OOA (Old Order Amish)

Inheritance: autosomal dominant
Genes: ALB



Familial Dysalbuminemic Hyperthyroxinemia

Clinical Characteristics

General description (for patients):

This is more a variation in a blood protein, albumin, than it is a disease.  The major risk of this condition occurs when certain thyroid tests erroneously suggest an overly active thyroid gland leading to unnecessary surgery on rare occasions.

Medical description: 

FDH is the most common cause of the inherited euthyroid hyperthyroxinemia condition.  It is always associated with high serum total T4 levels but normal TSH and free T4.  Rarely T3 is also elevated.  Among 22 members of an Amish kindred, the FDH phenotype was identified using the protein binding pattern of T4. Serum total T4 was elevated and two subjects had undergone partial thyroidectomies. While mean serum total iodothyronine values were significantly higher than in those without FDH, mean TSH and free T4 were not elevated confirming the euthyroid hyperiodothyroninemic status of FDH. The prevalence of autoimmune disease was not elevated among those with the FDH phenotype.


This is a specific variant of a number of mutations causing a disruption in normal albumin synthesis.  The mutation in a large Amish kindred is inherited as an autosomal dominant leading to enhanced thyroxin binding. The gene (ALB) for albumin synthesis is located on chromosome 4 and the Amish variant was linked to this locus (4q11-q13). Specifically, a SacI polymorphism was identified in exon 13.


Since those with the FDH phenotype are euthyroid, no treatment is required.  However, it is important to understand that, when total T4 is elevated, it is necessary to also determine the proportion of free T4 to avoid unnecessary thyroidectomy.



Ancillary treatments and support:

Monitoring thyroid status

Specialists and specialty centers:

Endocrinologist, internist.


Weiss, R.E., Sunthornthepvarakul, T., Angkeow, P., Marcus-Bagley, D., Cos, N., Alper, C.A., and Refetoff, S.:  Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a large Amish kindred.  J. Clin. Endocrinol. Metab. 80: 116-121, 1995. PubMed ID: 7829599

Yeo, P.P.B., Yabu, Y., Etzkorn, J. R., Rajatanavin, R., Braverman, L.E., and Ingbar, S.H.:  A four generation study of dysalbuminemic hyperthyroxinemia: diagnosis in the presence of an acquired excess of thyroxine-binding globulin.  J. Endocr. Invest. 10: 33-38, 1987. PubMed ID: 3110251


Thyroid Disease

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