We present a patient with
hyperthyroidism associated with
McCune-Albright syndrome (MAS). MAS is a sporadic
genetic disease characterized by
polyostotic fibrous dysplasia, cafe au lait cutaneous spots and endocrinopathies (peripheral
precocious puberty, thyroidopathies,
acromegaly, etc.). It is caused by an activating mutation of the gene for the Gs alpha
membrane-associated protein, which mediates the
thyrotropin (TSH)-induced and other
hormone-induced activation of
adenylyl cyclase. A 13-month-old girl was diagnosed with MAS.
Precocious puberty was treated initially with
testolactone and later with
oophorectomy. Subclinical
hyperthyroidism was detected biochemically at birth, and 10 months later, it became clinically evident, albeit mild, with absence of
goiter. A concomitant
liver dysfunction precluded treatment with thionamides and she was sporadically treated with beta-blockers. The combination of increased free
thyroxine (T4) and
triiodothyronine (T3) with low plasma
thyrotropin (TSH) levels in the absence of
thyroid-stimulating autoantibodies persisted until the age of 6 years, when she was referred to our unit.
Hyperthyroidism was then clinically evident with cardiac hyperactivity, and it was cured with administration of radioiodine (131I).
Thyroid disease is the second most common endocrinopathy associated with MAS, and since 1936, 63 cases of thyroidopathies have been described, including 19 nodular (14 with and 5 without
hyperthyroidism) and 23 diffuse (20 with and 3 without
hyperthyroidism)
goiters, and 18 cases of
hyperthyroidism without
goiter. The previously described somatic activating mutation of the gs alpha gene in the ovaries, the liver and the peripheral blood of our patient, in the absence of stigmata, autoimmunity might be incriminated for the secretory and mitotic activation of the thyroid gland. We suggest the treatment of choice of
hyperthyroidism in MAS patients should be 131I administration because: (a)
hyperthyroidism is very likely to recur after withdrawal of antithyroid medication; (b) the morbidity of these patients is elevated; (c) oophorectomized patients do not need to be advised to avoid procreation during the months after 131I administration; and (d) finally, even in the usual cases of
hyperthyroidism in childhood, 131I treatment is becoming more popular worldwide.