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1/10. An unusual steroid-producing ovarian tumour: case report.

    The rapid onset of virilization in a post-menopausal woman is usually the result of androgen secretion from a tumour of adrenal or ovarian origin. Androgen secreting neoplasms of the ovary are rare and usually show autonomous secretion. Rarely, these may be driven by the high levels of gonadotrophins seen in the post-menopausal state. We describe the case of a 67-year-old woman with high serum testosterone and estradiol in association with the high gonadotrophin levels usually associated with the post-menopausal state. All hormonal parameters showed a significant suppression over 12 h with administration of the GnRH antagonist, cetrorelix. This observation implies that excess hormone synthesis was of ovarian origin and was gonadotrophin driven. Localization of the tumour was not possible by conventional ultrasound or computerized tomography scanning, but was achieved by venous sampling. Complete cure was achieved by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with restoration of the endocrine profile to that expected for a post-menopausal woman. Rapidly acting GnRH antagonists, such as cetrorelix, offer a safe and useful diagnostic and therapeutic option in the management of ovarian steroid-secreting tumours, which show gonadotrophin dependency.
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ranking = 1
keywords = endocrine
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2/10. The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review.

    Although many prostate cancer cases relapse to a hormone-insensitive state, endocrine therapy involving androgen depletion by orchiectomy or by treatment with LHRH-analogue as well as blockade of the androgen receptor (AR) with anti-androgens remains a primary treatment option. quality of life (QOL) however, is a prime consideration of men choosing such an approach. In this report we discuss a synergistic combination of 150-mg bicaltumide (Casodex) and 5 mg finasteride (Proscar) in the treatment of a 69-year-old patient with a relapsed (biochemical failure) Gleason score 7 prostate cancer, initially treated with external beam radiation therapy. A successful clinical outcome as evidenced by undetectable serum PSA, bone scan density and overall general well-being was accomplished with minimal side effects. Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that the combination of bicaltumide-finasteride at the same ratio as used clinically, produced synergistic effects on the inhibition of cell proliferation and AR expression/phosphorylation. A more complete inactivation of the AR on this regimen may have had the effect of constraining the ability of the AR to mutate, and/or diminishing the ability of androgen independent clones to evolve. Thus, passage to androgen independence may have been slowed or arrested.
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ranking = 1.0080606118123
keywords = endocrine, bone
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3/10. Selecting adjuvant endocrine therapy for breast cancer.

    This year alone, more than 215,000 women in the united states will be diagnosed with, and over 40,000 will die from, invasive breast cancer. Recently, mortality from female breast cancer has declined despite an increase in its incidence. This decline corresponds with improved screening for prompt tumor detection, and advances in the treatment of early disease. Of these, endocrine therapy has played a prominent role. For women with estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive breast cancers, endocrine therapy has proven to be a major component of adjuvant therapy, but it is not effective in women whose breast cancers lack ERs and PRs. The selective estrogen-receptor modulator (SERM) tamoxifen has been well established as safe and effective in the adjuvant care of both pre- and postmenopausal women with hormone-receptor-positive early breast cancer. For premenopausal women, ovarian suppression is an important option to be considered. Additionally, the aromatase inhibitors have recently demonstrated utility in postmenopausal women. The ideal sequencing of treatment with tamoxifen and/or an aromatase inhibitor is the subject of several ongoing studies. Factors involved in selecting an appropriate endocrine regimen have grown considerably over the past decade. It is becoming more important for those caring for women with breast cancer to fully understand the available endocrine treatment options and the prognostic and predictive factors available to help select the most appropriate treatment. The goal of this article is to assist clinicians in making decisions regarding adjuvant hormonal therapy and to provide information regarding available clinical trials. To achieve this, the therapeutic options for hormonal therapy will be reviewed, as will prognostic and predictive factors used in making decisions. Finally, four cases illustrating these difficult decisions will be discussed, with recommendations for treatment.
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ranking = 8
keywords = endocrine
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4/10. Orbital metastasis from prostate cancer: an atypical case of neuroendocrine dedifferentiation during progression from hormone-sensitive to refractory stage.

    We report a case of orbital metastasis from a neuroendocrine dedifferentiated prostate cancer during progression from hormone-sensitive to hormone refractory stage. A patient receiving androgen deprivation for hormone-sensitive prostate cancer presented with sudden-onset right-sided ptosis and an increasing serum prostate-specific antigen level. Imaging studies revealed a mixed blastic and lytic lesion involving the right orbital wall and the right cavernous sinus. Comparison of the metastatic histology with the original pathology confirmed a histologic change to poorly differentiated prostate adenocarcinoma with neuroendocrine features. Local radiation of the lesion and palliative systemic chemotherapy resulted in marked short-term improvement of all presenting symptoms. Because prostate cancer metastasis involves hematogenous and lymphatic routes, we also evaluated expression of the vascular endothelial growth factor (VEGF) and receptors (VEGFR-1, VEGFR-2, and VEGFR-3) in the metastatic deposit by immunohistochemistry. Strong expression of VEGFR-2 and VEGFR-3 restricted to the malignant epithelium was noted. We recommend a second biopsy of atypical prostate metastasis associated with sudden change to aggressive clinical behavior in order to evaluate for dedifferentiation features before planning appropriate treatment interventions especially in patients who are candidates for systemic chemotherapy.
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ranking = 6
keywords = endocrine
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5/10. Changing strategies in the treatment of hormone-dependent breast cancer.

    Hormone Receptor concept provides better prediction of hormone dependency of breast cancer and therefore proper selection of therapy. The fate of receptors following hormonal manipulation is not clearly understood. It is suggested that in a hormone-dependent breast cancer, the cessation of response to one form of hormonal therapy is not an indication of emergence of hormone independence of the cancer. Contrary to the present belief, the author suggests that the hormone-dependent tumors retain their biological and biochemical characteristics in the recurrent tumor and therefore will respond to other forms of endocrine therapy. The presence of extraglandular synthesis of estrogen is considered as a major reason for the relapse of a regressing breast cancer following endocrine manipulation. A hypothesis is advanced for test in a clinical trial.
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ranking = 2
keywords = endocrine
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6/10. Cancer of the breast. Endocrine and hormonal therapy.

    Additive hormonal therapy remains the treatment of choice for disseminated breast cancer in postmenopausal women. patients with hormone-dependent tumors receive excellent and long-lasting palliation from alterations in the hormonal milieu. Now that hormone receptor assays are clinically available, responses can be accuratedly predicted in a large percentage of cases. tables 11--6 is a summary of additive hormonal therapy in postmenopausal patients. Endocrine ablative therapy remains of primary importance in premenopausal women because of the superior results, but androgens or antiestrogens may be helpful when patients are not surgical candidates. castration continues to be the initial approach, with adrenalectomy or hypophysectomy reserved for promising candidates. In postmenopausal women the initial choice is estrogens. The exceptions are those patients with metastases limited to bone, when androgens excel because of an equivalent objective response and superior subjective and metabolic effects. patients who respond to estrogens and then progress are observed for a rebound regression following the discontinuation of estrogen therapy. Whereas some who do not respond to androgens will respond to estrogens, the converse does not appear to be true (Kennedy, 1974). Currently progestins are the secondary hormonal agent of choice in postmenopausal women, but they may be displaced by antiestrogens as more data become available. In general, if a patient's tumor lacks estrogen receptors or the patient fails to respond to an adequate trial of endocrine or hormonal therapy, one should proceed directly to cytotoxic chemotherapy. A suggested plan for the integration of endocrine with hormonal therapy and both with other forms of palliation is diagrammed at the end of Chapter 12.
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ranking = 2.0080606118123
keywords = endocrine, bone
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7/10. Response of advanced breast cancer to total endocrine ablation after exacerbation on tamoxifen: results in seven patients and possible mechanism of action.

    Usage of tamoxifen in the treatment of advanced breast cancer is increasing and is advocated by some authors as primary therapy in all estrogen receptor positive cancer patients. tamoxifen is an incomplete estrogen antagonist with partial estrogen agonist activity as well. tamoxifen-induced exacerbation of breast cancer ("tamoxifen flare") is reported to occur in 4-20% or more of treated patients. Management of this condition has varied from stopping treatment to continued administration or reinstitution of tamoxifen after flare symptoms subside. Responses have occurred in some patients so treated, although the remissions do not appear durable. The seven patients with advanced breast cancer in this report experienced disease exacerbation with tamoxifen therapy. Endocrine ablation afforded all patients excellent pain relief and disease control with prolonged survival in six of the seven. There have been no studies directly examining the disease course in flare patients continuing on tamoxifen. Persistence in treating these patients with an incomplete antagonist-agonist may deprive them of full survival benefit possible through ablative procedures when used in sequential treatment.
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ranking = 4
keywords = endocrine
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8/10. ureteral obstruction secondary to metastatic breast carcinoma.

    An uncommon manifestation of breast cancer is ureteral obstruction secondary to metastatic disease. Five patients who recently developed this complication from two to 20 years after the diagnosis of breast cancer are described. Only two of the five patients had urinary symptoms. All of the patients were older, postmenopausal females who had bone metastases and all had responded to previous hormonal manipulation. Bone scanning was useful in detecting unsuspected hydronephrosis in two patients. Retroperitoneal disease appears to be a complication of long standing breast cancer which is usually hormonally dependent. Routine examination of the bone scan for renal asymmetry may aid in the diagnosis, especially in asymptomatic patients.
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ranking = 0.016121223624515
keywords = bone
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9/10. Endocrine characterization of the adrenal adenomas in a case of primary aldosteronism.

    A 48-year-old man with typical clinical and biochemical features of primary aldosteronism was revealed on operation to have two adrenocortical adenomas in the left gland. An ACTH-dependent pattern of aldosterone secretion was demonstrated in terms of the parallel circadian rhythm of aldosterone with cortisol and the exaggerated response to ACTH but not to angiotensin ii. aldosterone and cyclic amp release in vitro was studied using collagenase-dispersed cells of each adenoma. Not only the large adenoma but the small one showed basal and ACTH-stimulated releases of aldosterone greater than those by the adjacent tissue. In response to angiotensin ii and potassium, the small adenoma showed a larger maximum increment of aldosterone than the large adenoma. This difference in endocrine features of the two adenomas suggests a possible transformation in their nature during development. An exaggerated cyclic amp release by the adenomas in response to ACTH in vitro suggested the possible role of increased adenylate-cyclase activity in the hyperresponse of aldosterone to ACTH in this case.
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ranking = 1
keywords = endocrine
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10/10. Steroid receptor proteins in human meningiomas.

    Steroid receptor assays play an important role in determining the efficiency of endocrine therapy for patients with breast cancer. Other tumors could also be hormonally dependent and patients with these tumours might also benefit from endocrine manipulation. Thus, patients with meningiomas were tested for the presence or absence of estrogen and progesterone receptors. The results showed that a majority of meningiomas lacked estrogen receptors but contained large amounts of progesterone receptor. Therefore, it should be possible to use antiprogestin therapy in cases where complete surgical resection of meningiomas is not possible.
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ranking = 2
keywords = endocrine
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