Pediatric thyroid nodules: ultrasonographic characteristics and inter-observer variability in prediction of malignancy.

BACKGROUND: Pediatric thyroid nodules, while uncommon, have high malignancy risk. The objectives of the study were (1) to identify sonographic features predictive of malignancy; (2) to create a prediction model; and (3) to assess inter-observer agreement among radiologists. METHODS: All available cases of thyroid nodules, surgically removed between 2000 and 2009. Three radiologists reviewed the sonographic images; 2 pathologists reviewed the tissue specimens. Adult prediction models were applied. Interobserver variability was assessed. RESULTS: Twenty-seven subjects, mean age 13.1±3.4 years, were included. Nineteen nodules were differentiated thyroid carcinomas. On multivariate analysis, size was the only significant predictor of malignancy. On recursive partitioning analysis, size >35 mm with microcalcification and ill-defined margins yielded the best prediction model. Radiologist inter-observer agreement regarding malignancy was moderate (κ=0.50). CONCLUSIONS: Larger size, microcalcifications and ill-defined margins on ultrasound demonstrate the best predictive model for malignancy in the pediatric population. Experienced pediatric radiologists demonstrate moderate inter-observer agreement in prediction of malignancy.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

BACKGROUND: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. METHODS: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. RESULTS: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. CONCLUSIONS: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

The role of ultrasound in the follow-up of children with differentiated thyroid cancer.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy with relatively good prognosis in children. However, unlike adults, children usually present with more advanced disease and have a higher local recurrence and distant metastases. Thus surveillance for recurrence is a major goal of long-term follow-up. OBJECTIVE: This retrospective study evaluates the diagnostic value of ultrasound (US) imaging in the post-therapy surveillance of children with differentiated thyroid cancer. MATERIALS AND METHODS: We reviewed the charts of 54 children (40 girls; mean age 14.3 ± 3.6 years) with differentiated thyroid cancer treated with total or near-total thyroidectomy. Forty children (29 girls and 11 boys) who had routine follow-up US examinations (112 studies) were included for the evaluation of US accuracy in the follow-up of pediatric differentiated thyroid cancer. Histopathology, stimulated thyroglobulin determination, post-therapy whole-body iodine scan and clinical follow-up were used as the standards of reference. RESULTS: Mean period of follow-up was 34 months. The frequency of recurrence was 42% (17/40). Seventeen percent of the children had lung metastases either at presentation or on follow-up. In all cases of lung metastases, stimulated thyroglobulin level was greater than 10 ng/ml. The sensitivity was 85.7%, specificity 89.4%, negative predictive value 94.4% and positive predictive value 75% for US in detecting loco-regional recurrence in follow-up studies of pediatric differentiated thyroid cancer. In 17.3% (18/104) of studies, the results of stimulated thyroglobulin and US were discordant. CONCLUSION: US showed very good sensitivity and specificity and a high negative predictive value for evaluation of loco-regional involvement in follow-up of pediatric differentiated thyroid cancer. Diagnostic whole-body iodine scan is indicated when serum anti-thyroglobulin Ab is high, or in cases of discordant findings between US and stimulated thyroglobulin levels, or when stimulated thyroglobulin levels are >10 ng/ml (to evaluate for lung metastasis).

Children with congenital hypothyroidism have similar neuroradiological abnormal findings as healthy ones.

OBJECTIVE: To assess the neuroradiological findings of children with congenital hypothyroidism (CHT) compared to healthy controls (HC). PATIENTS AND METHODS: Thirty children with CHT, mean age 12.5 ± 1.6 years, 14 (44.8%) males, were compared with 38 HC mean age 11.7 ± 1.7 years, 16 (45.7%) males. Clinical data were collected from medical charts and questionnaires seeking information on family history, birth and perinatal period events, medications, and overall health history. Neurocognitive function was assessed for global intelligence, visual and verbal memory, and executive functioning using standardized tests. Neuroimaging was performed using 1.5 T magnetic resonance imaging and assessed by two pediatric radiologists. RESULTS: Children with CHT had a similar proportion of incidental findings as did the children in the HC group, at 43.3% and 39.5%, respectively, P = 0.69. Abnormalities of the sellar region were reported in 13.3% of CHT group and 7.9% of HC group, P = 0.46. Other incidental findings included cerebellar ectopia, choroidal fissure and pineal cysts, and multiple increased signal intensity foci. Neuroradiological findings were not associated with clinical and neurocognitive abnormalities. CONCLUSION: Neuroimaging of children with CHT demonstrated a similar incidence of structural abnormalities as in the healthy population. There is no association between those findings and neurocognitive function.

Thyroid cancer in childhood: a retrospective review of childhood course.

