title: Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism.
abstract: OBJECTIVE
  Although it has been recommended that serum free thyroxine (FT4) levels should be targeted to middle-upper normal levels during levothyroxine (l-T4) replacement therapy in patients with central hypothyroidism (CeH), the rationale has not been clarified.
  
  
  METHODS
  A retrospective single-center study enrolled 116 patients with hypothyroidism (CeH, n=32; total thyroidectomy (Tx), n=22; primary hypothyroidism (PH), n=33; and control benign thyroid nodule (C), n=29). The patients had received L-T4 therapy at the Kobe University Hospital between 2003 and 2013. They were stratified according to serum FT4 level (≥ 1.10 or <1.10 ng/dl), and body temperature (BT), serum free triiodothyronine (FT3) levels, FT3/FT4 ratio, and lipid profiles were compared. The effect of GH replacement therapy on thyroid function was also analyzed.
  
  
  RESULTS
  FT3 levels and FT3/FT4 ratios were significantly lower in patients with CeH than in patients with PH (P<0.05) or C (P<0.05). In patients with FT4 <1.10 ng/dl, BT was significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in patients with PH, whereas no differences were found in patients with FT4 ≥ 1.10 ng/dl. In patients with CeH, FT3 levels were higher in those with GH replacement therapy (P=0.018).
  
  
  CONCLUSIONS
  In CeH, patients with median-lower normal levels of serum FT4 exhibited lower serum FT3 levels and lower BT. These results support the target levels of serum FT4 as middle-upper normal levels during l-T4 replacement therapy in patients with CeH.
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan fukuokah@med.kobe-u.ac.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Fukuoka
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Genzo
authors.initials: G
authors.lastname: Iguchi
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Iwahashi
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hari
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Iga
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimoto
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Mukai
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sakaguchi
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.affiliation: Division of Diabetes and EndocrinologyKobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Diabetes and EndocrinologyKobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001831:Body Temperature / Q000502:physiology*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
chemical_list: D015415:Biomarkers; D014284:Triiodothyronine; D013974:Thyroxine