Central hypothyroidism improves with age in very young children with Prader-Willi syndrome

Abnormalities in the hypothalamic-pituitary-thyroid (HPT) axis have been implicated in Prader-Willi syndrome (PWS); however, limited information is currently available on age-dependent alterations in the HPT axis. We herein investigated age-dependent differences in thyroid hormone levels in PWS children.

Free T4 (FT4), free T3 (FT3) and thyroid-stimulating hormone (TSH) concentrations were retrospectively compared between genetically confirmed PWS children (N = 43, median age: 11.2 months) and controls (N = 85, median age: 14.5 months) matched for age, sex, body weight-SD score (SDS), height-SDS, body mass index-SDS and serum albumin level, a marker of the nutritional status. Subjects were subdivided into two groups based on their age: an infant group aged between 1 and 11 months (PWS: N = 22, controls: N = 30) and a toddler group aged between 12 and 47 months (PWS: N = 21, controls: N = 55). None of the subjects had ever been treated with growth hormone or levothyroxine.

After adjustments for confounding variables, in the infant group, FT4 levels (pmol/L) were significantly lower in PWS (11.24 in PWS vs 14.32 in controls, P = .0002), whereas no significant differences were observed in FT3 or TSH levels. In the toddler group, no significant differences were noted in FT4 (12.23 in PWS vs 15.31 in controls, P = .10), FT3 or TSH levels. The FT3/FT4 ratio was significantly increased in PWS in both groups. FT4 levels were positively correlated with age in PWS.

Infants with PWS had lower FT4 levels, but FT3 levels were normal, indicating that the levothyroxine replacement therapy may not need to be routinely performed.