Acromegaly

What is Acromegaly?

Acromegaly is a rare disease that happens when too much growth hormone is produced, usually due to a small benign tumor in the pituitary gland in the brain. This overproduction leads to an excess of insulin-like growth factor 1 (IGF-1), which results in larger than normal tissue growth. Attributes of this disease include facial changes, bigger hands, and feet. This disease also impacts many other body systems, like heart, joints, nerves, lungs, and can even cause tumors and affect metabolism. Early detection and treatment are vital to reduce health problems and deadly risks associated with this disease. Managing this condition often requires the coordination of a team of medical professionals.

What Causes Acromegaly?

Acromegaly, a condition that causes abnormal growth, can be caused by excess levels of growth hormone (GH) or the hormone that triggers its release (GHRH). The sources of this excess can vary.

The most typical cause of acromegaly is due to a specific kind of tumor, known as a somatotroph GH-secreting adenoma, which grows in a part of the brain called the anterior pituitary gland. This tumor is often linked with a mutation that activates a particular gene, the alpha subunit of the guanine nucleotide stimulatory protein gene.

Other causes of too much GH come from different pituitary tumors, which release multiple hormones, and GH-cell carcinomas. The condition can also run in families, and is linked to syndromes such as Multiple Endocrine Neoplasia type 1, Familial Acromegaly, McCune-Albright syndrome, and Carney complex.

In some cases, GH may be produced outside the pituitary gland, such as by other types of tumors like lymphomas or pancreatic-islet cell tumors. Excess GH might even occur due to an overuse of GH medication, which is known as iatrogenic GH excess.

Less commonly, acromegaly can be caused by an excess of GHRH. The sources of this excess can be central, meaning they originate in the brain, such as by certain types of brain tissue growths. Alternatively, they can be peripheral, or outside of the brain, such as by certain types of lung tumors, adrenal tumors, or even by certain types of thyroid cancer or pheochromocytoma.

Risk Factors and Frequency for Acromegaly

Acromegaly is a condition that affects around 4,600 out of every million people worldwide. Each year, there are roughly 116.9 new cases per million people, and the number of cases is on the rise.

• The average age when Acromegaly is diagnosed is 40 for men and 45 for women.
• Acromegaly typically shows up in people’s thirties.

Signs and Symptoms of Acromegaly

Acromegaly is a health condition that generally begins in one’s 30s or 40s and advances slowly. Some of the symptoms may include joint and wrist pain, sleep disorders, headaches, low sex drive or abnormal menstrual cycles in women and a deepened voice. Upon physical examination, common signs can be mapped out as:

This is an inclusive list, and an individual might present with some, all or none of these. So, it’s essential to consult a healthcare professional if suspected of this condition.

Testing for Acromegaly

Screening for the condition known as acromegaly is advised for individuals manifesting with certain particular features. The condition is known to be linked with other diseases such as sleep apnea, hypertension, advanced type 2 diabetes, severe joint pain, and carpal tunnel syndrome among others. However, the routine screening isn’t typically carried out for those with only a single disorder, such as sleep apnea, type 2 diabetes, or hypertension, for the reason that acromegaly is quite a rare disease.

The screening procedure assesses the level of IGF-1, a substance that unlike Growth Hormone(GH), remains steady throughout the day without altering due to sleep or physical activities. If the IGF-1 level is found to be elevated, it implies an excess of GH grown, and the next step would be imaging to identify its source. If the IGF-1 level is normal, we can mostly rule out the possibility of acromegaly. In cases where the test doesn’t provide a clear result, additional tests are performed. A typical one is administering 75g of glucose to the patient and measuring GH levels before and 2 hours later. The diagnosis of acromegaly is confirmed if the GH concentration rises to >1ng/mL after the glucose load. There are other tests, but are rarely needed. They come into play only if both the IGF-1 and GH tests are normal, despite the presence of suspicion of acromegaly.

For patients who have had positive tests for acromegaly, the next step is to do an imaging of the brain as the most common cause of acromegaly is a somatotroph adenoma. The recommended imaging method is a pituitary MRI, which can help visualize any masses. If there’s no identifiable mass, it could mean the adenoma is too small to be seen or there may be another source of excess GH. In this case, more imaging tests are done which may include a CT scan of the chest and abdomen or a DOTATE PET scan, along with measuring the GHRH level in the blood. If it’s over the normal limit of 300ng/mL, it means the GH excess might be coming from somewhere other than the pituitary.

Other necessary tests evaluate different pituitary hormones since adenomas can secrete multiple hormones at the same time and their size can affect the normal functioning of the pituitary gland. It’s also important to monitor for related conditions, including diabetes and high cholesterol. If there’s any sign of sleep apnea or heart failure, these need to be addressed with a sleep study and cardiac monitoring, respectively. Furthermore, visual checks or tests are necessary if there are concerns about vision or if any adenomas are found near to or pressing on the optic nerve. Depending on the guidelines observed, a colonoscopy could also be required.

One of the effective evaluations designed to monitor both the progression and the response to treatment for acromegaly patients is the SAGIT (Signs/Symptoms, Associated comorbidities, Growth hormone levels, IGF-1 levels, and Tumor features) evaluation.

Treatment Options for Acromegaly

The purpose of treating acromegaly, a condition where your body produces too much growth hormone, is to control the excess growth hormone and associated symptoms, manage related health issues, and improve overall survival.

Surgery is the first choice treatment, particularly for smaller tumors and larger ones causing pressure problems. Even if a cure isn’t likely, reducing the size of the tumor can make other treatments work better. Factors like the size of the tumor, the level of growth hormone, and whether it’s invaded nearby areas can predict how successful surgery will be.

There are a few different types of surgery to remove the tumor. Endoscopic transsphenoidal surgery is a minimally invasive procedure that involves using a special instrument (an endoscope) to remove the tumor through a small opening in the nose or upper lip. This method is good because it allows clear, wide viewing of the tumor to make sure no piece is left behind. Microscopic transsphenoidal surgery involves directly visualizing the tumor with a microscope. Both endoscopic and microscopic surgeries have similar success and complication rates. However, endoscopic surgery may provide better results for larger tumors due to its wider view, but more research is needed. Craniotomy is another surgical approach, but is only used when the tumor extends beyond its usual location.

Once the surgery is over, doctors closely monitor the patient’s urine output and salt levels to account for possible hormonal changes. Medical professionals also carefully observe adrenal function for appropriate post-operative care. A test for growth hormone may be done to assess remission, and a glucose tolerance test might be conducted as well.

In situations where the disease persists after surgery, the patient may require additional treatment, which could either be repeat surgery depending on their situation, medical management, or radiation.

Medication is considered in situations when surgery is too risky, the tumor can’t be completely removed, or the disease returns after initial surgical management. There are different types of medications, which act in different ways to control the overproduction of growth hormone. Side effects can occur and will differ based on the medication.

Radiation therapy is another treatment option considered when medical management can’t control the disease, there’s a recurrence after surgery, and medical therapy has failed. There are some side effects and precautions associated with radiation therapy, so it should be followed by careful monitoring.

In pregnant patients with acromegaly, their situation is carefully monitored as hormonal changes during pregnancy may influence the outcome. In most cases, the size of the tumor doesn’t change significantly during pregnancy. However, close monitoring is necessary, particularly for vision-related tests. If symptoms get worse, medical management could be restarted. In case the woman experiences visual problems, an MRI is needed to decide whether medical management or surgery is required.

What else can Acromegaly be?

There are several medical conditions and syndromes which can cause abnormal growth patterns. These include:

• Carney complex
• McCune-Albright syndrome
• Multiple endocrine neoplasia type 1
• Sotos syndrome (a genetic overgrowth syndrome)
• Beckwith-Wiedemann syndrome (a genetic overgrowth syndrome)
• Malan syndrome (a genetic overgrowth syndrome)
• Tatton-Brown-Rahman syndrome (a genetic overgrowth syndrome)
• Berardinelli–Seip lipodystrophy (a disorder causing tall stature in children)
• Disorders related to the abnormalities of natriuretic peptide C pathway (causing tall stature in children)
• Pachydermoperiostosis
• Use of Minoxidil

What to expect with Acromegaly

Acromegaly, a medical condition, has a high mortality rate mainly due to cancers and heart or lung disorders. People with acromegaly have a mortality rate higher than the general population by 1.2 to 3.3 times. Research also suggests that levels of a hormone called GH which drops after surgery, could impact overall survival. Therefore, if we can control these hormone levels, the survival expectancy of a person with acromegaly can be similar to people of the same age. Factors such as high hormone levels, heart disease, and hypertension can worsen the patient’s outlook. Even with normal hormone levels, the health issues linked with acromegaly usually continue, but treatment can mitigate severity and somewhat improve the quality of life.

The potential outcome for someone with acromegaly is influenced by many different factors. These include the patient’s age, their hormone levels at diagnosis, characteristics of their tumor including its size and behavior, as well as its specific mutations and other markers. Using these factors, doctors have classified acromegaly into three types, which can predict a patient’s prognosis and likelihood of responding to treatment.

Type 1 patients usually have the best outlook. They are older, with fewer symptoms and lower hormone levels. Their tumors are less aggressive, have a low growth rate (indicated by lower Ki67 levels), and exhibit signs of aging cells (indicated by higher p21 levels). This type usually does not extend into the region above the pituitary gland. Rather, it extends laterally into sinus areas which are easier to access for surgery. These tumors often respond better to medical treatment.

Type 2 prognosis is intermediate. The tumors can vary in terms of their structure, but they are usually not invasive. In comparison to Type 1, these patients have higher hormone levels at diagnosis.

Type 3 has the worst prognosis. These patients are younger, exhibit severe symptoms, and have high hormone levels at diagnosis. Their tumors are aggressive and extend into both the sinus area and the region above the pituitary gland, often compressing the nerve responsible for vision (the optic chiasm). These tumors may not respond well to medical therapy.

Possible Complications When Diagnosed with Acromegaly

People with high GH (Growth Hormone) and IGF-1 (Insulin-Like Growth Factor-1) levels often experience certain changes in their musculoskeletal system. These hormones stimulate the formation of bone around the surface, resulting in body growth. Some noticeable changes due to these hormones include a larger forehead, thicker jaws, separated teeth, and a thicker nose bone. Also, the hands and feet could become larger because of increased soft tissue, cartilage, and bone growth, leading to changes in shape. This can also result in back curvature and a hip tilt, and if the rib junctions overgrow, the ribs may spread out. All of these changes could potentially lead to pain in the joints and muscles.

Excessive sweating and oily skin are common complaints among people with high GH and IGF-1 levels. Their skin may also thicken and develop skin tags.

Carpal tunnel syndrome is a common nerve complication. Interestingly, rather than being a result of nerve compression from soft tissue and bone overgrowth, it’s thought to be due to swelling of the nerve itself. In some cases, brain blood vessel enlargement can occur which can lead to brain bleeding if these vessels rupture.

High blood pressure is common and can be caused by a variety of factors, including sleep apnea, insulin resistance, and too much fluid in the blood. Over time, excessive GH can make the heart muscle enlarge, leading to poor heart function. Initially, the heart appears overly active, but over time it can lead to thickened heart muscle and poor heart function. Heart abnormalities can also occur due to some fibrous changes in the heart.

Both insulin resistance and diabetes can occur in people with GH and IGF-1. The reason being that too much GH hampers the effect of insulin at the liver and peripheral tissues. The body tries to compensate for this by increasing beta-cell function to maintain normal blood sugar levels. Over time, constant insulin resistance and fat toxicity lead to beta-cell dysfunction and end with them dying off, thus causing diabetes.

People with high GH and IGF-1 levels also often suffer from sleep apnea. Problematic sleep can be caused by anatomical changes like enlarged tongue, overgrowth of the palate and uvula, and jaw changes. Some people experience central sleep apnea, while other abnormalities can occur due to chest shape changes, which affects breathing.

The risk of colon cancer in individuals with GH and IGF-1 is debatable. However, a significant study from 2008 found that people with these conditions had 2.5 and 4.3 times higher chances of developing colon growths and colon cancer, respectively. There is currently no agreement among guidelines on when to begin screening for colon cancer. Some guidelines recommend screening at the time of diagnosis, others starting at age 40. The frequency of follow-up screenings depends on the results of the initial screening. Sometimes, growths on the thyroid can also occur.

Preventing Acromegaly

Acromegaly is a condition that affects multiple systems in the body. Even after treatment, which helps to balance GH and IGF-1 hormone levels, might not fully reverse all the health issues related to this condition. Thus, regular check-ups with an endocrinologist and relevant specialists are crucial. It’s also important to note that even after successful treatment, the disease can come back, even after several years of being in remission. This makes the regular follow-ups incredibly important.

Many people with acromegaly often have a lower quality of life. This is due to the long-lasting nature of the disease, the treatment’s challenges, and the numerous associated health issues. Doctors have the responsibility to educate patients on what to expect from this disease and the treatment options available to help improve their quality of life.

It’s also important for patients to understand that if they have surgery for a pituitary adenoma, another condition often associated with acromegaly, there could be complications after the procedure. These may include conditions like panhypopituitarism or central diabetes insipidus. Patients need to alert their doctor immediately if they begin to show new or concerning symptoms, such as frequent urination. Moreover, additional treatments may be needed if the surgery does not completely cure the condition.