Familial dysalbuminemic hyperthyroxinemia
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Familial dysalbuminemic hyperthyroxinemia (FDH) rare genetic condition that is a common cause of [https://emedicine.medscape.com/article/118562-overview?form=fpf euthyroid hyperthyroxinemia] and is associated with mutations in the human serum albumin gene.{{cite journal |vauthors=Petitpas I, Petersen CE, Ha CE, etal |date=May 2003 |title=Structural basis of albumin–thyroxine interactions and familial dysalbuminemic hyperthyroxinemia |journal=Proceedings of the National Academy of Sciences, USA |volume=100 |issue=11 |pages=6440–5 |bibcode=2003PNAS..100.6440P |doi=10.1073/pnas.1137188100 |pmc=164465 |pmid=12743361 |doi-access=free}}{{Cite journal |last1=Fukaishi |first1=Takahiro |last2=Sekiguchi |first2=Yoshihiro |last3=Hara |first3=Yoshihito |date=2017 |title=Familial Dysalbuminemic Hyperthyroxinemia that was Inappropriately Treated with Thiamazole Due to Pseudo-thyrotoxic Symptoms |url=https://www.jstage.jst.go.jp/article/internalmedicine/56/16/56_8619-16/_article |journal=Internal Medicine |language=en |volume=56 |issue=16 |pages=2175–2180 |doi=10.2169/internalmedicine.8619-16 |issn=0918-2918 |pmc=5596280 |pmid=28781323}} It is an autosomal dominant condition that is often mistaken for resistance to thyroid hormone (RTH) syndromes or hyperthyroidism. {{Cite journal |last1=Dieu |first1=Xavier |last2=Bouzamondo |first2=Nathalie |last3=Briet |first3=Claire |last4=Illouz |first4=Frédéric |last5=Moal |first5=Valérie |last6=Boux de Casson |first6=Florence |last7=Bouhours-Nouet |first7=Natacha |last8=Reynier |first8=Pascal |last9=Coutant |first9=Régis |last10=Rodien |first10=Patrice |last11=Mirebeau-Prunier |first11=Delphine |date=2020-07-03 |title=Familial Dysalbuminemic Hyperthyroxinemia: An Underdiagnosed Entity |journal=Journal of Clinical Medicine |language=en |volume=9 |issue=7 |pages=2105 |doi=10.3390/jcm9072105 |doi-access=free |issn=2077-0383 |pmc=7408830 |pmid=32635414}}{{Cite journal |last1=Ruiz |first1=Miguel |last2=Rajatanavin |first2=Rajata |last3=Young |first3=Ruth A. |last4=Taylor |first4=Charles |last5=Brown |first5=Rosalind |last6=Braverman |first6=Lewis E. |last7=Ingbar |first7=Sidney H. |date=1982-03-18 |title=Familial Dysalbuminemic Hyperthyroxinemia: A Syndrome That Can Be Confused with Thyrotoxicosis |url=http://www.nejm.org/doi/abs/10.1056/NEJM198203183061103 |journal=New England Journal of Medicine |language=en |volume=306 |issue=11 |pages=635–639 |doi=10.1056/NEJM198203183061103 |pmid=6173750 |issn=0028-4793}} FDH is characterized by high levels of thyroxine (T4) and normal levels of thyroid stimulating hormone (TSH). Due to the mutations in the albumin gene, an abnormal albumin protein binds thyroid hormones with a high affinity than normal. This explains why those with familial dysalbuminemic hyperthyroxinemia have increased T4 levels and normal TSH levels.
