Diabetes Insipidus Overview

What is diabetes insipidus?

Despite the name, diabetes insipidus is not related to type 1 or type 2 diabetes (diabetes mellitus). Diabetes insipidus is a hormone disorder that occurs when the body doesn't produce enough antidiuretic hormone (ADH) or doesn't use the hormone effectively.

Symptoms
What are the symptoms of diabetes insipidus?
The symptoms of diabetes insipidus include extreme thirst and excessive urination. In a normal adult, the average amount of urine is 1.6 to 2.6 quarts per day. People who have diabetes insipidus may urinate up to 16 quarts a day. They may also have to get up frequently during the night to urinate, and may even wet the bed.

Causes & Risk Factors

What causes diabetes insipidus?
Diabetes insipidus has several causes. In some people, a part of the brain (called the hypothalamus) doesn't make enough antidiuretic hormone (ADH). ADH helps your body balance water in the urine and blood. In other cases, the pituitary gland (which is responsible for releasing the ADH into the body) doesn't release enough of the hormone. Damage to either the hypothalamus or the pituitary gland can cause diabetes insipidus. This can occur after a head injury, during brain surgery or when a tumor grows on the glands. Abnormalities in the kidneys can also cause diabetes insipidus. If the kidneys are abnormal, it can affect the way they process ADH. Diabetes insipidus can be caused by some medicines, such as lithium. About 30% of the time, doctors can't find the cause.

Diagnosis & Tests

How do you test for diabetes insipidus?

To check for diabetes insipidus, your doctor may order a urine test. This will show how much water is in your urine, and can rule out type 1 or type 2 diabetes (if you have type 1 or type 2 diabetes, there will be excess sugar in your urine). Your doctor might do a blood test to check for high sodium levels, which is another indication of diabetes insipidus. Your doctor may also order a water deprivation test. During this test, you aren't allowed to drink any liquids. The staff will weigh you, check your urine and blood every hour for several hours. If the results of the test show that you have diabetes insipidus, you will probably also have pictures taken of your brain with an MRI (magnetic resonance image) scan. The scans can show problems or tumors in the brain that could be causing your diabetes insipidus.

Treatment
How is diabetes insipidus treated?
If your symptoms are mild, you might not need treatment. However, your doctor will want to check on you more often. Also, you should make sure you always have something to drink, so your body doesn't get dehydrated. For more severe cases of diabetes insipidus, medicine is available to help the body produce or more effectively use ADH. One medicine called desmopressin is a synthetic form of ADH and comes in pill form, as an injection (shot) or as a nasal spray. If you take desmopressin, you shouldn't drink too much, or your body will get overloaded with fluids. Too much fluid in your body and make you feel sick, weak or dizzy. If tumors or abnormal growths on your hypothalamus or pituitary gland are causing your diabetes insipidus, your doctor may suggest surgery to remove the growths. If your diabetes insipidus is caused by kidney problems, your doctor may recommend that you reduce salt in your diet and to drink enough water to avoid dehydration. Medicines like hydrochlorothiazide (a water pill) may also help. Water pills help your body balance salt and water. If a medicine is causing diabetes insipidus, your doctor may prescribe another medicine that doesn't cause excessive thirst and urination. Talk to your doctor about which option is right for you.

What is diabetes insipidus?

Diabetes insipidus (DI) is a rare disease that causes frequent urination. The large volume of urine is diluted, mostly water. To make up for lost water, a person with DI may feel the need to drink large amounts and is likely to urinate frequently, even at night, which can disrupt sleep and, on occasion, cause bedwetting. Because of the excretion of abnormally large volumes of dilute urine, people with DI may quickly become dehydrated if they do not drink enough water. Children with DI may be irritable or listless and may have fever, vomiting, or diarrhea. Milder forms of DI can be managed by drinking enough water, usually between 2 and 2.5 liters a day. DI severe enough to endanger a person's health is rare. [Top]
What is the difference between diabetes insipidus and diabetes mellitus?

DI should not be confused with diabetes mellitus (DM), which results from insulin deficiency or resistance leading to high blood glucose, also called blood sugar. DI and DM are unrelated, although they can have similar signs and symptoms, like excessive thirst and excessive urination. DM is far more common than DI and receives more news coverage. DM has two main forms, type 1 diabetes and type 2 diabetes. DI is a different form of illness altogether. [Top]
How is fluid in the body normally regulated?

The body has a complex system for balancing the volume and composition of body fluids. The kidneys remove extra body fluids from the bloodstream. These fluids are stored in the bladder as urine. If the fluid regulation system is working properly, the kidneys make less urine to conserve fluid when water intake is decreased or water is lost, for example, through sweating or diarrhea. The kidneys also make less urine at night when the body's metabolic processes are slower.

The hypothalamus makes antidiuretic hormone (ADH), which directs the kidneys to make less urine.

To keep the volume and composition of body fluids balanced, the rate of fluid intake is governed by thirst, and the rate of excretion is governed by the production of antidiuretic hormone (ADH), also called vasopressin. This hormone is made in the hypothalamus, a small gland located in the brain. ADH is stored in the nearby pituitary gland and released into the bloodstream when necessary. When ADH reaches the kidneys, it directs them to concentrate the urine by reabsorbing some of the filtered water to the bloodstream and therefore make less urine. DI occurs when this precise system for regulating the kidneys' handling of fluids is disrupted. [Top]
What are the types of diabetes insipidus? Central DI

The most common form of serious DI, central DI, results from damage to the pituitary gland, which disrupts the normal storage and release of ADH. Damage to the pituitary gland can be caused by different diseases as well as by head injuries, neurosurgery, or genetic disorders. To treat the ADH deficiency that results from any kind of damage to the hypothalamus or pituitary, a synthetic hormone called desmopressin can be taken by an injection, a nasal spray, or a pill. While taking desmopressin, a person should drink fluids only when thirsty and not at other times. The drug prevents water excretion, and water can build up now that the kidneys are making less urine and are less responsive to changes in body fluids.
Nephrogenic DI

Nephrogenic DI results when the kidneys are unable to respond to ADH. The kidneys' ability to respond to ADH can be impaired by drugs-like lithium, for example-and by chronic disorders including polycystic kidney disease, sickle cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders. Sometimes the cause of nephrogenic DI is never discovered. Desmopressin will not work for this form of DI. Instead, a person with nephrogenic DI may be given hydrochlorothiazide (HCTZ) or indomethacin. HCTZ is sometimes combined with another drug called amiloride. The combination of HCTZ and amiloride is sold under the brand name Moduretic. Again, with this combination of drugs, one should drink fluids only when thirsty and not at other times.
Dipsogenic DI

Dipsogenic DI is caused by a defect in 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 or other drugs should not be used to treat dipsogenic DI because they may decrease urine output but not thirst and fluid intake. This fluid overload can lead to water intoxication, a condition that lowers the concentration of sodium in the blood and can seriously damage the brain. Scientists have not yet found an effective treatment for dipsogenic DI.

