McKenzie, Travis J.

Primary hyperparathyroidism is the most common cause of hypercalcemia. Follow-up can be resource-intensive and costly. The aim of this study was to determine if there is a subset of patients who can be defined cured earlier than six months. This was a retrospective study of patients who underwent parathyroidectomy between January 2012 and March 2014. Patients with a history of multiple endocrine neoplasia syndrome, and secondary or tertiary hyperparathyroidism were excluded. Patients with normal preoperative calcium and parathyroid hormone (PTH) and those without six months follow-up were excluded. Patients were divided into two groups: cured and not cured. Data analysis was performed between the two groups. A total of 509 patients were screened, and 214 met our inclusion criteria: 202 in the cured category and 12 in the not cured category (94% cure rate). There was no significant difference between age, gland weight, or pre-operative PTH. There was a statistically significant difference between final intraoperative PTH (IOPTH) (37 vs 55, P = 0.008) and per cent PTH decrease (69 vs 43%, P < 0.0001). There was a significant difference between intraoperative cure rate (P < 0.0006), imaging concordance (P = 0.0115), and solitary versus multiglandular disease (P = 0.0151). Subgroup analysis in patients with concordant imaging, solitary parathyroid adenoma, and IOPTH decrease by 50 per cent to normal or near-normal correlated with a six-month cure rate of 97 per cent. Patients with primary hyperparathyroidism with concordant imaging, single-adenoma pathology, and IOPTH decrease by 50 per cent to normal or near-normal levels (15–65 pg/mL) can be considered cured and may need less frequent follow-up.

Abstract Myelolipoma is the second most common adrenal tumor. Yet, systematic approach to these tumors remains poorly defined. Thus, we aimed to describe natural history of myelolipoma and to identify predictors of tumor growth and need for surgery. We conducted a retrospective longitudinal follow-up study of consecutive patients with myelolipoma. A total of 321 myelolipomas (median size, 2.3 cm [range, 0.5-18.0]) were diagnosed in 305 patients at median age of 63 years (25-87). Most myelolipomas were discovered incidentally (86.6%), whereas others were discovered on imaging done for cancer staging (8.8%) or during workup of mass effect symptoms (4.6%). Median duration of follow-up was 54 months (range, 0.03-267). Compared with myelolipomas &lt;6 cm, tumors ≥6 cm were more likely to be right-sided (59% vs 41%, P=0.02), bilateral (21% vs 3%, P &lt;.0001), cause mass effects symptoms (32% vs 0%, P&lt;.0001), have radiographic hemorrhagic changes (14% vs 1%, P&lt;.0001), and undergo adrenalectomy (52% vs 5%, P&lt;.0001). There was no difference in sex or age at diagnosis between the groups. Hemorrhagic changes were noted in 9 (3.0%) patients with median tumor size of 7.0 cm (range, 1.8-18.0). Concomitant adrenal hormone excess was diagnosed in 12/126 (9.5%) patients. Primary aldosteronism was noted in 9 patients: due to concomitant ipsilateral (n=3) or contralateral adrenocortical adenoma (n=3), or bilateral idiopathic adrenal hyperplasia (n=3). Autonomous cortisol excess was noted in 3 patients: due to concomitant contralateral (n=2) or ipsilateral adrenocortical adenoma (n=1). Of 162 patients with ≥6 months of imaging follow-up, tumor size change ranged from -10 to 115 mm (median, 0 mm) and tumor growth rate ranged from -5.6 to 140 mm/year (median, 0 mm/year). Tumor growth ≥1.0 cm (n=26, 16.0%) was associated with larger initial tumor size (3.6 vs 2.3 cm, P=0.02) and hemorrhagic changes on imaging (12% vs 2%, P=0.007), compared with &lt;1 cm size change. Myelolipomas with ≥1.0 cm growth were more likely to undergo adrenalectomy (35% vs 8%, P&lt;.0001). Among 37 (12%) patients that underwent adrenalectomy for myelolipoma, surgical indications included: large tumor size/tumor growth (32%), diagnostic surgery (27%), mass effect symptoms (14%), concomitant ipsilateral tumor leading to hormonal excess (11%), acute hemorrhage (8%), and concomitant resection during non-adrenal surgery (8%). In conclusion, most myelolipomas are discovered incidentally, whereas myelolipomas ≥6 are more likely to cause mass effect symptoms, have radiographic hemorrhagic changes, and more commonly undergo resection. Hormonal excess is rare and is usually attributed to concomitant adrenocortical adenoma or hyperplasia. Tumor growth ≥1.0 cm is associated with larger myelolipoma and presence of hemorrhagic changes. Surgical resection should be considered in symptomatic patients with large tumors, evidence of hemorrhage, or tumor growth.

