A Case of Gitelman's Syndrome

- Prof. Dr. Maheshkumar ‘s Unit Dr. Israel

History:
Present complaints:
complains of weakness of both lower and upper limbs for past 3 days
HOPI:
A 40 / M , Sanjivi , apparently healthy individual developed sudden onset weakness of both lower limbs involving both proximal n distal muscle groups 3 days back
6hrs later , pt developed weakness of both upper limbs equally involving proximal and distal muscles

H/o difficulty to stand from bed, getting up from squatting positions
H/o difficulty to turn from side- side in bed
H/o buckling of knee joints
H/o difficulty to raise the hand and mixing food
No H/o any sensory disturbances
No h/o any bowel bladder disturbances
No h/o suggestive of any cranial nerve involvement
No h/o fever cough sore throat
No h/o vomiting loose stools
No h/o excessive sweating ,
No h/o oliguria polyuria hematuria
No h/o seizure headache backpain
No h/o dysnoea palpitatios chest pain
No h/o any diuretic intake
No h/o recent vaccination , dog bite
Not a k/c/o HTN DM

o/e:
Pt conscious oriented afebrile fairly hydrated
No icterus cyanosis pallor pedal edema
P – 82 /min
BP – 100/70 mm hg
Single breath count : upto 26
CVS - S1 S2 heard . No murmur
RS - NVBS . No added sounds
PA – soft nontender. Bowel sounds +nt

CNS:
HMF – NAD
No meningeal involvement
Cranial nerves – normal
Spino – motor examination:
Tone: decreased in all 4 limbs
Power : upper limbs 4/5
lower limbs 2/5
DTR: bicep + +
triceps + +
supinator + +
knee + +
ankle + +
Plantar B/L no response
Sensory – normal
Cerebellar – normal
Autonomic system - normal

Provisional Diagnosis:
Quadriparesis
? GBS ? Hypokalemic
Investigation:
Hb: 12.8 gm %
TC : 8200
DC : P55, L37 , M8
PCV : 38.2 %
MCV : 87.3 fl
MCH : 27.7 pg
RBC : 4.4 million
Platelet : 2 lac
RBS : 323 mg% BUN:58 S. Cr : 1.1 Na+ : 138 K+: 3.1 PVT Reports Na + : 137 K+ : 2.17 HCO3- : 23.7 Cl- : 93.4 FBS : 109 mg/dl PLBS : 112 mg /dl

Nephrology Opinion:
suggested the following investigations:
ABG analysis
24 hrs urine electrolytes
USG abdomen
S. K+ levels monitoring
S. Ca+ and Mg + levels

ABG analysis :
pH : 7.56
HCO3 : 30.1 mmol/l
PaCO2 :49.0 mm Hg
Pa02 : 80.6 mm Hg
SaO2 : 96 %
Na+ : 138 mmol
K+ : 2.69mmol
Cl - : 96 mmol
INTERPREATION:
metabolic alkalosis with respiratory compensation

24 hrs urine report :
Volume : 4.43 lit
Protein : 332 mg /d
Na +: 225meq /d ( high )
K+ : 22.55 meq / d ( high )
Cl- : 320 meq / d ( high )
Ca+ : 56 mg /d ( low )
Mg+ : 155.5 mg /d ( normal )
SERUM LEVELS :
S. Ca +: 10.6 mg /dl ( high normal )
12.2 mg/ dl (GSH central lab report )
S. Mg+ : 1.9 mg/dl ( low normal )

USG :
B/L medical renal disease
RK : 9.8 x 4.6 cm
LK : 10.4 x 5
CMD preserved
Mildly increased cortical echoes in both kidneys
no evidence of calcinosis
LIVER , SPLEEN , PANCREAS : normal

Treatment given:
IV fluids ( RL )
Inj. Cefotaxime
Inj Ranitidine
Inj KCl ( 10 meq/hr for 4 hrs )
Syp. KCl
T. BCT
Diet adviced ( to include coconut water;citrus juices )
Course In Hospital:
the next day the power in the limbs improved.pt was able to walk.

Nephrology opinion :
f/s/o GITELMANN’s Syndrome

Hypokalemia can only occur for four reasons:
Decreased intake
Shift into cells
Extra-renal losses
Renal losses

Hypokalemia Urinary K + excretion < 15 mmol/d Assess acid-base status Metabolic acidosis Metabolic alkalosis Lower gastronitestinal K + loss Remote diuretic use Remote vomiting K + loss via sweat > 15 mmol/d Assess K + secretion TTKG > 4 TTKG < 2 Acid-base status Na + -wasting nephropathy Osmotic diuretic Diuretic Metabolic acidosis Diabetic ketoacidosis Proximal (type 2) RTA Distal (type 1) RTA Amphotericin B Metabolic alkalosis Hypertension ? Yes Mineralocorticoid excess Liddle’s syndrome No Vomiting Bartter’s syndrome Exclude diuretic abuse Hypomagnesemia

Causes of hypokalemia
Decreased intake : kidney can conserve to 5-25 mEq K+ daily; normal intake 40-120 daily.
Shift into cells:
Alkalosis
Insulin
Beta adrenergic stimuli
Stress
Beta agonists- e.g.: albuterol, ritodrine

Increased potassium entry into cells:
Hypokalemic periodic paralysis- typically oriental men with thyrotoxicosis; ? abnormal Ca++ channel; ? Increased Na/K atp ase activity.
Increased rbc uptake, e.g. after treatment with B12, folate.

