Diabetes Insipidus in Children
1. Akshay Rathod
2. Osmonova G. Zh.
(1. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. Teacher, Dept. Of Pediatrics, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Diabetes insipidus is an illness involving the inability to concentrate urine in an individual due to deficiency in the secretion of vasopressin in central diabetes insipidus, insensitivity in the response of the kidney to vasopressin in nephrogenic diabetes insipidus, or an individual consuming an unusual large volume of water in primary polydipsia. The clinical manifestations for diabetes insipidus include the presence of polydipsia, polyuria, and nocturia, while, in central diabetes insipidus, the course is insidious, and in nephrogenic diabetes insipidus, the course is gradual. Due to the developments in clinical, laboratory, imaging, and molecular biology tools, there has been an improvement in the etiological diagnosis in diabetes insipidus, especially in idiopathic diabetes insipidus, in which the etiological diagnosis has been achieved in 10%-20% patients compared to the previous diagnosis in 50%, thereby allowing an early treatment, thereby reducing an incidence associated with sequelae. Consequently, there is an utmost necessity in differentiating secondary diabetes insipidus, for instance, in diabetic insipidus involving consumption in patients suffering from nephrogenic diabetes insipidus, brain tumors, head injuries, infiltrative, autoimmunity, or central nervous system infections, in case involving patients suffering for central diabetes insipidus. In connection with management, there is an utmost necessity in utilizing desmopressin, i.e., an analogue for the management for diabetes insipidus, while an increase in consumption, reduction in consumption, as well as management utilizing diuretics and non-steroidal anti-inflammatories for insipidus diabetes associated with nephrogenic diabetes.
Introduction
Diabetes is a Greek word meaning “siphon”. It is from the verb *diabaine*, which means “to stand with legs apart, as in urination, or to go through. Insipidus is the Latin term for “without taste”. In in contrast to diabetes mellitus (DM), which affects the excretion of sweet urine, diabetes insipidus (DI) includes passing urine that is flavorless because of its relatively low sodium content. DI is a rare, but severe disorder, that can prove life-threatening due to its causes of fluid imbalance resulting in severe dehydration and Electrolyte disturbances
DI is distinguished by polydipsia, polyuria, Hypernatremia and dehydration. These types of DI; the most popular type of DI is the Neurological form, known as Central Diabetes Insipidus (CDI), which relies on a deficiency of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). Other names for CDI are in literature. It is also called pituitary, hypothalamic, neurohypophyseal or neurogenic DI. The second most common type of DI is nephrogenic diabetes insipidus (NID), which occurs due to the resistance of the renal tubules to ADH. NDI may be primary (idiopathic) or secondary, because of drugs and chronic ailments such as renal failure, sickle cell or polycystic kidney diseases.
Etiology
Deficiency of AVP secretion is termed as central DI, pituitary DI, or neuro-hypophyseal DI. Destruction of para-ventricular and supra-optic nuclei of the posterior pituitary by a tumor or surgery results in decreased ADH secretion and CDI. Alternatively, CDI may be idiopathic or inherited as either autosomal dominant or autosomal recessive trait in the locus 20p13. About 50% of central DI cases are idiopathic. It usually appears within 24 hours followed by a 2-3-week period of inappropriate antidiuresis. In a German study, only 8.7% of DI cases persisted for more than 3 months. Close follow up of patients diagnosed with idiopathic DI is necessary to detect slowly growing intracranial lesions. Other causes of central DI include infiltrative disorders (histiocytosis X, sarcoidosis), anorexia nervosa, infections such as viral meningitis toxoplasmosis, inflammatory conditions including lupus erythematosus, Wegener’s, and vascular lesions such as arteriovenous malformations or aneurysms. Among them, neurosurgical procedures, tumors, traumatic brain injury, tumors, infiltrative lesions, and malformations are the most frequent causes of DI. NDI can be secondary, which is more common, or primary. The acquired form can be secondary to drugs like lithium, amphotericin B, methicillin and rifampinor due to renal disorders. The congenital forms, which are less common but very severe and difficult to treat, are the X-linked, autosomal recessive and autosomal dominant forms. Majority of cases of hereditary nephrogenic DI have X-linkedinheritance. Hypercalcemia causes defective urinary concentrating ability which is generally reversible with correction of the hypercalcemia and may be associated with reductions both in sodium chloride reabsorption on the thick ascending limb of the loop of Henle, thereby interfering with the countercurrent mechanism. Persistent severe hypokalemia can have similar effects in the collecting tubule and the thick ascending limb of the loop of Henle. A variety of renal diseases can give rise to nephrogenic DI. Apart from lithium multiple medications are associated with nephrogenic DI.
Pathophysiology
Arginine vasopressin (ADH) is an anti-DI ADH is usually transported in the blood to the receptor sites on the basolateral surface of the collecting duct membrane. Activation of the ADH receptor increases cyclic adenosine monophosphate (cAMP) production through a G protein adenylate cyclase coupling, and stimulates protein kinase A; leading to increased recycling of the protein aquaporin in the plasma membrane, which enhances water entry into the cell from the lumen. Absence of ADH receptor does not allow the process to take place, causing inhibition of water intake and polyuria. Alternatively, defective or absent aquaporin impairs the process in the absence of normal arginine vasopressin receptor (AVPR2 or V2 receptor). There are different types of receptor for vasopressin. The V1 receptor present in the endothelial cells leads to a pressor effect by the activation of Ca++ pathway whereas the V2R is the one responsible for water reabsorption by activating cyclic adenosine monophosphate (cAMP) in the kidneys and opening of the aquaporin channels. Although there are many factors responsible for the secretion of vasopressin like nausea, acute hypoglycemia, glucocorticoid deficiency, smoking, the most important stimulus is increased plasma osmolality. The increase in plasma osmolality can be as small as 1%. The baro-regulatory system usually does not cause the secretion of vasopressin during the normal circumstances unless there is a large volume loss, in which case there is release of some amount of this hormone. Vasopressin acts as an antidiuretic by reabsorbing water via the principle cells of collecting ducts and the thick ascending loop of Henle, thereby increasing the plasma blood volume and decreasing the plasma osmolality. It can also cause contraction of the smooth muscles in the blood vessels and release of von Willebrand factor and is regulated at the para.