Gestational DI

Gestational DI occurs only during pregnancy and results when an enzyme made by the placenta destroys ADH in the mother. The placenta is the system of blood vessels and other tissue that develops with the fetus. The placenta allows exchange of nutrients and waste products between mother and fetus. 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. [Top]
How is diabetes insipidus diagnosed?

Because DM is more common and because DM and DI have similar symptoms, a health care provider may suspect that a patient with DI has DM. But testing should make the diagnosis clear. A doctor must determine which type of DI is involved before proper treatment can begin. Diagnosis is based on a series of tests, including urinalysis and a fluid deprivation test. Urinalysis is the physical and chemical examination of urine. The urine of a person with DI will be less concentrated. Therefore, the salt and waste concentrations are low and the amount of water excreted is high. A physician evaluates the concentration of urine by measuring how many particles are in a kilogram of water or by comparing the weight of the urine with an equal volume of distilled water. A fluid deprivation test helps determine whether DI is caused by one of the following:

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. Sometimes measuring blood levels of ADH during this test is also necessary. In some patients, a magnetic resonance imaging (MRI) of the brain may be necessary as well. [Top]
Points to Remember

Diabetes insipidus (DI) is a rare disease that causes frequent urination and excessive thirst. DI is not related to diabetes mellitus (DM). Central DI is caused by damage to the pituitary gland and is treated with a synthetic hormone called desmopressin, which prevents water excretion.

Nephrogenic DI is caused by drugs or kidney disease and is treated with hydrochlorothiazide (HCTZ), indomethacin, or a combination of HCTZ and amiloride. Scientists have not yet discovered an effective treatment for dipsogenic DI, which is caused by a defect in the thirst mechanism. Most forms of gestational DI can be treated with desmopressin. A doctor must determine which type of DI is involved before proper treatment can begin.

[Top]
Hope through Research

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research into many kinds of kidney disease, including diabetes insipidus. NIDDKsupported researchers are exploring the cellular and molecular mechanisms that control fluid regulation in the body. These studies will point the way to more effective treatments for DI. Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research. For information about current studies, visit www.ClinicalTrials.gov. The U.S. Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names appearing in this document are used only because they are considered necessary in the context of the information provided. If a product is not mentioned, the omission does not mean or imply that the product is unsatisfactory. [Top] A. Definisi Diabetes insipidus adalah suatu penyakit yang jarang ditemukan, penyakit ini diakibatkan oleh berbagai penyebab yang dapat mengganggu mekanisme neurohypophyseal-renal reflex sehingga mengakibatkan kegagalan tubuh dalam mengkonversi air. Kebanyakan kasus-kasus yang pernah ditemui merupakan kasus yang idiopatik yang dapat bermanifestasi pada berbagai tingkatan umur dan jenis kelamin. (Khaidir Muhaj, 2009) Diabetes insipidus (DI) merupakan kelainan di mana terjadi peningkatan output urin abnormal, asupan cairan dan sering haus. Ini menyebabkan gejala seperti frekuensi kemih, nokturia (sering terbangun di malam hari untuk buang air kecil) dan enuresis (buang air kecil disengaja selama tidur atau ngompol) Urin output. ditingkatkan karena tidak terkonsentrasi biasanya,. Akibatnya bukannya warna kuning, urin yang pucat, tidak berwarna atau berair tampilan dan konsentrasi diukur (osmolalitas atau berat jenis) rendah. Diabetes Insipidus adalah suatu kelainan dimana terdapat kekurangan hormon antidiuretik yang menyebabkan rasa haus yang berlebihan (polidipsi) dan pengeluaran sejumlah besar air kemih yang sangat encer (poliuri). Diabetes insipidus terjadi akibat penurunan pembentukan hormon antidiuretik (vasopresin), yaitu hormon yang secara alami mencegah pembentukan air kemih yang terlalu banyak. Hormon ini unik, karena dibuat di hipotalamus lalu disimpan dan dilepaskan ke dalam aliran darah oleh hipofisa posterior. Diabetes insipidus juga bisa terjadi jika

