Background: Antithyroid drugs, such as methimazole (MMI), are standard therapies for the medical management of thyrotoxicosis. Agranulocytosis is a rare but lethal adverse effect of antithyroid medications. We have reported 2 cases of MMI-induced agranulocytosis with similar risk factors that likely predisposed them to this adverse reaction. Case Report: Case 1 involved a 71-year-old woman, with a history of Graves disease, who presented with an altered mental status. She was recently discharged on 40 mg of MMI twice daily, and she continued this dose for 2 months. She was readmitted and found to have neutropenic fever in the setting of MMIinduced agranulocytosis. MMI was discontinued, and she was started on filgrastim. Her cell counts gradually improved, and she was subsequently discharged. Case 2 involved a 68-year-old woman, with a history of Graves disease, who presented with severe back pain, nausea, and vomiting. She was recently discharged on 10 mg of MMI twice daily, which was increased to 10 mg 3 times a day. She was readmitted to the hospital because of a septic shock in the setting of pneumonia, colitis, bacteremia, and MMI-induced agranulocytosis. A bone marrow biopsy showed a polyclonal infiltrate with up to 85% plasma cells. Despite treatment with antibiotics, filgrastim, and continuous renal replacement therapy, she ultimately passed away. Discussion: Although these cases had differing outcomes, they shared similar features and risk factors, including older age, female sex, and relatively higher doses of MMI. Conclusion: Close follow up and awareness of risk factors, such as age, female sex, and higher doses of MMI, may decrease the risk of MMI-induced agranulocytosis and fatal outcomes.

Introduction: Exogenous insulin antibodies are common in patients with type 1 diabetes mellitus (T1DM) on insulin. However, they are clinically irrelevant as a cause of hypoglycemia. We report a unique case of exogenous insulin antibody-mediated severe hypoglycemia in a patient with T1DM and Cushing syndrome. Case Report: A 55-year-old woman with T1DM on insulin pump presented with proximal muscle weakness and myalgia. She was diagnosed with Cushing syndrome due to an adrenal adenoma. Despite high serum cortisol, she had severe symptomatic episodic hypoglycemia with glucose levels <10 mg/dL requiring intermittent prolonged suspension of insulin pump. Surprisingly, she did not develop hyperglycemia or ketosis when off the insulin pump. During a witnessed hypoglycemic episode, serum insulin was 20.8 uIU/mL (NRR <19.7 uIU/mL), C-peptide <0.10 ng/mL (NRR 0.80-2.85 ng/mL), glucagon 11 pg/nl (NRR 8-57 pg/nl), and insulin antibody 4.1 U/mL (NRR <0.4/U/mL). She eventually underwent right adrenalectomy and was started on prednisone post-operatively resulting in a marked decrease in frequency of hypoglycemia. She was discharged on prednisone with plan for outpatient taper. Discussion: Our case highlights the complex nature of glycemic dysregulation in insulin antibody-mediated hypoglycemia. Literature review suggests that binding capacity and affinity to insulin, rather than the quantity of insulin antibodies, determines the severity of hypoglycemia. We hypothesize that high binding capacities in our patient resulted in rapid sequestration of exogenous insulin through formation of immunoglobulin-insulin complexes. The low affinity allowed for subsequent rapid release of insulin in a physiologically dyssynchronous manner resulting in hyperinsulinemic hypoglycemia. A distinctive aspect of our patient is the presence of severe hypoglycemia despite endogenous hypercortisolism, although she responded to prednisone. This finding may have implications for future research. Disclosure M. Amini: None. A. H. Khine: None. S. S. Lamba: None. S. Mishra: None. S. Naing: None. V. Babu: None.

