Central Diabetes Insipidus
From Holoprosencephaly
Diabetes Insipidus
Diabetes Insipidus (DI) refers to a disorder where the urine is inappropriately large in volume and too dilute (water like) given the plasma sodium (salt) level. Plasma sodium level is usually tightly regulated by a feedback loop from the hypothalamus (the brain) to the pituitary gland, to the kidney. Normally, an increase in plasma sodium level would be sensed in the hypothalamus and stimulate thirst as well as increased ADH (anti-diuretic hormones) secretion. Thirst usually leads to increased fluid intake. ADH is secreted by posterior pituitary and tells kidneys to hold on to more water. Holding onto more water lowers the plasma sodium level. Abnormal responses anywhere in this feedback loop can cause Diabetes Insipidus (DI).
DI can be categorized into central causes or nephrogenic. In central DI, there is a problem in the hypothalamus, the pituitary, or both. In nephrogenic DI, the kidneys do not respond appropriately to ADH. Children with HPE may develop central DI secondary to problems in the hypothalamus, the posterior lobe of the pituitary, or both. Despite the similar names, Diabetes Insipidus is not related to Diabetes Mellitus (which is sometimes called sugar diabetes).
Signs & Symptoms
Clinical findings of DI include irritability, polyuria (excessive urination), intense thirst, constipation (or pebble like hardened stools), evidence of dehydration, increased serum osmolality and hypernatremia (high blood sodium levels).
Significant hypernatremia is generally defined as > 160 meq/l. A normal plasma (blood fluid) sodium level is 140 meq/l. Hypernatremia is usually encountered in the setting hypovolemia (dehydration) which may occur with even mild illness. This occurs because the body loses fluid which is lower in salt content than plasma. Increased water loses can be due to fever, rapid breathing or sweating. Increased secretion of ADH and increased thirst (leading to increased fluid intake) are compensatory responses.
If, however, thirst cannot trigger an increase in oral fluid intake, because the condition of the child, then hypernatremia may result. Because of abnormal hypothalamic regulatory mechanisms, children with HPE are probably more prone to hypernatremia as well as hyponatremia (low blood sodium levels), both of which can be serious problems.
Diagnosis
Diagnosis is based on a series of blood tests, including urinalysis and a fluid deprivation test.
Plasma sodium levels are probably the most commonly ordered blood tests after CBC's (complete blood counts). Sodium levels are usually checked in children who are acutely ill and being admitted to the hospital or when seen in the ER because of dehydration/ vomiting; however, blood sodium levels may need closer monitoring with HPE.
Concentration of the urine is evaluated by measuring how many particles are in a kilogram of water (osmolality) or by comparing the weight of the urine to an equal volume of distilled water (specific gravity). The urine of a person with DI will be less concentrated. Therefore, the salt and waste concentrations are low, and the amount of water excreted is high. A fluid deprivation test helps determine whether DI is caused by (1) excessive intake of fluid, (2) a defect in ADH production, or (3) a defect in the kidneys' response to ADH. This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary.
Treatment
The treatment of choice for central DI is DDAVP and (desmopressin), a synthetic form of ADH, available in three forms: intranasal, injectable, and oral. Although many children may achieve control with fluids. Philosophy on how aggressive to be in treating DI varies widely among pediatric endocrinologists and pediatricians. Trying to tightly regulate plasma sodium with DDAVP and keeping fluid intake constant is very difficult often results in other problems. Some children with HPE and DI may do fine without DDAVP at all, but plasma sodium levels should checked frequently when they are ill, having more seizures, or are on IV fluids. Other children may need a single dose of DDAVP. Some may do well with increased GT water boluses when ill or increased access to fluids. How to treat central DI is complicated. There is no answer that is the same for all children.
Chronically untreated, this condition could cause seizures, organ failure and eventual death.
To learn more about sodium levels, hypernatremia, and diabetes insipidus in children with Holoprosencephaly,
see section: [What is partial diabetes insipidus?]
or visit: Discussion by Dr. Eric Levey
To learn more about DDAVP (Desmopressin), see: [Medication Index/DDAVP]
Sources:
Eric Levey, M.D.
NIDDK NIH
Resources:
www.diabetesinsipidus.org
