Treatment of Cushing's Disease With Cyproheptadine

Pearce, C J; Isaacs, A J; Gomez, Joan

doi:10.1016/s0140-6736(77)92585-5

Cited by 14 publications

(5 citation statements)

References 12 publications

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“…Three prospective studies with cyproheptadine or metergoline, however, have shown a normalization of cortisol in one of 11 (9%) patients with CD (591)(592)(593). Numerous case reports have documented a remission of CD after cyproheptadine treatment (594 -601), whereas others have not confirmed the efficacy of this drug in inducing the normalization of cortisol secretion in CD (602)(603)(604)(605)(606). In summary, clinical studies performed in CD patients have demonstrated that the response rate in patients treated with cyproheptadine or metergoline is not higher than 20% in the series of patients published in literature (467).…”

Section: Neuromodulatory Drugsmentioning

confidence: 99%

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: 99%

The Treatment of Cushing's Disease

et al. 2015

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“…Subsequent studies confirmed the efficacy of this drug in the management of some, though not all, patients with Cushing's disease and Nelson's syndrome (2)(3)(4)(5)(6)(7)(8). Bromocriptine, a dopaminergic agonist, likewise has been shown to lower plasma ACTH levels in some patients, and its clinical use is currently being evaluated (9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 93%

Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro.

Ishibashi¹,

Yamaji²

1981

J. Clin. Invest.

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A B S T R A C T In an attempt to delineate the mechanism and the site of action of cyproheptadine and dopaminergic agonists as well as hormones including thyrotropin-releasing hormone (TRH) and hydrocortisone, the effects of these substances on ACTH secretion from corticotroph adenoma cells in culture were examined. Dispersed cells of pituitary adenomas obtained at surgery from four patients with Nelson's syndrome and one subject with Cushing's disease formed a monolayer and actively secreted ACTH into the medium. When TRH (0.1,UM) was added to the medium, a significant increase in ACTH secretion was demonstrated by adenoma cells from two patients who responded to TRH preoperatively. Moreover, a doseresponse relationship between TRH concentrations and ACTH secretion was observed. Incubation of cells with cyproheptadine (1 or 0.1 ,uM) resulted in a significant decrease in ACTH release, and inhibited stimulation produced by TRH in one experiment. This effect of cyproheptadine was blocked when equimolar concentrations of serotonin was coincubated, whereas serotonin by itself did not affect ACTH secretion. Dopamine (0.1 ,uM) lowered ACTH accumulation in the medium, which was blocked by the addition of haloperidol. When hydrocortisone was added to the culture, dose-dependent suppression of ACTH secretion was demonstrated. TRH at an equimolar concentration reversed this effect, but, failed to overcome the inhibition induced by a higher concentration of hydrocortisone in cells from one adenoma studied. Cultured normal corticotrophs obtained from a patientThis work was presented in part at the Sixth International

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“…There is evidence to suggest that histamine crosses the blood-brain barrier in animals (Crossland & Mitchell, 1956;Snyder et al, 1964), although this has not been shown in man. Endogenous release of hypothalamic histamine may be markedly increased duringcold exposure (Taylor & Snyder, 1971), and its intraventricular injection in rats results in catalepsy and hypothermia (Pilc & Nowak, 1979). Besides his tamine there are other products of mast cell degra nulation, such as prostaglandin D2 and the leuko trienes, and one of histamine's metabolites, imidazoleacetic acid, when given parenterally to rats, has been shown to cause increased exploratory behaviour, hyperactivity, ataxia, and catalepsy (Marcus et al, 1971).…”

Section: Discussionmentioning

confidence: 99%

“…It is the drug of choice for cold urticaria (Wanderer et al, 1977), and has a greater therapeutic effect than other drugs with a more powerful anti histaminic action, probably due to its influencing the kinin system at tissue level. Cyproheptadine is also a serotonin antagonist, which has encouraged the suggestion that its use might be associated with psychiatric disturbance (Pearce et a!, 1977).…”

Section: Discussionmentioning

confidence: 99%