eMedicine Specialties > Endocrinology > Pituitary Gland
Diabetes Insipidus: Treatment & Medication
Updated: Sep 25, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- In an emergency, most patients with diabetes insipidus (DI) can drink enough fluid to replace their urine losses. Replace losses with dextrose and water or IV fluid hypo-osmolar to the patient's serum. Avoid hyperglycemia, volume overload, and overly rapid correction of hypernatremia. A good rule of thumb is to reduce serum sodium by 0.5 mmol/L/h. The water deficit may be calculated based on the assumption that body water is approximately 60% of body weight in kilograms.
- In case of inadequate thirst, desmopressin is the drug of choice.7 A synthetic analogue of AVP, desmopressin is available in subcutaneous, intranasal, and oral preparations.8 Generally, it can be administered 2-3 times per day. Patients may require hospitalization to establish fluid needs. Frequent electrolyte monitoring is recommended.
- Alternatives to desmopressin for pharmaceutical therapy for diabetes insipidus include synthetic vasopressin, as well as the nonhormonal agents chlorpropamide, carbamazepine, clofibrate (no longer on the US market), thiazides, and indomethacin (limited efficacy).
Surgical Care
- Postoperatively, administer the usual dose of desmopressin to patients with diabetes insipidus and administer (hypotonic) IV fluids to match urine output.
- After pituitary surgery, patients should undergo continuous monitoring of fluid intake, urine output, and specific gravities, along with daily measurements of serum electrolytes.9 In patients who develop diabetes insipidus, administer parenteral desmopressin every 12-24 hours, along with adequate fluid to match losses. Follow the specific gravity of the urine and administer the next dose of desmopressin when the specific gravity has fallen to less than 1.008-1.005 with an increase in urine output. When the patient can tolerate oral intake, thirst can become an adequate guide.
Consultations
In the setting of neurosurgery or head trauma, the diagnosis of diabetes insipidus may be obvious and even expected. The intensivists and the nurses who manage the patient acutely are in the best position to treat acutely. In the more subtle forms, and certainly in all chronic forms in which therapy is anticipated to be indefinite, the clinical endocrinologist is invaluable to establish the diagnosis and to design therapy.
Diet
- No specific dietary considerations exist in chronic diabetes insipidus, but the patient should understand the importance of adequate and balanced salt and water intake.
- Patients with diabetes insipidus also must take special precautions, such as when traveling, to be prepared to treat vomiting or diarrhea and to avoid dehydration with exertion or hot weather.
Medication
Treat diabetes insipidus (DI) with desmopressin and/or nonhormonal drugs. In central diabetes insipidus, the primary problem is a hormone deficiency; therefore, physiologic replacement with desmopressin is usually effective. Use a nonhormonal drug if response is incomplete or desmopressin is too expensive. Nonhormonal drugs usually are more effective in treating nephrogenic diabetes insipidus.
Hormones
These agents prevent complications of DI and reduce morbidity.
Desmopressin (DDAVP)
Synthetic analogue of arginine vasopressin with potent antidiuretic, but no vasopressor, activity.
Adult
5-20 mcg intranasal qd/bid
0.05-0.8 mg PO once or more daily
Pediatric
0.05-0.3 mg/d PO
Lithium and demeclocycline diminish ADH effects; chlorpropamide, fludrocortisone, and glucocorticoids enhance ADH response; monitor with pressor agents
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Observe for effects on blood pressure; institute fluid restriction in children to avoid hyponatremia or water intoxication
Vasopressin (Pitressin)
Has vasopressor and antidiuretic hormone (ADH) activity. Increases water resorption at collecting ducts (ADH effect) and promotes smooth muscle contraction throughout vascular bed of renal tubular epithelium (vasopressor effects). However, vasoconstriction is also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.
Decreases portal pressure in portal hypertension. A notable undesirable effect is coronary artery constriction that may dispose patients with coronary artery disease to cardiac ischemia. This can be prevented with concurrent use of nitrates.
