Macroprolactinoma with secondary resistance to dopamine agonists: a case report and review of the literature.

BACKGROUND: Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists. CASE PRESENTATION: A 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week. CONCLUSIONS: Surgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.

Dexamethasone suppression test versus selective ovarian and adrenal vein catheterization in identifying virilizing tumors in postmenopausal hyperandrogenism - a systematic review and meta-analysis.

OBJECTIVE: The diagnostic accuracy of tests in identifying virilizing tumors in postmenopausal hyperandrogenism is limited. This systematic review compares the dexamethasone suppression test against selective ovarian and adrenal vein sampling of androgens in distinguishing neoplastic from non-neoplastic causes of postmenopausal hyperandrogenism. METHODS: Diagnostic test accuracy studies on these index tests in postmenopausal women were selected based on pre-established criteria. The true positive, false positive, false negative, and true negative values were extracted and meta-analysis was conducted using the hierarchical summary receiver operator characteristics curve method. RESULTS: The summary sensitivity of the dexamethasone suppression test is 100% (95% CI 0-100%) and that for selective venous sampling is 100% (95% CI 0-100%). The summary specificity of the dexamethasone suppression test is 89.2% (95% CI 85.3-92.2%) and that for selective venous sampling is 100% (95% CI 0.3-100%). CONCLUSION: There is limited evidence for the use of dexamethasone suppression test or selective venous sampling in identifying virilizing tumors in postmenopausal hyperandrogenism.

Gonadotropin-Releasing Hormone Analogue Stimulation Test Versus Venous Sampling in Postmenopausal Hyperandrogenism.

Postmenopausal hyperandrogenism can be due to excessive androgen secretion from adrenal or ovarian virilizing tumors or nonneoplastic conditions. The etiology of postmenopausal hyperandrogenism can be difficult to discern because of limited accuracy of current diagnostic tests. This systematic review compares the diagnostic accuracy of the gonadotropin-releasing hormone (GnRH) analogue stimulation test against selective ovarian and adrenal vein sampling of androgens in distinguishing neoplastic from nonneoplastic causes of postmenopausal hyperandrogenism. Diagnostic test accuracy studies on these index tests in postmenopausal women were selected based on preestablished criteria. The true positive, false positive, false negative, and true negative values were extracted and meta-analysis was conducted using the hierarchical summary receiver operator characteristics curve method. The summary sensitivity of the GnRH analogue stimulation test is 10% (95% confidence interval [CI], 1.1%-46.7%) and that for selective venous sampling is 100% (95% CI, 0%-100%). Both tests have 100% specificity. There is limited evidence for the use of either test in identifying virilizing tumors in postmenopausal hyperandrogenism.

Kisspeptin signalling and its roles in humans.

Kisspeptins are a group of peptide fragments encoded by the KISS1 gene in humans. They bind to kisspeptin receptors with equal efficacy. Kisspeptins and their receptors are expressed by neurons in the arcuate and anteroventral periventricular nuclei of the hypothalamus. Oestrogen mediates negative feedback of gonadotrophin-releasing hormone secretion via the arcuate nucleus. Conversely, it exerts positive feedback via the anteroventral periventricular nucleus. The sexual dimorphism of these nuclei accounts for the differential behaviour of the hypothalamic-pituitary-gonadal axis between genders. Kisspeptins are essential for reproductive function. Puberty is regulated by the maturation of kisspeptin neurons and by interactions between kisspeptins and leptin. Hence, kisspeptins have potential diagnostic and therapeutic applications. Kisspeptin agonists may be used to localise lesions in cases of hypothalamic-pituitary-gonadal axis dysfunction and evaluate the gonadotrophic potential of subfertile individuals. Kisspeptin antagonists may be useful as contraceptives in women, through the prevention of premature luteinisation during in vitro fertilisation, and in the treatment of sex steroid-dependent diseases and metastatic cancers.