Acromegaly

Question 1

Aetiology of acromegaly

Answer 1

Pituitary somatotroph adenoma (95-99%)
Somatotroph hyperplasia with neuroendocrine tumours (hypothalamic or digestive) that produces GHRH

Question 2

Risk factors for acromegaly

Answer 2

GPR101 over-expression
Multiple endocrine neoplasia type 1 syndrome
Isolated familial acromegaly
McCune-Albright’s syndrome
Carney’s complex

Question 3

Symptoms of acromegaly

Answer 3

Headache
Visual field defects
Enlargement of supraorbital ridges, nose, hands and feet, thickening of lips and general coarseness of features
Enlarged tongue
Mandible grows, causing protrusion of the lower jaw (prognathism)
Excessive sweating (hyperhidrosis)
Join pain and dysfunction, arthralgia, backache
Carpal tunnel syndrome (median nerve compression)
Snoring (apnoea)
Fatigue
Hypertension, arrythmias
Prolactin → hypogonadism → reduced libido, amenorrhoea

Question 4

Signs of acromegaly on examination

Answer 4

excessive growth of various tissues:
- Periosteal bone
- Cartilage
- Fibrous tissue
- Connective tissue
- Internal organs (cardiomegaly, splenomegaly, hepatomegaly)

Frontal bossing
Bitemporal hemianopia
Broad nose
Macroglossia
Lower jaw protrusion due to mandible growth
Barrel chest, kyphosis
Splayed-like hands/fingers

Prolactin → hypogonadism → reduced libido, amenorrhoea

Question 5

Investigations for acromegaly

Answer 5

First line = IGF-1

Visual field and acuity assessment
ECG: ?cardiomyopathy

Basal/random GH + IGF-1
- GH<0.4 + normal IGF-1: acromegaly ruled out
- GH >0.4 and/or elevated IGF-1 → OGTT
OGTT: paradoxical rise in GH follow flucose load
Serum glucose: elevated
Bone profile: Ca+, PO4- elevated

MRI pituitary: enlarged pituitary gland/tumour
Echo: ?cardiomyopathy

Question 6

Management for acromegaly

Answer 6

Trans-sphenoidal surgery is the first line treatment. This involves going through the nose to scoop it out behind the sphenoid bone
Somatostatin analogues e.g. octreotide (monthly depot injection)
Dopamine agonists e.g. cabergoline (GH secreting pituitary tumours frequently express D2 receptors)
Radiotherapy

Yearly: Yearly GH, IGF-1 + OGTT, visual assessment, BMI, photos

Question 7

Complications of somatostatin analogues

Answer 7

GI side effects:
- Nausea
- Diarrhoea
- Gallstones

Question 8

Complications of acromegaly

Answer 8

Obstructive sleep apnoea
- Bone and soft tissue changes surrounding the upper airway leads to narrowing and subsequent obstruction during sleep
Hypertension
- Direct effects of GH/IGF-1 on the vascular tree
- GH mediated renal sodium
Cardiomyopathy
- Hypertension, diabetes mellitus, direct toxic effects of excess GH on myocardium
Increased risk of cancer
- Colonic polyps, regular screening with colonoscopy
Diabetes Mellitus (15%) or impaired glucose tolerance (40%)

Question 9

Prognosis for acromegaly

Answer 9

Associated with serious complications and premature death
Prognosis has improved due to modern surgical and pharmacological treatment and life expectancy is close to that of the general populations
Death :
- Cardiovascular disease 60%
- Respiratory complications 25%
- Cancer 15%