kadar hormon antidiuretik normal tetapi ginjal tidak memberikan respon yang normal terhadap hormon ini (keadaan ini disebut diabetes insipidus nefrogenik). B. Etiologi Diabetes insipidus bisa merupakan penyakit keturunan. Gen yang menyebabkan penyakit ini bersifat resesif dan dibawa oleh kromosom X, karena itu hanya pria yang terserang penyakit ini. Wanita yang membawa gen ini bisa mewariskan penyakit ini kepada anak laki-lakinya. Diabetes insipidus secara umum dapat disebabkan oleh beberapa hal, yaitu : 1. Hipotalamus mengalami kelainan fungsi dan menghasilkan terlalu sedikit hormon antidiuretik 2. Kelenjar hipofisa gagal melepaskan hormon antidiuretik ke dalam aliran darah 3. Kerusakan hipotalamus atau kelenjar hipofisa akibat pembedahan 4. Cedera otak (terutama patah tulang di dasar tengkorak) 5. Tumor 6. Sarkoidosis atau tuberkulosis 7. Aneurisma atau penyumbatan arteri yang menuju ke otak 8. Beberapa bentuk ensefalitis atau meningitis Berdasarkan etiologinya, Diabetes Insipidus dapat dibedakan menjadi dua, antara lain: 1. Diabetes Insipidus Central Adanya masalah di bagian hipotalamus (nucleus supraoptik, paraventikular, dan filiformis hipotalamus) yang mana sebagai tempat pembuatan ADH/ vasopresin, menyebabkan terjadi penurunan dari produksi hormon ADH.Kelainan hipotalamus dan kelenjar pituitari posterior karena familial atau idiopatik, disebut Diabetes Insipidus Primer. Kerusakan kelenjar karena tumor pada area hipotalamus pituitary, trauma, proses infeksi, gangguan aliran darah, tumor metastase dari mamae atau paru disebut Diabetes Insipidus Sekunder. Pengaruh obat yang dapat mempengaruhi sintesis dan sekresi ADH seperti phenitoin, alkohol, lithium carbonat. 2. Diabetes insipidus Nephrogenik Ginjal tidak memberikan respon terhadap hormon antidiuretik sehingga ginjal terus-menerus mengeluarkan sejumlah besar air kemih yang encer. Pada diabetes insipidus lainnya, kelenjar hipofisa gagal menghasilkan hormon antidiuretik. Diabetes Insipidus Nefrogenik dapat disebabkan oleh beberapa hal yaitu : 1. Penyakit ginjal kronik : ginjal polikistik, medullary cystic disease, pielonefretis, obstruksi ureteral, gagal ginjal lanjut. 2. Gangguang elektrolit : Hipokalemia, hiperkalsemia. 3. Obat-obatan : litium, demoksiklin, asetoheksamid, tolazamid, glikurid, propoksifen. 4. Penyakit sickle cell 5. Gangguan diet C. Manifestasi Klinis Keluhan dan gejala utama diabetes insipidus adalah : a. Poliuri 5-15 liter / hari b. Polidipsi c. Berat jenis urine sangat rendah 1001-1005 d. Peningkatan osmolaritas serum > 300 m. Osm/kg e. Penurunan osmolaritas urine < 50-200m. Osm/kg

Keluhan dan gejala utama diabetes insipidus adalah poliuria dan polidipsia. Jumlah produksi urin maupun cairan yang diminum per 24 jam sangat banyak. Selain poliuria dan polidipsia, biasanya tidak terdapat gejala-gejala lain, kecuali bahaya baru yang timbul akibat dehidrasi yang dan peningkatan konsentrasi zat-zat terlarut yang timbul akibat gangguan rangsang haus. Diabetes insipidus dapat timbul secara perlahan maupun secara tiba-tiba pada segala usia. Seringkali satusatunya gejala adalah rasa haus dan pengeluaran air kemih yang berlebihan. Sebagai kompensasi hilangnya cairan melalui air kemih, penderita bisa minum sejumlah besar cairan (3,8-38 L/hari). Jika kompensasi ini tidak terpenuhi, maka dengan segera akan terjadi dehidrasi yang menyebabkan tekanan darah rendah dan syok. D. Patofisiologi Vasopresin arginin merupakan suatu hormon antidiuretik yang dibuat di nucleus supraoptik, paraventrikular , dan filiformis hipotalamus, bersama dengan pengikatnya yaitu neurofisin II. Vasopresin kemudian diangkut dari badan sel neuron (tempat pembuatannya), melalui akson menuju ke ujung saraf yang berada di kelenjar hipofisis posterior, yang merupakan tempat penyimpanannya. Secara fisiologis, vasopressin dan neurofisin yang tidak aktif akan disekresikan bila ada rangsang tertentu. Sekresi vasopresin diatur oleh rangsang yang meningkat pada reseptor volume dan osmotic. Peningkatan osmolalitas cairan ekstraseluler atau penurunan volume intravaskuler akan merangsang sekresi vasopresin. Vasopressin kemudian meningkatkan permeabilitas epitel duktus pengumpul ginjal terhadap air melalui suatu mekanisme yang melibatkan pengaktifan adenolisin dan peningkatan AMP siklik. Akibatnya, konsentrasi kemih meningkat dan osmolalitas serum menurun. Osmolalitas serum biasanya dipertahankan konstan dengan batas yang sempit antara 290 dan 296 mOsm/kg H2O. Gangguan dari fisiologi vasopressin ini dapat menyebabkan pengumpulan air pada duktus pengumpul ginjal karena berkurang permeabilitasnya, yang akan menyebabkan poliuria atau banyak kencing. Selain itu, peningkatan osmolalitas plasma akan merangsang pusat haus, dan sebaliknya penurunan osmolalitas plasma akan menekan pusat haus. Ambang rangsang osmotic pusat haus lebih tinggi dibandingkan ambang rangsang sekresi vasopresin. Sehingga apabila osmolalitas plasma meningkat, maka tubuh terlebih dahulu akan mengatasinya dengan mensekresi vasopresin yang apabila masih meningkat akan merangsang pusat haus, yang akan berimplikasi orang tersebut minum banyak (polidipsia). Secara patogenesis, diabetes insipidus dibagi menjadi 2 yaitu diabetes insipidus sentral, dimana gangguannya pada vasopresin itu sendiri dan diabetes insipidus nefrogenik, dimana gangguannya adalah karena tidak responsifnya tubulus ginjal terhadap vasopresin. Diabetes insipidus sentral dapat disebabkan oleh kegagalan pelepasan hormone antidiuretik ADH yang merupakan kegagalan sintesis atau penyimpanan. Hal ini bisa disebabkan oleh kerusakan nucleus supraoptik, paraventrikular, dan filiformis hipotalamus yang mensistesis ADH. Selain itu, DIS juga timbul karena gangguan pengangkutan ADH akibat kerusakan pada akson traktus supraoptikohipofisealis dan aksin hipofisis posterior di mana ADH disimpan untuk sewaktuwaktu dilepaskan ke dalam sirkulasi jika dibutuhkan. DIS dapat juga terjadi karena tidak adanya sintesis ADH, atau sintesis ADH yang kuantitatif tidak mencukupi kebutuhan, atau kuantitatif cukup tetapi tidak berfungsi normal. Terakhir, ditemukan bahwa DIS dapat juga terjadi karena terbentuknya antibody terhadap ADH.

