Overview
Acromegaly
1. Clinical Overview
Summary
Acromegaly is a chronic, insidious condition caused by excess growth hormone (GH) secretion, almost always from a pituitary somatotroph adenoma. It leads to elevated insulin-like growth factor 1 (IGF-1), causing characteristic somatic and metabolic changes including acral enlargement, facial coarsening, and multi-system complications. Diagnosis is often delayed 7-10 years after symptom onset due to the slow, progressive nature of changes. Without treatment, acromegaly carries a 2-3 fold increased mortality risk, primarily from cardiovascular and cerebrovascular disease.
Key Facts
- Definition: Chronic excess of GH in adults after growth plate closure, causing tissue overgrowth
- Prevalence: 40-130 per million; incidence 3-4 per million per year
- Mortality/Morbidity: 2-3× increased mortality without treatment; normal life expectancy achievable with biochemical control
- Key Management: Trans-sphenoidal surgery (first-line); somatostatin analogues (post-op or if unfit for surgery)
- Critical Finding: Bitemporal hemianopia indicates chiasmal compression — urgent imaging and neurosurgical referral
- Key Investigation: IGF-1 (screening); oral glucose tolerance test (confirmatory); MRI pituitary
Clinical Pearls
"Ring Size and Shoe Size": Progressive increase in ring and shoe size is a classic early symptom often elicited on history — ask specifically!
Delayed Diagnosis: Average delay from symptom onset to diagnosis is 7-10 years. Compare old photographs to identify insidious facial changes.
Colorectal Cancer Risk: Patients with acromegaly have 2-3× increased risk of colorectal neoplasia — screening colonoscopy is mandatory.
Why This Matters Clinically
Acromegaly causes significant multi-system morbidity (cardiovascular disease, diabetes, sleep apnoea, osteoarthritis) and malignancy risk (especially colorectal). Early diagnosis and biochemical control normalise life expectancy. Visual field loss from chiasmal compression may be irreversible if delayed.
2. Epidemiology
Incidence & Prevalence
- Incidence: 3-4 per million per year
- Prevalence: 40-130 per million population
- Trend: Stable; possibly increasing detection due to wider MRI use
Demographics
| Factor | Details |
|---|---|
| Age | Peak diagnosis 40-50 years; symptoms often start a decade earlier |
| Sex | Male = Female (1:1 ratio) |
| Ethnicity | No ethnic predisposition; worldwide distribution |
| Geography | No significant regional variation |
Risk Factors
Non-Modifiable:
- MEN1 (Multiple Endocrine Neoplasia type 1) — rare familial association
- Carney complex — rare
- Familial isolated pituitary adenoma (FIPA)
- AIP gene mutations (younger onset, aggressive tumours)
Modifiable:
| Risk Factor | Relative Risk |
|---|---|
| None well-established | N/A |
| (Acromegaly is almost always due to sporadic pituitary adenoma) | — |
Aetiology Distribution:
| Cause | Frequency |
|---|---|
| Pituitary somatotroph adenoma | >5% |
| Ectopic GHRH-secreting tumour (carcinoid, lung) | <1% |
| Ectopic GH-secreting tumour | Very rare |
| Familial syndromes (MEN1, Carney complex) | 3-5% |
3. Pathophysiology
Mechanism
Step 1: Somatotroph Adenoma Formation
- Monoclonal proliferation of GH-secreting cells in anterior pituitary
- Sporadic mutations (GSP oncogene in 40%) or familial predisposition
- Autonomous GH secretion escapes normal feedback inhibition
Step 2: GH Excess and IGF-1 Elevation
- Excess GH stimulates hepatic production of IGF-1 (insulin-like growth factor 1)
- GH and IGF-1 act on multiple tissues via specific receptors
- IGF-1 mediates most of the somatic effects of GH
Step 3: Multi-System Effects
- Soft tissue/bone: Acral enlargement (hands, feet, jaw), soft tissue overgrowth (macroglossia, visceral enlargement)
- Metabolic: Insulin resistance, diabetes mellitus (30-40%)
- Cardiovascular: Cardiomyopathy, hypertension (30-50%), arrhythmias
- Respiratory: Obstructive sleep apnoea (>50%), upper airway narrowing
- Neoplastic: Increased colorectal polyp/cancer risk (IGF-1 is mitogenic)
- Musculoskeletal: Osteoarthritis, carpal tunnel syndrome
Classification
| Type | Definition | Features |
|---|---|---|
| Microadenoma | Pituitary adenoma <10mm | Better surgical outcomes; less likely to cause visual compromise |
| Macroadenoma | Pituitary adenoma ≥10mm | More common at diagnosis; may compress optic chiasm; lower surgical cure rates |
| Giant adenoma | Pituitary adenoma >0mm | Significant extension; often requires debulking + adjuvant therapy |
| Invasive adenoma | Invasion into cavernous sinus/bone | Poor surgical cure rates; medical therapy essential |
Anatomical/Physiological Considerations
The pituitary gland sits in the sella turcica, directly below the optic chiasm. Macroadenomas expanding superiorly compress the chiasm, causing the classic bitemporal hemianopia (loss of temporal visual fields bilaterally). Lateral expansion into the cavernous sinus involves cranial nerves III, IV, V1, V2, and VI.
