Signs and symptoms
Excessive urination and extreme thirst (especially for cold water and sometimes ice or ice water) are typical for DI. Symptoms of diabetes insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine is not sweet as it does not contain glucose and there is no hyperglycemia (elevated blood glucose). Blurred vision is a rarity. Signs of dehydration may also appear in some individuals since the body cannot conserve much (if any) of the water it takes in.
The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium.
In order to distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops). Urinalysis demonstrates a dilute urine with a low specific gravity. Urine osmolarity and electrolyte levels are typically low.
A fluid deprivation test helps determine whether DI is caused by:
excessive intake of fluid
a defect in ADH production
a defect in the kidneys’ response to ADH
This test measures changes in body weight, urine output, and urine composition when fluids are withheld and as dehydration occurs. The body’s normal response to dehydration is to concentrate urine and conserve water, so urine becomes more concentrated and urination becomes less frequent. Those with DI continue to urinate large amounts of dilute urine in spite of not drinking any fluids. Sometimes measuring blood levels of ADH during this test is also necessary.
To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.
If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging (MRI), is necessary to discover if a disease process (such as a prolactinoma, or histiocytosis, syphilis, tuberculosis or other tumor or granuloma) is affecting pituitary function. Most people with this form have either experienced past head trauma or have stopped ADH production for an unknown reason.
Habit drinking (in its severest form termed psychogenic polydipsia) is the most common imitator of diabetes insipidus at all ages. While many adult cases in the medical literature are associated with mental disorders, most patients with habit polydipsia have no other detectable disease. The distinction is made during the water deprivation test, as some degree of urinary concentration above isosmolar is usually obtained before the patient becomes dehydrated.
Electrolyte and volume homeostasis is a complex mechanism that balances the body’s requirements for blood pressure and the main electrolytes sodium and potassium. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.
The regulation of urine production occurs in the hypothalamus, which produces ADH in the supraoptic and paraventricular nuclei. After synthesis, the hormone is transported in neurosecretory granules down the axon of the hypothalamic neuron to the posterior lobe of the pituitary gland where it is stored for later release. In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex.
The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubule, specifically it acts on proteins called aquaporins which open to allow water into the collecting duct cells. This increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.
There are several forms of DI:
Main article: Neurogenic diabetes insipidus
Neurogenic diabetes insipidus, more commonly known as central diabetes insipidus, is due to a lack of vasopressin production in the brain.
Main article: Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus is due to the inability of the kidney to respond normally to ADH.
Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output. Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.
Gestational DI only occurs during pregnancy. While all pregnant women produce vasopressinase in the placenta, which breaks down ADH, this can assume extreme forms in GDI.
Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.
Diabetes insipidus is also associated with some serious diseases of pregnancy. These are pre-eclampsia, HELLP Syndrome and Acute fatty liver of pregnancy. These cause diabetes insipidus by activating hepatic vasopressinase. It is important to consider these if a woman presents with diabetes insipidus in pregnancy, because the treatment of these diseases requires delivery of the baby before the disease will improve. Failure to treat these diseases promptly can lead to maternal or perinatal mortality.
Central DI and gestational DI respond to desmopressin. Carbamazepine, an anti-convulsive medication, has also had some success in this type of DI. Also gestational DI tends to abate on its own 4 to 6 weeks following labour, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option.
Desmopressin will be ineffective in nephrogenic DI. Instead, the diuretic hydrochlorothiazide (a thiazide diuretic) or indomethacin can improve nephrogenic diabetes insipidus. Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia. It seems paradoxical to treat an extreme diuresis with a diuretic but the thiazide diuretics will increase proximal tubule reabsorption of sodium and water and decrease distal delivery of fluid to the distal nephron thereby decreasing excretion rates. Again, adequate hydration is important for patients with DI, as they may become dehydrated easily.
Lithium-induced nephrogenic DI may be effectively managed with the administration of amiloride, a potassium-sparing diuretic often used in conjunction with thiazide or loop diuretics. Clinicians have been aware of lithium toxicity for many years and traditionally have administered thiazide diuretics for lithium-induced polyuria and nephrogenic diabetes insipidus. However, recently amiloride has been shown to be a successful treatment for this condition.
^ Perkins RM, Yuan CM, Welch PG (March 2006). “Dipsogenic diabetes insipidus: report of a novel treatment strategy and literature review”. Clin. Exp. Nephrol. 10 (1): 637. doi:10.1007/s10157-005-0397-0. PMID 16544179.
^ Kalelioglu I, Kubat Uzum A, Yildirim A, Ozkan T, Gungor F, Has R (2007). “Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery”. Pituitary 10 (1): 8793. doi:10.1007/s11102-007-0006-1. PMID 17308961.
^ Finch CK, Kelley KW, Williams RB. Treatment of lithium-induced diabetes insipidus with amiloride. Pharmacotherapy. 2003 Apr;23(4):546-50. PMID 12680486
The public domain document “Diabetes Insipidus”, NIH Publication No. 01-4620, December 2000.
