- Due to the systemic effects of chronic growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess
- Usually due to a pituitary somatotroph adenoma (75% are macroadenomas >1cm)
- Rarely (<1% of cases) due to ectopic GHRH (from ectopic adenomas or GH secreting tumours eg NET)
- Diagnostic delay of around 10 years (and tends to be longer in women than men). Many of the symptoms and associated conditions are common.
- Prevalence around 6 in 100,000
Clinical features
- Changes in appearance (but can emerge late and progress slowly. Worth checking old photos to compare)
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- Large nose (prognathism)
- Prominent supraorbital ridges
- Prominent jaw
- Broad palms
- Macroglossia and widely spaced teeth
- Facial coarsening
- Increase in ring size and shoe size (90% at time of diagnosis)
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- Symptoms
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- Sweating (ask!)
- Snoring
- Headaches and visual disturbance
- Fatigue
- Joint pains
- Sexual dysfunction (ask about libido, erectile dysfunction, menstrual disorders)
- Voice change
- Depression
- Acne
- Constipation
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- Associated conditions
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- OSA
- Hypertension
- Carpal tunnel syndrome
- Diabetes (10%)
- HF
- Arthritis / arthralgia (eg early onset OA)
- Skin tags
- Hyperlipidaemia
- Secondary hypogonadism
- Colon cancer
- Hyperprolactinaemia (30%)
- Thyroid nodules
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- OSA, arthralgia, and carpal tunnel can often appear many years pre-diagnosis
- Examination – check BP, visual fields, aseess for hyperhidrosis
Diagnosis
- IGF-1 levels
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- The best initial test. Fairly stable throughout the day. No need to fast.
- Diagnosis suggested by >1.3x upper limit of normal for age (and characteristic clinical signs)
- False results can occur if history of uncontrolled diabetes, liver or kidney disease, at puberty, if malnourished, during pregnancy, oestrogen treatments or obesity
- IGF-1 is lower than usual in old age, obesity, DM
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- For confirmation / discordant findings
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- Recheck IGF-1 with Growth Hormone during an oral glucose tolerance test (confirmatory test)
- Growth Hormone is elevated in most acromegalics (and correlates with the size of adenoma), however can be high in normal people – therefore combine with OGTT (although OGTT not advised in diabetes)
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- MRI of pituitary (T1W with contrast)
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- Occasionally negative (consider microadenoma <2 or 3mm or ectopic source)
- Consider skull base CT if can’t perform MRI
- PET if MRI inconclusive
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- Check visual fields
- Check other hormone levels – prolactin elevation is common
- Genetic test – occasionally genetic cause eg AIP variants, MEN syndromes (1, 4 and 5), McCune-Albright, Carney Complex
- Differentials
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- Insulin mediated pseudoacromegaly – a very rare disorder of insulin resistance
- Primary hypertrophic osteoarthropathy (PHOA)
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- Clubbing is a feature (in contrast to acromegaly)
- Easily differentiated – normal hormone levels
- Can be secondary to lung cancer. Can be genetic.
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- Genetic syndromes – Sotos syndrome, Weaver syndrome, Cantu syndrome, Fragile X
- Pachydermoperiostosis
- Drugs – minoxidil, phenytoin
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Treatment
- Usually transphenoidal surgery (cure rates higher for small tumours)
- Often octreotide (can cause gallstones)
- Occasionally GH receptor antagonists or dopamine agonists
- Rarely radiation