Marianna Rachmiel

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.

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.

Evidence-based review of treatment and follow up of pediatric patients with differentiated thyroid carcinoma.

Childhood onset differentiated thyroid cancer (DTC) is distinct from the adult-onset disease being more aggressive at the time of initial evaluation with a higher risk category for disease recurrence; however, it is ultimately less lethal. International groups have outlined consensus statements detailing follow up and management guidelines for adult DTC, but since disease progression and markers are significantly different in childhood DTC compared to adults, management protocols may differ. Unfortunately, there is no consensus regarding the means of follow up, timing and management strategy regarding pediatric DTC. We performed an evidence-based review of DTC in children targeted to address the following questions: What is the most appropriate initial treatment? What is the goal of thyroid hormone replacement management? What is the approach to follow-up of childhood DTC? and, How should tumor recurrence/persistence be assessed and treated? We conducted a literature search using PubMed, Cochrane databases, guidelines from various international groups, and studies pertaining to pediatric DTC management and outcome in order to answer these questions. We suggest a pre-set algorithm and approach for the management of children with DTC according to our review.

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.

Final height in children with idiopathic growth hormone deficiency treated with a fixed dose of recombinant growth hormone.

There is no consensus regarding the optimal dosing of recombinant human growth hormone (rhGH) for children with growth hormone deficiency (GHD). Our objective was to evaluate the final adult height (FAH) in children with idiopathic GHD treated with a fixed rhGH dose of 0.18 mg/kg/week. We reviewed all charts of patients with idiopathic GHD treated with rhGH since 1985 who reached FAH. Ninety-six patients were treated for an average of 5.4 years. The mean age was 11.9 years, the mean height –2.87 standard deviation score (SDS) and the mean FAH was –1.04 SDS. Females had a lower predicted adult height than males at the initiation of therapy (–2.0 vs. –1.01 SDS; p = 0.0087) but a higher FAH – predicted adult height (1.08 vs. 0.04 SDS; p = 0.0026). In multiple regression analysis, the FAH SDS was positively related to the midparental height SDS, the height SDS at GH initiation and growth velocity during the first year of therapy, and negatively correlated with peak GH and bone age at initiation (r2 = 0.51; p < 0.005). Treatment of children with idiopathic GHD with a fixed dose of 0.18 mg/kg/week rhGH is sufficient to reach FAH within 2 SDS of the normal population range (84%) with an average FAH within –0.5 SDS of midparental height.

Increase in the incidence of type 1 diabetes in Israeli children following the Second Lebanon War.

Type 1 diabetes is an autoimmune disease occurring in genetically susceptible individuals. The precipitating cause is unclear. Recently, the Second Lebanon War exposed a large civilian population in northern Israel to significant psychological stress in the form of repeated barrages of missile attacks.

Young patients with both type 1 diabetes mellitus and asthma have a unique IL-12 and IL-18 secretory pattern

Rachmiel M, Bloch O, Shaul AA, Ben‐Yehudah G, Bistritzer Z, Weintrob N, Ofan R, Rapoport MJ. Young patients with both type 1 diabetes mellitus and asthma have a unique IL‐12 and IL‐18 secretory pattern.

Evidence-Based Review of Bone Strength in Children and Youth With Cerebral Palsy

Children with cerebral palsy have various risk factors for compromised bone health. Evidence concerning their bone fragility is gathering; however, there is no consensus regarding risk factors, indications for evaluation, follow-up, or treatment. We performed an evidence-based review targeted to address the following questions concerning children with cerebral palsy: Is bone strength impaired and what are the risk factors? Are these children at increased risk for bone fractures? What are the relations between bone mineral density and fracture risk? What methods can be used for bone health assessment? How can bone strength be improved? Currently, the most acceptable method for evaluating bone status in children is dual-energy x-ray absorptiometry. Evidence demonstrates reduced bone mass in children with cerebral palsy; yet, no clear association with fractures. Preventive methods are suggested.

Detecting intentional insulin omission for weight loss in girls with type 1 diabetes mellitus.

OBJECTIVE Intentional insulin omission is a unique inappropriate compensatory behavior that occurs in patients with type 1 diabetes mellitus, mostly in females, who omit or restrict their required insulin doses in order to lose weight. Diagnosis of this underlying disorder is difficult. We aimed to use clinical and laboratory criteria to create an algorithm to assist in the detection of intentional insulin omission. METHOD The distribution of HbA1c levels from 287 (181 females) patients with type 1 diabetes were used as reference. Data from 26 patients with type 1 diabetes and intentional insulin omission were analysed. The Weka (Waikato Environment for Knowledge Analysis) machine learning software, decision tree classifier with 10-fold cross validation was used to developed prediction models. Model performance was assessed by cross-validation in a further 43 patients. RESULTS Adolescents with intentional insulin omission were discriminated by: female sex, HbA1c>9.2%, more than 20% of HbA1c measurements above the 90th percentile, the mean of 3 highest delta HbA1c z-scores>1.28, current age and age at diagnosis. The models developed showed good discrimination (sensitivity and specificity 0.88 and 0.74, respectively). The external test dataset revealed good performance of the model with a sensitivity and specificity of 1.00 and 0.97, respectively. DISCUSSION Using data mining methods we developed a clinical prediction model to determine an individuals probability of intentionally omitting insulin. This model provides a decision support system for the detection of intentional insulin omission for weight loss in adolescent females with type 1 diabetes mellitus.

Alpha-1 antitrypsin therapy is safe and well tolerated in children and adolescents with recent onset type 1 diabetes mellitus†

Alpha‐1 antitrypsin (AAT) has been shown to reduce pro‐inflammatory markers and protect pancreatic islets from autoimmune responses in recent studies. Our aim was to evaluate its safety and tolerability in three different doses, in a pediatric population with recent onset type 1 diabetes mellitus (T1DM).