Clinical features of thyroid cancer in paediatric age. Experience of a tertiary centre in the 2000-2020 period.

PURPOSE: To describe the clinical features of a paediatric cohort affected by differentiated thyroid cancer (DTC) followed in a tertiary Department of Paediatric Endocrinology. METHODS: Clinical data of 41 patients affected by DTC in the 2000-2020 period were reviewed. RESULTS: The main risk factor was autoimmune thyroiditis (39%). Cytological categories were TIR3b in 39%, TIR4 in 9.8%, TIR5 in 51.2%. After total thyroidectomy, radioiodine treatment was performed in 38 subjects (92.7%). ATA low-risk category was assigned in 11 (30.5%), intermediate-risk category in 15 (41.7%), and high-risk category in 10 patients (27.8%). Age at diagnosis was 15.1 ± 0.92 years in low-risk category, 14.7 ± 0.59 in intermediate-risk category, 11.7 ± 0.89 years in high-risk category (p = 0.01). TIR3b was manly observed in low-risk class (63.6%), while TIR5 was mainly reported in intermediate and high-risk class (60 and 80% respectively) (p = 0.04). Post-surgery stimulated thyroglobulin was increased in high-risk class (407.8 ± 307.1 ng/ml) [p = 0.04]. Tumour size was larger in high-risk category (42.6 ± 2.6 mm), than in low and intermediate-risk categories (19.4 ± 3.5 mm and 28.5 ± 3.9 mm, respectively) (p = 0.008). Patients in intermediate and high-risk categories displayed more tumour multifocality (60 and 90% respectively) (p < 0.005). Disease relapse was mainly observed in high risk category (40%, p = 0.04). CONCLUSION: DTC in childhood is more aggressive than in adults, but the overall survival rate is excellent. The therapeutic approach is still heterogeneous, especially in low-risk category. Further studies are needed to standardise management and reduce disease persistence in childhood.

Hurthle cell carcinoma in childhood: A retrospective analysis of five cases and review of pediatric literature.

BACKGROUND: the available studies on Hurthle cell carcinoma (HCC) in pediatric age are scarce and based on isolated case reports. Aims of the present study were to review the available pediatric literature on HCC (2000-2019), to describe the cohort of children with this cancer histotype, and to estimate its relative prevalence in pediatric age. PROCEDURE: We retrospectively reconstructed an HCC course in five patients < 19 years who were identified in our departments during the period 2000-2019, and we reviewed the available pediatric studies on this differentiated thyroid cancer (DTC) variant. RESULTS: HCC occurred with a relative prevalence of 5.8% at a median chronological age of 12.5 years. None of HCC patients exhibited, at diagnosis, thyroid dysfunction, extensive lateral neck disease, or distant metastases, and all showed a persistent remission over time. Three patients showed, at diagnosis, antecedents of other diseases (Hashimoto's thyroiditis, neurofibromatosis type 1, and osteosarcoma). CONCLUSIONS: (1) In childhood, the relative prevalence of HCC among different thyroid cancer histotypes is 5.8%, that is close to the one previously reported both in the general population and in other less numerous children's cohorts; (2) HCC may develop even early, at the age of 7; (3) in childhood, HCC does not seem to have a more aggressive behavior when compared with other DTC histotypes; (4) antecedents of other diseases are not infrequent in the history of children with HCC.

Influence of Hashimoto Thyroiditis on the Development of Thyroid Nodules and Cancer in Children and Adolescents.

It is unclear whether patients with Hashimoto thyroiditis (HT) are predisposed to develop thyroid nodules and/or thyroid cancer. The objective of our study was therefore to assess the prevalence of thyroid nodules and/or cancer in patients with HT and to look for possible prognostic factors. A retrospective survey of 904 children/adolescents with HT (709 females, 195 males) regularly followed in nine Italian centers of pediatric endocrinology was performed. Median period of follow-up was 4.5 years (1.2 to 12.8 years). We evaluated free T4, TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies, and thyroid ultrasound yearly. One hundred seventy-four nodules were detected, with an annual incidence rate of 3.5%. Ten nodules were malignant (8 papillary and 2 papillary follicular variant), giving a 5.7% prevalence of cancer among patients with nodules. The severity of hypoechogenity at ultrasound, TPOAb, and free T4 serum concentrations were predictive for the appearance of new nodules. Furthermore, a positive correlation was observed between TPOAb titer and the development of thyroid cancer. In conclusion, HT seems to influence the development of thyroid nodules, but not cancer in children and adolescents.

