Acromegaly

Introduction

• Acromegaly is a rare neuroendocrine disorder, with a prevalence of approximately 3 – 13 cases per 100,000 people and an annual incidence rate of less than 1 case per 100,000 people. Both genders are equally affected.¹
• The pathophysiology of acromegaly is secondary to excessive secretion of growth hormone (GH) and associated insulin-like growth hormone factor 1 (IGF-1).
• Based on the source of excessive GH secretion, there are three broad causes of acromegaly (Table 1).²
  • Primary GH excess secretion,
  • Extra pituitary GH excess secretion, or
  • Growth hormone releasing hormone induced GH excess secretion.

• Pituitary adenoma accounts for more than 95 percent of acromegaly cases.²

Clinical Presentation^2,3,4

• Acromegaly usually has an insidious onset and progresses over many years.
• Acral enlargement and facial coarsening are the most common clinical manifestations.
• Headaches and visual disturbances may occur due to the underlying pituitary adenoma.
• Acromegaly is associated with comorbidities such as hypertension and diabetes. In addition, the risk of congestive heart failure is increased in acromegaly.
• Other features may include joint pain, sleep apnea, and soft tissue swelling.
• Table 3 summarizes the clinical features of acromegaly.

Diagnosis^2,3,4

• The diagnosis is often delayed by 5–10 years from the onset of clinical manifestations due to the insidious presentation.
• Measurement of IGF-1 levels is the first step once clinical suspicion of acromegaly arises.
• The current guidelines also suggest measuring IGF-1 levels in patients with other associated conditions, such as obstructive sleep apnea, diabetes, carpal tunnel syndrome, and hypertension. The level should be measured in all patients with a pituitary mass.
• If IGF‑1 is elevated or equivocal, the lack of GH suppression with an oral glucose load (< 1 μg/L) should be used to confirm the diagnosis.
• After biochemical diagnosis is confirmed, magnetic resonance imaging (MRI) is the preferred imaging modality. A computed tomography scan is an alternative option if an MRI is contraindicated.
• Other screening modalities, such as colonoscopy or thyroid ultrasound, may be indicated if excessive GH secretion is due to extra-pituitary causes.

Treatment^2,4

• The following guideline is from the European Society of Endocrinology
• The mortality rate correlates with the degree of GH and IGF-1 levels. The goal of treatment is to normalize IGF-1 serum levels and GH suppression.
• Transsphenoidal surgery is considered to be the primary treatment.
• Preoperative medical therapy such as somatostatin receptor ligands (SRL) is only indicated for patients with severe sleep apnea and severe cardiomyopathy.
• SRL is indicated for initial adjuvant medical therapy in a patient with severe symptoms. Dopamine agonists may be used in mild conditions.
• SRL is the primary medical therapy for a poor surgical candidate (e.g. extensive cavernous sinus extension). The addition of pegyisomant or carbergoline is necessary in patients with an inadequate response to maximal SRL.
• The guideline also recommends serial MRI for patients on medical therapy.
• Comorbid conditions should be managed according to standard guidelines, in addition to treating the underlying GH and IGF-1 excess.

Anesthetic Considerations

• Excessive GH with increased IGF-1 secretion in acromegaly causes various systemic changes.
• Please see the OA summary on anesthesia for pituitary surgery for more details. Link
• Key systemic changes with corresponding perioperative challenges will be discussed in this section.

Airway Changes

• In acromegaly, GH and IGF-1 stimulate the overgrowth of soft tissues and bones. There are significant alterations in airway anatomy, including narrowing, obstruction, and distortion.
• These changes may increase the risk of a difficult airway during both mask ventilation and endotracheal intubation.
• Table 3 summarizes the key airway changes along with corresponding clinical implications. In addition, Figure 1 demonstrates gradual changes in facial features in acromegaly.
• A comprehensive preoperative airway assessment and appropriate airway management planning are essential in patients with acromegaly.⁵

Cardiovascular Changes

• Acromegalic patients are prone to developing various cardiovascular comorbidities such as hypertension, arrhythmias, and congestive heart failure.

Hypertension

• Smooth muscle cell growth increases vascular resistance, while enhanced sodium reabsorption further expands plasma volume. Subsequently, the increase in cardiac output, along with these changes, results in hypertension³ (Figure 2).

Cardiomyopathy

• Biventricular concentric hypertrophy is a common cardiovascular finding in patients with acromegaly. It has a positive correlation with disease duration. There are three stages in the development of acromegalic cardiomyopathy.⁷
  • Early stage: Early development of biventricular concentric hypertrophy with hyperkinetic cardiac function
  • Intermediate stage: Gradual deterioration of diastolic and systolic cardiac function
  • Late stage: Severe systolic and diastolic dysfunction with structural dilation leading to congestive heart failure

Arrhythmias

• Arrhythmias are the leading cause of sudden cardiac death in acromegalic patients.
• Common clinical manifestations include sinus bradycardia and bundle branch block. Myocardial fibrosis is the leading cause of arrhythmias in these patients.⁷

Endocrine Changes

• Diabetes mellitus (DM) is common in patients with acromegaly. No specific intervention is required beyond the standard diabetic precautions.
• In addition, if the source of GH secretion is expected to be removed during surgical intervention, careful perioperative glucose monitoring is essential to avoid acute hypoglycemia.⁸

Musculoskeletal Changes

• Musculoskeletal manifestations, including enlarged extremities, osteoarthritis, and joint changes, are seen in acromegalic patients. For instance, severe carpal tunnel hypertrophy may compromise the collateral circulation of radial and ulnar arteries (Figure 3).
• A thorough preoperative evaluation of arterial blood flow, such as the Allen test or an angiogram, is necessary to avoid potential hand ischemia.
• In addition, as always, careful attention should be paid to intraoperative positioning.⁹