Iñiguez‐Ariza, Nicole M.

Abstract Objective The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). Design This is a single-center cohort study. Methods Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. Results Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 μg/dL, P = .002). Conclusions Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.

Purpose: Thyroid eye disease (TED) or Graves’ orbitopathy starts with an active inflammatory stage (active disease) followed by resolution of inflammation and progression to a fibrotic, inactive stage. In our practice, we have encountered cases that have not had active disease despite presence of fibrotic sequelae and disease progression. We aim to delineate the clinical characteristic of this unique group of patients. Methods: We conducted a single-center (Mayo Clinic Rochester) retrospective chart review of TED patients who throughout the course of their disease had only evidence for inactive TED, defined as clinical activity score <3. Results: Median age in the cohort (n = 19) was 54 years (IQR 47–61). 58% had a prior diagnosis of Graves’ disease (GD) before referral. 80% (n = 15) were euthyroid at the time of TED onset (median thyroid-stimulating hormone 1.7 mIU/L). The most common finding was diplopia (100%, n = 19) followed by proptosis (63%, n = 12). Interestingly the disease was asymmetric in 42% of cases. Overall median clinical activity score on presentation was 1 (IQR 0-1). Severity wise, 85% (n = 16) of patients were classified as moderate-to-severe during follow up. Orbital decompression was performed in only 1 case, while extraocular muscle surgery was performed in 13 cases. Conclusions: Quiet TED is a subgroup of TED patients that defies the classic disease paradigm. It presents primarily with diplopia and proptosis. Further evaluation of this group might identify useful insights in TED pathophysiology and help optimize therapeutic choices.

Abstract Ultrasound-guided percutaneous ethanol ablation procedures for locoregional recurrences in papillary thyroid carcinoma (PTC) can be repeatedly performed over years. Skin metastases (SM) from PTC generally portend a lethal prognosis. Our patient case report demonstrates the innovative use in low-risk PTC (LRPTC) of treatment modalities designed to prevent neck re-explorations and capable of eliminating both locoregional recurrences and SM. In 2004, a 48-year-old man presented with neck nodal metastases due to PTC. He underwent a near-total thyroidectomy and nodal dissection, confirming an 8-mm PTC involving 2 ipsilateral node metastases. Postoperatively, he received 2 doses of radioactive iodine (RAI) for remnant uptake (cumulative dose 338 mCi); posttherapy scanning was unrevealing. In 2007, he underwent right neck dissection for further node metastases. In 2008, a guided biopsy confirmed a level IV node metastasis. He was referred to our institution for ethanol ablation. Two node metastases were ablated and subsequently disappeared. During 2010-2016, he developed an additional 6 node metastases, which were treated with ethanol ablation; all disappeared on high-resolution sonography. FDG-PET-CT scans in 2009 and 2016 were negative for distant spread. In 2016, a SM in his right neck was removed by dermatologic surgery. In 2017-2018, 2 further SM were excised with negative margins, one after Mohs surgery. He has now been disease-free for 20 months. In conclusion, despite 3 neck surgeries and 2 RAI therapies, our patient repeatedly developed both locoregional recurrences and SM. All 11 disease foci were eliminated with minimally invasive procedures which should more often be considered as effective treatment options in LRPTC.

Abstract Context Clinical applications of genomic assessment of thyroid cancers are rapidly evolving. Objectives, Design, and Setting We studied tumor samples from patients with imminently threatening and rare thyroid cancers to identify genomic alterations that might correlate with outcomes and/or be productively therapeutically targetable. Patient Context Progressive and metastatic, and/or rare, thyroid cancers were studied, 2012 to 2016, at Mayo Clinic sites. Intervention The intervention was Foundation One tumor interrogation. Main Outcome Measures Main outcome measures included genomic alterations, patient characteristics, and overall survival. Results Samples from 55 patients were evaluated: 20 anaplastic thyroid cancers (ATCs) (36%), 25 radioactive iodine–refractory differentiated thyroid cancers (DTCs)/poorly differentiated thyroid cancers (PDTCs) (45%; 14 papillary thyroid cancer [PTCs], 6 PDTCs, 5 Hürthle cell cancers), 8 medullary thyroid cancers (MTCs) (15%), and 2 others (a spindle epithelial tumor with thymus-like differentiation, and a primary thyroid sarcoma). Overall, 72% of DTCs, 79% of ATCs, and 75% of MTCs were deemed to have potentially productively targetable alterations. The most commonly encountered mutation was of TERT promoter (56% of DTCs, 68% of ATCs)—but this is not presently targetable. Targetable BRAFV600E mutations were found in 40% of DTCs/PDTCs (83% of PTCs) and 32% of ATCs; of MTCs, 75% had targetable RET mutations, and 25% HRAS mutations. Of patient tumors with nonmutated BRAFV600E, 53% of DTC/PDTCs and 69% of ATCs had other potentially productively targetable mutations. Genomic alterations in our series of poor prognosis metastatic DTC/PDTCs also closely resembled those seen in ATC. Conclusions Whereas genomic interrogation of favorable prognosis thyroid cancer seems ill advised, potentially productively targetable mutations were demonstrated in the majority of tumors from patients with metastatic thyroid cancers requiring systemic therapy, suggesting a rationale for the selective application of this technology.

