Prolonged Ketosis in a Patient With Euglycemic Diabetic Ketoacidosis Secondary to Dapagliflozin

Since the approval of sodium-glucose cotransporter 2 (SGLT2) inhibitors by the US Food and Drug Administration for type 2 diabetes, there have been several reports of euglycemic diabetic ketoacidosis in patients using this class of medication. We present a case of euglycemic diabetic ketoacidosis where ketonemia and glucosuria persisted well beyond the expected effect of dapagliflozin. Our patient is a 50-year-old woman with type 2 diabetes since age 35 who was taking metformin and dapagliflozin. She presented with fatigue, constipation, and 3 days of reduced oral intake. Laboratory data indicated anion gap acidosis, ketonemia, severe hypokalemia, and minimally elevated blood glucose. She was treated with sliding scale short-acting insulin and electrolyte replacement until hospital day 6, when endocrinology was consulted. An insulin drip was initiated due to persistent ketonemia and reopening of the anion gap, despite improved oral intake and normoglycemia. On stopping the insulin drip on day 9, the β-hydroxybutyrate increased again. It finally stabilized within normal range with the initiation of basal subcutaneous insulin. This case indicates that clinical effects of dapagliflozin persist much longer than the reported half-life of 12.9 hours would predict. To prevent this potentially dangerous complication, patients taking SGLT2 inhibitors who become ill should discontinue the medication, undergo ketone evaluation, and start basal insulin, if ketones are positive. In addition, patients should be educated to stop their SGLT2 inhibitor at least 1 week prior to elective procedures

Severe TSH Elevation and Pituitary Enlargement After Changing Thyroid Replacement to Compounded T4/T3 Therapy

We present the first case of iatrogenic hypothyroidism as a result of compounded thyroid hormone (T4/T3) therapy. The thyroid replacement was changed from 175 µg levothyroxine (LT4) to 57/13.5 µg compounded T4/T3 daily in order to improve the T3 level, despite normal thyroid-stimulating hormone (TSH). This resulted in clinical manifestations of hypothyroidism and high TSH level (150 µIU/mL). Six months later, the patient was referred to our clinic for abnormal pituitary magnetic resonance imaging. On reinitiating a physiologic dose of LT4, clinical and biochemical abnormalities resolved and the pituitary gland size decreased. Our case emphasizes the importance of using TSH level to gauge dose adjustments in primary hypothyroidism. Also, it underscores the current American Thyroid Association recommendation against routine use of compounded thyroid hormone therapy

Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH) but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS) melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation