From the Guidelines
The primary treatment for Cushing's disease is selective adenomectomy, which is the first-line treatment of choice, as it maximizes the potential for normal pituitary tissue to remain in situ 1.
Treatment Overview
The treatment for Cushing's disease involves several options, including surgery, medication, and radiation therapy.
- Selective adenomectomy is considered the first-line treatment, with a strong recommendation and moderate-quality evidence 1.
- If surgery fails or is not possible, medication options such as steroidogenesis inhibitors (e.g., ketoconazole, metyrapone) or pituitary-directed drugs (e.g., pasireotide) may be considered 1.
- Radiation therapy, including pituitary radiotherapy, is a third-line option for patients with recurrent Cushing's disease not amenable to curative surgery 1.
Surgical Treatment
Surgical resection by selective removal of the adenoma is the optimal treatment for Cushing's disease, with low rates of post-operative hypopituitarism reported in several large studies 1.
- Repeat surgery may be considered for patients with persistent or recurrent disease, with a moderate recommendation and low-quality evidence 1.
- Early post-operative remission is associated with identification of the adenoma at surgery, whilst long-term remission correlates with a younger age, a smaller adenoma, and a morning serum cortisol level of <1 μg/dl after surgery 1.
Medical Treatment
Medical therapies, such as metyrapone or ketoconazole, may be offered to reduce the cortisol burden in patients awaiting definitive surgery or the effect of pituitary radiotherapy 1.
- However, due to their adverse effects, metyrapone and ketoconazole have a limited role in the long-term treatment of Cushing's disease 1.
- Other medication options, such as pasireotide and mifepristone, may also be considered, although their effects and safety in children are limited or unknown 1.
Radiation Therapy
Pituitary radiotherapy is a third-line option for patients with recurrent Cushing's disease not amenable to curative surgery, with a strong recommendation and moderate-quality evidence 1.
- Focal external beam radiotherapy is more rapidly effective in children with Cushing's disease than in adults, and is often initiated 2-4 weeks after unsuccessful transsphenoidal surgery 1.
- Stereotactic radiotherapy, fractionated proton beam, and gamma knife approaches have been proposed and utilized in adult Cushing's disease, although experience is limited in children 1.
From the FDA Drug Label
The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex. The treatment for Cushing's disease may involve the use of metyrapone, which works by reducing cortisol production.
- Metyrapone inhibits the 11-beta-hydroxylation reaction in the adrenal cortex, leading to a decrease in cortisol and corticosterone production.
- This decrease in cortisol production results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary. 2
From the Research
Treatment Options for Cushing's Disease
The treatment for Cushing's disease typically involves a combination of surgical and medical approaches.
- Surgical excision of an ACTH-producing pituitary tumor is the optimal therapy for Cushing's disease 3.
- Medical therapy may have either a primary or adjunctive role if the patient cannot safely undergo surgery, if surgery fails, or if the tumor recurs 3.
Medical Treatment
Medical treatment for Cushing's disease can be categorized into three broad mechanisms of action:
- Neuromodulatory compounds: modulate corticotropin (ACTH) release from a pituitary tumor 3.
- Steroidogenesis inhibitors: reduce cortisol levels by adrenolytic activity and/or direct enzymatic inhibition 3.
- Glucocorticoid antagonists: block cortisol action at its receptor 3.
Commonly Used Medications
Some commonly used medications for Cushing's disease include:
- Ketoconazole: effective as monotherapy in about 70% of patients 3.
- Mitotane: may be effective as a single agent 3.
- Metyrapone: may be effective as a single agent 3.
- Aminoglutethimide: generally must be given in combination 3.
- Etomidate: may be used when patients cannot take medications by mouth 3.
Additional Treatment Approaches
Additional treatment approaches for Cushing's disease may include:
- Radiation therapy: may be appropriate for patients not responsive to surgery and medication 4.
- Bilateral adrenalectomy: may be appropriate for patients not responsive to surgery and medication 4.
- Combination therapy: using drugs that target the corticotropic adenoma, such as pasireotide and/or cabergoline, and low-dose ketoconazole 5.