Surgical Management of Acromegaly

Acromegaly can distort physical appearance but is also life-threatening. Left untreated, it increases the risk of cardiovascular disease, diabetes, high blood pressure, lung disease, and colon cancer. In addition, the mass effect of large pituitary tumors can put pressure on optic nerves and cause loss of vision.

In approximately 99% of patients with acromegaly, the disease is caused by a growth hormone (GH) — producing pituitary adenoma (Figure 1). In the other 1%, the tumor is located elsewhere (eg, lungs, pancreas, or adrenal glands). Excess GH secreted in the bloodstream triggers the liver to produce insulin-like growth factor 1 (IGF-1), which stimulates growth of bones and soft tissue.

In adults who have reached their full height, the symptoms may occur gradually and remain unnoticed until the disease has progressed. Symptoms include enlargement of the jaw, forehead, hands, and feet as well as the tongue and other soft tissue. In children, because the skeleton is not yet fused, abnormal GH production also affects linear growth. The condition is referred to as gigantism, and accelerated linear growth often precedes weight gain in these children.

Physical changes are not the only route to diagnosis. Pituitary tumors may be discovered in patients with headaches or visual problems before external changes are evident. Diagnosis is made by an endocrinologist through imaging studies and a blood test for biochemical confirmation. The general appointment desk at Mayo Clinic automatically refers all patients with suspected pituitary disorders to a pituitary specialist in endocrinology who manages the case. From there, patients with tumors are sent for a neurosurgical consultation and to ophthalmology if the tumor is affecting vision.

Left, MRI scan of normal pituitary gland. Right, MRI scan of pituitary macroadenoma with suprasellar extension.

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Illustration of the transnasal surgical approach.

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Todd B. Nippoldt, M.D., and John Atkinson, M.D.

A Multispecialty Team Approach to Treatment
"The overall treatment goals are to achieve normal GH and IGF-1," says Todd B. Nippoldt, MD, in the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at Mayo Clinic's Rochester campus. John Atkinson, MD, a Mayo Clinic neurosurgeon, adds, "The question in each case is how best to get the tumor under control. It may be through surgical resection, radiotherapy, stereotactic radiosurgery, medical therapy, or some combination. This is a complex disease that overlaps many subspecialties and absolutely requires a team approach."

At Mayo Clinic, the team includes physicians from endocrinology, neurosurgery, radiology, anesthesiology, radiosurgery, otorhinolaryngology, and ophthalmology. A pituitary specialist in endocrinology is always the team leader.

Surgical Resection
Unless surgery poses risks for the patient, tumor resection is considered the first-line treatment. Medical therapies are available — those that block and those that suppress GH. However, they are expensive and do not affect the tumor itself. They may be used in conjunction with staged surgery for large tumors.

Transsphenoidal surgical resection can rapidly normalize GH levels in approximately 65% of patients with acromegaly. More than 120 such procedures are performed each year at Mayo Clinic in Minnesota. Surgical issues particular to acromegaly must be considered. For example, intubation and maintaining the airway can be difficult in patients with enlarged tongues and thickened oral airways. Mayo Clinic anesthesiologists typically use a fiberoptic endoscope as they intubate the patient, and they keep the airway open for longer than usual after surgery.

At Mayo, the transsphenoidal surgery to resect the tumor is performed by an otorhinolaryngologist and a neurosurgeon. Since the late 1990s, they have used a transnasal endoscopic approach, which shortens operating time, reduces postoperative discomfort, and is as effective as transseptal or sublabial endoscopic approaches (see Mayo Clinic Proceedings 1999;74:661-670). The surgeons typically use the nasal endoscope only for access to the sella turcica. An operating microscope is used for tumor removal. This approach has the additional advantages of endoscopic visualization and eliminating the need for an external incision and postoperative nasal packing.

In this procedure, the diameter of the working channel to the sella turcica is reduced by 50% and the view of the sella is 10° off center. These limitations are best managed in a large-volume pituitary practice in which experience enhances expertise.

Stereotactic Radiosurgery
The advantage of radiosurgery is highly focused delivery to the tumor with little radiation exposure to surrounding tissue. With nearly 4,000 patients treated to date, Mayo Clinic has one of the busiest radiosurgery practices in the world, successfully treating about 95% of pituitary adenomas. Recent acquisition of the new Leksell Gamma Knife Perfexion is expected to increase accuracy and precision in radiation delivery, to improve patient comfort, and to reduce treatment time by as much as 40% to 60%.

Radiosurgery may be an adjunct or alternative to surgical resection in selected patients. Patients with macroadenomas and considerable suprasellar extension usually are not considered good candidates. In patients with large tumors that extend into the cavernous sinus and are not fully removed by surgery, radiosurgery can be part of a staged approach. The tumor can initially be debulked, separating its superior surface from the optic nerves. Radiosurgery can then address the remaining tumor with little risk to cranial nerves.

Since 1990, 221 patients have undergone stereotactic radiosurgery for pituitary adenomas at Mayo Clinic in Minnesota. Of these patients, 90% had prior surgery, and 80% had tumors extending into the cavernous sinus. Radiosurgery stops tumor growth but is slow to reduce excess GH production. "We often use medical therapy while waiting for the effects of radiosurgery to work," explains Dr Nippoldt. Biochemical remission with radiosurgery is 3 times more likely in patients whose IGF-1 levels are less than 2.25 times the upper limit of normal. Biochemical remission, defined as a fasting GH level less than 2 ng/mL and normal IGF-1 adjusted for age and sex without suppressive medication, has occurred in approximately 80% to 90% of properly selected patients with acromegaly at Mayo Clinic. As Dr Nippoldt notes, biochemical remission is adversely affected by taking pituitary suppressive drugs before radiosurgery so patients are advised to discontinue these medications 8 weeks before the procedure.

Normalizing GH secretion in acromegaly can reduce swelling in soft tissue, but it cannot effect changes in the bone and general appearance. It can, however, improve mortality and prevent further organ damage.