Medical management of Cushing disease

Gross, Bradley A.; Mindea, Stefan A.; Pick, Anthony J.; Chandler, James P.; Batjer, H. Hunt

doi:10.3171/foc-07/09/e10

Cited by 11 publications

(28 citation statements)

References 33 publications

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“…Previous clinical reports showed that in CD patients, mitotane, owing to its adrenolytic action, is highly effective in the long-term suppression of hypercortisolism (Luton et al 1979, Schteingart et al 1980, at concentrations lower that those employed for ACC treatment (Gross et al 2007, Murao et al 2010, Baudry et al 2012, but central inhibitory actions have been overlooked.…”

Section: Discussionmentioning

confidence: 99%

Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function

Gentilin¹,

Tagliati²,

Terzolo³

et al. 2013

Journal of Endocrinology

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Medical therapy for Cushing's disease (CD) is currently based on agents mainly targeting adrenocortical function. Lately, pituitary-directed drugs have been developed, with limited efficacy. Mitotane, a potent adrenolytic drug, has been recently investigated for the treatment of CD, but the direct pituitary effects have not been clarified so far. The aim of our study was to investigate whether mitotane may affect corticotroph function and cell survival in the mouse pituitary cell line AtT20/D16v-F2 and in the primary cultures of human ACTHsecreting pituitary adenomas, as an in vitro model of pituitary corticotrophs. We found that in the AtT20/D16v-F2 cell line and in primary cultures, mitotane reduces cell viability by inducing caspase-mediated apoptosis and reduces ACTH secretion. In the AtT20/D16v-F2 cell line, mitotane reduces Pomc expression and blocks the stimulatory effects of corticotropinreleasing hormone on cell viability, ACTH secretion, and Pomc expression. These effects were apparent at mitotane doses greater than those usually necessary for reducing cortisol secretion in Cushing's syndrome, but still in the therapeutic window for adrenocortical carcinoma treatment. In conclusion, our results demonstrate that mitotane affects cell viability and function of human and mouse ACTH-secreting pituitary adenoma cells. These data indicate that mitotane could have direct pituitary effects on corticotroph cells.

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Section: Discussionmentioning

confidence: 99%

Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function

Gentilin¹,

Tagliati²,

Terzolo³

et al. 2013

Journal of Endocrinology

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“…

neurosurgical focus

Neurosurg Focus 38 (2):E14, 2015T he primary treatment for Cushing's disease is transsphenoidal adenomectomy; 12,22,76 remission rates are 70%-90%. 6,12,72,79 In a meta-analysis of 50 studies performed by Roelfsema et al, biochemical remission was found for 4207 (72.7%) of 5787 patients who had undergone a single surgical procedure.

…”

mentioning

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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“…adrenolytische Therapie, Gamma-Knife-Therapie oder experimentelle medikamentöse Therapien (z.B. Dopaminagonisten, Somatostatin-Analoga, Glitazone) erforderlich [15].…”

unclassified

Reversibles metabolisches Syndrom hormoneller Ursache

et al. 2008

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A 52-year-old male patient was admitted to the emergency department with dyspnea and hypertensive urgency. During the previous 6 months, the patient had noticed leg edema, weight gain (particularly in the face and abdomen), and impotence. 1.5 years ago, he was diagnosed with hypertension resistant to medication. After an accident at work 1 year ago, osteoporosis was diagnosed with vertebral and rib fractures. Measurement of sleeping midnight salivary cortisol levels together with 24-h urine free cortisol excretion and an overnight low-dose 1-mg dexamethasone suppression test proved overt hypercortisolism. The high-dose 8-mg dexamethasone suppression suggested an adrenal or ectopic source of hypercortisolism. By contrast, elevated adreno-corticotropic hormone (ACTH) levels and a corticotropin-releasing hormone stimulation test gave evidence for a pituitary source of hypercortisolism. However, pituitary magnetic resonance imaging failed to reveal a pituitary adenoma. Moreover, computed tomography scans of thorax and abdomen were negative. In this situation, an inferior petrosal vein sampling was performed and revealed an ACTH gradient (central-systemic) >3 with lateralization to the right side. The patient underwent a selective, partial, transsphenoidal resection and was cured from clinical signs and symptoms caused by hypercortisolism. Subsequent hormonal replacement therapy of postoperative pituitary insufficiency was necessary.

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Medical management of Cushing disease

Cited by 11 publications

References 33 publications

Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function

Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function

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

Reversibles metabolisches Syndrom hormoneller Ursache

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