Abstract
Purpose
Prompt initiation of l-thyroxine therapy in neonates with congenital hypothyroidism (CH) often prevents the performance of functional studies. Aetiological diagnosis is thus postponed until after infancy, when the required investigations are performed after l-thyroxine withdrawal. The aim of this study was to verify the efficacy and safety of new protocols for rhTSH (Thyrogen) testing during l-thyroxine replacement in the differential diagnosis of CH.
Methods
Ten CH patients (15–144 months old) were studied. Seven had neonatal evidence of gland in situ at the ultrasound examination performed at enrolment and received two rhTSH injections (4 μg/kg daily, i.m.) with 123I scintigraphy and perchlorate test on day 3. Three patients with an ultrasound diagnosis of thyroid dysgenesis received three rhTSH injections with 123I scintigraphy on days 3 and 4. TSH and thyroglobulin (Tg) determinations were performed on days 1, 3 and 4, and neck ultrasound on day 1.
Results
rhTSH stimulation caused Tg levels to increase in eight cases. Blunted Tg responses were seen in two patients with ectopia and hypoplasia. Interestingly, in two cases the association of different developmental defects was demonstrated. Perchlorate test revealed a total iodide organification defect in two patients, including one with a neonatal diagnosis of Pendred’s syndrome, who were subsequently found to harbour TPO mutations. rhTSH did not cause notable side-effects.
Conclusion
These new rhTSH protocols always resulted in accurate disease characterisation, allowing specific management and targeted genetic analyses. Thus, rhTSH represents a valid and safe alternative to l-thyroxine withdrawal in the differential diagnosis of CH in paediatric patients.
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References
Fisher DA. Management of congenital hypothyroidism. J Clin Endocrinol Metab 1991;72:523–9.
American Academy of Paediatrics & American Thyroid Association. Newborn screening for congenital hypothyroidism, recommended guidelines. Paediatrics 1993;91:1203–9.
Toublanc JE. Guidelines for neonatal screening programs for congenital hypothyroidism. Working Group for Neonatal Screening in Paediatric Endocrinology of the European Society for Paediatric Endocrinology. Acta Paediatr 1999;88(Suppl):13–4.
Devos H, Rodd C, Gagné N, Laframboise R, Van Vliet G. A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations. J Clin Endocrinol Metab 1999;84:2502–6.
DeVijlder JJM, Vulsma T. Hereditary metabolic disorders causing hypothyroidism. In: Braverman LE, Utiger DD, editors. Werner and Ingbar’s the thyroid, 8th edn. Philadelphia: Lippincott-Raven; 2000; p. 733–42.
Foley TP Jr. Congenital hypothyroidism. In: Braverman LE, Utiger RD, editors. Werner and Ingbar’s the thyroid, 8th edn. Philadelphia: Lippincott-Raven; 2000; p. 977–83.
Fugazzola L, Persani L, Mannavola D, Reschini E, Vannucchi G, Weber G, et al. Recombinant human TSH testing is a valuable tool for differential diagnosis of congenital hypothyroidism during L-thyroxine replacement. Clin Endocrinol 2003;59:230–6.
Fugazzola L, Cerutti N, Mannavola D, Crinò A, Cassio A, Gasparoni P, et al. Differential diagnosis between Pendred and pseudo-Pendred syndromes: clinical, radiologic, and molecular studies. Pediatr Res 2002;51:479–84.
Chanoine JP, Toppet V, Lagasse R, Spehl M, Delange F. Determination of thyroid volume by ultrasound from the neonatal period to late adolescence. Eur J Pediatr 1991;150:395–9.
Fugazzola L, Cerutti N, Mannavola D, Vannucchi G, Fallini C, Persani L, et al. Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect. J Clin Endocrinol Metab 2003;88:3264–71.
Clifton-Bligh RJ, Gregory JW, Ludgate M, John R, Persani L, Asteria C, et al. Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH. J Clin Endocrinol Metab 1997;82:1094–100.
Congdon T, Nguyen LQ, Nogueira CR, Habiby RL, Medeiros-Neto G, Kopp P. A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child. J Clin Endocrinol Metab 2001;86:3962–7.
Alberti L, Proverbio MC, Costagliola S, Romoli R, Boldrighini B, Vigone MC, et al. Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism. J Clin Endocrinol Metab 2002;87:2549–55.
Hsu CY, Wang SJ. Thyroid hemiagenesis accompanying an ectopic sublingual thyroid. Clin Nucl Med 1994;19:546–8.
Fugazzola L, Mannavola D, Vigone MC, Cirello V, Weber G, Beck-Peccoz P, et al. Total iodide organification defect: clinical and molecular characterization of an Italian family. Thyroid 2005;15:1085–8.
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Fugazzola, L., Persani, L., Vannucchi, G. et al. Thyroid scintigraphy and perchlorate test after recombinant human TSH: a new tool for the differential diagnosis of congenital hypothyroidism during infancy. Eur J Nucl Med Mol Imaging 34, 1498–1503 (2007). https://doi.org/10.1007/s00259-007-0377-6
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DOI: https://doi.org/10.1007/s00259-007-0377-6