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Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

Wright, Kyla; Fisher, Jason C.; Rothberger, Gary D.; Prescott, Jason D.; Allendorf, John D.; Patel, Kepal; Suh, Insoo
Background: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer"”Gallium-68 DOTATATE"”has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. Methods: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. Results: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. Conclusion: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.
SCOPUS:85175319745
ISSN: 0039-6060
CID: 5616582

Massive 4-Gland Parathyroid Hyperplasia Initially Detected as a Parathyroid Adenoma [Case Report]

Nicolich-Henkin, Sophie; Goldstein, Michael B; Roellke, Emma; Bilezikian, John P; Rothberger, Gary D
Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT), for which the only definitive treatment is surgery. Abnormalities in the parathyroid glands can be identified with various imaging modalities including ultrasound (US), sestamibi scan (MIBI), 4-dimensional computed tomography (4D-CT), and positron emission tomography/computed tomography (PET/CT). While it is not uncommon for parathyroid pathology to be undetected on imaging, this is more typical of low-volume hyperplasia and smaller-sized adenomas. We present the case of a 65-year-old man with PHPT who initially had a solitary parathyroid mass detected by US, but who was ultimately discovered to have massive PH with hyperplastic glands not visualized on US or MIBI. This atypical presentation may help guide providers in decisions on ordering and interpreting various imaging modalities for patients with PHPT. In this case, 4D-CT was the only modality in which large hyperplastic glands were identified, suggesting superior sensitivity. This case also highlights the importance of intraoperative parathyroid hormone testing to aid in diagnostic prediction.
PMCID:10768879
PMID: 38188905
ISSN: 2755-1520
CID: 5637092

Proportion of Malignancy and Evaluation of Sonographic Features of Thyroid Nodules Classified As Highly Suspicious Using ACR TI-RADS Criteria

Hussain, Najia; Goldstein, Michael B; Zakher, Mariam; Katz, Douglas S; Brandler, Tamar C; Islam, Shahidul; Rothberger, Gary D
OBJECTIVES/OBJECTIVE:The reported malignancy rate of highly suspicious thyroid nodules based on the ACR TI-RADS criteria (TI-RADS category 5 [TR5]) varies widely. The objective of our study was to determine the rate of malignancy of TR5 nodules at our institution. We also aimed to determine the predictive values of individual sonographic features, as well as the correlation of total points assigned to a nodule and rate of malignancy. METHODS:Our single-institution retrospective study evaluated 450 TR5 nodules that had cytology results available, in 399 patients over a 1-year period. Sonographic features and total TI-RADS points were determined by the interpreting radiologist. Statistical analyses included logistic regression models to find factors associated with increased odds of malignancy, and computing sensitivity, specificity, positive and negative predictive values of various individual sonographic features. RESULTS:Of the 450 nodules, 95 (21.1%, 95% exact confidence interval 17.4-25.2%) were malignant. Each additional TI-RADS point increased the odds of malignancy (adjusted odds ratio 1.35, 95% confidence interval 1.13-1.60, P < .001). "Very hypoechoic" was the sonographic feature with the highest specificity and positive predictive value for malignancy (95.5 and 44.8%, respectively), while "punctate echogenic foci" had the lowest positive predictive value (20.0%). CONCLUSIONS:The rate of malignancy of TR5 nodules at our institution was 21.1%, which is lower than other malignancy rates reported in the literature. The total number of points assigned on the basis of the TI-RADS criteria was positively associated with malignancy, which indicates that TR5 should be viewed as a spectrum of risk.
PMID: 36106704
ISSN: 1550-9613
CID: 5336322

The clinical significance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category 5 thyroid nodules: Not as risky as we think?

