Acromegaly
Definition
Acromegaly is a chronic endocrine disorder characterised by excessive growth hormone secretion.
Gigantism is NOT the same as acromegaly. Both are caused by excess growth hormone, but they differ in the age of onset. Gigantism's onset is before puberty (before epiphyseal fusion). Gigantism also results in tall stature, which is absent in acromegaly.
Aetiology
>95% cases are caused by growth hormone-secreting pituitary adenoma (somatotroph adenoma) [Ref]
Rare causes: [Ref]
- Ectopic growth hormone-releasing hormone secretion from neuroendocrine tumours (e.g. carcinoid tumours)
Risk Factors
Most cases are sporadic and not associated with identifiable risk factors. [Ref]
Certain genetic syndromes predispose one to pituitary adenomas: [Ref]
- MEN1 syndrome
- McCune-Albright syndrome
- Carney complex
- Familial isolated pituitary adenomas
Clinical Features
Clinical features can be grouped as following: [Ref]
| Category | Clinical features |
|---|---|
| Tumour mass effects |
|
| Musculoskeletal effects |
|
| Soft tissue effects |
|
Complications
Classic complications: [Ref]
- Risk of colorectal cancer
- Carpal tunnel syndrome (bilateral)
- Cardiomyopathy and cardiovascular diseases
- Obstructive sleep apnoea (from macroglossia)
- Secondary hypertension
- Secondary diabetes
- Thyroid goitre
Investigation and Diagnosis
Step 1 – Biochemical Testing
1st line: serum IGF-1 levels [Ref]
Confirmatory test: oral glucose tolerance test [Ref]
- Lack of growth hormone suppression (to <1 μg/L) is diagnostic of acromegaly
- Mechanism: growth hormone usually increases blood glucose. In a healthy person, when hyperglycaemia is induced, it would trigger a negative feedback, suppressing growth hormone secretion
Random serum GH level is not recommended because its secretion is pulsatile (varies throughout the day). Thus, a single random sample will not accurately reflect the growth hormone secretion.
On the other hand, IGF-1 is produced in the liver in response to growth hormone and has a much longer half-life, resulting in more stable and consistent levels throughout the day.
Step 2 – Imaging
Following biochemical diagnosis of acromegaly, pituitary MRI should be performed to assess the tumour size, appearance and parasellar extent. [Ref]
Alternative to MRI: CT
Management
Definitive Management
1st line: transsphenoidal surgery [Ref]
2nd line: medical therapy [Ref]
- Somatostatin receptor analogue (e.g. octreotide, lanreotide)
- Pegvisomant (growth hormone receptor antagonist)
- Dopamine agonist (e.g. cabergoline) – for mild disease
Growth hormone secretion (by the anterior pituitary) is regulated by the following hypothalamic hormones:
- GHRH – stimulates growth hormone secretion
- Somatostatin – inhibits growth hormone secretion
Therefore, to treat acromegaly, antagonising GHRH and agonising somatostatin is desired.
Dopamine agonists' effect is most pronounced on prolactinomas, but also inhibits growth hormone secretion in acromegaly to a lesser extent.
Complications Screening
Screening for the following complications is recommended: [Ref]
- Colorectal cancer (via colonoscopy)
- Assess for hypopituitarism (measure cortisol, T4, TSH, Lh, FSH, sex steroids and prolactin)
- Hypertension
- Diabetes
- Cardiovascular disease (including cardiomyopathy)
- Obstructive sleep apnoea
- Thyroid nodularity
- Osteoarthritis