Home Forums Other Specialities Endocrinology CUSHINGS SYNDROME – PART 2.

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    Definitive therapy of endogenous Cushing’s syndrome involves tumour resection.
    Indications for medical therapy include acutely ill patients in preparation for surgery, patients with unknown tumour location or unresectable lesions, patients unfit for surgery and patients with persistent raised glucocorticoid levels postoperatively.

    The treatment of choice in most patients is surgical but the metabolic consequences, including increased tissue fragility, poor wound healing, hypertension and diabetes mellitus, increase the risks of surgery.

    Drug therapy remains very important for normalising cortisol levels while awaiting the impact of more definitive treatment.
    Cortisol hypersecretion must be controlled prior to surgery or radiotherapy if at all possible.

    Metyrapone, ketoconazole, and mitotane can all be used to lower cortisol by directly inhibiting synthesis and secretion in the adrenal gland.
    Metyrapone and ketoconazole are enzyme inhibitors and have rapid onset of action; however, control of hypercortisolism is often lost with corticotropin oversecretion in Cushing’s disease.
    These drugs are not usually effective as long-term treatment and are used mainly for preparation for surgery or as adjunctive treatment after surgery or pituitary radiotherapy.

    Mitotane acts as an adrenolytic drug with delayed onset but long-lasting action but control of corticotropin oversecretion in Cushing’s disease is maintained.
    Medical treatment can also be used in patients who are unwilling or unfit for surgery. Treatment can be used long-term for patients with ectopic corticotropin secretion; however, adrenalectomy may be preferred.
    Etomidate can be used for acute control of severe hypercortisolaemia.

    Surgical treatment
    Is the treatment of choice for the following conditions:

    Pituitary tumours: trans-sphenoidal microsurgery.[14] Radiation therapy may be used as an adjunct for patients who are not cured.[15] Bilateral adrenalectomy may be necessary to control toxic cortisol levels.
    Adrenocortical tumours: require surgical removal. Laparoscopic surgery is now the treatment of choice for unilateral adrenal adenomas.[1]
    Removal of neoplastic tissue is indicated for ectopic ACTH production. Metastatic spread makes a surgical cure unlikely or impossible. Bilateral adrenalectomy is indicated if necessary to control toxic cortisol levels.

    Pituitary radiotherapy
    Persisting hypercortisolaemia after trans-sphenoidal surgery can be treated with pituitary radiotherapy.
    Conventional fractionated radiotherapy is very effective but is associated with long-term hypopituitarism and can be very delayed in effectiveness.

    Patients with Cushing’s syndrome often develop:

    Metabolic syndrome.
    Impaired glucose tolerance and diabetes.
    Hyperlipidaemia: raised LDL cholesterol and triglycerides.
    Coagulopathy: thrombophilia.
    Perforated viscera.
    Impaired immunity, including opportunistic fungal infections.
    Nelson’s syndrome, which may follow bilateral adrenalectomy for Cushing’s disease.
    A primary pituitary tumour, which may cause panhypopituitarism and visual loss.

    Patients with incompletely controlled Cushing’s syndrome have a five-fold excess mortality.
    The causes of premature death in untreated Cushing’s syndrome are vascular disease (myocardial infarction/stroke), uncontrolled diabetes mellitus and complications of diabetes, and infections.
    The usual course is chronic, with cyclic exacerbations and rare remissions.

    The prognosis is guardedly favourable with surgery.
    The rare adrenocortical carcinomas have a five-year survival rate of 30% or less.

    G Mohan.

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