RF14 | P984 Early Onset of Insulin Resistance In a Patient with ROHHAD(NET) Syndrome
Authors: Garibaldi Luigi , Zorkot Zeinab , Sastry Shruti 
Published: November 2022

Background

ROHHAD(NET) is a rare syndrome with a constellation of rapid-onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumors. The endocrine disruptions can include obesity, growth hormone dysregulation, hyperprolactinemia, sodium/water imbalances, central hypothyroidism, adrenal insufficiency and puberty disorders. There have been just over 100 cases described thus far and only one adult patient described with severe insulin resistance. We present a pediatric patient diagnosed with ROHHAD(NET) with overgrowth and extremely elevated insulin concentrations

Case

Our patient initially presented with severe obesity, rapid linear growth, abnormal lipids, and elevated fasting insulin at the age of 2.5 years. He progressively developed breathing abnormalities, hypothalamic dysfunction, autonomic dysregulation, and a neural crest tumor. With this group of symptoms, criteria for ROHHAD (NET) was met. He progressed to develop insulin resistance, hyperprolactinemia, diabetes insipidus, central hypothyroidism and central adrenal insufficiency. He also required right adrenalectomy for a poorly differentiated neuroblastoma and ganglioneuroblastoma.

Results

Evaluation of his obesity included a negative monogenic obesity genetic panel (&gt;30 genes tested), normal leptin levels (11.6 ng/ml) and borderline elevated IGF-1 levels 166 ng/ml (z-score 2.5). Glucose levels were usually in the normal range but increased into the diabetes range when he was stressed or sick. HbA1c ranged from 5.6-6.2% (Ref. range &lt;6%) between age 2.5 and 4.5 years. A standard oral glucose tolerance test with blood draws performed at 0, 30, 60 and 120 minutes showed glucose levels of 78,118,123 and 122 mg/dl, insulin of 36,302, 338 and 449 mIU/L and c-peptide levels of 2.9,13.2,14.5 and 16.3 ng/ml respectively. Age at this time was 3.0 years and height, weight and BMI were on the 100% (Z-score 4.28,6.95 and 4.28 respectively) and HbA1c was 5.7%

Management: Although glucose tolerance was normal, insulin and C-peptide concentrations were extremely elevated for age and prepubertal status, suggestive of marked insulin resistance. Subsequently, he was started on liquid Metformin 250 mg BID as an adjunct to a calorie-restricted diet. He tolerated this well. His response to therapy has been hard to assess given frequent illnesses and hospitalizations for his various comorbidities; however, he has shown no progression to hyperglycemia, except during acute sickness.

Conclusion

To the best of our knowledge, this is the youngest patient with ROHADD(NET) reported to have very elevated insulin levels. In addition to rapidly progressing obesity, he had impressive linear overgrowth. Hyperglycemia and insulin resistance could be secondary to severe associated obesity and/or speculatively related to his underlying condition. This case expands the reported morbidities associated with this often-fatal disease

Presentation: Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.