Association of genetic polymorphisms on methotrexate toxicity in patients with rheumatoid arthritis.

Cushings syndrome (CS) is a relatively rare disease characterized by autonomous hypersecretion of cortisol. The incidence of CS is estimated to be equal to 2-3 cases per million inhabitants per year. The incidence of acromegaly is 3-4 patients per 1 000 000 per year. The disease is caused by hypersecretion of growth hormone which is mainly caused by benign tumour of the pituitary gland. In our case report we present a 41- year old woman suffering from both Cushings syndrome and acromegaly. The patient was examined in National Institute of Endocrinology and Diabetology Ľubochňa for a centripetal type of obesity and hirsutism. Laboratory tests revealed high plasma cortisol levels without circulating variation, hypercortisoluria and elevated plasmatic levels of ACTH. A 2 mg dexamethasone blockade was performed without adequate cortisol suppression in serum and urine up to 8 mg blockade resulted in suppression of 24 hour urine free cortisol. A magnetic resonance imaging (MR) scan revealed suspect pikoadenoma of the pituitary gland (size 2mm). Subsequently trans-sphenoidal resection was performed. Histopathological and immunohistochemical examinations did not reveal the ACTH-producing pituitary adenoma. After surgery hypercortisolism persisted with newly revealed hypersomatotropism. Treatment with Ketoconazole at dose 200mg 1/ 2-0-1 and somatostatin analogues (Lanreotide) at dose 120mg every 42 days were initiated. Control magnetic resonance imaging of the sella demonstrated small tumour of pituary gland of size 3×5mm. Later 3 years after first surgery another trans-sphenoidal resection of residue was performed. Histological and immunohistochemical examinations did not confirm adenoma with ACTH and RH secretion. After second surgery, IGF-1 plasma levels were not normalized with persistence of hypercortisolism. The treatment with Lanreotide at the initial dose as well as Ketoconazole was reinitiated (with increased dose of Ketoconazole to 1-1-1 tbl per 200mg).