GIGANTISM AND ACROMEGALY Flashcards
what is growth hormone also known as?
somatotropin
what is growth hormone produced by?
anterior pituitary gland
what does GHRH signal?
it signals the release of GH when blood levels are low
what does GH stimulate the liver to produce?
insulin-like growth factor (IGF’S) -4 types
what are the growth effects of IGF’s on?
muscle, cartilage, bone
what does GH stimulate adipose cells to do?
break down stored fat- lipolysis
what 2 things does GH stimulate the liver to do regardless of IGF’s?
- liver to break down glycogen into glucose- glycogenolysis
- liver to produce glucose- gluconeogenesis
what did GH stimulate insulin to do?
increase insulin resistance in tissues- not moving glucose into cells = increased blood glucose levels
what is IGF-1 also known as?
somatomedin C
What is IGF-1 produced by?
produced by liver in response to growth hormone in circulation
What does IGF-1 bind to?
binds to IGF-1 receptors and insulin receptors to produce multiple effects
what are the effects of IGF-1?
- PROMOTES CELLULAR METABOLISM
- prevents cell death
- increase the rate of cell division and differentiation throughout body
what is IGF-1 effect on muscle growth?
stimulates amino acid uptake into muscle cells, which helps w/ protein production
what is IGF-1 effect on growth of long bones (growth spurs in puberty)?
- acts on epiphyseal cartilage (growth plates) of bones
- stimulates activity of osteoblasts in bones
- stimulates activity of chondrocytes in cartilage
what is gigantism?
abnormal linear growth d/t excessive action of IGF-1 by growth hormone prior to closure of epiphyseal plates
rare condition (about 100 cases reported in US)
is gigantism seen more in men or women?
men
what is gigantism caused by?
three things
- GH overproduction d/t primary disorder
- GHRH overproduction inducing pituitary overproduction of GH
- ectopic GH and/or GHRH secretion from tumors of the pancreas, lungs, and/or adrenal glands
what are the 2 different types of primary gigantism?
GH overproduction d/t PRIMARY DISORDER
- benign GH-producing pituitary adenoma (>95% cases)
- familial syndromes: multiple endocrine neoplasia types 1 or 4; McCune-Albright syndrome
what are the clinical features of gigantism?
- rapid and excessive height growth (long bones) and weight gain
- patients commonly >6’6” tall - large hands and feet
- macrocephaly
- coarse facial features (frontal bossing and prominent jaw)
- hyperhidrosis
what is acromegaly?
abnormal growth d/t excess of growth hormone after close of the epiphyseal plates
rare condition
what age and gender does acromegaly occur?
develops in middle-aged adults
mean age at dx: 40-45 y/o
WOMEN OVER MEN
how does acromegaly progress?
very slowwww. onset to dx: roughly 12 years
what is acromegaly caused by?
- GH overproduction d/t PRIMARY DISORDER
- benign GH-producing pituitary adenoma
- familial syndromes: multiple endocrine neoplasia types 1 or 4; McCune-Albright syndrome - GHRH overproduction inducing pituitary overproduction of GH
- Ectopic GH and/or GHRH secretion from tumors of pancreas, lungs, and/or adrenal glands
what is a clinical feature that occurs to the skin in acromegaly?
hyperhidrosis, cystic acne, acrochordons
what happens to the voice in acromegaly and why?
deep coarse voice due to the hypertrophy of pharyngeal and laryngeal tissue
what are some coarse facial features of acromegaly?
- enlargement of eyebrows/ forehead -> frontal bossing
- widening of nose
- thickened lips
what happens to the hands and feet in acromegaly?
large and broad hands and feet
what clinical feature of acromegaly happens to the head?
headaches and temporal hemianopia (dependent on size of pituitary tumor)
what are some other important clinical features other than the ones already stated?
macroglossia, prominent jaw (prognathism and malocclusion), widening between teeth, carpal tunnel, sleep apnea, HTN, cardiomegaly, insulin resistance leading to diabetes mellitus
what is a clinical feature of acromegaly pertaining to other hormones?
decrease in secretion of other pituitary hormones - most commonly GONADOTROPIN
whats a clinical feature of acromegaly in females?
menstrual dysfxn, hot flashes, vaginal atrophy
whats a clinical feature of acromegaly in males?
ED, libido loss, decreased facial hair growth, small testicles
what laboratory testing is first line in confirming acromegaly?
serum IGF-1 because it is increased in 3-10x
it can be also used to monitor response to therapy
what is another testing method other than IGF-1 that can be used to dx acromegaly?
oral glucose test/GH suppression test
what does the oral glucose test do?
helps determine if pituitary is releasing too much GH
how is the oral glucose test performed?
drink a sugar drink of 75 g of glucose
measure serum GH before and after 2 hours
>1 ng/mL is abnormal -> normally with an increase in blood glucose, growth hormone is suppressed (LOW GH LEVEL)
what is the first step in imaging for acromegaly dx?
MRI of pituitary-> GH- secreting pituitary adenoma (majority of cases)
what is the second method of imaging in acromegaly dx if MRI normal?
chest and abdominal CT -> extra-pituitary acromegaly if MRI of pituitary is normal
what is the surgical treatment option for acromegaly?
removal of tumor via endoscopic endonasal technique (transsphenoidal adenectomy)
- best chance for a cure
what happens with incomplete remission following surgery?
MEDICATIONS:
1. dopamine agonists (bromocriptine) -helps to lower levels of GH and IGF-1
2. GH-receptor- antagonists (pegvisomant) -normalize elevated IGF-1levels
3. somatostatin analogs (octreotide) -reduce growth hormone production
what is the goals/risks of radiation therapy in acromegaly cases?
goal: reduce tumor size
risk: possible damage to other normal pituitary cells
complications of acromegaly:
HTN
heart problems (cardiomyoptahy)-> referral to cardiology
T2 diabetes
thyroid goiter
increased risk of developing colon cancer and thyroid cancer
- colonoscopy screening every 3-5 years
- yearly exam of thyroid gland-> thyroid US if any masses or enlargement is detected
