Table 1.
Characteristics of the studies included in this review.
| Author | Year | Country | Participants (female/male) |
Mean/median age (SD/IQR) | Threshold for vitamin B12 deficiency (pg/mL) | TD evaluated |
Vitamin B12 levels in healthy participants Mean (SD) |
Vitamin B12 levels in patients with TD Mean (SD) |
Patients with TD and vitamin B12 deficiency (frequency %) | Patients with TD and normal/high levels of vitamin B12 (frequency %) | Vitamin B12 assay method | Patients with AITD and APCA (+) (frequency %) | Patients with AITD and APCA(-) (frequency %) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Das et al. | 2012 | India | 60(42/18) | 36(19 - 67) | NR | Hypothyroidism | NR | NR | 9(15) | 51(85) | NR | NR | NR |
| Wang et al. | 2012 | Taiwan | 380(346/34) | 62 (12) | <200 | AITD | 701.9(181.4) | 665.5(286) | 12(6.32) | 178(93.68) | NR | 48(12.7) | 332(87.3) |
| Velarde-Mayol et al. | 2014 | Spain | 409(342/34) | 78(8) | <199 | AITD | NR | NR | 76(18.58) | 333(81.42) | NR | NR | NR |
| Venerito et al. | 2015 | Germany | 34(NR/NR) | 55 (13) | NR | AITD | NR | NR | 1(2.94) | 33(97.06) | NR | 11(32.35) | 23(64.65) |
| Bhuta et al. | 2019 | India | 60(48/12) | NR(NR) | <210 | Hypothyroidism | NR | NR | 17(28.3) | 43(71.7) | FEI | NR | NR |
| Sattar-Lakho et al. | 2018 | Pakistan | 145(48/97) | 42(8.9) | <150 | Hypothyroidism | NR | NR | 105(72.41) | 40(27.6) | NR | NR | NR |
| Kumari et al. | 2015 | India | 350(250/100) | 32 (11) | <200 | AITD | NR | NR | 194(55.43) | 156 (44.57) | NR | NR | NR |
| Carrol et al. | 2015 | United States of America | 80(61/19) | 55(17) | <200 | AITD | 655.8 (342.7) | 606.8 (281.8) | 0. 0(0) | 36 (100) | ECLIA | 4(11.11) | 32(88.89) |
| Siddique et al. | 2017 | Pakistan | 225(122/103) | 47(7) | NR | Hypothyroidism | NR | NR | 54(24) | 171(76) | CLIA | NR | NR |
| Jabbar et al. | 2008 | Pakistan | 116(95/21) | 44 (13) | <200 | Hypothyroidism | NR | NR | 47(41.52) | 69(59.48) | RIA | NR | NR |
| Jabeen et al. | 2016 | Pakistan | 204(197/7) | 37 (11) | <200 | Hypothyroidism | NR | NR | 112(54.9) | 92(45.1) | RIA | NR | NR |
| Adnan et al. | 2019 | Iraq | 70(NR/NR) | NR(NR) | <400 | Hypothyroidism | 788.62(138.21) | 462.06(224.93) | NR | NR | Spectrophotometry | NR | NR |
| Şanver et al. | 2022 | Turkey | 261(261/0) | 46(15) | NR | AITD | 377(287) | 351(188) | NR | NR | CLIA | NR | NR |
| Twito et al. | 2015 | Israel | 120(108/12) | 50(16) | NR | AITD | NR | NR | NR | NR | NR | 34(28.3) | 86(71.3) |
| Utiyama et al. | 2017 | Brazil | 243(213/30) | 45 (13) | NR | AITD | NR | NR | NR | NR | NR | 49(20.16) | 194(75.84) |
| Howel et al. | 1967 | England | 74(65/9) | NR(NR) | NR | AITD | NR | NR | NR | NR | NR | 5(6.76) | 69(93.24) |
| Tozzoli et al | 2010 | Italy | 208(187/21) | 43(29) | NR | AITD | NR | NR | NR | NR | NR | 51(24.5) | 157(75.48) |
| Gerenova et al. | 2013 | Bulgaria | 151(142/9) | 49(1.2) | NR | AITD | NR | NR | NR | NR | NR | 51(33.77) | 100(66.23) |
