Acromegaly: Symptoms, Types, Causes and Treatment

Acromegaly is a complex hormonal disorder that slowly changes the body, often going unrecognized for years. Although relatively rare, its impact on health and quality of life is significant. Understanding its symptoms, different forms, underlying causes, and modern treatment approaches is crucial for timely diagnosis and effective management. This article presents an in-depth exploration of acromegaly, supported by the latest research and consensus guidelines.

Symptoms of Acromegaly

Acromegaly develops insidiously, often escaping early detection due to the slow and progressive nature of its symptoms. People with acromegaly typically experience a combination of physical changes and systemic health problems, which can significantly affect their quality of life if left untreated.

Main Symptom	Description	Prevalence/Impact	Source(s)
Acral enlargement	Enlargement of hands, feet, fingers, toes	~90% at diagnosis	2 3 4 5
Facial changes	Coarse features: brow, nose, lips, jaw	~65%; early, often subtle	2 4 5
Oral symptoms	Jaw protrusion, dental spacing, malocclusion	~62%	2 4 5
Headache	Persistent or recurrent	~59%	5 1
Fatigue	Daytime tiredness, asthenia	~53-79%	3 5
Snoring/sleep apnea	Loud snoring, sleep disturbances	~46-81%	3 5
Joint pain	Arthralgia, arthritis	~34%	5 2
Skin changes	Oily, thickened skin, increased sweating	~35-47%	5 2
Hypertension	High blood pressure	Common comorbidity	1 5 13
Metabolic symptoms	Diabetes, glucose intolerance	Elevated risk	1 2 5 13
Tumor effects	Vision changes, hypopituitarism	Variable, due to mass effect	1 5 9

Table 1: Key Symptoms of Acromegaly

Physical Changes

The most recognizable signs of acromegaly are those that result from abnormal growth of bone and soft tissue. These include:

• Acral enlargement: Patients almost universally notice larger hands and feet, with rings and shoes no longer fitting. Fingers and toes become thick and spade-like in appearance, often years before diagnosis 2 3 4 5.
• Facial feature coarsening: The brow and jaw become more prominent, the nose widens, lips thicken, and skin folds deepen. These changes are subtle at first and slowly intensify, making them easy to overlook until they become pronounced 2 4 5.
• Oral and jaw changes: Enlargement of the jaw (mandibular prognathism) leads to dental malocclusion and increased spacing between teeth, often noticed by dentists 2 4 5.

Systemic and Functional Symptoms

Acromegaly also affects multiple body systems, leading to:

• Headaches: Result from tumor pressure or hormonal effects, present in over half of patients 5 1.
• Fatigue and muscle weakness: Daytime tiredness, decreased stamina, and general asthenia are reported by most patients 3 5.
• Sleep disturbances: Loud snoring and sleep apnea are common due to upper airway soft tissue overgrowth, significantly impacting quality of life 3 5.
• Joint pain (arthralgia): Due to cartilage and bone changes, leading to arthritis that can be disabling 2 5.
• Skin changes: Patients may notice increased oiliness, sweating (hyperhidrosis), and thickened skin 5 2.

Comorbidities and Complications

Left untreated, acromegaly can lead to:

• Hypertension and cardiovascular disease: High blood pressure, arrhythmias, and left ventricular hypertrophy increase the risk of heart failure and premature death 1 5 13.
• Metabolic disorders: Insulin resistance, impaired glucose tolerance, and diabetes are common, often reversible with early treatment 1 2 5 13.
• Neoplastic risks: Increased risk of colon polyps and certain cancers, such as thyroid and colorectal cancer, even after control of acromegaly 1 5.
• Tumor mass effects: Large pituitary tumors may cause vision problems or hypopituitarism due to local pressure 1 5 9.

Early Recognition

Unfortunately, because many symptoms overlap with common conditions and physical changes occur gradually, acromegaly is often not diagnosed until 5–10 years after onset. Early recognition of the combination of acral and facial changes with systemic comorbidities is essential for timely diagnosis 2 3 4 5.

