Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 23;13(2):e13523.
doi: 10.7759/cureus.13523.

Diabetes Insipidus: Pathogenesis, Diagnosis, and Clinical Management

Cody M Mutter  1 , Trevor Smith  1 , Olivia Menze  1 , Mariah Zakharia  1 , Hoang Nguyen  1
Affiliations
Review

Diabetes Insipidus: Pathogenesis, Diagnosis, and Clinical Management

Cody M Mutter et al. Cureus. .

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.

Keywords: antidiuretic hormone; central diabetes insipidus; diabetes insipidus; dipsogenic diabetes insipidus; gestational diabetes insipidus; nephrogenic diabetes insipidus; vasopressin.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Osmoreceptors in the hypothalamus detect increased serum osmolality.
Upon detecting the increased serum osmolality, the hypothalamus sends signals from the supraoptic and paraventricular nuclei to the posterior pituitary via magnocellular neurons to release antidiuretic hormone (ADH) (vasopressin). ADH then reaches the distal convoluted tubules (DCT) of the kidneys and binds to its receptors. This binding causes aquaporin-2 channels to move from the cytoplasm into the apical membrane of the DCT, allowing water to flow back into the bloodstream. As a result, the osmoreceptors in the hypothalamus detect the subsequent decrease in osmolality in the serum and reduces the production of ADH.
Figure 2
Figure 2. ADH function on cells of the collecting duct.
ADH: antidiuretic hormone; AQP2: aquaporin-2 receptors; PKA: protein kinase A.
Figure 3
Figure 3. Central diabetes insipidus is due to a deficiency in the production of ADH, often resulting from damage to the pituitary gland. This leads to dilute urine.
ADH: antidiuretic hormone; AQP2: aquaporin-2 receptors; PKA: protein kinase A.
Figure 4
Figure 4. Nephrogenic diabetes insipidus is caused by a defect in the renal tubules. This defect leads to a decreased response to ADH, resulting in dilute urine.
ADH: antidiuretic hormone; AQP2: aquaporin-2 receptors; PKA: protein kinase A.
Figure 5
Figure 5. Dipsogenic diabetes insipidus is caused by excessive fluid intake or damage to the thirst-regulating mechanism of the hypothalamus, resulting in dilute urine.
ADH: antidiuretic hormone; AQP2: aquaporin-2 receptors; PKA: protein kinase A.
Figure 6
Figure 6. Gestational diabetes Insipidus is caused by an increased concentration of placental vasopressinase, which destroys the mother’s ADH. This leads to large amounts of dilute urine.
ADH: antidiuretic hormone; AQP2: aquaporin-2 receptors; PKA: protein kinase A.
Figure 7
Figure 7. Urine osmolality in water deprivation test.
DI: diabetes insipidus.
See this image and copyright information in PMC

References

    1. Diabetes insipidus. Christ-Crain M, Bichet DG, Fenske WK, Goldman MB, Rittig S, Verbalis JG, Verkman AS. Nat Rev Primers. 2019;5:54. - PubMed
    1. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Moeller HB, Rittig S, Fenton RA. Endocrine Rev. 2013;34:278–301. - PMC - PubMed
    1. Antidiuretic hormone: normal and disordered function. Robertson GL. Endocrinology. 2001;30:671–694. - PubMed
    1. Hickey J. The Clinical Practice of Neurological and Neurosurgical Nursing. Philadelphia, PA: Lippincott Williams & Wilkins; Fluid and metabolic disorders in neuroscience patients; pp. 195–205.
    1. Neuroimaging of central diabetes insipidus—when, how and findings. Adams NC, Farrell TP, O’Shea A. Neuroradiology. 2018;60:995–1012. - PubMed

LinkOut - more resources