TSH and FT4 concentrations in congenital central hypothyroidism and mild congenital thyroidal hypothyroidism

In central hypothyroidism (CeH) free thyroxine (FT4) concentrations are low while TSH concentrations may be low, normal or even slightly elevated due to reduced bioactivity. Congenital CeH (CCeH) may be isolated or part of multiple pituitary hormone deficiency (MPHD). To test our hypotheses that (1) TSH concentrations have a more U-shaped distribution in children with CCeH compared to children with a normally functioning hypothalamic-pituitary-thyroid-axis, and (2) TSH concentrations in children with CCeH with MPHD are higher compared to children with isolated CCeH. We also studied whether FT4 levels are helpful in distinguishing CCeH from mild primary CH (CH-T). Dutch neonatal screening TSH and first diagnostic TSH and FT4 were analyzed of all children diagnosed with permanent CCeH between 1995 and 2012. Controls were children with TBG deficiency. FT4 concentrations in CCeH were compared to those in CH-T with TSH-values in the same range as those of CCeH. We studied 120 children with CCeH (isolated CCeH, N=50; MPHD, N=70) and 350 controls. Screening TSH concentrations were not significantly different (p =0.055) but diagnostic TSH values were significantly different between the CCeH group and the control group (p=0.037). TSH was significantly higher in MPHD compared to isolated CCeH (p=0.004). FT4 concentrations were significantly lower in CCeH compared to mild CH-T (p <0.0005). TSH values in CCeH have a more U-shaped distribution compared to controls with the TSH concentrations in CCeH with MPHD. FT4 levels were significantly lower in CCeH compared to CH-T