Thyroid function in patients with Prader-Willi syndrome: an Italian multicenter study of 339 patients.

Background Prader-Willi syndrome (PWS) is a genetic disorder due to loss of expression of paternally transcribed genes of the imprinted region of chromosome 15q11-13. PWS is characterized by peculiar signs and symptoms and many endocrine abnormalities have been described (growth hormone deficiency, hypogonadotropic hypogonadism). The abnormalities of thyroid function are discussed in literature and published data are discordant. The aim of our study was to report the thyroid function in patients with PWS to identify the prevalence of thyroid dysfunction. Methods Thyroid function tests were carried out in 339 patients with PWS, aged from 0.2 to 50 years. A database was created to collect personal data, anthropometric data, thyroid function data and possible replacement therapy with L-thyroxine. Subjects were classified according to thyroid function as: euthyroidism (EuT), congenital hypothyroidism (C-HT), hypothyroidism (HT - high thyroid-stimulating hormone [TSH] and low free thyroxine [fT4]), central hypothyroidism (CE-H - low/normal TSH and low fT4), subclinical hypothyroidism (SH - high TSH and normal fT4), and hyperthyroidism (HyperT - low TSH and high fT4). Results Two hundred and forty-three out of 339 PWS patients were younger than 18 years (71.7%). The prevalence of thyroid dysfunction was 13.6%. Specifically, C-HT was found in four children (1.18%), HT in six patients (1.77%), CE-H in 23 patients (6.78%), SH in 13 patients (3.83%), and HyperT in none. All other subjects were in EuT (86.4%). Conclusions Hypothyroidism is a frequent feature in subjects with PWS. Thyroid function should be regularly investigated in all PWS patients both at the diagnosis and annually during follow-up.

Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation.

OBJECTIVE: Thyroid function may recover in patients with Hashimoto's thyroiditis (HT). DESIGN: To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. SETTING: Nine Italian pediatric endocrinology centers. PATIENTS: 148 children and adolescents (25 m and 123 f) with HT on treatment with l-thyroxine for at least one year. INTERVENTION AND MAIN OUTCOME MEASURE: Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. RESULTS: At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5%) patients, after 6 months in 13 patients (6.99%), after 12 months in 12 patients (8.6%), and after 24 months in an additional 3 patients (3.1%). At 24 months, 34 patients (34.3%) still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. CONCLUSIONS: This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level <10 U/L at the time of diagnosis should be considered.

The Evolution of Thyroid Function after Presenting with Hashimoto Thyroiditis Is Different between Initially Euthyroid Girls with and Those without Turner Syndrome.

AIM: To prospectively investigate, during a 5-year follow-up, whether the prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS. DESIGN: In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid functional test results at HT diagnosis, we followed up the evolution of thyroid status over time. RESULTS: At the end of follow-up, the TS girls exhibited higher TSH levels, lower fT4 levels, and lower prevalence rates of both euthyroidism and subclinical hypothyroidism, but higher prevalence rates of both overt hypothyroidism and hyperthyroidism, irrespective of the karyotype. CONCLUSIONS: An association with TS is able to impair the long-term prognosis of thyroid function in girls with HT. Such an effect occurs irrespective of thyroid functional test results at HT diagnosis and is not necessarily linked with a specific karyotype.

Five-Year Prospective Evaluation of Thyroid Function Test Evolution in Children with Hashimoto's Thyroiditis Presenting with Either Euthyroidism or Subclinical Hypothyroidism.