Wright, Kyla; Brandler, Tamar C; Fisher, Jason C; Rothberger, Gary D; Givi, Babak; Prescott, Jason; Suh, Insoo; Patel, Kepal N
BACKGROUND:Although the prevalence of thyroid nodules is high, few prove to be malignant. Based on sonographic features, the American College of Radiology Thyroid Imaging Reporting and Data System categorizes malignancy risk of thyroid nodules with associated management recommendations for each category level. Malignancy rates among nodules with a highly suspicious Thyroid Imaging Reporting and Data System category 5 warrant examination in the context of additional risk stratification tools, including cytopathology and molecular testing. METHODS:All patients who underwent fine-needle aspiration biopsy for Thyroid Imaging Reporting and Data System category 5 nodules from January 2018 to September 2021 in a large integrated academic health system were reviewed. Using the Bethesda System for Reporting Thyroid Cytopathology, categories V and VI were set as malignant. Molecular testing (ThyroSeq version 3; Rye Brook, NY) yielding ≥50% risk of malignancy was deemed positive and correlated with surgical pathology. RESULTS:A total of 496 Thyroid Imaging Reporting and Data System category 5 nodules were identified. On fine-needle aspiration cytopathology, 61 (12.3%) were malignant. The breakdown included Bethesda System for Reporting Thyroid Cytopathology I, 15 (3%); II, 362 (73%); III, 52 (10.5%); IV, 5 (1%); V, 6 (1.3%); and VI, 55 (11.1%). Of Bethesda System for Reporting Thyroid Cytopathology III/IV nodules with molecular testing (n = 53), 24.5% yielded positive results. In total, 42 (8.5%) nodules underwent surgical resection, most of which were Bethesda System for Reporting Thyroid Cytopathology VI (n = 26, 61.9%). Of excised nodules, 33 (78.6%) nodules were malignant, 6 (14.3%) benign, and 3 (7.1%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features. All Thyroid Imaging Reporting and Data System category 5 nodules with malignant cytology (Bethesda System for Reporting Thyroid Cytopathology V/VI) that underwent surgery were malignant on histopathology. On average, the total Thyroid Imaging Reporting and Data System points were higher in malignant nodules compared with benign (9.3 vs 7.3; P = .015). Moreover, benign nodules more frequently received Thyroid Imaging Reporting and Data System points when the radiologist was unable to determine composition or echogenicity (33% vs 3% among malignant nodules; P = .01). CONCLUSION/CONCLUSIONS:Thyroid Imaging Reporting and Data System category 5 designation in thyroid nodules is associated with a lower risk of malignancy than previously reported. Benign and malignant nodules with Thyroid Imaging Reporting and Data System category 5 designation have discrepancies in certain Thyroid Imaging Reporting and Data System characteristics and individual points assigned, which may offer an opportunity for quality improvement and standardization measures in ultrasound reporting practices.
PMID: 36511283
ISSN: 1532-7361
CID: 5379322

Utility of Thyroid Function Testing in the Inpatient Setting

Goldstein, Michael; Islam, Shahidul; Piccione, Julie; Migasiuk, Laura; Rothberger, Gary
BACKGROUND:Previous studies have reported low value of ordering inpatient thyroid function tests (TFTs), with few changes in clinical management resulting from these tests. This study was designed to evaluate how often testing TFTs during hospitalization leads to medication initiation or adjustment, and to determine if the frequency of medication initiation or adjustment differs based on the indication for testing. METHODS:This is a retrospective observational study of 2278 patients who had TFTs tested while admitted to an academic hospital during a 5-month period. Indications for ordering TFTs were determined by reviewing clinical documentation, and those with abnormal tests were reviewed to assess whether thyroid medication was initiated or adjusted. RESULTS:The percentage of abnormal TFTs that led to medication initiation or adjustment was 15.1%, 12.2%, and 6.0%, for those tested on the basis of history of functional thyroid disease, suspicion of thyroid dysfunction, and reasons not directly related to thyroid dysfunction, respectively. Overall, 63 patients were started on thyroid medication or had their thyroid medication dose adjusted, which represents 10.1% of those with abnormal TFTs and only 2.8% of those tested. CONCLUSION/CONCLUSIONS:Abnormal TFTs are common, but a disproportionate amount of tests are needed to find a small percentage of clinically significant thyroid dysfunction, of which only a low percentage lead to changes in management. Education on this topic should be provided to inpatient providers to limit thyroid function testing to instances in which they are clinically indicated and abnormal results would lead to changes in management.
PMID: 35793752
ISSN: 1530-891x
CID: 5280442

Correlation of hemoglobin A1c and outcomes in patients hospitalized with COVID-19

