Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life.

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

Thyroid Disorders Following Hematopoietic Stem Cell Transplantation in Childhood: Impact of Conditioning Regimen on Thyroid Dysfunction, Volume Changes, and Occurrence of Nodules.

Thyroid late effects are among the most frequent sequelae reported after pediatric hematopoietic stem cell transplantation (HSCT). Although the detrimental effects of radiotherapy on the developing thyroid gland have been extensively assessed, the role of chemotherapy-only conditioning regimens remains controversial. We aimed to describe the occurrence, monitoring, and management of thyroid function disorders (ie, Graves disease, Hashimoto thyroiditis, and nonautoimmune hypothyroidism), nodules, and volumetric changes over a 20-year observation period in a single pediatric transplantation unit. In addition, we assessed the impact of different conditioning regimens on thyroid health. The study population for this retrospective observational analysis comprised 244 pediatric patients who underwent HSCT for malignant or nonmalignant diseases between 1999 and 2018 and for whom at least 4 thyroid function tests and 1 or more thyroid ultrasound(s) assessed sequentially after HSCT were available. The 15-year cumulative incidence of either autoimmune or nonautoimmune thyroid dysfunctions (34%, SE 5.3%) did not differ statistically between total body irradiation (TBI)-based and chemotherapy-based regimens (P = .23). Indeed, the cumulative incidence after busulfan (Bu)-based conditioning was overall superimposable to that recorded after TBI (10-year cumulative incidence, 22.2% versus 25.9%, respectively). Nevertheless, the cumulative incidence of nonautoimmune hypothyroidism was statistically higher after Bu-based conditioning (12.4%, SE 3.7%) than after other chemotherapy-only-based conditioning regimens (3.1%, SE 3.1%; P = .02, 5-year cumulative incidence), treosulfan (Treo) included. The overall cumulative incidence of nodules was low for the first 5 years after HSCT (1.9%, SE .9%) but subsequently increased steeply over time, with a 15-year cumulative incidence as high as 52.1% (SE 7.5%). TBI-conditioned patients had a higher 15-year cumulative incidence of nodules (66.8%, SE 9.1%) compared with patients receiving chemotherapy-only regimens (33.6%, SE 9.5%; P = .02), whereas age >10 years at transplantation showed a protective effect (hazard ratio, .42, 95% confidence interval, .2 to .88). Finally, a systematic sonographic follow-up highlighted a progressive statistically significant reduction in thyroid anteroposterior diameter among patients conditioned with TBI (P = .005), but not in those who received chemotherapy-only regimens. TBI and younger age at HSCT have a statistically significant detrimental effect on the occurrence of thyroid nodules, both benign and malignant. TBI and Bu expose patients to a higher cumulative incidence of thyroid dysfunction compared with other chemotherapy-only regimens, Treo included. Accordingly, Bu can be considered the most thyrotoxic agent among those administered as a part of a chemotherapy-only conditioning regimen. Finally, patients conditioned with TBI, but not those with other regimens, show a progressive decrease in thyroid volume over time, as assessed by sequential ultrasound examinations.

Thyroid function disorders and secondary cancer following haematopoietic stem cell transplantation in pediatrics: State of the art and practical recommendations for a risk-based follow-up.

Thyroid disorders (TD) represent a remarkable share of all the late morbidities experienced following pediatric haematopoietic stem cell transplantation (HSCT), with long-term reported occurrence often exceeding 70%. In addition, the data collected on wide cohorts of survivors assessed longitudinally outlined a progressive increase in the cumulative incidence of TD as far as 30 years following transplantation. Accordingly, a life-long monitoring of thyroid health is warranted among patients exposed to HSCT in childhood, in order to early detect TD and undertake a prompt dedicated treatment. Although several national and international consortia have provided recommendations for the early detection of thyroid disorders among childhood cancer survivors exposed to radiotherapy and alkylating agents, no guidelines specifically and thoroughly focused on HSCT-related TD have been published to date. As stem cell transplantation has become the standard-of-care in a growing body of non-oncological conditions, this urge has become pivotal. To highlight the challenging issues specifically involving this cohort of patients and to provide clinicians with the proposal of a practical follow-up protocol, we reviewed published literature in the light of the shared experience of a multidisciplinary team of pediatric oncologists, transplantologists, pathologists and endocrinologists involved in the long-term care of HSCT survivors. As a final result, we hereby present the proposals of a practical and customized risk-based approach to tailor thyroid health follow-up based on HSCT-related detrimental factors.