BACKGROUND: Whether the course of thyroid function in Hashimoto's thyroiditis (HT) differs in children who present with either euthyroidism or subclinical hypothyroidism (SH) has been incompletely investigated. AIM: Using a five-year prospective evaluation of 234 children with HT and no prognostic risk factors, this study investigated whether the evolution of the thyroid status is influenced by the biochemical pattern at initial diagnosis. RESULTS: In the entire series, thyrotropin values significantly increased during follow-up, while free thyroxine values decreased and the proportion of children with a thyroid dysfunction increased from 27.3% to 47.4% (p = 0.0001). An increasing proportion of cases with severe thyroid dysfunction was identified, especially among the 64 patients presenting with SH (group B), but also among the 170 children presenting with euthyroidism (group A) at initial diagnosis. At the end of follow-up, the prevalence of children with overt hypothyroidism was 12.3% in group A compared with 31.2% in group B (p = 0.0007). In the overall population, however, the majority of patients (52.6%) exhibited biochemical euthyroidism at the end of follow-up. CONCLUSIONS: Children with HT may develop a deterioration of thyroid status during the first five years of disease. Such a trend may be observed, even in the patients who initially present with a mild biochemical picture (either SH or euthyroidism). A total of 57.1% of initially euthyroid children remain euthyroid, and 40.6% of patients with initial SH normalize thyroid function within five years after HT diagnosis. The patients presenting with SH are more prone to the risk of developing severe thyroid dysfunction over time.

In children with autoimmune thyroid diseases the association with Down syndrome can modify the clustering of extra-thyroidal autoimmune disorders.

BACKGROUND: It is known that the association with Down syndrome (DS) can affect the phenotypic expression of autoimmune thyroid diseases (AITDs), whilst is unknown whether the clustering of extra-thyroidal autoimmune diseases (ETADs) may also be atypical in DS children. METHODS: The aim of this study was to investigate the clustering of ETADs in 832 children with AITDs divided in two groups with or without DS (A and B, respectively) and in four subgroups of patients aged either <6 or ≥6 years. RESULTS: The rate of children with ETADs was significantly higher in Group A; in particular, alopecia areata (p=0.00001) and vitiligo (p=0.00001) were found more often in Group A irrespective of age, whilst the distribution of T1 diabetes mellitus was not different in the two groups. Celiac disease prevalence was significantly higher in DS patients only in the older subgroup. CONCLUSIONS: The association with DS may be able to modify the clustering of ETADs in the children with AITDs by favoring the aggregation of some specific diseases such as alopecia areata and vitiligo.

Ultrasound surveillance for radiation-induced thyroid carcinoma in adult survivors of childhood cancer.

INTRODUCTION: The optimal surveillance strategy to screen for thyroid carcinoma childhood cancer survivors (CCS) at increased risk is still debated. In our clinical practice, beside neck palpation we routinely perform thyroid ultrasound (US). Here we describe the results obtained using this approach. METHODS: We considered all CCS referred to our long term clinic from November 2001 to September 2014. One hundred and ninety-seven patients who had received radiation therapy involving the thyroid gland underwent US surveillance. Thyroid US started 5 years after radiotherapy and repeated every 3 years, if negative. RESULTS: Among 197 CCS previously irradiated to the thyroid gland, 74 patients (37.5%) developed thyroid nodules, and fine-needle aspiration was performed in 35. In 11 patients the cytological examination was suspicious or diagnostic for malignancy (TIR 4/5), whereas a follicular lesion was diagnosed in nine. Patients with TIR 4/5 cytology were operated and in all cases thyroid cancer diagnosis was confirmed. The nine patients with TIR 3 cytology also underwent surgery and a carcinoma was diagnosed in three of them. Prevalence of thyroid cancer was 7.1%. Tumour size ranged between 4 and 25 mm, but six (43%) were classified T3 because of extra-thyroidal extension. Six patients had nodal metastases; in eight patients the tumour was multifocal. At the time of the study all patients are disease free, without evidence of surgery complications. CONCLUSION: Applying our US surveillance protocol, the prevalence of radiation-induced thyroid cancer is high. Histological features of the thyroid cancers diagnosed in our cohort suggest that most of them were clinically relevant tumours.

