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Diabetes Insipidus
DI
Diabetes insipidus is a disorder of the secretion or action of antidiuretic hormone characterized by polyuria and polydipsia. It may be central or nephrogenic.

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WIKIDATA, Public Domain

Presentation

The patients of diabetes insipidus present to the hospital with the complaint of polyuria and/or dehydration. The patient may pass 5 to 20 or even more liters of urine in 24 hours. The urine has a very low specific gravity and osmolality.

As the patient loses a lot of water, signs of dehydration start appearing. The mouth becomes dry and the skin loses its elasticity. The patient also has excessive thirst (polydipsia).

Entire Body System

  • Fatigue

    Signs of dehydration include: thirst, dry skin, sluggishness, fatigue, dizziness, confusion and nausea. If you are severely dehydrated, you can even experience seizures, permanent brain damage and death. [draxe.com]

    […] such as hypercalcemia, hypokalemia, sarcoidosis, amyloidosis, and sickle cell disease Symptoms Symptoms may include: Increased urination, especially during the night Extreme thirst Nighttime urination Dehydration —fast heart rate, dry skin and mouth, fatigue [lahey.org]

    Symptoms of dehydration include: Dry skin Dry mucous membranes (sticky mouth) /reduced tears Sunken appearance to eyes Sunken fontanelles (soft spot in the skull) in infants Fatigue/sleepiness Weight loss Headache Irritability Low body temperature Muscle [histio.org]

    Dehydration can cause: Dry mouth Changes in skin elasticity Thirst Fatigue Electrolyte imbalance Diabetes insipidus can cause an imbalance in electrolytes — minerals in your blood, such as sodium and potassium, that maintain the fluid balance in your [mayoclinic.org]

    […] temperature (hyperthermia) unexplained weight loss In older children, symptoms of diabetes insipidus include: wetting the bed (enuresis) – although most children who wet the bed do not have diabetes insipidus loss of appetite feeling tired all the time (fatigue [nhs.uk]

  • Weight Loss

    Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. [ncbi.nlm.nih.gov]

    Symptoms of dehydration include: Dry skin Dry mucous membranes (sticky mouth) /reduced tears Sunken appearance to eyes Sunken fontanelles (soft spot in the skull) in infants Fatigue/sleepiness Weight loss Headache Irritability Low body temperature Muscle [histio.org]

    The symptoms characteristic of CDI are polyuria and polydipsia, usually associated with weight loss. Nocturia is common and in children often presents as enuresis. [orpha.net]

    This leads to dehydration and the symptoms include: Rapid weight loss (over 5 pounds in one to two days) Fast heartbeat Sunken eyes Fever Headache Mouth dryness Weak muscles High sodium in the blood Low Blood Pressure Any of the above symptoms could be [newhealthguide.org]

  • Enuresis

    […] symptoms that could suggest diabetes insipidus include: excessive crying irritability slower than expected growth high body temperature (hyperthermia) unexplained weight loss In older children, symptoms of diabetes insipidus include: wetting the bed (enuresis [nhs.uk]

    Symptoms: polyuria and polydipsia, enuresis, FTT/poor growth, unexplained fevers, constipation Diagnosis: elevated serum Na in patients with abnormal thirst mechanism and dilute urine (as above) vs failure to concentrate urine after a water deprivation [utmb.edu]

    Mild cases may present with unremitting enuresis (bed-wetting). Risk Factors Brain tumor or pituitary gland tumor. Head Injury Infections such as meningitis, encephalitis, tuberculosis. Sarcoidosis Family history of diabetes insipidus. [rxmed.com]

    Nocturia is common and in children often presents as enuresis. Polyuria is characterized by a urine volume in excess of 150 ml/kg/24h at birth, 100-110 ml/kg/24h until the age of 2 years, and 40-50 ml/kg/24h in older children and adults. [orpha.net]

  • Malnutrition

    […] polyangiitis Most idiopathic or congenital causes result in central DI Nephrogenic diabetes insipidus (NDI) Certain medications, such as lithium—the most common cause of NDI Kidney disease such as polycystic kidney disease Kidney infection or blockage Protein malnutrition [lahey.org]

    The condition may be fatal in adults due to: Severe muscle weakness Malnutrition Pneumonia Lung failure The major causes of death with this condition are cancer and lung disease. [medlineplus.gov]

    If the muscles in your esophagus are affected, you can have problems swallowing (dysphagia), which can cause weight loss and malnutrition. Aspiration pneumonia. [mayoclinic.org]

