Kamran S.C.,Thyroid Section |
Marqusee E.,Thyroid Section |
Kim M.I.,Thyroid Section |
Pou K.,Harvard University |
And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013
Context: Thyroid nodule size is routinely measured, although its impact on thyroid cancer risk is unclear. Objective: Our objective was to evaluate the association of nodule size upon cancer risk. Design, Setting, and Patients: We conducted a retrospective cohort analysis at an academic hospital with 4955 consecutive patients evaluated between 1995 and 2009. Intervention: Ultrasound and ultrasound-guided fine-needle aspiration of nodules>1 cm was done. Indeterminate and malignant nodules were referred for surgery, and histopathology was reviewed. Main Outcome Measure: The presence and histological subtype of cancer was evaluated. Results: Of 7348 evaluated nodules, 927 (13%) were cancerous. Of those 1.0 to 1.9 cm in diameter, 10.5% were cancerous. In contrast, of those >2.0 cm, 15% were cancerous (P < .01). However, nodules 2.0 to 2.9, 3.0 to 3.9, and >4 cm were cancerous in 14%, 16%, and 15% of cases (P = .14), respectively, demonstrating no graded increase in risk beyond the 2-cm threshold. When malignant, the proportion of papillary carcinoma decreased (nodules 1.0-1.9 cm, 92% of cases; 2.0-2.9 cm, 88%; 3.0-3.9 cm, 83%; >4 cm, 74% [P < .01]), while follicular carcinoma increased (1.0-1.9 cm, 6%; 2.0-2.9 cm, 7%; 3.0-3.9 cm, 12%; >4 cm, 16% [P < .01]) as nodules enlarged. Nodules size did not influence cytology distribution or risk of false-negative aspirates. Conclusions: Increasing thyroid nodule size impacts cancer risk in a nonlinear fashion. A threshold is detected at 2.0 cm, beyond which cancer risk is unchanged. However, the risk of follicular carcinomas and other rare thyroid malignancies increases as nodules enlarge. Copyright © 2013 by The Endocrine Society.
Luongo C.,Thyroid Section |
Martin C.,Thyroid Section |
Vella K.,Harvard University |
Marsili A.,Thyroid Section |
And 6 more authors.
Endocrinology | Year: 2015
The type 2 iodothyronine deiodinase (D2) is essential for feedback regulation of TSH by T4. We genetically inactivated in vivo D2 in thyrotrophs using a mouse model of Cga-driven cre recombinase. Pituitary D2 activity was reduced90%in the Cga-cre D2 knockout (KO) mice compared with control Dio2fl/fl mice. There was no growth or reproductive phenotype. Basal TSH levels were increased 1.5- to 1.8-fold, but serum T4 and T3 were not different from the controls in adult mice. In hypothyroid adult mice, suppression of TSH by T4, but not T3, was impaired. Despite mild basal TSH elevation, the TSH increase in response to hypothyroidism was 4-fold reduced in the Cga-cre D2KO compared with control mice despite an identical level of pituitary TSH α- and α-subunit mRNAs. In neonatal Cga-cre D2KO mice, TSH was also 2-fold higher than in the controls, but serum T4 was elevated. Despite a constant TSH, serum T4 increased 2-3-fold between postnatal day (P) 5 and P15 in both genotypes. The pituitary, but not cerebrocortical, D2 activity was markedly elevated in P5 mice decreasing towards adult levels by P17. In conclusion, a congenital severe reduction of thyrotroph D2 causes a major impairment of the TSH response to hypothyroidism. This would be deleterious to the compensatory adaptation of the thyroid gland to iodine deficiency. Copyright © 2015 by the Endocrine Society.
Frates M.C.,Harvard University |
Marqusee E.,Thyroid Section |
Benson C.B.,Harvard University |
Alexander E.K.,Thyroid Section
Journal of Ultrasound in Medicine | Year: 2013
Objectives: To describe the sonographic characteristics of subacute granulomatous (De Quervain) thyroiditis. Methods: We retrospectively identified all patients at our institution during the last 11 years who had thyroid sonography with findings suggestive of subacute granulomatous thyroiditis. We then reviewed clinical data and laboratory results to establish the clinical diagnosis. A final diagnosis of subacute granulomatous thyroiditis was made on the basis of clinical symptoms, suppressed thyrotropin, an elevated erythrocyte sedimentation rate, and/or reduced or absent radionuclide uptake while hyperthyroid. Results: Our study population consisted of 35 patients. Twenty-seven patients (79.4%) met clinical criteria for subacute thyroiditis. Symptoms included neck pain in 26 of 27 patients with subacute thyroiditis. The erythrocyte sedimentation rate ranged from 22 to 101 mm/h. In 21 cases (77.8%), sonography revealed focal, poorly defined, nonovoid areas of decreased echogenicity. Findings were bilateral in 16 patients and unilateral in 5. In the remaining 6, the gland or an entire lobe was diffusely heterogeneous. Color Doppler interrogation was performed in 20 patients. Flow was decreased to the sonographically abnormal areas in 19 (95%) and slightly increased in 1 patient. In all 9 patients who underwent radionuclide scanning, focal defects or large areas of decreased or absent uptake were found during the time of suppressed thyrotropin. Enlarged lymph nodes were noted in 16 patients (59.3%). Conclusions: The positive predictive value of sonography for diagnosing subacute granulomatous thyroiditis is 79.4%. The most common sonographic appearance is poorly defined regions of decreased echogenicity with decreased vascularity in the affected areas. © 2013 by the American Institute of Ultrasound in Medicine.
Nou E.,Thyroid Section |
Kwong N.,Thyroid Section |
Alexander L.K.,Thyroid Section |
Cibas E.S.,Harvard University |
And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Introduction: The optimal timing for repeat evaluation of a cytologically benign thyroid nodule greater than 1 cm is uncertain. Arguably, the most important determinant is the disease-specific mortality resulting from an undetected thyroid cancer. Presently there exist no data that evaluate this important end point. Methods: We studied the long-term status of all patients evaluated in our thyroid nodule clinic between1995and2003withinitiallybenignfine- needleaspiration(FNA)cytology. Thefollow-upinterval wasdefinedfromthe time of the initialbenignFNAtoanyoneof the following factors: thyroidectomy, death, or the most recent clinic visit documented anywhere in our health care system. We sought to determine the optimal timing for repeat assessment based on the identification of falsely benign malignancy and, most important, disease-related mortality due to a missed diagnosis. Results: One thousand three hundred sixty-nine patients with 2010 cytologically benign nodules were followed up for an average of 8.5 years (range 0.25-18 y). Thirty deaths were documented, although zero were attributed to thyroid cancer. Eighteen false-negative thyroid malignancies were identifiedandremoved at amean4.5 years (range 0.3-10 y) after the initial benign aspiration. None had distant metastasis, and all are alive presently at an average of 11 years after the initial falsely benign FNA. Separate analysis demonstrates that patients with initially benign noduleswho subsequently sought thyroidectomy for compressive symptoms did so an average of 4.5 years later. Conclusions: An initially benign FNA confers negligable mortality risk during long-term follow-up despite a low risk of identifying several such nodules as thyroid cancer. Because such malignancies appear adequately treated despite detection at a mean 4.5 years after falsely benign cytology, these data support a recommendation for repeat thyroid nodule evaluation 2-4 years after the initial benign FNA. Copyright © 2014 by the Endocrine Society.