The transient pubertal free thyroxine dip should not be misinterpreted as central hypothyroidism: a case series

During puberty, free thyroxine (fT4) concentrations transiently decrease with a nadir around Tanner stage 3. Due to the interindividual variation in timing of pubertal onset, this transient fT4 dip occurs at different ages and becomes less apparent within an age-specific reference interval (RI). This may result in fT4 concentrations temporarily falling below the lower limit of the RI when age-specific instead of Tanner stage-specific RIs are used. As thyroid stimulating hormone (TSH) levels usually remain within the age-specific RI, the resulting biochemical profile resembles central hypothyroidism and frequently triggers extensive, but often unnecessary diagnostic work-ups. We present two cases of asymptomatic adolescents with low fT4 concentrations in combination with a normal TSH, in whom central hypothyroidism was initially suspected but subsequently excluded. In all cases, fT4 concentrations normalized later in puberty without intervention. This phenomenon likely reflects increased peripheral conversion of T4 to triiodothyronine (T3) under the influence of growth hormone and sex steroids. Awareness of this physiological phenomenon is essential to avoid misdiagnosis, overtreatment, and undue psychological stress. Our findings highlight the need for Tanner stage-specific fT4 RIs to guide thyroid function interpretation in adolescents.