Adult
5-10 U SC q3-6h
Pediatric
2.5-10 U SC bid/qid
Lithium, demeclocycline, and alcohol diminish ADH effects; chlorpropamide and fludrocortisone or glucocorticoids enhance ADH effects
Documented hypersensitivity; coronary artery disease; hypertension; angina
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in cardiovascular disease, seizure disorders, nitrogen retention, asthma, or migraine; excessive doses may result in hyponatremia
Hypoglycemics
These agents help relieve diuresis.
Chlorpropamide (Diabinese)
Promotes renal response to ADH.
Adult
125-250 mg PO bid
Pediatric
Not recommended
NSAIDS, salicylates, sulfonamides, warfarin, monoamine oxidase inhibitors (MAOIs), and beta blockers may enhance hypoglycemia
Documented hypersensitivity; type I diabetes; severe renal or hepatic impairment; thyroid dysfunction
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
Hypoglycemia may occur
Anticonvulsants
Certain antiepileptic drugs, such as carbamazepine, have proven helpful in DI.
Carbamazepine (Tegretol)
Amelioration by releasing ADH. Not useful in total DI and generally not a first-line drug.
Adult
100-300 mg PO bid
Pediatric
Not recommended
Serum levels may increase significantly within 30 d of danazol coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; carbamazepine may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels)
Documented hypersensitivity; history of bone marrow suppression; MAOI use
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
Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBCs and serum iron baseline prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness
Antilipemic agents
Certain antilipemic drugs, such as clofibrate, may increase the release of ADH in partial DI.
Clofibrate (Atromid-S)
No longer on US market. May release ADH in partial DI.
Adult
500 mg PO bid
Pediatric
Not recommended
Rifampin decreases serum level and effect; anticoagulant effect of warfarin may be potentiated, with an increase in prothrombin time (PT); chlorpropamide may increase hypoglycemia; probenecid increases serum level and effect
Documented hypersensitivity; hepatic or renal insufficiency; biliary cirrhosis
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
Consider tumorigenicity; caution in breastfeeding, cardiac disease, and hypothyroidism
Diuretics
These agents may reduce flow to the ADH-sensitive distal nephron.
Hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide)
Thiazide diuretic that decreases urinary volume in absence of ADH. May induce mild volume depletion and cause proximal salt and water retention, thereby reducing flow to the ADH-sensitive distal nephron. Effects are additive to other agents.
Adult
25-50 mg PO qd or divided bid
Pediatric
Not recommended
Alcohol, antihypertensive drugs, and other diuretics increase diuretic effect; corticosteroids and other diuretics increase hypokalemic effect; decreases hypoglycemic effect of insulin and oral agents; increases lithium serum levels; NSAIDs decrease diuretic and antihypertensive effects
Documented hypersensitivity; renal dysfunction
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Considered pregnancy risk category D by some experts; observe for changes in fluids and electrolytes
Nonsteroidal Anti-inflammatory Agents (NSAIDs)
Their mechanism of action is not known, but they may act by inhibiting prostaglandin synthesis.
Ibuprofen (Ibuprin, Advil, Motrin)
Inhibition of prostaglandin synthesis reduces delivery of solute to distal tubules, reducing urine volume and increasing urine osmolality. Usually used in nephrogenic DI.
Adult
600-800 mg PO tid
Pediatric
Not recommended
Aspirin decreases serum levels; antiplatelet effect of low-dose aspirin can be compromised; increases serum levels of digoxin, methotrexate, lithium; increases effect of anticoagulants; decreases hypotensive effects of ACE inhibitors and furosemide
Documented hypersensitivity; advanced renal disease; GI bleeding or risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category D in third trimester; fluid retention, platelet effects, and renal disease may occur
Indomethacin (Indocin)
Inhibition of prostaglandin synthesis reduces delivery of solute to distal tubules, reducing urine volume and increasing urine osmolality. Usually used in nephrogenic DI.