Background: Familial hypokalemic periodic paralysis (FHPP) is a rare condition characterized by episodes of painless muscle weakness associated with hypokalemia. It can be precipitated by heavy exercise and high carbohydrate meals. There have been cases illustrating treatment options to decrease the frequency of episodic weakness. However, insulin use in patients with FHPP has not been well studied or documented in literature. Clinical Case: A 21-year-old male with known FHPP (heterozygous positive CACNA1S R1239H mutation) presented with nausea, vomiting, abdominal pain, and profound weakness. He had 1/5 strength in his upper and lower extremities bilaterally on examination. He was found to be in diabetic ketoacidosis (DKA). Insulin drip was initiated per DKA protocol and eventually converted to subcutaneous insulin. He continued to be weak and persistently hypokalemic, requiring potassium replacement (200 mEq/day). He had been on acetazolamide as preventive treatment for FHPP. It was switched to spironolactone in efforts to better control his potassium levels. His strength improved gradually, and he recovered 5/5 strength in his upper and lower extremities bilaterally by day 3 of admission. His weakness did not acutely worsen after receiving subcutaneous insulin. Further testing revealed elevated glutamic acid decarboxylase (GAD) antibodies consistent with type 1 diabetes mellitus (T1DM). His serum potassium on discharge was 4.4 mEq/L. He was discharged with subcutaneous insulin, potassium chloride 40 mEq three times daily, and spironolactone 100 mg daily. After discharge, serum potassium levels remained stable and potassium requirement decreased significantly to 40 mEq once daily. Conclusion: This case illustrates the management dilemma between an unusual combination of diseases. The balance of potassium levels between insulin use in T1DM and FHPP creates significant challenges. Fortunately, the use of subcutaneous insulin in this patient did not appear to trigger episodic weakness. Further studies of hypokalemic periodic paralysis are critical to the institution of appropriate therapy and prevention of symptoms in patients with these conditions. Careful replacement and monitoring of potassium is recommended as patients require high doses of potassium during acute episodes of flaccid paralysis, and requirement significantly decreases after an acute episode.

Introduction Thyroid storm is a rare, life-threatening condition with a high mortality rate approaching 10-30%. The mainstay of treatment includes initiation of therapy directed against the thyroid, supportive intensive care, and treatment of any precipitating factors. We report three cases of patients with thyroid storm and successful therapeutic use of plasmapheresis when traditional therapy was contraindicated. Clinical Cases Case 1 A 22-year-old male with no known past medical history, presented with fever, shortness of breath, and syncope. Labs showed TSH 0. 014 mIU/L (range 0.4-4.5), FT4 4.30 ng/dL (range 0.9-2.2), TSI 546% (range <140), and TPO 20 U/mL (range <60). He was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 60). He was initially treated with propylthiouracil (PTU), hydrocortisone, propranolol, and Lugol's iodine solution. He developed transaminitis and shock liver so was not able to continue PTU or trial methimazole. He underwent 4 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Case 2 A 37-year-old female with known Graves’ disease (non-adherent to antithyroid drug), presented with shortness of breath and palpitations. Labs showed TSH <0. 01 mIU/L (range 0.4-4.5), FT4 4.83 ng/dL (range 0.9-2.2), and FT3 6. 0 pg/mL (range 2.3-4.2). Burch-Wartofsky score was 40 and supported the diagnosis of thyroid storm. She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed transaminitis and there was also concern for methimazole-induced insulin autoimmune syndrome, so methimazole was discontinued. She underwent 3 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Case 3 A 31-year-old female with no known past medical history, presented with shortness of breath and altered mental status requiring intubation. Labs showed TSH <0. 01 mIU/L (range 0.4-4.5), FT4 4.65 ng/dL (range 0.9-2.2), FT3 25.2 pg/mL (range 2.3-4.2), TSI 467% (range <140), TPO 375 U/mL (range <60). She was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 90). She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed pulmonary alveolar hemorrhage and it was unclear if this was due to methimazole, thus methimazole was discontinued. She underwent 5 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Conclusion Plasmapheresis can be an effective and safe treatment option in thyroid storm when there are contraindications for antithyroid drugs or when rapid normalization of thyroid hormone levels is needed. It should be considered as a stabilizing measure as it leads to marked improvement of thyrotoxicosis within 3-5 days, allowing thyroidectomy for definitive therapy. Presentation: No date and time listed