title: Recombinant human TSH testing is a valuable tool for differential diagnosis of congenital hypothyroidism during L-thyroxine replacement.
abstract: OBJECTIVE
  The differential diagnosis of congenital hypothyroidism (CH) is aimed to distinguish transitory from permanent forms, to optimize L-thyroxine (L-T4) therapy to replacement or TSH-suppressive regimens, and to reach accurate definition of the clinical and biochemical phenotype for subsequent genetic investigations and counselling. Therefore, L-T4 therapy is presently withdrawn in most instances and investigations are performed in a disturbing hypothyroid state.
  
  
  METHODS
  The availability of recombinant human TSH (rhTSH) prompted us to assess its efficacy in the differential diagnosis of CH during L-T4 therapy.
  
  
  METHODS
  Eight adult patients with permanent CH remained on L-thyroxine and underwent a new protocol for rhTSH (Thyrogen) testing with injections [4 g/kg/day intramuscularly (i.m.)] at days 1, 2 and 3. At day 3, 123I was administered and uptake obtained after 2 and 24 h. Serum TSH and thyroglobulin (Tg) levels were measured at days 1-4. Neck ultrasound was carried out in all cases.
  
  
  RESULTS
  Serum TSH reached levels > 20 mU/l at day 2 and remained above 30 mU/l on days 3 and 4. Stimulation of Tg levels was seen in five patients with peak at day 4. Lingual thyroid was documented at scintigraphy (TS) in three Tg-responsive patients who were previously diagnosed as having thyroid agenesia. In one patient with dyshormonogenesis and high Tg, TS confirmed the presence of goitre with positive perchlorate test. TS was negative in the remaining four cases. All tests indicated complete agenesia in one, whereas a minimal Tg response was marker of nearly complete agenesia in another. The last two TS-negative patients had hypoplastic glands at ultrasound, and refractoriness to TSH stimulation was confirmed by absent Tg response.
  
  
  CONCLUSIONS
  We report the first application of rhTSH for differential diagnosis of patients with permanent CH, avoiding the undesirable transient hypothyroidism consequent to L-T4 withdrawal. The data obtained led to the change of the diagnosis at presentation in 4/8 patients and to a more accurate description of the clinical picture in all patients. The proposed protocol has been proved to cause Tg increases even in the presence of small amounts of responsive thyroid cells. The rhTSH testing led to the desired disease characterization, thus allowing specific management and targeted genetic analyses.
authors.affiliation: Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.forename: Deborah
authors.initials: D
authors.lastname: Mannavola
authors.forename: Eugenio
authors.initials: E
authors.lastname: Reschini
authors.forename: Guia
authors.initials: G
authors.lastname: Vannucchi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Weber
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
mesh_terms: D000328:Adult; D000368:Aged; D003409:Congenital Hypothyroidism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis* / Q000188:drug therapy; D007273:Injections, Intramuscular; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011877:Radionuclide Imaging; D011994:Recombinant Proteins; D013954:Thyroglobulin / Q000032:analysis; D013961:Thyroid Gland / Q000002:abnormalities* / Q000000981:diagnostic imaging; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*
chemical_list: D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine