Acromegaly

Acromegaly    YQ54C8JKYS4B
Acromegaly, pituitary, hypophysis
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
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
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.
Symptoms:
  • Sweating
  • Headache (due to local pressure)
  • Increase size of hands and feet (increase ring and shoe size)
  • Oligo/amenorrhoea
  • Infertility
  • Proximal muscle weakness
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
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)

Management:
1. 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
2. Medical:
  1. Somatostatin analoges: e.g. lanreotide, octreotide (IM injections) 
  2. 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
3. Radiotherapy:
  • If surgery is inappropriate
  • Adjuvant to surgery
Follow up
Yearly
GH and IGF-1 measurement +/- OGTT
Visual fields
Clinical photos
Cardiovascular assessment. Aim for GH < 5mU/L to reverse mortality risk


Complications

    Diabetes Mellitus (10%), Impaired glucose tolerance (25%) [GH is counter regulatory to insulin]
    Vascular
        HTN
        Cardiomyopathy
        Heart failure
        Increased risk of IHD and stroke
    Osteoporosis
    Obstructive sleep apnoea [due to soft tissue swelling in larynx]
    Malignancy- It is still controversial whether acromegaly increases risk of developing colonic polyps and colonic carcinoma
    Hypopituitarism +/- local mass effect


Prognosis

    High mortality if untreated
    Mortality increased by 2-3 fold mainly due to cardiovascular risk



Examining for Acromegaly
Very common station in OSCEs although the condition itself is rare. Usually in OSCE the patient will have been treated, and thus the disease is not active, but many of the physical feature may remain.

Hands

    Size of the hands – compare to your own. Often grossly enlarged
    Skin fold thickness – again, compare to your own. Often increased in acromegaly
    Palm – feel for boggyness of the palm
    Sweating – feel the palms for sweating
    Thenar eminence / median sensory distribution – check for thenar eminence wasting and sensation on the lateral 3 ½ fingers (carpal tunnel syndrome)
    Proximal myopathy – check the power in the upper arm



Face

    Prominent supra-orbital ridges
    Large tongue
    Large ears
    Prognathism – an ‘underbite’ – the lower teeth protrude out below the upper ones



Visual Fields

    Check the visual fields


Cardiovascular system

    Check the BP (may be raised)
    Check for cardiomegaly

o   Displaced apexed beat
o   Raised JVP

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