Familial Dysalbuminemic Hyperthyroxinemia Induced by Mutation R218H of Albumin
1. Department of Endocrinology, The Second People’s Hospital of Guangdong Province, Guangzhou 510317, China
2. Department of Endocrinology & Metabolism, Forsea Insurance Guangzhou General Hospital, Guangzhou 511325, China
| Abstract: | Familial Dysalbuminemic Hyperthyroxinemia (FDH) is thought of no clinical significance, but tends to to misdiagnosed and mistreated as Graves’ hyperthyroidism with long time. In a Chinese family to explore clinical characteristics, hereditary features and gene variation of FDH and its effect on pregnancy. Methods: Two propostitus (a father and his son) with hyperthyroidism were re-diagnosed as FDH due to the canonical profile of measured thyroid hormones. After screening thyroid function of the whole family, eight affected of FDH were identified among total thirteen lineal relatives. They were studied in terms of clinical history, biochemical and hormone examination, thyroid imaging and TSH secreting test by dexamethasone and bromocriptine. Three members accepted gene analysis with the next generation sequencing followed by Sanger method. Productive history was investigated in five spouse of the whole family. Results: In the two propostitus, FDH exhibited very high total thyroxine (T4) and mild high total triiodinethyronine (T3), and normal free T4 and T3 besides normal thyroid stimulating hormone (TSH). In addition, ultrasound discovered diffuse goiter and enhanced blood flow, and 99mTc uptake increased, while TSH receptor antibody and pituitary MRI scan remained normal. Other six family members had similar changes of the thyroid hormones and normal TSH which could be suppressed dramatically by dexamethasone and bromocriptine, then were suspected of FDH and thereafter confirmed with gene analysis. Among these eight FDH, four were misdiagnosed with hyperthyroidism and mistakenly received anti-thyroid medication at least one year. Gene analysis of three members revealed R218H variation of albumin gene. Conclusions: R218H associated FDH shows canonical changes of thyroid hormones with increased thyroid function, high penetrance and misdiagnose rate with hyperthyroidism, it exerts no effect on pregnancy. |
| Keywords: | Familial Dysalbuminemic Hyperthyroxinemia; Misdiagnosis; Graves’ Disease; Albumin Gene |
| DOI: | 10.57237/j.mrf.2022.01.004 |
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Received: 6 September 2022
Accepted: 17 October 2022
Published Online: 15 December 2022
References
| [1] | Kragh-Hansen U, Galliano M, Minchiotti L. Clinical, genetic, and protein structural aspects of familial dysalbuminemic hyperthyroxinemia and hypertriiodothyroninemia [J]. Front Endocrinol (Lausanne), 2017, 8: 297. DOI: 10.3389/fendo.2017.00297. |
| [2] | Heufelder A E, Klee G G, Wynne A G, Gharib H. Familial dysalbuminemic hyperthyroxinemia: cumulative experience in 29 consecutive patients [J]. Endocr Pract, 1995, 1 (1): 4-8. DOI: 10.4158/EP.1.1.4. |
| [3] | Minchiotti L, Caridi G, Campagnoli M, et al. Diagnosis, phenotype, and molecular genetics of congenital analbuminemia [J]. Front Genet, 2019, 10:336. DOI: 10.3389/fgene.2019.00336. |
| [4] | Refetoff S, Abnormal thyroid hormone transport.Endotext [Internet].www.endotext.org.Last Update: July 15, 2015. |
| [5] | 叶蕾, 韩如来, 姜小华, 等.促甲状腺激素不适当分泌综合征61例病例总结 [J]. 中华内分泌代谢杂, 2015, 31 (11): 925-930. |
| [6] | 戴维信, 刘振元, 郭芝生, 等. 一个家族性异常白蛋白高甲状腺素血症的表型和基因型分析 [J]. 中华医学遗传学杂志, 2005, 22 (1): 40-43. |
| [7] | 王诗玮, 彭诗乔, 李玉姝, 单忠艳. 家族性白蛋白异常性高甲状腺素血症一例并文献复习 [J]. 中华内分泌代谢杂志, 2020, 36 (11): 961-965. |
| [8] | 王坤玲, 何向辉, 张桂芝, 朱梅.家族性异常白蛋白血症性高甲状腺素血症合并甲状腺癌一例报道及文献复习 [J]. 中华内分泌代谢杂志, 2018, 34 (7): 602-603. |
| [9] | Liu H, Ran J, Chen C, et al. A Chinese family with familial dysalbuminemic hyperthyroxinemia (FDH) due to R242H mutation on human albumin gene: reevaluating the role of FDH in patients with asymptomatic hyperthyroxinemia [J]. Int J Endocrinol, 2019, 2019: 5947415. DOI: 10.1155/2019/5947415. |
| [10] | Lai S, Gopalakrishnan G, Li J, et al.Familial dysalbuminemic hyperthyroxinemia (FDH), albumin gene variant (R218S), and risk of miscarriages in offspring [J]. Am J Med Sci, 2020, 360 (5): 566-574. DOI: 10.1016/j.amjms.2020.05.035. |
| [11] | 尹卓娜, 金文胜, 许卫国, 等. 一个X连锁先天性肾上腺发育不良家系的DAX1基因突变研究 [J]. 中华医学遗传学杂志, 2019, 036 (005):456-461. |
| [12] | 金文胜, 郭燕燕, 宋丹丹,等. 一个新的AVPR2基因缺失-框移突变所致X连锁肾性尿崩症家系 [J]. 中华内分泌代谢杂志, 2017, 33 (7): 602-604. |
| [13] | 尹卓娜, 金文胜, 张晓宇,等. 伴促甲状腺激素瘤的多发性内分泌腺瘤病1型一例报道及文献复习 [J]. 中华内分泌代谢杂志, 2020, 36 (01): 43-50. |
| [14] | Kienitz T, Quinkler M, Strasburger CJ, Ventz M. Long-term management in five cases of TSH-secreting pituitary adenomas: a single center study and review of the literature [J]. Eur J Endocrinol, 2007, 157 (1): 39-46. DOI: 10.1530/EJE-07-0098. |
| [15] | Sachmechi I, Schussler GC. Familial dysalbuminemic hyperthyroxinemia in pregnancy [J]. Eur J Endocrinol, 1995, 133 (6): 729-31. DOI: 10.1530/eje.0.1330729. |
| [16] | Sarne DH, Refetoff S. Normal cellular uptake of thyroxine from serum of patients with familial dysalbuminemic hyperthyroxinemia or elevated thyroxine-binding globulin [J]. J Clin Endocrinol Metab, 1988, 67 (6): 1166-70. DOI: 10.1210/jcem-67-6-1166. |
| [17] | Adu-Gyamfi EA, Wang YX, Ding YB. The interplay between thyroid hormones and the placenta: a comprehensive review [J]. Biol Reprod, 2020, 102 (1): 8-17. DOI: 10.1093/biolre/ioz182. |
| [18] | Torremante P, Kirschner W, Muche R, Flock F. Maternal euthyroid hyperthyroxinemia may reduce preterm birth rate in multiparous women [J]. Open Journal of Obstetrics and Gynecology, 2017, 7: 623-638. DOI: 10.4236/ojog.2017.76065. |
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