The effect of sodium valproate in Cushing's disease, Nelson's syndrome and Addison's disease

Reincke, Martín; Allolio, Bruno; Kaulen, D.; Jaursch-Hancke, Cornelia; Winkelmann, W.

doi:10.1007/bf01726927

Cited by 14 publications

(9 citation statements)

References 16 publications

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“…In the early 1980s, several reports described patients with CD responsive to treatment with valproic acid (594,604,(612)(613)(614). Despite these, placebo-controlled studies of the acute effects of valproic acid infusion did not demonstrate ACTH-lowering effects in 17 patients with CD (615)(616)(617). Longer periods of treatment similarly failed to show a clinical or hormonal improvement in the near totality of patients patients with CD after 3 weeks to 3 months of treatment (618,619).…”

Section: Neuromodulatory Drugsmentioning

confidence: 86%

The Treatment of Cushing's Disease

et al. 2015

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Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery, and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease; or as postsurgical treatment, in cases of failure or incomplete surgical tumor resection; or as bridging therapy before, during, and after radiotherapy while waiting for disease control; or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analog pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of Cushing's syndrome when associated with impairment of glucose metabolism in case of the lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.

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Section: Neuromodulatory Drugsmentioning

confidence: 86%

The Treatment of Cushing's Disease

et al. 2015

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“…One of the more common radiosurgical techniques used to manage Cushing's disease is GK radiosurgery. 7,43,50,85,70 Vik-Mo et al published a study in which 10 patients with Nelson's syndrome underwent GK treatment. 84 On average, tumor volume decreased by 32% for 9 patients but not at all for 1 patient.…”

Section: Surgical Treatmentmentioning

confidence: 99%

“…40 Even when other reports are taken into consideration, effectiveness of sodium valproate for Nelson's syndrome remains inconclusive. 35,48,70 Temozolomide is an orally administered alkylating agent capable of crossing the blood-brain barrier. Its active form is methyl-triazeno-imidazole-carboxamide, which methylates DNA at the O 6 position of guanine.…”

Section: Medical Therapymentioning

confidence: 99%

Nelson's syndrome: a review of the clinical manifestations, pathophysiology, and treatment strategies

Patel¹,

Eloy

Liu

2015

FOC

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Nelson's syndrome is a rare clinical manifestation that occurs in 8%–47% of patients as a complication of bilateral adrenalectomy, a procedure that is used to control hypercortisolism in patients with Cushing's disease. First described in 1958 by Dr. Don Nelson, the disease has since become associated with a clinical triad of hyperpigmentation, excessive adrenocorticotropin secretion, and a corticotroph adenoma. Even so, for the past several years the diagnostic criteria and management of Nelson's syndrome have been inadequately studied. The primary treatment for Nelson's syndrome is transsphenoidal surgery. Other stand-alone therapies, which in many cases have been used as adjuvant treatments with surgery, include radiotherapy, radiosurgery, and pharmacotherapy. Prophylactic radiotherapy at the time of bilateral adrenalectomy can prevent Nelson's syndrome (protective effect). The most promising pharmacological agents are temozolomide, octreotide, and pasireotide, but these agents are often administered after transsphenoidal surgery. In murine models, rosiglitazone has shown some efficacy, but these results have not yet been found in human studies. In this article, the authors review the clinical manifestations, pathophysiology, diagnostic criteria, and efficacy of multimodal treatment strategies for Nelson's syndrome.

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“…Of the patients with the ectopic Cushing's syndrome 2 had small cell bronchial carcinoma, 1 had an islet cell carcinoma with diffuse metastases to the liver, 1 patient had metastatic medullary carcinoma, 1 patient had a benign bronchial carcinoid and 1 patient suffered from the occult ectopic Cushing's syndrome [4]. The cases of the latter 2 patients have been reported in detail e1sewhere [13]. The patient with a corticotropic macroadenoma confirmed by transsphenoidal neurosurgery showed elevated plasma Acnf levels without evidence of Cushing's disease.…”

Section: Patieots Aod Methodsmentioning

confidence: 99%