E. Penatalaksanaan 1. Terapi cairan parenteral Untuk mencegah dehidrasi, penderita harus selalu minum cairan dalam jumlah yang cukup ketika mereka merasa haus karena penyakit diabetes insipidus merupakan suatu kelainan dimana terdapat kekurangan hormon antidiuretik yang menyebabkan rasa haus yang berlebihan dan pengeluaran sejumlah besar air kemih yang sangat encer sehingga penderita bayi dan anak-anak harus sering diberi minum. 2. Jika hanya kekurangan ADH, dapat diberikan obat Clorpropamide, clofibrate untuk merangsang sintesis ADH di hipotalamus. 3. Jika berat diberikan ADH melalui semprotan hidung dan diberikan vasopressin atau desmopresin asetat (dimodifikasi dari hormon antidiuretik). Pemberian beberapa kali sehari berguna untuk mempertahankan pengeluaran air kemih yang normal. Terlalu banyak mengkonsumsi obat ini dapat menyebabkan penimbunan cairan, pembengkakan dan gangguan lainnya. 4. Obat-obat tertentu dapat membantu, seperti diuretik tiazid (misalnya hidrochlorothiazid/HCT) dan obat-obat anti peradangan non-steroid (misalnya indometacin atau tolmetin). 5. Pada DIS yang komplit, biasanya diperlukan terapi hormone pengganti (hormonal replacement) DDAVP (1-desamino-8-d-arginine vasopressin) yang merupakan pilihan utama. Selain itu, bisa juga digunakan terapi adjuvant yang mengatur keseimbangan air, seperti: Diuretik Tiazid, Klorpropamid, Klofibrat, dan Karbamazepin. F. Pemeriksaan Diagnostik Ada sebuah cara untuk mendiagnosa penyebab suatu poliuria adalah akibat Diabetes Insipidus, bukan karena penyakit lain. Caranya adalah dengan menjawab tiga pertanyaan yang dapat kita ketahui dengan anamnesa dan pemeriksaan. Pertama, apakah yang menyebabkan poliuria tersebut adalah pemasukan bahan tersebut (dalam hal ini air) yang berlebihan ke ginjal atau pengeluaran yang berlebihan. Bila pada anamnesa ditemukan bahwa pasien memang minum banyak, maka wajar apabila poliuria itu terjadi. Kedua, apakah penyebab poliuria ini adalah factor renal atau bukan. Poliuria bisa terjadi pada penyakit gagal ginjal akut pada periode diuresis ketika penyembuhan. Namun, apabila poliuria ini terjadi karena penyakit gagal ginjal akut, maka akan ada riwayat oligouria (sedikit kencing). Ketiga, Apakah bahan utama yang membentuk urin pada poliuria tersebut adalah air tanpa atau dengan zat-zat yang terlarut. Pada umumnya, poliuria akibat Diabetes Insipidus mengeluarkan air murni, namun tidak menutup kemungkinan ditemukan adanya zat-zat terlarut. Apabila ditemukan zat-zat terlarut berupa kadar glukosa yang tinggi (abnormal) maka dapat dicurigai bahwa poliuria tersebut akibat DM yang merupakan salah satu Differential Diagnosis dari Diabetes Insipidus. Jika dicurigai penyebab poliuria adalah Diabetes Insipidus, maka harus dilakukan pemeriksaan untuk menunjang diagnosis dan untuk membedakan apakah jenis Diabetes Insipidus yang dialami karena penatalaksanaan dari dua jenis diabetes insipidus ini berbeda. Ada beberapa pemeriksaan pada Diabetes Insipidus, antara lain: 1. Hickey Hare atau Carter-Robbins Hickey-Hare tes adalah uji endokrin untuk menyelidiki osmoregulasi. Cairan NaCl hipertonis diberikan IV dan akan menunjukkan bagaimana respon osmoreseptor dan daya pembuatan ADH.

a. Infus dengan dexrose dan air sampai terjadi dieresis 5 ml/menit (biasanya 8-10 ml/menit). b. Infuse di ganti dengan NaCl 2,5% dengan jumlah 0,25 ml/menit/kg BB di pertahankan selama 45 menit c. Urin ditampung selama 15 menit. Penilaian : kalau normal dieresis akan menurun secara mencolok Perhatian : pemeriksaaan ini cukup berbahaya 2. Fluid deprivation Pemeriksaan yang paling sederhana dan paling dapat dipercaya untuk diabetes insipidus adalah water deprivation test. Selama menjalani pemeriksaan ini penderita tidak boleh minum dan bisa terjadi dehidrasi berat. Oleh karena itu pemeriksaan ini harus dilakukan di rumah sakit atau tempat praktek dokter. Pembentukan air kemih, kadar elektrolit darah (natrium) dan berat badan diukur secara rutin selama beberapa jam. Segera setelah tekanan darah turun atau denyut jantung meningkat atau terjadi penurunan berat badan lebih dari 5%, maka tes ini dihentikan dan diberikan suntikan hormon antidiuretik. 3. Uji nikotin Produksi vasopressin oleh sel hipotalamus langsung dirangsang oleh nikotin. Obat yang di pakai adalah nikotin salisilat secara IV. Akibat sampingnya adalah mual, muntah. Penilaian : kalau normal dieresis akan menurun secara mencolok Perhatian : pemeriksaan ini cukup berbahaya 4. Pemeriksaan laboratorium Menunjukkan kadar natrium yang tinggi dalam darah dan air kemih yang sangat encer. Fungsi ginjal lainnya tampak normal. Apapun pemeriksaannya, prinsipnya adalah untuk mengetahui volume, berat jenis, atau konsentrasi urin. Sedangkan untuk mengetahui jenisnya, dapat dengan memberikan vasopresin sintetis, pada Diabetes Insipidus Sentral akan terjadi penurunan jumlah urin, dan pada Diabetes Insipidus Nefrogenik tidak terjadi apa-apa. Hal yang perlu diperhatikan dalam pemeriksaan diabetes insipidus adalah : Pertama, apakah yang menyebabkan poliuria tersebut adalah pemasukan bahan tersebut (dalam hal ini air) yang berlebihan ke ginjal atau pengeluaran yang berlebihan. Bila pada anamnesa ditemukan bahwa pasien memang minum banyak, maka wajar apabila poliuria itu terjadi. Kedua, apakah penyebab poliuria ini adalah faktor renal atau bukan. Poliuria bisa terjadi pada penyakit gagal ginjal akut pada periode diuresis ketika penyembuhan. Namun, apabila poliuria ini terjadi karena penyakit gagal ginjal akut, maka akan ada riwayat oligouria (sedikit kencing). Ketiga, apakah bahan utama yang membentuk urin pada poliuria tersebut adalah air tanpa atau dengan zat-zat yang terlarut. Pada umumnya, poliuria akibat Diabetes Insipidus mengeluarkan air murni, namun tidak menutup kemungkinan ditemukan adanya zat-zat terlarut. Apabila ditemukan zat-zat terlarut berupa kadar glukosa yang tinggi (abnormal) maka dapat dicurigai bahwa poliuria tersebut akibat DM yang merupakan salah satu Differential Diagnosis dari Diabetes Insipidus. Diagnosis diabetes insipidus semakin kuat jika sebagai respon terhadap hormon antidiuretik: - pembuangan air kemih yang berlebihan berhenti - tekanan darah naik - denyut jantung kembali normal. BAB III

