Acromegaly Flashcards
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Acromegaly
Define acromegaly.
A rare, chronic disease caused by excessive secretion of growth hormone (GH), usually due to a pituitary somatotroph adenoma. It is associated with increased morbidity and premature mortality if not appropriately treated.
What age does acromegaly usually occur? What is the most common cause of it?
- 30-50yrs men or women
- Benign pituitary adenoma
- Acromegaly has an insidious onset and diagnostic delay is common.
What is the aetiology of acromegaly?
Pituitary somatotroph adenoma in 95-99% of cases - GNAS1 gene mutation
- Prolactin co-secretion in mixed lactotroph and somatotroph tumour in 25-30% of cases
Rarely neuroendocrine tumours release GHRH and cause somatortoph hyperplasia
Which hormones are secreted by the anterior and posterior pituitary?
Hormones secreted by the anterior pituitary gland are:
- adrenocorticotrophic hormone (ACTH),
- growth hormone (GH),
- follicle stimulating hormone (FSH),
- lutenising hormone (LH),
- thyroid stimulating hormone (TSH)
- prolactin.
Posterior pituitary hormones are
- antidiuretic hormone (ADH)
- oxytocin
Describe the growth hormone axis. How is this dysregulated in acromegaly?
Pituitary somatotroph adenomas chronically secrete excess GH –> stimulating IGF-1 (insulin like growth factor 1 production) –> clinical manifestation of disease
What is the difference between a microadenoma and macroadenoma? What do you call an invasive pituitary adenoma?
Microadenoma = <10mm; macroadenoma = >10mm
Extension = suprasellar; invasive = parasellar
What are the signs and symptoms of acromegaly?
Pituitary mass effect:
- headaches
- visual field defects
- cranial nerve palsies in parasellar tumour extension
GH anf IGF1
- acral and soft tissue changes
- excessive sweating
- thick skin
- skin tags
- soft tissue hypertrophy
- glucose intolerance/diabetes - increased appetite, polyuria/polydipsia
- hypertension
- cardiac hypertrophy, arrhythmias
- organomegaly - goitre, prostate etc
- sleep apnoea
- fatigue
- arthralgia
- coarse facial features
- proganthism
- prominent supra-orbital ridges
- macroglossia
- jaw and nose enlagement
- frontal bossing
- separation of teeth
- carpal tunnel syndrome
- sexual functioning
- reduced libido
- infertility
- amenorrhoea/oligomenorrhoea
- galactorrhoea
- erectile dysfunction
Children:
- gigantism/increased height - effects of GH before epiphyses start to fuse
- primary amenorrhoea
What is the mechanism behins soft tissue hypertrophy in acromegaly?
Soft-tissue hypertrophy is usually due to intradermal accumulation of glycosaminoglycans secondary to GH/insulin-like growth factor 1 actions
What signs/symptoms should prompt you to screen for acromegaly?
- Pituitary adenoma
- Profuse sweating
- Acral growth
- Coarsening facial features
Associated with: Carpal tunnel syndrome, arthralgia, diabete, amenorrhoea, hypertension, sleep anoea.
Which of these are signs of acromegaly? (6)
- Prognathism
- Cardiomegaly
- Abdominal striae
- Acne
- Exophthalmos
- Macroglossia
- Hepatosplenomegaly
- Diabetic retinopathy
- Pathological pigmentation
- Extensor plantar responses
- Prognathism
- Cardiomegaly
- Acne
- Macroglossia
- Hepatosplenomegaly
- Diabetic retinopathy
What investigations would you do to diagnose acromegaly?
Serum IGF-1 levels (DIAGNOSTIC) - also used to monitor disease.
Glucose suppression test (OGTT) - overtaken by IGF1 testing; can be used to confirm diagnosis. Measure GH; there is failure of normal GH suppression to less than 2mU/l(or <1mcg/L) in response to glucose,
- But positive in anorexia, uncontrolled diabetes, hypothyroidism, Cushing’s
MRI pituitary - shows adenoma (CT is less effective)
- NB: dexamethasone suppression test is for Cushing’s; SynACTHen test is for Addison’s*
- Other:*
- GHRH - high if ectopic release from neuroendocrine tumours
- Tumour localisation - octreoscan, gallium-68 DOTATATE
- Prolactin - often high
- Plasma cortisol - may be low
- Estradiol or testosterone - testosterone deficiency in 50% of men; low estradiol in women
- Visual field testing
How do you manage acromegaly?
Surgery(1st line in most) - trans-sphenoidal hypophysectomy - reserved for young patients or those with pressure symptoms. Repeat hormonal tests 6 weeks after surgery and offer adjuvant
Medical: in order of choice:
- somatostatin analogues - octreotide
- GH receptor antagonist e.g. pegvisomant, OD SC injection.
- dopamine agonist e.g. bromocriptine/carbegoline, superseded by octreotide
Radiotherapy - external beam radiation - used in older patients
NB: ketoconazole is used for Cushing’s treatment.
What could be a cause of paraesthesias in the hand in acromegaly?
Carpal tunnel syndrome
- entrapment of the median nerve under the transverse carpal ligament at the wrist. More common in women
Causes of carpal tunner: idiopathic (most), soft tissue swelling, pregnancy, gout, acromegaly, RA, myxoedema, amyloidosis.
What are the complications of acromegaly? What is the prognosis?
- Hypertension
- Left ventricular hypertrophy, cardiomyopathy, arrhythmia, valvular heart disease, and ischaemic heart disease
- Sleep apnoea
- Articular cartilage hypertrophy
- Diabetes
- Pre-cancerous colonic polyps
- Carpal tunnel syndrome
- Hypopituitarism - compression or surgery
Prognosis - reduced QOL, premature death and serious complications but recently improved with treatment so is now similar to general population.
