Growth Hormone Disorders

Question 1

What does growth hormone do? Feedback loop?

Answer 1

Growth hormone is also called somatotropin.

• It is an anabolic hormone that stimulates growth, cell reproduction, and renewal
• made and stored and released by the anterior pituitary
• raises the concentration of glucose and fatty acids to fuel growth
• stimulates the production of IGF-1
  
  • mediates many of the physiologic effects of GH because GH can’t cross some cell membranes
• Functions include
  
  • increase in calcium retention, increase in muscle mass, stimualtes growth of all internal organs except the brain. decreaes liver glucose uptake, promotes lypolysis, promotes gluconeogenesis, helps maintain homeostasis, maintain function of pancreatic islets, increase protein synthesis.

Feed Back loop

• see picture
• But in words, The hypothalamus releases GHRH which stimualtes the anteiror pituitary to release Growth hormone. Growth hormone can also be stimulated by ghrelin produced in the stomach. Growth hormone then goes to the liver to produce IGF-1. Together IGF-1 and GH have effects on the body
• GH and IGF have effects on
  
  • liver to stimulate gluconeogenesis, and glycogenolysis, and stop glycogenesis
  • adipose to stimulate lipolysis and stop lypogeneiss
  • bone and muscle to begin protein synthesis and grow.
• IGF-1 and growth hormone both act on the anterior pituitary and the hypothalamus via a negative feedback loop.

Question 2

Growth hormone deficiency, def, epidemiology, patho, when to test

Answer 2

• A deficiency of growth hormone that manifests in infancy, childhood, or adulthood

epidemiology

• estimates vary widely depending on criteria, but somewhere between 1:4000 and 1:1000 live births
• Somewhre between 3 and 30% are familial
• adults its rare
• Children patho
  
  • congenital:genetic mutations
  • trauama
  • cns tumor
  • infection
  • radiation
  • idiopathic
• adults
  
  • pituitary tumors - mc
  • extrapituitary tumors
  • surgery
  • radiation
  • TBI
  • SAH
  • CNS infections
  • idiopathic

clinical features

• Congenital: neonatal
  
  • Abnormal postnatal growth
    
    • may not be ovious until 6-12 months
  • May have severe hypoglycemia if combined with ACTH deficiency
  • If combined with conadotropin deficiency, can have microphallus, cryptochidism, scrotal hypoplasia
  • may have prolonged jaundice
  • slower muscular development with delayed motor milestones
• children - aquired
  
  • change in growth rate
  • delayed bone age
  • increase in adiposity
  • infantile voice
  • thin, sparse hair growth
  • immature face
  • slower muscular development with delayed motor milestones
  • puberty may be delayed
• adults
  
  • reduced muscle mass and strength
  • baldness
  • reduced bone mass and osteoporosis
  • reduced energy
  • increased body fat, especially around the waist
  • lipid abnormalities
  • reduced concentration
  • impaired psychological well-being
  • insulin resistance
  • greater mortality
    
    • especially from CV dz.

When to test?

• test if there is growth failure, height curve has deviated downwards across 2 major height percentile curves or growing less than
  
  • 2.2 inches/year for 2-4 year olds
  • 2 inches a year for 4-6 year olds
  • 1.6 inches a year for 6-puberty boys
  • 1.8 inches a year for 6 puberty girls
• Severe short stature
• features concerning hypothalamic pituitary dysfunction combined with decelerating growth, hypoglycemia and hypoplasia
• deficits in other hypothalamic pituitary hormones

Question 3

Growth hormone deficiency diagnosis and treatment kids vs adults

Answer 3

• 1st measure IGF-1
• If low, need to confirm with 2 provocative stimulation tests that theres an inadequate rise of GH
  
  • insulin, deep sleep, glucagon, L-DOPA, vigorous exercise, arginine
• May also need an MRI of hypothalamic-pituitary region
• Insulin is very slowly given, blood drawn every 15 minutes to look for GH changes.

ddx

• hypothyroidism
• turner syndrome
• chronic systemic disease
• poor nutrition
• familial short stature
• anorexia nervosa
• child abuse

treatment

• start with recombinant human GH Sq daily
• start asap for best results
• adjust based upon IGF-1 levels and growth response
• continue at least until linear growth is nearly complete
• s/e: headaches are most common
• If tumor causing: surgical removal.

Treatment in adults

• Tumor: surgical removal
• GIven GH is controversial
  
  • endocrine society recommends giving GH but research is mixed
• patient values and preferences are importnat
• monitored by IGF-1 levels –> want to maintain IGF based on the age group
• s/e, peripheral edeam, arthralgias, carpal tunnel syndomre, paraesthesias.

Prognosis

• Untreated –
  
  • higher mortalitty, lean body mass, low bone density, increase in fracture, increase in hypertension, high cholesterol
  • children that take GH do better the earlier its started
  • With GH replacement, patietns may have improvements in body composisiton
• Definitely need an endo referral. may also need nuerosurgery referral
  *

Question 4

Growth Hormone Excess, def/cause

Answer 4

• Excess secretion of GH can cause gigantism in youth and acromegaly in adulthood
  
  • Gigantism: occurs in children before the closure of epiphyses so there is excess growth of long bondes
  • Acromegaly: occurs in adults after closure of epiphyses so there isn’t long bone invovlemnt –> hands, feet, jaw, internal organs affected

epidemiology

• gigantism
  
  • extremely rare,
  • less than 100 cases to date
• acromegaly
  
  • also rare
  • 5-9 people per million
  • usually 40-50 at diagnosis

Pathophysiology

• Excess secretion of GH –> excess secretion of IGF-1 –> s/s of the dz
• Almost always caused by a pituitary adenoma
  
  • usually benign macroadenomas
  • usually sporadic, sometimes familial
  • rarely malignant –> can be locally invasive though
• Mixed cell tumors often cosecrete prolactin
• Peripheral tumor- carcinoid, sclc
• some familial syndomres have acromegaly as a component

s/s

• Enlargement, elongation, coarsenign of the hands, feet, jaw, and internal organ involvement
• HTN, DM, cardiomegaly and CHF common
• Doughy, moist handshaek
• macroglossia, deep, coarse voice, OSA
• spinal stenosis
• arthalgias
• weight gain
• hypogonadism, decrease in libido, ED, irregular menses
• temporal hemianopsia
• headache
• skin thickening, hyperhidrosis, acne, acanthosis nigricans, skin tags, colon polyps.
• Early changes –> might see a change in ring size

Question 5

Growth hormone excess dx and tx.

Answer 5

Diagnosis

• 1st check for increase in IGF 1 random sample
• Next check a fasting 8 hour, non ill, and no exercise that day
  
  • serium IGF-1, prolactin, glucose, LFTs, and BUN/Cr, TSH
  • 1 hour glucose toleracne test (gold standard)
    
    • shows failure of GH to suppress
    • Normally high glucose would suppress GH
• Finally: pituitary MRI to identify lesion

tx

• Transphenoidal resection if possible
• somatostatin analogs: octreotide or lanretide
  
  • can cause shrinakge of the pituitary adenoma
  • can be used in those who fail surgery
• Dopamine agnosis: carbergoline, or bromocriptine - not as effective
  
  • may inhibit GH secretion
• Pegvisomant
  
  • GH receptor antagonist
  • blocks hepatic IGF-1 production

Prognosis/referral

• Lifespan typically decreased by 10-15 years
• Mortality rate is 2-3x higher than the general population
  
  • most from CV disease
  • increased cancer
    
    • men - colon cancer, esophageal, melanoma
• Should see endo
  
  • and neuro for surgery