Central Diabetes Insipidus: Symptoms and Treatment

Central Diabetes Insipidus is a rare disease condition that must not be confused with nephrogenic diabetes insipidus.

Although both are types of diabetes insipidus, in central diabetes insipidus, you do not have sufficient levels of ADH (Antidiuretic hormone) or vasopressin. These insufficient levels are due to a damaged hypothalamus or pituitary gland.

Central diabetes mellitus is the most common form of diabetes insipidus. Its symptoms are almost similar to those of nephrogenic diabetes insipidus but it has an entirely different cause.

Central diabetes insipidus (CDI) should also not be confused with diabetes mellitus, a condition in which your pancreas does not produce enough insulin or your body does not use the insulin that is produced properly.

Both conditions might have some common symptoms but different hormones are affected in both conditions.

They are both referred to as “diabetes” because they both cause excessive thirst and frequent urination.

The term “diabetes” is derived from the Greek word “diabainein,” which means “to pass through” — similar to the liquids that quickly pass through your body in these conditions.

What is the role of vasopressin in central diabetes insipidus?

The primary defect in central diabetes insipidus is a relative or absolute deficiency of arginine vasopressin.

Vasopressin or ADH is a hormone that primarily acts on the kidneys. Its primary function is to inhibit fluid loss via the kidneys and hence retain water. Lack of vasopressin will result in excessive urination and dehydration if the thirst mechanism is also impaired.

Vasopressin is released by the posterior lobe of the pituitary gland but it is initially synthesized in the hypothalamus. It acts on the distal tubules in the kidney and increases the permeability of water in the distal tubules.

Thus, any damage to the hypothalamus or the pituitary gland might lead to central diabetes insipidus. This results in little to no vasopressin which greatly disturbs water homeostasis.

Types of Central Diabetes Insipidus

There are two common forms of Central Diabetes Insipidus:

Primary Central Diabetes Insipidus:

This form of CDI is genetic and occurs due to mutations on chromosome 20 that cause vasopressin gene abnormalities.

These congenital abnormalities are mostly autosomal and the disease symptoms appear in early childhood.

Secondary Central Diabetes Insipidus

Secondary CDI can be acquired or it can be caused due to various reasons such as cranial injuries, hypophysectomy (surgical removal of the pituitary gland), skull fractures, tumors, granulomas, or vascular lesions.

Why do people develop Central Diabetes Insipidus?

Central diabetes insipidus is caused by a partial or complete lack of vasopressin. This deficiency is usually caused by damage to your hypothalamus, pituitary gland, or the tissue connecting them (pituitary stalk).

Among the specific causes are:

• Damage to the hypothalamus or pituitary gland due to surgical procedures.
• A head injury or a skull fracture can cause damage to your hypothalamus or pituitary gland.
• Sarcoidosis or tuberculosis-related inflammation.
• Brain tumors like craniopharyngioma and germinoma.
• Histiocytosis of Langerhans cells (a rare disorder that can damage tissue or cause lesions to form in one or more places in your body).
• A gene mutation on chromosome 20.

Symptoms of Central Diabetes Insipidus:

Central Diabetes Insipidus can occur abruptly at any age but the most common age of onset is between 10 to 20 years.

The symptoms might vary according to the type of CDI.

For primary CDI the most common symptoms are

• Polydipsia (excessive fluid intake of more than 3 L/day)
• Polyuria (excessive urination with dilute urine and specific gravity < 1.005)
• Dehydration
• Hypovolemia

For secondary CDI these symptoms might be present with

• Associated lesions
• Head injury or skull fractures
• Tumors

Diagnosis of Central Diabetes Insipidus:

CDI has a lot of common symptoms with diabetes mellitus and nephrogenic diabetes insipidus so, for an accurate diagnosis, your healthcare provider might run a number of diagnostic tests.

It is important to check blood sugars and exclude the diagnosis of diabetes mellitus first as DM is very common.

The next important clue to the diagnosis is peeing excessively. The patient may be asked to measure the total volume of urine per 24 hours. In patients with diabetes insipidus, the 24-hour volume usually exceeds 4 L.

In addition, patients may have electrolyte abnormalities, importantly, hypernatremia (high plasma sodium levels). Specific tests may follow the initial investigations which include the water deprivation test.

Water Deprivation Test

It is the simplest and most reliable method to diagnose diabetes insipidus either central or nephrogenic.

This test involves not drinking water or any liquid for some hours to see the body’s response. If you have CDI, you’ll continue to have excessive urination despite water deprivation.

Once you have tested positive for CDI some other tests might be done to distinguish it from nephrogenic diabetes insipidus.

• Blood tests to check ADH levels
• Urine analysis to check the osmolality and specific gravity of the urine.

In diabetes insipidus, the urine osmolality will be less than 300 mOsm/Kg despite dehydration. This means that despite the body being water deficient, the person is passing dilute and excessive urine.

If the person loses 3% of the body weight during the water deprivation test or two consecutive urinary osmolalities have a difference of less than 30 mOsm/Kg, the patient is given synthetic ADH.

Synthetic ADH administration:

To differentiate between central and nephrogenic diabetes insipidus, synthetic ADH is given. This determines the kidney’s response to ADH.

After the administration of synthetic ADH administration, the urine volume will markedly reduce and plasma osmolality will increase to more than 750 mOsm/Kg indicating adequate urine concentration.

However, an adequate response is only seen in patients with central diabetes insipidus. Those with nephrogenic DI will not have an adequate response.

For further digging out the cause of central diabetes insipidus, imaging tests may be done including MR of the brain, serum calcium levels, and tests for tuberculosis and sarcoidosis.

Treatment of Central Diabetes Insipidus:

Treatment of central diabetes insipidus can be done through hormone replacement therapy and by treating any correctable cause (such as fractures, injuries, or tumors).

Without proper management, this condition can cause permanent damage to the kidneys.

Two main types of drugs are prescribed for hormone replacement therapy:

1.       Hormonal therapy:

Hormonal drugs are alternatives or synthetic analogs of vasopressin such as Desmopressin. These drugs have prolonged antidiuretic activity with minimum vasoconstrictive effects.

Desmopressin is suitable for both children and adults. Its dose ranges from 10-40 mcg for individuals older than 12 years. And 2.5 to 10 mcg twice a day for children of age 3 months-12 years.

2.       Nonhormonal therapy:

The three most commonly used non-hormonal drugs for CDI are:

• Diuretics such as thiazides (These reduce urine volume in partial and complete CDI primarily as a consequence of reducing extracellular fluid (ECF) volume and increasing proximal tubular resorption).
• Prostaglandin inhibitors (They may reduce urine volume)
• Vasopressin-releasing drugs (reduce the need for vasopressin)

Serious Complications of Central Diabetes Insipidus

CDI usually doesn’t cause any serious complications if it is managed properly. But if the treatment is delayed then it can cause some serious complications.

The most common complication resulting from untreated CDI is dehydration, which occurs when your body loses too much fluid and electrolytes to function properly.

If dehydration is not treated it might cause:

• Brain damage
• Seizures
• Fever
• Irregular heartbeat
• Developmental delays
• Fatigue and dizziness