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Background: The treatment of advanced medullary thyroid carcinoma (MTC) has evolved significantly over the past decade. The discovery of genetic abnormalities in MTC has led to the development of targeted therapies such as vandetanib and cabozantinib. Other kinase inhibitors (KI), such as sorafenib, have been investigated in this setting and are an alternative therapeutic option. The lack of specificity of these KIs to a single target may result in additional, unexpected effects. In this report, we describe a patient with metastatic MTC and Ectopic ACTH (adrenocorticotropic hormone) Syndrome in whom treatment with sorafenib resulted in complete resolution of hypercortisolism. Summary: A 45-year-old male with progressive metastatic MTC presented with clinical manifestations suspicious for Cushing's syndrome. Investigation revealed ACTH-dependent hypercortisolism suggestive of Ectopic ACTH Syndrome. Treatment with sorafenib 400 mg twice a day was initiated resulting in a rapid and significant reduction of cortisol and ACTH levels associated with dramatic clinical improvement. The rapid and effective control of hypercortisolism in the absence of a significant tumor reduction raises the question of whether sorafenib may have a direct effect on ACTH or cortisol hypersecretion. Conclusions: This report suggests a previously unknown potential effect of sorafenib on the pituitary-adrenal axis. Further studies will be necessary to investigate the role of sorafenib in other cases of ACTH excess and to understand the mechanisms by which it alters steroid synthesis, action, or secretion. [ABSTRACT FROM AUTHOR]

Background: The treatment of advanced medullary thyroid carcinoma (MTC) has significantly evolved over the past decade. The discovery of genetic abnormalities in MTC led to the development of targeted therapies such as vandetanib and cabozantinib. Other kinase inhibitors (KI), such as Sorafenib, have been investigated in this setting and are an alternative therapeutic option. The lack of specificity of these KIs to a single target may result in additional, unexpected effects. In this report, we describe a patient with metastatic MTC and ectopic ACTH syndrome in whom treatment with Sorafenib resulted in complete resolution of hypercortisolism. Summary: A 45 year-old male with progressive metastatic MTC presented with clinical manifestations suspicious for Cushing's syndrome. Investigation revealed ACTH-dependent hypercortisolism suggestive of ectopic ACTH syndrome. Treatment with Sorafenib 400 mg twice a day was initiated resulting in a rapid and significant reduction of cortisol and ACTH levels associated with dramatic clinical improvement. The rapid and effective control of hypercortisolism in the absence of a significant tumor reduction raises the question whether sorafenib may have a direct effect on ACTH or cortisol hypersecretion. Conclusions: This report suggests a previously unknown potential effect of sorafenib on the pituitary-adrenal axis. Further studies will be necessary to investigate the role of sorafenib in other cases of ACTH excess and to understand the mechanisms by which it alters steroid synthesis, action or secretion. [ABSTRACT FROM AUTHOR]

Long term use of high doses of estrogen and the presence of chronic hyperprolactinemia may, at least in the rat, provoke lesions in the tuberoinfundibular dopaminergic (TIDA) neurons responsible for the control of prolactin (Prl) secretion. This occurrence, which is not yet well documented in humans, may have taken place in a patient on chronic oral hormonal contraceptive (OC) treatment who was seen for primary hypothyroidism, hyperprolactinemia and a pituitary mass. After thyroid hormone replacement, OC withdrawn and bromocriptine treatment, this patient could not maintain normal Prl levels, unless continuously treated with a dopaminergic agonist even when MRI was indicative of a normal situation. Function of TIDA neurons was investigated by TRH test (200 microg IV) performed before and after treatment with 25 mg carbidopa plus 250 mg L-dopa every 4 hours for one day. Basal TSH was normal (3.9 microU/mL) whereas basal Prl was high (67.5 ng/mL); both TSH and Prl levels appropriately increased after TRH: peaks 31.8 microU/mL and 157.8 ng/mL, respectively. After treatment with carbidopa/L-dopa, basal TSH (1.6 microU/mL) and Prl (34 ng/mL) decreased and the response to TRH was partially blocked (10.3 microU/mL and 61 ng/mL, respectively). In spite of a normal response, we discuss the possibility that the persistence of hyperprolactinemia is due to lesion of the TIDA neurons produced by the long term use of high doses of estrogens and by the presence of chronic hyperprolactinemia.