Case discussion/ topic review
Moderator-Dr. D R Mishra
Presenter- Santosh K Dhungana
MD GP JR II
case
59/ F presented to ER◦ Vomiting of blood 4 episodes◦ Passage of black tarry stool 2 episode
Assoc. dizzinessNo h/o headache/ LOC/ abn. body mvmnts/
alt. behaviorNo SOB/ chest painNo fever/ burning micturition/ PV bleedingNo complaints of vision problems
Past HxNo h/o similar episodeh/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
Personal hxAvid alcohol consumer500-750 ml of home made “raksi” for 30 yrs150-225 gms/daySmoking 10 sticks/day for 30 yrs15 pack years
examination
conscious/ oriented to TPP
pallor +b/l hands large joint deformity over DIPsenlarged b/l great toes
and fleshy feetenlarged faceprominent nosevoice deepened
VitalsBP 110/70pulse 84/m tmp- 98F r/r- 22/m
Abdominal examination-Slightly distended, umbilicus centralScar of tubectomyAll quad. moving equally with respirationSlight tenderness over epigastrium on
deep palpationLiver palpable on deep inspirationTympanic/ no shifting dullnessBowel sounds present
Respi/ cardiac sys WNLHMF intact
inv
Blood gr- A positive
Hb- 7.1Hct- 22.7%TLC- 17,500N-84 L- 16Plt- 93,000PT/ INR- 20/1.61
glucose- (R)- 112LFT total protein- 5.9Bil t/d- 1.8/0.6ALT/AST- 34/144Ur/cr- 57/0.5Na/K- 148/ 3.0RA- <8Serology- neg
USG- Hepatomegaly (18.7 cm) with increased and heterogenous echotexture and irregular surface with mild ascites s/o chronic liver diseaseThickened GB wall and with GB sludgeMin. b/l pleural effusion
CXR
cardiomegaly
heel pad thickness 30mm (N 21mm)
sella- length 18mm (N-17 mm) and height 15 mm (N-13 mm)
clinical dx
CLD ethanol inducedportal hypertension, ascitis w/o SBPPresented with UGI bleed in the form of hematemesis and melena sec to ?variceal bleed/ ?drug induced erosive gastritiswith anemia sec to blood losswith coagulopathyw/o HECPC- B, DF- 34with suspected acromegaly
mgmnt
inj. Octeotride inj. KCl inj. Pantoprazole inj. ceftriaxoneBlood transfusionDaily weight and abd girth
chartingRBS monitoring
course in hospital
UneventfulNo bleeding from NGNo black stoolNo postural drop in BPVitals stable
Patient left hospital on 3rd day against medical advice
acromegaly
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
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
somatostatin
>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
epidemiologyprevalence of acromegaly -8 to 13 cases per
100,000men and women -equally affectedmean age at diagnosis- early- to mid-40s disease often goes undiagnosed for many
years, especially in the early stagesmore 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 believedon average- a 2x increase in mortality and a
10-year reduction in life expectancy
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
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
s/senlargement of the heart and kidneysanti-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- osteoarthritisspinal kyphoscoliosis and excessive bone
growth (skeletal hyperostosis)
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% Coronary artery
disease 7%
when to suspect?
when patients have 2 or more of-new-onset diabetesdiffuse arthralgiasnew-onset or difficult-to-control hypertension cardiac disease - biventricular hypertrophy
and diastolic or systolic dysfunction fatigue, headachescarpal tunnel syndromediaphoresis, loss of vision, colon polyps, and
progressive jaw malocclusion.
diagnosis
Biochemical confirmationhypersecretion 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
Serum IGFBP-3 concentrationIGFBP-3 secretion, like IGF-I is GH-dependent, serum IGFBP-3 concentrations are elevated in patients with acromegaly
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 visceromegalyCT/ MRI for sella size and tumor extension
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 growthameliorate comorbidities restore mortality rates to normal preserve pituitary function
medical therapySomatostatin 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
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
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
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
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”
long term managementMonitoring Clinical and biochemical evaluation — Following
initial treatment, patients should be evaluated every three to four months
measurement of serum IGF-1 levelsPatients 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.
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
Literature search
references
Harrison's Principles of Internal Medicine, 18th Ed
UpToDate 21.2http://www.medscape.com/medicalstudentshttp://www.ncbi.nlm.nih.gov/pubmed/
THANK YOU
finally…
Photograph of the patient's hand and her son….