Adrenal Liposarcoma: A Novel Presentation of Multiple Endocrine Neoplasia Type 1.

Background/Objective: Multiple endocrine neoplasia type 1 (MEN1) syndrome results from genetic sequence variations of the tumor suppressor MEN1 gene, which codes for the protein menin. Individuals with MEN1 are prone to developing multiple tumors involving the endocrine and nonendocrine organs. MEN1 associated with liposarcomas has not been documented previously. We highlight a case of MEN1 presenting with a metastatic adrenal liposarcoma. Case Report: A 41-year-old Hispanic man with a history of nephrolithiasis and skin lesions presented to the emergency department with abdominal pain. He was found to have a right adrenal mass measuring 7.9 cm with extension into the liver and primary hyperparathyroidism. He had multiple paternal first-degree relatives with similar skin lesions, hypercalcemia, and tumors of the brain, thoracic cavity, abdomen, and thyroid. The mass was identified as a metastatic pleiomorphic adrenal liposarcoma on surgical pathology. Genetic testing revealed a germline pathogenic sequence variation of the MEN1 gene. Discussion: Liposarcomas are rare malignant tumors with an annual incidence of 2.5 cases per 1 million. Although lipoma formation is a commonly described manifestation of MEN1, liposarcomas have not been associated with MEN1 previously. A potential mechanism of this association is through the role of menin in inducing adipocyte differentiation via peroxisome proliferator-activated receptor-γ activation, a highly expressed protein in liposarcomas. Conclusion: Liposarcomas should be included in the differential of MEN1-related tumors.

Evaluation and Management of Patients Referred for Post-Bariatric Surgery Hypoglycemia at a Tertiary Care Center.

PURPOSE: Following bariatric surgery, patients can develop non-specific symptoms self-described as hypoglycemia. However, confirming hypoglycemia can be technically challenging, and therefore, these individuals are frequently treated empirically. This study aimed to describe what diagnostic evaluation and therapeutic interventions patients referred for post-bariatric surgery hypoglycemia undergo. METHODS: Retrospective observational cohort study of patients with a history of bariatric surgery was evaluated for post-bariatric surgery hypoglycemia in a tertiary referral center from 2008 to 2017. We collected demographic and bariatric surgery information, clinical presentation of symptoms referred to as hypoglycemia, laboratory and imaging studies performed to evaluate these symptoms, and symptom management and outcomes. RESULTS: A total of 60/2450 (2.4%) patients who underwent bariatric surgery were evaluated in the Department of Endocrinology for hypoglycemia-related symptoms. The majority were middle-aged women without type 2 diabetes who had undergone Roux-en-Y gastric bypass. Thirty-nine patients (65%) completed a biochemical assessment for hypoglycemia episodes. Six (10%) had confirmed hypoglycemia by Whipple's triad, and four (6.7%) met the criteria for post-bariatric surgery hypoglycemia based on clinical and biochemical criteria. All patients were recommended dietary modification as the initial line of treatment, and this intervention resulted in most patients reporting at least some improvement in their symptoms. Eight patients (13%) were prescribed pharmacotherapy, and two patients required additional interventions for symptom control. CONCLUSIONS: In our experience, evaluation for hypoglycemia-related symptoms after bariatric surgery was rare. Hypoglycemia was confirmed in the minority of patients. Even without establishing a diagnosis of hypoglycemia, dietary changes were a helpful strategy for symptom management for most patients.

Worse Pituitary Adenoma Surgical Outcomes Predicted by Increasing Frailty, Not Age.

