in 72 h and the patient was definitely extubated by the 11th day. Hematologic disturbances decreased and no blood transfusion would be required after the 8th day. The patient would keep sequellas of the poisoning. Thin motricity would still be altered and polyuria would remain. Diffuse alopecia was promptly observed, with no iron deficiency or thyroid disturbance.ConclusionIn addition to presenting this case report, we herein discuss the drug causality, the consequences, and the plausible pathophysiology of these five situations.

Polyuria: A Pathophysiologic Approach

A 22-year-old man presented with a 3-week history of increased thirst, polydipsia, and polyuria. He described consuming large volumes of water and waking up multiple times throughout the night to drink and urinate. He also endorsed symptoms of fatigue and frequent headaches. Prior to this, he had been well. There was no history of diuretic use, lithium use, or renal disease. There was no prior head trauma, cranial irradiation, or intracranial pathology. He denied consumption of nutritional or protein supplements. Clinical exam revealed a well appearing young man with normal heart rate and blood pressure. Visual fields and general neurologic exam were grossly normal.Baselines investigations revealed serum sodium ranging from 141–142 mmol/L (reference range 133–145 mmol/L), creatinine 92 umol/L (50–120 umol/L), random glucose 5.4 mmol/L (3.3–11.0 mmol/L), potassium 4.0 (3.3–5.1 mmol/L) and ionized calcium 1.25 mmol/L (1.15–1.35 mmol/L).A 24-hour urine collection was arranged, and returned a urine volume of 5.6L (normal less than 3 litres/24 hours). Further investigations revealed a serum sodium of 142 mmol/L, serum osmolality 306 mmol/kg (280–300 mmol/kg), and urine osmolality of 102 mmol/kg (50–1200 mmol/kg). AM cortisol was 372 nmol/L (200–690 nmol/L). These results demonstrated inability to concentrate the urine, despite the physiologic stimulus of hyperosmolarity. Based on this, a presumptive diagnosis of diabetes insipidus was made. The patient was instructed to drink as much as he needed to satiate his thirst, and to avoid fluid restriction. The patient was started on DDAVP intranasal spray, which provided immediate relief from his symptoms. Magnetic resonance imaging of the brain revealed an unremarkable pituitary gland with abnormal thickening of the pituitary stalk and loss of the posterior pituitary bright spot. This confirmed the diagnosis of central diabetes insipidus, presumed secondary to infiltrative disease affecting the pituitary stalk.

Incidence of Central Diabetes Insipidus in Children Presenting with Polydipsia and Polyuria

Polydipsia and polyuria are common reasons for referral to the Pediatric Endocrine clinic. In the absence of hyperglycemia, diabetes insipidus (DI) should be considered. The objectives of the study were to determine the prevalence of central DI (CDI) in a group of children presenting for evaluation of polydipsia and polyuria, and to determine if predictive features were present in patients in whom the diagnosis of DI was made. The study was a retrospective chart review of children presenting to the endocrine clinic with complaints of polydipsia and polyuria over a 5-year period. The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 males) were reviewed. CDI was diagnosed in 8 (20%) children based on abnormal water deprivation test (WDT) results. All but one patient had abnormal magnetic resonance imaging (MRI) findings, the most common being pituitary stalk thickening. Children with DI were older (7.86 ± 4.40 vs. 4.18 ± 3.20 years, P = .01) and had a higher propensity for cold beverages intake and unusual water-seeking behaviors compared to those without DI. Baseline WDT also revealed higher serum sodium (Na) and osmolality. The incidence of CDI in children presenting with polydipsia and polyuria is low. Factors associated with higher likelihood of pathology include older age, propensity for cold beverage intake, and higher baseline serum Na and osmolality on a WDT. BMI = body mass index CDI = central diabetes insipidus DI = diabetes insipidus Na = sodium WDT = water deprivation test.

Buccally Administered Intranasal Desmopressin Acetate for the Treatment of Neurogenic Diabetes Insipidus in Infancy.