4. Clinical Presentation
Symptoms
Typical Presentation (Insidious — often 5-10 years before diagnosis):
Atypical Presentations:
Signs
Red Flags
[!CAUTION] Red Flags — Urgent assessment required if:
- Bitemporal hemianopia or any visual field defect (optic chiasm compression — urgent MRI and neurosurgery referral)
- Sudden severe headache, visual loss, nausea/vomiting (pituitary apoplexy — medical emergency)
- Signs of adrenal insufficiency (hypopituitarism — risk of adrenal crisis)
- New cranial nerve palsy (cavernous sinus invasion)
- Symptoms/signs of colorectal malignancy (increased cancer risk)
Progressive enlargement of hands and feet (100%) — rings no longer fit, shoes increase in size
Common presentation.
Facial coarsening — frontal bossing, prominent supraorbital ridges (90%)
Common presentation.
Excessive sweating (hyperhidrosis) (60-80%)
Common presentation.
Headache (50-60%)
Common presentation.
Joint pain (osteoarthritis, especially large joints) (50-70%)
Common presentation.
Fatigue and weakness (40-50%)
Common presentation.
Snoring and obstructive sleep apnoea (>50%)
Common presentation.
5. Clinical Examination
Structured Approach
General:
- Compare with previous photographs (old ID cards) — assess for progressive change
- Body habitus, height (gigantism if pre-pubertal onset)
- Voice quality (deep/husky)
Specific System Examination:
- Face: Frontal bossing, supraorbital ridge prominence, prognathism, macroglossia, wide-spaced teeth
- Hands: Spade-like, soft tissue thickening, increased ring/glove size, Tinel's sign (carpal tunnel)
- Feet: Broad, increased shoe size
- Skin: Thick, oily, hyperhidrosis, skin tags
- Thyroid: Goitre
- Cardiovascular: BP, apex beat (cardiomegaly), heart sounds
- Neurological: Visual fields (confrontation), cranial nerves
Special Tests
| Test | Technique | Positive Finding | Sensitivity/Specificity |
|---|---|---|---|
| Confrontation visual fields | Bring finger from periphery in all quadrants | Bitemporal hemianopia | Screening; formal fields required |
| Formal perimetry (Humphrey/Goldmann) | Automated visual field testing | Bitemporal hemianopia or superior quadrantanopia | Gold standard |
| Tinel's sign (wrist) | Tap over carpal tunnel | Paraesthesiae in median nerve distribution | ~60%/~67% for carpal tunnel |
| Photograph comparison | Compare with photos from 5-10 years ago | Progressive facial coarsening | N/A — clinical tool |
6. Investigations
First-Line (Bedside)
- Blood pressure — hypertension common (30-50%)
- Finger-prick glucose — diabetes screening
- Visual field assessment (confrontation) — bitemporal hemianopia
Laboratory Tests
| Test | Expected Finding | Purpose |
|---|---|---|
| Serum IGF-1 | Elevated for age/sex | Screening test — reflects integrated GH secretion |
| Oral Glucose Tolerance Test (OGTT) | GH fails to suppress <1 μg/L (or <0.4 μg/L with sensitive assays) | Confirmatory — gold standard |
| Random GH | Often elevated but can be normal (pulsatile) | Supportive; not definitive |
| Prolactin | May be elevated (co-secretion or stalk effect) | 30% have co-secretion |
| Pituitary function | May show hypopituitarism | Early morning cortisol, TFTs, gonadotrophins, sex hormones |
| Fasting glucose/HbA1c | Elevated in 30-40% | Diabetes screening |
| Lipid profile | Variable | Cardiovascular risk assessment |
Imaging
| Modality | Findings | Indication |
|---|---|---|
| MRI pituitary (gadolinium-enhanced) | Pituitary adenoma (microadenoma <10mm or macroadenoma ≥10mm); chiasmal compression | Gold standard imaging |
| CT head (if MRI contraindicated) | Sellar mass, bone changes | Alternative if MRI not possible |
| CXR / CT chest (if ectopic suspected) | Carcinoid or GHRH-secreting tumour | If pituitary MRI negative |
| Echocardiogram | LVH, cardiomyopathy, valvular disease | Complication screening |
Diagnostic Criteria
Biochemical Diagnosis (Endocrine Society):
