Contents
Introduction
Acromegaly is a disorder that occurs due to an excess secretion of growth hormone (GH), after the fusion of the growth plates. The most obvious, and often the earliest sign is enlargement of the hands and feet. Sufferers also often have very tall stature, and distinctive facial features including enlarged jaw, brow and nose.
95% of causes are caused by a pituitary adenoma – a type of pituitary tumour which is otherwise benign.
Diagnosis is performed by means of an oral glucose tolerance test (OGTT) –similar to that used in the diagnosis of type 2 diabetes.
- Glucose suppresses GH. In a normal OGTT, GH levels will be undetectable. In acromegaly, GH levels remain elevated despite glucose ingestion
Acromegaly should be differentiated by gigantism – which instead results from excess growth hormone before fusion of the growth plates.
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 (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, rather than acromegaly
- 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
- Tall stature
- Coarsening of facial features
- Prominent supra-orbital ridges
- Prognathism (prominent lower jaw)
- Enlarged nose
- Increased interdental spacing
- Macroglossia (enlarged tongue)
- “Doughy”, spade-like hands
- Carpal 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 is performed for patients with a positive OGTT
- 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
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
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
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
- 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 features 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 bogginess 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
- Displaced apex beat
- Raised JVP