Novel compound heterozygous mutation of SLC12A3 in Gitelman syndrome co-existent with hyperthyroidism: A case report and literature review

Table 1 Laboratory findings of the proband on admission

Characteristic	Detection value	Reference range	Characteristics	Detection value	Reference range
Age (yr)	29	-	Hormones
Height (cm)	163.0	-	Thyroid stimulating hormone (μU/mL)	< 0.005	0.27-4.2
Weight (kg)	49.0	-	Free triiodothyronine (pmol/L)	13.46	3.1-6.8
Body mass index (kg/m2)	18.4	-	Free tetraiodothyronine (pmol/L)	37.15	12-22
Blood pressure (mmHg)	112/78	-	Anti-thyroid peroxidase antibody (U/mL)	18.2	< 34
Biochemistry			Antithyroglobulin antibody (U/mL)	179.6	< 115
Total cholesterol (mmol/L)	4.23	< 5.20	Thyrotrophin receptor antibody (U/L)	2.8	0-1.75
Triglyceride (mmol/L)	1.32	< 1.70	Aldosterone (pg/mL), upright position	451.0	40-310
High-density lipoprotein (mmol/L)	0.89	1.04-1.55	Renin (pg/mL), upright position	454.0	4-38
Low-density lipoprotein (mmol/L)	2.12	< 3.40	Aldosterone (pg/mL), supine position	287	10-160
eGFR (mL/min/1.73 m2)	120.3	-	Renin (pg/mL), supine position	206	4-24
Serum uric acid (μmol/L)	391.0	155-357	Parathyroid hormone (pg/mL)	34.1	15-65
Alanine transaminase (U/L)	13	7-40	Adrenocorticotrophic hormone (pg/mL)
Aspartate aminotransferase (U/L)	17	13-35	8 am	15.76	1.6-13.9
Total bilirubin (μmol/L)	28.4	< 21.0	4 pm	12.35	-
Direct bilirubin (μmol/L)	8.6	< 8.0	0 am	5.02	-
Sodium (mmol/L)	137.0	137-147	Serum cortisol (μg/dL)
Potassium (mmol/L)	3.09	3.5-5.3	8 am	12.03	6.02-18.4
Chloride (mmol/L)	94.5	99-110	4 pm	8.14	2.3-11.9
Calcium (mmol/L)	2.33	2.11-2.52	0 am	4.29	-
Magnesium (mmol/L)	0.60	0.65-1.25	Arterial blood gas analysis
24-h urinary electrolytes			pH	7.49	7.35-7.45
Sodium (mmol/24 h)	127.60	137-257	pCO2 (mmHg)	40	35-45
Potassium (mmol/24 h)	67.98	36-90	pO2 (mmHg)	135	80-100
Chloride (mmol/24 h)	166.10	170-250	HCO3- (mmol/L)	30.5	22-27
Calcium (mmol/24 h)	0.24	2.5-7.5	Base excess (mmol/L)	6.6	-2.3-2.3
Phosphate (mmol/24 h)	13.39	16.15-42	Potassium (mmol/L)	2.4	3.5-5.5
Urine volume (L/24 h)	1.10	-

Table 2 Results of thyroid function tests on admission and follow-up

Date	FT3 (3.1-6.8 pmol/L)	FT4 (12-22 pmol/L)	TSH (0.27-4.2 μU/mL)	TGAb (< 115 U/mL)	TPOAb (< 34 U/mL)	TRAb (0-1.75 U/L)
October 2020	23.28	48.61	< 0.005	NA	NA	3.69
November 2020	23.46	37.15	< 0.005	179.6	18.2	2.80
31 December 2020	3.97	12.66	0.28	NA	NA	NA
09 February 2021	4.83	14.57	1.64	NA	NA	NA
26 April 2021	5.18	15.50	1.83	NA	NA	NA
23 July 2021	5.82	16.80	2.66	NA	NA	NA
15 December 2021	6.03	16.41	1.68	24.56	25.48	1.38

FT3: Free triiodothyronine; FT4: Free tetraiodothyronine; TSH: Thyroid stimulating hormone; TPOAb: Anti-thyroid peroxidase antibody; TGAb: Antithyroglobulin antibody; TRAb: Thyrotrophin receptor antibody; NA: Not available.

