a rare presentation of acromegaly as upper GI bleeding and discussion on diagnosis of same with simple tests and management

1. Case discussion/ topic review
Moderator-Dr. D R Mishra
Presenter- Santosh K Dhungana
MD GP JR II

2. case
59/ F presented to ER
◦ Vomiting of blood 4 episodes
◦ Passage of black tarry stool 2 episode
Assoc. dizziness
No h/o headache/ LOC/ abn. body mvmnts/ alt.
behavior
No SOB/ chest pain
No fever/ burning micturition/ PV bleeding
No complaints of vision problems

3. Past Hx
No h/o similar episode
h/o multiple joint pain for 5 yrs
◦ Involving both small n large joints of hands and
feet
◦ Stiffness of joints few minutes in the morning
◦ Deformity of small joints of hands for 1 yr
◦ Took various medications for the same
No h/o DM, Htn, PTB

4. Personal hx
Avid alcohol consumer
500-750 ml of home made “raksi” for 30 yrs
150-225 gms/day
Smoking 10 sticks/day for 30 yrs
15 pack years

5. examination
conscious/ oriented to TPP
pallor +
b/l hands large
joint deformity over DIPs
enlarged b/l great toes and
fleshy feet
enlarged face
prominent nose
voice deepened
Vitals
BP 110/70
pulse 84/m
tmp- 98F
r/r- 22/m

8. Abdominal examination-
Slightly distended, umbilicus central
Scar of tubectomy
All quad. moving equally with respiration
Slight tenderness over epigastrium on deep
palpation
Liver palpable on deep inspiration
Tympanic/ no shifting dullness
Bowel sounds present
Respi/ cardiac sys WNL
HMF intact

9. inv
Blood gr- A positive
Hb- 7.1
Hct- 22.7%
TLC- 17,500
N-84 L- 16
Plt- 93,000
PT/ INR- 20/1.61
glucose- (R)- 112
LFT total protein- 5.9
Bil t/d- 1.8/0.6
ALT/AST- 34/144
Ur/cr- 57/0.5
Na/K- 148/ 3.0
RA- <8
Serology- neg
USG- Hepatomegaly (18.7 cm) with increased and
heterogenous echotexture and irregular surface with mild
ascites s/o chronic liver disease
Thickened GB wall and with GB sludge
Min. b/l pleural effusion

10. CXR
cardiomegaly
heel pad thickness 30mm (N
21mm)

11. sella- length 18mm (N-17 mm) and height 15 mm (N-13
mm)

12. clinical dx
CLD ethanol induced
portal hypertension, ascitis w/o SBP
Presented with UGI bleed in the form of hematemesis and
melena sec to ?variceal bleed/ ?drug induced erosive
gastritis
with anemia sec to blood loss
with coagulopathy
w/o HE
CPC- B, DF- 34
with suspected acromegaly

13. mgmnt
inj. Octeotride
inj. KCl
inj. Pantoprazole
inj. ceftriaxone
Blood transfusion
Daily weight and abd girth
charting
RBS monitoring

14. course in hospital
Uneventful
No bleeding from NG
No black stool
No postural drop in BP
Vitals stable
Patient left hospital on 3rd day against medical
advice

15. acromegaly

16. acromegaly
a chronic metabolic syndrome resulting from
excessive production of GH by the anterior pituitary
gland after epiphyseal plate closure in puberty.
excess GH causes gradual enlargement of the body
tissues
excess GH secretion in children or adolescents
gigantism

17. Growth hormone, together with IGF-1, is critical to
promoting linear growth during childhood and
puberty
IGF-1 mimics the actions of insulin by stimulating
metabolic changes, including protein synthesis, cell
proliferation, and increases in muscle mass,
cartilage, and bone growth
Growth hormone acts at the level of the
hypothalamus to increase somatostatin and
suppress GHRH via a mechanism known as GH
auto feedback
IGF-1 directly inhibits pituitary GH secretion

18. somatostatin

19. >90% of cases of acromegaly -caused by a benign
tumor of the pituitary gland  adenoma
◦ Microadenoma vs macroadenoma- size, freq.
rarely, caused by ectopic growth hormone
releasing hormone (GHRH) or GH-secreting
neuroendocrine tumors
Ectopic GHRH secretion accounts for only 0.5
percent of cases of acromegaly
In acromegaly, autonomous pituitary tumor
secretion of GH results in elevated GH
GH hypersecretion induces the liver to produce
higher serum levels of IGF-1

21. epidemiology
prevalence of acromegaly -8 to 13 cases per
100,000
men and women -equally affected
mean age at diagnosis- early- to mid-40s
disease often goes undiagnosed for many years,
especially in the early stages
more recent findings of the DETECT study of 6673
unselected primary care patients  a higher
prevalence of 103.4 cases per 100,000
may be more prevalent than generally believed
on average- a 2x increase in mortality and a 10-
year reduction in life expectancy

22. clinically
s/s of acromegaly result from chronic elevations of
IGF-1 and GH levels
excess GH can lead to disfigurement, comorbidities,
and mortality
comorbidities of acromegaly reflect a wide range of
hormone-induced changes
as adenomas expand  compress surrounding brain
tissues, including the optic nerve

23. signs/ symptoms
facial changes- prominent forehead, heavy cheek
bones and brow ridge, mandibular prognathism,
and jaw malocclusion
acral changes- enlarged hands and feet,
hyperhidrosis, thickening of the skin
soft tissue changes- enlargement of the tongue
and vocal cords- deepening of the voice
headache, snoring, paresthesias, sexual
dysfunction, goiter, carpal tunnel syndrome, visual
field defects

