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T Skoric, M Korsic, K Zarkovic, V Plavsic, N Besenski, L Breskovac, Z Giljevic and J Paladino

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

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I Pentz-Vidovic, T Skoric, G Grubisic, M Korsic, T Ivicevic-Bakulic, N Besenski, J Paladino, V Plavsic and K Zarkovic

OBJECTIVE: To demonstrate the clinical course in a young female with gonadotroph adenoma causing ovarian stimulation. PATIENT AND METHODS: Our patient was a 23-year-old woman with a history of oligomenorrhea who had previously undergone bilateral ovarian wedge resection owing to the clinical appearance of polycystic ovaries. Two years later, she sought treatment for headache, galactorrhea, history of spotting and lower abdominal distension. FSH, LH, beta-LH, inhibin A and B, estradiol, prolactin (PRL), and beta-chorionic gonadotrophin (beta-CG) were measured, and the responses of FSH, LH and beta-LH to thyrotrophin-releasing hormone (TRH) were documented. Immunohistochemical analysis of the tumor tissue was performed after surgery. Five years after the trans-sphenoidal surgery, the patient again became oligomenorrheic. A large recurrent adenoma was diagnosed on CT one year later. Transvaginal ultrasound showed ovaries of normal size with multiple small cystic formations simulating a polycystic pattern, While the patient was awaiting surgery, a pituitary apoplexy occurred. Emergency decompressive surgery was performed and the patient fully recovered. RESULTS: Enlarged ovaries were found on ultrasound examination simulating a hyperstimulation-like pattern. At that time, elevated levels of FSH (13.4IU/l) and marginally elevated levels of beta-LH (1.43ng/ml) were found, whereas the level of LH (0.5IU/l) was subnormal. Plasma estradiol was markedly supranormal (6150pmol/l). Levels of inhibin A and B were elevated (326pg/ml and 588pg/ml respectively). The prolactin level (70ng/ml) was increased, whereas beta-chorionic gonadotrophin (beta-CG) was normal. Significantly increased FSH, LH, and beta-LH responses to TRH stimulation were documented. Pituitary macroadenoma was found on MRI scan and removed by trans-sphenoidal surgery. Immunohistochemical examination showed high positivity for beta-CG and LH, and slight positivity for FSH. Five years after the surgery, estradiol was elevated (1160pmol/l), whereas basal levels of LH (4.65IU/l) and FSH (3.98IU/l) were not suppressed. After the second operation, immunostaining of the adenoma tissue confirmed the previous findings. CONCLUSIONS: Measurement of gonadotrophins in our case did not prove to be a method for identifying a large recurrent gonadotroph pituitary adenoma. The sonographic ovarian imaging varied from a polycystic- to an ovarian hyperstimulation-like pattern during the evolution of the tumour.