Acromegaly Is Most Often Diagnosed Late, but With the Right Treatment, some Complications Can Be Reversible

Acromegaly is a disease with many consequences and complications, but despite its characteristic changes, the diagnosis is often made late, and there have been no significant improvements over the past 20–30 years. Although complications can be reversible with the right treatment, outcomes improve when treatment is initiated earlier.

Acromegaly is often only diagnosed once the patient has developed several characteristic features, as well as complications from the increased production of growth hormone. At the same time, studies show that patients are seen by doctors from different specialties before the diagnosis is made, says Andrea Giustina, professor of endocrinology at the Vita-Salute San Raffaele University and director of the endocrine and metabolic division at San Raffaele Hospital.

In this interview article, Andrea Giustina provides insight into how acromegaly develops, the diagnostic and treatment options and strategies, and the consequences of a delayed diagnosis.

Why is acromegaly often diagnosed late, and how can doctors catch it earlier?

Acromegaly is a disease that may seem easy to diagnose because it characteristically changes the patient’s facial features and increases the size of the hands and feet. Therefore, there should ideally be no delay in making the diagnosis.

However, the changes that occur in the patient are very subtle and develop slowly. As a result, patients often do not notice them themselves, and the same applies to family members and doctors. The changes are too slow and gradual. In a way, the patient becomes accustomed to these changes, which is why it often takes someone who does not see the patient every day to suspect the disease.

Sometimes it is the general practitioner who identifies it, but often the patient sees several different doctors for other reasons. In general, awareness of the disease outside the endocrine specialty is limited, even though it is clinically relevant. Acromegaly affects not only appearance but also the patient’s overall health and increases the risk of mortality.

It is estimated that, on average, a patient sees at least four doctors before the diagnosis is made. This can delay the diagnosis by many years, and many patients are only diagnosed about five years or more after the first signs and symptoms appear. Diagnostic delay is therefore a classic problem, and there have been little significant improvements over the past 20–30 years.

In a review published in The New England Journal of Medicine at the end of 2025, the focus was placed on non-endocrinologists. Endocrinologists are generally better at diagnosing acromegaly, as it is a hormonal disease caused by a pituitary adenoma that produces excessive growth hormone.

Outside the field of endocrinology, awareness of acromegaly is often low. Therefore, it is important to reach physicians who treat patients for complications—for example, cardiologists (for hypertension and cardiomyopathy), neurologists (for headaches), and dentists, since the face, teeth, and tongue are all heavily affected.

By increasing awareness among these professional groups, they can highly contribute to shortening the diagnostic delay at considering the diagnosis when they encounter something unusual in their practice, thereby initiating the necessary diagnostic process.

Which test is most useful for monitoring acromegaly—growth hormone or IGF-1?

This is a very relevant question, as it is closely linked to what I mentioned earlier: when non-specialists suspect acromegaly, which test should they order to confirm that suspicion?

Intuitively, one might think that growth hormone is the best marker, since in acromegaly the pituitary gland produces too much growth hormone. Therefore, it would seem logical to measure growth hormone in the blood.

However, growth hormone is secreted in pulses—even in healthy individuals. These normal, physiological fluctuations can be confused with the elevated levels seen in patients with acromegaly. As a result, it is not uncommon for a patient to be mistakenly assessed as normal because the growth hormone level at the time of measurement falls within the so-called normal range, which often include levels that can be reached during a physiological peak.

Instead, Insulin-like Growth Factor 1 (IGF-1) is used, as it is the systemic mediator of the effects of growth hormone. IGF-1 is produced in response to growth hormone and is far more stable in the bloodstream than growth hormone. However, IGF-1 levels are influenced by age, so it is important to use age-adjusted reference values. An elevated, age-corrected IGF-1 level is therefore the best test to confirm the clinical suspicion of acromegaly.

How is the best treatment for acromegaly chosen?

Basically, the best treatment is still considered to be surgery, in which the pituitary adenoma is removed via the classic transsphenoidal approach, where the surgeon enters through the nose and the sphenoid bone to reach the pituitary gland. The pituitary can be accessed through the nose because it is separated from the nasal cavity by the sphenoid sinus, which is a pneumatic cavity.

Unfortunately, the GH secreting pituitary adenoma is often quite large at the time of diagnosis, mainly due to delayed diagnosis. By definition, an adenoma larger than 1 cm is defined macroadenoma. When the tumor is large, it is more difficult to remove it completely, and therefore, the likelihood of cure with surgery is lower. It is estimated that only around 50% of patients with acromegaly can be cured by surgery, which nevertheless remains the first-line treatment for the vast majority of patients.

If surgery is not curative, treatment proceeds to medical therapy, typically with first-generation somatostatin analogs as the first choice. These drugs resemble the body’s own somatostatin, a neuropeptide from the hypothalamus that inhibits the secretion of, among other substances, growth hormone. They have a relatively long duration of action and are often administered as monthly injections, and they can control the disease in about 50% of patients.

If this treatment is not sufficient, second-line therapies are used, including newer somatostatin analogues or drugs that block the peripheral effects of growth hormone.

With these treatments, most patients achieve disease control, but a smaller group remains inadequately treated. In such cases, radiotherapy of the remaining pituitary adenoma is recommended, often using highly precise methods such as Gamma Knife. Gamma Knife is an advanced type of stereotactic radiotherapy.

How are the long-term health problems caused by acromegaly managed?

This is clearly an issue that largely depends on how quickly and how effectively we are able to bring the disease under control. In fact, several of the complications of the disease are reversible if biochemical control of acromegaly is achieved. In such cases, follow-up is not particularly difficult, as the disease is brought under control relatively quickly, even though some complications may already be present at the time of diagnosis. Although these complications are present at diagnosis, some of them can still be reversible.

The major clinical problem is when, in some cases, acromegaly is not adequately controlled. In these situations, complications may continue to develop and worsen rather than improve during follow-up.

In such cases, specific treatment targeting the affected tissues or organs is required. This applies, for example, to conditions such as hypertension and diabetes.

For this reason, patients should ideally be treated at so-called “centres of excellence” for pituitary tumors (PTCOE). These centers meet several quality criteria, including the presence of a multidisciplinary team of specialists. This includes not only endocrinologists and neurosurgeons but also other specialists who can help in diagnosis and follow-up and in managing complications that are irreversible or cannot be reversed due to insufficient disease control.

In such settings, the patient can receive the best possible care. Not only can the pituitary tumor and its activity be treated or controlled, but the patient’s overall health status can also be managed—potentially reducing the increased mortality that is unfortunately still seen in some patients with acromegaly.