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Perie Adorable-Wagan, MD
Objectives
To evaluate patients presenting with polyuria To present a diagnostic approach in a patient suspected with Diabetes insipidus To briefly review pathophysiology of Diabetes insipidus To discuss management of Diabetes insipidus
IDENTIFYING DATA
30 year old Female Single Roman Catholic OFW Nurse Quezon City Jan 25, 2006
CHIEF COMPLAINT
TMC
Review of Symptoms
Skin: supple skin,no skin pigmentation HEENT: no headache,no dizziness,no seizures, no visual changes or eye pain, no photophobia, no tinnitus, no hearing loss, no nose bleeding, no hoarseness, no dysphagia. Respiratory: no shortness of breath, no cough, no hemoptysis
Review of Symptoms
Cardiovascular: no easy fatigability, no palpitation ,No chest pain, orthopnea, , no paroxysmal nocturnal dyspnea Gastrointestinal: no abdominal pain, nausea,vomiting Genitourinary: (+)urinary frequency due to her increase water intake , no dysuria, no hematuria
Review of Symptoms
Neuromuscular: no proximal muscle weakness Metabolic : no heat intolerance, no weight loss, regular appetite
PHYSICAL EXAMINATION
BP: 130/80 HR: 100 RR: 130/80 Temp: 37 wt: 51kg Skin supple skin, no skin pigmentation HEENT: anicteric sclera, pink conjunctivae, moist lips and buccal mucosa, no neck vein distention,no palpable neck mass, no cervical lympadenopathy
PHYSICAL EXAMINATION
HEART: adynamic precordium, regular rate regular rhythm, no murmur Abdomen: soft, normoactive bowel sound, no tenderness Extremities: no tremors, no cyanosis, no edema
SALIENT FEATURES
30 year old female No known medical comorbidities Polyuria and polydipsia
ADMITTING IMPRESSION
DIABETES INSIPIDUS
EVALUATION OF POLYURIA
1. Is This True Polyuria or Just Urinary Frequency? 2. If True Polyuria, is this a Water Diuresis or a Solute Diuresis? 3. If If a Water Diuresis, Is This Diabetes Insipidus or Primary Polydipsia?
Frequent voiding of small volumes of concentrated urine is indicative of bladder dysfunction caused by infection or other local disease.
A 24-hour urine collection provides objective confirmation of true polyuria when the volume exceeds 3 L or 50 mL/kg.
Solute diuresis
Water diuresis
Evaluation of Polyuria
Polyuria >3L/24hrs
Diabetes Mellitus
Uosm 59mOsm/kg
Posm 293mOsm/kg
Serum Na 140
Interpretation
Normal response Urine osmolality 2-4x greater than that of plasma osmolality With Exogenous vasopressin resulting in less than 9% further increase in urine osmolality
Endocrine Protocols 2011 1st edition
Interpretation
Complete Central Diabetes Insipidus Urine osmolality is low compared to plasma osmolalilty in response to water deprivation but more than 50% increase in urine osmolality after vasporessin administration
Interpretation
Partial Central DI Increase 9-50% urine osmolality after vasopressin Nephrogenic DI Urine osmolality fail to increase to greater than plasma osmolality with exogenous vasopressin. Increase < 10% urine osmolality
Endocrine Protocols 2011 1st edition
Interpretation
Primary Polydipsia Concentrate urine only slightly Less than 9% rise in urine osmolality
Patients result
DIAGNOSTIC ALGORITHM
DIAGNSOTIC ALGORITHM
DIAGNOSTIC ALGORITHM
Management
1. ADH replacement a.)Pitressin(vasopressin tannate in oil). IM Every 2 to 4 days and provides relief 24 to 72 hours. Its side effects include abdominal cramping, hypertension, and angina. The disadvantages of these preparations prompted the development of oral agents to aid in antidiuresis.
Management
b.)Desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP) Drug of choice for long-term therapy of central diabetes insipidus. synthetic V2R (ADH receptor) agonist It can be given IV, PO, intranasally. For all dosage forms, the starting dosage is 10 g at night to relieve nocturia. A morning dose can be added if symptoms persist during the day.
Management
c.)Chlorpropamide (Diabinese) decreases the clearance of solute free water, but only if the neurohypophysis has some residual secretory capacity. Its antidiuretic effect is likely due to raising the sensitivity of the epithelium of the collecting duct to low concentrations of circulating ADH. d.)Carbamazepine (Tegretol) reduces the sensitivity of the osmoregulatory system of ADH secretion raises the sensitivity of the collecting duct to the hydroosmotic action of the hormone.
