Acromegaly

Acromegaly is a rare condition. It affects approximately 50 to 70 people per million; each year, it is newly diagnosed in about 10 people per million residents *. The condition is usually diagnosed between the ages of 20 and 50, with an average age of diagnosis of about 45 years *.

Due to the increased secretion of growth hormone, physical appearance usually changes gradually.

Typical signs and possible consequences include:

• coarser facial features, as well as enlargement of the nose, lower jaw, and tongue
• larger hands and feet—rings or shoes no longer fit
• diabetes and high blood pressure
• impaired heart function
• vision problems with larger tumors due to pressure on the optic nerves
• joint pain
• carpal tunnel syndrome

To make a diagnosis, the level of the hormone IGF-1 in the blood is first measured. IGF-1 is produced primarily in the liver in response to growth hormone (GH) released by the pituitary gland. Because IGF-1 levels fluctuate less than GH levels, they are particularly useful for diagnostic purposes. Age-specific reference ranges must be taken into account during evaluation.

If the results are inconclusive, an oral glucose tolerance test may also be performed. In healthy individuals, the release of growth hormone is suppressed after ingesting a sugar solution. If this suppression does not occur, it confirms the diagnosis of acromegaly.

In addition, the other pituitary hormones are tested. Prolactin levels are also often elevated – either due to pressure from the tumor on the pituitary stalk or because the tumor secretes prolactin in addition to growth hormone.

If blood tests confirm acromegaly, the pituitary gland is examined using magnetic resonance imaging (MRI). This reveals the exact location and size of the tumor. If surgery is planned, a computed tomography (CT) scan may also be useful to assess the bony structures.

Pituitary adenomas

Treatment options for acromegaly include surgery, medication, and radiation therapy.

Surgery to remove the tumor is usually the first and most important step in treatment. For extensive tumors, several procedures are often combined. These therapies complement one another and are tailored to the individual patient at a specialized, interdisciplinary center.

The goal of the surgery is to remove the tumor as completely and safely as possible and to normalize hormone levels. Overall, a cure can be achieved in about 60–70% of those affected *, *, *, *, *, *, *, *, *,*. The prospects for success depend in particular on the following factors:

• Tumor size *, *, *, *
• Extent of invasion into the sinus cavernosus  *, *, *, *, *, *, *
• Surgical technique and experience of the treatment team

For microadenomas with a diameter of less than one centimeter, remission rates are approximately 75–85%. For macroadenomas, they are around 50–65%  *, *, *.

The endoscopic surgical technique offers particular advantages for extensive tumors. For small, centrally located tumors, microscopic procedures achieve comparable results  *, *, *.

Even if complete removal is not possible, surgery may still be beneficial. Reducing the size of the tumor often lowers growth hormone levels as well *. This can make subsequent drug therapy more effective. If necessary, radiation therapy can also be administered.

After surgery, the removed tumor tissue is examined. This confirms that the tumor was producing growth hormone. The examination also provides insights into the tumor’s behavior, the risk of recurrence, and its potential response to medication.

Growth hormone-producing tumors belong to the so-called Pit-1 cell line. Some of these tumors produce prolactin in addition to growth hormone.

Under the microscope, two tumor types are distinguished *:

• Densely granulated tumors typically produce more growth hormone. They often cause more pronounced symptoms, are more likely to be detected at an earlier stage, and generally respond better to somatostatin analogs *, *, *, *, * .
• Low-granularity tumors usually produce less growth hormone. Symptoms may therefore be less noticeable. These tumors are often larger at the time of diagnosis, grow more aggressively, and respond less well to somatostatin analogs *, *, *. Therefore, surgical removal that is as complete as possible is particularly important.

Certain features on MRI can also provide clues about the tumor type and its potential response to medication  *, *.

After surgery, growth hormone (GH) levels usually drop rapidly. A level below 1.5–2.0 ng/mL after 2–3 days indicates a successful procedure *, *, *, *, *, *, * . The drop in hormone levels also causes fluid to be excreted from the tissues. As a result, urine output may be temporarily increased.

The IGF-1 level normalizes more slowly and is checked no earlier than 12 weeks after surgery *. In some cases, it may continue to decline during the first year. Both GH and IGF-1 are taken into account when assessing the success of treatment.