The Diabetes Insipidus Foundation, Inc
Information on Diabetes Insipidus
Endocrine pathology: endocrine diseases (E00-35, 240-259)
types: (type 1, type 2, MODY 1 2 3 4 5 6) complications (coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy)
insulin receptor (Rabson-Mendenhall syndrome) Insulin resistance
Hypoglycemia beta cell (Hyperinsulinism) G cell (Zollinger-Ellison syndrome)
gonadotropin (Kallmann syndrome, Adiposogenital dystrophy) CRH (Tertiary adrenal insufficiency) vasopressin (Neurogenic diabetes insipidus) general (Hypothalamic hamartoma)
anterior (Acromegaly, Hyperprolactinaemia, Pituitary ACTH hypersecretion) posterior (SIADH) general (Nelson’s syndrome)
anterior (Kallmann syndrome, Growth hormone deficiency, ACTH deficiency/Secondary adrenal insufficiency) posterior (Neurogenic diabetes insipidus) general (Empty sella syndrome, Pituitary apoplexy, Sheehan’s syndrome, Lymphocytic hypophysitis)
Iodine deficiency Cretinism (Congenital hypothyroidism) Myxedema Euthyroid sick syndrome
Hyperthyroxinemia (Thyroid hormone resistance, Familial dysalbuminemic hyperthyroxinemia) Hashitoxicosis Thyrotoxicosis factitia Graves’ disease
Acute infectious Subacute (De Quervain’s, Subacute lymphocytic) Autoimmune/chronic (Hashimoto’s, Postpartum, Riedel’s)
Endemic goitre Toxic nodular goitre Toxic multinodular goitre
Primary Secondary Tertiary Osteitis fibrosa cystica
aldosterone: Hyperaldosteronism/Primary aldosteronism (Conn syndrome, Bartter syndrome, Glucocorticoid remediable aldosteronism) AME Liddle’s syndrome 17 CAH
cortisol: Cushing’s syndrome (Pseudo-Cushing’s syndrome)
sex hormones: 21 CAH 11 CAH
aldosterone: Hypoaldosteronism (21 CAH, 11 CAH)
cortisol: CAH (Lipoid, 3, 11, 17, 21)
sex hormones: 17 CAH
ovarian: Polycystic ovary syndrome Premature ovarian failure
testicular: enzymatic (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency) Androgen receptor (Androgen insensitivity syndrome)
general: Hypogonadism (Delayed puberty) Hypergonadism (Precocious puberty)
Gigantism Dwarfism/Short stature (Laron syndrome, Psychosocial)
Autoimmune polyendocrine syndrome (APS1, APS2) Carcinoid syndrome Multiple endocrine neoplasia (1, 2A, 2B) Progeria Woodhouse-Sakati syndrome
endocrine navs: anat/physio/dev/hormones, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc
Urinary system Pathology Urologic disease / Uropathy (N0039, 580599)
.0 Minimal change .1 Focal segmental .2 Membranous
.3 Mesangial proliferative .4 Endocapillary proliferative .5/.6 Membranoproliferative/mesangiocapillary
Type I RPG/Type II hypersensitivity
Type II RPG/Type III hypersensitivity
Post-streptococcal Lupus (DPN) IgA/Berger’s
Type III RPG/Pauci-immune
Wegener’s granulomatosis Microscopic polyangiitis
RTA (RTA 2)
Liddle’s syndrome RTA (RTA 1) Diabetes insipidus (Nephrogenic)
Renal papillary necrosis
Hydronephrosis Pyonephrosis Reflux nephropathy
Acute tubular necrosis
Interstitial nephritis (Pyelonephritis, Danubian endemic familial nephropathy)
Renal failure (Acute renal failure, Chronic renal failure) Uremic pericarditis Uremia
Renal artery stenosis Hypertensive nephropathy Renovascular hypertension
Analgesic nephropathy Renal osteodystrophy Nephroptosis Abderhalden-Kaufmann-Lignac syndrome
Ureteritis Ureterocele Megaureter
Cystitis (Interstitial cystitis/painful bladder syndrome, Hunner’s ulcer, Trigonitis, Hemorrhagic cystitis) Neurogenic bladder Vesicointestinal fistula Vesicoureteral reflux
Urethritis (Non-gonococcal urethritis) Urethral syndrome Urethral stricture/Meatal stenosis
Obstructive uropathy Urinary tract infection Retroperitoneal fibrosis Urolithiasis (Kidney stone, Renal colic) Malacoplakia
urinary system navs: anat/physio/dev, noncongen/acid+base/congen/neoplasia, symptoms+signs/eponymous, proc
Sex linkage: X-linked disorders
Chronic granulomatous disease (CYBB) Wiskott-Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease
Haemophilia A Haemophilia B X-linked sideroblastic anemia
Androgen insensitivity syndrome/Kennedy disease KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita
amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome
carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb
lipid storage disorder: Fabry’s disease
mucopolysaccharidosis: Hunter syndrome
purine-pyrimidine metabolism: Lesch-Nyhan syndrome
mineral: Menkes disease
X-Linked mental retardation: Coffin-Lowry syndrome Fragile X syndrome MASA syndrome X-linked alpha thalassemia mental retardation syndrome Siderius X-linked mental retardation syndrome
eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia
other: Charcot-Marie-Tooth disease (CMTX2-3) Pelizaeus-Merzbacher disease SMAX2
Skin and related tissue
Dyskeratosis congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy
Becker’s muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi-Hnermann syndrome
Alport syndrome Dent’s disease X-linked nephrogenic diabetes insipidus
No primary system
Barth syndrome McLeod syndrome Simpson-Golabi-Behmel syndrome
X-linked hypophosphatemia Focal dermal hypoplasia Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan-Fryns syndrome
Categories: Endocrinology | Nephrology | DiabetesHidden categories: Articles needing additional references from February 2009 | All articles needing additional references