    Some common complications are: skin ulcers gastric ulcers difficulty breathing lung infections problems swallowing malnutrition weight loss Dermatomyositis can also be associated with conditions such as: Raynaud’s phenomenon myocarditis interstitial lung [healthline.com]

  • Anemia

     B) Nephrogenic diabetes insipidus  Systemic diseases involving the kidney  Multiple myeloma  sickle cell anemia  Polycystic kidney disease  Pyelonephritis  Medications such as lithium 6. [slideshare.net]

    Other conditions like high calcium in the blood, polycystic kidney disease and sickle cell anemia can also affect the kidneys. It can also be caused by rare genetic kidney disease. [newhealthguide.org]

    Here are the things I have been tested for: -Thyroid problems(I saw an endocrinologist) -Anemia(probably iron deficiency) -Vitamin d deficiency -Sleep apnea -Diabetes Insipidus I am currently working w/a sleep specialist. [ourhealth.com]

    AOH, absence of heterogeneity; RARS, refractory anemia with ring sideroblasts; RAEB-T, refractory anemia with excess blasts in transformation; sAML, secondary AML; RCMD, refractory cytopenia with multilineage dysplasia; UPD, uniparental disomy. [jstage.jst.go.jp]

Gastrointestinal

  • Polydipsia

    Diabetes insipidus is a disease characterized by polyuria and polydipsia due to inadequate release of arginine vasopressin from the posterior pituitary gland (neurohypophyseal diabetes insipidus) or due to arginine vasopressin insensitivity by the renal [ncbi.nlm.nih.gov]

    Someone with psychogenic polydipsia may try to drink some water during this test, despite strict instructions against drinking. [medicalnewstoday.com]

    Definition and Epidemiology Polydipsia and polyuria with dilute urine, hypernatremia, and dehydration are the hallmarks of diabetes insipidus in infants and children. [pedsinreview.aappublications.org]

    The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). [doi.org]

  • Constipation

    Consume plenty of high-fiber foods and fruit juices to prevent or treat constipation. When to Call a Doctor See a doctor immediately if you develop symptoms of diabetes insipidus. [healthcommunities.com]

    An infant or young child with diabetes insipidus may have the following signs and symptoms: Heavy, wet diapers Bed-wetting Trouble sleeping Fever Vomiting Constipation Delayed growth Weight loss When to see a doctor See your doctor immediately if you [mayoclinic.org]

    Symptoms: polyuria and polydipsia, enuresis, FTT/poor growth, unexplained fevers, constipation Diagnosis: elevated serum Na in patients with abnormal thirst mechanism and dilute urine (as above) vs failure to concentrate urine after a water deprivation [utmb.edu]

    Disease definition Nephrogenic diabetes insipidus (NDI) is characterized by polyuria with polydipsia, recurrent bouts of fever, constipation, and acute hypernatremic dehydration after birth that may cause neurological sequelae. [orpha.net]

    Constipation. Mild cases may present with unremitting enuresis (bed-wetting). Risk Factors Brain tumor or pituitary gland tumor. Head Injury Infections such as meningitis, encephalitis, tuberculosis. Sarcoidosis Family history of diabetes insipidus. [rxmed.com]

  • Loss of Appetite

    Symptoms of an electrolyte imbalance may include: Weakness Nausea Vomiting Loss of appetite Muscle cramps Confusion Feb. 16, 2019 [mayoclinic.org]

    […] the bed (enuresis) – although most children who wet the bed do not have diabetes insipidus loss of appetite feeling tired all the time (fatigue) Page last reviewed: 2 April 2019 Next review due: 2 April 2022 [nhs.uk]

    Feeling very thirsty and drinking more liquid than usual Losing weight without trying Dry skin Feeling confused, weak, and dizzy Fatigue Headaches and vision changes Children may have irritability, a loss of appetite, and slow growth How is diabetes insipidus [drugs.com]

Cardiovascular

  • Hypotension

    We report vasopressin (AVP) responses to hypotension in nine patients with ADI and nine controls. [ncbi.nlm.nih.gov]

    Anti-diuretic hormone Secretion increased by: hyperosmolality or hypotension stress, emotional stimuli trauma, surgery, pain exercise, increased temperature positive pressure ventilation cholinergic and beta agonist drugs nicotine angiotensin II barbiturates [aic.cuhk.edu.hk]

Neurologic

  • Irritability

    This can cause tiredness, irritability and difficulty concentrating, which can affect your daily life further. You may also feel generally unwell and "run down" much of the time for no apparent reason. [nhs.uk]

    In the absence of a source of fluid, patients become increasingly thirsty and irritable and ultimately stuporous and comatose as a result of hyperosmolality and decreased extracellular fluid volume. [britannica.com]

