title: Macro-thyrotropin: a case report and review of literature.
abstract: BACKGROUND
  Isolated elevation of TSH in the absence of thyroid symptoms can be very rarely caused by a macromolecule formed between TSH and Ig (macro-TSH), confounding the interpretation of thyroid function test results.
  
  
  OBJECTIVE
  We described the use of several commonly available laboratory-based approaches to investigate an isolated TSH elevation [232 mIU/liter; free T(4), 10 pmol/liter (reference interval, 10.0-23.0 pmol/liter), Vitros platform] in a clinically euthyroid elderly gentleman, which led to the diagnosis of macro-TSH.
  
  
  RESULTS
  TSH concentration of the patient was significantly lower (122 mIU/liter) when measured on the Advia Centaur platform. Serial dilution of the patient's sample showed a nonlinear increase in TSH recovery at increasing dilution (nonlinearity). Polyethylene glycol precipitation and mixing the patient's sample with a hypothyroid patient sample showed reduced TSH recovery, suggesting the presence of a high molecular weight interfering substance and excess TSH binding capacity, respectively. Heterophile blocking tube studies and rheumatoid factors were negative. Gel filtration chromatography demonstrated a TSH peak fraction that approximated the molecular size of IgG; together with the excess TSH binding capacity, this indicated the presence of TSH-IgG macro-TSH. A review of 12 macro-TSH case reports showed that samples with macro-TSH produce over-recovery with dilution, return negative results on anti-animal and anti-heterophile blocking studies, and commonly have recovery of less than 20% when subjected to polyethylene glycol precipitation.
  
  
  CONCLUSIONS
  Macro-TSH is an underrecognized laboratory interference. Routine laboratory techniques described above can help diagnose this rare entity. A close dialogue between the physician and the laboratory is important in approaching such cases.
authors.affiliation: Department of Laboratory Medicine, National University Hospital, Singapore. lohtp@yahoo.com
authors.forename: Tze Ping
authors.initials: TP
authors.lastname: Loh
authors.forename: Shih Ling
authors.initials: SL
authors.lastname: Kao
authors.forename: David J
authors.initials: DJ
authors.lastname: Halsall
authors.forename: Sue-Anne Ee Shiow
authors.initials: SA
authors.lastname: Toh
authors.forename: Edmund
authors.initials: E
authors.lastname: Chan
authors.forename: Su Chin
authors.initials: SC
authors.lastname: Ho
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Chin Meng
authors.initials: CM
authors.lastname: Khoo
mesh_terms: D005189:False Positive Reactions; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000175:diagnosis*; D007074:Immunoglobulin G / Q000097:blood* / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D013960:Thyroid Function Tests / Q000592:standards*; D013972:Thyrotropin / Q000097:blood* / Q000737:chemistry*; D013974:Thyroxine / Q000097:blood
chemical_list: D007074:Immunoglobulin G; D013972:Thyrotropin; D013974:Thyroxine