Endocrine Abstracts

Introduction: Cushing syndrome is a complex disease with multisystemic manifestations. It includes skin and connective tissue abnormalities, in which glucocorticoids reduce the synthesis and production of collagen, resulting in skin thinning, subcutaneous vascular tissue frailty and mucocutaneous bleeding.

Case report: A 59-year-old woman with history of hypertension, type 2 diabetes, hypercholesterolemia, and chronic kidney disease, was admitted to the Intensive Care Unit due to severe hypokalaemia. In the past months, she referred muscle weakness, asthenia, weight gain, and more recently elevated blood pressure with headaches. Physical examination at admission revealed a cushingoid phenotype and haemorrhagic diathesis (petechiae on the abdominal girdle and lower limbs). Blood work-up was consistent with ACTH-dependent hypercortisolism and MRI showed a pituitary macroadenoma invading adjacent structures. Unexpectedly, the patient developed subconjunctival haemorrhage, epistaxis, bleeding at puncture sites, and diffuse petechiae. No menorrhagia, haematuria, gastrointestinal bleeding or hemarthrosis occurred. The patient was not taking acetylsalicylic acid, non-steroidal anti-inflammatory drugs, or anticoagulants. Considering the mucocutaneous diathesis, the patient was submitted to an extensive diagnostic study which included grade I thrombocytopenia (100-110×10⁹/l) (reference range: 170-430×10⁹/l), normal coagulation time (PT, aPTT and TT), increased fibrinogen level, normal platelet aggregation studies by Platelet Function Analyser (PFA-100) and Aggregometry test, increased Von Willebrand factor and activity, and increased VIII factor. Given the absence of platelet or coagulation abnormalities that could justify the haemorrhagic diathesis, it was assumed to be related with vascular and subcutaneous fragility secondary to hypercortisolism. A skin biopsy was not carried out because of the established skin diathesis and since it would not change the therapeutic attitude. The bleeding diathesis did not allow for surgical intervention. Following multidisciplinary discussion, mifepristone was initiated at 200mg/day, leading to significant improvement in the haemorrhagic diathesis. The patient underwent bilateral adrenalectomy due to the risk of a neurosurgical procedure. However, postoperatively, the patient developed multisystem organ failure of unknown origin resulting in the patient’s demise.

Conclusion: The authors report on a case of severe Cushing disease, whose main clinical manifestations were the hypokalaemia and haemorrhagic diathesis. Mucocutaneus haemorrhage is not usually severe in Cushing’s, often being the thromboembolic events the clinician’s major concern from the haematological standpoint. Medical treatment with mifepristone rapidly improved both conditions and can be considered a treatment option in this setting. Clinical heterogeneity in Cushing disease is very wide and a multidisciplinary approach should be undertaken to improve patient care.