ASUHAN KEPERAWATAN 1 Pengkajian A. Data Demografi Identitas pada klien yang harus diketahui diantaranya: nama, umur, agama, pendidikan, pekerjaan, suku/bangsa, alamat, jenis kelamin, status perkawinan, dan penanggung biaya. B. Riwayat Sakit dan Kesehatan 1. Keluhan utama Biasanya pasien merasa haus, pengeluaran air kemih yang berlebihan, sering keram dan lemas jika minum tidak banyak. 2. Riwayat penyakit saat ini Pasien mengalami poliuria, polidipsia, nocturia, kelelahan, konstipasi 3. Riwayat penyakit dahulu Klien pernah mengalami Cidera otak, tumor, tuberculosis, aneurisma/penghambatan arteri menuju otak, hipotalamus mengalami kelainan fungsi dan menghasilkan terlalu sedikit hormone antidiuretik, kelenjar hipofisa gagal melepaskan hormon antidiuretik kedalam aliran darah, kerusakan hipotalamus/kelenjar hipofisa akibat pembedahan dan beberapa bentuk ensefalitis, meningitis. 4. Riwayat penyakit keluarga Adakah penyakit yang diderita oleh anggota keluarga yang mungkin ada hubungannya dengan penyakit klien sekarang, yaitu riwayat keluarga dengan diabetes insipidus. 5. Pengkajian psiko-sosio-spiritual Perubahan kepribadian dan perilaku klien, perubahan mental, kesulitan mengambil keputusan, kecemasan dan ketakutan hospitalisasi, diagnostic test dan prosedur pembedahan, adanya perubahan peran. C. Pemeriksaan Fisik ( ROS : Review of System ) Pemeriksaan fisik pada klien dengan diabetes insipidus meliputi pemeriksaan fisik umum per system dari observasi keadaan umum, pemeriksaan tanda-tanda vital, B1 (breathing), B2 (Blood), B3 (Brain), B4 (Bladder), B5 (Bowel), dan B6 (Bone). 1. Pernafasan B1 (breath) RR = 20 x/mnt, tidak ada sesak nafas, tidak ada batuk pilek, tidak memiliki riwayat asma dan suara nafas normal. 2. Kardiovaskular B2 (blood) TD = 130/80 mmHg, nadi = 84 x/mnt, suhu = 36,5 oC, suara jantung vesikuler. Perfusi perifer baik, turgor kulit buruk, intake= 295 mosmol/L (n= <290 mosmol/L) - Urea N: <3 mg/dl.(normal= 3 7,5 mmol/L) - Kreatinin serum: 75 IU/L. (n= <70 IU/L) - Bilirubin direk: 0,08 mg/dl. (n= 0,1 0,3 mg/dl) - Bilirubin total: 0,01 mg/dl. (n= 0,3 1 mg/dl) - SGOT: 38 U/L. (n= 0 25 IU/L) - SGPT: 18 U/L. (n= 0 25 IU/L) 2 Analisis Data

No. Data Etiologi Masalah Keperawatan 1. Data Subjektif : px mengatakan haus, badan terasa lesu. Data Objektif : intake= <2500 cc/hr, output= 3000 cc/hr, IWL = 500 cc/hr, turgor kulit buruk. Diabetes Insipidus Hiperosmolaritas serum Merangsang haus Pergantian air tidak adekuat Volume cairan tubuh berkurang kurangnya volume cairan dalam tubuh 2. Data Subjektif : pasien mengatakan sering kencing terlebih pada malam hari. Data Objektif : Poliuria sangat encer( 3000cc/hr +IWL 500cc/hr), dengan berat jenis 1.010, osmolalitas urin 50-150 mosmol/L. Diabetes Insipidus Penurunan osmolaritas urin Hilangnya banyak cairan (urin) poliuria Perubahan eliminasi urin 3. Data Subjektif : pasien mengatakan tidak tahu tentang pengobatan dan perawatan penyakitnya Data Objektif : klien tidak mengikuti instruksi secara akurat Riwayat Diabetes Insipidus keluarga Minimnya informasi tentang pengobatan dan perawatan DI Kurang pengetahuan 3 Diagnosa Keperawatan 1. Kurangnya volume cairan dalam tubuh berhubungan dengan ekskresi yang meningkat dan intake cairan yang tidak adekuat. 2. Perubahan eliminasi urine berhubungan dengan ketidakmampuan tubulus ginjal mengkonsentrasikan urine karena tidak terdapat ADH. 3. Kurang pengetahuan berhubungan dengan kurang informasi mengenai proses penyakit, pengobatan dan perawatan diri. 4. intervensi Keperawatan 1. Kurangnya volume cairan dalam tubuh berhubungan dengan ekskresi yang meningkat dan intake cairan yang tidak adekuat. Tujuan: Menyeimbangkan masukan dan pengeluaran cairan Kriteria Hasil : a. I = O b. Tidak terdapat tanda-tanda dehidrasi ( turgor baik, mata tidak cowong) c. TTV dalam batas normal (n =120/80mmHg). Intervensi Rasional 1.Mandiri

