Endocrine Abstracts

Introduction

Hadju Cheney syndrome (HCS) is a rare progressive and debilitating genetic disorder that is characterized by a high degree of phenotypical pleiotropy. We report the first clinical case of a 44-year-old patient with HCS, diabetes and adrenal insufficiency (AI).

Observation

A 44-year-old patient with a history of myocardial infarction at the age of 33 and diabetes for 2 years on oral antidiabetic drugs is admitted for switching to insulin therapy. On examination, he had short stature, facial dysmorphism, early tooth loss with diffuse acroosteolysis on standard radiograph. The biological assessment showed a normal phosphocalcic balance. Bone densitometry showed diffuse osteoporosis. The renal ultrasound and the cardiac ultrasound were without abnormalities. Faced with the characteristic polymalformative syndrome, the diagnosis of HCS has been made and the genetic study looking for a mutation in the NOTCH2 gene is underway. In addition, the patient presented repeated episodes of hypoglycemia during his hospitalization with an inappropriate cortisolemia at the time of the hypoglycaemia, which allowed us to retain the diagnosis of AI very probably of central origin. The patient was put on hydrocortisone.

Discussion

HCS is a rare genetic skeletal syndrome. The diagnosis of this syndrome was made in our patient based on the characteristic clinical features and imaging findings in hands, feet and skull. Recently it has been shown that restricted range of mutations in the terminal exon of NOTCH 2 causes this syndrome. There has been no report about the linking of HCS and DM, although several studies addressed the pancreas and Notch signaling. Discussing the type of diabetes in our patient was therefore a bit difficult, we ruled out type 1 diabetes as well as mitochondrial diabetes. Type 2 remains the most likely with rapid recourse to insulin therapy. In addition, cranial dysplasia can be the cause of pituitary insufficiency which could explain the adrenal insufficiency in our patient. However, there was no other pituitary insufficiency.

Conclusion

Until this case, there has been no reported case of HCS with DM and AI. The present case indicates that there may be a link between HCS and DM in regard to the mutation of NOTCH2. Confirmation awaits further studies of the relationship between insulin secretion and NOTCH2 signaling.