Diabetes insipidus overview

# Overview
Diabetes insipidus (DI) is a syndrome characterized by the excretion of abnormally large volumes of dilute urine. It can be classified into three fundamentally different types that must be distinguished from one another in order to facilitate appropriate diagnosis and treatment. These are central DI (also called neurogenic DI), which occurs due to inadequate production and secretion of antidiuretic hormone, arginine vasopressin (AVP); nephrogenic DI, which occurs due to renal insensitivity to the antidiuretic effect of AVP; and primary polydipsia (also known as psychogenic DI), which occurs due to the suppression of arginine vasopressin secretion by excessive fluid intake. Patients with DI typically present with excessive day and nighttime urination and excessive fluid intake in order to compensate for the lost fluids in urine, which may lead to electrolyte imbalances such as hypo- or hypernatremia. The causes of diabetes insipidus are unique to each variation of the disease, and a treatment plan should be targeted toward the underlying cause of the disease.

# Historical Perspective
The history of diabetes insipidus dates back as the early 1670s when Thomas Willis noted that there was a difference in the taste of urine produced by different patients who presented with polyuria and polydipsia. This marked the beginning of the research into the difference between the popularly known diabetes mellitus and diabetes insipidus.

# Classification
Diabetes insipidus can be classified into three types: Central, nephrogenic, and psychogenic diabetes insipidus. Some rare types of diabetes insipidus include gestational diabetes insipidus which occurs only in pregnancy; autoimmune diabetes insipidus caused by an autoimmune reaction and thirst related diabetes insipidus.

# Pathophysiology
The posterior pituitary consists of paraventricular and the supra-optic nuclei that synthesizes oxytocin and arginine vasopressin respectively. In Central DI, there is an absence of vasopressin which is responsive to the exogenous administration of desmopressin. On the contrary, in nephrogenic DI, solute excretion and all filtration functions of the kidney are normal but urine is hypotonic and there is a characteristic resistance to the antidiuretic effects of both endogenous and exogenous administration of vasopressin. More than 55 different genetic mutations resulting in a defective prohormone and a deficiency of AVP have been identified in familial central diabetes. Many conditions have been associated with the development of diabetes insipidus such as Wolfram syndrome also known as DIDMOAD, Langerhans cell histiocytosis (LCH), sickle cell disease and amyloidosis.

# Causes
Diabetes insipidus is caused by a variety of factors. The causes for each subtype of diabetes insipidus is classically different. It is important to identify these underlying causes of the various forms in order to appropriately diagnose and treat each type.

# Differentiating Diabetes insipidus from other Diseases
Diabetes insipidus must be differentiated from other diseases that cause polyuria which is defined as a urine output exceeding 3 L/day in adults and 2 L/m2/day in children, increased frequency or nocturia and polydipsia. It is important to know that levels of hypo or hypernatremia is not sufficient to describe the underlying cause of diabetes insipidus.

# Epidemiology and Demographics
The prevalence of diabetes insipidus is estimated to be 3:100,000 individuals worldwide. The prevalence and incidence of both central and nephrogenic DI does not vary by gender. Similarly, no significant racial predilection in prevalence among ethnic groups have been found.
With both central and nephrogenic DI, inherited causes account for approximately 1-2% of all cases. An incidence of about 1 in 20 million births for nephrogenic DI caused by AQP2 mutations has been documented.

# Risk Factors
The risk factors in the development of diabetes insipidus vary depending on the type of DI caused. There are a few risk factors in the development of central DI which include genetic mutations, pituitary disorders, hypothalamic injury, head tumors. The most potent risk factor in the development of nephrogenic diabetes insipidus is lithium use; as lithium has a very narrow therapeutic index of 0.4-0.8 mmol/L . Excessive water intake has been identified to be the only risk factor associated with psychogenic DI; also pregnancy is the for gestational DI.

# Screening
According to the USPSTF screening for diabetes insipidus is not recommended.

# Natural History, Complications and Prognosis
Diabetes insipidus if left untreated results in an elevation in serum sodium and osmolality. The hyperosmolarity seen in these patients may also present with neurologic symptoms such as confusion, altered mental status, seizures, coma and death. The two major complications of diabetes insipidus are dehydration and electrolyte imbalance. Some research also demonstrates that there is decrease in bone mineral density seen in patients with diabetes insipidus. However the mechanism of development is not clearly understood neither is the treatment clearly accounted for because treatment of diabetes insipidus does not reverse the disorder.

# Diagnosis

## History and Symptoms
Clinical examination may provide important clues to possible underlying diagnoses. The age at which symptoms develop together with the pattern of fluid intake, may influence subsequent investigation of diabetes insipidus. The primary symptoms are persistent polyuria and polydipsia, and young children may have severe dehydration, vomiting, constipation, fever, irritability, sleep disturbance, failure to thrive and growth retardation.

## Physical Examination
Depending on the time of presentation, patients with diabetes insipidus usually appear generally weak without any focal neurologic findings. However, physical examination of patients with diabetes is usually remarkable for signs of dehydration, such as tachycardia, tachypnea, hypotension, and dry mucus membranes.

## Laboratory Findings
There are a couple of laboratory investigations that can be carried out in order to diagnose diabetes insipidus. Some of them include plasma sodium and urine osmolality, measurement of urine output, plasma and urine ADH measurement.

## Electrocardiogram
There are no electrocardiogram findings associated with diabetes insipidus.

## Chest X Ray
There are no chest X ray findings associated with diabetes insipidus.

## CT
There are no CT scan findings associated with diabetes insipidus.

## MRI
There are no MRI findings associated with diabetes insipidus.

## Echocardiography or Ultrasound
There are no echocardiography or ultrasound findings associated with diabetes insipidus.

## Other Imaging Findings
There are no other imaging findings associated with diabetes insipidus.

## Other Diagnostic Studies
There are no other diagnostic studies recommended for diabetes insipidus.

# Treatment

## Medical Therapy
The hallmark symptoms of both central and nephrogenic diabetes insipidus (DI) are polyuria, nocturia, and polydipsia due to a concentrating defect. Treatment of central diabetes insipidus is primarily aimed at decreasing the urine output, usually by increasing the activity of antidiuretic hormone (ADH, also called arginine vasopressin or AVP). However, nephrogenic diabetes insipidus (DI) results from resistance of the kidney to the actions of antidiuretic hormone(ADH). As a result, patients with this disorder are not likely to have a good response to hormone administration (as DDAVP) or to drugs that increase either the renal response to ADH or ADH secretion and so other treatment options must be explored.

## Surgery
Surgical intervention is not recommended for the management of diabetes insipidus.

## Primary Prevention
Majority of the cause of diabetes insipidus are idiopathic. However, for the ones in which the causes are known, prevention of the causes can help in avoiding diabetes insipidus.

## Secondary Prevention
The secondary prevention of diabetes insipidus is same as its primary prevention.

## Cost-Effectiveness of Therapy

## Future or Investigational Therapies

# Case Studies

## Case #1