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Non-islet cell tumor-induced hypoglycemia (NICTH) secondary to phyllodes tumor is extremely rare but potentially life threatening if not treated promptly. We report a case of a 46-year-old Indian female without underlying diabetes mellitus who presented with a large breast tumor and recurrent severe symptomatic hypoglycemia. Investigations supported the diagnosis of NICTH. The hypoglycemia only resolved after corticosteroids and mastectomy. This case highlights the importance of considering NICTH in the evaluation of patients with voluminous tumor and hypoglycemia.

Introduction: Antithyroid drugs (ATDs) are recommended effective treatment for uncontrolled Graves’ disease but achieves maximal antithyroid effects between 6 to 12 weeks. Cholestyramine sequesters thyroid hormones in the intestine and enhances its fecal excretion. Steroids inhibits the conversion of thyroxine to triiodothyronine peripherally and blocks thyroid hormone production. We hypothesize that adjunctive cholestyramine or prednisolone to ATDs may reduce circulating thyroid hormones and improve biochemical control. Methods: In this multicenter, open labelled, parallel-group trial, we randomly assigned in a 1:1:1 ratio, adult Graves’ disease patients with moderate to severe hyperthyroidism (FT4 levels > 40 pmol/L) to receive either adjunctive cholestyramine 4g twice daily or prednisolone 30 mg daily in tapering down doses in addition to standard treatment or standard treatment alone for 4 weeks. Standard treatment was carbimazole 30mg daily and propanolol 40mg BD for 4 weeks. The primary endpoint was change from baseline for FT4 and FT3 levels at the end of 2 and 4 weeks of intervention. Safety endpoints including gastrointestinal adverse events, hypokalemia, hypothyroid and hyperglycemia were recorded. Results: A total of 107 patients were screened and 97 patients randomised. Baseline demographics, clinical and biochemical characteristics were similar between the groups. The baseline median FT4 levels were 51.6 pmol/L (42.2-71.1) and FT3 levels 22.5 pmol/L (5.7-30.8). Both FT4 and FT3 declined at two and four weeks from baseline but were no different between the three groups. At week 2, median FT4 levels declined by 43.3% (25.8-53.3), 39.8% (19.1-55.1) and 33.4% (20.1-62.0) (p=0.988) and at 4 weeks, 50.9% (33.3-63.8), 57.8% (39-70.9), 55.8% (36.2-72.0) (p =0.362) in the cholestyramine, prednisolone and standard treatment group respectively. Median FT3 levels reduced by 51.2% (22.8- 58.9), 59.9% (38.9-69.3) and 50.9% (26.9-63.9) (p=0.084) at week 2 and 60% (39.2-67.9), 67.5% (38.4-78.4), 63.1% (45.7-69.3) (p=0.387) in the corresponding cholestyramine, prednisolone and standard treatment only group. A higher number of gastrointestinal adverse events: constipation, bloating, diarrhea, abdominal pain and vomiting were observed in the cholestyramine group in the first 2 weeks of treatment and no difference in the incidence of hypokalemia between groups. Conclusion: Adjunctive cholestyramine or prednisolone did not improve the biochemical control of uncontrolled moderate to severe Graves’ disease when added to ATDs. The additional use of cholestyramine resulted in a higher number of gastrointestinal adverse events but were mild and self-limiting.