The treatment of neurogenic diabetes insipidus (DI) in infancy is challenging and complicated by fluid overload and dehydration. Therapy with subcutaneous (SC), intranasal (IN), or oral tablet desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) remains difficult to titrate in infants. Assess the efficacy and safety of buccally administered IN DDAVP for the management of infants with neurogenic DI. Retrospective review of clinical and laboratory data of 15 infants (mean age, 4.5 mo) with neurogenic DI treated at a tertiary care center. Treatment was with diluted IN DDAVP formulation (10 mcg/mL) administered buccally via a tuberculin syringe to the buccal mucosa. After initial DDAVP titration of 2-3 days, IN DDAVP doses ranged from 1 to 5 mcg twice daily given buccally. Mean serum sodium concentration at DI diagnosis was 159 ± 6.6 mmol/L (range, 151-178) and improved to 142 ± 3.5 mmol/L (range, 137-147) with the buccally administered IN DDAVP. Normal sodium concentrations were established without major fluctuations. Serum sodium was then maintained in the outpatient setting at a mean of 145.7 ± 4.8 mmol/L (mean duration of follow-up, 11 mo). Buccally administered IN formulation of DDAVP provides a practical and safe treatment alternative for neurogenic DI in infancy. Our approach avoided severe hypo- and hypernatremia during DDAVP titration and ongoing outpatient management of DI. The possibility for smaller dosage increments and ease of administration make IN DDAVP administered buccally preferable over other DDAVP treatment options in infants.

Potential Clinical Utility of Copeptin (C-terminal provasopressin) measurements in clinical medicine.

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.

Third Molar Extractions: Are we over prescribing the Cone Beam CT?

Case report: A 36 year old female patient was referred by the dentist complaining of persistent pain after extraction of LL5. Of relevance, in the past medical history, is the diagnosis of diabetes insipidus 21 years previously, for which the patient remains on supportive hormone treatment. An initial periapical radiograph showed the presence of a radiolucent ‘lytic’ lesion in the region of LL5. CT scans of chest, abdomen and pelvis were unremarkable. MRI of the head and neck confirmed concurrent involvement of the left maxilla and maxillary sinus with disease extending into the left lateral orbit and left lateral rectus muscle. There were also changes in the sphenoidal sinus area, involving the pituitary territory. Curettage of the lesion confirmed the presence of LCH by histopathology. There was significant bone regeneration in the portion of the mandible where diagnostic curettage was initially carried out. A focus of residual disease beneath two lower left molar teeth resulted in extraction of these teeth at the same time as further curettage with the aim to further control the mandibular disease. The patient has been referred to an endocrine specialist and is commencing a course of systemic chemotherapy. Conclusion: Diabetes insipidus is frequently found in patients with LCH. This interesting case highlights the importance of past medical history in making a clinical diagnosis and the multidisciplinary approach to management.

Diabetes insipidus - a rare complication of major flame burn: case report

Background : Diabetes insipidus is a syndrome characterised by polyuria which is associated with urinary frequency, enuresis, nocturia and polydipsia. We present this case to highlight the significant role of high degree of clinical suspicion and interdisciplinary management resulting in a rewarding outcome in a limited resource environment. Method and result : A 35year old man presented with 31% Total Body Surface Area (TBSA) flame burn injury. He was resuscitated with intravenous Ringer’s lactate. He however developed polyuria on the fifth day post burn with urinary output ranging between 2.5 – 15ml/kg/hr. Urine specific gravity ranged between 1.000 – 1.005. A clinical diagnosis of diabetes insipidus was made. He was treated with vasopressin and desmopressin and the burn wounds were managed without skin grafting. The symptoms of DI resolved at 32nd day post- burn. Conclusion : Diabetes insipidus is a rare occurrence in patients with burns. Therefore, high index of suspicion is needed to detect and effectively manage its occurrence. Key words : Polyuria, enuresis, frequency, nocturia, polydipsia

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.

