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Maynard M.A.,Thyroid Program | Marino-Enriquez A.,Brigham and Womens Hospital | Fletcher J.A.,Brigham and Womens Hospital | Fletcher J.A.,Dana-Farber Cancer Institute | And 18 more authors.
New England Journal of Medicine | Year: 2014

Gastrointestinal stromal tumors (GISTs) are resistant to traditional chemotherapy but are responsive to the tyrosine kinase inhibitors imatinib and sunitinib.1 The use of these agents has improved the outcome for patients but is associated with adverse effects, including hypothyroidism. 2 Multiple mechanisms of this effect have been proposed, including decreased iodine organification3 and glandular capillary regression.4 Here we report the finding of consumptive hypothyroidism caused by marked overexpression of the thyroid hormone-inactivating enzyme type 3 iodothyronine deiodinase (D3) within the tumor. Affected patients warrant increased monitoring and may require supernormal thyroid hormone supplementation. Copyright © 2014 Massachusetts Medical Society.

Marsili A.,Brigham and Womens Hospital | Ramadan W.,Tufts University | Harney J.W.,Brigham and Womens Hospital | Mulcahey M.,Thyroid Program | And 10 more authors.
Endocrinology | Year: 2010

Because of its large mass, relatively high metabolic activity and responsiveness to thyroid hormone, skeletal muscle contributes significantly to energy expenditure. Despite the presence of mRNA encoding the type 2 iodothyronine-deiodinase (D2), an enzyme that activates T4 to T3, very low or undetectable activity has been reported in muscle homogenates of adult humans and mice. With a modified D2 assay, using microsomal protein, overnight incubation and protein from D2 knockout mouse muscle as a tissue-specific blank, we examined slow- and fast-twitch mouse skeletal muscles for D2 activity and its response to physiological stimuli. D2 activity was detectable in all hind limb muscles of 8- to 12-wk old C57/BL6 mice. Interestingly, it was higher in the slow-twitch soleus than in fast-twitch muscles (0.40 ± 0.06 vs. 0.076 ± 0.01 fmol/min·mg microsomal protein, respectively, P < 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P < 0.01) and 300% (P < 0.001) increase in D2 activity after 4 and 8 wk treatment with antithyroid drugs, respectively, with no changes in D2 mRNA. Neither D2 mRNA nor activity increased after an overnight 4 C exposure despite a 10-fold increase in D2 activity in brown adipose tissue in the same mice. The magnitude of the activity, the fiber specificity, and the robust posttranslational response to hypothyroidism argue for a more important role for D2-generated T3 in skeletal muscle physiology than previously assumed. Copyright © 2010 by The Endocrine Society.

Gupta A.,Thyroid Program | Ly S.,Thyroid Program | Castroneves L.A.,Thyroid Program | Frates M.C.,Brigham and Womens Hospital | And 26 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Thyroid cancer is the most common endocrine malignancy, but due to its rare occurrence in the pediatric population, the cancer risk of childhood thyroid nodules is incompletely defined, and optimal management of children with suspected nodules is debated. Objective: The aim was to study the presenting features and cancer risk of sporadic childhood thyroid nodules using a standardized clinical assessment and management plan. Design and Setting: Boston Children's Hospital and Brigham and Women's Hospital collaborated to create a multidisciplinary pediatric thyroid nodule clinic and implement a standardized assessment plan. Upon referral for a suspected nodule, serum TSH was measured and hypothyrotropinemic patientsunderwent123I scintigraphy. All othersunderwentthyroid ultrasonography,andif this confirmed nodule(s) ≥ 1 cm, ultrasound-guided fine-needle aspiration was performed. Medical records were retrospectively reviewed and compared to a control population of 2582 adults evaluated by identical methods. Patients and Results: Of 300 consecutive children referred for the initial evaluation of suspected thyroid nodules from 1997 to 2011, 17 were diagnosed with autonomous nodules by scintigraphy. Neck ultrasonography performed in the remainder revealed that biopsy was unnecessary in over half, either by documenting only sub-centimeter nodules or showing that no nodule was present. A total of 125 children met criteria for thyroid biopsy, which was performed without complication. Their rate of cancer was 22%, significantly higher than the adult rate of 14% (P = .02). Conclusions: Neck ultrasonography and biopsy were key to the evaluation of children with suspected thyroid nodules. Although the relative cancer prevalence of sonographically confirmed nodules ≥ 1 cm is higher in pediatric patients than adults, most children referred for suspected nodules have benign conditions, and efforts to avoid unnecessary surgery in this majority are warranted. Copyright © 2013 by The Endocrine Society.

Gupta A.,Thyroid Program | Ly S.,Thyroid Program | Castroneves L.A.,Thyroid Program | Frates M.C.,Brigham and Womens Hospital | And 30 more authors.
Journal of Pediatrics | Year: 2014

In a retrospective analysis of childhood thyroid nodules, 18% were radiographic incidentalomas and 41% were discovered by a clinician's palpation; 40% were discovered by patients' families. The latter group had the largest nodules and highest rates of thyroid cancer metastasis, suggesting opportunities for earlier detection through annual well-child visits. © 2014 Mosby Inc.

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