Armando Grossi

Recombinant Thyrotropin Use in Children and Adolescents with Differentiated Thyroid Cancer: A Multicenter Retrospective Study

CONTEXTnAlthough recombinant human TSH (rhTSH) is widely used in differentiated thyroid cancer (DTC) to aid diagnostic follow-up procedures and radioiodine thyroid remnant ablation, almost all clinical investigation was in adults.nnnOBJECTIVEnThe aim of this study was to characterize rhTSH clinical safety and peak TSH response in DTC patients 18 yr old or younger.nnnDESIGN AND SETTINGnWe conducted a retrospective study involving 23 tertiary referral centers in 12 European, Asian, and Oceanian countries.nnnPATIENTSnOne hundred DTC patients (69% female, 31% male, 84% papillary, 61% N1, 18% M1) ages 4.9-18 yr at first rhTSH administration were studied.nnnINTERVENTIONSnA total of 181 rhTSH courses were administered (range, one to eight per patient; 42% of patients received two or more courses), 92% using the approved adult regimen (one 0.9 mg im injection daily on two consecutive days), 34% including thyroid hormone withdrawal for less than 7 d (mini-THW).nnnMAIN OUTCOME MEASURESnClinical adverse event (AE) incidence, type, and severity, and peak post-rhTSH serum TSH concentrations were assessed.nnnRESULTSnNo clinical AEs occurred in 88% of rhTSH courses. Most common clinical AEs were nausea (5% of courses) and vomiting (3%). Multiple or severe AEs were rare (0.6% and 2.8% of courses, respectively); serious AEs were absent. Peak TSH concentration post-rhTSH exceeded 25 mU/liter in approximately 98% of courses. In logistic regression analyses, the rhTSH regimen, mini-THW, peak TSH concentration, body mass index (BMI), or peak TSH concentration/unit of BMI were not associated with clinical AE occurrence. In analyses of covariance, higher BMI was associated with lower peak TSH concentrations.nnnCONCLUSIONSnrhTSH was clinically well tolerated in pediatric DTC patients although courses preponderantly comprised the adult regimen, and repeated courses were frequent. Both the adult and reduced-dose regimens almost always sufficiently elevate TSH in children and adolescents.

Turner Syndrome and Diabetes

Turner syndrome (TS) is associated with a significant risk of developing autoimmune diseases, including type 1 diabetes. Suggested etiopathogenic mechanisms include inactivation and transcriptional silencing of genes in the X chromosome during early embryonic development, leading to abnormal thymic deletion of autoreactive T-lymphocytes, with impaired immune recognition and tolerance; deletion of genes (i.e., FOWP3) playing a crucial role for the function of natural regulatory T-cells; and upregulation of proinflammatory cytokines. On the other hand, abnormal gametogenesis and nondysjunctional events could be secondary to abnormal autoimmune responsiveness. Starting in childhood, TS patients also present an increased rate of insulin resistance and type 2 diabetes in comparison with age-matched controls. The negative role of the haploinsufficiency of the genes on the Xp chromosome on the transcription factors involved in pancreatic islet and β-cell function, as well as hormonal and metabolic factors, have been suggested. The role of growth hormone treatment and timing of pubertal induction on metabolic profile is still a subject of debate.

Endocrinology: Thyroid Carcinoma

Differentiated thyroid carcinoma (DTC) is rare in childhood, but is the most frequent tumor of endocrine glands in children and adolescents (0.2–0.5/100,000/year), and is more aggressive with regard to clinical course. Total thyroidectomy, followed by ablative radioiodine therapy, is recommended; on the other hand, less aggressive treatment modalities should be taken into consideration, due to the high life expectancy of these patients and the potential impairment of quality of life.

Smart-web support: un nuovo strumento per la condivisione delle cure in patologie pediatriche complesse. Protocollo di studio

: As devices for learning, smart-web support (SWS) multimedia hypertexts on the web now provide more versatile and interactive reading systems than those traditionally available in static printed texts. Designing similar tools for clinical practice would make complex scientific information easier to comprehend, and present the various therapeutic options to patients as minimally alarming graphical representations. In a pilot project we intend to produce a SWS tool for parents or tutors of children with primary differentiated thyroid cancer (DTC), a heretofore rare disease whose incidence has increased over recent years. The SWS hypertexts, pre-digested by the multidisciplinary team caring for these children, will be inserted in a single web page (canvas) including shared sheets explaining the best surgical options (decision aids). To make evidence-based information easier to understand and help information sharing, the decision aids will combine text and graphics. The canvas will store data for the multimedia files in a cloud storage system, opened via a link. To measure parents and tutors understanding and appreciation of the information provided on the web, the canvas will include questionnaires to investigate satisfaction, eventual barrier encountered, and type of surgical therapy chosen. The SWS tool should allow users to obtain all the information in a relatively short time and improve parents and childrens satisfaction with the surgical options proposed. The results obtained will be useful for developing similar SWS devices for other complex paediatric diseases.