Abate, Ejigayehu G.

Abstract Primary hyperparathyroidism is most commonly caused by a single parathyroid adenoma. Multiple and ectopic adenomas are less common and can present diagnostic challenges. We present the case of a 57-year-old woman with hypercalcemia, hypercalciuria, and inappropriately normal parathyroid hormone (PTH) levels. Sestamibi scan did not demonstrate abnormal uptake; however, contrast-enhanced 4-dimensional computed tomography imaging reported 2 candidate lesions described as tubular shaped structures located posterior to the inferior pole of each thyroid lobe. Surgical exploration was performed and the surgical pathology reported hypercellular parathyroid tissue resected from the left inferior thyroid bed and benign thymic tissue with embedded hypercellular parathyroid tissue resected from the right inferior thyroid bed. Postoperative calcium levels normalized, and the patient remained eucalcemic at 1-year follow-up. This case underscores the importance of embryologic understanding and thorough surgical exploration in patients with biochemically confirmed primary hyperparathyroidism and inconclusive imaging.

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1,152 patients have been evaluated with an overall solve rate of 14.1% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

Abstract The liver plays an important role in bone and mineral metabolism of patients with end-stage liver disease. These patients are known to have an increased risk of osteoporosis and fractures before liver transplant (LT) with reported fracture incidence of 10-56%. The cause is multifactorial, which includes their underlying liver disease, chronic illness, vitamin D deficiency, and hyponatremia. The impact of hyperglycemia and diabetes mellitus on bone health in liver transplant recipients is not known. Hypothesis: Hyperglycemia increases risk of fracture and osteoporosis in pre- LT patients undergoing LT. Methods: To answer this question, we did a retrospective chart review of consecutive first time, single organ LT recipients at our institution from 2011-2014, who had BMD performed prior to transplantation. We identified 393 patients but included only 209 patients who carried a diagnosis of hyperglycemia or diabetes (type 2 DM, type 1 DM, steroid induced DM and hyperglycemia). BMD was defined based on WHO criteria as Normal, osteopenia and osteoporosis. Hemoglobin A1C was divided into 4 quartiles (A1C ≤5.6%, 5.7-6.4%, 6.5-7.9%, and ≥8%); fasting blood glucose was defined as any venous glucose checked before 9am and labeled as a fasting lab in the chart. Fasting blood glucose was divided into those with BG<100, 101-125, 126-200, >200 mg/dL. We chose labs closest to the transplant date. Pre LT fracture was compared with hemoglobin A1C and BMD as well as fasting glucose. STATA statistical program was used to calculate Fisher T-test. Results: Baseline characteristics of our cohort were as follows. Median BMI was 27.9 (16.2, 45.6). Majority had hepatitis C (33%), NASH 12%, and alcoholic liver disease 23%. Average MELD score was 15 (6-40). Average wait time to transplant was 90 days. 29% of patients had normal BMD, 46% osteopenia and 25% osteoporosis. From the total 209 patients reviewed, 17 had a fracture prior to transplant of which 14/17 had vertebral fractures. The only variable that correlated with risk of fracture was hemoglobin A1C. Higher level of Hemoglobin A1C correlated with the presence of fracture p= 0.04. BMD did not correlate with fracture p= 0.28. There was no association between BMD and Fasting glucose level p=0.55. There was no correlation between fasting glucose and risk of fracture p=0.44. Discussion: This study suggests that a correlation between the presence of pre LT fracture and HgA1C exists. Other factors such as BMD and fasting BG did not correlate with fracture. Those with higher hemoglobin A1C prior to liver transplant might be at risk for fracture compared to those without diabetes or hyperglycemia (A1C <5.7). Benefit of diabetes control for bone health in this population is not known, however we speculate that those with lower A1C, thus better glucose control, have a lower risk of fracture thus aggressive glucose control should be part of the pre transplant care.