Adult
25-50 mg PO bid/tid
75 mg SR PO bid; not to exceed 200 mg/d
Pediatric
Not established
Coadministration with aspirin increases risk of inducing serious NSAID-related side 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 in patients 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 or renal insufficiency
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
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category D in third trimester; 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 there is persistent leukopenia, granulocytopenia, or thrombocytopenia)
More on Diabetes Insipidus |
| Overview: Diabetes Insipidus |
| Differential Diagnoses & Workup: Diabetes Insipidus |
 Treatment & Medication: Diabetes Insipidus |
| Follow-up: Diabetes Insipidus |
| References |
| Further Reading |
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References
Earley LE, Orloff J. The mechanism of antidiuresis associated with the administration of hydrochlorothiazide to patients with vasopressin-resistant diabetes insipidus. J Clin Invest. Nov 1962;41(11):1988-97.
Kristof RA, Rother M, Neuloh G, et al. Incidence, clinical manifestations, and course of water and electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective observational study. J Neurosurg. Feb 6 2009;[Medline].
Seckl J, Dunger D. Postoperative diabetes insipidus. BMJ. Jan 7 1989;298(6665):2-3. [Medline].
Hadjizacharia P, Beale EO, Inaba K, et al. Acute diabetes insipidus in severe head injury: a prospective study. J Am Coll Surg. Oct 2008;207(4):477-84. [Medline].
Spanakis E, Milord E, Gragnoli C. AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. J Cell Physiol. Dec 2008;217(3):605-17. [Medline].
Hedrich CM, Zachurzok-Buczynska A, Gawlik A, et al. Autosomal dominant neurohypophyseal diabetes insipidus in two families. Molecular analysis of the vasopressin-neurophysin II gene and functional studies of three missense mutations. Horm Res. 2009;71(2):111-9. [Medline].
Richardson DW, Robinson AG. Desmopressin. Ann Intern Med. Aug 1985;ID - NIH5M01(2):228-39. [Medline].
Vande Walle J, Stockner M, Raes A, et al. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf. Sep 2007;2(3):232-8. [Medline].
Ausiello JC, Bruce JN, Freda PU. Postoperative assessment of the patient after transsphenoidal pituitary surgery. Pituitary. 2008;11(4):391-401. [Medline].
Charmandari E, Brook CG. 20 years of experience in idiopathic central diabetes insipidus [letter]. Lancet. Jun 26 1999;353(9171):2212-3. [Medline].
Czernichow P, Robinson AG. Diabetes insipidus in man. Frontiers of Hormone Research. 1985;13-24.
Pivonello R, De Bellis A, Faggiano A, et al. Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology. J Clin Endocrinol Metab. Apr 2003;88(4):1629-36. [Medline].
Robertson GL. Diagnosis of diabetes insipidus. Frontiers of Hormone Research. 1985;13:176-89.
Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders. 4th ed. New York, NY:. McGraw-Hill;1994:698-720.
Further Reading
Related eMedicine topics:
Diabetes Insipidus [Pediatrics: General Medicine]
Hypernatremia [Emergency Medicine]
Hypernatremia [Nephrology]
Hypernatremia [Pediatrics: Cardiac Disease and Critical Care Medicine]
Lithium Nephropathy
Pituitary Disease and Pregnancy
Clinical guidelines:
ACR Appropriateness Criteria® neuroendocrine imaging. American College of Radiology - Medical Specialty Society. 1999 (revised 2008). 11 pages. NGC:007007
Clinical trials:
Copeptin in the Diagnosis and Differential Diagnosis of Diabetes Insipidus. The CoSIP-Study
Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
Keywords
diabetes insipidus, antidiuretic hormone, ADH, DDAVP, desmopressin, vasopressin, diabetes urine, arginine vasopressin, central diabetes insipidus, nephrogenic diabetes insipidus, polyuria, polydipsia, hypernatremia, dehydration, craniopharyngioma, pineal tumors, primary intracranial tumors, idiopathic diabetes insipidus
