Diabetes insipidus

Diabetes insipidus (DI) is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of more than 3 liters a day [1,2]. Central DI results from inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland. Besides central DI further underlying etiologies of DI can be due to other primary forms (renal origin) or secondary forms of polyuria (resulting from primary polydipsia). All these forms belong to the Polyuria Polydipsia Syndrom (PPS). In most cases central and nephrogenic DI are acquired, but there are also congenital forms caused by genetic mutations of the AVP gene (central DI) [3] or by mutations in the gene for the AVP V2R or the AQP2 water channel (nephrogenic DI) [4]. Primary polydipsia (PP) as secondary form of polyuria includes an excessive intake of large amounts of fluid leading to polyuria in the presence of intact AVP secretion and appropriate antidiuretic renal response.Differentiation between the three mentioned entities is difficult [5], especially in patients with Primary polydipsia or partial, mild forms of DI [1,6], but different tests for differential diagnosis, most recently based on measurement of copeptin, and a thorough medical history mostly lead to the correct diagnosis. This is important since treatment strategies vary and application of the wrong treatment can be dangerous [7]. Treatment of central DI consists of fluid management and drug therapy with the synthetic AVP analogue Desmopressin (DDAVP), that is used as nasal or oral preparation in most cases. Main side effect can be dilutional hyponatremia [8].In this review we will focus on central diabetes insipidus and describe the prevalence, the clinical manifestations, the etiology as well as the differential diagnosis and management of central diabetes insipidus in the out- and inpatient setting.     

Diabetes insipidus in the head-injured patient

Diabetes insipidus (DI) is an uncommon but important complication in the head-injured population. A retrospective review of all trauma patients admitted to the intensive care unit (ICU) during a 4-year period who developed DI was undertaken. The incidence of DI was 1.3 per cent in ICU trauma admissions and 2.9 per cent in traumatic head injuries admitted to the ICU. The overall mortality was 69 per cent (18/26). The mean onset time of DI in nonsurvivors (1.5 +/- 0.7 days) was shorter compared to survivors (8.9 +/- 10.2 days) (P < 0.001). All patients who died developed DI within the first 3 days of hospitalization. Patients who develop DI early in their course have a higher mortality than those who develop DI later in their hospital course. The development of diabetes insipidus after head injury carries a 69 per cent mortality rate, and if the onset is within the first 3 days after injury, mortality rate rises to 86 per cent.     

Beitrag zum posttraumatischen Diabetes insipidus

Zusammenfassung Der posttraumatische Diabetes insipidus neurohormonalis als Ausdruck einer traumatisch gest?rten Zwischenhirn-Hypophysenfunktion ist selten. In der Therapie bewu?tloser Sch?delhirnverletzter ist eine genaue Flüssigkeitsbilanz von besonderer Bedeutung, da bei diesen Patienten die Polydipsie als Alarmsymptom eines Diabetes insipidus fehlt und folgenschwere Elektrolytentgleisungen m?glicherweise erst sp?t erkannt werden. Infolge der au?erordentlich gro?en Regenerationskraft der Neurohypophyse und der gro?en Regulationsbreite des neurosekretorischen Systems bilden sich leichte Diabetesinsipidus-Formen fast immer zurück. Auch bei schweren Formen gelingt es, unter entsprechender Elektrolyt- und Substitutionstherapie mit ADH in Kombination mit Tegretol eine Ausheilung oder doch zumindest eine wesentliche Besserung zu erreichen.

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Summary The post-traumatic diabetes insipidus neurohormonalis as symptom of a traumatically disturbed function of hypothalamus and neurohypophysis is comparatively rare.—Regarding the intensive care of unconscious craniocerebral injured persons an exact balance of body-water is of particular importance, since in case of these patients: the polydipsia having the signification of an alarming symptom of diabetes insipidus is missing and since disturbances of electrolytic metabolism of great consequence are often diagnosed at a later date.—In consequence of the effective regeneration force of the neurohypophysis and of the function of hypothalamus, slight forms of diabetes insipidus recede nearly always. —Even in case of occurrence of more severe forms it is possible by an appropriate therapy with electrolytes or with substitution of ADH in combination with Tegretol to achieve a normal function or at least a substantial change recovery.

     

Diabetes insipidus associated with propofol anesthesia

Diabetes insipidus is a clinical entity that is often seen in neurosurgical patients either during or immediately after transsphenoidal hypophysectomy. Rarely, diabetes insipidus can manifest as a new entity months later in patients who have previously had an intracranial injury or operation.     

Diabetes insipidus and nonobstructive dilation of urinary tract

Two cases of diabetes insipidus (hypothalamic and nephrogenic) with massive nonobstructive trabeculation and dilation of the bladder and hydroureteronephrosis are reported. The cases are evaluated thoroughly — radiologically and urodynamically. Treatment options are discussed, including the use of an important new drug, dDAVP. The general subject of diabetes insipidus and its urologic implications is reviewed.     

Diabetes insipidus secondary to penetrating thoracic trauma.

Three cases of diabetes insipidus following non-cranial trauma are presented. They are believed to be the first of their kind reported. The etiology, pathogenesis and differential diagnosis of diabetes insipidus are discussed. The literature if briefly reviewed and similarities between patients with DI due to long bone trauma with fat embolism, post open heart surgery hypotension, Sheehan's syndrome following postpartum hemorrhage, DI and our own patients are discussed. It is concluded that the diabetes insipidus is caused by selective disruption of posterior pituitary circulation due to fat globules, thrombi and hypovolemia resulting in hypoxia and tissue necrosis.     

