World J Nephrol Urol

World Journal of Nephrology and Urology, ISSN 1927-1239 print, 1927-1247 online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Nephrol Urol and Elmer Press Inc

Journal website http://www.wjnu.org

Case Report

Volume 000, Number 000, January 2016, pages 40-47

Gitelman Syndrome: An Important Cause of Severe Hypokalemia and Periodic Paralysis

Figure 1. The photograph of the patient, please notice on foot weakness and both legs fell laterally (black arrow).

Figure 2. Electrocardiograph of the patient note the typical hypokalemic pattern of myocardial repolarization disturbance with depressed ST segment, wide and bizzare T wave deflection, the occurrence of U wave (black arrow) and prolonged QTc interval (580 ms).

Figure 3. Pathophysiology of Gitelman syndrome. The primary abnormality is defective Cl- reabsorption in the DCT due to inactivating mutations in the NCCT gene. This leads to the main features of the syndrome, which are hypokalemic metabolic alkalosis, secondary hyperaldosteronism, normotension, hypomagnesemia, hypocalciuria and blunted response to angiotensin II. DCT, distal convoluted tubule; NCCT, thiazide-sensitive Na-Cl cotransporter. Source: Shaer AJ. Am J Med Sci 2001, with permission.

**Table 1.** Biochemical Investigation in the Hospital
Investigations	January 16, 2009 (admission)	Third day	First week	Third week (before discharge)	Normal value
The calculations are: TTKG = ([K] urine/(U/P) osmolality)/[K] plasma; FE_K (%) = ([K] urine × [Cr] plasma)/([Cr] urine × [K] plasma). NT: not tested; TSHs: sensitive thyroid stimulating hormone; PAC: plasma aldosterone concentration; PRA: plasma renin activity, PCO₂: partial pressure of carbon dioxide; FE_K: excretion fraction of potassium; TTKG: transtubular potassium concentration gradient. ^aFrom reference: Elisaf M and Siamopoulos KC (Postgrad Med J 1995). ^bFutrakul et al (Am J Kidney Dis 1999). ^cBettinelli A, et al (J Pediatr 1992). *Abnormal value.
Plasma electrolyte
Sodium	138.2	135.4	139.3	137	135 - 145 mEq/L
Potassium*	1.5	3.2	2.1	3.6	3.5 - 5.0 mEq/L
Chloride	90.0	86.0	96.0	92.0	95 - 110 mEq/L
Calcium	9.2	10.3	9.0	9.4	9.0 - 10.2 mEq/L
Magnesium*	1.3	1.0	1.8	2.1	1.9 - 7.4 mEq/L
Creatinine	0.82	0.76	0.91	0.88	0.7 - 1.4 mg/dL
Plasma osmolality	289.5	287.5	294.7	291	285 - 295 mOsm/kg
CPK*	1,236	748	314	55	29 - 200 IU/L
Endocrine evaluation
Triiodothyronine	NT	1.12	NT	NT	0.8 - 2.0 ng/mL
Free thyroxine	NT	120.5	NT	NT	60 - 120 mMol/L
TSHs	NT	2.6	NT	NT	0.3 - 5.0 IU/mL
Plasma aldosterone*	NT	NT	93.0	NT	< 15 ng/dL
PRA*	NT	NT	17.8	NT	0.7 - 3.3 ng/mL/h
PAC/PRA ratio	NT	NT	5.2	NT	< 30
Blood gas analysis
pH*	7.5	NT	7.4	NT	7.35 - 7.45
PCO₂	32	NT	37	NT	35 - 45 mm Hg
Bicarbonate*	31.3	NT	25	NT	18 - 23 mEq/L
Base excess*	11.7	NT	4.4	NT	± 2.5
Urine electrolyte excretion per 24 h
Sodium*	NT	402.0	164.9	173.0	60 - 220 mEq
Potassium*	NT	41.8	32.4	21.7	< 10 mEq
Urine osmolality	NT	542	651	363	250 - 900 mOsm/kg
FEK*	NT	29.4	NT	22.6	9.6% (4.6 - 20.4)^a
TTKG*	NT	6.9	NT	8.2	6.0 (4.1 - 10.5)^b
Chloride*	NT	281.0	184.0	158.0	60 - 200 mEq
Calcium*	NT	19.2	16.9	96.9	50 - 400 mg/g cr
Creatinine	NT	33.6	NT	41.5	25 - 400 mg/dL
Calcium/creatinine ratio*	NT	0.04	NT	0.23	≥ 0.2 mg/mg^c

Table 1. Biochemical Investigation in the Hospital

Investigations

January 16, 2009 (admission)

Third day

First week

Third week (before discharge)

Normal value

The calculations are: TTKG = ([K] urine/(U/P) osmolality)/[K] plasma; FE_K (%) = ([K] urine × [Cr] plasma)/([Cr] urine × [K] plasma). NT: not tested; TSHs: sensitive thyroid stimulating hormone; PAC: plasma aldosterone concentration; PRA: plasma renin activity, PCO₂: partial pressure of carbon dioxide; FE_K: excretion fraction of potassium; TTKG: transtubular potassium concentration gradient. ^aFrom reference: Elisaf M and Siamopoulos KC (Postgrad Med J 1995). ^bFutrakul et al (Am J Kidney Dis 1999). ^cBettinelli A, et al (J Pediatr 1992). *Abnormal value.

