Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary

Ross, W. M.; Evered, David; Hunter, Peter; Benaim, M E; Cook, David B.; Hall, R. J. C.

doi:10.1016/s0009-9260(79)80135-x

Cited by 30 publications

(20 citation statements)

References 9 publications

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“…However, patient 2, who received ketoconazole treatment alone, had the same cortisol and ACTH patterns as the four patients who received pituitary radiation and ketoconazole. Furthermore, it is generally agreed (21,22) and has been our experience that the effects of pituitary radiation become apparent only after 6 months to 1 yr, or even longer. Further investigation in different patients may shed light on the mechanism by which ketoconazole interferes with the hypothalamic-pituitary-adrenal axis.…”

Section: Discussionmentioning

confidence: 93%

Prolonged Treatment of Cushing's Disease by Ketoconazole

Sonino

Boscaro

Merola

et al. 1985

The Journal of Clinical Endocrinology & Metabolism

112

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Ketoconazole, used in clinical practice as an antifungal medication, recently was found to be a potent inhibitor of gonadal and adrenal steroidogenesis in vitro and in vivo. The effects of prolonged treatment with this agent in Cushing's disease were investigated in five patients who had recurrent severe hypercortisolism after selective transsphenoidal surgery. The patients received the drug for at least 2 months. Urinary cortisol markedly decreased in all patients immediately after the beginning of treatment with ketoconazole (800 mg/day) and remained within low normal levels when the daily dose was lowered to 600 mg/day. Plasma cortisol also decreased. After 4-6 weeks of treatment, the clinical features of the disease regressed in all patients without signs of toxicity. These findings indicate that ketoconazole may be a valuable drug for the management of patients with Cushing's disease because of its ability to correct hypercortisolism quickly.

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Section: Discussionmentioning

confidence: 93%

Prolonged Treatment of Cushing's Disease by Ketoconazole

Sonino

Boscaro

Merola

et al. 1985

The Journal of Clinical Endocrinology & Metabolism

112

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“…Other series reported remission rates of 66 and 80% after 9 and 12 months, respectively, in children [59] and 100% in adults [60]. About 40 months after medical pretreatment the remission rate following conventional radiotherapy was between 36.8 [61] and 92.9% [62]. When radiotherapy was administered following incomplete surgical removal of the adenoma, the remission rate was 70% [63] in adults and 100% in children [64].…”

Section: Role Of Additional Treatmentmentioning

confidence: 97%

“…The remission rate is 55.6 vs. 52%, respectively [66]. Regarding complications, insufficiency of one pituitary axis is reported in 8.3-80% of the cases when radiotherapy is applied alone or in combination with medical treatment [59,62]. According to one series, when radiotherapy is combined with microsurgery the incidence of panhypopituitarism is 3.3%, and deficits for one or more hormones are reported in 7.1-86% [63][64][65] of the cases.…”

Section: Role Of Additional Treatmentmentioning

confidence: 99%

Treatment of Cushing’s Disease: A Retrospective Clinical Study of the Latest 100 Cases

Hofmann

Fahlbusch²

2006

Frontiers of Hormone Research

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We evaluate the current role of microsurgery for Cushing's disease (CD) and the efficacy of adjuvant treatment modalities. The standard treatment for primary CD remains transsphenoidal surgery followed by adjuvant therapy in cases with persisting hypercortisolism. Moderately severe cases are treated with radiotherapy, while in the very severe adrenalectomy is performed. In our series of primary CD (March 1997 to September 2004, mean observation period 18.8 months) adenomas were confirmed intraoperatively in 84.0% of the cases. Remission was achieved in 75.0% and recurrence was observed in 4.8% of the patients. Complications occurred in 2.0% of the cases and all resolved without resulting in permanent morbidity. In the literature, the rates of intraoperative confirmation of an adenoma vary between 59.1 and 100%, remission rates between 42 and 100%, and recurrence rates between 3.0 and 63.2% depending on the experience of the surgeon and on the definition of remission. These rates have not improved significantly over the years. In experienced hands selective adenomectomy remains the least damaging and most effective treatment modality since it results in rapid clinical improvement if performed successfully. Therefore, it remains the treatment of choice. Patients not cured by surgery alone benefited from a combination of adjuvant treatment tailored to their specific needs using medications, radiation and/or adrenalectomy. In this fashion, we achieved normalization of cortisol levels in 79% and improvement in another 18% of the patients. We expect these rates to increase further once patients treated with radiotherapy begin to experience its full effect within the next few years.

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“…Subsequently, Jeffcoate et al (52) reported treatment of 13 patients with CD with a dose of 0.5-4 g of metyrapone daily; the patients showed good clinical and biochemical improvement on metyrapone despite a rise in plasma ACTH levels. Metyrapone was thus shown to control hypercortisolism in anticipation of more permanent treatment such as pituitary radiotherapy in adults (53) and children (54,55). Several small retrospective series and case reports further explored the efficacy of metyrapone alone or in combination with KTZ (56) ( Table 4).…”

Section: Metyraponementioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome

Daniel

Newell‐Price

2015

European Journal of Endocrinology

111

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Steroidogenesis enzyme inhibitors are the mainstay of medical therapy in Cushing's syndrome (CS). Ketoconazole (KTZ) and metyrapone are the most commonly used agents. Although there is considerable experience of their use in individual specialist centres, these drugs have not been rigorously tested in prospective clinical trials. Clinicians face uncertainties and concerns with respect to the safety profile of these agents, and best means to monitor effect. We review steroidogenesis inhibitors in the management of CS, including older agents (KTZ, metyrapone, etomidate and mitotane) and those currently under development (LCI699, non-racemic KTZ), and offer a practical approach for their use in clinical practice.

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Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary

Cited by 30 publications

References 9 publications

Prolonged Treatment of Cushing's Disease by Ketoconazole

Prolonged Treatment of Cushing's Disease by Ketoconazole

Treatment of Cushing’s Disease: A Retrospective Clinical Study of the Latest 100 Cases

THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome

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