PURPOSE: Increasing patient age has been associated with worse outcomes after pituitary adenoma resection in previous studies, but the prognostic value of frailty compared with advancing age on pituitary adenoma resection outcomes has not been clearly evaluated. METHODS: The National Surgical Quality Improvement Program from 2015 to 2019 was queried for data for patients aged >18 years who underwent pituitary adenoma resection (n = 1454 identified patients). Univariate and multivariate analyses of age and frailty (5-factor modified frailty index [mFI-5]) were performed on 30-day mortality, major complications, extended length of stay (eLOS), discharge destination, and readmission and reoperation. The receiver operating characteristic curve analysis was performed to compare effect of age and mFI-5. RESULTS: On univariate analysis, increasing frailty was significantly associated with greater risk of unplanned readmission (frail: odds ratio [OR], 1.9; 95% confidence interval [CI], 1.2-3.2; severely frail: OR, 6.9; 95% CI, 2.4-19.8) and a major complication (frail: OR, 3.6; 95% CI, 2.1-6.1). Severe frailty was also associated with nonhome discharge (OR, 10.6; 95% CI, 3.2-35.8) and eLOS (OR, 4.5; 95% CI, 1.5-13.4). Increasing age was not associated with any of these outcome measures. Multivariate analysis also demonstrated similar trends. In receiver operating characteristic curve analysis, the mFI-5 score showed higher discrimination for major complications compared with age (area under the curve: 0.624 vs. 0.503; P < 0.001). CONCLUSION: Increasing frailty, and not advancing age, was an independent predictor for major complications, unplanned readmissions, eLOS, and nonhome discharge after pituitary adenoma resection, suggesting frailty to be superior to age in preoperative risk stratification in this patient population.

Resolving the Egg and Cholesterol Intake Controversy: New Clinical Insights Into Cholesterol Regulation by the Liver and Intestine.

OBJECTIVE: Cardiovascular disease is the number one cause of death. Achieving American Heart Association low-density lipoprotein (LDL) cholesterol treatment goals is very difficult for many patients. The importance of a low cholesterol diet is controversial and not emphasized by most physicians. Of critical importance is determining whether each individual is a "hyper- or hypo-absorber" of dietary cholesterol. Furthermore, the quantity of each individual's baseline daily dietary cholesterol and saturated fat intake is important in assessing the effect of added egg yolk cholesterol and saturated fat on blood LDL cholesterol. METHODS: Gut cholesterol is absorbed via a specific enteric receptor (the Niemann- Pick-like receptor). Dietary cholesterol contributes one fourth of the absorbed cholesterol, while the remaining gut cholesterol is derived from secreted bile cholesterol. This dietary quantity of cholesterol is significant when other determinants are constant. For some individuals, dietary cholesterol has no adverse effects and in others, a significant elevation in blood LDL cholesterol may occur. RESULTS: There are no readily available blood tests to determine the effect of egg yolk cholesterol and saturated fat on an individual's plasma LDL cholesterol. However, a one month trial of a low cholesterol and saturated fat diet will provide the needed information to make clinical decisions. CONCLUSION: This article delineates the mechanisms that are altered by genetic and environmental factors that determine the net effects of dietary cholesterol and saturated fat on circulating LDL cholesterol. It then makes a practical clinical recommendation based on these mechanisms.

Measurement of apolipoprotein B levels helps in the identification of patients at risk for hypertriglyceridemic pancreatitis.

BACKGROUND: Severe hypertriglyceridemia (HTG) is a common cause of acute pancreatitis, although even moderate HTG may elevate this risk. Identifying patients who are prone to hypertriglyceridemic pancreatitis (HTGP) can facilitate early, preventative interventions. OBJECTIVE: To examine advanced lipoprotein profile (ALP) of hypertriglyceridemic patients with and without HTGP to identify lipid and lipoprotein parameters which may help improve risk stratification. METHODS: This was a retrospective cohort study of adult patients with serum triglycerides (TGs) ≥ 500 mg/dL who underwent ALP testing. Chart reviews were conducted to identify those who developed HTGP or not. Comparisons of lipid profiles of patients with and without HTGP were performed using chi-square or rank-sum tests. ROC curves were generated to identify lipid and lipoprotein parameters which helped improve prediction of HTGP beyond serum TG levels. RESULTS: Fifty-eight subjects were included in the analysis. Twenty had at least one documented episode of HTGP. Among patients with HTGP, median serum TG concentrations were 2832 mg/dL vs. 978 mg/dL in the non-pancreatitis group (p < 0.001). Chylomicron TG/total TG, chylomicron TG/VLDL TG, chylomicron TG/apoB, total TG/total Cholesterol, and total TG/apoB were significantly higher among the pancreatitis group. Total serum TG/apoB had the best discriminant value for predicting HTGP with an AUC-ROC of 0.87 (p < 0.001). A cutoff of >10.6 was associated with a sensitivity of 90% and specificity of 75%. CONCLUSION: Measurement of serum apoB levels and calculation of serum TG/apoB ratio may help identify hypertriglyceridemic patients at risk for HTGP.