Extra-renal losses of potassium:

Gastrointestinal losses of potassium
Gastric juice contains 5 – 10 mEq K+/L.
Intestinal fluids contain 20 – 50 mEq/L

Hypokalemia from loss of gastric fluid.
Loss of hydrogen ion increases plasma bicarbonate.
Coexisting volume depletion increases aldosterone secretion.
Increased delivery of bicarbonate to the distal nephron obligates a cation. In the setting of increased aldosterone levels, sodium is retained and potassium excreted.
Potassium loss is most prominent early.
Actual losses in gastric juice are relatively small.

Diarrheal losses are usually accompanied by metabolic acidosis
Villous adenoma
Laxative abuse

Sweat losses- 5 – 10 mEq/L

The kidney and potassium
Nearly all potassium filtered at the glomerulus is reabsorbed in the proximal nephron. Urinary potassium is the result of distal potassium secretion.
To excrete potassium, the kidney requires an adequate number of nephrons, aldosterone, and a circulation adequate to provide adequate distal delivery of sodium for sodium/potassium exchange.

Renal losses of potassium
Diuretics- activate the renin-angiotensin-aldosterone cascade.
Primary aldosteronism/increased steroids.
Presentation of a non-resorbable anion distally, obligating a cation, which will lead to increased potassium excretion in the presence of aldosterone.
Bicarbonate
Penicillin derivatives
Betahydroxybutyrate

Renal losses of potassium
Renal tubular acidosis
Proximal, especially with therapy
Some distal types
Type IV RTA patients are typically hyperkalemic
Hypomagnesemia
Polyuria

What data do we want to diagnose the cause of hypokalemia in this pt?
Urinary potassium: 24 hour values better than spot specimens.
Aldosterone and renin levels.
Blood pressure measurements.
A history.

Therefore:
Potassium is being lost in the urine.
Primary aldosteronism is r/o by normal blood pressures.
ABG r/o renal tubular acidosis.
Diuretic abuse R/o history

Bartter’s and Gitelman’s syndromes
Bartter’s syndrome is usually diagnosed in childhood, sometimes associated with growth and mental retardation. The defect is impaired NaCl reabsorption in the loop of Henle. Findings are similar to administration of a loop acting diuretic:
Salt loss leading to volume depletion and activation of the renin-angiotensin system
Increased urinary calcium

Bartter’s and Gitelman’s Syndromes
3 or 4 types of Bartter’s have been identified:
Defects in the luminal Na-K-Cl transporter
Defects in the luminal potassium channel
Defects in the basolateral chloride channel

Gitelman’s syndrome
Like Bartter’s an autosomal recessive disorder, but not usually diagnosed early in life.
Findings mimic administration of a thiazide diuretic: the defect is in the Na-Cl transporter.
Patients may complain of polyuria, cramps.
They do not have hypercalciuria, but typically have low serum magnesium levels.

Gitelman’s syndrome
Diagnosis is made by history as well as lab findings. Lab findings are indistinguishable from thiazide use:
Hypokalemia, hypomagnesemia, increased renin and aldosterone levels, decreased urinary calcium.
Genetic screening?

1: Clin Nephrol. 2001 Mar;55(3):233-7. Related Articles, Links
Mimicry of surreptitious diuretic ingestion and the ability to make a genetic diagnosis. Schepkens H , Hoeben H , Vanholder R , Lameire N . Department of Internal Medicine, University Hospital Gent, Belgium. katrien.vanrenterghem@rug.ac.be Gitelman's syndrome, also known as "hypocalciuric variant of Bartter's syndrome", is a cause of chronic hypokalemia and hypomagnesemia in adults. A specific gene has been found responsible for this disorder, encoding the thiazide-sensitive NaCl coporter (TSC) in the distal convoluted tubule. We describe a psychiatric patient with chronic symptomatic hypokalemia and hypomagnesemia whose electrolyte disturbances were subsequently misdiagnosed as an acute alcohol and benzodiazepine withdrawal syndrome, as chronic diuretic abuse and as a classical Bartter's syndrome. Finally, genetic investigation revealed the presence of mutations in the SLC12A3 gene leading to the proper diagnosis of Gitelman's syndrome. We emphasize that Gitelman's syndrome should be suspected in every hypokalemic patient with biochemical resemblance of diuretic ingestion, especially when repeated toxic screens for diuretics are negative. The ability to make a molecular-genetic diagnosis can be of practical benefit in confusing clinical settings.

Gitelman’s syndrome: treatment
Potassium
Magnesium
Aldactone or amiloride
ACEI’s
NSAIDS of no benefit

General comments about the treatment of hypokalemia
Think about the cause of the hypokalemia you are treating? A cellular shift, e.g. hypokalemic periodic paralysis, will require a lot less potassium to correct than hypokalemia from potassium loss.
Orally or i.v.? Orally is safer; limit i.v. repletion to 20 mEq./hour except in very unusual circumstances- then monitor.

Anticipate: has K+ loss stopped or will it be ongoing?
Are you giving other drugs that will influence K+ levels? E.g. NSAIDs, ACEIs, ARBs.
Generally, use KCl vs. other preparations.
Followup with repeat levels- consider using the replacement protocols.

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A Case of Gitelman's Syndrome

by Stanley Medical College, Department of Medicine

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