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.

Abstract Introduction: Cowden syndrome patients are at an increased risk of developing differentiated thyroid carcinoma (DTC). There are limited studies of thyroid cancer biology within this population. We aimed to describe the frequency and progression of DTC in this population. Method: We reviewed all patients with clinically or genetically confirmed Cowden syndrome treated at our institution between 1979 and 2017. Presentation, operative details, pathology, and adjuvant treatment for all thyroid diseases were analyzed. Results: Forty-seven patients were identified. Thirty-seven received a clinical diagnosis while 10 tested positive on genetic testing for the PTEN gene. Average follow-up time was 10 years. Twenty-three patients underwent a total thyroidectomy. Nine patients were diagnosed with thyroid cancer, with a mean age of 28.5 years, 4 cases of the follicular variant of papillary thyroid cancer (PTC), 4 of PTC, and 1 of cystic PTC. One patient required an interval lateral neck dissection but no patients developed distant metastasis. Fourteen patients underwent thyroidectomy, 12 due to follicular adenoma, Hürthle cell adenoma, or multinodular goiter, 1 due to Graves’ disease, and 1 who elected to undergo a prophylactic thyroidectomy. No mortality was associated with thyroid cancer in these patients. Conclusion: Patients with Cowden syndrome are at a significantly increased risk of developing DTC and have a younger age of onset. In this study, 20% of the patients with Cowden syndrome were diagnosed with DTC, but distant metastasis and overall mortality were absent. Clinical features were similar to those of sporadic DTC, proving that, apart from screening, Cowden syndrome-related DTC can be treated in similar fashion.

AbstractIntroductionDue to the rarity of malignant insulinoma, a lack of the literature describing factors affecting outcomes exists. Our aim was to review malignant insulinoma incidence, characteristics and survival trends.MethodsWe identified all patients with malignant insulinoma in the SEER registries from 1973 to 2015. Incidence, neoplasm characteristics and factors affecting cancer‐specific survival (CSS) were described.ResultsA total of 121 patients were identified. The crude annual overall incidence was low (range 0.0–0.27 cases per million person years). The largest proportion had localized disease (40%), while 16% had regional disease, 39% distant metastatic disease, and stage was unreported in 5%. Most neoplasms were in the body/tail of the pancreas, followed by the head of the pancreas. Grade was reported in 40% of patients; only a single patient reported as having grade IV with the remainder all grades I/II. Surgical resection was performed in 64% of patients. Within surgical patients, the median primary neoplasm size was 1.8 cm. Regional lymph nodes were examined in 57.1% of surgical patients, while 34% of examined nodes were positive. The median CSS was 183 months. On multivariable analysis, surgical resection, male sex and absence of metastatic disease were associated with superior survival.ConclusionWhile the greatest proportion of patients with malignant insulinoma present with localized disease, regional lymph node involvement was found in 34% of whose nodes were tested. Further studies are needed to assess the role of lymph node dissection in improving survival and preventing recurrence given the observed frequency of lymph node involvement.