a. Pantau BB (input dan output) b. Pantau tanda-tanda dehidrasi c. Pantau TTV 2. Kolaborasi a. Berikan terapi cairan dengan mengganti vasopressin atau dengan penyuntikan intramuskuler ADH. 3. HE Anjurkan pasien untuk minum banyak (2000-2500 cc/hari) 1.Mandiri a. Untuk mengetahui tingkat dehidrasi b. Untuk mengetahui tingkat dehidrasi c. Memantau keadaan pasien 2. Kolaburasi a. Menghindari dehidrasi 3.Menghindari dehidrasi 2. Perubahan eliminasi urine berhubungan dengan penurunan produksi ADH Tujuan : Eliminasi urine kembali normal Kriteria Hasil : eliminasi urine kembali normal (0,5-1 cc/kg BB/jam) Intervensi Rasional 1. Mandiri a. Pantau eliminasi urine yang meliputi frekuensi, konsistensi, bau, volume, dan warna dengan tepat. 2. Kolaborasi a. Berikan terapi vasopressin atau dengan penyuntikan intramuskuler ADH. b. Tes deprivasi cairan dilakukan dengan cara menghentikan pemberian cairan selama 8-12 jam atau sampai terjadi penurunan BB. 1. Mandiri a. Untuk mengetahui perubahan kondisi pasien b. Untuk mengembalikan pola normal eliminasi urine. 2. Kolaburasi a. Untuk mengetahui respon ginjal terhadap pemberian hormon ADH b. Untuk menghindari gagal ginjal 3. Kurang pengetahuan berhubungan dengan kurang informasi mengenai proses penyakit, pengobatan dan perawatan diri. Tujuan: Memberi pemahaman kepada pasien terhadap penyakit pasien

Kriteria Hasil: a. Klien dapat mengungkapkan mengerti tentang proses penyakit dan mengikuti instrukasi yang diberikan secara akurat. Pengarahan obat-obatan, gejala untuk dilaporkan dan perlunya mendapatkan gelang waspada medis. Intervensi Rasional 1. Mandiri: a. Jelaskan konsep dasar proses penyakit. b. Jelaskan pentingnya tindak lanjut rawat jalan yang teratur. c. Jelaskan perlunya untuk menghindari obat yang dijual bebas. 1.Mandiri a. Memberi pemahaman kepada pasien b. Agar pasien tahu pentingnya pemantauan penyakit c. Untuk menghindari semakin parahnya penyakit

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:

Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP]) Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney[1]

Two other forms are gestational DI and primary polydipsia (dipsogenic DI); both are caused by deficiencies in AVP, but the deficiencies do not result from a defect in the neurohypophysis or kidneys.
Essential update: Predicting permanent diabetes insipidus in children with craniopharyngioma

A retrospective analysis of 102 consecutive operations for craniopharyngioma (45 in children and 57 in adults) was carried out with the aim of determining the incidence, predictors, and early postoperative course of DI in this setting.[2] Postoperative DI was more common in children than in adults (80% vs 63%). Children also had a significantly higher incidence of permanent DI (55.6%), and radical excision was found to be a predictor of this result in pediatric patients (though not in adult patients, for whom previous tumor surgery and new-onset hypopituitarism were stronger predictors of permanent DI). The triphasic response, wide intraday serum sodium fluctuations, and hyponatremia were all more common in children as well. These findings suggest that postoperative DI may be more difficult to manage in pediatric patients and that additional alertness is required to detect the triphasic response in this group.[2]

Signs and symptoms

The predominant manifestations of DI are as follows:

Polyuria: The daily urine volume is relatively constant for each patient but is highly variable between patients (3-20 L) Polydipsia Nocturia

The most common form is central DI after trauma or surgery to the region of the pituitary and hypothalamus, which may exhibit 1 of the following 3 patterns:

Transient Permanent Triphasic (observed more often clinically)

In infants with DI, the most apparent signs may be the following:

Crying Irritability Growth retardation Hyperthermia Weight loss

In children, the following manifestations typically predominate:

Enuresis Anorexia Linear growth defects Fatigability

If the condition that caused DI also damaged the anterior pituitary or hypothalamic centers that produce releasing factors, patients may present with the following:

Excessive fatigue Diminished libido or erectile dysfunction Headache Dry skin Hair loss

Physical findings vary with the severity and chronicity of DI; they may be entirely normal or may include the following:

Hydronephrosis, with pelvic fullness, flank pain or tenderness, or pain radiating to the testicle or genital area Bladder enlargement in some patients Dehydration if the thirst mechanism is impaired or access to fluid is restricted

See Clinical Presentation for more detail.

Diagnosis

If the clinical presentation suggests DI, laboratory tests must be performed to confirm the diagnosis, as follows:

A 24-hour urine collection for determination of urine volume Serum electrolyte concentrations and glucose level Urinary specific gravity Simultaneous plasma and urinary osmolality Plasma ADH level

Additional studies that may be indicated include the following:

Water deprivation (Miller-Moses) test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis Pituitary studies, including magnetic resonance imaging (MRI) and measurement of circulating pituitary hormones other than ADH

See Workup for more detail.

Management

Most patients with DI can drink enough fluid to replace their urine losses. When oral intake is inadequate and hypernatremia is present, provide fluid replacement as follows:

Give dextrose and water or an intravenous fluid that is hypo-osmolar with respect to the patients serum; do not administer sterile water without dextrose IV Administer fluids at a rate no greater than 500-750 mL/hr; aim at reducing serum sodium by approximately 0.5 mmol/L (0.5 mEq/L) every hour

Pharmacologic therapeutic options include the following:

Desmopressin (drug of choice for central DI[3, 4] ) Synthetic vasopressin Chlorpropamide Carbamazepine (rarely used; employed only when all other measures prove unsatisfactory) Clofibrate (no longer on the US market) Thiazides Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin (may be used in nephrogenic DI, but only when no better options exist)

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 h) of dilute urine (< 300m Osm/kg). DI has 2 major forms: central and nephrogenic.

