title: 3,5,3'-Triiodothyronine thyrotoxicosis due to increased conversion of administered levothyroxine in patients with massive metastatic follicular thyroid carcinoma.
abstract: OBJECTIVE
  Some patients with massive metastatic thyroid carcinoma exhibit T(3) thyrotoxicosis. We investigated the prevalence and cause of T(3) thyrotoxicosis and the clues to the diagnosis.
  
  
  METHODS
  Serum free T(3) (FT(3)), free T(4) (FT(4)), and TSH were measured in patients with massive metastases from papillary, follicular, or medullary thyroid carcinomas (31, 20, and seven patients, respectively). Patients without recurrence served as controls. Thyrotoxic patients were reexamined 1 wk after withdrawal of levothyroxine. Type 1 and type 2 iodothyronine deiodinase (D1 and D2) activities were measured in three tumor tissues from thyrotoxic patients.
  
  
  RESULTS
  The serum FT(3) level and FT(3)/FT(4) ratio in the follicular carcinoma (FC) group were significantly higher than those in the papillary carcinoma group or patients without recurrence. Four patients (20%) in the FC group but none in the other groups demonstrated T(3) thyrotoxicosis or a FT(3)/FT(4) ratio greater than 3.5. One week after withdrawal of levothyroxine, both FT(3) and FT(4) levels decreased. Retrospective measurements of FT(3) in frozen stored sera demonstrated that FT(3) exceeded the upper normal limit when FT(4) began to decrease but remained within the normal range. Tumor tissues showed high D1 and D2 activities.
  
  
  CONCLUSIONS
  Twenty percent of patients with massive metastatic FC exhibited T(3) thyrotoxicosis, most likely due to increased conversion of T(4) to T(3) by tumor expressing high D1 and D2 activities. Occasional measurement of serum FT(3) in addition to FT(4) and TSH is recommended in patients with massive metastatic FC, especially when serum FT(4) decreases on fixed doses of levothyroxine.
authors.affiliation: Department of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Japan. miyauchi@kuma-h.or.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzuka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Amino
authors.forename: Nagaoki
authors.initials: N
authors.lastname: Toyoda
authors.forename: Emiko
authors.initials: E
authors.lastname: Nomura
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Nishikawa
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015995:Prevalence; D013960:Thyroid Function Tests; D013964:Thyroid Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D013971:Thyrotoxicosis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D013974:Thyroxine / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000009:adverse effects* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D014284:Triiodothyronine; D007453:Iodide Peroxidase; D013974:Thyroxine