Endocrine Abstracts

Introduction: Fibrous dysplasia (FD)/McCune Albright Syndrome (MAS) is a rare disorder affecting bone and hormonal glands. In FDMAS patients, autonomous GH hypersecretion (GH+) is the most common endocrinopathy after Precocious Puberty and has a great impact on the morbidity and complication rate in patients with craniofacial fibrous dysplasia. However clinical and biochemical features of GH over secretion can be subtle and awareness is warranted. We aimed to explore the GH/IGF-I axis in FDMAS.

Methods: We included 163 patients with measurements of GH/IGF-1. Patients with MAS and GH+ were compared with MAS-patients without GH-. Growth hormone excess was diagnosed by Growth Hormone suppression Test (GST) with 75 grams of glucose, cut off value of 1.45 mU/l. GST is performed in our center in case of progressive Craniofacial FD (CFD), phenotypic changes or IGF-1 levels >1.0SD as typical complaints of acromegaly are often lacking in FDMAS.

Results: 38 (68.4% females) MAS patients were included,10 had GH excess. In the GH+ group, 7 had prolactin co-secretion. All 10 subjects had precocious puberty and CFD, 7 had skull base involvement. Patients with GH+ were diagnosed with FDMAS at a younger age, 3.5 (0-14 yrs) vs 12 years (1-51 yrs) than GH- patients, P<0.01. Median age of GH+ diagnosis was 36 years (7-43 yrs). GH+ was more frequent in males, 7 vs 3. A pituitary microadenoma could be detected in 3 patients (30%). GH+ correlated with visual impairment (P<0.001, r=0.267), n=7 subjects (70%) resulting in blindness in 4. IGF1 levels at time of GH+ diagnosis were within the normal range in 60% of FDMAS GH+ subjects, 48 nmol/l (24.3-88.3) SD 1.95, albeit significantly higher than FDMAS GH- patients, P=0.007. Alkaline phosphatase-(ALP) at first presentation was higher in FDMAS GH+ (P<0.01), also after correction for disease severity. All GH+ patients were started on medical treatment as surgery was not feasible. After 12 months IGF-1 levels dropped to 37.3 nmol/l (17.30-50.60), SD 0.5 (P=0.04). In addition, ALP decreased as well from 1131.5 U/l to 598.5 U/l, P=0.034.

Conclusion: In this cohort of FDMAS patients, GH excess was observed in 26% of patients. 60% had IGF-1 levels < 2.5 SD and could only be diagnosed with GST. GH excess was associated with more visual impairment and higher bone turnover. Early diagnosis using GST should be performed as in 60% of subjects IGF-1 levels were within the normal range as treatment is of upmost importance to prevent complications in the future.