Two Cases of Severe Insulin Resistance in Pregnancy: A New Diagnosis of <i>INSR</i> Variant and a Patient with SHORT Syndrome

Insulin sensitivity decreases during pregnancy; hence, higher insulin requirements occur in cases of preexisting insulin resistance. In pregnant patients with extremely high insulin requirements, a monogenic etiology may be present. We present 2 cases of severe insulin resistance in pregnancy. Heterozygous insulinreceptor (<i>INSR</i>) pathogenic gene variants were detected in a 31-year-old woman with a high body mass index and type 2 diabetes mellitus who needed up to 2200 units/day of insulin. A 25-year-old woman with lipodystrophy and insulin resistance, associated with SHORT syndrome (short stature, hyperextensible elbows, ocular depression, teeth eruption) due to a heterozygous <i>PIK3R1</i> pathogenic variant developed insulin requirements up to 766 units/day after exposure to exogenous steroids. Few case reports describe patients with <i>INSR</i> variants in pregnancy but none among women with coexisting obesity. No previous cases of SHORT syndrome in pregnancy have been described. These cases serve as a reminder to consider differential diagnoses for severe insulin resistance presenting in pregnancy and highlight a need for future research regarding treatment options.