Diagnosis
The diagnosis of DI can sometimes be challenging because the non-specific symptoms of crying, inability to feed, failure to thrive, and irritability are common to many babies. Thus, high clinical suspicion is required. Besides the complete medical and physical examination, including the child’s daily fluid intake, diet intake, medication, as well as bowel and bladder (voiding) habits, the diagnosis of this condition may involve the following:
Assessment of the first morning urine specific gravity may also be of value. However, in situations of suspected DI, accurate 24-hour urine output with correct measurement of its volume is crucial to confirm the presence of polyuria in the first place. The presence of diluted urine associated with high serum sodium levels and serum osmolality clearly confirms the diagnosis of DI. The serum sodium level in this condition may be high > 150mmol/L, and serum osmolality > 300 mosmol/kg. When serum osmolality > 300 mosmol/ kg with low urinary osmolality (<300 mosmol/ kg) in a case of pathologic polyuria and polydipsia, DI becomes definitive.
Blood levels of serum potassium, and calcium are also necessary to exclude secondary polyuria caused by hypokalemia and/or hypercalcemia, which can impair the kidney’s concentrating ability. The water deprivation test, (WDT) establishes the diagnosis of DI and helps differentiate CWD and NDI on the basis of response to the vasopressin analog. The WDT should ideally be carried out by an experienced person. The response to water deprivation test would include increased urine osmolality to > 450 mosm/ kg, increased urine to serum osmolality of 1.5, and increased concentration of urine to serum osmolality of 1. The response to water deprivation would occur in CWD, and to the vasopressin analog in CDI, but not in NDI, which would render unresponsive to ADH. However, patients with CWD would show poor ability to increase the concentration of urine, and in CDI, as well as in NDI, this response could be partial. Thus, differential diagnosis among CWD, CDI, and NDI can sometimes be difficult because all of them are potentially capable of producing similar increases in urinary osmolality in the WDT. The hypertonic saline test presents an alternate approach to WDT, which, in turn, helps in diagnosing DI and other polyureic states. This approach involves calculating the relationship of serum osmolality to blood concentration of arginine vasopressin (AVP) levels. The test of well-established use in adults, with limited exceptions supporting its use in children. Mohn et al from UK used this test in-five children (11 months-18 years) with diagnostic problems. MRI pituitary and hypothalamus are an essential component of evaluation of the underlying cause of CDI, and should always include the post-gadolinium injection contrast examination, looking for an ectopic focus of hypertrophy stalk. Renal Ultrasonography is useful in excluding primary renal pathologies such as polycystic renal diseases and ureteric obstruction. Mega hydronephrosis and mega-ureter are not uncommonly observed in children with long-lasting polyuria and polydipsia. Gene studies have been made available form familial forms of CDI and NDI.
Management
Management’s first step in DI management begins with patients’ education regarding the diseases and their management. The management aims are basically focusing on reducing polyuria and thirst so that the patient can grow well and have a normal life-style. This can be done in several ways, i.e., free access to water; for DI patients, enough fluid can bedrunk to compensate for urine losses. In cases where oral replacement fails due to hypernatremia, the same losses can be replaced by dextrose in water or IV hypotonic fluids compared to patient’s serum osmolarity. Patients who are on DI can drink enough amounts to compensate for urine losses. However, in cases where oral intake is inadequate and where they have developed hypernatremia, then the same amounts can be replaced by dextrose in water or IV hypo-osmolar fluids, depending on the patient’s osmolality differences in the blood. However, there is no role for administration of sterile water in IV replacement as it can cause hemolysis in the recipient. To prevent complications like high sugar levels, volume expansion, and precipitous drop in plasma osmolarity, administration for the patients can be carried out in slow fashion, reducing plasma levels by 0.5 mmol/L (0.5 in every mEq/L in each hour. Careful attention, in fact, can be taken in an intensive care unit. Regarding diet, management mainly relates to maximal free water excretion. Changes in dietary regulation can help in reducing solute load on the kidney, which has been proved advantageous in reducing NDI. Low sodium diet (1 mmol/kg/day).
Prognosis
The Central DI that occurs after pituitary surgery generally remits in days to weeks but, if injury to the stalk has occurred, even central DI can be permanent. The clinical course that follows central DI is much more one of inconvenience to daily activities rather than being a life-threatening condition. The modality that is currently available with Desmopressin is good for controlling symptoms but patients need to be observed very closely for adverse reactions to medication and for situations like water intoxication and hypernatremia. Prognosis of NDI is satisfactory if and only if there was a possibility to resolve that particular etiology.
Conclusion
DI is not a rare pediatric problem. The presentation will vary depending on the age of onset and the underlying cause. The water deprivation test can be seen as a useful tool in confirmation, if the presentation is unusual, and to distinguish among the causes, but it needs to be done under close observation by trained personnel who has knowledge on the test itself. The management plan of DI is essentially directed towards managing the cause. Desmopressin is the drug of choice in cases of CDI, and the oral form has more preference. The use of a combination of thiazide diuretic oral drugs appeared quite effective in cases of NDI.
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