eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Diabetes Insipidus: Treatment & Medication
Updated: Feb 6, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
- Treat patients with diabetes insipidus (DI) in an inpatient setting because of the risk of severe dehydration. Destructive or compressive intracranial lesions mandate inpatient stay.
- Distinguishing between central and nephrogenic etiology is essential to the treatment modality.
Surgical Care
- Demonstration of an intracranial mass necessitates surgical care.
Consultations
- Nephrologist
- Endocrinologist: The presence of central diabetes insipidus should prompt an evaluation of anterior pituitary function.
- Diagnostic radiologist
Diet
- Provide affected infants a breast milk diet to decrease solute load. Protein should comprise 6% of caloric intake, and sodium should be reduced to 0.7 mEq/kg/d.
- Provide young children 8% of their caloric intake as protein to enable normal growth. Sodium intake must be maintained at 0.7 mEq/kg/d.
Activity
- Activities resulting in increased insensible water loss should be moderated in the presence of massive urinary water loss to prevent dehydration.
- Heat exposure should be minimized, especially when participating in sports.
Medication
For central diabetes insipidus (CDI), the treatment of choice is desmopressin (a synthetic vasopressin analogue). It is available in parenteral, intranasal, and oral dosage forms. The doses widely vary depending on the preparation used, so take care to correctly calculate the dose. Other useful medications include chlorpropamide and thiazide diuretics. The latter 2 can result in a 25-75% reduction in urine volume and can be used in combination with each other.
Nephrogenic diabetes insipidus (NDI) cannot be effectively treated with desmopressin because the receptor sites are defective and the kidney is prevented from responding. Thiazide diuretics, amiloride,5 and indomethacin or aspirin are useful when coupled with a low-solute diet.
Pituitary hormones
Diabetes insipidus of central origin is due to absence of vasopressin secretion by the pituitary. Consequently, use of a synthetic vasopressin analogue (ie, desmopressin) is required. The natural compound vasopressin (ie, antidiuretic hormone [ADH]) may be used to diagnose nephrogenic diabetes insipidus. It has a very short natural half-life. This permits its safe use in distinguishing central diabetes insipidus from nephrogenic diabetes insipidus by obviating prolonged fluid accumulation in the former. As an aqueous preparation, it can be administered parenterally, intramuscularly, or subcutaneously.
Desmopressin acetate (DDAVP)
A synthetic analogue (1-[3-mercaptopropionic acid]-8-D-arginine vasopressin monoacetate trihydrate) of pituitary ADH. Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.
Dosage must be individualized. Drug is supplied as parenteral (4 mcg/mL), nasal (100 mcg/mL rhinal tube), and PO (0.1- and 0.2-mg tab) preparations.
Adult
0.5-1 mL/d (2-4 mcg/d) IV/SC divided bid
0.1-0.4 mL/d (10-40 mcg) intranasally divided bid/tid
0.1-1.2 mg/d PO divided bid/tid
Pediatric
0.05-0.5 mL/d (0.2-2 mcg/d) IV/SC divided bid
0.05-0.3 mL/d (5-30 mcg/d) intranasally qd or divided bid/tid
>4 years: 0.05-0.2 mg/d PO divided bid/tid
Coadministration with demeclocycline and lithium decreases effects; fludrocortisone and chlorpropamide increase effects of desmopressin
Documented hypersensitivity; platelet-type von Willebrand disease; water loss due to NDI
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Use carefully and monitor serum sodium and body weight because of the danger of overdose and consequent water intoxication; hyponatremia may occur from overdose; every patient must be individually evaluated for optimal dose
Vasopressin (Pitressin)
Has vasopressor and ADH activity. Increases water resorption at distal renal tubular epithelium (ADH effect) and promotes smooth muscle contraction throughout vascular bed of renal tubular epithelium (vasopressor effects). However vasoconstriction also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.
Use only the aqueous preparation, which has a short half-life. Vasopressin tannate in oil, which has a longer action, should not be used.
Adult
0.5 mU (0.0005 unit)/kg/h IV continuous infusion initially, dilute in 0.9% NaCl or 5% glucose to 0.1-1 U/mL; dosage may be doubled q30min prn; not to exceed 10 mU/kg/h
5-10 U IM/SC bid/qid prn; not to exceed 60 U/d
Pediatric
IV: Administer as in adults
IM/SC: 2.5-10 U IM/SC bid/qid prn
Decreased biological activity reported with lithium, demeclocycline, epinephrine, heparin, and alcohol; increased biological activity reported with chlorpropamide, carbamazepine, tricyclic antidepressants, clofibrate, and fludrocortisone
Documented hypersensitivity; chronic renal disease with nitrogen retention
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use with care in seizure disorders, migraines, asthma, vascular disease, renal disease, cardiac disease, goiter, and arteriosclerosis
Diuretic agents
Thiazide diuretics impair sodium chloride reabsorption in the distal tubule, reducing the loss of free water to the collecting system and increasing urine concentration. Reduction in urine volume derives from a concomitant action on the proximal tubule, which causes enhanced reabsorption of isoosmotic sodium chloride from the glomerular filtrate, thus drawing additional water along. The net result of both processes is a smaller volume and a higher concentration of the urine.
Hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide)
Thiazide diuretic.
Combination of decreased free water delivery to distal tubule and increased sodium chloride reabsorption in proximal tubule underlies the efficacy in DI therapy.
Adult
25-50 mg/d PO
Pediatric
<2 years: 2-4 mg/kg/d PO bid/qd; not to exceed 37.5 mg/d
>2 years: 2-4 mg/kg/d PO bid/qd; not to exceed 100 mg/d
Thiazides may decrease effects of anticoagulants, antigout agents, and sulfonylureas; thiazides may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants
Documented hypersensitivity; anuria; renal decompensation
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor urine output and serum electrolytes carefully; caution in renal disease, hepatic disease, gout, DM, and systemic lupus erythematosus
Amiloride (Midamor)
Potassium-sparing diuretic. Has a potassium-sparing effect, so risk of hypokalemia is decreased in combination with hydrochlorothiazide. In addition, the 2 agents are synergistic with respect to antidiuresis.
Adult
5-10 mg/d PO; not to exceed 20 mg/d
Pediatric
Titrate dose gradually, not to exceed 20 mg/1.73 m2/d PO divided bid/tid; may induce nausea in children <4 y
Concomitant therapy with potassium supplementation may increase serum potassium levels so use caution and monitor serum potassium levels frequently if concomitant use of these agents is indicated because of demonstrated hypokalemia; lithium generally should not be administered with diuretics because they may reduce renal clearance and add a high risk of lithium toxicity; administration of nonsteroidal anti-inflammatory agents can reduce diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics when used concomitantly, observe patient closely to determine if desired effect of diuretic is obtained; indomethacin and potassium-sparing diuretics, including amiloride, may be associated with increased serum potassium levels, consider potential effects on potassium kinetics and renal function
Documented hypersensitivity; elevated serum potassium levels (>5.5 mEq/L); impaired renal function; acute or chronic renal insufficiency; evidence of diabetic nephropathy
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor electrolytes and renal function carefully if evidence of renal functional impairment is present, ie, BUN >30 mg/100 mL or serum creatinine levels >1.5 mg/100 mL
Nonsteroidal anti-inflammatory agents
These agents act synergistically with thiazides to diminish urine volume, although precise mechanism is unknown.
Indomethacin (Indocin)
Nonsteroidal prostaglandin inhibitor with antipyretic properties.
Adult
25 mg PO bid/tid; not to exceed 200 mg/d
Pediatric
<2 years: Do not use
>2 years: 2 mg/kg/d PO divided bid/qid doses; not to exceed 150 mg/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; GI bleeding; renal insufficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia is present)
Sulfonylurea compounds
These compounds are an alternative therapy to desmopressin and can be used in combination with thiazide diuretics. Sulfonylurea compounds have the reported property of causing a syndrome identical to inappropriate ADH secretion.
Chlorpropamide (Diabinese)
Promotes renal response to ADH. In CDI, ADH secretion is absent, although ADH receptor sites remain present in the kidney. Thus, interaction of the receptors with sulfonylurea compounds can produce a physiologic antidiuresis.
Dosage must be individualized. Available only in tab form.
Adult
150-250 mg/d PO initially, slowly increase in 50 mg/d increments q3-5d if hypoglycemia does not supervene; not to exceed 750 mg/d
Pediatric
Not established; limited data suggest a starting dose of 50 mg/d PO, may increase by 50 mg/d increments q3-5d; not to exceed 150 mg/d; carefully monitor blood glucose
Clofibrate, fenfluramine, histamine (H2) antagonists, androgens, azole antifungals, anticoagulants, chloramphenicol, fluconazole, gemfibrozil, magnesium salts, methyldopa, MAOIs, probenecid, salicylates, sulfinpyrazone, urinary acidifiers, and sulfonamides may enhance hypoglycemic effects; nicotinic acid, PO contraceptives, isoniazid, hydantoins, estrogens, diazoxide, corticosteroids, cholestyramine, beta-blockers, calcium channel blockers, phenothiazines, rifampin, thiazide diuretics, urinary alkalinizers, and sympathomimetics may decrease hypoglycemic effects; may increase effects of digitalis glycosides
Documented hypersensitivity; ketoacidosis; type 1 DM
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor carefully for hypoglycemia, hyponatremia, and fluid overload; caution in hepatic and renal impairment; cardiovascular disorders may occur
More on Diabetes Insipidus |
| Overview: Diabetes Insipidus |
| Differential Diagnoses & Workup: Diabetes Insipidus |
 Treatment & Medication: Diabetes Insipidus |
| Follow-up: Diabetes Insipidus |
| Multimedia: Diabetes Insipidus |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
Keywords
diabetes insipidus, DI, hypernatremia, thirst, polydipsia, dehydration, central diabetes insipidus, CDI, nephrogenic diabetes insipidus, NDI, failure to thrive, nocturia, fecalith, Wolfram syndrome, diabetes mellitus, optic atrophy, mental retardation, hypokalemia, hypercalcemia
