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.

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.

Graves disease in children: thyroid-stimulating hormone receptor antibodies as remission markers.

OBJECTIVE: To evaluate clinical and biochemical features of 115 children (98 female, mean age 11.3 ± 3.5 years) with Graves disease to identify possible determinants of remission. STUDY DESIGN: We defined as positive outcome the improvement of clinical features and restoration of euthyroidism or induction of hypothyroidism after antithyroid drug (ATD) therapy and as negative outcome hyperthyroidism persistent over 2 years of ATD therapy or relapsed after ATD withdrawal. RESULTS: Thirty-eight children (33%) had remission after 2 years of ATD therapy. The absence of goiter at diagnosis was correlated with a better outcome. Median thyroid-stimulating hormone receptor antibody (TRAb) values at diagnosis were significantly lower in patients with a positive outcome (P = .031). We found a significant relationship between the time required for TRAb normalization and the patient outcome; TRAb normalization within 1 year from time of Graves disease diagnosis was significantly more common among patients with a positive outcome (P < .0001), and the mean time for TRAb normalization was significantly shorter in patients with a positive outcome (1.3 ± 0.8 years) compared with that observed in patients with a negative outcome (2.5 ± 2.7 years, P = .026). CONCLUSIONS: Although no clinical variable investigated is constantly associated with a definite outcome, the absence of goiter at the diagnosis may be associated with a better outcome. The most relevant predictor of Graves disease outcome was serum level; TRAb at time of Graves disease diagnosis less than 2.5 times the upper reference limit, TRAb normalization during ATD, and TRAb normalization timing each may predict positive outcomes. These results may have a role in the empiric clinical management of pediatric patients with Graves disease.

α-Fetoprotein assay on dried blood spot for hepatoblastoma screening in children with overgrowth-cancer predisposition syndromes.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) and hemihyperplasia (HH) are overgrowth conditions with predisposition to hepatoblastoma for which early diagnosis patients undergo cancer screening based on determination of the tumor marker α-fetoprotein (αFP). Repeated blood draws are a burden for patients with consequent compliance issues and poor adherence to surveillance protocol. We sought to analyze feasibility and reliability of αFP dosage using an analytical micromethod based on blood dried on filter paper (DBS). METHODS: Overall 143 coupled αFP determinations on plasma and DBS collected simultaneously were performed, of which 31 were in patients with hepatoblastoma predisposition syndromes and 112 were in controls. The plasma αFP dosage method was adapted to DBS adsorbed on paper matrix for newborn screening. RESULTS: There was strong correlation between plasmatic and DBS αFP (r2 = 0.999, P < 0.001). Cohen's k coefficient for correlation was 0.96 for diagnostic cut-off of 10 U/ml (P < 0.001), commonly employed in clinical practice. The measurements on plasma and DBS were highly overlapping and consistent. CONCLUSION: The DBS method allowed to dose αFP reliably and consistently for the concentrations commonly employed in clinical settings for the screening of hepatoblastoma, opening new scenarios about conducting cancer screening in overgrowth syndromes.

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.

Serum thyrotropin concentration in children with isolated thyroid nodules.

OBJECTIVE: To investigate the correlation between serum thyroid-stimulating hormone (TSH) concentration and nodule nature in pediatric patients with thyroid nodules, with the aim of identifying a marker able to differentiate benign and malignant nodules. STUDY DESIGN: This was a retrospective analysis of serum TSH concentrations in a multicentric case series of 125 pediatric patients with benign and malignant thyroid nodules. RESULTS: Of the 125 patients, 99 had benign thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2 follicular). Final diagnosis was based on surgery in 57 cases and on a benign cytology plus clinical follow-up in 68 cases. Serum TSH concentration was significantly higher in patients with thyroid cancer compared with those with benign nodules (3.23 ± 1.59 mU/L vs 1.64 ± 0.99 mU/L; P < .001). Binary logistic regression analysis revealed that serum TSH was the sole predictor of malignancy (P < .001). Dividing the patient cohort into 5 groups based on serum TSH quintiles (TSH cutoffs 0.40, 1.00, 1.50, 1.80, and 2.80 mU/L), we observed that cancer prevalence increased in parallel with serum TSH (P < .001), with respective rates of 0%, 4%, 16%, 32%, and 52% in the 5 quintile groups. CONCLUSION: Because cases with malignant nodules are most likely seen in the upper normal serum TSH range (ie, >2.8 mU/L), serum TSH concentration can serve as a predictor of thyroid cancer in pediatric patients with thyroid nodules and can inform the decision of when to submit patients to further investigation by cytology.

