Endocrine Abstracts

Case history: This 27 year female was first seen at GSTT in 2012, having had treatment for acromegaly due to a presumed GH-secreting adenoma in 2007 (Trans-sphenoidal surgery × 2, EBRT (2007), pegvisomant (2007-2012 (discontinued due to adverse effects)), & GammaKnife SRS (2011). GH and IGF-1 remained elevated and further treatment with pegvisomant/ SSA was declined. Abnormal bone growth with jaw and skull asymmetry was evident from age 10 years and final height was 182 cm. Imaging confirmed extensive polyostotic fibrous dysplasia. Café-au-lait pigmentation was present resulting in a clinical diagnosis of McCune Albright Syndrome (MAS). In 2014 genetic testing of blood lymphocytes did not confirm GNAS1 mutation. The acromegaly remained uncontrolled (average IGF-1 ~75 nmol/l) with SSA used for a brief period in 2016 with little biochemical response.

Investigations: Spinal imaging was performed in 2016 and demonstrated a left adrenal mass (4.4 cm, characterised as an adenoma). ACTH was undetectable with elevated cortisol (UFC 1023 nmol/24hrs) confirming autonomous cortisol secretion, which has only rarely been reported in adults with MAS. Laparoscopic adrenalectomy was performed in 2017 and post-operatively there was cortisol insufficiency (which has persisted to 2024). Although clinical features of Cushing’s syndrome were thought to be mild pre-adrenalectomy, post-operatively there was weight loss and reduction in facial fullness and reduced abdominal adiposity. Despite no GH-directed treatment the IGF-1 fell into the age-matched reference range following the adrenalectomy, suggesting cross-talk between the adrenal adenoma and pituitary GH secretion, possibly by production of GHRH (unproven). In 2017 analysis of bone obtained from TSS demonstrated low-level mosaicism for the GNAS c.601C>T pathogenic sequence variant confirming MAS. The patient is currently 38 years of age and clinically well. Bone turnover markers are non-elevated. Bisphosphonate therapy has not been used. Pregnancy is being considered.

Conclusions: MAS is rare, affecting 1:100000 to 1:1000000 people. The disorder is characterized by the classic triad of polyostotic fibrous dysplasia (POFD), cafe-au-lait skin pigmentation, and peripheral precocious puberty. MAS is clinically heterogeneous and may include thyrotoxicosis, pituitary gigantism, and Cushing’s syndrome (usually in neonates with bilateral adrenal disease). Our case highlights the MAS is a clinical diagnosis and routine peripheral blood mutation testing may fail to demonstrate a mutation. This patients experience emphasizes the need for long-term surveillance and vigilance for development of endocrine neoplasia and associated hormone excess in MAS.