Cydney Fenton

Over‐expression of hepatocyte growth factor/scatter factor (HGF/SF) and the HGF/SF receptor (cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma

The study determined if hepatocyte growth factor/scatter factor (HGF/SF) or the HGF/SF receptor (cMET) might be important for metastasis in thyroid cancer.

Differentiated Thyroid Carcinoma That Express Sodium-Iodide Symporter Have a Lower Risk of Recurrence for Children and Adolescents

The sodium-iodide symporter (NIS) is expressed by papillary (PTC) and follicular (FTC) thyroid carcinoma, and is essential for iodine uptake. We hypothesized that PTC and FTC with detectable NIS immunostaining would be more amenable to radioactive iodine (131I) treatment and follow a more benevolent course. To test this, we determined NIS expression by immunohistochemistry in 23 PTC, 9 FTC, and 12 benign thyroid lesions from children and adolescents. NIS expression was determined by two blinded examiners and graded as absent = 0, minimal = 1, moderate = 2, intense = 3, and very intense = 4. NIS was detected in 35% (eight of 23) of PTC, 44% (four of 9) of FTC, 25% (two of eight) of benign tumors, and 100% (four of four) of autoimmune lesions. The intensity of NIS expression was similar in PTC (0.61 ± 0.24), FTC (0.56 ± 0.24), and benign tumors (0.50 ± 0.33) but was more intense in autoimmune lesions (3.0 ± 0.7, p < 0.005). Distant metastases were found only among PTC with undetectable NIS (two of 15, 13%), and recurrence developed exclusively from PTC and FTC with undetectable NIS (four of 20, 20%versus zero of 12, p = 0.043). The dose of iodine 131 required to achieve remission in the five patients with PTC who had undetectable NIS (213.3 ± 53 mCi) was greater than that required by patients with similar age and extent of disease for whom NIS expression is unknown (109 ± 22 mCi, p = 0.06). We conclude that NIS expression is associated with a lower risk of recurrence for PTC and FTC of children and adolescents.

Nitrotyrosine, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) are increased in thyroid tumors from children and adolescents

Nitric oxide (NO) is a reactive cell signal that controls vascular tone and is generated by inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) NO synthase (NOS). We hypothesized that NO could be important for growth of thyroid tumors and tested this hypothesis, by staining 41 papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), and 15 benign thyroid lesions for iNOS, eNOS and nitrotyrosine (N-TYR). Staining intensity was determined by 2 blinded, independent examiners, and quantified from grade 1 (absent) to grade 4 (intense). Average N-TYR staining of benign adenomas (2.5±0.42, p=0.009), PTC (3.10±0.12, p=0.001), FTC (2.44±0.30, p=0.001), and autoimmune lesions (3.25±0.48, p=0.019) were greater than that of multinodular goiter (1.0 for all 3) and surrounding normal thyroid (1.1±0.1). Average iNOS staining of benign adenomas (2.6±0.37), PTC (2.7±0.16), FTC (2.4±0.26) and autoimmune lesions (3.5±0.29) were all greater than that of surrounding normal thyroid (1.1±0.1, p<0.008), but there were too few multinodular goiters to achieve a significant difference (no.=2, 3.0±1.0). Average eNOS staining of benign adenomas (2.9±0.40), multinodular goiters (3.5±0.5), PTC (3.24±0.18), FTC (3.5±0.50), and autoimmune lesions (2.8±0.6) were also greater than that of surrounding normal thyroid (mean= 1.4±0.2, p<0.001). N-TYR staining correlated with that of vascular endothelial growth factor (VEGF, r=0.36, p=0.007) and the number of lymphocytes/high power field (r=0.39, p=0.004). Recurrent disease developed only from carcinoma with moderate-intense N-TYR staining, but there were too few recurrent tumors to achieve statistical significance (p=0.08). We conclude that NO is produced by benign adenomas, PTC and FTC suggesting that NO could be important in vascularization of thyroid tumors and autoimmune thyroid diseases.

Pseudohypoparathyroidism Type 1a with Congenital Hypothyroidism

Pseudohypoparathyroidism type la (PHP-1a) is an uncommon disorder that results from an inactivating mutation in the GNAS gene. It can present with resistance to several hormones, in addition to parathyroid hormone (PTH). Patients may have the classic Albrights hereditary osteodystrophy (AHO) phenotype and can develop resistance to thyroid stimulating hormone (TSH), gonadotropins, growth hormone releasing hormone (GHRH), and other hormones that rely on the Gsalpha protein to regulate signal transmission at their receptors. We report two siblings with PHP-1a and congenital hypothyroidism. The patients were found to have a heterozygous mutation at nucleotide 305 in exon 4 (c305C-->A) of the GNAS gene, which has not been previously linked to congenital hypothyroidism.

Thyroglobulin messenger ribonucleic acid levels in the peripheral blood of children with benign and malignant thyroid disease

Reverse transcriptase–PCR has identified thyroglobulin mRNA (Tg mRNA) in peripheral blood of normal adults and adults with thyroid cancer. However, no children were studied. The primary objective of this study was to determine whether whole blood Tg mRNA levels differ between benign and malignant thyroid disease in children. The secondary goals were to determine whether whole blood Tg mRNA levels vary with age or pubertal development among children with thyroid disease. Whole blood Tg mRNA levels were determined in 38 children (29 girls, nine boys; median age, 14.5 y; range, 4.8–20.4 y) with benign and malignant thyroid disease and correlated with diagnosis, age, pubertal status, thyroid size, and serum levels of free thyroxine, TSH, and Tg protein. Tg mRNA levels ranged from 3.3 to 104 pg Eq/μg total thyroid RNA (mean, 28 ± 20.2 pg Eq/μg total thyroid RNA) and were similar in benign and malignant disorders (p = 0.67). However, in children with previously treated papillary thyroid cancer, Tg mRNA levels directly correlated with total body 131I uptake (p = 0.026) and serum Tg protein (p = 0.037). There was no difference between boys and girls, and no change with pubertal maturation. In children with benign thyroid disease, Tg mRNA levels correlated with serum TSH (p = 0.031), but not with diagnosis, age, Tanner stage, or thyroid size. We conclude that Tg mRNA levels are similar in children with benign and malignant thyroid disease and unchanged by age or pubertal status, but correlated with tumor burden in previously treated papillary thyroid cancer.

How Do the Results of the Diabetes Control and Complications Trial Relate to the Practice of Pediatrics: Who Should Have Intensive Management?

The DCCT showed that any improvement in glycemic control decreases the risk of long-term complications. Although expensive, time consuming, and associated with increased risks of hypoglycemia and obesity, improved glycemic control is of benefit as long as hypoglycemia is avoided. Specific HbA1c target levels must be individualized and age appropriate.

Endocrine emergencies : Recognizing signs and symptoms

Endocrine emergencies may present to the pediatric practitioner in the office setting in a variety of forms. Four of the more common pediatric endocrine emergencies (DKA, symptomatic hypoglycemia, adrenal insufficiency, and hypocalcemia) have been discussed here. The recommended approach to a child or adolescent with an endocrine emergency involves recognizing clinical disease, stabilizing the patient with basic and advanced life support intervention, and transferring the patient to a facility which can provide appropriate definitive care.

Over-Expression of c-MET Is Associated with Increased Recurrence in Childhood Thyroid Cancer

Over-Expression of c-MET Is Associated with Increased Recurrence in Childhood Thyroid Cancer