Some patients with subclinical hypothyroidism
have mutations in the gene for the thyrotropin receptor
(November 2002)
The background of the study. Subclinical
hypothyroidism (high serum thyrotropin [TSH] but normal serum thyroid
hormone concentrations) is common, and is usually caused by autoimmune
thyroid disease. This study was done to determine if patients with
subclinical hypothyroidism who had no evidence of autoimmune thyroid
disease might have mutations in the gene for the TSH receptor that
reduced the activity of the receptor.
How the study was done. The study
subjects were 10 patients (age range, 23 days to 25 years) with
subclinical hypothyroidism and their parents and siblings. The patients'
initial serum TSH concentrations ranged from 6.6 to 46.0 mU/L; all
had normal serum concentrations of free thyroxine and antithyroid
peroxidase, antithyroglobulin, and anti-TSH receptor antibodies.
Ultrasonography revealed thyroid hypoplasia in two patients and
a normal thyroid gland in eight patients.
DNA was extracted from peripheral blood leukocytes, and the structure
of the gene for the TSH receptor was determined. The mutations found
in the patients were introduced into cells to determine the effect
of the mutation on the activity of the receptor, as compared with
the activity of the normal TSH receptor.
The results of the study. Five different
mutations in the TSH-receptor gene were detected in 4 of the 10
patients. A parent or sibling of most of the patients had the same
mutation, and they also had high serum TSH concentrations. Fewer
TSH receptors were detected on cells carrying the mutated genes
as compared with cells carrying the normal gene.
The conclusions of the study. Mutations
in the gene for the TSH receptor gene can cause subclinical hypothyroidism.
The original article. Alberti L,
Proverbio MC, Costagliola S, Romoli R, Boldrighini B, Vigone MC,
Weber G, Chiumello G, Beck-Peccoz P, Persani L. Germline mutations
of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism.
J Clin Endocrinol Metab 2002;87:2549-55.
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