Hyperthyroidism in McCune-Albright Syndrome with a Review of Thyroid Abnormalities Sixty Years After the First Report

We present a patient with hyperthyroidism associated with McCune-Albright syndrome (MAS). MAS is a sporadic genetic disease characterized by polyostotic fibrous dysplasia, café au lait cutaneous spots and endocrinopathies (peripheral precocious puberty, thyroidopathies, acromegaly, etc.). It is caused by an activating mutation of the gene for the G_sα 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 β-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 g_sα 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 world-wide.