24. s/s
enlargement of the heart and kidneys
anti-insulin effects- decreased glucose utilization in
peripheral tissues and hyperinsulinemia, insulin
resistance, glucose intolerance, and diabetes
mellitus
myocardial hypertrophy, hypertension, diastolic
dysfunction, heart failure
renal dysfunction
thickening of periarticular soft tissue structures-
osteoarthritis
spinal kyphoscoliosis and excessive bone growth
(skeletal hyperostosis)

25. clinical features with frequency
Coarsening of facial features
99%
Acral enlargement (eg,
change in size of feet and
hands) 99%
Soft-tissue swelling 95%
Headache 77%
Excessive sweating 62%
Menstrual disturbance 56%
Peripheral neuropathy 53%
Paresthesias 50%
Impotence 41%
Hypertension 41%
Visual field impairment
39%
Daytime somnolence 32%
Osteoarthritis 31%
Muscle weakness 30%
Carpel tunnel syndrome
28%
Abnormal or excessive
localized or generalized
hair growth 28%
Diabetes mellitus 24%
Hyperprolactinemia 18%
Goiter 10.5%
Galactorrhea 10%

26. when to suspect?
when patients have 2 or more of-
new-onset diabetes
diffuse arthralgias
new-onset or difficult-to-control hypertension
cardiac disease - biventricular hypertrophy and
diastolic or systolic dysfunction
fatigue, headaches
carpal tunnel syndrome
diaphoresis, loss of vision, colon polyps, and
progressive jaw malocclusion.

27. diagnosis
Biochemical confirmation
hypersecretion of GH and IGF-1.
◦ GH secretion
pulsatile, diurnal
 fasting, exercise, stress, and sleep
clearance is rapid (plasma half-life about 20 mins)
standard test – oral glucose tolerance test
◦ GH nadir <1.0 mcg/L (within 2 hrs)
◦ AACE- serum OGTT GH nadir- lowered to 0.4 ng/mL to increase
the sensitivity of the test.
IGF-1 levels mirror GH levels and are stable throughout the day
and relatively unaffected by meals
IGF-1 level- compared with age- and sex-dependent normative
data

28. Serum IGFBP-3 concentration
IGFBP-3 secretion, like IGF-I is GH-dependent, serum
IGFBP-3 concentrations are elevated in patients with
acromegaly

29. Radiological
◦ skull lat. view for sella size, jaw prominence
◦ CXR for cardiomegaly
◦ X- ray of hands, spine and pelvis for hypertrophic
arthropathy
◦ Heel pad thickness
USG for visceromegaly
CT/ MRI for sella size and tumor extension

31. management
Goal-
lower the serum IGF-1 and GH concentration to
within the reference range for the patient's age and
gender
ablate or arrest tumor growth
ameliorate comorbidities
restore mortality rates to normal
preserve pituitary function

32. medical therapy
Somatostatin analogs - Octreotide and lanreotide
◦ Normalization of serum IGF-1 concentration occurs in
40 to 75% of patients
◦ Side effects — nausea, abdominal discomfort,
bloating, loose stools, fat malabsorption, GB calculi
◦ Octreotide- long-acting form- i/m injection once a
month
initial dose is 20 mg/month
increased to 30 mg, then to 40 mg/ month
◦ Lanreotide- i/m form- 30 mg every 7 to 14 days.
deep s/c form- 60 to 120 mg every 4 to 6 weeks

33. Dopamine agonists
◦ Bromocriptine- Initial: 1.25-2.5 mg daily
◦ increasing by 1.25-2.5 mg daily as necessary
every 3-7 days
◦ usual dose: 20-30 mg/day (maximum: 100
mg/day)
◦ Cabergoline
◦ in combination with a somatostatin analog
◦ s/e -nausea, light headedness, mental fogginess
◦ dose- 0.5 mg once a week or
◦ 0.25 mg twice a week
◦ up to 1.0 mg twice a week

34. Pegvisomant-
◦ GH receptor antagonist
◦ Dose- 40 mg loading and 10 mg daily s/c
◦ 5 mg increments, max - 30 mg/day
◦ serum IGF-1 concentration measured every 4-6
weeks
◦ s/e- transaminitis
◦ Monitor LFTs

35. Trans-sphenoidal surgery
treatment of choice for
◦ patients with somatotroph adenomas that are small
◦ large but still resectable
◦ large and cause visual impairment
Has to be performed by the most experienced pituitary
neurosurgeons

36. radiation therapy
effective in reducing the size of somatotroph
adenomas and decreasing GH and IGF-1
concentrations
mainly for patients whose disease is not controlled
by surgery or medical therapy
“Gamma knife”

38. long term management
Monitoring
Clinical and biochemical evaluation — Following
initial treatment, patients should be evaluated
every three to four months
measurement of serum IGF-1 levels
Patients who are being treated with a medication
should have the dose adjusted, if necessary
In patients well controlled on medical therapy,
biochemical testing (serum GH, IGF-1) every six
months
Other pituitary hormones should be evaluated
yearly.

39. Adenoma size — MRI should be repeated yearly
for the first several years after initial treatment and
less often thereafter
Visual field assessment is indicated
Systemic evaluation — Acromegaly appears to be
associated with an excess risk of colonic polyps
Comprehensive cardiovascular evaluation should
be performed regularly, and hypertension and heart
failure should be treated

40. Literature search

42. references
Harrison's Principles of Internal Medicine, 18th Ed
UpToDate 21.2
http://www.medscape.com/medicalstudents
http://www.ncbi.nlm.nih.gov/pubmed/
THANK YOU

43. finally…
Photograph of the patient's hand and her son….