Background: Primary thyroid lymphoma (PTL) is a rare condition representing <5% of thyroid malignancies with diffuse large B-cell lymphoma (DLBCL) as the most common subtype (1). Although not commonly managed in the endocrine sphere, identification is paramount to prognosis and treatment. We present a case of PTL to highlight the importance of diagnostic scrutiny and clinical follow up. Clinical Case: A 69-year-old man with a history of Hashimoto’s thyroiditis presented with an enlarging neck mass. The patient noted development of a left-sided anterior neck mass 3 days prior to seeking care. He denied compressive symptoms and B symptoms (weight loss, fevers, and night sweats). Physical exam revealed a large, firm left-sided thyroid nodule. Serum studies were notable for TSH 39.1 mcIU/mL (0.30-4.7 mcIU/mL), FT4 0.9 ng/dL (0.80-1.70 ng/dL), and TPO Ab 127 IU/mL (<=20 IU/mL). Levothyroxine 100 mcg daily was started. Neck ultrasonography showed a 54 mm hypoechoic, solid left thyroid nodule without calcifications. No abnormal cervical lymph nodes were present. FNA revealed a mixed population of small lymphocytes with no monoclonal B cell population or T cell aberrancies on flow cytometry. In the setting of ongoing nodular growth, the patient underwent core needle biopsy which revealed DLBCL (Ki67 proliferation index >80%, EBV-EBER negative). For diagnostic confirmation and staging, a whole-body FDG-PET scan was performed with an intensely FDG-avid left thyroid mass and no metabolic evidence of additional lymphoproliferative disease. Bone marrow biopsy did not show lymphomatous involvement. The patient was diagnosed with primary thyroid lymphoma and started on chemotherapy with R-CHOP. Conclusion: PTL commonly presents as a rapidly enlarging, painless neck mass that may be accompanied by B symptoms. Hashimoto’s thyroiditis is a known risk factor. Our case in particular required more diligence in the setting of an FNA with mixed lymphoid cells and negative flow cytometry. Initial differential diagnosis included intrathyroidal lymph node, Hashimoto’s thyroiditis, thyroid adenoma/malignancy with a false FNA, and lymphoma. Notably, FNA biopsy is only associated with 71% sensitivity in diagnosing PTL, whereas core biopsy has a 93% sensitivity rate (2). Upon histopathologic disease diagnosis, collaboration with oncology is needed for further staging and initiation of chemotherapy +/- radiation. References: (1) Pavlidis ET, Pavlidis TE. A Review of Primary Thyroid Lymphoma: Molecular Factors, Diagnosis and Management. J Invest Surg. 2019;32(2):137-142. (2) Diaconescu MR, Costea I, Glod M, Diaconescu S. An Unwonted Clinicopathological Subtype of Thyroid Primary Lymphoma. Chirurgia. 2016;111(5):428-431.

Background: Hypercalcemia is a common complication of advanced malignancy, affecting up to 30% of cancer patients through various mechanisms (1). Hypercalcemia has rarely been described in gastrointestinal stromal tumors (GIST), with fewer than ten case reports as of 2018 (1,2). We describe a case of calcitriol-mediated hypercalcemia in a patient with GIST. Clinical Case: An 80-year-old woman with a history of metastatic GIST and nivolumab-induced type 1 diabetes and thyroiditis presented with dramatic progression of metastatic peritoneal disease and new severe hypercalcemia with acute kidney injury. On hospital admission, calcium (Ca) was 15.1 mg/dL (8.6-10.3 mg/dL), ionized Ca was 1.98 mmol/L (1.09-1.29 mmol/L), and creatinine was 2.56 mg/dL (0.6-1.3 mg/dL, baseline 1.8 mg/dL). She was treated with IV fluids and 45 mg of IV pamidronate with initial Ca improvement to 10.7 mg/dL over the next 48 hours. Additional workup showed that 25-hydroxyvitamin D was 18 ng/dL (20-50 ng/dL), PTH was 9 pg/mL (11-51 pg/mL), PTHrP was 3.1 pmol/L (0.0-3.4 pmol/L), and calcitriol was elevated to 172 pg/mL (19.9-79.3 pg/mL). Prior chest/abdomen/pelvis CT scans had not shown bony metastases or granulomas. After stopping IV fluids, Ca rose to 12.2 mg/dL the next day. Prednisone 20 mg daily was started which stabilized Ca levels and lowered calcitriol to 17.4 pg/mL after two weeks. She also began a new regimen of cabozantinib. Prednisone was tapered to 10 mg daily and she continues to maintain normal Ca levels with the addition of home health IV fluids three times a week. Conclusion: GIST tumors are a rare cause of hypercalcemia of malignancy. Although hypercalcemia of malignancy is most often due to tumor-secreted PTHrP or bony metastases, a small percentage of cases are mediated by excess calcitriol production. There is a growing number of case reports, including this case, to suggest that calcitriol-mediated hypercalcemia is the most common cause of hypercalcemia in GIST tumors (2-4). Glucocorticoids may be used to decrease calcitriol production and help maintain eucalcemia. Definitive therapy for hypercalcemia in these patients involves decreasing tumor burden by treatment of the underlying malignancy (3). References: (1) Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-9. (2) Hart T, Sinitsky D, Shamsiddinova A, Rohatgi A. Refractory hypercalcaemia secondary to localised gastrointestinal stromal tumour. Ann R Coll Surg Engl. 2018;100(6):e136-e138. (3) Hygum K, Wulff CN, Harsløf T, et al. Hypercalcemia in metastatic GIST caused by systemic elevated calcitriol: a case report and review of the literature. BMC Cancer. 2015;15:788. (4) Barbaryan A, Bailuc S, Poddutoori P, et al. Gastrointestinal Stromal Tumor Induced Hypercalcemia. Case Rep Oncol Med.2017;4972017.

Background: Spontaneous bilateral adrenal hemorrhage (BAH) is a rare complication of antiphospholipid syndrome (APS), which is the most common identifiable risk factor for BAH. Although adrenal dysfunction is generally irreversible, adrenal function might be preserved or even recover in rare cases1. Clinical case: A 48 year-old man with history of hypertension and gout presented with right upper quadrant abdominal pain following trauma to his left leg. He was found to have a left lower extremity deep vein thrombosis and bilateral pulmonary emboli (PE) and was started on anticoagulation therapy. He continued to have abdominal pain and a CT abdomen revealed BAH. Three am cortisol level was 21 mcg/dL (8–25 mcg/dL), ACTH 37 pg/mL (6–59 pg/mL), aldosterone <3 ng/dL (4–31 ng/dL), renin 2.6 ng/mL/hr (0.2–1.6 ng/mL/hr), sodium 130 mmol/L (135–146 mmol/L) and potassium 4.3 mmol/L (3.6–5.3 mmol/L). Patient was hemodynamically stable and did not report symptoms of adrenal insufficiency. Hypercoagulable work-up was consistent with APS and Lupus. Despite normal cortisol levels, he was started on hydrocortisone in the setting of anticoagulation and recent hemorrhage. Given low aldosterone with slightly high renin he was also started on fludrocortisone. Six weeks after discharge, his morning cortisol was 6 mcg/dL and ACTH was elevated at 76 pg/mL which was concerning for adrenal insufficiency. However, 250 mcg IM ACTH stimulation test showed peak cortisol of 17 mcg/dL which is considered adequate. Aldosterone and renin levels normalized so fludrocortisone was discontinued. Patient subsequently self-discontinued all medications for 1 month with no symptoms of adrenal insufficiency, and later restarted hydrocortisone on his own. Repeat ACTH stimulation test showed baseline ACTH 57 pg/mL with peak cortisol of 17 mcg/dL. Patient was tapered off hydrocortisone and displayed no subsequent symptoms of adrenal insufficiency. Conclusion: This case highlights the need to consider APS in patients with spontaneous BAH. Additionally, patients with BAH may have relatively preserved adrenal function. There is limited data to guide when steroid replacement is necessary for patients without clear adrenal insufficiency. It may be reasonable to monitor these patients off hydrocortisone replacement with close monitoring. 1. Ramon I, Mathian A, Bachelot A, et al. Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients. J Clin Endocrinol Metab. 2013;98(8):3179–3189.