Signs and symptoms
Familial dysalbuminemic hyperthyroxinemia is usually asymptomatic. The clinical features are not specific and vary from patient to patient. In some cases, symptoms such as those seen in hyperthyroidism have been recorded like: palpitations, weight loss, [https://www.ninds.nih.gov/health-information/disorders/tremor tremors], and anxiety.{{Cite journal |last1=Zhao |first1=Linlin |last2=Zhou |first2=Yingying |last3=Huang |first3=Fengjiao |last4=He |first4=Xiaoyang |last5=Mei |first5=Guili |last6=Wang |first6=Shoujun |last7=Zhao |first7=Yanyan |date=2023-02-14 |title=Clinical characteristics of familial dysalbuminemic hyperthyroxinemia in Chinese patients and comparison of free thyroxine in three immunoassay methods |journal=Frontiers in Endocrinology |language=English |volume=14 |doi=10.3389/fendo.2023.1102777 |doi-access=free |issn=1664-2392 |pmc=9971560 |pmid=36864842}}
Cause
The mutations in the albumin gene cause an increase in T4 levels because the albumin now binds more readily to T4. Despite the increased levels of T4, TSH levels remain normal.{{Cite journal |last1=Khoo |first1=Serena |last2=Lyons |first2=Greta |last3=Solomon |first3=Andrew |last4=Oddy |first4=Susan |last5=Halsall |first5=David |last6=Chatterjee |first6=Krishna |last7=Moran |first7=Carla |date=2020-02-26 |title=Familial dysalbuminemic hyperthyroxinemia confounding management of coexistent autoimmune thyroid disease |url=https://edm.bioscientifica.com/view/journals/edm/2020/1/EDM19-0161.xml |journal=Endocrinology, Diabetes & Metabolism Case Reports |language=en-US |volume=2020 |issue=1 |doi=10.1530/EDM-19-0161 |issn=2052-0573 |pmc=7077549 |pmid=32101523}} Because of [https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Fact-Sheet genetic sequencing], the following albumin gene variants have been recorded in patients with FSH: p.Arg218His (R218H), p.Arg218Pro (R218P), p.Arg218Ser (R218S), p.Arg222Ile (R222I), and p.Leu66Pro (L66P).
Pathophysiology
The pathophysiology of familial dysalbuminemic hyperthyroxinemia involves the mutation of the albumin gene, leading to increased binding of thyroid hormones, particularly T4, to albumin. This causes an elevation in total T4 levels without a corresponding increase in free T4, which is why those with this mutation have no clinical symptoms because their thyroid still functions normally. {{Cite journal |last1=Ting |first1=Matthew J M |last2=Zhang |first2=Rui |last3=Lim |first3=Ee Mun |last4=Ward |first4=Bryan K |last5=Wilson |first5=Scott G |last6=Walsh |first6=John P |date=2021-04-01 |title=Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests |journal=Journal of the Endocrine Society |language=en |volume=5 |issue=4 |pages=bvab012 |doi=10.1210/jendso/bvab012 |doi-access=free |issn=2472-1972 |pmc=7940171 |pmid=33728390}}
Diagnosis
File:202403 protein gel electrophoresis equipment.svg
Due to patients generally being asymptomatic, diagnosis of familial dysalbuminemic hyperthyroxinemia is usually made incidentally when abnormal thyroxine levels are detected during routine testing such as a thyroid function test. To be certain, gene sequencing could also be performed to confirm the diagnosis of FDH. This would also allow for the patient and providers to know which albumin gene variant that particular patient has. Protein electrophoresis can also be used to confirm a diagnosis of FDH. {{Citation |last1=Weiss |first1=Roy E. |title=Chapter 78 - Thyroid Function Testing |date=2016-01-01 |work=Endocrinology: Adult and Pediatric (Seventh Edition) |pages=1350–1398.e11 |editor-last=Jameson |editor-first=J. Larry |url=https://linkinghub.elsevier.com/retrieve/pii/B9780323189071000780 |access-date=2024-11-05 |place=Philadelphia |publisher=W.B. Saunders |doi=10.1016/b978-0-323-18907-1.00078-0 |isbn=978-0-323-18907-1 |last2=Refetoff |first2=Samuel |editor2-last=De Groot |editor2-first=Leslie J |editor3-last=de Kretser |editor3-first=David M. |editor4-last=Giudice |editor4-first=Linda C.}} This test measures specific proteins in the blood and in the case of testing for FDH, albumin would be the protein that is isolated.
Treatment/management
Prognosis
Epidemiology
References
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External links
{{Medical resources|DiseasesDB=32942|ICD10=|ICD9=|ICDO=|OMIM=103600|MedlinePlus=|eMedicineSubj=|eMedicineTopic=|MeshID=D050010}}
{{Thyroid disease}}