Dr.

Aniqa Shahid PGR MU-1

History
My patient named Razia Aslam w/o Muhammad Aslam. 32 Years old female. Resident of Gulberg Faisalabad. Presented on 4-12-11 in Medical OPD with the following complaints for last 4 months. Frequent large urine. Night wakening for urine. Extreme thirst. Lethargy.

HOPI
My patient was in her usual state of health four months back when for the first time while observing fasts during the month of Ramadan she noticed that she was unable to keep her fast after mid day due to extreme feeling of thirst which was specifically for water. Meanwhile she was frequently passing large volume of colorless urine, So by the end of fast she turned out to be very lethargic & thirsty.

HOPI (Contd.)
She used to drink more than fifteen glass of water in a day with 7-8 times using toilet and about six to seven times during night when she had to get up from sleep d/t thirst and to use toilet. She used to finish her glass in one gulp rather than sipping it over a period of time. She never collected the urine but gave H/O large volumes of urine every time.

HOPI (Contd.)
Her frequent wakening during night due to thirst and passing of urine was making her anxious. History of good appetite. No history of head injury or surgery No H/O dizziness, vertigo, palpitations or heat intolerance. No History of anxiety or other psychiatric illness.

No history of any visual disturbance or headache. No H/O diabetes mellitus. History of regular menstrual cycle. No history of galactorrhoea. No history of any change in bowel habits No H/O joint pains No H/O any respiratory problem. No H/O cardiovascular illness.

Family History

No family history of similar complaints. No history of diabetes, HTN or renal problems. Married with three live issues. Two daughters and one son. Eldest aged 12 years and youngest aged 6 years.

Drug/Medical History
No history of previous illness or any drug therapy, hospitalization or surgery.

Socio-Economic Status
Patient belongs to a middle class family. She is a house wife and her husband works in a factory. They are living in their own home.

GPE
A young lady sitting comfortably in the bed with following vitals. BP 110/70 P/R 84/min R/R 16/min Dry oral Mucosa No other signs of dehydration Pallor Cyanosis Jaundice -JVP not raised

Edema Not Present Cervical, axillary or inguinal lymph nodes not palpable.

CNS:
Mental status examination: ( Conscious ,alert , well oriented in time and space. MMSE normal ) Motor and sensory system intact. Cerebellum : Intact Cranial nerves : Intact

RESPIRATORY SYSTEM :
Inspection: Palpation: Percussion: Auscultation : All normal

CARDIOVASCULAR SYSTEM :
Precordium shape was normal with no visible pulsations Apex beat normally localized . Ist and second heart sounds heard with no added sounds.

GIT:

Normal shape Non distended Non tender No visceromegaly Bowel sounds audible

Lab Investigations

CBC:

Hb ESR WBCs Plt

13.2g/dl 12 5900/cmm 3,15,000

Urea S. Creatinine S. Albumin S. Protein Blood Glucose Random

18mg/dl 0.5mg/dl 4.6mg/dl (3.8-5.1) 7.2mg/dl (6.2-8) 85mg/ dl

Electrolytes Na 146 mmol/l Cl 102 mmol/l K 3.7 mmol/l HCO3 23mmol/l S. Calcium 9.7g/dl S. Phosphorus 4.2g/dl

Urine complete Examination :

Specific gravity 1.006 (1.010- 1.025) Colorless Turbidity Deposits Albumin - Nil Sugar Nil PH 5 Blood Ketones -

Pus cells 0 RBCs 0 Epith cells 0

Crystals 0 Casts -

Ultrasound of Abdomen Pelvis - Normal Chest XRay normal ECG normal

DIABETES INSIPIDUS

Brain MRI

D/D

Psychogenic CRF Metabolic

Hypercalcemia secondary to renal disease

Iatrogenic

IV fluid overload Diuretics

Neoplastic

Pituitary Adenoma

D/D

Toxic

Aminoglycosides NSAIDS

Vascular(Hypovolemia) Inflammatory / infectious Pyelonephritis Immune complex glomerulonephritis

Water deprivation test

Free fluids until 7:30 am Light breakfast at 6:30 am No tea, no coffee, no smoking
Hours 0 1 2 3 4 5 6 7 Weight 51.0 kg 50.5 kg 50.0 kg 49.8 kg 49.6 kg 49.4 kg 49.2 kg 49.0 kg Urine Vol 700 600 700 500 299.4 S.Osm 293.0 Urine osm 101

Stage 2 : Give Desmopressin 20ug through intranasal spray. Measure urine Osmolality hourly for the next 4 hours.

