Diabetes insipidus (DI) is a rare endocrine disorder characterized by the inability to regulate water balance in the body, leading to excessive urination and thirst. Despite its rarity, DI poses challenges due to its potential life-threatening complications if left untreated.
While not as prevalent as diabetes mellitus, its impact on those affected is significant. DI exhibits a low incidence rate, estimated at 1 in 25,000 individuals annually, with a prevalence of approximately 1 in 25,000 to 1 in 30,000 in the general population. It affects both males and females equally.
Diabetes insipidus (DI) arises from dysfunction in the antidiuretic hormone (ADH) system, affecting water balance regulation. Central (cranial) DI results from inadequate production or secretion of ADH by the hypothalamus or posterior pituitary, often due to trauma, tumors, or infections. Nephrogenic DI stems from kidney insensitivity to ADH, caused by genetic mutations or acquired conditions and sometimes medical conditions.
The above abnormalities leads to production of very large amounts of dilute urine, usually more than 3L per day due to impaired water resorption by kidneys.
What are Causes of Diabetes Insipidus (DI)?
The following is a list of causes of DI in a grouped manner.
1. Structural Abnormalities:
- Tumors (e.g., pituitary adenomas)
- Trauma to the head or hypothalamus can damage the pituitary gland
- Hemorrhage in the head
2. Genetic Disorders:
- Familial forms of nephrogenic DI (e.g., X-linked recessive NDI)
- Autosomal dominant forms of central Diabetes Insipidus
3. Infections:
- Meningitis
- Encephalitis
- Tuberculosis involving the hypothalamus or pituitary gland
4. Autoimmune Disorders:
- Autoimmune hypophysitis
- Lymphocytic hypophysitis
5. Medications:
Certain medication usually cause Nephrogenic DI.
- Lithium (used for bipolar disorder)
- Demeclocycline (antibiotic)
- Foscarnet (antiviral)
6. Idiopathic: No identifiable cause, often seen in cases of central DI where structural abnormalities and other causes have been ruled out.
Signs and Symptoms
- Polyuria: Passing large volumes of urine frequently
- Polydipsia: Excessive thirst since you are losing water uncontrollable
- Dehydration
- Some may display signs of hypernatremia such as fatigue, weakness and even seizures.
Blood Tests
In people with suspected Diabetes Insipidus, the following blood tests are done:
Blood U&E: Urea and electrolytes in the blood assess electrolyte imbalance and renal function. Glomerular filtration rate (GFR) and creatinine is also done in the same test.
Blood HbA1C: It is done to exclude Diabetes mellitus. This is because frequent thirst and frequent micturition are also Signs of Diabetes mellitus.
Brain MRI may be required in Cranial DI.
An important diagnostic test is Urine to Serum Osmolality Ratio (U:P). Normally, Blood osmolality (concentration of all chemicals in the blood) is between 285-295mOsmol/kg. Urine Osmolality on the other side is 2 times higher than that. Patients with significant DI have an U:P ratio that is less than 2:1.
Another way to diagnose diabetes insipidus is to do 8 hour water deprivation test, explained below.
How to do Water Deprivation Test
The test is used to diagnose DI and to differentiate cranial from nephrogenic causes.
It has two main stages. The patient should not take any tea, coffee or smoking. They can eat light breakfast before 7:30am.
Stage 1 (Fluid deprivation for 8 hours)
Fluid deprivation start at 8:00am, the patient is instructed to empty the bladder and not drink any fluids.
The patient is done weight every hour for 8 hours, if at any point the she loses > 3% body weight, then urgent serum (blood) osmolality test is done. If serum osmolality is more than 300mOsmol/kg, the patient is diagnosed with DI.
If the patient has osmolality less than 300, you continue the test and do serum osmolality every 4 hours. Urine collected every 2 hours to measure volume and osmolality.
The test is stopped if urine osmolality remains above 600 after 8 hours (at 16:00) of fluid deprivation.
Stage 2 (Differentiate Cranial from Nephrogenic DI)
In this stage, if the patient has dilute urine after 8 hours (urine osmolality < 600), Desmopressin 4mcg IM is given and she can drink water at this stage. Urine Osmolality is then measured every hour for 4 hours in this stage.
If urine osmolality rises to above 600mOsmol/kg after desmopressin, then the patient has cranial Diabetes insipidus. If there is no change in urine concentration (osmolality), then DI is nephrogenic.
Treatment of Diabetes Insipidus (DI)
Treatment of Cranial Diabetes Insipidus is with administration of des-amino-des-aspartate-arganine vasopressin (DDAVP) or simple Desmopressin. This is a synthetic analogue of ADH. It is also important to do Pituitary gland function test as well.
Nephrogenic DI treatment is done by treating the cause, for example if the patient is on medications like Lithium (for Bipolar mood Disorder), it is better to stop and substitute it. Thiazide diuretics like bendroflumethiazide 5-10mg per day are helpful.
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