Central DI is characterized by decreased secretion of antidiuretic hormone (ADH)also known as arginine vasopressin (AVP)which gives rise to polyuria and polydipsia by diminishing the persons ability to concentrate urine. Other terms for central DI are neurogenic, pituitary, and neurohypophyseal DI. (See Etiology, Presentation, and Workup.) Nephrogenic DI is characterized by a decrease in the ability to concentrate urine because of resistance to ADH action in the kidney.[1] Nephrogenic DI can be observed in chronic renal insufficiency, lithium toxicity, hypercalcemia, hypokalemia, glucosuria, and tubulointerstitial disease. (See Etiology, Presentation, and Workup.) Two other forms of DI are gestational DI and primary polydipsia. Both are caused by deficiencies in AVP, but the deficiencies do not result from a defect in the neurohypophysis or kidneys. Gestational DI results from degradation of vasopressin by a placental vasopressinase. Primary polydipsia (dipsogenic DI) results from a primary defect in osmoregulation of thirst. The exact location of the lesion is not known, but structural lesions may exist, as dipsogenic DI has been reported in tuberculous meningitis, multiple sclerosis, and neurosarcoidosis. Rarely, DI may be hereditary.[3] Hereditary nephrogenic DI manifests in early infancy, often before the age of 1 week. Hereditary central DI typically manifests in childhood. For more information on DI in children, see Pediatric Diabetes Insipidus. Pharmacologic treatment of DI generally involves the use of desmopressin (1-deamino-8-Darginine vasopressin [DDAVP]), nonhormonal drugs, or both. Patients must be instructed in simple principles of water balance to avoid dehydration and water intoxication (if they are not carefully monitoring water intake). (See Treatment.)
Physiology of water balance

The normal range of plasma osmolality is between 275 and 295 mOsm/kg. The ability of the kidneys to modify the concentration of urinary solutes ranges between 501200 mOsm/kg. Healthy adults on a normal diet excrete 8001200 mOsm of solute daily. Thus, to excrete 1000 mOsm of solute, the obligate urinary water excretion would be 1000 mOsm per 1200 mOsm/kg water, which translates into 0.8 kg (0.8 L) of water per day. This urine is maximally concentrated and appears dark yellow or orange in color. If this requirement for obligate water excretion is not met, solutes accumulate, leading to uremia. Conversely the maximum volume of urine (secondary to limits imposed by renal dilutional capacity) is 20 L of water per day (1000 mOsm per 50 mOsm/kg water). This maximally dilute urine is colorless. The maintenance of water balance in healthy humans is principally accomplished through 3 robust, interrelated determinants: thirst, AVP, and the kidneys. In addition, recognition of a fourth factor, apelin, has emerged in recent years. Apelin is a bioactive peptide that is widely distributed throughout the body. In the brain, it is expressed in supraoptic and paraventricular nuclei, as well as in other sites, and has specific receptors located on vasopressinergic neurons. Apelin acts as a potent diuretic neuropeptide that inhibits ADH release.

AVP is the primary determinant of free water excretion in the body. Its main target is the kidney, where it acts by altering the water permeability of the cortical and medullary collecting tubules. Water is reabsorbed by osmotic equilibration with the hypertonic interstitium and returned to the systemic circulation. The actions of AVP are mediated through at least 2 receptors, as follows[5, 6] :

V1 - Mediates vasoconstriction, enhancement of corticotrophin release, and renal prostaglandin synthesis V2 - Mediates the antidiuretic response

Effects of reduced AVP or ADH

The vasoconstrictor effect of AVP is negligible in humans. No clinically significant defects in blood pressure regulation or cortisol secretion are apparent in patients with DI. Diminished or absent ADH production can be the result of a defect in 1 or more sites in the neurohypophysis. These include the hypothalamic osmoreceptors, the supraoptic or paraventricular nuclei, and the supraopticohypophyseal tract.
Response to volume decrease

Ordinarily, a decrease in the extracellular fluid (ECF) volume elicits the following simultaneous responses:

Aldosterone secretion - To preserve sodium retention Thirst - To raise water intake AVP secretion - To increase water retention

Volume depletion activates baroreceptor mechanisms that exert similar effects on aldosterone, thirst, and AVP, whereas osmoreceptor-mediated mechanisms impact thirst and AVP secretion only. Osmoreceptors for thirst are solute specific, responding preferentially to increased sodium levels in the ECF. Thus, elevated glucose levels in diabetes mellitus do not induce thirst; rather, the increased thirst in uncontrolled diabetes mellitus is secondary to volume depletion from osmotic diuresis. DI is usually an acquired disorder, with central DI having different causes than does nephrogenic DI. In rare cases, central or nephrogenic DI may be an inherited disorder.
Central diabetes insipidus

Central DI has many possible causes. According to the literature, the principal causes of central DI and their oft-cited approximate frequencies are as follows:

Idiopathic - 30%

Malignant or benign tumors of the brain or pituitary - 25% Cranial surgery - 20% Head trauma - 16%[7]