Central adrenal insufficiency in young adults with Prader-Willi syndrome.

OBJECTIVE: A high prevalence (60%) of central adrenal insufficiency (CAI) has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. We have assessed CAI in adults with PWS using the low-dose short synacthen test (LDSST). DESIGN: Basal cortisol and ACTH, and 30-min cortisol after the administration of 1 µg synacthen, were determined in 53 PWS adults (33 females). A peak cortisol value of ≥500 nmol/l was taken as normal. Hormonal profiles were analysed in relation to gender, genotype and phenotype. Deficient patients were retested by high-dose short synachten test (HDSST) or a repeat LDSST. RESULTS: Mean ± SD basal cortisol and ACTH were 336·6 ± 140·7 nmol/l and 4·4 ± 3·7 pmol/l respectively. Cortisol rose to 615·4 ± 135·0 nmol/l after LDSST. Eight (15·1%) patients had a peak cortisol response <500 nmol/l, with a lower mean ± SD (range) basal cortisol of 184·9 ± 32·0 (138·0-231·7) compared with 364·1 ± 136·6 (149·0-744·5) in normal responders (P < 0·001). Seven of the eight patients underwent retesting, with 4 (7·5%) showing persistent suboptimal responses. Basal and peak cortisol correlated in females (r = 0·781, P < 0·001). Logistic regression revealed that only female gender and baseline cortisol were predictors of cortisol peaks (adjusted R square 0·505). CONCLUSIONS: Although CAI can be part of the adult PWS phenotype, it has a lower prevalence (7·5%) than previously reported. Clinicians are advised to test PWS patient for CAI. Our study also shows that basal cortisol is closely correlated with adrenal response to stimulation, indicating that its measurement may be helpful in selecting patients for LDSST.

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.

The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto's thyroiditis and isolated hyperthyrotropinaemia: a 3-year follow-up.

OBJECTIVE: The natural history of Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors. DESIGN: This is retrospective cross-sectional study. PATIENTS: Three hundred and twenty-three patients with HT (88 boys and 235 girls) and 59 with IH (30 boys and 29 girls), mean age 9·9 ± 3·8 years were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but <100% of the upper limit (G1). All IH subjects had elevated TSH. Potential risk factors for thyroid failure were evaluated after 3 years and included the presence or familiarity for endocrine/autoimmune diseases, premature birth, signs and symptoms of hypothyroidism, TSH levels, antithyroid antibodies and thyroid volume. RESULTS: HT: Of those with HT, 170 G0 patients remained stable, 31 moved to G1 and 35 to G2 (hypothyroidism). Thirty-six G1 children moved to G0, 17 remained stable and 34 moved to G2. Of patients with IH: 23 normalized, 28 remained stable and eight became overtly hypothyroid. In patients with HT, the presence of coeliac disease, elevated TSH and thyroid peroxidase antibodies (TPOAb) increased the risk of developing hypothyroidism by 4·0-, 3·4- and 3·5-fold, respectively. The increase in TSH levels during follow-up was strongly predictive of the development of hypothyroidism. In patients with IH, no predictive factor could be identified. CONCLUSIONS: Coeliac disease, elevated TSH and TPOAb at presentation and a progressive increase in TSH are predictive factors for thyroid failure in HT patients.

Assessment of central adrenal insufficiency in children and adolescents with Prader-Willi syndrome.

