# A Case of Antibody-Mediated Recurrent Hypoglycemia in a Patient With Mixed Connective Tissue Disease

## TL;DR

A patient with mixed connective tissue disease experienced recurrent hypoglycemia due to insulin antibodies, diagnosed as Hirata’s disease and treated with dietary changes and steroids.

## Contribution

This case highlights the importance of considering IAS in patients with autoimmune conditions and hypoglycemia.

## Key findings

- The patient had elevated insulin and insulin antibody levels with normal C-peptide, indicating antibody-mediated hypoglycemia.
- The patient improved after dietary changes, prednisone, and stopping hydroxychloroquine.
- IAS was confirmed as the cause of hypoglycemia, not an insulinoma.

## Abstract

Insulin Autoimmune Syndrome (IAS) is a rare autoimmune condition in which the body produces antibodies to insulin, leading to recurrent episodes of severe hypoglycemia accompanied by elevated serum insulin and insulin antibody levels. Hypoglycemia can mimic neurological conditions such as stroke. Also known as Hirata’s disease, IAS occurs in patients with autoimmune conditions or a genetic predisposition. IAS is typically treated with immunosuppressive agents, including steroids and rituximab, and patients often undergo thorough evaluations to rule out more common causes of hypoglycemia. Here, we present a case of a patient with pulmonary arterial hypertension (type 1) and mixed connective tissue disease who experienced persistent and recurrent symptomatic hypoglycemia, with glucose levels as low as 35 mg/dL (1.94 mmol/L). C-peptide, a marker of endogenous insulin production, was within normal limits at 2.9 ng/mL (0.96 nmol/L) while the patient was hypoglycemic (glucose <60 mg/dL (3.3 mmol/L)), indicating inappropriate insulin secretion. Total insulin levels were markedly elevated at 7,000 µU/mL (48,615.00 pmol/L), and free insulin levels were elevated at 24 µU/mL (166.68 pmol/L), which initially raised concern for an insulinoma. However, insulin antibodies were evaluated and found to be significantly elevated at >625 µU/mL (>4,340.63 pmol/L), confirming the diagnosis of Hirata’s disease. The patient improved following dietary modifications, initiation of prednisone, and discontinuation of home hydroxychloroquine.