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Diabetes is a Greek word that is related to urination; insipidus means without taste. This term was used to describe a condition that is characterized by passing large amounts of diluted urine that has low-sodium content, which is why it is called tasteless. Diabetes mellitus, on the other hand, is characterized by passing sweet urine due to hyperglycemia.
Two situations are implicated in the etiology of Pediatric Diabetes Insipidus:
Central DI (also called neurohypophyseal or neurogenic DI) occurs due to deficient secretion of antidiuretic hormone (ADH). The most common etiologies of central diabetes insipidus in children include head trauma, tumors, and a variety of neurosurgical procedures. Malignant neoplasms and destructive lesions of the pituitary gland or the hypothalamus are responsible for most cases.
Nephrogenic DI occurs when the renal tubules are unresponsive to vasopressin, which is caused by certain medications, chronic disorders, or genetic conditions that affect the kidney.
Epidemiology of Diabetes Insipidus in Children
The exact incidence of central diabetes insipidus due to tumors, malformations, or neurosurgical procedures in children is unknown. The estimated incidence of central diabetes insipidus due to genetic causes is around 3 cases per 100,000. X-linked nephrogenic diabetes insipidus is a very rare condition; the estimated incidence in boys is 4 cases per million.
Nephrogenic and central diabetes insipidus is more common in boys than girls. Genetic forms of central diabetes insipidus typically present within the first year of life. Inherited forms of nephrogenic diabetes insipidus are more commonly seen during early infancy and even in neonates.
The prognosis of central diabetes insipidus depends on the etiology. Primary central diabetes insipidus has an excellent prognosis if recognized early enough and properly treated. On the other hand, children with central diabetes insipidus secondary to invasive lesions, malformations, or tumors usually have a less favorable prognosis.
Nephrogenic diabetes insipidus has been linked to an increased risk of learning difficulties and psychomotor delay, but the prognosis is usually good if the child has adequate access to excessive amounts of water.
Pathophysiology of Diabetes Insipidus
The reason for water loss in DI is different from that caused by diabetes mellitus. With DI, the renal tubular collecting ducts cannot concentrate urine because of ADH deficiency or resistance to ADH. Therefore, the posterior pituitary gland, which secretes ADH, regulates urine concentration through water reabsorption by the collecting duct. Therefore, the lack of ability to conserve water through reabsorption in the collecting duct deprives the body of water but does not affect sodium levels. This results in an extremely diluted, heightened urine output that leads to hypernatremia. This is followed by polydipsia because the thirst mechanism stimulates the replacement of body water.
Furthermore, ADH production occurs in the posterior pituitary gland and is regulated by the paraventricular and supraoptic nuclei, which respond to alterations in osmolality. If the paraventricular or supraoptic nuclei or the posterior pituitary is destroyed by a tumor, pressure, or surgical operation, it reduces the production of ADH and central DI.
The most common etiologies
The most common etiologies of central diabetes insipidus in children include head trauma, tumors, and a variety of neurosurgical procedures. Malignant neoplasms and destructive lesions of the pituitary gland or the hypothalamus are responsible for most cases.
An autosomal dominant variant of central diabetes insipidus is caused by a mutation in the prepro-arginine vasopressin gene on locus 20p13. An autosomal recessive form of the disease also exists; it is characterized by central diabetes insipidus and associated with diabetes mellitus, optic atrophy, and mental retardation. The mutation responsible for this form of central diabetes mellitus has been localized to locus 4p16.
Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus is usually caused by an x-linked mutation that affects the antidiuretic arginine vasopressin V2 receptor gene found on locus Xq28. The autosomal recessive and autosomal dominant forms of nephrogenic diabetes insipidus also exist, but the ratio of the x-linked form of the disease to the other forms is 9:1.
- The genetic receptor or aquaporin mutations
- Chronic renal disease
- Renal malformations
Causes of increased urine volume
The cause of increased urine volume and urine dilution in diabetes insipidus is either arginine vasopressin deficiency or resistance to the hormone. Central diabetes insipidus is characterized by a partial or absolute deficiency of the arginine vasopressin hormone, whereas nephrogenic diabetes insipidus is characterized by renal tubular resistance to this hormone. Water uptake in the renal tubules is impaired in either case, and polyuria develops.
Clinical Presentation of Diabetes Insipidus in Children
Children with diabetes insipidus can present with non-specific symptoms, such as poor feeding, failure to thrive, and irritability. Children might become feverish due to dehydration. Constipation and excessively wet diapers may also occur in infants. Older children usually show irritability, symptoms suggestive of dehydration, polyuria, nocturia, and polydipsia. Central diabetes insipidus usually has an acute and sudden onset.
Physical examination reveals:
- Dry mucous membranes
- Increased capillary refill time
- Decreased tearing
Hypotension is a late presentation of severe dehydration and possibly hypovolemic shock. Infants and children with severe dehydration have decreased skin turgor and a weak pulse.
If dehydration and hypernatremia are not corrected, children might develop seizures. Long-term sequelae of uncorrected hypernatremia include the development of mental retardation and learning disorders. Seizures put the infant at an increased risk of sudden death. Death can be caused by either the seizure itself or by hypovolemic shock.
Diagnostic Workup for Diabetes Insipidus in Children
The first diagnostic test for the workup of diabetes insipidus is a urine analysis to check the urine specific gravity of a first-morning urine sample. The urine is usually diluted. In most cases, serum sodium levels are elevated, and serum osmolarity can be greater than 300 mOsm/kg.
When the above investigations indicate diabetes insipidus, a 24-hour urine collection is indicated. The total urine output is usually elevated, while the number of osmoles excreted per day is low.
Water deprivation test
To confirm the diagnosis of diabetes insipidus and differentiate between central and nephrogenic forms of the disease, a water deprivation test is indicated. Urine and blood osmolality are first checked at baseline. Afterward, deprive the patient of water after breakfast. Water deprivation should be limited to seven hours for children and four hours for infants. During the deprivation period, measure serum and urine osmolality every two hours. If polyuria persists, administer intranasal desmopressin.
The interpretation of the water deprivation test is as follows:
The normal response for the water deprivation test and desmopressin is a urine-to-serum osmolality ratio of 1.5 or higher or an increase in that ratio of 1.0 or more from baseline. This normal response is expected in central diabetes insipidus, but not in nephrogenic diabetes insipidus.
Once the diagnosis of central diabetes insipidus is made, one should start looking for possible structural causes. A cranial magnetic resonance imaging study is indicated to exclude pituitary gland tumors, cysts, or hypoplasia.
Treatment of Diabetes Insipidus in Children
Once the diagnosis of diabetes insipidus is made, the child should be admitted to the hospital for inpatient care to correct dehydration and establish the etiology of diabetes insipidus. Children with pituitary gland lesions that are known to cause central diabetes insipidus should be offered a neurosurgical consultation and surgical intervention if necessary.
After adequate intravenous rehydration of the patient, desmopressin should be started for patients with central diabetes insipidus. Desmopressin is available in intranasal, oral, and parenteral forms. Thiazide diuretics might also be needed to lower the urine output and can be combined with desmopressin.
|NASAL DDAVP||Oral DDAVP|
|Rapid onset||Slower onset|
|Damage to the nasal mucosa||Variable GI absorption|
|Not good for infants||Easy to administer to infants|
Desmopressin is ineffective against nephrogenic diabetes insipidus. Thiazide diuretics, amiloride, and indomethacin, coupled with a low-solute diet, are the stadard treatment options for nephrogenic diabetes insipidus in children.