CENTRAL DIABETES INSIPIDUS

Introduction

Central diabetes insipidus (CDI) results from any condition that impairs the synthesis, transport, or release of antidiuretic hormone (ADH), also known as arginine vasopressin (AVP). It occurs equally in both sexes. It effects all ages.

Introduction

ADH is produced in the hypothalamus and travels along nerve fibers to the posterior pituitary, where it is stored and released. ADH promotes reabsorption of water in the collecting duct of nephrons. Increased plasma osmolality stimulates release of ADH in normal people. Patients with CDI secrete lower than normal levels of plasma ADH in response to elevated plasma osmolality.

Introduction

In patients with CDI, the degree of polyuria is primarily determined by the degree of ADH deficiency. The urine output can range from 3 L/day in mild partial DI to over 15 L/day in patients with severe disease. CDI can be worsened or first diagnosed during pregnancy, when ADH catabolism is increased by vasopressinases released from the placenta.

Etiology

Idiopathic DI:

Accounts for 30 to 50% of cases of CDI. Autoimmune destruction of the ADH hormone-secreting cells in the hypothalamus.
Neurosurgery Brain trauma Primary or metastatic brain tumors Infiltrative diseases (Langerhans cell histiocytosis,Wegeners granulomatosis)

Etiology

Radiation to the brain Infection such as meningitis or encephalitis Cerebral edema Intracranial hemorrhage Familial DI: Also called familial neurohypophyseal diabetes insipidus (FNDI). Autosomal dominant Mutations in the ADH gene. Patients progressively develop ADH deficiency.

Etiology

Hypoxic or ischemic encephalopathy Acute fatty liver of pregnancy: Transient CDI has been associated with it but no mechanism has been identified. Wolfram syndrome (or DIDMOAD syndrome): Autosomal recessive CDI, DM, optic atrophy, and deafness. CDI is due to loss of ADH-secreting neurons in the hypothalamus and impaired processing of ADH precursors.

Symptoms

The major symptoms of central DI are polyuria and polydipsia. Polyuria is defined as a urine output of over 3 L/day in adults. Polyuria must be differentiated from frequency and nocturia, which are not associated with an increase in total urine output. The onset of polyuria is usually abrupt in CDI. This is in contrast to nephrogenic DI and primary polydipsia, in which onset of polyuria is almost always gradual.

Symptoms

Nocturia is often the first sign of CDI. This is because urine is usually most concentrated in the morning due to lack of fluid ingestion overnight. As a result, nocturia is usually the first manifestation of a loss of concentrating ability. Thus, a relatively dilute urine is excreted, with a urine osmolality of less than 200 mOsmol/kg. Dry skin and constipation are other symptoms that may occur in CDI.

Diagnosis

Most patients have a high-normal or only mildly elevated plasma sodium concentration, usually greater than 142 mEq/L. In addition, the plasma osmolality usually remains around values only slightly above 290 mOsm/kg (normal is 280-295 mOsm/kg). This occurs because the initial loss of water results in concurrent stimulation of thirst, which minimizes the degree of net water loss.

Diagnosis

Stimulation of thirst does not occur, however, when CDI is due to a central lesion that impairs thirst causing hypodipsia or adipsia. In such cases, the plasma sodium concentration can exceed 160 meq/L and the plasma osmolality will rise significantly also. This also occurs if a patient has no access to water. Withholding water in patients with CDI can result in severe dehydration.

