Central diabetes insipidus (CDI) is a disease in which large volumes of dilute urine (polyuria) are excreted due to deficiency of arginine vasopressin (AVP), also called antidiuretic hormone (ADH). Known causes of CDI include mass lesions such as germinomas and craniopharyngiomas, infiltrative disease such as Langerhans cell histiocytosis and sarcoidosis, trauma resulting from surgery or an accident, neoplastic metastases, and midline cerebral and cranial malformations. In rare cases, the underlying cause can be genetic defects in AVP synthesis.43 In addition, roughly one quarter of adult cases and half childhood cases are considered idiopathic.44,45
CDI may present as either transient or permanent. Due to the inability to concentrate urine, patients with CDI may develop dehydration and metabolic abnormalities, including hypernatremia, that can be life threatening if not recognized and treated in a timely manner with AVP or the AVP analog, desmopressin, and appropriate fluids.46
1.2.1.1 Prevalence and Incidence
Data on the epidemiology of CDI are limited. A 2007-2011 study using linked data from the Danish National Prescription Registry, and Danish National Patient Registry identified 1,285 patients with CDI during the 5-year period of the study. The average overall 5-year prevalence of CDI was estimated to be 23 patients per 100,000 inhabitants. The average annual incidence was reported to be three to four new cases per 100,000 inhabitants.47
CDI is a common complication of pituitary surgery. The reported incidence of post-surgical CDI ranges between 1 to 67%, most likely due to inconsistencies in the definition of CDI across the literature.46 Post-surgical CDI can be transient or permanent, further complicating the definition. Traumatic brain injury and subarachnoid hemorrhage can also result in CDI. Table 8 summarizes available data on the prevalence and incidence of CDI by cause.
| CAUSE | DATA SOURCE | POPULATION | PREVALENCE | REFERENCE | |
| TEMPORARY CDI | PERMANENT CDI | ||||
| Transsphenoidal pituitary adenoma surgery | Medical records, Stanford University School of Medicine | US (n=857) | 18.3% | 2.0% | Nemergut et al. 200548 |
| Transsphenoidal pituitary adenoma surgery | Medical records University of Bonn, Germany | Germany (n=57) | 38.5% | 8.7% | Kristof et al. 200949 |
| Transsphenoidal pituitary adenoma surgery | Systematic review of international studies (1990-2011) | International
(n=5,643) |
10.23% | 4.25%
|
Ammirati et al. 201315 |
| Endoscopic transsphenoidal surgery of sellar and parasellar lesions | Detroit Medical Center, department of neurosurgery records (2006-2011) | US (n=172) | 8.7% | 8.1% | Schreckinger et al. 201346 * |
| Traumatic brain injury ** | Beaumont Hospital head trauma database; Dublin | Ireland; age 15-65 years, (n=102) | 21.6% | 6.9% | Agha et al. 200450 |
| Subarachnoid hemorrhage (SAH) *** | Medical records from clinical centers | Italy; age 51.9±2.2 years; (n=32) | 6.25% | 2.8% | Aimeretti et al. 200551 |
Notes: *, Tumor volume and histopathology (Rathke’s cleft cyst and craniopharyngioma) are significant predictors of post-surgical CDI. Significant indicators of development of the disorder were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of desmopressin (an increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity). ** CDI was diagnosed as plasma sodium > 145 mmol/liter in presence of polyuria of > 3.5 liter per 24 hours and dilute urine (osmolality < 300 mOsm/kg); ***, DI was diagnosed by massive dilute urine volume (> 2.5-3 liter per 24 hour) with low urine osmolality (< 300 mOsm/kg).
One study reported that gestational CDI has a prevalence of up to 1 in 30,000 pregnancies, and may be due to a variety of causes that predate pregnancy or start during gestation.52
Because the placenta produces vasopressinase, an enzyme that degrades vasopressin, pregnancy may make manifest previously undiagnosed subclinical CDI. Furthermore, since polyuria is often considered normal during pregnancy, clinicians caring for pregnant women are recommended to consider screening for gestational CDI (along with gestational diabetes mellitus) in those who develop polyuria and polydipsia, as it could be associated with serious underlying pathology.53
1.2.1.2 Demographic Differences
Studies have reported that CDI is more prevalent in children and older adults (>80 years of age).47 Primary tumors of the pituitary fossa result in CDI in 50% of children and 30% of adults, while head trauma to the posterior pituitary gland accounts for 2% of cases in children and 17% in adults.54 Table 9 illustrates the age-specific prevalence of CDI in Denmark.
| AGE | PREVALENCE PER 100,000 |
| 0 – 9 years | 43.6 |
| 10 – 19 years | 34.0 |
| 20 – 29 years | 9.7 |
| 30 – 39 years | 11.8 |
| 40 – 49 years | 16.9 |
| 50 – 59 years | 19.0 |
| 60 – 69 years | 22.5 |
| 70 – 79 years | 26.3 |
| 80 – 89 years | 35.6 |
| 90+ years | 34.5 |
Source: Juul et al. 2014 47
Among adults, 9% of CDI results from inadvertent neurosurgical damage to the posterior pituitary gland, 8% from metastatic carcinoma, and 6% from intracranial hemorrhage and hypoxia. A post-infectious disease process and histiocytosis X cause CDI in 2% and 16% of children, respectively.54
No data on ethnic/racial differences in the epidemiology of CDI are available.
1.2.1.3 Life Expectancy and Mortality
In a prospective study of all patients admitted to the surgical ICU of a level I trauma center with severe head injury (n=436), CDI occurred in 15.4% of all patients and it was identified as an independent risk factor for death.55
1.2.1.4 Key Trends and Health Outcomes
In general, the diagnostic standard for CDI is a water deprivation test with an assessment of AVP activity; however, test interpretation and AVP measurement are often challenging.56
Recent data on a newly available assay for copeptin, the C terminus of the AVP precursor, provide promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol for CDI; however, this assay is not yet readily available commercially.56
Importantly, since CDI may be the end result of a number of conditions that affect the hypothalamic-neurohypophyseal system, patients should undergo further diagnostic testing aimed to identify the underlying cause of the disorder. Because such conditions may also affect the anterior pituitary, an evaluation of anterior pituitary function is also usually indicated.43
Desmopressin acetate is the synthetic analog of AVP and has been used for treating CDI for over 40 years, in a variety of formulations: intranasal solution, injectable solution, conventional tablets, and tablets that dissolve in the mouth.57,58