Acromegaly

• Syndrome that results from excessive

secretion of growth hormone (GH)
• Annual incidence is three to four per
million people
• Mean age at diagnosis is 40 to 45
years.
• Occurs after fusion of the epiphyseal
growth plates
– in a child or adolescent is called
pituitary gigantism
R o b e rt P e rsh in g W a d lo w - 8 '1 1 . 1 " ( 2 7 2 cm )
 Causes of Acromegaly

Melmed S. N Engl J Med 2006;355:2558-2573

 Causes of Acromegaly
• Primary GH excess • GH excess
– GH-cell adenoma – Pancreatic islet-cell
– Mixed GH-cell and tumor
PRL-cell adenoma – Lymphoma
– Mammosomatotroph- – Iatrogenic
cell adenoma
• GHRH excess
– Plurihormonal
adenoma • Central ectopic (<1
– GH-cell carcinoma percent)
– Familial syndromes – Hypothalamic
hamartoma,
• Multiple choristoma,
endocrine
neoplasia-I ganglioneuroma
(GH-cell • Peripheral ectopic (1
adenoma)
• Familial percent)
acromegaly – Bronchial carcinoid,
• McCune-Albright pancreatic islet-cell
syndrome tumor, small cell
(rarely- lung cancer,
adenoma)
adrenal adenoma,
 Clinical Features
• Attributable to high serum concentrations of
both GH and insulin-like growth factor-I
(IGF-I)
• somatic and metabolic effects
• Somatic effects, stimulation of growth of
many tissues
– Skin, connective tissue, cartilage, bone,
viscera, and many epithelial tissues
• Metabolic effects
– Nitrogen retention, insulin antagonism and
lipolysis.
• Local symptoms
– Headache, visual field defects (classically
 Clinical Features
• Disturbance of pituitary hormones
secretion
– Most commonly gonadotropins
– Hyperprolactinemia
– Hypothyroidism and hypoadrenalism
occur less commonly
• Increased risk of neoplasm
– increased risk of colon polyps and
cancer
– And also others
Physiology of GH
 Clinical Features of Acromegaly

Melmed S. N Engl J Med 2006;355:2558-2573

Symptoms and Signs
 Orofacial manifestations
• Enlargement of the tongue and lips
• Prognathism, which is accompanied
by a change in the relative position
of teeth, resulting in malocclusion.
• Gingival hypertrophy
• Dental mobility
La te ra l sku ll ra d io g ra p h sh o w s e n la rg e d se lla
tu rcica
 Investigations
• GH levels
– Normal adult levels are < 1 mU/L
– Except during stress or a ‘GH pulse’.
• Glucose tolerance test
– Failed suppression of GH.
– 25% of acromegalics have a diabetic glucose tolerance
test.
• IGF-1 levels
• Visual field examination
– Hemi-upper quadranopia to bitemporal hemianopia.
• MRI scan of pituitary if above tests abnormal
• Pituitary function
– Partial or complete anterior
• Prolactin – mild to moderate hyperprolactinaemia
– Stalk effect or co-secreting adenoma
Diagnosis and Treatment of Acromegaly

Melmed S. N Engl J Med 2006;355:2558-2573

 Pituitary Microsurgery
• Small, large but still
resectable, or
large and cause
visual impairment
• Large adenomas
that are not
entirely accessible
surgically, with
subsequent
adjuvant therapy
• Endoscopic
transnasal,
transsphenoidal
pituitary
 Medical Therapy


• Dopamine agonist
– Use if surgery does not produce clinical
remission or normalization of GH
– Cabergolin; most successful if tumor
secretes both prolactin and GH
• Somatostatin analogs
– Use if acromegaly persists despite pituitary
surgery
– Octreotide (short and long acting)
•  GH receptor antagonist
•    – Pegvisomant
Octreotide
 Radiotherapy
• Conventional
• Gamma
knife/Stereotactic
radiosurgery
• Proton beam