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 73 NUMBER 1 JANUARY 2006
Management
d.) Clofibrate (Atromid-S) stimulates residual ADH production in patients with partial central diabetes insipidus. e.)Thiazide diuretics decreasing sodium and chloride absorption in the distal tubule, therefore allowing more sodium absorption and therefore water absorptionin the proximal tubule.
DIABETES INSIPIDUS
Disorder of a large volume of urine (diabetes) that is hypotonic, dilute, and tasteless (insipid). Four pathophysiologic mechanisms related to vasopressin produce large volumes of dilute urine and polydipsia:
1. Hypothalamic (central or neurohypophyseal) diabetes insipidus with inability to secrete and usually to synthesize vasopressin in the neurohypophyseal system 2. Nephrogenic diabetes insipidus wherein there is an inappropriate renal response to vasopressin 3. Transient diabetes insipidus of pregnancy produced by the accelerated metabolism of vasopressin 4. Primary polydipsia wherein the initial pathophysiology is the ingestion of fluid rather than the excretion of fluid
Kronenberg: Williams Textbook of Endocrinology, 11th ed.
Copeptin in the Differential Diagnosis of the Polydipsia-Polyuria Syndrome Revisiting the Directand Indirect Water Deprivation Tests
J Clin Endocrinol Metab, May 2011, 96(5):15061515
Wiebke Fenske,* Marcus Quinkler,* Daniela Lorenz, Kathrin Zopf, Ulrike Haagen,Jana Papassotiriou, Andreas F. H. Pfeiffer, Martin Fassnacht, Stefan Stork,and Bruno Allolio
Copeptin
Background: The water deprivation test (WDT) with direct or indirect measurement of plasma arginine vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia polyuria syndrome. In theory, direct measurement of AVP is highly attractive but is hampered by technical difficulties.
Copeptin
Objective: The aim of the studywasto evaluate the utility of copeptin, a surrogate of AVPsecretion, in the diagnostic work-up of the polyuria-polydipsia syndrome and to compare its performance with the current diagnostic standard. Setting and Design: In two tertiary referral centers, 20 healthy subjects and 50 patients with polydipsia-polyuria syndrome underwent WDT with measurements of both plasma AVP and copeptin levels. The reference diagnosis was based on clinical information and treatment response
J Clin Endocrinol Metab, May 2011
Copeptin
C-terminal part of the AVP precursor cosecreted with AVP from the neurohypophysis higher ex vivo stability much easier to measure than AVP Recently developed copeptin assay demonstrated excellent and robust performance with an analytical detection limit of 0.4 pmol/liter
Results
Results:
Baseline cut-off value >20pmol/L Nephrogenic DI
Primary Polydipsia Sensitivity 82% specificity 92%
> 3pmol/L
4 out 9 CDI
2 out 2 NDI
Results
Nonetheless, due to the substantial overlap of baseline and stimulated copeptin data points between primary poly-dipsia and partial central DI patients the discriminative value of a single copeptin measurement turned out to be limited.
Authors Summary
In summary, copeptin a promising diagnostic potential. If confirmed in additional series, determination of baseline copeptin may become a simple method to identify patients with nephrogenic DI and severe forms of central DI
References:
1. 2. 3. 4. Baylis,Peter. Posterior Pituitary 1997 The Medicine Group (Journals) Villa,Michael. Endocrine Protocols. Handbook of Interpreation of results. 2011 Slovik, David. Evaluation and Management of Adult patient with Polyuria. Williams and Wilkins 2009 Nils G. Morgenthaler,* Joachim Struck, Christine Alonso, and Andreas Bergmann Assay for the Measurement of Copeptin, a Stable Peptide Derived from the Precursor of Vasopressin: Clinical Chemistry 52:1 112119 (2006) AMGAD N. MAKARYUS, MD, SAMY I. McFARLANE, MD, MPH Diabetes insipidus: Diagnosis and treatment of a complex disease : CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 73 NUMBER 1 JANUARY 2006 Wiebke Fenske,* Marcus Quinkler,* Daniela Lorenz. Copeptin in the Differential Diagnosis of the Polydipsia-Polyuria SyndromeRevisiting the Direct and Indirect Water Deprivation Tests. J Clin Endocrinol Metab, May 2011, 96(5):15061515
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