Metamorphic thyroid autoimmunity in Down Syndrome: from Hashimoto's thyroiditis to Graves' disease and beyond.

BACKGROUND: It is known that Hashimoto's thyroiditis (HT) may progress to Graves' disease (GD) and that this phenomenon may be more frequent in the patients with Down syndrome (DS). AIMS: To shed light on the relationships between Down syndrome (DS) and metamorphic thyroid autoimmunity. PATIENTS AND METHODS: We reconstructed the conversion process from HT to GD in 12 DS children. All the data recorded at HT diagnosis and throughout the time interval from entry to GD presentation were retrospectively taken from patients' files, as well as those recorded at GD diagnosis and during the subsequent evolution. From GD diagnosis all patients underwent methimazole treatment, at a dose that was adjusted on the basis of clinical findings and thyroid tests. RESULTS: Time interval between HT and GD was not different in the seven patients who received during that time a L-thyroxine (L-T4) treatment than in those who were not treated. After methimazole onset all patients exhibited a prolonged remission of hyperthyroidism. In 8/12 patients this treatment is still being continued 2-7 years after its initiation. The mean methimazole dosage needed to maintain euthyroidism in these eight patients was 0.12 ± 0.02 mg/kg/day. In the remaining four patients methimazole was withdrawn from 1.9 to 7 years after its initiation and no relapses were recorded 2.0-2.1 years after its withdrawal. These patients developed, 0.1-0.3 years after methimazole withdrawal, a picture of overt hypothyroidism and needed treatment with L-T4, that is now being continued. No patients needed non-pharmacological therapies. CONCLUSIONS: 1) DS children might be incline to manifest over time a phenotypic metamorphosis from HT to GD and to subsequently fluctuate from hyperthyroidism to hypothyroidism; 2) in DS GD may have a mild biochemical and clinical course.

Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology.

AIM: To follow-up for 5 years thyroid status evolution in 127 girls with mild (TSH 5-10 mU/l) subclinical hypothyroidism (SH) of different etiologies. PATIENTS: The population was divided into two age-matched groups of 42 and 85 girls with either idiopathic (group A) or Hashimoto's thyroiditis (HT)-related SH (group B). Group B was in turn divided into three subgroups, according to whether SH was either isolated or associated with Turner syndrome (TS) or Down syndrome (DS). RESULTS: At the end of follow-up the rate of girls who became euthyroid was higher in group A (61.9% vs 10.6%), whereas the rates of patients who remained SH (55.3% vs 26.2%), became overtly hypothyroid (30.6% vs 11.9%) or required levothyroxine (l-T4) therapy (63.5% vs 23.8%) were higher in group B. Among the girls of group B, the risk of remaining SH or developing overt hypothyroidism was higher in the subgroups with TS or DS than in those with isolated HT. CONCLUSIONS: Long-term prognosis of mild and idiopathic SH is frequently benign, even though a l-T4 treatment may be needed throughout follow-up in almost a quarter of cases; long-term prognosis is different in the girls with either idiopathic or HT-related SH; and the association with either TS or DS impairs the outcome of HT-related SH.

Predictors of Malignancy in Children with Thyroid Nodules.

OBJECTIVE: To evaluate the diagnostic accuracy of clinical, laboratory, and ultrasound (US) imaging characteristics of thyroid nodules in assessing the likelihood of malignancy. STUDY DESIGN: Data from 184 children and adolescents with thyroid nodules were evaluated and compared with respective cytologic/histologic outcomes. A regression model was designed to assess the predictors associated with malignancy and to calculate ORs. RESULTS: Twenty-nine malignant neoplasms (25 papillary, 1 medullary, 3 Hurtle-cell carcinomas), 8 follicular adenomas, and 147 goitrous nodules (92 based on cytology, 55 on follow-up) were diagnosed. Fine-needle aspiration biopsy diagnostic accuracy, sensitivity, and specificity were 91%, 100%, and 88%, respectively. Male sex, compression symptoms, palpable lymphopathy, thyroid stimulating hormone concentration, microcalcifications, indistinct margins, hypoechoic US pattern, pathologic lymph node alterations, and increased intranodular vascularization were associated with malignancy. Regular margins, mixed echoic pattern, and peripheral-only vascularization were associated with benignity. During follow-up, nodule growth was associated with malignant disease, especially with levothyroxine therapy. A multivariate analysis confirmed that microcalcifications, hypoechoic pattern, intranodular vascularization, lymph node alterations, and thyroid stimulating hormone concentration were independent predictors of malignant outcome. For each predictor, we provide sensitivity, specificity, and positive/negative predictive values. CONCLUSIONS: Clinical, laboratory, and US features of nodules can be used as predictors of malignancy in children. Although none has diagnostic accuracy as high as that of fine-needle aspiration biopsy, these predictors should be considered in deciding the diagnostic approach of children with thyroid nodules.