Disease monitoring in nonalcoholic steatohepatitis (NASH) is limited by absence of noninvasive biomarkers of disease regression or progression. We aimed to examine the role of multiparametric three‐dimensional magnetic resonance elastography (3D‐MRE) and magnetic resonance imaging proton density fat fraction (MRI‐PDFF) in the detection of NASH regression after interventions. This is a single‐center prospective clinical trial of 40 patients who underwent bariatric surgery. Imaging and liver biopsies were obtained at baseline and 1 year after surgery. The imaging protocol consisted of multifrequency 3D‐MRE to determine the shear stiffness at 60 Hz and damping ratio at 40 Hz, and MRI‐PDFF to measure the fat fraction. A logistic regression model including these three parameters was previously found to correlate with NASH. We assessed the model performance in the detection of NASH resolution after surgery by comparing the image‐predicted change in NAFLD activity score (delta NAS) to the histologic changes. A total of 38 patients (median age 43, 87% female, 30 of 38 with NAS ≥ 1, and 13 of 38 with NASH) had complete data at 1 year. The NAS decreased in all subjects with NAS ≥ 1 at index biopsy, and NASH resolved in all 13. There was a strong correlation between the predicted delta NAS by imaging and the delta NAS by histology (r = 0.73, P < 0.001). The strength of correlation between histology and the predicted delta NAS using single conventional parameters, such as the fat fraction by MRI‐PDFF or shear stiffness at 60 Hz by MRE, was r = 0.69 (P < 0.001) and r = 0.43 (P = 0.009), respectively. Conclusion: Multiparametric 3D‐MRE and MRI‐PDFF can detect histologic changes of NASH resolution after bariatric surgery. Studies in a nonbariatric setting are needed to confirm the performance as a composite noninvasive biomarker for longitudinal NASH monitoring.

Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 × 10−9; IG FDR = 6.3 × 10−12]. In DG, properdin expression correlated with GCSI bloating ( r = −0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-ζ type, and complement C2 correlated with 4 h gastric retention ( r = −0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis. NEW & NOTEWORTHY This study uses SOMAscan, a novel proteomics assay for determination of altered proteins and associated molecular pathways in human gastroparesis. Seventy-three proteins were changed in diabetic gastroparesis, 132 in idiopathic gastroparesis compared with controls. Forty proteins were common in both. Macrophage-based immune dysregulation pathway was most significantly affected in both diabetic and idiopathic gastroparesis. Proteins involved in the complement and prostaglandin synthesis pathway were associated with symptoms and gastric emptying delay in diabetic gastroparesis.

AbstractIntroductionPatients undergoing unilateral adrenalectomy for primary aldosteronism (PA) may have a solitary adenoma, unilateral hyperplasia, or multiple adenomas on final pathology. This study investigated whether the underlying pathological diagnosis was associated with differences in clinical presentation and postoperative outcomes.MethodsA retrospective cohort study of patients undergoing unilateral adrenalectomy for PA from 2004 to 2015 at our institution was performed. Baseline clinical and laboratory parameters, as well as postoperative biochemical and hypertension cure rates, were compared across the three aforementioned pathological groups.ResultsOf 206 patients who met criteria for inclusion, 152 (73.8%) had a single adenoma, 33 (16%) had unilateral hyperplasia, and 21 (10.2%) had multiple unilateral adenomas. Patients with unilateral hyperplasia were more likely to be male (81.2% vs 57.9%, P = .03), undergo left‐sided adrenalectomy (78.8% vs 47.4%, P < .01), and had a lower median adrenal venous sampling lateralization index (9.8 vs 19.8, P = .04) compared to those with solitary, but not multiple unilateral adenomas. No differences were seen in age, duration of hypertension, preoperative plasma aldosterone levels, plasma renin activities, 24‐h urinary aldosterone excretion, serum potassium concentrations, and the number of preoperative antihypertensive medications across all three pathological groups. All patients achieved biochemical cure following adrenalectomy, and no significant differences in the rates of hypertension cure or improvement were observed in comparisons across pathological subtype.ConclusionsClinical presentation and postoperative outcomes are similar regardless of underlying pathology in patients with PA. Because one in four patients may harbor unilateral hyperplasia or multiple adenomas, total unilateral adrenalectomy should be performed as the operation of choice over adrenal‐sparing approaches.