Types of Acromegaly

Acromegaly is not a single disease, but rather a syndrome with several underlying forms, each with distinct clinical and pathological features. Understanding these types is important for accurate diagnosis and personalized treatment.

Type	Distinguishing Feature	Prevalence/Notes	Source(s)
Classic (Pituitary)	GH-secreting pituitary adenoma	>95% of cases	2 6 8 9 11
Ectopic Acromegaly	Non-pituitary GH or GHRH secretion	<1%	7 9 10
Gigantism	Onset before growth plate closure	~5% (children/adolesc.)	2 6 9
Tumor subtypes	Densely/sparsely granulated, mixed, others	Pathological variants	6 9

Table 2: Types of Acromegaly

Classic Acromegaly (Pituitary Origin)

• Pituitary adenomas: The overwhelming majority of acromegaly cases are due to benign tumors of the pituitary gland that secrete excess growth hormone (GH). These may be:
  • Pure somatotroph adenomas (densely or sparsely granulated)
  • Mixed cell adenomas (e.g., somatotroph-lactotroph)
  • Plurihormonal tumors 2 6 8 9 11

Each subtype can differ in tumor behavior, hormone secretion, and response to treatment 6 9.

Ectopic Acromegaly

• Non-pituitary sources: Rarely, acromegaly arises from GH or more often GHRH secretion by tumors in other parts of the body (e.g., lungs, pancreas, or neuroendocrine tumors), stimulating the pituitary to secrete excess GH 7 9 10. Ectopic acromegaly is important to distinguish as pituitary surgery is ineffective in these cases.

Gigantism

• Pediatric onset: When GH excess begins before the closure of growth plates in children or adolescents, it leads to excessive linear growth—gigantism. This is a rare form (about 5% of cases) and presents with similar features as acromegaly, but with marked height increase 2 6 9.

Tumor Subtypes and Rare Variants

• Pathological variants: Tumors are further classified based on cell type, hormone production, and microscopic appearance, such as acidophil stem cell, mammosomatotroph, or poorly differentiated tumors, each with unique clinical profiles 6 9.

Causes of Acromegaly

Acromegaly results from chronic exposure to excess growth hormone, but the underlying causes are diverse and sometimes complex.

Cause	Mechanism	Frequency/Notes	Source(s)
Pituitary adenoma	GH-secreting benign tumor	~95-99%	2 6 8 9 11
Ectopic GHRH secretion	NETs (lung, pancreas) stimulate pituitary	Rare (<1%)	7 9 10
Ectopic GH secretion	NETs or other tumors directly secrete GH	Extremely rare	7 9 10
Pituitary hyperplasia	Due to chronic GHRH stimulation	Rare	7 9
Genetic/environmental	Underlying predisposition, not fully defined	Uncommon, unclear	9

Table 3: Causes of Acromegaly

Pituitary Adenomas

Most cases are caused by a benign tumor (adenoma) of the anterior pituitary gland. These tumors arise from somatotroph cells and secrete excess GH, which in turn stimulates the liver to produce insulin-like growth factor 1 (IGF-1), the true mediator of tissue overgrowth and metabolic effects 2 6 8 9 11.

• Subtypes: Densely and sparsely granulated somatotroph adenomas, mixed hormone-producing tumors, and other rare variants exist, each with different clinical and therapeutic implications 6 9.

Ectopic GHRH and GH Secretion

Rarely, tumors outside the pituitary (most commonly neuroendocrine tumors of the lung or pancreas) secrete GHRH, which stimulates the pituitary to enlarge and overproduce GH. In even rarer instances, these tumors directly produce GH 7 9 10.

• Diagnostic challenges: Ectopic cases may mimic pituitary adenoma on imaging due to secondary pituitary hyperplasia, making hormone assays and search for primary tumors essential 7 10.