Peculiarities of presentation and evolution over time of Hashimoto's thyroiditis in children and adolescents with Down's syndrome.

BACKGROUND: Studies concerning presentation and evolution over time of Hashimoto's thyroiditis (HT) in children with Down's syndrome (DS) are few, are based on limited study populations and do not include control HT groups without DS. The aim of this multicenter study was to shed further light on the relationships between DS and HT in childhood. DESIGN: In this retrospective study we compared thyroid function patterns at HT presentation in 2 groups of children with (group A) or without DS (group B), including 146 and 553 cases, respectively. All group A patients were subsequently re-examined after a median interval of 5.1 years in order to prospectively re-evaluate the evolution over time of thyroid function patterns in DS. RESULTS: In group A, female predominance, age at HT diagnosis and rates of familiarity for thyroid diseases were significantly lower than in group B, whilst the association with non-thyroidal autoimmune diseases was more frequent. The hormonal patterns that were most frequently found in the 2 groups were, respectively, subclinical hypothyroidism (in group A) and euthyroidism (in group B). Thyroid dysfunctions were, overall, more frequent in group A (86.3 vs 45.7%, p<0.001). At re-evaluation, DS children exhibited further deterioration of thyroid function with some cases switching towards Graves' disease (GD). CONCLUSIONS: HT in DS children: a) presents earlier, is not associated with female predominance and is more frequently associated with other autoimmune diseases; b) presents only very infrequently with a euthyroid hormonal profile; c) in a limited rate of cases switches with time to GD.

Levothyroxine requirement in congenital hypothyroidism: a 12-year longitudinal study.

The aim of the replacement therapy with levothyroxine in congenital hypothyroidism (CH) is to correct hypothyroidism and ensure normal growth and neuropsychological development. Few data are available about the appropriate dose during childhood and early adolescence; therefore, we performed a multicenter observational study in a large population of patients with CH to assess the required levothyroxine dose to obtain euthyroidism. We recruited 216 patients with permanent CH classified into three groups (agenesia, ectopia, and in situ gland) on the basis of the thyroid imaging. The levothyroxine dose was recorded at 6 and 12 months and then yearly until 12 years of age. The daily levothyroxine requirement progressively decreased during the follow-up, irrespective of etiology. It was significantly lower in patients with in situ gland than in patients with athyreosis during the entire study period and with ectopic gland from the age of 1 year. The levothyroxine requirement at 6 months of age was correlated with the requirement at each later time-point. The daily dose was modified less frequently in patients with in situ thyroid (36 %) than in patients with ectopic gland (41.4 %) or with athyreosis (43.6 %). Patients with in situ gland required a lower dose than the other two subgroups. The dose at 6 months seems predictive of the requirement until 12 years of age. Euthyroidism may be achieved in pre-school and in-school patients by 3-4 and 2-3 µg/kg/day (70-90 and 60-80 µg/m(2)/day) of levothyroxine, respectively.

Meningiomas after cranial radiotherapy for childhood cancer: a single institution experience.

