title: The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center.
abstract: BACKGROUND
  Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-producing C-cell tumor. In hereditary cases, a germline RET mutation is found in 98% of families. Because MTC is cured only if intrathyroidal, prophylactic thyroidectomy is recommended in the gene carrier (GC).
  
  
  OBJECTIVE
  The aim was to determine whether thyroidectomy performed when stimulated CT becomes detectable is as safe as prophylactic thyroidectomy and to identify the serum CT cutoff able to distinguish intrathyroidal from extrathyroidal MTC.
  
  
  METHODS
  Eighty-four GC were prospectively enrolled; 53 of the 84 underwent total thyroidectomy, one refused surgery, and 30 with normal basal and stimulated CT were under surveillance. The follow-up ranged from 2 to 18 yr.
  
  
  RESULTS
  GC operated on for elevated stimulated CT included 27 GC with a positive peak CT at the screening and four cases who became positive after 4 yr. All of them had intrathyroidal MTC and no node metastases; all were cured after a mean follow-up of 7.5 yr. Among those operated on for detectable basal CT, intrathyroidal tumors were found when CT was below 60 pg/ml, whereas either node metastases or larger tumors were observed when CT was above 60 pg/ml. No correlation among serum CT, age, and type of RET mutation was observed. Thirty GC were still biochemically negative at the annual control.
  
  
  CONCLUSIONS
  The time of thyroidectomy in GC with negative CT could be personalized and safely planned when stimulated CT becomes positive, independent of the type of RET mutation and patient's age. In this series, a basal CT below 60 pg/ml was always associated to an intrathyroidal localization of MTC.
authors.affiliation: Department of Endocrinology and Metabolism, World Health Organization Collaborating Center for the Diagnosis and Treatment of Thyroid Cancer and Other Thyroid Diseases, University of Pisa, Pisa, Italy. relisei@endoc.med.unipi.it
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.forename: Giulia
authors.initials: G
authors.lastname: Renzini
authors.forename: Valeria
authors.initials: V
authors.lastname: Bottici
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosci
authors.forename: Eleonora
authors.initials: E
authors.lastname: Molinaro
authors.forename: Laura
authors.initials: L
authors.lastname: Agate
authors.forename: Virginia
authors.initials: V
authors.lastname: Cappagli
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Piero
authors.initials: P
authors.lastname: Berti
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Faviana
authors.forename: Clara
authors.initials: C
authors.lastname: Ugolini
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002116:Calcitonin / Q000097:blood*; D018278:Carcinoma, Neuroendocrine; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010347:Patient Care Planning; D061214:Patient Safety; D057285:Precision Medicine / Q000379:methods*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics / Q000601:surgery*; D013965:Thyroidectomy / Q000009:adverse effects / Q000379:methods / Q000706:statistics & numerical data*; D013997:Time Factors; D055815:Young Adult
chemical_list: D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human