    If there’s any redness or irritation, don’t use the product. [healthline.com]

    Symptoms of dehydration include: Dry skin Dry mucous membranes (sticky mouth) /reduced tears Sunken appearance to eyes Sunken fontanelles (soft spot in the skull) in infants Fatigue/sleepiness Weight loss Headache Irritability Low body temperature Muscle [histio.org]

  • Confusion

    If you experience the signs of dehydration, such as confusion, dizziness or sluggishness, seek immediate care. [draxe.com]

    Diabetes insipidus, not to be confused with the more common diabetes mellitus, is a relatively rare disorder resulting from a failure to produce sufficient amounts of vasopressin, also known as antidiuretic hormone (ADH). [healthcommunities.com]

    Diabetes insipidus and diabetes mellitus should not be confused. The two conditions are unrelated, with diabetes insipidus a completely different type of illness. Diabetes mellitus is also far more common. [diabetes.co.uk]

    It should not be confused with the more common diabetes mellitus, also known as sugar diabetes, which results from too much sugar in the blood. [histio.org]

  • Headache

    She consulted due to a headache with warning signs associated with altered visual acuity. Brain MRI was performed which showed signs of a non-adenomatous lesion with suprasellar and hypothalamic extension. [ncbi.nlm.nih.gov]

    This can result in: headaches dizziness feeling bloated hyponatraemia – a low level of sodium (salt) in your blood Symptoms of hyponatraemia include: a severe or prolonged headache confusion nausea and vomiting If you think you may have hyponatraemia, [nhs.uk]

    Symptoms of a ibuprofen overdose to look out for include: a ringing in the ears, blurred vision, headaches, confusion, dizziness, drowsiness and skin rashes. 5 Natural Treatments 1. [draxe.com]

    Symptoms of dehydration include: Dry skin Dry mucous membranes (sticky mouth) /reduced tears Sunken appearance to eyes Sunken fontanelles (soft spot in the skull) in infants Fatigue/sleepiness Weight loss Headache Irritability Low body temperature Muscle [histio.org]

  • Meningism

    (inflammation of the meninges, the membranes that cover the brain and spinal cord) Sarcoidosis (a rare inflammation of the lymph nodes and other tissues throughout the body) Tuberculosis Nephrogenic diabetes insipidus is the result of a defect in the [chop.edu]

    Additionally, this is the first report of a case of sterile meningitis caused by ischemic pituitary apoplexy. [go.galegroup.com]

    (inflammation of the meninges, the membranes that cover the brain and spinal cord) Sarcoidosis (a rare inflammation of the lymph nodes and other tissues throughout the body) Family heredity Certain drugs like lithium What are the symptoms of diabetes [stanfordchildrens.org]

    Diabetes insipidus can be caused by several conditions, including the following: malfunctioning hypothalamus damage to hypothalamus or pituitary gland during surgery brain injury tumor tuberculosis blockage in the arteries leading to the brain encephalitis meningitis [hopkinsmedicine.org]

  • Lethargy

    She had a 3-month history of lethargy, reduced appetite, weight loss, cough and intermittent fevers. [ncbi.nlm.nih.gov]

    If you lose too much water, you could have: Unexplained weakness Lethargy Muscle pains Irritability How Is It Diagnosed? If you have this condition, you’ll probably wind up at the doctor for help with your thirst and constant need for a bathroom. [webmd.com]

    In children, additional symptoms of CDI can include lethargy, irritability, growth retardation, weight loss, fever, vomiting or diarrhea. In secondary CDI, further manifestations may be present resulting from the secondary cause. [orpha.net]

    Case presentation A thirty year old female with adenocarcinoma of rectum was admitted with increasing lethargy, headache and drowsiness. She deteriorated rapidly and had cardiac arrest, following which she remained comatose. [bmcresnotes.biomedcentral.com]

Urogenital

  • Polyuria

    Diabetes insipidus is a disease characterized by polyuria and polydipsia due to inadequate release of arginine vasopressin from the posterior pituitary gland (neurohypophyseal diabetes insipidus) or due to arginine vasopressin insensitivity by the renal [ncbi.nlm.nih.gov]

    Definition and Epidemiology Polydipsia and polyuria with dilute urine, hypernatremia, and dehydration are the hallmarks of diabetes insipidus in infants and children. [pedsinreview.aappublications.org]

    The first step in the diagnosis of the patient with polyuria is determining whether the polyuria is due to a solute diuresis or a water diuresis. [clinicaladvisor.com]

