What is the Best Treatment for Acromegaly?

Acromegaly Treatment Guide: Latest Advances & Proven Strategies

Acromegaly is a rare hormonal disorder occurring from abnormally high growth hormone production that happens due to the functioning of benign pituitary tumours. When left untreated or if the diagnosis is not done on time, it can cause slow physical changes, result in increased cardiovascular risks, and lead to organ enlargement.

In recent times, acromegaly treatment strategies aim to normalise growth hormone levels and alleviate the related symptoms via multimodal approaches. The details have been discussed below.

Best Treatment Options for Acromegaly

The best treatment solution for acromegaly is decided based on the specific tumour characteristics, treatment accessibility and a patient’s overall health. However, in the majority of situations, transsphenoidal surgery remains the most optimal treatment method.

Provided below are some viable treatment options for acromegaly:

1.  Surgical Intervention

Also referred to as endoscopic transnasal surgery, it helps remove pituitary tumours from the nasal cavity and boasts an overall success rate of 70-80% in accomplishing biochemical remission.

Surgeons opt for the surgical procedure only for microadenomas (tumours less than 10 mm in size) and well-defined macroadenomas. The process is so effective that it can accommodate rapid hormone normalisation and symptom relief.

2.  Pharmacological Therapies

Because of their comparatively lower success rates (40-60%), endocrinologists choose these therapies as the second-best treatment option. A patient is recommended to avoid surgery when it is contraindicated or if the expected results are not achievable.

The first-line medications normally include:

• Somatostatin analogues (octreotide/lanreotide): These synthetic hormones can help achieve biochemical control and prevent harmful symptoms through monthly injections.
• Dopamine agonists (cabergoline): It is a dopaminergic medication often suggested for mild acromegaly cases and needs to be taken orally.

Next, the second-line pharmacological options cover:

• Growth hormone antagonists (pegvisomant): Pegvisomant is used for blocking growth hormone receptors directly. However, the concerned patients require daily injections to sustain the effects.
• Pasireotide: It is a multi-receptor-targeted analogue for octreotide-resistant cases.

3.  Radiation Therapy

Doctors reserve radiation therapy for aggressive tumours that are generally unresponsive to other forms of treatment. Stereotactic radiosurgery (SRS) is a highly specialised radiation therapy that maintains exceptional accuracy while eradicating benign pituitary tumours.

Moreover, the SRS procedure has delivered a 50-60% efficacy in improving a patient's quality of life and is much less invasive compared to traditional surgery, though outcomes vary based on tumour characteristics and prior therapies.

Now that you have gone through the general treatment strategies, consider taking a look at the specific treatment order for classic acromegaly cases:

1. Step 1: Doctors consider the possibilities of surgical intervention for accessible tumours.
2. Step 2: If postoperative insulin-like growth factor-1 (IGF-1) levels stay elevated, your healthcare group will proceed with medical therapies, as mentioned.
3. Step 3: For complex cases, endocrinologists recommend combination regimens; for instance, it can be somatostatin analogues along with pegvisomant medication.
4. Step 4: Finally, the last resort will be radiation therapy.

What is the New Treatment for Acromegaly?

Recent advances focus on improving drug efficacy and targeting novel pathways:

1.  Medication Therapies

• Mycapssa: This is the first FDA-approved oral octreotide with comparable efficacy to injections. It has maintained IGF-1 control in 58% of patients during trials. Moreover, it eliminates injection-site complications.
• Pasireotide: Pasireotide is a selective somatostatin receptor type 2available as subcutaneous injections or long-acting release (LAR) formulations, that suppresses growth hormone production. This medication has shown 83% efficacy in maintaining biochemical control during phase 3 trials. Its once-daily dosing has improved growth hormone adherence.

2.  Extended-Release Formulations

Since extended-release formulations are used, patients have less need for doses and develop fewer negative side effects. The treatment consists of monthly injections, which makes it easier for patients to care for themselves. Lanreotide PRF, at this point, is being developed so patients may receive it every 6 months, which would also reduce the need for frequent visits to the doctor.

3.  Targeted Molecular Therapies

Targeted molecular therapies for acromegaly include CRN00808 (paltusotine), an oral non-peptide somatostatin receptor 2 (SST2) agonist currently in Phase 3 trials. It suppresses growth hormone secretion by selectively activating SST2 receptors.

Another approach, IONIS-GHR-LRx (cimdelirsen), utilises antisense oligonucleotides to inhibit growth hormone receptor synthesis, reducing IGF-1 levels in Phase 2 trials. Both therapies aim to improve treatment convenience and efficacy.

How are New Acromegaly Therapies Better?

The following table depicts how the emerging acromegaly treatment options are more effective than the traditional ones:

Effective acromegaly management requires individualised strategies combining surgical expertise, advanced pharmacological agents, and innovative therapies.

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