Pictorial and short descriptions of four patients of acromegaly with some notes!

1. Some Real Life experiences with 4 patients of
acromegaly!
Dr. Rajat SR Biswas,MD

2. • Welcome You All

3. • Case -1

7. A 55 years male admitted with CVD with right hemiplegia with
aspiration. He has prognathism and acral enlargement. Hands
and legs are compared with a person of same age and built.

8. Case -2

12. • MRI of the patient showing
pitutary Macroadenoma.

13. Case 3

18. Simian crease in a Down baby

19. • Case four
• CMSOGH

27. Loss of pulsatility of GH in acromegaly
(umIU/L)

35. Definition
• Disproportionate skeletal tissue and soft
tissue overgrowth
• Results from hyperplasia of pituitary
somatotroph cells and excessive growth
hormone production
• First described by Verga in 1864

36. Incidence and presentation
• 5 cases per million
• In a study of 600 cases commonest presenting
symptoms
– Acral and facial changes
– Hyperhydrosis
– Headaches
– Paraesthesia
– Hypertension
– Goitre
– Rarely visual field defects
– Frontal skull bossing

37. Diagnosis
• Historically variable reliability of GH assays
• Acronegaly results in
– Excessive GH throughout the day
– Loss of bursts
• High random GH not useful
• Low random GH <0.04µg/l makes diagnosis
unlikely
• IGF-I vs OGTT

38. GH physiology
• Produced in anterior pituitary gland
• Stimulated by
– GHRH from hypothalamus
– Ghrelin (gut)
• Inhibited by
– somatostatin via SSTR 2 and 5 receptor subtypes
• SS regulates the timing and amplitude of GH release
• GH receptors widely expressed in liver, fat and muscle

39. OGTT
• 75g oral glucose load is neuroendocrine stimulus
that should suppress GH secretion
• GH should drop to <1.0µg/l during 2 hours
following glucose load (sample at 0, 30, 60 and
120mins)
• False positives
– Obesity
– Renal failure
– Oestrogen replacement
– Diabetes mellitus

40. IGF-I
• Polypeptide target of GH
• Synthesised
– Liver (80%)
– Bone
– Muscle
– Kidney
• Endocrine and paracrine hormone
• Mediates growth actions of GH
• IGF-I receptor found ubiquitously

41. IGF-I
• Relatively stable (unlike GH)
• Positively correlated with GH
• Age-matched controlled levels required (levels
fall 14% per decade)
• Falsely low levels in
– Renal failure
– Hepatic failure
– Oestrogen replacement

42. Management
• Surgery- 1st line
• Medical and Radiotherapy- 2nd line

43. The role of surgery
• Transphenoidal hypopyhsectomy gold standard in
dedicated centre
– `75-95% cure rate in intrasellar microadeomas
– 40-65% cure for macroadenomas
• Complications on 1% of patients
– Transient occulomotor palsies
– Deterioration of vision
– Carotid artery injury
– Epistaxis/CSF leak
– DI (transient or permanent)

44. Primary medical therapy?
• Only indicated in treatment of
macroadenomas
– ie invasion into the cavernous sinus
• May increase the cure rate with tumour
shrinkage prior to surgery

45. Medical therapy
• 3 drug classes
– Somatostatin receptor ligands
– Dopamine agonists
– GHRH antagonists

46. SRLs
• Target the somatostatin 2 and 5 receptor subtypes in
pituitary and directly on the liver to inhibit IGF-I synthesis
• Octreotide LAR and lanreotide Autogel no head-to-head
stduies
• Indications
– Those who refuse surgery/are too unfit
– Failure of surgical cure
– Primary therapy if surgical cure unlikely
– Whilst waiting for radiotherapy to take effect
• 75% will see a 25% tumour shrinkage
• Biochemical control in 34-45% of patients
• SE – abdominal bloating, gallstones/sludge
• NB may interfere with GH response to OGTT

47. GHR antagonist
• Pegvisomant
– Binds to peripheral GH receptors blocking function
– GH levels increase ?due to impairment of IGF-I negative
feedback on somatotroph secretion
• Daily injection 1030mg (£50-100 daily!)
• Indicated
– No biochemical control despite surgical and medical therapy
• Risks
– Tumour growth
– Abnormal LFTs (25%)
– lipohypertrophy
• ?GHR antagonist in combination with SRL

48. Radiotherapy
• Fractionated or gamma-knife
• 50% biochemical cure at 10 years
• Usually second or third line
• Indicated in those
– Not cured by surgery to remove need for lifelong
medical Rx
– After debulking surgery
– In those who have failed SRL therapy and are at
risk of tumour growth from GHR antagonist Rx

49. Risks of radiotherapy
• Hypopituitism in 50%
• TSH 27%
• LH/FSH 18%
• ACTH 15%
• Visual defects 5%
• Secondary tumours?
• Radiation vasculopathy
• Neurocognitive defects

50. Prognosis
• Life expectancy reduced by 10%
• Mortality determined by
Random GH<2.5µg/L or suppressed <1µg/L
– Normalisation of IGF-1
– Age
– HTN
– Diabetes
– Cardiac disease
– Duration of disease
• GH <2.5µg/L RR 1.1
• GH > 2.5µg/L RR 1.9
• IGF-I>95% confidence interval – SMR 3.4 fold increase
• IGF-I <2SD below the mean had only 1.2 fold increase in
SMR
• Effects on tumour mass

51. Follow-up
• IGF-I and OGTT at 3 months
• Continued follow-up biochemically
• (GH is not measured in GHR antagonist therapy)
• OGTT not helpful in SRL therapy
• MRI
– 3-6 months post-op
– May not need to be regular if biochemically “cured”6
months after commencing GHR antagonist
• Pituitary function 3 months post-surgery
• ITT

52. Summary
• Diagnosis and natural history of acromegaly
• IGF-I and GH measurements and relevance as
prognostic indicators
• Surgical, medical and radiotherapy options
• A management and follow-up strategy for
acromegaly

53. Thanks