HYPERTHYROIDISM IN MCCUNE-ALBRIGHT-SYNDROME WITH A REVIEW OF THYROID ABNORMALITIES 60 YEARS AFTER THE FIRST REPORT

We present a patient with hyperthyroidism associated with McCune-Albri ght syndrome (MAS). MAS is a sporadic genetic disease characterized by polyostotic fibrous dysplasia, cafe au lait cutaneous spots and endoc rinopathies (peripheral precocious puberty, thyroidopathies, acromegal y, etc.). It is caused by an activating mutation of the gene for the G (s) 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 t reated initially with testolactone and later with oophorectomy. Subcli nical hyperthyroidism was detected biochemically at birth, and 10 mont hs later, it became clinically evident, albeit mild, with absence of g oiter. A concomitant liver dysfunction precluded treatment with thiona mides and she was sporadically treated with beta-blockers. The combina tion of increased free thyroxine (T-4) and triiodothyronine (T-3) with low plasma thyrotropin (TSH) levels in the absence of thyroid-stimula ting autoantiibodies 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 radioi odine (I-131). Thyroid disease is the second most common endocrinopath y associated with MAS, and since 1936, 63 cases of thyroidopathies hav e been described, including 19 nodular (14 with and 5 without hyperthy roidism) and 23 diffuse (20 with and 3 without hyperthyroidism) goiter s, and 18 cases of hyperthyroidism without goiter. The previously desc ribed somatic activating mutation of the g(s) alpha gene in the ovarie s, the liver and the peripheral blood of our patient, in the absence o f stigmata, autoimmunity might be incriminated for the secretory and m itotic activation of the thyroid gland. We suggest the treatment of ch oice of hyperthyroidism in MAS patients should be I-131 administration because: (a) hyperthyroidism is very likely to recur after withdrawal of antithyroid medication; (b) she morbidity of these patients is ele vated; (c) oophorectomized patients do not need to be advised to avoid procreation during the months after I-131 administration; and (d) fin ally, even in the usual cases of hyperthyroidism in childhood, I-131 t reatment is becoming more popular worldwide.