| Test | Result | Interpretation |
|---|---|---|
| IGF-1 | Elevated above age/sex reference | Suggests GH excess |
| OGTT | GH nadir >1 μg/L (>.4 μg/L with sensitive assay) | Confirms autonomous GH secretion |
Diagnosis confirmed by:
- Elevated IGF-1 (age/sex matched)
- PLUS failure of GH suppression on OGTT
- PLUS imaging confirmation of pituitary adenoma (in vast majority)
7. Management
Management Algorithm
Acute/Emergency Management (if applicable)
Pituitary Apoplexy (emergency):
- IV hydrocortisone 100mg stat (assume hypopituitarism)
- IV fluids for circulatory support
- Urgent MRI pituitary
- Neurosurgical and endocrine consultation
- May require emergency trans-sphenoidal decompression
Conservative Management
- Patient education: Explain disease, treatment options, monitoring
- Cardiovascular risk management: BP control, lipid management, diabetes optimisation
- Sleep apnoea: CPAP if diagnosed on polysomnography
- Complication screening (see below)
Medical Management
| Drug Class | Drug | Dose | Duration |
|---|---|---|---|
| Somatostatin Analogue (1st-line medical) | Octreotide LAR | 10-30 mg IM every 4 weeks | Long-term |
| Somatostatin Analogue | Lanreotide Autogel | 60-120 mg SC every 4 weeks | Long-term |
| GH Receptor Antagonist | Pegvisomant | 10-30 mg SC daily | Long-term (normalises IGF-1 in >0%) |
| Dopamine Agonist (if co-secretion) | Cabergoline | 0.5-3 mg/week PO | Long-term; ~30% response alone |
Notes:
- Somatostatin analogues achieve biochemical control in ~55% and tumour shrinkage in 30-50%
- Pegvisomant is highly effective for IGF-1 normalisation but does not shrink/affect tumour — needs MRI monitoring
- Combination therapy often needed
Surgical Management
Indications:
- First-line treatment for most patients (curative intent)
- Urgent if chiasmal compression with visual field loss
- Debulking even if cure unlikely (reduces tumour burden for medical therapy)
Procedure:
- Trans-sphenoidal surgery (TSS): Endoscopic or microscopic approach via nasal/sphenoid route
- Microadenomas: 80-90% biochemical remission
- Macroadenomas: 40-60% remission (lower if invasive)
Radiotherapy:
- Third-line (after surgery + medical therapy failure)
- Stereotactic radiosurgery (SRS) or fractionated radiotherapy
- Slow onset of effect (years); risk of hypopituitarism (30-50% at 10 years)
Disposition
- Admit if: Pituitary apoplexy, pre-operative preparation, severe complications
- Discharge if: Stable, outpatient investigation and treatment planning
- Follow-up: MDT pituitary clinic; post-op IGF-1 at 12 weeks; long-term annual review
8. Complications
Immediate (Minutes-Hours)
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Pituitary apoplexy | Rare (1-2%) | Sudden headache, visual loss, collapse | IV steroids, fluids, urgent neurosurgery |
| Post-operative CSF leak | 2-5% post-TSS | Clear nasal discharge | Lumbar drain; surgical repair if persistent |
| Post-operative hypopituitarism | 5-10% | Fatigue, hypotension, hyponatraemia | Hormone replacement |
Early (Days-Weeks)
- Diabetes insipidus (post-surgery): Usually transient; DDAVP if needed
- SIADH (post-surgery): Hyponatraemia; fluid restriction
- Meningitis (post-surgery): Rare; antibiotics
Late (Months-Years)
- Cardiovascular disease: Cardiomyopathy, heart failure, arrhythmias, hypertension
- Diabetes mellitus: 30-40%
- Obstructive sleep apnoea: >50%; persists even after treatment in many
- Osteoarthritis: Progressive joint disease
- Colorectal neoplasia: 2-3× increased risk — colonoscopy screening essential
- Hypopituitarism: Post-surgery or post-radiotherapy
- Tumour recurrence: 10-20% over 10 years
9. Prognosis & Outcomes
Natural History
Untreated acromegaly carries a 2-3 fold increased mortality, primarily from cardiovascular disease (heart failure, stroke), respiratory complications, and malignancy. Average life expectancy without treatment is reduced by approximately 10 years.
