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Acromegaly

In This Article

Acromegaly is a disorder that occurs due to an excess secretion of growth hormone (GH)

 

Epidemiology

  • Prevalence is approximately 40-60 million
  • Affects M: F with a ratio of 1: 1
  • Mainly affects people between the ages of 30-50 years
 
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Pathophysiology

  • GH (or somatotropin) is secreted by the anterior pituitary gland
  • GH stimulates soft tissue and skeletal growth indirectly through the secretion of insulin like growth factor-1 (IGF-1) from the liver.
  • The production of GH is regulated by GH-releasing hormone and GH-inhibiting hormone (somatostatin), both released from the hypothalamus
  • Acromegaly occurs due to hyper secretion of GH
  • 99% of time this occurs from a pituitary tumour
  • Pituitary tumours are almost always benign, and divided into macroadenoma (>1cm) and microadenoma (<1cm)
  • Rarely ectopic secretion of GH-releasing hormone occurs from carcinoid tumours
 
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Clinical features

  • If excess GH secretion occurs before epiphyses have fused, then gigantism results
  • Most commonly though GH releasing pituitary tumours occur in adults, leading to acromegaly
  • Clinical features occur due to excess hormone secretion, local pressure, and hypopituitarism.
 
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Symptoms

  • Sweating
  • Headache (due to local pressure)
  • Increase size of hands and feet (increase ring and shoe size)
  • Oligo/amenorrhoea
  • Infertility
  • Proximal muscle weakness
 
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Signs

  • Coarsening of facial features
    • Prominent supra-orbital ridges
    • Prognathism (prominent lower jaw)
  • Increased interdental spacing
  • Macroglossia (enlarged tongue)
  • Doughy spade like hands
  • Carpel tunnel syndrome
  • Hoarse voice
 
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Investigations

  • Random GH measurements – GH is secreted in a pulsatile manner, with secretion increasing in stress, sleep and puberty, and reducing in pregnancy. Therefore random GH measurements are not very useful for diagnosis
  • Serum IGF-1 – This can be used as a screening test, In most cases serum IGF-1 levels correlate with GH secretion over the past 24 hrs
  • OGTT  - This is the diagnostic test for acromegaly. Normally rising levels of glucose inhibit GH secretion, thus in the OGTT, GH levels should be undetectable (< 2mU/L) once glucose is administered. However, in acromegaly there is a failure to suppress GH secretion.
  • MRI of pituitary fossa
  • Investigate any potential complications
    • Full pituitary hormone profile  (hypopituitarism)
    • Visual fields and acuity   (bitemporal hemianopia can occur due to compression of optic chiasm by pituitary tumour)
    • Fasting glucose   (IGT)
    • ECG, echo (Heart failure)
 
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Management

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Surgical

  • Trans-sphenoidal surgery
    • First line treatment
    • High cure rates for microadenoma
    • Post op  (3 months) investigations needed.
    • Measure GH day curve or repeat OGTT
    • Pituitary function tests to check for hypopituitarism
    • If GH remains high, further second line medical or radiotherapy needed
 
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Medical

  • Somatostatin analogues, e.g. lanreotide, octreotide (IM injections)
  • Side effects
    • Pain at injection site
    • GI- N&V, abdominal pain, flatulence, diarrhoea, gallstones
    • Impaired glucose tolerance
    • Highly selective GH receptor antagonist (pegvisomant [ s.c injections] ) is available for patients with inadequate response to surgery, radiation or both and to treatment with somatostatin analogues
 
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Radiotherapy

  • If surgery is inappropriate
  • Adjuvant to surgery
 
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Follow up

  • Yearly
  • GH and IGF-1 measurement +/- OGTT
  • Visual fields
  • Clinical photos
  • Cardiovascular assessment. Aim for GH < 5mU/L to reverse mortality risk
 
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