Patel, Amy J; Klek, Stanislaw P; Peragallo-Dittko, Virginia; Goldstein, Michael; Burdge, Eric; Nadile, Victoria; Ramadhar, Julia; Islam, Shahidul; Rothberger, Gary D
BACKGROUND:) level and poor outcomes in hospitalized patients with diabetes and COVID-19. METHODS:results for each patient were divided into quartiles; 5.1-6.7% (32-50 mmol/mol), 6.8-7.5% (51-58 mmol/mol), 7.6-8.9% (60-74 mmol/mol), and >9% (>75 mmol/mol). The primary outcome was in-hospital mortality. Secondary outcomes included admission to an intensive care unit, invasive mechanical ventilation, acute kidney injury, acute thrombosis, and length of hospital stay. RESULTS:Five hundred and six patients were included. The number of deaths within quartiles 1 through 4 were 30 (25%), 37 (27%), 34 (27%) and 24 (19%), respectively. There was no statistical difference in the primary or secondary outcomes between the quartiles except acute kidney injury was less frequent in quartile 4. CONCLUSIONS:should not be used for risk stratification in these patients.
PMCID:8286241
PMID: 34284145
ISSN: 1530-891x
CID: 4981152

Utility of thyroid function testing in the inpatient setting [Meeting Abstract]

Goldstein, M; Piccione, J; Migasiuk, L; Islam, S; Rothberger, G
Thyroid function tests (TFTs) are routinely checked in hospitalized patients with or without pre-existing thyroid disease, sometimes even without suspicion of thyroid derangement. Although alternative diagnoses may explain presentations, cultural norms often encourage routine assessment. The objective of this study was to evaluate whether routine measurement of TFTs is beneficial, unnecessary, or even harmful in cost-effective care for hospitalized patients. This is a retrospective observational study of 2278 patients admitted to an academic hospital over a 5.5-month period who had their TFTs checked. Chart notes were reviewed to evaluate for preadmission diagnosis of thyroid disease and clinical indications for ordering TFTs. Results of thyroid function testing were reviewed. Medical records of those with abnormal TFTs were reviewed to assess whether thyroid medication was initiated or adjusted. Of the thyroid function tests ordered, 20.1% were ordered due to suspicion of thyroid dysfunction, 20.8% due to history of thyroid disease, and 59.0% for reasons not directly related to thyroid dysfunction. 27.3% of those tested had abnormal results. The percentage of abnormal TFTs that led to medication initiation or adjustment was 15.1%, 12.1%, and 5.7%, for those tested on the basis of history of thyroid disease, suspicion of thyroid dysfunction, and reasons not directly related to thyroid dysfunction, respectively. Overall, 65 patients were started on thyroid medication or had the dosage of their thyroid medication adjusted, which represents 10.4% of those with abnormal TFTs and only 2.9% of those tested. Abnormal thyroid function test results are common, but a disproportionate amount of tests are needed to find a small percentage of clinically significant thyroid dysfunction, of which only a low percentage lead to changes in management. TFTs checked for reasons not directly related to thyroid dysfunction had the lowest percentage of results that led to medication initiation or adjustment, while those checked on the basis of history of thyroid disease had the highest. Education on this topic should be provided to inpatient providers to limit thyroid function testing to instances in which they are clinically indicated and abnormal results would lead to changes in management
EMBASE:636273775
ISSN: 1557-9077
CID: 5179412

Continuous Subcutaneous Insulin Infusions vs. Multiple Daily Injections of Insulin in Hospitalized Patients: Glycemic Trends in the First 24 Hours of Admission