A cure or good disease control is considered to have been achieved if *, *:

• the GH level is below 1.0 ng/ml or, in the glucose tolerance test, below 0.4 ng/ml, and
• the IGF-1 level falls within the normal range for age and sex.

Slightly elevated IGF-1 levels may initially be observed in certain cases *. In up to 20% of patients, the GH and IGF-1 levels do not match after surgery *. In such cases, the measurements are repeated and, if necessary, supplemented by a glucose tolerance test. The next steps depend on the results of individual follow-up examinations *, *.

A follow-up MRI is usually performed 2–3 months after surgery.

If the disease cannot be adequately controlled by surgery, drug therapy usually follows *.

Other options include repeat surgery or radiation therapy.

Reoperation is more challenging and offers a lower chance of cure than the initial procedure. Depending on the size and extent of the residual tumor, however, a cure can still be achieved in about 50% of cases  *, *, *.

Radiation therapy is considered when medication is not sufficiently effective and reoperation is not possible *. Its effects usually take time to become apparent, though they generally occur more quickly with radiosurgery than with conventional radiation therapy. Overall, the disease can be controlled in 50–70% of cases using this approach.

Through the combination of surgery and drug therapy, acromegaly can be controlled in approximately 85–90% of those affected *, *.

Various classes of drugs are available for drug therapy. Somatostatin analogs such as octreotide or lanreotide are frequently used. They inhibit the release of growth hormone and can shrink the tumor. Long-acting formulations are typically administered every four weeks. The dosage is adjusted individually based on efficacy and tolerability. Somatostatin analogs can control the disease in about half of those affected *.

Another option is pasireotide. Since this medication can raise blood sugar levels, regular monitoring is necessary.

For milder cases, the dopamine agonist cabergoline may also be used.

Pegvisomant blocks the effects of growth hormone in the body, thereby lowering IGF-1 levels. For this reason, IGF-1 – rather than growth hormone – is measured to monitor the course of the disease. Since pegvisomant does not directly inhibit hormone production or tumor growth, the tumor’s size is monitored regularly via MRI.

Radiation therapy is primarily considered when tumor tissue remains after surgery and the disease cannot be adequately controlled with medication. Since its effects usually take time to become apparent, it is specifically used as an adjunctive treatment.

Since the tumor is often located close to the optic nerve and other hormonal functions of the pituitary gland may be impaired, careful planning is essential. Radiation therapy should therefore be performed at a specialized center *.

Acromegaly can affect various organs and bodily functions. For this reason, potential comorbidities must be monitored and treated regularly – even after successful treatment of acromegaly *.

High blood pressure and heart problems

About half of those affected have high blood pressure *. Blood pressure should be monitored at the time of diagnosis and every six months thereafter *. After successful surgery, it may return to normal in some cases.

To evaluate heart function, an ECG and at least one echocardiogram are recommended at the time of diagnosis  *. Successful treatment of acromegaly can improve heart function.

Diabetes and blood lipids

About one-third of those affected develop diabetes. Therefore, blood sugar and the long-term blood sugar level (HbA1c) should be monitored at the time of diagnosis and every 3–6 months thereafter. If levels are elevated, appropriate treatment is initiated. Monitoring blood lipids is also advisable.

Sleep apnea

Many patients suffer from nighttime breathing pauses, a condition known as obstructive sleep apnea. It is advisable to evaluate this condition at the time of diagnosis. If necessary, continuous positive airway pressure (CPAP) therapy is initiated.

After successful treatment of acromegaly, sleep apnea may improve as swelling in the throat subsides. Permanent bone changes, however, usually do not resolve.

Bones and musculoskeletal system

Vertebral fractures and other bone fractures occur more frequently in acromegaly *. Bone density should therefore be monitored at the time of diagnosis and subsequently based on disease activity *. Effective management of acromegaly is likely to have a positive effect on bone health.

Colon cancer screening

People with acromegaly have a slightly increased risk of certain cancers, particularly colon cancer. A colonoscopy is therefore recommended at the time of initial diagnosis. Further screenings are conducted as part of regular colon cancer screening.