  • Nocturia

    Additionally, patients develop the need to urinate at night (nocturia), leading to sleep deprivation and daytime sleepiness. Desmopressin, a synthetic ADH analog, is the treatment of choice in central DI. [amboss.com]

    During her first week of treatment, she developed polyuria, nocturia and polydipsia and was diagnosed with central diabetes insipidus. [ncbi.nlm.nih.gov]

    What is nocturia? Nocturia is when a person has to wake up at night to pass urine. If this happens more than twice a night, it can be a problem. Nocturia is common in older people. It can cause problems in day-to-day life. [continence.org.au]

    Nocturia may be the main symptom in less severe DI and is often the first clue to its diagnosis. [clinicaladvisor.com]

  • Nocturnal Polyuria

    Dosing is started at night to give relief for nocturnal polyuria, and day-time dosages are added as per need to control day-time symptoms. It can be given nasally, parenterally, or orally. Oral preparation is preferred for patients with sinusitis. [hindawi.com]

  • Bladder Distention

    Examination should focus on signs of dehydration, possible bladder distention, anterior pituitary hormone hyper- or hyposecretion, tumoral syndrome (headache, bitemporal hemianopsia, diplopia), and systemic signs of granulomatosis or cancer. [em-consulte.com]

Workup

The diagnosis of diabetes insipidus is established by the use of the following investigations [6].

  • Plasma osmolality: Since the amount of antidiuretic hormone is not measurable in the serum, the osmolality of the plasma is tested. It is significantly raised in diabetes insipidus. A plasma osmolality greater than 300 mOsm/kg is diagnostic of diabetes insipidus.
  • Urine osmolality: The osmolality of the urine is less than 600 mOsm/kg in diabetes insipidus.
  • Water deprivation test: The objective of water deprivation test is to establish the diagnosis of diabetes insipidus and to determine whether the cause is central or nephrogenic. In central diabetes insipidus, the osmolality of urine increases from less than 600 mOsm/kg to over 660 mOsm/kg after the administration of desmopressin, an analogue of anti-diuretic hormone. In nephrogenic diabetes insipidus, the concentration of the urine remains the same even after the administration of desmopressin.

Serum

  • Hyponatremia

    chronic hyponatremia should be assumed and slowly corrected. [elsevier.es]

    The patient's symptoms of headache and vomiting corresponded to his hyponatremia and resolved with treatment of his hyponatremia during each hospitalization. [jaoa.org]

    Hyperglycemia-induced hyponatremia—Calculation of expected serum sodium depression. New England Journal of Medicine 1973;289:843–844. Google Scholar 3. Hillier TA, Abbott RD, Barrett EJ. [doi.org]

    Taking too much DDAVP or taking it when you do not really need it can lead to your body holding onto too much water and a condition called hyponatremia. [ccpd.ucsf.edu]

    Therefore, treatment of an elderly person with DI requires special attention to avoid hyponatremia. [endocrinologyadvisor.com]

Treatment

Rehydration

The patients suffering from diabetes insipidus have to be rehydrated with intravenous or oral fluids depending upon their severity of dehydration.

Central diabetes insipidus

An analog of antidiuretic hormone called desmopressin is the treatment of choice for central diabetes insipidus. The bioavailability of desmopressin in oral form is negligible. Therefore, it is usually given in the form of nasal spray. It may also be given intramuscularly if the patient is acutely ill [7].

Nephrogenic diabetes insipidus

Thiazide diuretics have a paradoxical effect and decrease polyuria in both central and nephrogenic diabetes insipidus. A combination of indomethacin and hydrochlorothiazide or indomethacin and amiloride may be used in nephrogenic diabetes [8] [9] [10]. In addition, the use of low salt diet may be advised to reduce thirst and to lower the excretion of water.

Prognosis

With proper treatment, the prognosis for the people suffering from diabetes insipidus is excellent. Central diabetes insipidus responds to treatment much more easily than nephrogenic diabetes insipidus.

Although the patients of diabetes insipidus rapidly become dehydrated, mortality from it is rare in previously healthy adult patients. Children and the elderly are at a higher risk of mortality from severe dehydration.

Etiology

Diabetes insipidus is of two types, central and nephrogenic.

Central diabetes insipidus

Central diabetes insipidus results from deficient production of antidiuretic hormone (ADH) in the hypothalamus or their inability to reach the posterior pituitary from where they are released in the blood [1]. It is most commonly associated with hypothalamic or high stalk lesions such as craniopharyngioma, sarcoidosis, histiocytosis X, tuberculous meningitis, encephalitis and syphilis [2]. Head injuries and surgeries may also cause damage to the hypothalamus. Pituitary tumors with suprasellar extension or metastases to the pituitary may also cause central diabetes insipidus. Central diabetes insipidus may also have idiopathic or genetic etiologies [3].

