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….