Table 3 SLC12A3 pathogenic variants identified in Gitelman syndrome complicated with thyroid disease to date

Case no.	Sex	Age	Serum potassium (mmol/L)	Serum magnesium (mmol/L)	Thyroid disease	Mutation type	DNA nucleotide change	Amino acid change	Ref.
1	F	29	3.09	0.60	GD	Compound heterozygote	c.488C>T	p.Thr163Met	This study
							c.2612G>A	p.Arg871His	This study
							c.1171_1178dupGCCACCAT	p.Ile393fs	This study
2	F	40	3.30	0.74	HT	Compound heterozygote	c.2552T>A	p.Leu849His	[37]
							c.2561G>A	p.Arg852His
3	F	28	1.70	0.62	GD	Homozygote	c.2552T>A	p.Leu849His	[37]
4	F	18	3.20	0.86	GD	Compound heterozygote	c.1015A>C	p.Thr339Pro	[38]
							c.2573T>A	p.Leu858His
5	F	50	3.00	0.66	GD	Compound heterozygote	c.539C>A	p.Thr180Lys	[38]
							c.1045C>T	p.Pro349Ser
6	F	56	2.80	0.49	GD	Homozygote	c.1706C>T	p.Ala569Val	[38]
7	F	14	2.20	NA	GD	No mention	c.791G>C	p.Gly264Ala	[39]
8	M	16	2.27	0.40	GD	Compound heterozygote	c.1456G>A	p.Asp486Asn	[40]
							c.2102_2107delACAAGA	No mention
9	F	42	3.20	0.50	HT	Compound heterozygote	c.248G>A	p.Arg83Gln	[41]
							NC_000016.10:g.56872655_56872667	No mention
							(gcggacatttttg>accgaaaatttt)
10	M	2	1.57	NA	GD	Compound heterozygote	c.1077C>G	p.Asn359Lys	[42]
							c.1567G>A	p.Ala523Thr
11	M	45	2.11	0.54	GD	Homozygote	1562_1564delTCA	p.522delIle	[43]
12	M	21	2.10	NA	GD	Compound heterozygote	c.539C>A	p.Thr180Lys	[44]
							c.2573T>A	p.Leu858His
13	M	35	1.80	NA	GD	Homozygote	c.1145C>T	p.Thr382Met	[45]
14	F	30	2.52	0.48	HT	Compound heterozygote	c.486_490delinsA	p.Thr163fs	[46]
							c.506-1G>A
15	F	34	2.33	NA	HT	Compound heterozygote	c.953T>G	p.Phe318Cys	[47]
							c.1196G>A	p.Arg399His
							c.1664C>T	p.Ser555Leu
16	M	50	2.88	0.43	GD	Compound heterozygote	c.179C>T	p.Thr60Met	[48]
							c.1567G>A	p.Ala523Thr
17	F	46	2.30	0.43	GD	Heterozygote	c.185C>T	p.Thr60Met	[49]
18	M	21	2.64	0.36	GD	Homozygote	c.2744G>A	p.Arg913Gln	[49]
19	F	50	2.66	0.62	GD	Compound heterozygote	c.179C>T	p.Thr60Met	[50]
							c.863T>G	p.Leu288Arg
20	M	39	1.90	0.52	GD	Compound heterozygote	c.1841C>T	p.Ser614Phe	[51]
							c.2968G>A	p.Arg990Lys
21	F	41	2.60	0.40	AP	Compound heterozygote	c.964+2T>C		[51]
							c.179C>T	p.Thr60Met
22	F	20	NA	NA	SAT	Compound heterozygote	c.1456G>A	p.Asp486Asn	[52]
							c.506-1G>A
23	F	47	NA	NA	GD	Compound heterozygote	c.1016C>T	p.Thr339Ile	[52]
							c.1925G>A	p.Arg642His

GD: Graves’ disease; HT: Hashimoto’s thyroiditis; SAT: Subacute thyroiditis; AP: Antibody-positive; F: Female; M: Male; NA: Not available.