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

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.

Massive 4-Gland Parathyroid Hyperplasia Initially Detected as a Parathyroid Adenoma.

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.

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

OBJECTIVES: 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.

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?

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: 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.

Utility of Thyroid Function Testing in the Inpatient Setting.

OBJECTIVE: Previous studies have reported a 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 the thyroid function during hospitalization leads to medication initiation or adjustment and to determine whether 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 underwent TFTs tested while admitted to an academic hospital during a 5-month period. The indications for ordering TFTs were determined by reviewing clinical documentation, and those with abnormal test results 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 based on a 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 represented 10.1% of those with abnormal TFTs and only 2.8% of those tested. CONCLUSION: Abnormal TFTs are common, but a disproportionate number of tests are needed to find a small percentage of clinically significant thyroid dysfunction, of which only a low percentage leads 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.

Correlation of Hemoglobin A1C and Outcomes in Patients Hospitalized With COVID-19.

OBJECTIVE: Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19). We conducted this study to determine if there is a correlation between hemoglobin A1C (HbA1C) level and poor outcomes in hospitalized patients with diabetes and COVID-19. METHODS: This is a retrospective, single-center, observational study of patients with diabetes (defined by an HbA1C level of ≥6.5% or known medical history of diabetes) who had a confirmed case of COVID-19 and required hospitalization. All patients were admitted to our institution between March 3, 2020, and May 5, 2020. HbA1C results for each patient were divided into quartiles: 5.1% to 6.7% (32-50 mmol/mol), 6.8% to 7.5% (51-58 mmol/mol), 7.6% to 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: A total of 506 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 among the quartiles, except that acute kidney injury was less frequent in quartile 4. CONCLUSION: There was no significant association between HbA1C level and adverse clinical outcomes in patients with diabetes who are hospitalized with COVID-19. HbA1C levels should not be used for risk stratification in these patients.

Low Free T3 Is Associated With Worse Outcomes in Patients in the ICU Requiring Invasive Mechanical Ventilation.

OBJECTIVE: Critical illness causes a decrease in serum free triiodothyronine (T3) levels. This condition, known as nonthyroidal illness syndrome (NTIS), is associated with poor outcomes. The association of NTIS and outcomes in patients in the intensive care unit (ICU) requiring mechanical ventilation has not been well studied. This study aimed to determine the impact of NTIS on the outcomes of these patients. METHODS: This prospective study included 162 patients in the ICU who underwent mechanical ventilation. Serum free T3 levels were tested on the day of initiation of mechanical ventilation. The rates of in-hospital mortality and ventilator-free days (VFDs) at day 28 after the initiation of mechanical ventilation were compared between patients with low (<2.3 pg/mL) and normal (≥2.3 pg/mL) free T3 levels. Patients who died while on mechanical ventilation were assigned a VFD of 0. RESULTS: Low T3 was present in 60% of study patients. The in-hospital mortality rate of the entire cohort was 39%, and the mean and median VFDs at day 28 were 13.5 and 21 days, respectively. Compared to patients with normal free T3, patients with low free T3 had higher in-hospital mortality (52% vs 19%, P < .001) and less mean and median VFDs at day 28 (10.7 vs 18 and 0 vs 23, respectively. P < .001 for both mean and median VFDs). CONCLUSIONS: The presence of low T3 due to NTIS in patients in the ICU requiring mechanical ventilation is associated with poor outcomes.

THYROTOXIC PERIODIC PARALYSIS IN A COMPETITIVE BODYBUILDER WITH THYROTOXICOSIS FACTITIA.

OBJECTIVE: 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: 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: 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: TPP is a rare complication of thyrotoxicosis that should be considered in bodybuilders who are presenting with acute muscle weakness.

ISOLATED PARAGANGLIOMA IN A PATIENT WITH VHL P.L163F MUTATION.