Index of Suspicion

Index of Suspicion

Current State and Future Perspectives in the Diagnosis of Diabetes Insipidus: A Clinical Review

The differential diagnosis of diabetes insipidus (DI) is often challenging but essential, because treatment may vary substantially. This article analyzes the database and performance of currently used differential diagnostic tests for DI and discusses future perspectives for diagnostic improvement. A review of electronic and print data comprising original and review articles retrieved from the PubMed or Cochrane Library database up to January 2012 was conducted. The search term "polyuria polydipsia syndrome" was cross-referenced with underlying forms of disease and associated clinical, diagnostic, and therapeutic MeSH terms. In addition, references from review articles and textbook chapters were screened for papers containing original data. Search results were narrowed to articles containing primary data with a description of criteria for the differential diagnosis of DI. Fifteen articles on differential diagnosis of DI were identified, mainly consisting of small series of patients, and mostly covering only part of the differential diagnostic spectrum of DI. Test protocols differed, and prospective validation of diagnostic criteria was consistently missing. Inconsistent data were reported on the diagnostic superiority of direct plasma arginine vasopressin determination over the indirect water deprivation test. Both test methods revealed limitations, especially in the differentiation of disorders with a milder phenotype. The available data demonstrate limitations of current biochemical tests for the differential diagnosis of DI, potentially leading to incorrect diagnosis and treatment. The newly available assay for copeptin, the C terminus of the vasopressin precursor, holds promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol in DI.

Antidiuretic response of a horse affected with pituitarypars intermediadysfunction to desmopressin acetate

Summary Central diabetes insipidus (DI) was diagnosed in a 20-year-old American Quarter Horse gelding that was concomitantly affected with pituitary pars intermedia dysfunction (PPID). The diagnosis of DI was supported by a positive response to administered desmopressin acetate. Diagnosis of PPID was supported by physical appearance and elevated plasma adrenocorticotropic hormone concentration following domperidone administration. The horse's physical condition improved following treatment with pergolide but long-term treatment with desmopressin was not undertaken and severe polyuria and polydipsia persisted. Desmopressin acetate appears to be useful for the diagnosis of DI in mature horses concomitantly affected with PPID.

Langerhans Cell Histiocytosis Presenting with Headache and Sellar Mass in an Adult

Introduction Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by aberrant proliferation of a specific dendritic (Langerhans) cell belonging to the monocyte macrophage system. 1 These cells can infiltrate virtually any organ without inducing dysfunction. 2 LCH is encountered more often in children, with a peak age range of 1-3 years and an incidence of 3-5 cases per million per year and a male to female ratio of 2:1. 3 LCH is rare in adults and the incidence may be underestimated due to the fact that many cases likely go undiagnosed. In order of decreasing frequency, the presenting symptoms are skin rash, dyspnea or tachypnea, polyuria and polydipsia, bone pain, lymphadenopathy, weight loss, fever, gingival hypertrophy, ataxia, and memory problems. 4 Regarding the endocrine system, LCH has a particular predilection for involvement of the hypothalamo–pituitary axis (HPA), leading to diabetes insipidus (DI) in up to 50% of cases. In a recent analysis, DI was the most common and permanent consequence of LCH, occurring in 24% of patients. 5 Other endocrine deficiencies can develop in up to 20% of patients. 5,6 Endocrine manifestations include DI followed by growth hormone deficiency with a median latency of about one year, followed by gonadotropin deficiency with a median latency of about seven years from the diagnosis of DI. ACTH and TSH deficiency also have been described. 7

A Case of Increased Desmopressin Requirement Following Growth Hormone Administration in a Patient With a History of Histiocytosis

•Patient developed breakthrough from desmopressin with increased thirst and urination 2 weeks after beginning GH disorder, of unknown etiology, characterized by histiocytic proliferation. It may be a reactive disease caused by abnormal immune regulation (3). LCH can involve multiple or single organs. DI is a common finding in this condition frequently The cause of the increased desmopressin requirement has not been explained. Fluid shifts with the initiation of growth hormone therapy may play a role in this need. While it is well known that dosedependent and transient edema may occur with growth Test Result manage n e pe a r c endocrine clinic for several years following the diagnosis of diabetes insipidus (DI) and langerhan cell histiocytosis (LCH) of pituitary. She has been receiving oral desmopressin (brand name) on a stable regimen with few •No growth for 1 1⁄2 -2 years prior to initial presentation