Endocrine Abstracts

Introduction: We describe a patient with Cushing’s disease caused by a pituitary macroadenoma treated by double transsphenoidal surgery, stereotactic radiosurgery and steroidogenesis inhibitors and also the challenging management of a patient with multiple comorbidities, including chronic leg ulcers, which are related to increased morbidity and health costs.

Case report: In October 2019, a 67-year-old patient presented with intense headache, left temporal visual impairment and pituitary macroadenoma (3.4 cm). He was diagnosed with Cushing’s disease (serum cortisol=17.55 mcg/dl after 2 mg/day x48h Dexamethasone, ACTH=197 pg/ml), optic chiasm syndrome and thyrotropin and gonadotropin insufficiency. The patient had significant comorbidities: secondary hypertension and diabetes, episodes of tachyarrhythmia and femoral artery stenosis. After transsphenoidal surgery, despite 3 months remission of hypercortisolism (basal serum cortisol=0.14 mcg/dl), a 2.1 cm remnant progressive tumor along with biochimical hypercortisolism-serum cortisol=14 mg/dl after 1 mg Dexamethasone, led to a 6 months dopamine agonist treatment. In 2020, progressive chronic ulceration appeared in the lower limbs. Despite the January 2021 second transsphenoidal operation, in June 2021, the hypercortisolism worsened: severe hypokaliemia (2.5 mmol/l despite potassium replacement), uncontrolled diabetes (HbA1c=11%), BP=220 mmHg despite triple therapy, so a steroidogenesis inhibitor and glucocorticoid receptor blocker therapy were initiated. Afterwards, right opthalmoplegia and severe headaches appeared. Pituitary apoplexy and stroke were ruled out by MRI showing a tumoral remnant, invasive in both cavernous sinuses. The treatment was continued only with Metyrapone 500 mg/day. In August 2021, the patient developed adrenal insufficiency while using Metyrapone (BP=110/70 mmHg, serum glucose=69 mg/dl, serum cortisol=1.57 mcg/dl), so Prednisone 5 mg/day was prescribed, thus receiving block and replace regimen. The patient was treated with gamma knife radiosurgery in September 2021. Afterwards, the infected leg ulcers with Grame negative bacteriae forced him to become wheelchair-bound, requiring repeated hospital admissions, with two episodes of acute renal injury. In January 2022, laboratory tests found persistent hypercortisolism (serum cortisol=20 mcg/ml after 1 mg Dexamethasone without any treatment). Block and replace regimen was restarted. The cardiovascular examination established the need for bilateral thigh amputation, for now, only one having being performed.

Conclusions: This case highlights how the multiple and aggressive complications of Cushing’s disease can significantly affect the quality of a patient’s life. The chronic leg ulcers, the risks of hospitalisation and the drug toxicity eventually led to amputation. Furthermore, achieving eucortisolism is a constant challenge in the management of recurrent Cushing’s disease. Consequently, rigorous and repeated long-term follow-up evaluations of this condition are mandatory.