We report the case of a 15-year-old Caucasian girl who was diagnosed with
Silver-Russell syndrome at the age of four and a half years.
Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum
growth hormone levels were high, and an
insulin-like growth factor 1 generation test did not increase
insulin-like growth factor 1 levels (baseline
insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the
growth hormone receptor gene, which is characteristic of
Laron syndrome. On the basis of these results, the diagnosis of primary
growth hormone insensitivity syndrome was made, and recombinant
insulin-like growth factor 1
therapy was initiated. The patient's treatment was well tolerated, but unexplained
central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age.
CONCLUSION: The most important functional tests for the diagnosis of
growth hormone insensitivity are the
insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant
insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained
central hypothyroidism occurred during treatment.