AbstractObjectiveComprehensive data about patients with bilateral pheochromocytoma are limited. We aimed to describe the clinical presentation, genetic analysis, treatment and outcomes of patients with bilateral pheochromocytoma.DesignA retrospective study at a tertiary care centre.PatientsAll patients with bilateral pheochromocytoma evaluated at Mayo Clinic in Rochester, Minnesota between January 1951 and December 2015.MeasurementsTumour size, genetic testing, plasma/urine metanephrines and catecholamines.ResultsA total of 94 patients (51% women) were diagnosed with bilateral pheochromocytoma at a median age at first presentation of 31 years (range, 4‐70). Bilateral disease was noted in 8.0% of pheochromocytoma patient overall and 37.5% of patients 18 years of younger. Most patients presented with synchronous tumours (80%). Median time to metachronous tumours was 4.5 years (range, 1‐38). Genetic disease was identified in 75 (80%) patients, including MEN 2A (42.6%), VHL (19.1%), MEN 2B (9.6%) and NF1 (8.5%). Excess catecholamines were present in 97% of patients. Patients with synchronous pheochromocytoma commonly underwent simultaneous bilateral adrenalectomy (99%), and 18 (24%) had cortical‐sparing surgery. Multicentric tumours were reported in 23 of 77 (30%) patients with available data. Recurrent disease was found in 9.6% of patients, and 8.5% developed metastatic disease. Median follow‐up was 8.5 years. At the study conclusion, 4 patients had died due to pheochromocytoma or adrenalectomy.ConclusionsBilateral pheochromocytoma occurred in 7.0% of adults with pheochromocytoma and 37.5% of paediatric patients. Genetic disease was identified in 80% of patients, predominantly MEN2A. Multicentric tumours were common, but most were still cured following adrenalectomy.

Abstract Neuroendocrine tumors (NET) represent up to 0.5% of all new cancers and can be functional or non-functional. Epidemiologic data on NET in Mexico is very limited. To delineate the clinical characteristics of patients with functional NET at a tertiary national referral center in Mexico we performed a retrospective cohort study (January 1987-June 2019). The target study population was adults with functional NET with biochemical and histopathological confirmation. Results: 126 patients with functional NET were included in this study. The median follow-up was 47.4 months (IQR 10.8 to 93.7). Most were female (64.3%). The mean age at diagnosis was 46.3 ± 14.48 years. The most frequent insulinomas (59.5%), followed by (12.7%) carcinoid tumors, gastrinomas (11.1%), ACTHomas (10.3%), VIPomas (2.4%) glucagonomas (2.4%) and PPomas (1.6%). Nineteen subjects (15.1%) had genetic syndromes, mainly MEN1 (89.5%); and 8.7% had other neoplasms, most frequently non-functional gastrointestinal (GI) carcinoids (36.3%) and thyroid cancer (18.8%). The median duration of symptoms prior to diagnosis was 24 months (IQR 7.75 to 48). The most common locations were, the GI tract (86.5%), whereas 7.1% were outside the GI tract and 6.4% were of unknown primary origin. Functional NETs outside GI tract were localized primarily in lungs (66.6%). Functional pancreatic NETs occurred more commonly in the tail (39.6%). 24.6% had locoregional or distant metastasis during follow-up. The most frequent metastatic sites were liver (86.5%), regional lymph nodes (59.8%) and bone (13.5%). The most common treatment was surgery (87.3%, with 13.6% ≥2), followed by 18.3% somatostatin receptor analogues and 11.1% cytotoxic chemotherapy. Most subjects (73%) had complete remission with first line therapy, but 14.1% had recurrence at a median of 50.7 months (IQR 15.4 to 97.6). Subjects with an incomplete remission progressed after a median of 14.85 months (IQR 10 to 38.9). Conclusions: The clinical characteristics of functional NET treated at a tertiary center in Mexico are similar to those in other population and geographic locations described in the literature.

AbstractObjectiveWe aimed to describe clinical course of myelolipoma and to identify predictors of tumour growth and need for surgery.DesignA retrospective study.PatientsConsecutive patients with myelolipoma.ResultsA total of 321 myelolipomas (median size, 2.3 cm) were diagnosed in 305 patients at median age of 63 years (range, 25‐87). Median follow‐up was 54 months. Most myelolipomas were incidentally detected (86%), whereas 9% were discovered during cancer staging and 5% during workup of mass effect symptoms. Thirty‐seven (12%) patients underwent adrenalectomy. Compared to myelolipomas <6 cm, tumours ≥6 cm were more likely to be bilateral (21% vs 3%, P < .0001), cause mass effect symptoms (32% vs 0%, P < .0001), have haemorrhagic changes (14% vs 1%, P < .0001) and undergo adrenalectomy (52% vs 5%, P < .0001). Among patients with ≥6 months of imaging follow‐up, median size change was 0 mm (−10, 115) and median growth rate was 0 mm/y (−6, 14). Compared to <1 cm growth, ≥1 cm growth correlated with larger initial size (3.6 vs 2.3 cm, P = .02), haemorrhagic changes (12% vs 2%, P = .007) and adrenalectomy (35% vs 8%, P < .0001).ConclusionsMost myelolipomas are incidentally discovered on cross‐sectional imaging. Myelolipomas ≥6 are more likely to cause mass effect symptoms, have haemorrhagic changes and undergo resection. Tumour growth ≥1 cm is associated with larger myelolipoma and haemorrhagic changes. Adrenalectomy should be considered in symptomatic patients with large tumours and when there is evidence of haemorrhage or tumour growth.

AbstractObjectivesLong-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA).MethodsHistologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated.ResultsFollow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM).ConclusionsAppropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.