Halstrom, Amanda; Moledina, Iram; Peragallo-Dittko, Virginia; Ancona, Karena; Islam, Shahidul; Klek, Stanislaw; Rothberger, Gary
BACKGROUND/UNASSIGNED:Continuous subcutaneous insulin infusion (CSII) is a common diabetes treatment modality. Glycemic outcomes of patients using CSII in the first 24 hours of hospitalization have not been well studied. This timeframe is of particular importance because insulin pump settings are programmed to achieve tight outpatient glycemic targets which could result in hypoglycemia when patients are hospitalized. METHODS/UNASSIGNED:This retrospective cohort study evaluated 216 hospitalized adult patients using CSII and 216 age-matched controls treated with multiple daily injections (MDI) of insulin. Patients using CSII did not make changes to pump settings in the first 24 hours of admission. Blood glucose (BG) values within the first 24 hours of admission were collected. The primary outcome was frequency of hypoglycemia (BG < 70 mg/dL). Secondary outcomes were frequency of severe hypoglycemia (BG < 40 mg/dL) and hyperglycemia (BG ≥ 180 mg/dL). RESULTS/UNASSIGNED: = 0.06). CONCLUSIONS/UNASSIGNED:Patients using CSII experienced fewer events of both hypoglycemia and hyperglycemia in the first 24 hours of hospital admission than those treated with MDI. Our study demonstrates that CSII use is safe and effective for the treatment of diabetes within the first 24 hours of hospital admission.
PMID: 33563036
ISSN: 1932-2968
CID: 4931892

THYROTOXIC PERIODIC PARALYSIS IN A COMPETITIVE BODYBUILDER WITH THYROTOXICOSIS FACTITIA [Case Report]

Patel, Amy J; Tejera, Stephanie; Klek, Stanislaw P; Rothberger, Gary D
Objective/UNASSIGNED:We report a case of thyrotoxic periodic paralysis (TPP) in a bodybuilder who developed paralysis secondary to thyrotoxicosis factitia after taking a supplement containing thyroid hormone. Interestingly, the patient had no intrinsic thyroid disease. Prompt recognition of thyrotoxicosis is critical to avoid progression of paralysis and subsequent complications. Methods/UNASSIGNED:We discuss a 27-year-old body builder who presented after a 3-day bodybuilding competition with sudden upper and lower extremity paralysis. He admitted to taking anabolic steroids, a supplement containing an unknown amount of thyroid hormone for 2 weeks, and furosemide 40 mg twice daily with near-complete fluid restriction for 3 days. Results/UNASSIGNED:Laboratory results showed a thyroid-stimulating hormone (TSH) level of <0.010 μIU/mL (normal, 0.3 to 5.8 μIU/mL), normal total triiodothyronine level, elevated free thyroxine level of 3.6 ng/dL (normal, 0.8 to 1.9 ng/dL), and potassium level of 1.9 mEq/L (normal, 3.7 to 5.2 mEq/L). Thyroid peroxidase antibody, thyroid-stimulating immunoglobulin, and thyroglobulin antibody levels were normal. Thyroid uptake was 1% (normal, 8 to 25%) after administration of I-123 and thyroglobulin level was 9 ng/mL (normal, 1.4 to 29.2 ng/mL). The patient was treated with normal saline infusion, magnesium supplementation and a total of 230 mEq of potassium within 12 hours of hospitalization. Muscle weakness resolved within this time period and potassium level normalized. By the third day of hospitalization free thyroxine level also normalized and TSH improved to 0.1 mIU/L. Conclusion/UNASSIGNED:TPP is a rare complication of thyrotoxicosis that should be considered in bodybuilders who are presenting with acute muscle weakness.
PMCID:7511107
PMID: 32984532
ISSN: 2376-0605
CID: 4981142

Non-autoimmune hyperthyroidism caused by a somatic mosaic GNAS gene mutation involving part of the thyroid gland

Franca, Monica M; Levine, Robert L; Pappa, Theodora; Ilaka-Chibuluzo, Sandra; Rothberger, Gary D; Dumitrescu, Alexandra M; Refetoff, Samuel
Non-autoimmune hyperthyroidism caused by activating mutations in the GNAS gene is a rare condition. Here we report a 5-year-old girl diagnosed with non-autoimmune hyperthyroidism and tall stature harboring a somatic mosaic gain-of-function mutation in the GNAS gene (NM_080425.3: c.2530C>T;p.Arg844Cys previously reported as NM_000516.5:c.601C>T;p.Arg201Cys) and referred thereafter as R201C, in three of four quadrants of the thyroid gland. Provision of a molecular diagnosis may avoid unnecessary complete ablation of the thyroid gland.
PMID: 31910104
ISSN: 1557-9077
CID: 4294852