eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Diabetes Insipidus: Treatment & Medication

Author: James CM Chan, MD, Professor of Pediatrics, University of Vermont College of Medicine; Director of Research, The Barbara Bush Children's Hospital, Maine Medical Center
Coauthor(s): Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Feb 6, 2009

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

References

  1. Bichet DG, Arthus MF, Lonergan M, et al. X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis. J Clin Invest. Sep 1993;92(3):1262-8. [Medline][Full Text].

  2. Friedman E, Bale AE, Carson E, et al. Nephrogenic diabetes insipidus: an X chromosome-linked dominant inheritance pattern with a vasopressin type 2 receptor gene that is structurally normal. Proc Natl Acad Sci U S A. Aug 30 1994;91(18):8457-61. [Medline][Full Text].

  3. Wildin RS, Antush MJ, Bennett RL. Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus. Am J Hum Genet. Aug 1994;55(2):266-77. [Medline].

  4. Faerch M, Christensen JH, Corydon TJ, et al. Partial nephrogenic diabetes insipidus caused by a novel mutation in the AVPR2 gene. Clin Endocrinol (Oxf). Mar 2008;68(3):395-403. [Medline].

  5. Alon U, Chan JC. Hydrochlorothiazide-amiloride in the treatment of congenital nephrogenic diabetes insipidus. Am J Nephrol. 1985;5(1):9-13. [Medline].

  6. Blackett PR, Seif SM, Altmiller DH, Robinson AG. Familial central diabetes insipidus: vasopressin and nicotine stimulated neurophysin deficiency with subnormal oxytocin and estrogen stimulated neurophysin. Am J Med Sci. Nov-Dec 1983;286(3):42-6. [Medline].

  7. Davies JH, Penney M, Abbes AP, et al. Clinical features, diagnosis and molecular studies of familial central diabetes insipidus. Horm Res. 2005;64(5):231-7. [Medline].

  8. Garofeanu CG, Weir M, Rosas-Arellano MP, et al. Causes of reversible nephrogenic diabetes insipidus: a systematic review. Am J Kidney Dis. Apr 2005;45(4):626-37.

  9. Leung AK, Robson WL, Halperin ML. Polyuria in childhood. Clin Pediatr (Phila). Nov 1991;30(11):634-40. [Medline].

  10. Libber S, Harrison H, Spector D. Treatment of nephrogenic diabetes insipidus with prostaglandin synthesis inhibitors. J Pediatr. Feb 1986;108(2):305-11. [Medline].

  11. Mulders SM, Bichet DG, Rijss JP, et al. An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. J Clin Invest. Jul 1 1998;102(1):57-66. [Medline][Full Text].

  12. Pivonello R, Colao A, DiSomma C, et al. Impairment of bone status in patients with central diabetes insipidus. J Clin Endocrinol Metab. Jul 1998;83(7):2275-80. [Medline][Full Text].

  13. Saborio P, Tipton GA, Chan JC. Diabetes insipidus. Pediatr Rev. Apr 2000;21(4):122-9; quiz 129. [Medline].

  14. Soylu A, Kasap B, Ogun N, et al. Efficacy of COX-2 inhibitors in a case of congenital nephrogenic diabetes insipidus. Pediatr Nephrol. Dec 2005;20(12):1814-7. [Medline].

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

Contributor Information and Disclosures

Author

James CM Chan, MD, Professor of Pediatrics, University of Vermont College of Medicine; Director of Research, The Barbara Bush Children's Hospital, Maine Medical Center
James CM Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of University Professors, American Chemical Society, American Heart Association, American Medical Association, American Physiological Society, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, New York Academy of Sciences, Society for Experimental Biology and Medicine, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: MDS Pharma Salary Employment

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
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