Authors' objectives: The main objective of the report is answering the question raised about if the genetic diagnostic application improves expectancy and quality of life in those individuals carrying RET mutations, and as a result, doomed to suffer from medullary thyroid cancer. For that purpose, the report is intending to determine if genetic diagnosis allows for identifying mutationcarriers earlier in the disease than in individuals identified by biochemical screening, and if the patients operated according to genetic diagnosis have better prospective for life than those operated following clinical symptoms. The secondary aim of the report is the cost-effectiveness analysis of diagnostic strategies (genetic and biochemical) for MEN2 syndrome.

Authors' results and conclusions: Neither clinical trials, nor cohort studies, nor case and control studies were found in the systematic search. 17 studies were located that met the established inclusion criteria. They were observational studies without control group, and had low quality. All of them were case series with great variability in size of the study sample, and great heterogeneity in populations, surgeries as well as in the patients’ follow-up. All these seriously hinder the evidence backed by their conclusions. Morbidity associated to surgery, damage to recurrent nerve and hyperthyroidism were not assessed in all papers. Concerning damage to recurrent nerve, those papers that provided data did not observe any permanent damage. Hyperthyroidism provoked by thyroids extirpation was not mentioned by most of the articles. Only one paper showed the existence of blinded hyperthyroidism in a great amount of patients, i.e. their tests showed normal levels of T4 hormone (free thyroid hormone); but, they also showed high levels of TSH (thyroid stimulating hormone), which pointed at the fact that patients were given inappropriate doses of thyroxine. The histologies performed to the thyroidectomised individuals reported that most of asymptomatic subjects carrying RET mutations had histological alterations in thyroids. Moreover asymptomatic carriers were reported to have MTC, some of them were already in metastatic phases, but their biochemical testing showed normal levels. All studies informed the results from the surgery were biochemical healing, i.e. they measured calcitonin levels after surgery, and checked if their rates were normal (healing) or remained high (persistence of disease). Most of the studies reported that the operated asymptomatic subjects’ biochemical, healing rate was higher than symptomatic individuals’ one. However, patients’ follow-up time was not enough, so conclusive data on the disease’s recurrence was hindered from being obtained, since an insufficient follow-up time usually provides more optimistic results that those gotten after waiting the proper time. The economic assessment showed that genetic screening is more effective and costs less than biochemical screening as performed in population at risk for MTC because of belonging to families affected by MEN 2 syndrome.

Authors' recommendations: Plasma calcitonin biochemical testing, as basal as stimulated by pentagastrin, is a good marker of the existence of thyroids’ histological alteration, but is not useful to distinguish between C-cell hyperplasia and MTC. Besides, the biochemical testing provides a great number of false-negative rates.The histologies of the subjects operated according to genetic testings and who had no calcitonin level alterations, as basal as stimulated by pentagastrin, present earlier stages of the disease than the histologies found in individuals with biochemical alterations or clinical symptoms.It is important to mention that patients with disease-related symptoms suffer from nodular and distal metastases more frequently.The results from all the papers pinpoint that surgery at an early age, before any biochemical sign related to thyroids C cell disorders appear, confers better prospective for biochemical healing and the disease is less likely to recur.The strategy addressing control and diagnosis of MEN2 syndrome by genetic testing is considered to be the dominant strategy as opposed to control and diagnosis strategy via biochemical testing. RECOMMENDATIONS:Although the outcomes are fine, such papers lack methodological quality, so that the proposal cannot be recommended in general terms, especially for the risk it carries to damage the recurrent nerve in neck and parathyroid glands during surgery, above all in very young patients. However, it is advisable the genetic testing of individuals from familiesaffected by MEN 2 syndrome, since the test identifies RET mutation carriers early.

Authors' methods: Review

Project Status: Completed

URL for project: https://www.aetsa.org/publicacion/analisis-de-mutaciones-en-el-gen-ret-para-la-realizacion-de-tiroidectomias-profilacticas-en-individuos-en-riesgo-de-cancer-medular-de-tiroides/

Year Published: 2008

URL for published report: https://www.aetsa.org/download/publicaciones/antiguas/AETSA_2006-09_RET.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Spain

Organisation Name: Andalusian Health Technology Assessment Area

Contact Address: Area de Evaluacion de Tecnologias Sanitarias Sanitarias de Andalucia (AETSA) Avda. Innovación, s/n Edificio Arena 1. Sevilla (Spain) Tel. +34 955 006 309

Contact Name: aetsa.csalud@juntadeandalucia.es

Contact Email: aetsa.csalud@juntadeandalucia.es

Copyright: Andalusian Agency for Health Technology Assessment (AETSA)