| Yadav et al. | 2019 | India | 100(88/12) | 33(7) | <211 | Hypothyroidism | NR | NR | 12(12) | 88(88) | NR | NR | NR |
| Checchi et al. | 2008 | Italy | 391(351/40) | 55.3(15) | NR | AITD | NR | NR | NR | NR | NR | 155(39.6) | 236(60.4) |
| Lahner et al. | 2008 | Italy | 128(107/21) | 54 (20–76) | NR | AITD | NR | NR | NR | NR | NR | 110(86.7) | 18(13.3) |
| Chan et al. | 2009 | China | 56(40/16) | 75(46) | NR | AITD | NR | NR | NR | NR | NR | 37(66.07) | 19(33.93) |
| Morawiec-Szymonik et al. | 2019 | Poland | 51(35/16) | NR(NR) | NR | AITD | NR | NR | NR | NR | NR | 29(56.86) | 22(43.14) |
| Khan et al. | 2019 | India | 75(45/30) | NR(NR) | <211 | Hypothyroidism | NR | NR | 45(60) | 30(40) | NR | NR | NR |
| Colleran et al. | 2003 | United States of America | 31(NR/NR) | NR(NR) | <200 | Hyperthyroidism | 418 (219) | 514 (210) | 1(4.76) | 20(95.24) | CLIA | NR | NR |
| Alperin et al. | 1970 | United States of America | 88(NR/NR) | NR(NR) | <200 | Hyperthyroidism | 572(183) | 347(144) | 2(5.9) | 32(94.1) | NR | NR | NR |
| Nitu et al. | 2016 | India | 100(100/0) | NR(NR) | NR | Hyperthyroidism | 276.08 (120.01) | 341.5(25.58 ) |
NR | NR | HPLC | NR | NR |
| Kumar et al. | 2019 | India | 400(NR/NR) | NR(NR) | NR | Hypothyroidism | 456.43(243.54) | 211.34(121.45) | NR | NR | CLIA | NR | NR |
| Tripathi et al. | 2019 | India | 350(214/136) | 33.78(13.9) | NR | Hypothyroidism | 483.93(264.7 4) | 210.45(129.3) | NR | NR | NR | NR | NR |
| Berker et al. | 2009 | Turkey | 42(42/0) | 24 (2.8) | NR | Hyperthyroidism | 235 (86.9) | 209.5 (36.3) | 0(0) | 42(100) | CLIA | NR | NR |
| Khubchandani et al. | 2015 | India | 100(72/28) | 39.48(14.19) | <200 | Hypothyroidism | 365.17(45.82) | 187.38(35.89) | 32(64) | 18(36) | CLIA | NR | NR |
| Choudhary et al. | 2021 | India | 150(86/64) | NR(NR) | <200 | Hypothyroidism | NR | NR | 38(25.3) | 112(74.7) | NR | NR | NR |
| Garcia-Garcia | 2010 | Spain | 148(137/11) | 45(15) | NR | AITD | NR | NR | NR | NR | NR | 30(20.27) | 118(79.73) |
| Castoro et al. | 2016 | Italy | 242(207/35) | 41 (12–78) | NR | AITD | NR | NR | NR | NR | NR | 57(23.55) | 185(76.45) |
| Alexandraki et al. | 2014 | Greece | 120(98/22) | 51 (13) | NR | AITD | NR | NR | NR | NR | NR | 38(31.67) | 82(68.33) |
| Souka et al. | 2018 | United Arab Emirates | 60(60/0) | 40.8(9.5) | NR | Hypothyroidism | 371.75(201.48) | 279.25(362.9) | NR | NR | ECLIA | NR | NR |
| Ozmen et al. | 2006 | Turkey | 47(35/12) | 51(35–66) | NR | Hypothyroidism | 474.93(327.21) | 475.61(172.63) | NR | NR | CLIA | NR | NR |
| Min-Yu et al. | 2014 | South Korea | 17541(6209/11332) | 41.8 (10) | NR | Hypothyroidism | 421(95.3) | 423 (91.3) | NR | NR | CLIA | NR | NR |
| SH | 421(95.3) | 423 (91.3) | NR | NR | |||||||||
| Srikrishna et al. | 2015 | India | 440(377/63) | 48.41(11.65) | <211 | Hypothyroidism | 412(93) | 327(90) | NR | NR | ECLIA | NR | NR |
| SH | 412(93) | 393(99) | NR | NR | |||||||||
| Sengul et al. | 2004 | Turkey | 58(58/0) | 42.3 (10.85) | NR | Hypothyroidism | 241.4 (33.47) | 250.69 (110.13) | NR | NR | CLIA | NR | NR |
| SH | 241.4 (33.47) | 250.69 (110.13) | NR | NR | |||||||||
| Luboshitzky et al. | 2002 | Israel | 91(91/0) | 48(13) | <192 | Hypothyroidism | 298(135) | 317(140) | NR | NR | CLIA | NR | NR |
| SH | 298(135) | 317(140) | NR | NR | |||||||||
| Çakal et al. | 2007 | Turkey | 46(NR/NR) | 41.4(14.1) | <145 | Hypothyroidism | 244.2(47.2) | 236.4(102) | NR | NR | CLIA | NR | NR |
| SH | 244.2(47.2) | 245.1(88.8) | NR | NR | |||||||||
| Nedrebo et al. | 1998 | Norway | 438(250/188) | 48(19–89) | NR | Hypothyroidism | 508.13(39.02) | 724.93(122.45) | NR | NR | CLIA | NR | NR |
| Hyperthyroidism | 508.13(39.02) | 577.23(104.37) | NR | NR | |||||||||
| Diekman et al. | 2001 | Netherlands | 96(75/21) | 38 (22–79) | NR | Hypothyroidism | 410.56(161.24) | 453.92(253.38) | NR | NR | RIA | NR | NR |
| Hyperthyroidism | 471.54(197.83) | 462.05(188.34) | NR | NR | |||||||||
| Calcaterra et al. | 2019 | Italy | 220(184/36) | NR(NR) | NR | AITD | NR | NR | 4(40) | 6(60) | CLIA | 10(4.55) | 210(95.45) |
| Hypothyroidism | NR | NR | 3(37.5) | 5(62.5) | |||||||||
| Hyperthyroidism | NR | NR | 1(33.3) | 2(66.7) | |||||||||
| Dagdelen et al. | 2012 | Turkey | 327(NR/NR) | NR(NR) | <200 | AITD | NR | NR | 51(15.6) | 276(84.4) | NR | NR | NR |
| Hypothyroidism | NR | NR | 50(18.25) | 224(81.75) | |||||||||
| Hyperthyroidism | NR | NR | 1(1.9) | 52(98.1) | |||||||||
| Leineweber et al. | 2016 | United States of America | 494(NR/NR) | NR(NR) | <200 | AITD | NR | NR | 19(4.8) | 379(95.2) | NR | 88(22.1) | 310(77.9) |
| Hypothyroidism | NR | NR | 18(4) | 439(96) | |||||||||
| Hyperthyroidism | NR | NR | 4(10.8) | 33(89.2) | |||||||||
| Meling et al. | 2022 | Norway | 458(331/127) | NR(NR) | <200 | AITD | NR | NR | 48(10.5) | 410(89.5) | NR | NR | NR |
| Hypothyroidism | NR | NR | 36(9.5) | 344(90.5) | |||||||||
| Hyperthyroidism | NR | NR | 12(15.4) | 66(84.6) | |||||||||
| Wiebolt et al. | 2011 | Netherlands | 882(751/132) | 50(14) | <130 | AITD | NR | NR | 66(8.85) | 680(91.15) | NR | 73(12.2) | 525(87.8) |
| Hypothyroidism | NR | NR | 30(8.8) | 310(91.2) | |||||||||
| Hyperthyroidism | NR | NR | 36(7.6) | 436(92.4) | |||||||||
| Raju et al. | 2021 | India | 50(27/23) | 45(12.8) | <200 | AITD | NR | NR | 17(70) | 7(30) | RIA | NR | NR |
| Hypothyroidism | NR | NR | 26(52) | 24(48) | |||||||||
| SH | NR | NR | 16(57.14) | 12(42.86) | |||||||||
| Ness-Abramof et al. | 2006 | Israel | 115(108/7) | 47 (15) | <133 | AITD | NR | NR | 32(27.8) | 83(72.2) | CLIA | NR | NR |
| Hypothyroidism | NR | NR | 27(28.7) | 67(71.3) | |||||||||
| Hyperthyroidism | NR | NR | 3(17.6) | 14(82.4) | |||||||||
| Morel et al. | 2009 | France | 226(NR/NR) | 56 (20–94) | <180 | AITD | 435(574.8) | 588.75(972.59) | NR | NR | CLIA | NR NR | |
| Hypothyroidism | 435(574.8) | 557(1001.4) | NR | NR | |||||||||
