title: Follicular variant of papillary thyroid carcinoma presenting as toxic nodule in an adolescent: coexistent polymorphism of the TSHR and Gsα genes.
abstract: BACKGROUND
  Autonomously functioning, "hot", thyroid nodules are not common in children and adolescents. Such nodules are not considered alarming because they are assumed to be benign adenomas. Herein, we present a 15-year-old girl with a papillary thyroid carcinoma of 3.5 cm in diameter, which was functionally autonomous and scintigraphically hot.
  
  
  METHODS
  The patient, initially referred to our Endocrine Unit because of a thyroid nodule, returned 6 months later for symptoms of hyperthyroidism. Hyperthyroidism was confirmed biochemically. Radioactive iodine ((131)I) thyroid scintigraphy was consistent with an autonomous thyroid nodule. As per guidelines, the patient underwent surgery and a pathological examination revealed papillary carcinoma, follicular variant. The excised nodule was examined for activating mutations of the thyrotropin receptor (TSHR), Gsα (GNAS1), H-RAS, N-RAS, K-RAS, and BRAF genes by direct sequencing. No mutations were found. Nevertheless, two combined nonfunctioning mutations were detected: a single-nucleotide polymorphism (SNP) of the TSHR gene, in exon 7, at codon 187 (AAT→AAC, both encoding asparagine), and a SNP within exon 8 of the Gsα gene at codon 185 (ATC→ATT, both encoding isoleucine). Both SNPs were also identified in the germline DNA of the patient. The same SNPs were sought in the parents and brother of our patient. Her father was heterozygous for the TSHR SNP, her mother heterozygous for the Gsα SNP, and her brother was wild type.
  
  
  CONCLUSIONS
  This case demonstrates that the presence of hyperfunctioning thyroid nodule(s) does not rule out cancer and warrants careful evaluation, especially in childhood and adolescence to overlook malignancy.
authors.affiliation: Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. rmruggeri@unime.it
authors.forename: Rosaria Maddalena
authors.initials: RM
authors.lastname: Ruggeri
authors.forename: Alfredo
authors.initials: A
authors.lastname: Campennì
authors.forename: Salvatore
authors.initials: S
authors.lastname: Giovinazzo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Saraceno
authors.forename: Teresa Manuela
authors.initials: TM
authors.lastname: Vicchio
authors.forename: Dario
authors.initials: D
authors.lastname: Carlotta
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Cucinotta
authors.forename: Carmelo
authors.initials: C
authors.lastname: Micali
authors.forename: Francesco
authors.initials: F
authors.lastname: Trimarchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tuccari
authors.forename: Sergio
authors.initials: S
authors.lastname: Baldari
authors.forename: Salvatore
authors.initials: S
authors.lastname: Benvenga
mesh_terms: D000293:Adolescent; D000328:Adult; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D002864:Chromogranins; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D006980:Hyperthyroidism / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011989:Receptors, Thyrotropin / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery
chemical_list: D002864:Chromogranins; D011989:Receptors, Thyrotropin; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs