title: Medically induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study.
abstract: BACKGROUND
  Clinical studies have shown that interventional lowering of serum free thyroxine (FT4) may be associated with extended survival in patients with some terminal cancers. The report of success with this approach in glioblastoma multiforme caused involvement of the author (A.H.) in the prospective consultative management of 23 end-stage solid tumor patients in whom hypothyroxinemia was induced to prolong life.
  
  
  METHODS
  Patients were self-referred or recommended by attending physicians to the author (A.H.) and had advanced cancers of the brain, ovary, lung, pancreas, salivary gland, and breast or had mesothelioma or soft-tissue sarcoma. Hypothyroxinemia was achieved in euthyroid patients by using methimazole, with the addition of 3,3',5-triiodo-L-thyronine (L-T3) to prevent hypothyroidism and suppress endogenous thyrotropin (TSH). In patients with pre-existent primary hypothyroidism, T3 administration was substituted for T4 replacement. Serum FT4 and TSH concentrations were serially monitored to enable adjustments to drug therapy and prevent clinical hypothyroidism. Survival was measured from the date of hypothyroxinemia induction with T3 or methimazole plus T3. Outcomes were compared with the odds of death based on the Surveillance Epidemiology and End Results and American Joint Committee on Cancer databases and literature reports.
  
  
  RESULTS
  The survival time of 83% (19 of 23) of patients exceeded the 20% expected 1-year survival for this hypothyroxinemic, end-stage cancer group. The difference between actual and expected survival was significant.
  
  
  CONCLUSIONS
  Although this is an uncontrolled observational experience with frank limitations, compassionate medical induction of hypothyroxinemia should be considered for patients with advanced cancers to whom other avenues of treatment are closed.
authors.affiliation: Departments of Radiation Oncology and Neuroradiology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Aurora, Colorado, USA; ProMed Cancer Centers, Shanghai, People's Republic of China; Department of Medicine, Albany Medical College, Albany, New York, USA; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, USA hercbergs@gmail.com.
authors.forename: Aleck
authors.initials: A
authors.lastname: Hercbergs
authors.affiliation: Departments of Radiation Oncology and Neuroradiology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Aurora, Colorado, USA; ProMed Cancer Centers, Shanghai, People's Republic of China; Department of Medicine, Albany Medical College, Albany, New York, USA; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Johnson
authors.affiliation: Departments of Radiation Oncology and Neuroradiology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Aurora, Colorado, USA; ProMed Cancer Centers, Shanghai, People's Republic of China; Department of Medicine, Albany Medical College, Albany, New York, USA; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, USA.
authors.forename: Osnat
authors.initials: O
authors.lastname: Ashur-Fabian
authors.affiliation: Departments of Radiation Oncology and Neuroradiology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Aurora, Colorado, USA; ProMed Cancer Centers, Shanghai, People's Republic of China; Department of Medicine, Albany Medical College, Albany, New York, USA; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Garfield
authors.affiliation: Departments of Radiation Oncology and Neuroradiology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Aurora, Colorado, USA; ProMed Cancer Centers, Shanghai, People's Republic of China; Department of Medicine, Albany Medical College, Albany, New York, USA; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003979:Diazonium Compounds / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced / Q000401:mortality* / Q000473:pathology; D008297:Male; D008713:Methimazole / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D003979:Diazonium Compounds; D014284:Triiodothyronine; D008713:Methimazole; C035514:N-2-diazo-3,3,3-trifluoropropionyl-3,5,3'-triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
keywords: Cancer; Hypothyroxinemia; Survival; Triiodothyronine