PANCYTOPENIA SECONDARY TO AUTOIMMUNE VITAMIN B12 DEFICIENCY IN GRAVES DISEASE.

OBJECTIVE: To describe a case of Graves disease (GD) and coexistent pancytopenia associated with autoimmune vitamin B12 deficiency. While thyrotoxicosis and antithyroid drugs can cause pancytopenia, other autoimmune conditions such as vitamin B12 deficiency can occur, leading to severe anemia and pancytopenia. METHODS: A 19-year-old female with GD treated with methimazole presented with thyrotoxicosis and evidence of pancytopenia. Diagnostic studies included a complete blood cell count, peripheral blood smears, thyroid function tests, and a bone marrow biopsy. RESULTS: White blood cells were 2.4 × 109 cells/L (reference range [RR] is 3.4 to 9.6 × 109 cells/L), hemoglobin was 7.9 g/dL (RR is 11.6 to 15.0 g/dL), neutrophil count was 1.2 × 109 cells/L, and platelets were 84 × 109 cells/L (RR is 157 to 371 × 109 cells/L). Thyroid-stimulating hormone was <0.01 mIU/L (RR is 0.50 to 4.30 mIU/L), free thyroxine was 3.7 ng/dL (RR is 1.0 to 1.6 ng/dL), and total triiodothyronine was 221 ng/dL (RR is 91 to 218 ng/dL). Due to suspicion for drug-induced pancytopenia, methimazole was discontinued. Three days later, she was hospitalized for a syncopal episode with a further decline in hemoglobin to 6.7 g/dL, neutrophils to 0.68 × 109 cells/L, and platelets to 69 × 109 cells/L. Bone marrow biopsy findings showing marrow hypercellularity and hypersegmented neutrophils suggested vitamin B12 deficiency. Vitamin B12 was <70 ng/L (RR is 180 to 914 ng/L). Intramuscular vitamin B12 injections were initiated, and pancytopenia resolved within 1 month. CONCLUSION: Although rarely described in the literature, autoimmune vitamin B12 deficiency can be missed as an underlying etiology for pancytopenia in patients with GD. The clinical picture can be further confounded when these patients are treated with antithyroid drugs known to cause bone marrow suppression.

The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic.

Background: Levothyroxine (LT4) is the mainstay of therapy for hypothyroidism. Yet, despite physician efforts at dose titration, some patients remain hypothyroid on LT4 doses in excess of weight-based calculations, a condition known as refractory hypothyroidism. The LT4 absorption test (LT4AT) has been proposed to have utility in these patients by enabling distinction of LT4 malabsorption from pseudomalabsorption, a condition of intentional nonadherence. Given its rare use in clinical practice, we reviewed our institution's experience with the LT4AT to assess its impact on management of refractory hypothyroidism. Methods: We reviewed the charts of 16 patients diagnosed with refractory hypothyroidism and who had completed the LT4AT between January 2015 to January 2019. The primary aim was to determine the utility of this test in distinguishing LT4 malabsorption from pseudomalabsorption. Secondary aims were to determine whether the results of this test impacted physicians' management decisions, as well as to report on clinical outcomes at follow-up. Our LT4AT is a six-hour test wherein patients receive a weight-based dose of LT4 followed by serial measurements of total thyroxine (TT4) and thyrotropin (TSH). Percentage absorption is calculated using the following formula, with normal absorption being ≥60%: [Formula: see text] Results: Percentage absorption was calculated in 13 of 16 patients due to lack of TT4 data for 3 patients. Absorption was impaired in one patient (% absorbed = 0), who had known causes of malabsorption. The remaining 12 patients had normal absorption by hour 4 of the test (% absorption 60-158) in conjunction with upward TT4 trends. Clinical follow-up ranged from 1 to 32 months (median 6.5 months), with 11 patients having follow-up data. Six of these had normal or suppressed TSH values at most recent follow-up, and four had improved but persistent TSH elevations. The one said patient with malabsorption improved with intravenous LT4. Conclusions: The LT4AT can provide valuable information for distinguishing malabsorption from pseudomalabsorption. Our findings support the combined use of calculated percentage absorptions with TT4 trends for at least a four-hour time frame when making determinations regarding absorption.