Pituitary Hyperplasia

Chronic stimulation of the pituitary by excess GHRH (from ectopic or hypothalamic sources) can cause pituitary hyperplasia and secondary acromegaly 7 9.

Genetic and Environmental Factors

While most cases are sporadic, some may have underlying genetic predispositions or be part of syndromes (e.g., MEN-1), but these account for a minority of patients 9.

Treatment of Acromegaly

Effective management of acromegaly requires a multidisciplinary approach. Advances in surgery, medication, and radiotherapy have transformed outcomes for most patients, often restoring life expectancy to normal with successful treatment.

Treatment	Mechanism/Goal	Indications	Source(s)
Transsphenoidal surgery	Remove pituitary tumor	First-line for most	11 12 15
Medical therapy	Suppress GH/IGF-1, shrink tumor	Adjunct/primary if inoperable	11 12 15
Radiotherapy	Tumor control when surgery/meds insufficient	Select cases	11 12 15
Ectopic tumor removal	Excise non-pituitary source	Ectopic acromegaly	7 10
Comorbidity management	Treat hypertension, diabetes, sleep apnea	All patients	1 13 14

Table 4: Treatment Options in Acromegaly

Surgical Treatment

• Transsphenoidal surgery: The gold standard for pituitary adenomas, aiming for complete tumor removal and rapid normalization of GH/IGF-1. Success rates are higher for smaller tumors and in experienced centers 11 12 15.
• Ectopic tumor surgery: In cases of ectopic GHRH or GH secretion, surgical removal of the primary tumor (e.g., lung or pancreatic NET) can be curative 7 10.

Medical Therapy

For patients not cured by surgery, inoperable tumors, or those unfit for anesthesia, medication is essential:

• Somatostatin receptor ligands (SRLs): Octreotide, lanreotide, and pasireotide inhibit GH release and can shrink tumors 11 12 15.
• GH receptor antagonists: Pegvisomant blocks GH action at peripheral tissues, reducing IGF-1 11 12.
• Dopamine agonists: Cabergoline and others may help in milder cases or as adjuncts 11 12 15.

Choice of medication depends on tumor size, hormone levels, comorbidities, and patient preference 12.

Radiotherapy

• Used when surgery and medication fail to fully control the disease.
• Modern techniques (e.g., stereotactic radiosurgery) reduce risks but benefits may take years to manifest 11 12 15.

Management of Comorbidities

• Hypertension, diabetes, sleep apnea, joint disease, and cancer risks all require active management, even after acromegaly control 1 13 14.
• Early and effective treatment can reverse some complications, improving quality of life and survival 1 13.

Long-Term Monitoring

• Lifelong follow-up is necessary to monitor for recurrence, manage comorbidities, and screen for associated cancers (especially colon) 1 5 14.
• A multidisciplinary team—including endocrinologists, neurosurgeons, radiologists, and other specialists—optimizes patient outcomes 15.

Conclusion

Acromegaly is a rare but serious disorder with multisystem effects and complex management needs. Early recognition and a personalized, multidisciplinary approach are essential for optimal patient outcomes.

Key Takeaways:

• Symptoms develop slowly: Most patients have acral and facial changes along with systemic issues (hypertension, diabetes, joint pain) 2 3 4 5.
• Multiple forms: While most cases are due to pituitary adenomas, rare forms include ectopic hormone secretion and gigantism 2 6 7 9.
• Diagnosis can be delayed: Overlapping symptoms with common conditions often postpone diagnosis for years 3 4 5.
• Treatment is highly effective: Surgery, medication, and radiotherapy can normalize hormone levels and restore life expectancy when applied appropriately 11 12 13 15.
• Ongoing care is vital: Lifelong monitoring and management of comorbidities remain necessary for all patients 1 5 14 15.

Awareness of the diverse presentations and advances in therapy can help ensure timely diagnosis and improved quality of life for those affected by acromegaly.