Acromegaly

Acromegaly is a rare endocrine disorder that results in the excessive secretion of growth hormone (GH) after closure of the epiphyses during puberty, leading to the growth of bone, cartilage, and soft tissue in adults. The condition can be caused by a pituitary adenoma or other tumors that secrete GH-releasing hormone (GHRH) or GH. Acromegaly is a progressive disorder that can cause significant morbidity and mortality if left untreated.

Case:

Mr. John is a 40-year-old male who presented to the endocrine clinic with complaints of enlargement of hands and feet, facial changes, and excessive sweating. He reported having these symptoms for the past 5 years, which have been progressively worsening. He denied any significant past medical or surgical history. His family history was unremarkable. Physical examination revealed coarse facial features, large hands and feet, prominent supraorbital ridges, and enlarged tongue. His laboratory investigations showed elevated GH and insulin-like growth factor-1 (IGF-1) levels, confirming the diagnosis of acromegaly.

Pathophysiology:

The excessive secretion of GH in acromegaly results in increased production of IGF-1, which is responsible for the clinical manifestations of the disease. The excess IGF-1 stimulates bone growth, leading to acral and facial changes, including enlargement of hands, feet, and facial bones, and soft tissue growth, causing thickened skin, prominent supraorbital ridges, and enlarged tongue. The increased GH and IGF-1 levels can also cause systemic effects, including insulin resistance, diabetes, hypertension, and cardiovascular disease.

Signs and Symptoms:

The signs and symptoms of acromegaly can be gradual and insidious, leading to a delay in diagnosis. Common features of acromegaly include:

Enlargement of hands, feet, and facial bones
Coarsening of facial features, including a prominent jaw and forehead
Thickening of the skin and soft tissues
Excessive sweating
Fatigue and weakness
Joint pain and stiffness
Headaches
Visual disturbances
Menstrual irregularities in women
Erectile dysfunction in men
Investigation:

The diagnosis of acromegaly is made based on clinical features, laboratory investigations, and imaging studies. The initial screening test is a measurement of serum IGF-1 levels, which are elevated in the majority of patients with acromegaly. If the IGF-1 level is elevated, a confirmatory test with an oral glucose tolerance test (OGTT) is done to assess the suppression of GH levels. GH levels are expected to be suppressed to less than 0.4 ng/mL in response to glucose ingestion in normal individuals. However, in patients with acromegaly, GH levels remain elevated despite glucose ingestion. Magnetic resonance imaging (MRI) of the pituitary gland is done to identify the underlying cause of the GH excess, such as a pituitary adenoma or other tumors.

Treatment:

The goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal levels and prevent the progression of clinical features and complications. The treatment options include:

Surgery: Transsphenoidal surgery is the first-line treatment for most patients with pituitary adenomas causing acromegaly. The surgery aims to remove the tumor and restore normal pituitary function.

Radiation therapy: Radiation therapy is used in patients who have residual or recurrent tumors after surgery. It is also used as a primary treatment in patients who are not candidates for surgery.

Medical therapy: Medical therapy is used as adjunctive treatment in patients with persistent disease after surgery or those who are not candidates for surgery. The medications used in detail about medical therapy and advise (dos and don’ts) for patients with acromegaly.

Medical therapy for acromegaly involves the use of drugs that either decrease GH secretion or block the action of GH and IGF-1. The choice of medication depends on the underlying cause of the GH excess and the individual patient’s response to therapy. The following are the commonly used medications for the treatment of acromegaly:

Somatostatin analogs (SSAs): These drugs mimic the action of somatostatin, a hormone that inhibits GH secretion. Octreotide and lanreotide are the two commonly used SSAs. These drugs are given as injections, either subcutaneously or intramuscularly, every 4-6 weeks. They are effective in reducing GH and IGF-1 levels in up to 70% of patients with acromegaly.

Dopamine agonists: Bromocriptine and cabergoline are dopamine agonists that can suppress GH secretion in some patients with acromegaly. These drugs are effective in approximately 20-30% of patients and are usually used as adjunctive therapy.

GH receptor antagonists: Pegvisomant is a GH receptor antagonist that blocks the action of GH and reduces IGF-1 levels. It is given as a daily subcutaneous injection and is effective in reducing IGF-1 levels in up to 90% of patients.

Dos and Don’ts for patients with acromegaly:

Do attend regular follow-up visits with your endocrinologist to monitor your GH and IGF-1 levels and adjust your medication as needed.

Do maintain a healthy lifestyle, including regular exercise and a balanced diet, to prevent or manage complications such as diabetes, hypertension, and cardiovascular disease.

Don’t stop or change your medication without consulting your endocrinologist.

Don’t use over-the-counter supplements or medications without consulting your endocrinologist, as they can interfere with your treatment.

Do inform your healthcare providers about your acromegaly diagnosis and medications, as they can affect the management of other medical conditions.

Do monitor for signs and symptoms of complications, such as diabetes, hypertension, and cardiovascular disease, and seek medical attention if needed.

In conclusion, acromegaly is a rare but serious endocrine disorder that can lead to significant morbidity and mortality if left untreated. The diagnosis is made based on clinical features, laboratory investigations, and imaging studies. The treatment options include surgery, radiation therapy, and medical therapy, depending on the underlying cause of the GH excess. Patients with acromegaly should attend regular follow-up visits with their endocrinologist, maintain a healthy lifestyle, and adhere to their treatment plan to prevent or manage complications.

References:

Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest. 2009;119(11):3189-3202.

Katznelson L, Laws Jr ER, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951.

Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone–receptor antagonist pegvisomant. N Engl J Med. 2000;342(16):1171-1177.