OBJECTIVE: Paragangliomas (PGLs) are one of the many neoplasms associated with von Hippel-Lindau (VHL) disease. VHL disease type 2C is a unique subtype characterized by the presence of a PGL or pheochromocytoma without other VHL-associated neoplasms. This report describes a rare germline mutation in the VHL gene in a patient with isolated PGL. METHODS: The clinical presentation, urinary metanephrines and normetanephrines, computed tomography scan, meta-iodobenzylguanidine scintiscan, surgical pathology, and genetic testing of a patient with PGL and a rare VHL gene mutation are described. A literature review is also presented. RESULTS: A 23-year-old, Indian woman was incidentally found to have an indeterminate 4.2 × 3.6 × 3.2-cm mass adjacent to the liver. A 36-year-old first cousin was recently diagnosed with a PGL. Her 24-hour urinary metanephrines were 6,886 µg/g creatinine (reference range is 81 to 330 µg/g creatinine) and normetanephrines were 6,810 µg/g creatinine (reference range is 20 to 158 µg/g creatinine). Surgical pathology revealed a PGL adjacent to a normal adrenal gland. Genetic testing revealed a mutation in VHL p.L163F. Surveillance for other tumors associated with VHL disease has been negative thus far. Her cousin has not undergone genetic testing despite recommendations to do so. CONCLUSION: We present the first reported case of PGL in a patient with VHL disease caused by a missense mutation in VHL p.L163F. To date, reports of this rare mutation have only involved patients with pheochromocytoma and without other tumors associated with VHL disease, suggesting that VHL p.L163F mutation may cause a VHL disease type 2C phenotype.

Nonautoimmune Hyperthyroidism Caused by a Somatic Mosaic GNAS Mutation Involving Part of the Thyroid Gland.

Nonautoimmune hyperthyroidism caused by activating mutations in the GNAS gene is a rare condition. In this study, we report a five-year-old girl diagnosed with nonautoimmune 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 to 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.

Method of detection of thyroid nodules: correlation with frequency of fine-needle aspiration and malignancy rate.

BACKGROUND: Thyroid nodules are commonly found by screening, and the clinical implications are unclear. METHODS: We retrospectively studied 460 patients who were evaluated for thyroid nodules. Medical records were queried to determine how the nodules were detected. We compared the rates of fine needle aspiration (FNA) and malignancy between nodules detected clinically, incidentally on imaging, or by screening. RESULTS: Nodules were detected clinically in 184 patients (40%), incidentally in 121 patients (26%), and by screening in 155 patients (34%). The rates of FNA and malignancy were lower for patients with nodules detected by screening (28% and 1%, respectively), compared to patients with clinically apparent nodules (75% and 15%) and patients with incidental nodules (69% and 8% [P < .001]). CONCLUSION: Thyroid nodules detected via screening has a lower rate of FNA and is less likely to be diagnosed as a malignancy compared to nodules detected clinically or incidentally on imaging. Thyroid ultrasound examinations should be reserved for nodules that are clinically apparent or to evaluate nodules found incidentally on imaging.

Usefulness of Serum Triiodothyronine (T3) to Predict Outcomes in Patients Hospitalized With Acute Heart Failure.

Thyroid hormone plays an important role in cardiac function. Low levels of serum triiodothyronine (T3) due to nonthyroidal illness syndrome may have adverse effects in heart failure (HF). This study was designed to assess the ability of T3 to predict in-hospital outcomes in patients with acute HF. In total, 137 patients without thyroid disease or treatment with drugs which affect TH levels, who were hospitalized with acute HF were prospectively enrolled and studied. TH levels were tested upon hospital admission, and outcomes were compared between patients with low (<2.3 pg/ml) and normal (≥2.3 pg/ml) free T3 levels as well as between those with low (<0.6 ng/ml) and normal (≥0.6 ng/ml) total T3 levels. Low free T3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and higher rates of intensive care unit admission (31.8% vs 16.9%, p = 0.047), with a trend toward increased need for invasive mechanical ventilation (9.0% vs 1.4%, p = 0.056). Low total T3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and increased need for invasive mechanical ventilation (9.8% vs 1.3%, p = 0.045). In conclusion, low T3 predicts worse hospital outcomes in patients with acute HF and can be useful in the risk stratification of these patients.

Evaluation of surgical outcomes and gallbladder characteristics in patients with biliary dyskinesia.

INTRODUCTION: This study was designed to compare symptomatic outcomes following cholecystectomy in patients with biliary dyskinesia. MATERIALS AND METHODS: From 1999 to 2006 at New York University Medical Center, 197 adults underwent hepatobiliary scintigraphy with cholecystokinin administration to evaluate gallbladder ejection fraction (GBEF). Biliary dyskinesia was demonstrated in 120 patients based on decreased GBEF of