Endocrine Abstracts

The association of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) are widely and to with good effect used in the treatment of many neoplasms. Much evidence of endocrine side effects has been reported for both ICIs and TKIs especially to the pituitary and thyroid functions; however, there are few records of primary adrenal insufficiency. We report the case of a 44-year-old soldier, examined for elevated hematocrit findings. Abdominal ultrasound and thoracoabdominal CT scan revealed a left renal tumor with bilateral pulmonary nodules and right iliac lytic lesion. Underwent left nephrectomy, histology revealed a renal clear-cell renal Ca with variant renal vein invasion by sarcomatoid cells (grade 4). pT3a. Adjuvant therapy with pembrolizumab and axitinib was started. Eight weeks later fT4 serum levels were elevated (2.15 ng/dl) with suppressed TSH (0.07 mUI/l) (normal range: 0.8-1.8 and 0.35-4.6, respectively). The endocrinologist advised TPOAb and TRAb resulted present and absent, respectively; a pseudonodular picture is was detected on ultrasound and a diffuse hypocaptation is was found on thyroid scintigraphy, suggestive of thyrotoxic-onset thyroiditis. Therapy with bisoprolol alone was started; after 4 months the hyperthyroidism evolved into hypothyroidism and therapy with L-thyroxine was started. At the same time, the pituitary-adrenal axis was also studied with evidence of normal cortisol (13.5 mg/dl) and elevated ACTH serum levels (128 pg/ml) (normal range 6-28 and 0.0-46.0, respectively) suggestive of primary hypoadrenalism and cortisone acetate was started; the anti21OH Abs were negative. The patient maintained a good quality of life and given the good response of the tumor, documented by a CT scan, the oncological therapy was continued. To the restaging CT scan after 10 months of therapy, despite the excellent clinical conditions of the patient and good hormonal compensation, the presence of a right adrenal lesion of 1.6 cm was instead detected, with increased glucose metabolism on PET/CT scan 18F-FDG with clearly reduced subcentimeter lung lesions on CT scan, and nonhypermetabolic on PET/CT scan, and disappearance of the right iliac lytic lesion. Right adrenalectomy was performed. Histology revealed a clear cell renal Ca metastasis. In conclusion : 1. Immune-mediated thyroiditis with transient hyperthyroidism appeared after 8 weeks of therapy followed by hypothyroidism; 2. primary hypoadrenalism, negative for Ab21OH, appeared after 4 months of therapy; 3. good clinical, pulmonary and bone response to therapy with pembrolizumab and axitinib was obtained, but appearance at 10 months of right adrenal lesion as a heterogeneous response to therapy.