A Case of Type B Insulin Resistance Syndrome Demonstrating Improvement After Leuprolide Administration

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 758-785-Diabetes Case Reports: Type 1, Type 2, MODY & Complications
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-776
Andrew Paul Demidowich*, Jalaja Joseph, Mahtab Niyyati, Rebecca J Brown* and Phillip Gorden
National Institutes of Health, Bethesda, MD
Background: Type B insulin resistance syndrome (TBIR) is caused by autoantibodies to the insulin receptor causing severe insulin resistance. Classically, patients with underlying autoimmune disease present with hyperglycemia, profound weight loss, acanthosis, and ovarian hyperandrogenism due to hyperinsulinemia. Unlike typical PCOS, patients are lean and have normal lipids. We present a case of TBIR with hyperandrogenism and hyperglycemia, with marked improvement after leuprolide administration.

Case: A 32 year old African American woman presented with secondary amenorrhea, virilization, weight loss of 25 lbs over six months, polyuria, and polydipsia.  Work up showed hyperandrogenism [total testosterone (T) 450(2-45ng/dl); free T 25.6(0.2-5.0pg/mL)] and hyperglycemia (fasting glucose 265mg/dl).  Pelvic ultrasound revealed enlarged ovaries. Ovarian venous sampling demonstrated T >1500ng/dL bilaterally.  To suppress T, leuprolide depot injection 11.25mg was empirically given. Within weeks, the patient noted a dramatic improvement in her symptoms, glycemic control, and skin color. 

The patient was referred to the National Institutes of Health 3 months after leuprolide.  Physical exam revealed extensive acanthosis of the face and extensor surfaces, coarse facial features and generalized loss of fat. BMI was 19.7kg/m2.  Labs showed a suppressed gonadotropic axis [LH 0.4U/L; FSH 2.1U/L; total T <20.0(<81ng/dl)], euglycemia [fasting glucose 62mg/dl; insulin 29.3(6-27mcU/ml)] and a lipid profile [Cholesterol 142mg/dl; Trig 56mg/dl; HDL 123mg/dl; LDL-C 8mg/dl] suggestive of hypobetalipoproteinemia.  Immune tests were consistent with mixed connective tissue disease. Patient was lost to follow up and labs 18 months later redemonstrated hyperandrogenic state [LH 8.7U/L; FSH 5.9U/L; total T 476ng/dl], hyperglycemia [fasting glucose 122mg/dl; insulin 279.6] and lipid profile [Cholesterol 116mg/dl; Trig 44mg/dl; HDL 76mg/dl; LDL-C 31mg/dl; FFA 0.49(0.1-0.8mEq/L);ApoB 33(55-125mg/dl)].

Conclusion: This is a unique case of TBIR with hyperandrogenism and hyperglycemia that improved after leuprolide depot. The reduction in androgens after leuprolide suggest that gonadotropins may play a permissive role in stimulation of ovarian androgen production by insulin.  Alternatively, this patient’s simultaneous reduction in both insulin resistance and hyperandrogenism could represent a spontaneous remission of TBIR that coincided with leuprolide administration.

Disclosure: PG: Employee, Amylin Pharmaceuticals. Nothing to Disclose: APD, JJ, MN, RJB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm