Acromegaly and GH-Secreting Pituitary Tumours Flashcards
Acromegaly Dance
Inspection
1. Coarse facial features - deepening forehead and nasolabial crease, facial wrinkles, enlarged nose
2. Prognathism - clench teeth malocclusion (lower teeth overbite upper teeth)
3. Macroglossia
4. Enlarged and sweaty hands and feet - large pores, thick dorsum
5. Skin tags over axilla, acanthosis nigricans
6. Hypertrichosis
7. Gynaecomastia in males
Examination
1. CN 2 - bitemporal hemianopia
2. CN 3, 4, 6 - tumour compression syndrome
3. Fundoscopy - optic atrophy
4. Goitre
5. Carpal tunnel syndrome - Tinel and Phalen sign
6. Proximal myopathy
7. Cardiomegaly and cardiomyopathy, pacemaker
8. Kyphosis, joint pain
Think
Complications of acromegaly
What is acromegaly?
Excessive GH secretion by pituitary gland in adulthood leading to progressive enlargement of hands, feet, facial features and systemic complications
Incidence: 5 in 1 million cases pe year
Regulation of GH
Stimulation: GHRH (and dopaminergic hormones that inhibits somatostatin release)
Inhibition: somatostatin (and adrenergic hormones that inhibits GHRH release)
What are the causes of acromegaly?
- Think GH secretions, GHRH secretions, exogenous
- GH secreting pituitary adenoma
- Benign monoclonal GH secreting adenoma (90%)
- Rapid growing adenoma - in younger adults, may secrete prolactin leading to male hypogonadism
- Primitive acidophil stem cell adenoma - gigantism
- Rarely pituitary carcinoma - Familial
- MEN 1
- Neurofibromatosis
- McCune-Albright syndrome - Extra-pituitary secretion
- Lymphoma
- Pancraetic islet cell tumours - GHRH secretion
- Gangliocytoma (hypothalamic tumour)
- Phaeochromocytoma
- Medullary thyroid carcinoma
- Adrenal adenoma
- Small cell ca, bronchial ca - Exogenous growth hormones
Pathogenesis of acromegaly
1. Growth promotion
A. GH triggers IGF-1 production in liver, stimulates protein synthesis
- Bone, cartilage - linear growth
- Organomegaly
- Increased lean muscle mass
2. Anti-insulin effect
A. IGF-1 on adipose tissue
- Increased lipolysis, FFA usage
- Reduced adiposity
B. Impaired carbohydrate metabolism (diabetogenic)
- Reduced cellular glucose uptake
- Increased blood glucose level
3. Cellular proliferation
A. Chondroitin sulphate synthesis
- Increased skin sweating
- Soft tissue compression of median nerve (CTS)
What are the clinical features of acromegaly?
A. Enlarging appearance, coarse face/skin and complications B. Excessive GH on metabolism and organomegaly C. Tumour compressive syndromes - CN2,3,4,6 D. Other excessive pituitary hormones
A. Change in appearance (enlargement)
1. Hands, feet, head enlargement
- Unfit ring / glove / shoe / hat sizes
2. Coarse facial features, maxillofacial enlargement
- Change in appearance over time (compare with NRIC)
- Big tongue, jaw prognathism, biting problem
3. Thickened soft tissues, oily and coarse skin
- Skin tags -> correlates with colonic polyps
- Hyperhidrosis
- Acanthosis nigricans over neck and axilla
4. Arthralgia
5. Weight gain
B. Excessive GH
1. Neck, tongue, thyroid enlargement -> OSA, snoring, narcolepsy, hoarse voice
2. Increased body hair, sexual hair
3. Fatigue
4. Hypercalcaemia, hyperphosphataemia
5. Hypertriglyceridaemia
6. Organomegaly and complications
C. Tumour compressive syndrome
1. Headache
2. CN 3, 4,6 palsy - eye movement
4. CN2 visual field defect - bitemporal hemianopia
D. Excessive prolactin and other hormones
1. FSH, LH - menstrual abnormalities (amenorrhoea, oligomenorrhoea)
2. Galactorrhoea
3. Reduced libido, erectile dysfunction
What are the complications of acromegaly?
- Cardiomyopathy and heart failure
- Arthralgia, arthritis
- Proximal myopathy
- Carpal tunnel syndrome
- Goitre
- OSA
- Colonic polyps, change in bowel habits
- DM
- Erectile dysfunction / reduced libido (hypogonadism)
- Pituitary apoplexy
What is the single best clue in examining patient with suspected acromegaly?
Old driver’s license / NRIC / photographs
- Serial photographs show gradual disfigurement
What are the common cause of death in patients with acromegaly?
- Cardiovascular disease, heart failure
- Diabetes complications
- Sleep apnoea and sudden death
- Malignancy
Investigations for acromegaly
- High serum IGF-1 (normal: 100-260ug/L)
- Caution: Falsely reduced in mild acromegaly, malnutrition, hepatic or renal failure - High serum GH levels in fasting state after glucose suppression
- OGTT 75g loading -> suppresses GH to < 1mcg/L after 2 hours (normal)
- Abnormal: elevated (insufficient suppression)
- Caveats: not reliable in DM, hepatic or renal disease, obesity, pregnancy, estrogen therapy - Serum GHRH
- MRI pituitary gland
- Assess tumour size, location, invasiveness - Other pituitary hormones
Outline the management for acromegaly
Opening
Multidisciplinary team - Endocrine, neurosurgery, psychologist
Definitive
1. Transphenoidal hypophysectomy
2. Medical management as adjunct or if surgery is contraindicated
- Somatostatin analogue - octreotide -> inhibits GH release
- GH receptor antagonist - pegvisomant
- Dopamine agonist - cabergoline, bromocriptine
3. Stereotactic radiotherapy - slow and takes months to years to work (often used as adjuvant)
- Eventual hypopituitarism, vision deficits, secondary tumour, cerebrovascular events, cognitive effects
Monitoring of response
Serum GH, IGF-1
Describe the mechanism of action of somatostatin analogues in treatment of acromegaly
What are the indications of somatostatin analogues?
How effective are somatostatin analogues?
What are the side effects?
GH-secreting tumours express somatostatin receptors and respond to exogenous somatostatin -> analogues reduces GH levels
Indications
1. Pre-surgery - improve comorbidities
2. Perioperative while awaiting radiotherapy
3. Indefinitively if refractory to surgery
Outcomes
- 20-35% achieve biochemical remission or symptomatic improvement
- 60% tumour shrinkage
- Does NOT cure acromegaly, stopping leads to recurrence
Side effects
1. GI side effects
2. Gallstone formation
3. Hypotension
Describe the mechanism of action of pegvisomant
Pegvisomant - human GH receptor antagonist
- Competes with endogenous GH for binding to receptor, blocks IGF-1 production
- Effective in 66% patients
Side effects
1. Transaminitis (transient)
Monitoring of post-treatment for acromegaly
- IGF-1 normal levels
- Random GH < 1 mcg/L
- MRI pituitary gland
Repeat every 6-12 months
Other monitoring
4. Endoscopy TRO colonic lesions
5. Pituitary hormone
6. Visual field testing
“Doctor, what symptoms and abnormalities will improve after treatment?
Improvements
1. Some facial features, hands and feet size
2. Osteoarthritis
3. Excessive sweating
4. DM, hypertension and cardiovascular risks
Persistent
1. Bony overgrowth of facial bones
2. Permanent cardiac dysfunction/cardiomyopathy
