Acromegaly Flashcards
What is the definition of acromegaly?
excess growth hormone in adults. (giantism due ti excess GH in children)
what is the epidemiology of acromegaly?
- Rare (3 per million/yr) and is caused by a benign pituitary GH-producing adenoma in almost all cases
- Equal prevalence between males and females
- Incidence is highest in middle age i.e. 40 +
what is the aetiology of acromegaly?
- Most cases are due to a benign GH-producing pituitary tumour
- In rare cases is due to hyperplasia e.g. ectopic GH-releasing hormone from a carcinoid tumour
what are the risk factors for acromegaly?
- 5% are associated with MEN-1 (multiple endocrine neoplasia-1)
what is the brief pathophysiology of acromegaly?
- Increased GH either secreted due to pituitary tumour or due to ectopic carcinoid tumour, travels to tissues such as the liver where it binds to reporters resulting in an increase in IGF-1
- This stimulates skeletal and soft tissue growth giving rise to ‘giant-like’ appearance and symptoms
- Local tumour expansion in the pituitary can result in compression of surrounding structures resulting in headaches & visual field loss
what are the key presentation of acromegaly?
onset insidious, usually many years between onset if symptoms and diagnosis
what are the signs of acromegaly?
- Skin darkening
- Coarsening face with wide nose
- Prognathism (relationship between mandible/maxilla with base of skull)
- Big supraorbital ridge
- Interdental separation
- Rings become tight
- Fatigue
- Deep voice
- Carpal tunnel syndrome in 50%
- Large tongue - macroglossia
what are the symptoms of acromegaly?
- Headaches - very common
- Increased size of hands & feet - acral enlargement
- Excessive sweating
- Visual deterioration
- Snoring
- Wonky bite - malocclusion
- Increase weight
- Decreased libido
- Amenorrhea
- Arthralgia and backache
- Acroparaesthesia - tingling and numbness of the extremities
what is the first line investigation for acromegaly?
glucose levels, Ca2+ levels, phosphate levels (all high)
what are the gold standard investigations for acromegaly?
- Glucose tolerance test (GTT):
• Can be diagnostic if there is no suppression of glucose
• Since normally glucose should inhibit GH release - Insulin-like growth factor (IGF-1):
• Almost always raised in acromegaly and fluctuate less than GH - thus is DIAGNOSTIC - Visual field examination - can be bilateral temporal hemianopia due to
pituitary adenoma - MRI scan of the pituitary fossa
- Pituitary function testing to look for partial or complete hypopituitarism
- ECH and ECHO to look at heart and sign of cardiomyopathy
- Old photos if possible, so can see changes
- Serum prolactin can be raised as a result of pituitary adenoma
what other investigations could be done for acromegaly?
- Plasma GH levels:
• Can exclude acromegaly if random GH is undetectable or GH < 0.4 ng/ ml and there is normal IGF-1
• But a detectable value is NON-DIAGNOSTIC since: - GH secretion is pulsatile
- GH increases in; stress, sleep, puberty and pregnancy
- If detected then proceed to glucose tolerance test (GTT)
what are the differential diagnoses for acromegaly?
Several genetic overgrowth syndromes, such as Beckwith–Wiedemann (IGF2), Weaver (EZH2), Malan (NFIX), and Tatton–Brown–Rahman (DNMT3) syndromes, or diseases that feature tall stature
how is acromegaly managed?
• Trans-sphenoidal surgery - to remove tumour and correct/prevent tumour compression of surrounding structures e.g. optic chiasm
• Somatostatin analogues (SSA) e.g. IM OCTREOTIDE or IM LANREOTIDE
- Inhibits GH release
- S/E; GI & abdominal cramps, flatulence, loose stools
• GH receptor antagonists e.g. SC PEGVISOMANT:
- Given if intolerant to SSA
- Suppresses IGF-1
• Dopamine agonist e.g. ORAL CABERGOLINE or ORAL BROMOCRIPTINE:
- Weakly control IGF-1
- Not as effective as the other two
- Advantage since oral administration, rapid onset and no hypopituitarism
Radiotherapy:
- Stereotactic radiotherapy can be used which is more accurate than conventional and provides better tumour localisation and irradiation whilst reducing radiation to normal brain tissue
- Using gamma knife, LINAC or proton beam
how is acromegaly monitored?
Periodic evaluation of levels of GH and IGF-1, the biochemical markers of this disease. Although the results of these two tests are usually concordant, they can be discrepant and how to proceed when they are can be a challenging clinical problem.
what are the complications of acromegaly?
- Impaired glucose tolerance (40%)
- Diabetes mellitus (15%)
- Sleep apnea (due to excess soft tissue in larynx - pauses in breathing whilst sleeping)
- Hypertension, left ventricular hypertrophy, cardiomyopathy, arrhythmias, ischaemic heart disease, stroke
- Colon cancer
- Arthritis
