Valproate in Cushing's Syndrome

Allolio, Bruno; Winkelmann, W.; Kaulen, D.; Hipp, F. X.; Mies, R.

doi:10.1016/s0140-6736(82)90422-6

Cited by 22 publications

(5 citation statements)

References 7 publications

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“…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). The lack of efficacy of valproic acid was also demonstrated in a more recent study in which valproic acid was administered at the dosage of 600 mg/d for 3 months in 19 patients with CD, before or after unsuccessful pituitary surgery; no patients normalized their urinary cortisol levels during the period of treatment (620).…”

Section: Neuromodulatory Drugsmentioning

confidence: 96%

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: 96%

The Treatment of Cushing's Disease

et al. 2015

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“…Furthermore, sodium valproate may also have an affect on the post-synaptic GABA receptor, and again enhance GABA biological activity. Published reports find sodium valproate improving some cases with Cushing's disease (Koppeschaar et al 1982), but not others (Allolio et al 1982). One case reported was of a response to both cyproheptadine and valproate (Koppeschaaretal 1983).…”

Section: Discussionmentioning

confidence: 98%

The Medical Treatment of the Hypersecreting Pituitary Gland

Corenblum

1985

Can. j. neurol. sci.

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Pituitary adenomas may produce local endocrine and neurological effects, as well as systemic metabolic complications due to hormonal hypersecretion. Medical therapy with pharmacological agents has been developed and is based on the neurotransmitter regulation of normal pituitary hormonal secretion. 189 patients with secretory pituitary adenomas underwent medical therapy for the hypersecretory state. 156 of these were prolactin-secreting adenomas, 16 of which were in males. The response of bromocriptine was almost universal with lowering of serum prolactin and reversal of the clinical symptoms, as well as tumor shrinkage of most large adenomas with suprasellar extension. 23 patients with acromegaly were treated with bromocriptine, with 11 noting clinical improvement, and decreased tumor size in two. Five patients with Cushing's disease were treated with cyproheptadine, with only one showing a biochemical and clinical improvement. Two patients with Nelson's syndrome each had progressive tumor growth stabilized with cyproheptadine and bromocriptine in one, and sodium valproate in the other. There appears to be a role for medical therapy in the majority of prolactin-secreting pituitary tumors, some growth hormone secreting pituitary tumors, and selected adrenocorticotropin secreting-pituitary tumors. RESUME: Traitement medical de la glande pituitaire hypersecretrice Les adenomes pituitaires peuvent produire des effets locaux endocriniens et neurologiques ainsi que des complications metaboliques systemiques dues a I'hypersecretion hormonale. Une approche therapeutique a ete developpee, basee sur la regulation par les neurotransmetteurs de la secretion pituitaire hormonale normale. 189 patients avec adenomes pituitaire secretants out recu un traitement mddical de leur etat hypersecretoire. Dans 156 cas, il s'agissait d'adenomes secretant la prolactine dont 16 chez des males. La reponse a la bromocriptine est presque uniforme avec chute de la prolactine serique et renversement des symptomes cliniques. II y eut aussi un rapetissement des tumeurs, surtout des gros adenomes avec extension suprasellaire. 23 patients avec acromegalic furent traites a la bromocriptine. II noterent une amelioration clinique et chez 2, la tumeur a diminue de grosseur. Cinq cas de maladie de Cushing furent traites a la cyproheptadine, un seul montant une amelioration biochimique et clinique. Une tumeur progressive s'est vue stabilised dans sa croissance chez 2 cas de maladie de Nelson, Tun avec la cyproheptadine et la bromocriptine, l'autre avec le valproate de sodium. II semble done y avoir une approche medicale possible dans le traitement de la majorite des tumeurs pituitaires secretant la prolactine, pour certaines tumeurs pituitaires secretant I'hormone de croissance et pourquelques rares tumeurs secrdtant I'adrenocorticotropine.

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“…Remission may persist occasionally after cessation of cyproheptadine in both Cushing's disease (Kasperlick-Zulaska et al, 1980;Griffith & Ross, 1981;Wiesen et al, 1983) and Nelson's syndrome (Aronin & Krieger, 1980). The anticonvulsant sodium valproate, a GABA transminase inhibitor, has been shown to induce a decrease of plasma ACTH levels in Nelson's syndrome both during chronic treatment (Jonesetaf., 1981) and inacuteexperiments(Eliasetal., 1981) but appeared not to be effective in Cushing's disease (Allolio et al, 1982). The dopamine agonist bromocriptine has been shown to induce a fall in plasma ACTH levels in some patients with Cushing's disease (Lamberts et al, 1980) whereas clinical and biochemical improvement has been obtained occasionally during chronic treatment with bromocriptine (Boscaro et al, 1983).…”

Section: H P F Koppeschaar Et Almentioning

confidence: 99%

Response to Neurotransmitter Modulating Drugs in Patients With Cushing's Disease

Koppeschaar¹,

Croughs²,

Thijssen³

et al. 1986

Clinical Endocrinology

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We designed a systematic study of patients with Cushing's disease to compare the results of acute experiments with cyproheptadine, sodium valproate and bromocriptine with the results of chronic treatment with sodium valproate. In 13 patients the plasma cortisol response to single doses of 2.5 mg bromocriptine, 6 mg cyproheptadine and 300 mg sodium valproate was assessed over 4-8 h. All patients were then treated with sodium valproate 200 mg three times a day for a period of 3 months. Subjects were classified as responders when there was a reduction in plasma cortisol by at least 50% below the basal level in two consecutive plasma samples during one of these tests, and/or clinical remission and normalization of cortisol production rate during sodium valproate treatment. Four patients responded significantly to at least one of the agents (group I) and 9 did not (group II). In group I three patients were bromocriptine responsive and one of these responded also to cyproheptadine; in this patient both sodium valproate and cyproheptadine were able to induce a remission during chronic treatment. In the one patient of the responder group who was bromocriptine insensitive, sodium valproate treatment also induced a remission. In two patients of the responder group sodium valproate treatment was ineffective. However, in both patients chronic treatment with bromocriptine induced a marked clinical improvement associated with a decrease of cortisol production rate. There was no difference between the groups in sex, age, clinical presentation, duration or severity of hypercortisolism. In one patient in group I a macroadenoma with suprasellar extension was present, while a microadenoma was detected in four patients in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

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Valproate in Cushing's Syndrome

Cited by 22 publications

References 7 publications

The Treatment of Cushing's Disease

The Treatment of Cushing's Disease

The Medical Treatment of the Hypersecreting Pituitary Gland

Response to Neurotransmitter Modulating Drugs in Patients With Cushing's Disease

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