PURPOSE: Childhood cancer survivors (CCS) treated with cranial radiation therapy (CRT) are at risk of developing meningiomas. The aim of this study was to evaluate the cumulative incidence of meningiomas in a cohort of CCS who previously underwent CRT. METHODS: We considered all CCS who received CRT and were followed up at the "Transition Unit for Childhood Cancer Survivors" in Turin. Even though asymptomatic, they had at least one brain computed tomography or magnetic resonance imaging performed at a minimum interval of 10 years after treatment for pediatric cancer. RESULTS: We identified 90 patients (median follow-up 24.6 years). Fifteen patients developed meningioma (median time from pediatric cancer, 22.5 years). In four patients, it was suspected on the basis of neurological symptoms (i.e., headache or seizures), whereas all other cases, including five giant meningiomas, were discovered in otherwise asymptomatic patients. Multiple meningiomas were discovered in four CCS. Ten patients underwent surgical resection. An atypical meningioma (grade II WHO) was reported in four patients. One patient with multiple meningiomas died for a rapid growth of the intracranial lesions. A second neoplasm (SN) other than meningioma was diagnosed in five out of the 15 patients with meningioma and in ten out of the 75 CCS without meningioma. Cox multivariate analysis showed that the occurrence of meningioma was associated with the development of other SNs, whereas age, sex, or CRT dose had no influence. CONCLUSIONS: CCS at risk of the development of meningioma deserve close clinical follow-up, especially those affected by other SNs.

Underlying Hashimoto's thyroiditis negatively affects the evolution of subclinical hypothyroidism in children irrespective of other concomitant risk factors.

BACKGROUND: The pediatric literature does not contain any studies comparing the evolution of Hashimoto's thyroiditis (HT)-related subclinical hypothyroidism (SH) with idiopathic SH longitudinally. AIM AND DESIGN: In the present study, the two-year evolution of HT-related SH in 32 children with no concomitant risk factors (group A) was compared to that observed in 90 age-matched children with idiopathic SH (group B). The aim was to ascertain whether the association with HT could, per se, affect the evolution of thyroid status over time in SH children irrespective of other coexisting factors, such as thyromegaly, association with other autoimmune diseases, and/or concomitant therapies. RESULTS: During the two-year follow-up, the percentage of children whose thyrotropin (TSH) values increased >10 mIU/L was significantly higher in group A (p<0.0005), whereas the percentages of those who either maintained a stable TSH (5-10 mIU/L) or normalized the TSH (<5 mIU/L) were significantly higher in group B (p<0.025). Moreover, the percentage of children who developed a pathological thyroid enlargement during follow-up was significantly higher in group A (p<0.0005). CONCLUSIONS: The association with HT exerts a negative influence on the evolution over time of mild SH, irrespective of other concomitant risk factors. In children with mild and HT-related SH, the risk of a deterioration in thyroid status over time is high (53.1%), while the probability of spontaneous TSH normalization is relatively low (21.9%). In contrast, in children with mild and idiopathic SH, the risk of a deterioration in thyroid status over time is very low (11.1%), whereas the probability of spontaneous TSH normalization is high (41.1%).

Prevalence of cardiovascular risk factors in long-term survivors of childhood cancer: 16 years follow up from a prospective registry.

BACKGROUND: Childhood cancer survivors (CCSs) have an increased risk of overweight and dyslipidaemia, but the distribution and the potential relationships between anticancer therapies and cardiovascular risk factors have been heterogeneously and not prospectively described. METHODS: All consecutive CCSs with primary cancer diagnosed between 1973-2007 and subsequently referred to our outpatient clinic were enrolled. Hypercholesterolaemia (total cholesterol >200 and/or low density lipoprotein (LDL)>160 mg/dl) was the primary end point, hypertriglyceridaemia (triglycerides >200 mg/dl) and body mass index >30 kg/m(2) the secondary end points. Cox multivariate adjustments were performed to account for differences in cancer and treatments. RESULTS: A total of 340 patients were included (197 male, 143 female; mean age at last follow-up 24.1 ± 3.2). The most common diagnosis were haematological malignancies (n = 227) and brain tumours (n = 51). After a median follow-up of 16.1 years, hypercholesterolaemia was diagnosed in 67 CCSs (20%), hypertriglyceridaemia in 20 CCSs (6%) and obesity in 28 CCSs (8%). Total body irradiation and growth hormone deficiency increased the risk of both hypercholesterolaemia (hazard ratio (HR) = 2.7; confidence interval (CI) 1.2-4.4 and HR = 2.3; CI 1.1-4.9; all p < 0.05) and hypertriglyceridaemia (HR = 6.5; CI 1.4-31 and HR = 7.2; CI 1.1-43; all p < 0.05). The risk of hypercholesterolaemia was also higher in CCSs who underwent autologous haematopoietic stem cell transplantation (HR = 3.2; CI 1.7-5.9; p < 0.001) or platinum-based chemotherapy (HR = 2.7; CI 1.5-4.9; p < 0.001), whereas a previous diagnosis of brain tumour (HR = 10; CI 1.2-45; p < 0.05) and anthracyclines exposure (HR = 1.3; CI 1.2-26; p < 0.05) significantly predicted obesity. CONCLUSION: CCSs show a high and variable risk for developing dyslipidaemia and obesity, depending on cancer diagnosis and treatments. Therefore, they need accurate and tailored control of their cardiovascular risk profile.

Growth impairment after TBI of leukemia survivors children: a model- based investigation.

BACKGROUND: Children receiving Total Body Irradiation (TBI) in preparation for Hematopoietic Stem Cell Transplantation (HSCT) are at risk for Growth Hormone Deficiency (GHD), which sometimes severely compromises their Final Height (FH). To better represent the impact of such therapies on growth we apply a mathematical model, which accounts both for the gompertzian-like growth trend and the hormone-related 'spurts', and evaluate how the parameter values estimated on the children undergoing TBI differ from those of the matched normal population. METHODS: 25 patients long-term childhood lymphoblastic and myeloid acute leukaemia survivors followed at Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital (Turin, Italy) were retrospectively analysed for assessing the influence of TBI on their longitudinal growth and for validating a new method to estimate the GH therapy effects. Six were treated with GH therapy after a GHD diagnosis. RESULTS: We show that when TBI was performed before puberty overall growth and pubertal duration were significantly impaired, but such growth limitations were completely reverted in the small sample (6 over 25) of children who underwent GH replacement therapies. CONCLUSION: Since in principle the model could account for any additional growth 'spurt' induced by therapy, it may become a useful 'simulation' tool for paediatricians for comparing the predicted therapy effectiveness depending on its timing and dosage.

Final height and body mass index in adult survivors of childhood acute lymphoblastic leukemia treated without cranial radiotherapy: a retrospective longitudinal multicenter Italian study.

BACKGROUND: Young adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with protocols including cranial radiotherapy demonstrate a persistent weight gain and reduced final height. Published reports on the effects on growth of different oncologic therapies are conflicting and difficult to interpret because they combined children treated with both cranial irradiation and multi-agent chemotherapy. Our study investigated the effect of chemotherapy alone on body mass index (BMI) and on growth at the achievement of final height in a homogeneous cohort of Italian childhood ALL survivors. METHODS: We retrospectively studied 162 Caucasian patients treated on the Italian Association of Pediatric Hematology and Oncology protocols without radiotherapy between 1989 and 2000 at five Italian centers with 107 inclusions (58 males). Height- and BMI-standard deviation score (SDS) were collected at diagnosis of ALL, at the end of treatment and at the achievement of final height. Changes in height SDS and BMI SDS with time were analyzed using dependent sample Student's t-test. RESULTS: A significant reduction of height-SDS was documented during treatment in both genders. This reduction of height-SDS was not followed by an appropriate catch-up growth, despite the achievement of a mean final height within the normal range. At diagnosis females showed a lower mean BMI-SDS than males. During treatment, in the whole population, BMI-SDS increased significantly. After it, while males lost BMI-SDS, females showed its persistent increase. CONCLUSIONS: Survivors of childhood ALL generally seemed to achieve a normal final height with a BMI within the normal range. These parameters appeared to be only minimally affected by chemotherapy. Nevertheless, height catch-up growth was not completed after chemotherapy in both genders and all patients experienced an increase of BMI-SDS during chemotherapy that only females seemed to conserve until the achievement of final height.