SAT-250 A Case of Late Recurrent Cushing’s Disease Presenting with Proximal Myopathy

Abstract

Patients with Cushing’s disease (CD) present with a variety of symptoms and comorbidities including central obesity, hypertension, hyperglycemia, fatigue, weakness, insomnia and mood changes. Proximal myopathy is one of the classical signs of hypercortisolism and patients typically report difficulty rising from a seated position or climbing stairs. Due to variability in clinical presentation, with some patients showing subtle or few symptoms, the diagnosis of CD can be delayed. We describe a patient with late recurrent CD whose primary symptom was proximal myopathy. A 63 yr. old man presented to our clinic with complaints of progressive muscle weakness and fatigue. He had been successfully treated for CD at age 35 with transsphenoidal pituitary adenomectomy. He had been on hormonal replacement therapy for panhypopituitarism since surgery including levothyroxine, testosterone and glucocorticoids. He noted progressive weakness for several years prior to presentation in our clinic. Earlier evaluations revealed vitamin B12 and vitamin D deficiency, but supplementation did not lead to significant symptom improvement. He suffered two episodes of unprovoked deep venous thrombosis with pulmonary embolism and developed a left biceps tear that required hospital admission. During admission, his muscle weakness was exacerbated by immobility and he was subsequently referred to endocrinology for consideration of steroid induced myopathy. He had been on physiologic glucocorticoid replacement since diagnosed with panhypopituitarism. At the time of our evaluation, he was able to ambulate with a walker, but was unable to climb stairs, drive a car and required assistance with activities of daily living. His only other symptoms were fatigue and insomnia. Laboratory testing after holding prednisone revealed: morning cortisol 31.7 mcg/dl (reference interval [RI], 4.0-22.0), ACTH 128 pg/mL (RI 6 - 50), FSH <0.7 mIU/mL (RI 1.6 - 8.0), LH <0.2 mIU/mL (RI 1.6 - 15.2), testosterone 85 ng/dL (RI 250 - 827), IGF-1 55 ng/mL (RI 41 - 279), prolactin 4.9 ng/mL (RI 2.0 - 18.0), TSH 0.01 mIU/L (RI 0.40 - 4.50), free T4 1.5 ng/dL (RI 0.8 - 1.8), HbA1c 6.8% (RI <5.7%). Prednisone was discontinued and hypercortisolism was confirmed by 1 mg overnight dexamethasone (dex) suppression test (Cortisol 32.4 mcg/dL, dex 517 ng/dL, RI 180-550 ng/dL) and elevated 24 h urine free cortisol 315.4 mcg/24h (RI 4.0 - 50.0). 8 mg DST showed mild cortisol suppression (Cortisol 21.2 mcg/dL, dex >1000 ng/dl). MRI confirmed recurrent tumor (1.2 x 0.8 x 1.3 cm) extending into the right cavernous sinus and the patient underwent repeat transsphenoidal tumor resection. Pathology confirmed ACTH adenoma. Our case report highlights that patients with CD can have late recurrences and require long term monitoring for return of hypercortisolism, even in cases of prior panhypopituitarism.