Plasma electrolyte

Sodium

138.2

135.4

139.3

137

135 - 145 mEq/L

Potassium*

1.5

3.2

2.1

3.6

3.5 - 5.0 mEq/L

Chloride

90.0

86.0

96.0

92.0

95 - 110 mEq/L

Calcium

9.2

10.3

9.0

9.4

9.0 - 10.2 mEq/L

Magnesium*

1.3

1.0

1.8

2.1

1.9 - 7.4 mEq/L

Creatinine

0.82

0.76

0.91

0.88

0.7 - 1.4 mg/dL

Plasma osmolality

289.5

287.5

294.7

291

285 - 295 mOsm/kg

CPK*

1,236

748

314

29 - 200 IU/L

Endocrine evaluation

Triiodothyronine

1.12

0.8 - 2.0 ng/mL

Free thyroxine

120.5

60 - 120 mMol/L

TSHs

2.6

0.3 - 5.0 IU/mL

Plasma aldosterone*

93.0

< 15 ng/dL

PRA*

17.8

0.7 - 3.3 ng/mL/h

PAC/PRA ratio

5.2

< 30

Blood gas analysis

pH*

7.5

7.4

7.35 - 7.45

PCO₂

35 - 45 mm Hg

Bicarbonate*

31.3

18 - 23 mEq/L

Base excess*

11.7

4.4

± 2.5

Urine electrolyte excretion per 24 h

Sodium*

402.0

164.9

173.0

60 - 220 mEq

Potassium*

41.8

32.4

21.7

< 10 mEq

Urine osmolality

542

651

363

250 - 900 mOsm/kg

FEK*

29.4

22.6

9.6% (4.6 - 20.4)^a

TTKG*

6.9

8.2

6.0 (4.1 - 10.5)^b

Chloride*

281.0

184.0

158.0

60 - 200 mEq

Calcium*

19.2

16.9

96.9

50 - 400 mg/g cr

Creatinine

33.6

41.5

25 - 400 mg/dL

Calcium/creatinine ratio*

0.04

0.23

≥ 0.2 mg/mg^c

**Table 2.** Data on Renal Clearance Studies
	C_H2O (mL/min)	C_Cl (mL/min)	FE_Na (%)	FE_K (%)	FE_Cl (%)	DFCR (%)	FDDC (%)
U_osm: urinary osmolality; C_H2O: maximal free water clearance; C_Cl: chloride clearance; Fe_Na: fractional excretion of sodium; FE_K: fractional excretion of potassium; FE_Cl: fractional excretion of chloride; DFCR: distal fractional chloride reabsorption; FDDC: fractional distal delivery of chloride. The parameter used are: 1) solute-free water clearance (C_H2O) = V × (1 - U_osm/P_osm), where V is urine flowrate in mL/min, U_osm is urine osmolality, and P_osm is plasma osmolality; 2) chloride clearance (C_Cl) = V × U_Cl/P_Cl, where U_Cl is urinary chloride concentration, and P_Cl is plasma chlorid concentration; 3) distal fractional chloride reabsorption (DFCR) = C_H2O/[C_H2O + C_Cl]; 4) fractional distal delivery of chloride (FDDC) = [C_H2O + C_Cl]/creatinine clearance; 5) fractional excretion of solute (FE_X) = 100 × [U_x/P_x] × [P_cr/U_cr], where P_cr is plasma creatinine concentration, and U_cr is urinary creatinine concentration. X was taken for Na, K and Cl.
Basal	5.6	1.7	2.49	31.5	2.1	83.4	18.2
Thiazide	6.7	2.1	12.1	59.6	7.5	78.4	30.8
Furosemide	1.1	20.4	26.2	72.5	30.5	7.2	51.8

Table 2. Data on Renal Clearance Studies

C_H2O (mL/min)

C_Cl (mL/min)

FE_Na (%)

FE_K (%)

FE_Cl (%)

DFCR (%)

FDDC (%)

U_osm: urinary osmolality; C_H2O: maximal free water clearance; C_Cl: chloride clearance; Fe_Na: fractional excretion of sodium; FE_K: fractional excretion of potassium; FE_Cl: fractional excretion of chloride; DFCR: distal fractional chloride reabsorption; FDDC: fractional distal delivery of chloride. The parameter used are: 1) solute-free water clearance (C_H2O) = V × (1 - U_osm/P_osm), where V is urine flowrate in mL/min, U_osm is urine osmolality, and P_osm is plasma osmolality; 2) chloride clearance (C_Cl) = V × U_Cl/P_Cl, where U_Cl is urinary chloride concentration, and P_Cl is plasma chlorid concentration; 3) distal fractional chloride reabsorption (DFCR) = C_H2O/[C_H2O + C_Cl]; 4) fractional distal delivery of chloride (FDDC) = [C_H2O + C_Cl]/creatinine clearance; 5) fractional excretion of solute (FE_X) = 100 × [U_x/P_x] × [P_cr/U_cr], where P_cr is plasma creatinine concentration, and U_cr is urinary creatinine concentration. X was taken for Na, K and Cl.

Basal

5.6

1.7

2.49

31.5

2.1

83.4

18.2

Thiazide

6.7

2.1

12.1

59.6

7.5

78.4

30.8

Furosemide

1.1

20.4

26.2

72.5

30.5

7.2

51.8