BACKGROUND: Thyroid cancer (TC) is an uncommon childhood malignancy, but the incidence may be increasing. Recent American Thyroid Association guidelines focus primarily on adult data. Natural history studies of TC in childhood are important to determine outcomes. The objectives of this study were to describe the demographics and outcomes in children with TC treated at The Hospital for Sick Children, Toronto, from 1983 to 2006. We hypothesized that childhood TC was increasing at our institution. METHODS: Cases of papillary TC (PTC) (including follicular variant PTC) and follicular TC (FTC) were identified from pathology databases. Chart review was performed, and data were extracted on clinical, treatment, and outcome variables. RESULTS: Sixty-one cases were identified, and complete data were available in 54, including 36 girls and 18 boys. There was no statistical change in numbers of cases diagnosed yearly during the study period. Younger children were more likely to have metastases at presentation or during follow-up. Pathological TC diagnosis included 40 PTC, 1 diffuse-sclerosing papillary, 7 follicular variant PTC, and 6 FTC. There was no difference in pathology findings between children less than or greater than 10 years old. Five patients had a history of previous malignancy, and five had a history of previous thyroid conditions. Three patients were born in areas of high TC endemnicity. Twenty-three patients had thyroiditis on pathology examination. All patients underwent total thyroidectomy, and 53/54 patients received therapeutic radioactive iodine ablation. Twenty-seven patients had metastases at presentation (19 lymph nodes only, 2 lung only, and 6 lymph node and distant) and 6 developed distant metastases during follow-up (3 lung, 2 thymus, and 1 paraspinal). Male sex was associated with development of metastases during follow-up. On multiple regression, tumor size was predicted positively by PTC but not by age, sex, or metastases at presentation or during follow-up. CONCLUSION: We did not find evidence of increasing numbers of cases of TC diagnosed yearly during the study period, or difference in tumor aggressiveness, or between outcomes in children aged less than or greater than 10 years. Children with metastases at presentation or during follow-up were likely to be younger than children without metastases. There is a need for prospective, collaborative multicenter studies of TC.

Primary amenorrhea as a manifestation of polycystic ovarian syndrome in adolescents: a unique subgroup?

OBJECTIVE: To compare clinical and metabolic features of adolescents having primary amenorrhea (PA) and polycystic ovarian syndrome (PCOS) with those having oligomenorrhea or secondary amenorrhea (OM/SA) and PCOS. DESIGN: Retrospective case-control study. SETTING: Endocrine Gynecology Clinic at The Hospital for Sick Children, Toronto, Ontario, Canada. PATIENTS: Girls and young women aged 14 to 18 years having PA and PCOS (n = 9) seen during a 2(1/2)-year period were compared with control subjects having OM/SA and PCOS (n = 18) randomly selected during the same period. INTERVENTION: Medical record review was performed to assess clinical, biochemical, and ultrasonographic measures, as well as response to a progesterone challenge. MAIN OUTCOME MEASURES: Differences in response to the progesterone challenge, hyperandrogenism, and the presence of features of the metabolic syndrome. RESULTS: Compared with adolescents having OM/SA, adolescents having PA demonstrated older age at pubarche, higher androstenedione levels, greater prevalence of family history of obesity, a tendency toward no withdrawal bleeding in response to the progesterone challenge, and more features associated with the metabolic syndrome (acanthosis nigricans, higher diastolic blood pressure, and lower high-density lipoprotein cholesterol level). No significant correlation was demonstrated between response to the progesterone challenge, metabolic features, and androstenedione levels. CONCLUSION: Adolescents with PA and PCOS exhibit increased features of the metabolic syndrome and higher androstenedione levels and may represent a more severe spectrum of a common condition.

Insulin analogues in children and teens with type 1 diabetes: advantages and caveats.

This article reviews the advantages to and caveats of the use of newer insulin formulations (insulin analogues) and regimens in children and teens who have type 1 diabetes, their affect on glycemic control, frequency of hypoglycemic events, daily insulin requirements, and adverse affects such as excessive weight gain, which provides a further major challenge in adolescents. We also address briefly the use of adjunctive agents in the treatment of type 1 diabetes in children and teens.

Symptomatic urinary tract infections following voiding cystourethrography.

The objective of this study was to assess the frequency of symptomatic urinary tract infections (UTIs) following voiding cystourethrography (VCUG) while using prophylactic antibiotics. Medical records of 421 patients who underwent a VCUG during a period of 4 years were reviewed. Three hundred forty-nine had a VCUG following a febrile UTI, and 72 had the test for evaluation of hydronephrosis. All received prophylactic antibiotics and were evaluated within 7-10 days following the VCUG. One hundred seventy-two children (41%) had an abnormal VCUG. Seven of 421 children (1.7%) had symptoms suggestive of UTI. Two had culture negative pyuria; one had Escherichia Coli UTI, and four had Pseudomonas aeruginosa UTI. On multivariate logistic regression analysis, the risk factors contributing to the development of UTI following VCUG were the presence of vesicoureteral reflux (VUR) and its severity (odds ratio [OR] 2.52; 95% confidence interval [CI] 2.24, 2.83, p =0.001; and OR 2.32; 95% CI 2.05,2.62, p =0.04, respectively). The incidence of VCUG-induced UTI in children receiving prophylactic antibiotic therapy is low. There is a relatively high rate of Pseudomonas UTI, especially in children with moderate to severe reflux. We recommend that children with symptoms suggesting a UTI following a VCUG should be treated for Pseudomonas aeruginosa pending culture results.

Congenital muscular dystrophy in Israeli families.

Twelve patients from 11 Israeli families with congenital muscular dystrophy were evaluated between 1991 and 2001. There were six males and six females, of whom six were merosin negative and six were merosin positive. Serum creatine kinase levels were highly elevated in the merosin-negative group. Four of the children were cognitively normal but nonambulant. Two had unusual clinical findings of severe cognitive and motor developmental dysfunction. Four infants in the merosin-positive group who had normal serum creatine kinase levels had early-onset severe motor weakness and died within the first year of life owing to ventilatory insufficiency. The other two were ambulant and had normal cognitive development and elevated serum creatine kinase levels. Noteworthy, two of the six children with merosin-negative congenital muscular dystrophy had cognitive impairment, and four of the six children with merosin-positive congenital muscular dystrophy had a severe form of the disease with ventilatory insufficiency and death during infancy.