Pituitary carcinoma with endolymphatic sac metastasis.

Pituitary carcinoma is characterized by the presence of a metastatic lesion(s) in a location non-contiguous with the original pituitary tumor. The mechanism(s) of malignant transformation are not known. A 15 year-old male was diagnosed in 1982 with a pituitary macroadenoma and acromegaly (random GH 67 ng/ml and no suppression by oral glucose). His prolactin was normal between 18 and 23 ng/ml. Transcranial resection in July 1983 was followed by radiation therapy. The tumor was immunopositive for GH and prolactin. The proliferation MIB-1 index was 0-1%. With aqueous Octreotide 100 mcg 4× daily both GH and IGF-1 became normal. The patient was lost to follow-up and was treated by his local physician. In 2001, his IGF-1 level was 1271 ng/ml, and his random GH was 1.8-2.4 ng/ml by ILMA despite progressive increase in the dose of Sandostatin LAR to 140 mg/month in divided doses. Prolactin remained normal or minimally increased between 15 and 25 ng/ml. In 2009 he was diagnosed with the tumor in the location of left endolymphatic sac. Histological examination showed low grade pituitary carcinoma strongly immunopositive for prolactin but negative for GH. MIB-1 antibody labeled 0-5% cells. In 2012 endoscopic resection of the pituitary tumor remnant was attempted. Immunohistochemical stains were strongly immunopositive for both prolactin and GH, similar to his original pituitary tumor. The MIB-1 proliferation index was low from 0 to 1%. To our knowledge this is the first case of pituitary carcinoma in the endolymphatic sac region. The dichotomy between the cell population of the pituitary lesion (GH/prolactin producing) and the metastasis (purely prolactin-producing) may suggest that the metastatic pituitary lesion derived from a clone distinct from the original one.

Tamoxifen as a therapeutic agent in acromegaly.

OBJECTIVE: Administration of high doses of estrogens to patients with acromegaly has been shown to improve symptomatology of acromegaly and glucose tolerance more than 50 years ago. Selective estrogen receptor modulators (SERMs) mimic the effects of estrogen in bone, liver and the cardiovascular system, but function as an anti-estrogen in endometrial and breast tissue. In this study, we evaluated hormonal effects of a SERM, tamoxifen, in active acromegalic patients with particular emphasis on its use in males. DESIGN: We studied 15 men and 2 post-menopausal women with biochemically-active acromegaly despite the fact that other modalities were ineffective in normalizing their insulin-like growth factor-1 (IGF-1) levels. All patients were treated with tamoxifen 20-40 mg daily for 2-11 months (median of 4 months). METHODS: IGF-1 and growth hormone (GH) levels were assessed immediately before the beginning of treatment and at 2-4 monthly intervals thereafter. Baseline and treatment levels of total and bioavailable testosterone were measured in men. RESULTS: Tamoxifen did not affect basal GH secretion, but it decreased circulating IGF-I in 14 patients (82%) by an average of 90 ± 4 mcg/L, (p = 0.005), and normalized plasma IGF-I in 8 patients (47%). Total and bioavailable testosterone levels increased in all evaluable men (n = 8). Tamoxifen was well tolerated. CONCLUSION: Tamoxifen might be useful in the treatment of patients with biochemically-mild active acromegaly, but longer term studies are warranted.