| Mehmet et al. | 2012 | Turkey | 200(173/27) | 44.9(14.2) | <189 | Hypothyroidism | 299.1 (205.5) |
400.2 (314.5) |
18(18) | 82(82) | NR | NR | NR |
| SH | 299.1 (205.5) |
348.5(211.8) | 25(25) | 75(75) | |||||||||
| Caplan et al. | 1975 | United States of America | 103(NR/NR) | 56.8 (2.1) | <200 | Hypothyroidism | 412 (213.12) | 450 (231.98) | NR | NR | Microbiological assay | NR | NR |
| Hyperthyroidism | 412 (213.12) | 499 (253.65) | NR | NR | |||||||||
| Ranjan et al. | 2020 | India | 150(NR/NR) | NR(NR) | NR | Hypothyroidism | 314.85 (41.1) | 277.2 (37.89) | NR | NR | CLIA | NR | NR |
| SH | 314.85 (41.1) | 277.2 (37.89) | NR | NR | |||||||||
| Onat et al. | 2003 | Turkey | 85(74/11) | 59.93 (19.84) | NR | Hypothyroidism | 521.92 (121.45) | 225.6 (97.16) | NR | NR | CLIA | NR | NR |
| Hyperthyroidism | 521.92 (121.45) | 359.36 (323.15) | NR | NR | |||||||||
| Photam et al. | 2014 | India | 47(NR/NR) | NR(NR) | NR | Hyperthyroidism | 205(111.85) | 249(165.18) | NR | NR | NR | NR | NR |
| AITD | 205(111.85) | 249(165.18) | NR | NR | |||||||||
| Miskiewicz et al. | 2015 | Poland | 8(5/3) | 33 (22–68) | NR | AITD | NR | NR | 2(25) | 6(75) | NR | 1(12.5) | 7(87.5) |
| Hyperthyroidism | NR | NR | 2(25) | 6(75) | |||||||||
| Orzechowska-Pawilojc et al. | 2007 | Poland | 61(61/0) | 37.9(10.3) | <179 | AITD | 420.83(142.07) | 329.69(154.37) | 3(9.7) | 28(90.3) | CLIA | NR | NR |
| Hypothyroidism | 420.83(142.07) | 329.69(154.37) | 3(9.7) | 28(90.3) | |||||||||
| Nicolaou et al. | 2014 | Greece | 115(99/16) | 47.7(12.9) | NR | AITD | NR | NR | 19(16.5) | 96(83.5) | NR | 33(28.7) | 82(71.3) |
| Hypothyroidism | NR | NR | 19(16.5) | 96(83.5) | |||||||||
| Aon et al. | 2022 | Kuwait | 93(80/13) | 34(14) | <133 | Hypothyroidism | NR | NR | 15(33.3) | 30(66.7) | CLIA | NR | NR |
| SH | NR | NR | 23(47.9) | 25(52.1) | |||||||||
| Aktaş et al. | 2020 | Turkey | 130(115/15) | 41.4(1.9) | <200 | AITD | NR | NR | 60(46.15) | 70(53.85) | CLIA | NR | NR |
| Hypothyroidism | NR | NR | 60(46.15) | 70(53.85) | |||||||||
| Nalbant et al. | 2016 | Turkey | 211(194/17) | 39.31(11.44) | NR | AITD | 261.5(109.3) | 259(105.1) | 51(24.17) | 160(75.83) | CLIA | NR | NR |
| Hyperthyroidism | 261.5(109.3) | 239(68.7) | NR | NR | |||||||||
| Hypothyroidism | 261.5(109.3) | 249.3(85.9) | 51(24.17) | 160(75.83) | |||||||||
| Erdal et al. | 2008 | Turkey | 43(39/4) | 48.5(4.7) | <193 | AITD | NR | NR | 0(0) | 43(100) | CLIA | NR | NR |
| Hypothyroidism | NR | NR | 0(0) | 43(100) | |||||||||
| SH | NR | NR | 0(0) | 43(100) | |||||||||
AITD, autoimmune thyroid disease; APCA, anti-parietal cell antibodies; CLIA, chemiluminescence immunoassay; ECLIA, electrochemiluminescence immunoassay; FEI, fluorescence enzyme immunoassay; HPLC, high-performance liquid chromatography; IQR, interquartile range; NR, not reported; RIA, radio immunoassay; SH, subclinical hypothyroidism; SD, standard deviation; TD, thyroid disorder; 95% CI, 95% confidence interval.