Outcomes with Treatment
| Variable | Outcome |
|---|---|
| Mortality (treated) | Normalised if biochemical control achieved (IGF-1 and GH targets met) |
| Surgical cure (microadenoma) | 80-90% biochemical remission |
| Surgical cure (macroadenoma) | 40-60% biochemical remission |
| Biochemical control (medical therapy) | 55% with somatostatin analogues; >0% with pegvisomant |
| Recurrence | 10-20% over 10 years |
Prognostic Factors
Good Prognosis:
- Microadenoma (<10mm)
- Complete surgical resection
- Biochemical control (normalised IGF-1 and GH <1 μg/L)
- Young age at diagnosis
- Absence of cardiovascular/metabolic complications
Poor Prognosis:
- Invasive macroadenoma (especially cavernous sinus invasion)
- Failure to achieve biochemical control
- Established cardiovascular disease, diabetes
- Delayed diagnosis with significant complications
10. Evidence & Guidelines
Key Guidelines
- Endocrine Society Clinical Practice Guideline: Acromegaly (2014, updated 2021) — Recommends IGF-1 for screening, OGTT for confirmation; surgery first-line; medical therapy for residual disease. Endocrine Society
- Pituitary Society Consensus: Acromegaly Management (2018) — Emphasises MDT approach; outlines targets for biochemical control; recommends complication screening. Pituitary Society
Landmark Trials
Colao A et al. (Pasireotide Phase 3, 2014) — Randomised trial of pasireotide LAR vs octreotide/lanreotide in acromegaly.
- 358 patients randomised
- Key finding: Pasireotide achieved biochemical control in 31.3% vs 19.2% for other SSAs; higher hyperglycaemia risk
- Clinical Impact: Pasireotide available for SSA-resistant patients; hyperglycaemia needs monitoring
Trainer PJ et al. (Pegvisomant Trial, 2000) — Key efficacy study of pegvisomant.
- 112 patients treated
- Key finding: IGF-1 normalised in >90% of patients
- Clinical Impact: Established pegvisomant as highly effective for IGF-1 normalisation when SSAs inadequate
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| Trans-sphenoidal surgery (first-line) | 2a | Cohort studies; guideline consensus |
| Somatostatin analogues (SSAs) | 1b | RCTs; meta-analyses |
| Pegvisomant | 1b | RCTs (Trainer et al.) |
| Radiotherapy (adjunctive) | 2b | Retrospective series; long-term follow-up |
| Colonoscopy screening | 2a | Cohort studies showing increased neoplasia risk |
11. Patient/Layperson Explanation
What is Acromegaly?
Acromegaly is a rare condition where your body makes too much growth hormone. This usually happens because of a small, non-cancerous tumour (called an adenoma) in the pituitary gland — a pea-sized gland at the base of your brain. Because the changes happen slowly over many years, it often takes a long time to be diagnosed.
Why does it matter?
Too much growth hormone causes your body to keep growing in certain areas, even in adulthood:
- Your hands, feet, and face (especially the jaw) may enlarge
- Many organs can grow larger, including your heart
- It can cause diabetes, high blood pressure, and heart problems
- There is an increased risk of bowel polyps and cancer, so screening is important Without treatment, acromegaly can shorten life expectancy, but with proper treatment, most people live normal, healthy lives.
How is it treated?
- Surgery: The most common first treatment. Surgeons remove the pituitary tumour through your nose (no visible scars). This cures many patients, especially if the tumour is small.
- Medication: If surgery doesn't work completely, injections (like octreotide or lanreotide) can control hormone levels. Another medicine (pegvisomant) blocks the hormone's effects.
- Radiotherapy: Sometimes used if surgery and medicines aren't enough. It works slowly over several years.
What to expect
- Treatment is very effective — most people achieve good hormone control
- You'll need regular blood tests and scans to monitor hormone levels and the tumour
- Some effects (like enlarged hands/feet) may not fully reverse, but further growth stops
- You'll need a colonoscopy to check for bowel polyps
- A team of specialists (endocrinologists, neurosurgeons, eye doctors) will look after you
When to seek help
- Urgent: Sudden severe headache with vision problems (pituitary apoplexy — rare but serious)
- Soon: Any change in vision, new weakness, or fainting
- Routine: Keep follow-up appointments to monitor your condition
12. References
Primary Guidelines
- Katznelson L, et al. Acromegaly: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. PMID: 25356808
- Melmed S, et al. A Consensus Statement on Acromegaly Therapeutic Outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. PMID: 29880977
Key Trials
- Trainer PJ, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000;342(16):1171-1177. PMID: 10770982
- Colao A, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014;99(3):791-799. PMID: 24423299
Further Resources
- Pituitary Foundation (UK): Patient Information
- UpToDate: Acromegaly: Clinical manifestations and diagnosis
- Radiopaedia: Pituitary macroadenoma
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists. This content does not constitute medical advice for individual patients.