Nephrogenic diabetes insipidus

It results from the lack of response of renal tubules to antidiuretic hormone [4]. It is associated with renal damage with may result from genetic defects (sex linked recessive defects, cystinosis), metabolic abnormalities (such as hypokalemia and hypercalcemia), drug therapy (with lithium or demeclocycline) or heavy metal poisoning. It may also be caused by other conditions such as pyelonephritis, renal amyloidosis, multiple myeloma and Sjogren syndrome.

Epidemiology

Not much data is available regarding the epidemiology of diabetes insipidus. However, it is a rare disease with a prevalence of 3 per 100,000 people in the United States [5]. The prevalence is equal in men and women. Various ethnic groups also have equal tendencies for the development of diabetes insipidus.

Pathophysiology

Antidiuretic hormone is a nonpeptide hormone that is formed in the hypothalamus and stored in the posterior pituitary. Its primary effect is on the epithelial cells of the renal collecting tubules where it augments the resorption of water independently of the solutes. This causes dilution of the blood serum and concentration of the urine.

Diabetes insipidus results due to a decreased effect of antidiuretic hormone. The cause may be central or nephrogenic. Central diabetes insipidus results from an ineffective production of antidiuretic hormone; whereas in nephrogenic diabetes insipidus, the cells of the kidney fail to respond to it.

Prevention

There are no documented ways to prevent the development of diabetes insipidus.

Summary

Diabetes insipidus is an endocrine disease characterized by the persistent excretion of excessive quantities of dilute urine and constant, excessive thirst. It results from a decreased action of antidiuretic hormone - the posterior pituitary hormone that is responsible for the suppression of urination by increasing the resorption of water in the renal collecting tubules. It may be due to a decreased production of antidiuretic hormone or the inability of the renal cells to respond to it.

Diabetes insipidus is treated by the administration of desmopressin (an analog of antidiuretic hormone) along with thiazide diuretics. The disease is fatal unless adequate rehydration and proper treatment is ensured.

Patient Information

The pituitary gland is a small gland located at the base of the brain. One of the hormone it secretes is called antidiuretic hormone. This hormone acts on the kidneys and causes absorption of water back into the blood, thereby preventing the excessive loss of water in the urine. In diabetes insipidus, there is either a reduced production or inadequate effect of antidiuretic hormone which causes the loss of a large amount of water in the urine. The patients develop dehydration and excessive thirst. With proper treatment, there is an excellent control of the disease.

References

  1. Gu F, Jin Z, Zhang D. [The etiology and clinical characteristics of central diabetes insipidus, a retrospective study of 408 cases]. Zhonghua yi xue za zhi. Oct 2001;81(19):1166-1171.
  2. Garcia Garcia E, Lopez Siguero JP, Milano Manso G, Martinez Valverde A. [Etiology of central diabetes insipidus in children]. Anales espanoles de pediatria. Jul 1999;51(1):53-55.
  3. Babey M, Kopp P, Robertson GL. Familial forms of diabetes insipidus: clinical and molecular characteristics. Nature reviews. Endocrinology. Dec 2011;7(12):701-714.
  4. Earley LE, Orloff J. The Mechanism of Antidiuresis Associated with the Administration of Hydrochlorothiazide to Patients with Vasopressin-Resistant Diabetes Insipidus. The Journal of clinical investigation. Nov 1962;41(11):1988-1997.
  5. Saborio P, Tipton GA, Chan JC. Diabetes insipidus. Pediatrics in review / American Academy of Pediatrics. Apr 2000;21(4):122-129; quiz 129.
  6. Laczi F. [Diabetes insipidus: etiology, diagnosis, and therapy]. Orvosi hetilap. Nov 17 2002;143(46):2579-2585.
  7. Laczi F. [Treatment of diabetes insipidus]. Orvosi hetilap. Mar 28 2004;145(13):699-702.
  8. Allen HM, Jackson RL, Winchester MD, Deck LV, Allon M. Indomethacin in the treatment of lithium-induced nephrogenic diabetes insipidus. Archives of internal medicine. May 1989;149(5):1123-1126.
  9. Finch CK, Kelley KW, Williams RB. Treatment of lithium-induced diabetes insipidus with amiloride. Pharmacotherapy. Apr 2003;23(4):546-550.
  10. Alon U, Chan JC. Hydrochlorothiazide-amiloride in the treatment of congenital nephrogenic diabetes insipidus. American journal of nephrology. 1985;5(1):9-13.
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