Transient nephrogenic diabetes insipidus associated with pregnancy

The coexistence of diabetes insipidus and pregnancy is uncommon and can be associated with worsening of the diabetes insipidus. We report a patient who developed a transient nephrogenic diabetes insipidus associated with a pregnancy complicated by preeclampsia. The diabetes insipidus resolved spontaneously within several days after delivery.     

Diabetes insipidus due to pituitary metastasis from bladder cancer

We report a 41-year-old man with bladder cancer who developed polyuria following successful treatment of hypercalcemia and who was found to have a transitional cell carcinoma within the pituitary gland at autopsy. He also had widespread bone metastases. Although primary urogenital cancers rarely metastasize to the pituitary, the patient's clinical course led us to suspect metastatic disease from the bladder cancer. Metastasis to the pituitary gland is more common than generally thought and should be considered in patients with advanced cancer who develop polyuria and polydipsia.     

Diabetes insipidus after carbon monoxide poisoning and smoke inhalation

Diabetes insipidus was encountered in a 58-year-old woman after injury in an closed space fire. Carboxyhemoglobin measured 26% after 30 minutes of assisted ventilation with an FIO2 of 1.0. The failure of antidiuretic hormone was a sign of a diffuse cerebral insult caused by carbon monoxide poisoning. The hormonal deficit was easily corrected by exogenous vasopressin. Mortality was related to the cerebral lesion.     

Diabetes and the kidney in pregnancy

The prevalence of diabetes in pregnant women is increasing, with 4% of deliveries in the United States occurring in women with pregestational or gestational diabetes. The proteinuria of late pregnancy is exaggerated in women with diabetes. However, diabetic women with preserved renal function before pregnancy appear to have little risk of deterioration of kidney function during pregnancy. Women with impaired renal function before pregnancy may be at risk for permanent decline of renal function during pregnancy, although it is unclear whether this represents the effect of pregnancy or the natural history of their diabetic renal disease. Preeclampsia, which is more common in women with diabetes, may be difficult to diagnose in this group of women. From the currently available literature, there appears to be no negative effect of pregnancy on the long-term progression of diabetic renal disease if renal function is normal and marked proteinuria is absent, but in light of recent findings in which preeclampsia appears to be associated with an increased risk of end-stage renal disease, large cohort studies will be necessary before this question can be definitively answered.     

Zur Diagnostik des Diabetes insipidus unter besonderer Berücksichtigung hypophysektomierter Patienten

Zusammenfassung Verschiedene, am gleichen Patienten durchgeführte Stimulationsteste für die ADH-Sekretion (17-Std.-Durstversuch, Carter-Robbins-Test, osmotische Diurese) zeigen eine ausgezeichnete Korrelation. Auf Grund dieser Ergebnisse werden Richtlinien zur möglichst einfachen Diagnostik einer Konzentrationsstörung vorgeschlagen. In den meisten Fällen kann allein schon auf Grund eines exakt durchgeführten Durstversuchs eine Konzentrationsstörung nachgewiesen (höchste Urinosmolalität < 500 mOsm/kg) bzw. ausgeschlossen (höchste Urinosmolalität > 750 mOsm/kg) werden. Lediglich bei einer höchsten Urinosmolalität im 17-Std.-Durstversuch zwischen 500 und 750 mOsm/kg müssen aufwendigere und den Patienten mehr belastende Tests (z. B. Carter-Robbins-Test) eingesetzt werden, um das Vorliegen bzw. den Grad einer Konzentrationsstörung endgültig diagnostizieren zu können. ADH-Injektionen dienen dabei zur Differenzierung zwischen einem ADH-Mangel und einer mangelhaften ADH-Ansprechbarkeit der Niere. Unsere Untersuchungen an hypophysektomierten Patienten (N=29) zeigen auch bei Patienten ohne polyurisch-polydiptisches Syndrom (N=22) eine gegenüber Normalpersonen signifikant eingeschränkte Konzentrationsleistung im 17-Std.-Durstversuch.

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Concerning the diagnosis of diabetes insipidus with especial reference to the hypophysectomized patient

Summary The results of three different stimulation tests for ADH (17 hours thirst period, Carter-Robbins-test, osmotic diuresis) correlate well in the same patient. Because of this we propose a simplified procedure for the detection of failure to produce a concentrated urine. In most cases merely on the basis of a precisely executed thirst period test, one can either recognize an abnormality of concentration (highest urine osmolality less than 500 mOsm/kg), or exlude it (highest urine osmolality greater than 750 mOsm/kg). Only when the highest urine osmolality lies between 500 and 750 mOsm/kg after a 17 hour thirst must more painstaking tests (e.g. Carter-Robbins test) be employed to determine both the presence of and the degree of a failure to produce a concentrated urine. An injection of ADH can be used to differentiate between a deficiency of ADH and a defective response of the kidneys to ADH. Our investigations on hypophysectomized patients (n=29) showed that also in patients without the syndrome of polyuria-polydypsia (n=22), there was a significantly reduced capacity to concentrate urine during a 17 hour thirst period, as compared with normal people.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft (SFB 51).