Water Restriction Test

In healthy individuals, water deprivation increases plasma osmolality, which stimulates secretion of ADH by the posterior pituitary. This then acts on the kidney to increase urine osmolality to 1000 to 1200 mOmol/kg and to restore plasma osmolality to normal levels. Giving exogenous ADH does not increase urine osmolality further because it is already maximal in response to an individuals endogenous release of ADH.

Water Restriction Test

The test should be continued until one of the following occurs: The urine osmolality reaches a normal value, which is above 600 mOsm/kg, indicating that both ADH release and effect are intact. The urine osmolality is stable on 2 or 3 successive measurements despite a rising plasma osmolality. The plasma osmolality exceeds 295 to 300 mOsm/kg.

Water Restriction Tests

Interpretation:

Normal subjects and primary polydipsia: Urine osms are greater than plasma Osms after water restriction. Urine osms increase minimally (<10%) after exogenous ADH. Central Diabetes Insipidus:

Nephrogenic Diabetes Insipidus: Urine osms remain less than plasma osms. After ADH, urine osms increase by less than 50%.

Urine osms remain less than plasma osms after water restriction. After ADH is given, urine osms increase 100% in complete CDI and over 50% in partial CDI.

Treatment

There are several medications available for the treatment of CDI, of which desmopressin is the most common.

Desmopressin

Desmopressin is a two-amino acid substitute of ADH that has potent antidiuretic activity but no vasopressor activity. It is also known as dDAVP, which stands for 1-deamino-8-D-arginine vasopressin. It is currently the drug of choice for longterm therapy of CDI to control polyuria. It is safe during pregnancy for both the mother and the fetus.

Desmopressin

The initial aim of therapy is to reduce nocturia, in order to provide adequate sleep. Thus, the first dose is usually given in the late evening to control nocturia. After that is achieved, control of daily diuresis is the goal. The size of and necessity for a daytime dose is determined by the effectiveness of the evening dose and any recurrence of polyuria during the day.

Desmopressin

A initial dose of 10 micrograms of the intranasal form is given at bedtime. This dose is titrated up in 5 microgram increments as needed depending on the response of the nocturia. The typical daily maintenance dose is 10 to 20 micrograms once or twice daily.

Desmopressin

An oral tablet preparation is also available. Absorption of the oral form is decreased 40-50% when taken with meals. The oral form has about 1/10 to 1/20 the potency of the nasal form because only about 5% is absorbed from the gut. It is recommended to start with the nasal form before attempting a trial of oral therapy.

Risks of Desmopressin

Potential risks of desmopressin include water retention and the development of hyponatremia. This may occur because once dDAVP is given, the patient has nonsuppressible ADH activity and may be unable to excrete ingested water normally. This can be avoided by giving the minimum daily dose required to control the polyuria.

Other Drugs

The other agents available are less effective and associated with more adverse effects than desmopressin. Chlorpropamide, carbamazepine, and clofibrate can be used in cases of partial CDI and can lower the urine output by as much as 50%.

Other Drugs

Chlorpropamide:
An oral hypoglycemic agent. Acts by promoting the renal response to ADH or dDAVP. The usual dose is 125 to 250 mg, once or twice a day. Higher doses may produce a somewhat greater response but also increase the risk of hypoglycemia.

Other Drugs

Carbamazepine:
An anticonvulsant. Enhances ADH release and raises the sensitivity of the collecting duct to it. 100 to 300 mg twice daily is the typical dose.

Other Drugs

Clofibrate:
A lipid lowering agent. Stimulates residual ADH production in the hypothalamus, therefore increasing ADH release from the posterior pituitary. 500 mg every six hours is the usual dose.

THANK YOU

References

Bichet, Daniel G. Diagnosis of polyuria and diabetes insipidus. UpToDate. 2007. Makaryus, Amgad N.; McFarlane, Samy I. Diabetes insipidus: Diagnosis and treatment of a complex disease. Cleveland Clinic Journal of Medicine. Volume 73, Number 1, January 2006. Rose, Burton D; Bichet, Daniel G. Treatment of central diabetes insipidus. UpToDate. 2007. Sands, Jeff M., Bichet, Daniel G. Nephrogenic Diabetes Insipidus. Ann Intern Med. 2006; 144:186-194.