Idiopathic DI Idiopathic central DI presumably develops when cells in the hypothalamus are damaged or destroyed. Identification of antibodies against AVP-secreting cells and advances in imaging techniques have made idiopathic cases less common than they previously were. Increasingly, the role of inflammation and autoimmunity in DI is being recognized. Cases of lymphocytic hypophysitis were possibly classified as idiopathic prior to improved imaging studies. This disorder is characterized by lymphocytic infiltration of the stalk and posterior pituitary. Magnetic resonance imaging (MRI) may show abnormalities in these structures. Antibodies directed against vasopressin cells have been found in patients with idiopathic central DI; however, these antibodies have also been found in patients with Langerhans cell histiocytosis (LCH) or germinomas, which indicates that this finding can not be considered a reliable marker of autoimmune etiology in central DI. Indeed, reliance on AVP antibodies may delay the diagnosis of LCH or germinoma. Given the possible diagnostic confusion, close clinical and MRI follow-up is necessary. Serial contrast-enhanced brain MRIs (every 3-6 months for the first 2 years) in patients with central DI who have pituitary stalk thickening may shorten the time to diagnosis of germinoma by as much as 1 year. The role of human chorionic gonadotropin (hCG) in the early diagnosis of germinoma is not fully established. A negative result for hCG in the cerebrospinal fluid (CSF) does not exclude germinoma. Tumor-associated DI Primary intracranial tumors causing DI include craniopharyngiomas, germinomas, and pineal tumors, among others. The appearance of other hypothalamic manifestations may be delayed for as long as 10 years in these cases. Craniopharyngioma is a benign tumor that arises from squamous cell nests in the primitive Rathke pouch. It is the most frequent pediatric intracranial neoplasm, accounting for nearly 54% of cases. Central DI insipidus and multiple pituitary hormone deficiencies are common manifestations in childhood craniopharyngiomas. Surgery is the preferred treatment. Postoperative DI The frequency with which DI develops after neurosurgery varies with the surgerys scope. Approximately 10-20% of patients experience DI after transsphenoidal removal of an adenoma, compared with 60-80% of those who have undergone excision of large tumors.

Not all cases of postoperative DI are permanent. In a German study of metabolic disturbances after transsphenoidal pituitary adenoma surgery, only 8.7% of DI cases persisted for more than 3 months.[8] Postoperative polyuria does not necessarily indicate DI. The most common causes of postoperative polyuria are excretion of excess fluid administered during surgery and an osmotic diuresis resulting from treatment for cerebral edema.[9] DI in head trauma Central DI can be an acute or chronic complication of head injury or subarachnoid hemorrhage.[7, 10] Risk factors for acute DI include penetrating trauma and severe head trauma.[7] Other forms of pituitary dysfunction (eg, adrenocorticotropic hormone deficiency) may accompany posttraumatic DI.[10] The dysfunction may be transient or, less commonly, may develop gradually.[11] Hereditary central DI Approximately 10% of central DI cases are familial (although some experts suggest that familial DI may be underdiagnosed).[12] Most of these cases show autosomal dominant inheritance and result from a defect in the AVP-NP2 gene on chromosome 20p13. The defect results in the production of mutant prohormone that is toxic to the neuron and eventually destroys it.[13, 14, 15] There are also autosomal recessive forms of DI, which result from defects in the AVP-NP2 (AVP neurophysin) gene, as well as in the WFS1 gene. The latter gene encodes for wolframin, a tetrameric protein that may serve as a novel endoplasmic reticular calcium channel in pancreatic beta cells and neurons. Mutations in WFS1 lead to Wolfram syndrome, which is also known by the acronym DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, Deafness).[16] Another recessive form of central DI results from the production of biologically inactive AVP. In addition, an X-linked form of neurohypophyseal DI exists. A specific genetic defect has not been identified.[3] Genetic testing to determine the specific etiology can obviate the search for another cause.[3] Finding a genetic anomaly will also answer recurrence risk questions for the family, and may prove to be helpful with treatment options. Additional causes Other causes of central DI include the following:

Cancer - Eg, metastatic lung cancer, lymphoma, leukemia Hypoxic encephalopathy Granulomatous disease - Eg, histiocytosis X, sarcoidosis, tuberculosis, Wegener granulomatosis Anorexia nervosa

Vascular lesions - Eg, arteriovenous malformations, aneurysms, Sheehan syndrome, sickle cell disease, aortocoronary bypass

Nephrogenic diabetes insipidus

In adults, nephrogenic DI most often develops as a result of lithium toxicity or hypercalcemia. Impairment of urinary concentration occurs in up to 20% of patients taking lithium, as a result of dysregulation of the aquaporin system in principal cells of the collecting duct.[17, 18] Prolonged elevation of serum calcium concentrations above 11 mg/dL (2.75 mmol/dL can also impair urinary concentrating ability. Other causes of acquired nephrogenic DI include the following:

Hypokalemia Renal disease - Eg, from sickle cell disease, amyloidosis Pregnancy (transient) Hyperglycemia (osmotic diuresis)

In addition to lithium, other drugs that can reduce urinary concentrating ability include the following:

Amphotericin B Cidofovir Demeclocycline Didanosine Foscarnet Ofloxacin Orlistat

Hereditary nephrogenic DI Hereditary nephrogenic DI is relatively rare.[4] The most common inherited form results from mutations in the AVP receptor 2 gene (AVPR2) on chromosome Xq28.[19] Defects in the AVP receptor cause resistance to the antidiuretic effect of vasopressin. Because hereditary nephrogenic DI is an X-linked disorder, most cases occur in males; however, cases occasionally arise in females as a result of skewed X inactivation.[20] Approximately 1% of familial nephrogenic DI cases result from mutations in AQP2 (aquaporin 2), a gene on chromosome 12q13 that gives rise to a water channel that is expressed exclusively in the kidneys collecting ducts. Autosomal recessive and autosomal dominant forms of nephrogenic DI from AQP2 mutations have been reported.[3] DI is uncommon in the United States, with a prevalence of 3 cases per 100,000 population.[21] No significant sex-related differences in central or nephrogenic DI exist, with male and female prevalence being equal. Similarly, no significant differences in prevalence among ethnic groups have been found.

With both central and nephrogenic DI, inherited causes account for approximately 1-2% of all cases. An incidence of about 1 in 20 million births for nephrogenic DI caused by AQP2 mutations has been cited.[22] The prognosis for patients with DI is generally excellent, depending on the underlying illness. In nephrogenic DI caused by medication (eg, lithium), stopping the medication may help to restore normal renal function; after many years of lithium use, however, permanent nephrogenic DI may occur. DI-related mortality is rare in adults as long as water is available. Severe dehydration, hypernatremia, fever, cardiovascular collapse, and death can ensue in children and elderly people, as well as in persons with complicating illnesses.