Treatment of Cushing’s Disease

Cushing’s disease is also called tertiary or secondary hypercortisolism, Cushing disease, and Itsenko-Cushing disease. It causes Cushing’s syndrome, in which there are increased secretion levels of adrenocorticotropic hormone.

Some of the common symptoms include weight gain, high blood pressure, irritability, poor short-term memory, lowered immune response, extra fat around the neck, poor concentration, fatigue and excess hair growth in women.

Transsphenoidal Surgery

The initial treatment of Cushing’s disease is surgical resection of the adrenocorticotropic hormone (ACTH) secreting pituitary gland tumor. The removal is by endoscopic surgery, known as transsphenoidal surgery.

There are two possible ways the surgeon can get to the tumor. The first is endonosal approach, meaning the endoscope is inserted through the nostril, and the second is the sublabial approach, through an incision under the top lip.

Some tumors do not have a clear-cut border between the tumor and the pituitary gland. In these cases, careful sectioning through the pituitary gland can be required to establish the location of the tumor. The chances of successful resection is higher in patients where the tumor was identified at initial surgery in compare to patients where no tumor was found initially.

Overall remission rates in Cushings Disease patients with microadenomas undergoing the surgical removal are in the area of 65%-90%, and the remission rate in patients with macroadenomas are lower than 65%.

In patients where the disease persists after this initial sugary, treatment with repeated pituitary surgery is done, as soon as the active disease is evident. Reoperation, however, has a lower success rate and increases the risk of pituitary insufficiency.

Radiation Therapy

pituitary gland diagramPituitary radiation therapy is an additional option for the treatment of postoperative persisting Cushings Disease after unsuccessful transsphenoidal surgery. External-beam pituitary radiation therapy is most effective for pediatric Cushings Disease, with cure rates of 80%-88%.

Hypopituitarism, specifically growth hormone deficiency (GHD) is reported as the single most common late morbidity of this treatment; GHD has been reported in 36% and 68% of the patients undergoing post pituitary RT for Cushing’s disease.

Bilateral Adrenalectomy

Another treatment is the surgical removal both adrenal glands, known as a bilateral adrenalectomy. It provides immediate reduction of cortisol levels as well as control of hypercortisolism.

However, it requires education of patients, since lifelong glucocorticoid and mineralocorticoid replacement therapy is needed for these patients. One of the big complications of this treatment is progression of Nelson’s syndrome which is caused by enhance level of tumor growth and ACTH secretion post adrenalectomy in 8%-29% of patients with CD.

Thankfully, cases of Cushing’s disease are rare. A longitudinal study done in Spain reported a 0.004% prevalence of Cushing’s disease. In a post-treatment study of 3,525 cases of transsphenoidal surgery for Cushing’s disease, the in-hospital mortality rate was 0.7%; the complication rate was 42.1%. Diabetes insipidus, fluid and electrolyte abnormalities, and neurological deficits were the most common complications reported.

Resources:

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2. Voyadzis JM, Guttman-Bauman I, Santi M, Cogen P.
Hypothalamic hamartoma secreting corticotropin-releasing hormone. Case report.”.
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3. C. W. Burke.
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Image: Michele Angelo Petrone, Wellcome Images