WBR0502

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Author [[PageAuthor::Serge Korjian M.D., Ayokunle Olubaniyi, M.B,B.S [1] (Reviewed by Serge Korjian)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Behavioral Science/Psychiatry
Sub Category SubCategory::Endocrine
Prompt [[Prompt::A 7-year-old boy is brought to the pediatrics clinic for fever of 39 °C (102.2 °F), cough, and wheezing for the past week. Over the last 24 hours, the child has developed nausea, vomiting, and watery diarrhea. The child's past medical history is significant for neurofibromatosis, asthma, and seizure disorder. He is currently taking daily albuterol and valproic acid. His mother explains that she was diagnosed with insulin-dependent diabetes mellitus at his age and fears he may have developed it too. On physical examination, you note a lethargic and ill-appearing boy. His heart rate is 96/min, blood pressure is 124/84 mm Hg, temperature is 36.8°C (98.2°F), and respiratory rate is 28/min. You decide to admit the child for evaluation and monitoring. Over the next two days, the patient has recurrent episodes of hypoglycemia, with fingerstick glucose levels as low as 33 mg/dL. Both episodes occur at night, with the mother alerting the nurses each time. Further investigation reveals a serum insulin level of 2344 µU/mL (5–25 µU/mL) and a C-peptide level of 0.7 ng/mL (0.8–4.0 ng/mL). What is the most likely diagnosis in this patient?]]
Answer A AnswerA::Insulinoma
Answer A Explanation AnswerAExp::Insulinomas are an endogenous source of insulin that release C-peptide as part of the production process of insulin. C-peptide would be elevated along with insulin levels in patients with insulinoma.
Answer B AnswerB::Sulfonylurea intake
Answer B Explanation AnswerBExp::Sulfonylureas are insulin secretagogues that increase endogenous insulin thus increasing C-peptide concentrations.
Answer C AnswerC::Exogenous insulin administration
Answer C Explanation AnswerCExp::Given this patient's high insulin levels and low C-peptide, exogenous administration of insulin is the most likely etiology.
Answer D AnswerD::Type 1 diabetes mellitus
Answer D Explanation [[AnswerDExp::Patients with documented type 1 diabetes mellitus who are on insulin therapy can commonly have episodes of hypoglycemia that often only require dose adjustment of their insulin. However, this patient has never been diagnosed with diabetes mellitus, and should not be on therapy. Diabetes mellitus type 1 as a sole etiology would likely cause hyperglycemia.]]
Answer E AnswerE::Adrenal insufficiency
Answer E Explanation AnswerEExp::Adrenal insufficiency is an important cause of hypoglycemia, but given the documented elevation in insulin levels, it is low on the list of differentials.
Right Answer RightAnswer::C
Explanation [[Explanation::The patient in this scenario is presenting for recurrent hypoglycemic episodes that are most likely related to exogenous administration of insulin. The classical triad in of patients with true hypoglycemia is known as the Whipple's triad. It consists of (1) symptoms known or likely to be caused by hypoglycemia, (2) a low plasma glucose measured at the time of the symptoms, and (3) a relief of symptoms when glucose level is restored to normal. In patients who are not diabetic, a thorough work-up to uncover the etiology of hypoglycemia is indicated. Insulin levels followed by C-peptide (with or without proinsulin) measurement in patients with elevated insulin levels are required as a primary assessment. In patients with elevated C-peptide, further evaluation for sulfonylurea abuse, insulinoma, or autoimmune hypoglycemia. Autoimmune syndromes are a rare cause of hypoglycemia and can be diagnosed by screening for specific antibodies. Sulfonylureas are insulin secretagogues that increase endogenous insulin thus increasing C-peptide concentrations. In patients with low C-peptide i.e. low endogenous production of insulin, and high insulin levels, the cause is exogenous insulin administration and is almost always factitious. This patient is a victim of Munchausen's syndrome by proxy, where the mother induced a health condition in the child while under her care by injecting him with her own insulin.

Educational Objective: Exogenous insulin abuse is a common phenomenon that presents with true hypoglycemia (Whipple's triad) with elevated insulin levels and low C-peptide and proinsulin.
References: Scarlett JA, Mako ME, Rubenstein AH, et al. Factitious hypoglycemia. Diagnosis by measurement of serum C-peptide immunoreactivity and insulin-binding antibodies. N Engl J Med. 1977;297(19):1029-32.]]

Approved Approved::Yes
Keyword WBRKeyword::Insulin, WBRKeyword::Insulinoma, WBRKeyword::Munchausen's syndrome by proxy, WBRKeyword::Hypoglycemia, WBRKeyword::C-peptide
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