OBJECTIVE: A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of Prader-Willi syndrome (PWS) children. These results were not confirmed in investigations with low [Low-Dose Tetracosactrin Stimulation Test (LDTST), 1 µg] or standard-dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS. DESIGN: Cross-sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre. PATIENTS: Eighty-four children with PWS. MEASUREMENTS: Assessment of adrenal response by morning cortisol and ACTH dosage, and 1-µg tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm; below this threshold, patients were submitted to a second test. Responses were correlated with the patients' clinical and molecular characteristics to assess genotype-phenotype correlation. RESULTS: Pathological cortisol peak responses to the LDTST were registered in 12 patients (14.3%) who had reduced basal (169.4 ± 83.3 nm) and stimulated (428.1 ± 69.6 nm) cortisol levels compared to patients with normal responses (367.1 ± 170.6 and 775.9 ± 191.3 nm, P < 0.001). Body mass index standard deviation score was negatively correlated with basal and peak cortisol levels (both P < 0.001), and the patients' ages (P < 0.001). In patients with deletion on chromosome 15, the cortisol peak was significantly lower than that in uniparental disomy (UPD) cases (P = 0.030). At multiple regression analysis, the predictors of peak response were basal cortisol, age, and UPD subclass (r(2) = 0.353, P < 0.001). Standard-dose (250 µg) tetracosactrin test confirmed CAI in 4/12 patients (4.8% of the cohort). CONCLUSIONS: Our results support the hypothesis that, albeit rare, CAI may be part of the PWS in childhood.

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.

Ultrasound screening for thyroid carcinoma in childhood cancer survivors: a case series.

CONTEXT: Childhood cancer survivors need regular monitoring into young adulthood and beyond, because they are at risk for developing late-onset complications of cancer therapy, including second malignancies. OBJECTIVE: This study focuses on the use of thyroid ultrasound to screen for thyroid carcinoma in a population of childhood cancer survivors. PATIENTS: A total of 129 subjects who had received radiotherapy to the head, neck, or upper thorax for a pediatric cancer were studied in the setting of a long-term follow-up unit. DESIGN: Thyroid ultrasound usually began 5 yr after radiotherapy and was repeated every third year, if negative. Median follow-up time since childhood cancer diagnosis was 15.8 yr (range 6.1-34.8 yr). Solid thyroid nodules were found in 35 patients. Fine-needle aspiration was performed in 19 patients, of which 14 had nodules above 1 cm. MAIN OUTCOME MEASURE: The main outcome measure was the finding of not palpable thyroid cancers. RESULTS: Cytological examination of specimens diagnosed papillary carcinoma in five patients who underwent surgery. The cytological diagnosis of papillary thyroid carcinoma was confirmed in all cases by histological examination. Notably, only two of these patients had palpable nodules; the other three were smaller than 1 cm and were detected only by ultrasound. However, histological examination showed nodal metastases in two of these. CONCLUSIONS: Although ultrasound screening for thyroid cancer in the general population is not cost effective and could lead to unnecessary surgery, due to false positives, we believe that in childhood cancer survivors who received radiotherapy involving the head, neck, or upper thorax, it would be worthwhile.

The Italian National Survey for Prader-Willi syndrome: an epidemiologic study.

Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4-46.7). Two hundred thirty-eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity-related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death.

Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia.

BACKGROUND: A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM). PROCEDURES: Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1-2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period. RESULTS: All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7-14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression. CONCLUSIONS: High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.

Four new cases of PHACES syndrome: variable phenotypic expression and endocrine features.

AIM: PHACES syndrome is a neurocutaneous condition characterized by the coexistence of large facial haemangiomas and at least one feature among posterior fossa malformations, cardiac and arterial anomalies, eye defects and sternal clefting. We review and discuss the phenotypes and the endocrine aspects of PHACES syndrome, hypothesizing that endocrine anomalies, although rare, could be considered as feature of the disease. METHODS: We described four new cases representative of the wide variable phenotype of this syndrome, commenting on the possible phenotypic expression. RESULTS: Two children displayed endocrine anomalies, sporadically described among PHACES subjects. One of them developed a transient hyperthyreotropinemia induced by interferon alpha-2alpha treatment for a giant facial haemangioma, while the second presented with congenital hypothyroidism with an in situ thyroid gland, a trait previously unreported in the syndrome. CONCLUSION: PHACES syndrome has a wide variable phenotypic expression and endocrine anomalies, especially hypothyroidism, may represent a trait of the syndrome and should be always investigated.

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.