Diabetes Insipidus: Pathogenesis, Diagnosis, and Clinical Management

Abstract

Diabetes insipidus (DI) is an endocrine condition involving the posterior pituitary peptide hormone, antidiuretic hormone (ADH). ADH exerts its effects on the distal convoluted tubule and collecting duct of the nephron by upregulating aquaporin-2 channels (AQP2) on the cellular apical membrane surface. DI is marked by expelling excessive quantities of highly dilute urine, extreme thirst, and craving for cold water. The two main classifications of DI are central diabetes insipidus (CDI), characterized by a deficiency of the posterior pituitary gland to release ADH, and nephrogenic diabetes insipidus (NDI), characterized by the terminal distal convoluted tubule and collecting duct resistance to ADH. The two less common classifications include dipsogenic DI, characterized by excessive thirst due to a low osmotic threshold, and gestational DI, characterized by increased concentration of placental vasopressinase during pregnancy. Treatment of DI is dependent on the disease classification, but severe complications may arise if not tended to appropriately. The most important step in symptom management is maintaining fluid intake ahead of fluid loss with emphasis placed on preserving the quality of life. The most common treatment of CDI and gestational DI is the administration of synthetic ADH, desmopressin (DDAVP). Nephrogenic treatment, although more challenging, requires discontinuation of medications as well as maintaining a renal-friendly diet to prevent hypernatremia. Treatment of dipsogenic DI is mainly focused on behavioral therapy aimed at regulating water intake and/or administration of antipsychotic pharmaceutical therapy. Central and nephrogenic subtypes of DI share a paradoxical treatment in thiazide diuretics.

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

“…In NDI plasma concentrations of AVP are characteristically elevated, mostly as a result of an acquired abnormality 10 (Table 1). Inherited NDI is rare, with an estimated incidence of approximately 1 per 1,000,000 population per year.…”

Endocrine Disorder in Patients With Craniopharyngioma

“…Central DI is usually the cause of hypernatremia, specific replacement therapy for central DI is usually straightforward and primarily aims at ameliorating symptoms (polyuria and polydipsia) by replacing ADH ( 104 ). The urine volume is reduced 1–2 h after administration, and the action time varies from 6 to 18 h ( 105 ). Nasal feeding purified water is recommended to correct hypernatremia when necessary.…”

Diabetes insipidus: A rare endocrine complication of immune check point inhibitors: A case report and literature review

“…The prevalence of hypophysitis depends on the type and the dose of ICI; 70% of cases were due to cytotoxic T-lymphocyte protein 4 (CTLA-4) blockade, 23% to programmed cell death protein 1 (PD-1) blockade, or in 2% of the cases to its ligand (PD-L1) blockade, and in 3.9% to combination therapy (CTLA-4 and PD-1) (2)(3)(4). At present, the CTLA-4 antibodies (Abs), ipilimumab, PD-1 Abs nivolumab, pembrolizumab, cemiplimab and PD-L1 Abs atezolizumab, avelumab, and durvalumab are Food and Drug Administration (FDA)-and European Medicines Agencies (EMA)-approved (5,6).…”