Background: McCuneAlbright syndrome (MAS) is a rare disease with a prevalence of <1 to 100 000. It is caused by early post-zygotic mutations in the GNAS1 gene. Classically it presents with precocious puberty, fibrous dysplasia and café-au-lait spots. Other endocrinopathies may be hyperthyroidism, GH excess, Cushing syndrome, and renal phosphate wasting.
Case report: A 17-year-old girl diagnosed with MAS at the age of 11 on basis of all three classical signs and hypophosphatemia who had been lost to the follow-up during the next 6 years. At age of 17 years she appeared having short stature (<5th percentile), frequent bone fractures and bone deformations. Endocrine investigations revealed low free T4 (fT4 4.9, reference range 12.621.0 pmol/l) with an inappropriately normal TSH (2.2, ref. 0.54.3 mU/l) and low IGF1 (67, ref. 194680 μg/l). Clinically euthyroid. Her cortisol, prolactin, FSH, LH and oestradiol levels were normal. Due to the very low free T4, she was started with levothyroxine 50 μg/die. Due to the poor growth, low IGF1 and low TSH, arginine stimulation test and pituitary MRT were done to rule out GH deficiency and pituitary lesion. Both were normal (peak GH 56 mU/l). Thyroid ultrasound was normal and no anti-TPO antibodies were present. One month after commencing levothyroxine treatment, serum free T4 concentration remained low (fT4 9 pmol/l and TSH 0.96 mU/l,) and her levothyroxine dose was increased to 75 μg/die. Clinically she was euthyroid. After 1 month, free T4 remained still below reference range (9.6 pmol/l), but her free T3, measured first time, was increased (8.35 pmol, ref. 3.937.70 pmol/l) and TSH became supressed (0.03 mU/l). Clinically slight tachycardia occurred. Iatrogenic hyperthyroidism was diagnosed and treatment with levothyroxine was stopped.
Conclusions: In patients with MAS free T3 should be always measured together with free T4 and TSH to estimate the thyroid function. Low free T4 in our case was probably due to the increased T3 to T4 ratio due to a cAMP-mediated intrathyroidal increased activity of type 1 and type 2 5′-deiodinase (Celi et al., JCEM 2008).
20 - 22 Sep 2014
European Society for Paediatric Endocrinology