01-14 Growth D/o

Question 1

List the hormones involved in growth

Answer 1

POSITIVE GROWTH
GHRH
GH
IGF-I
IGF-3BP
Ghrelin
Sex Hormones
L-Thyroxine

INHIBIT/COUNTER-REG
Somatostatin

Question 2

How is the GH axis regulated?

Answer 2

Ghrelin from gut, ?other sources → stimulates hypothalamus → GHRH (+) and Somatostatin (-) → Ant Pit → GH to serum → binds to GHBP → liver → synth of both IGF-1 & IGFBP-3 →

Question 3

GH
—Direct Actions
—Indirect Actions

Answer 3

DIRECT
—counter-reg hormones: ↑ lipolysis and ↑ [gluc]
—Kindey: ↑ calciuresis and ‪↓‬ PO4 excretion; retains K, Na, Cl, Mg
—?bone density

INDIRECT
—stimulates IGF-1 production in the liver

Question 4

IGF

Answer 4

IGF-2 - fetal development
IGF-1 - post-fetal developments

BOTH: ubiquitous, made by many mesenchymal cells; both stimulate Type I IGF receptor (a tyr kinase) downstream pathway of which is similar to insulin
(a.k.a. somatomedins)

Question 5

IGFBPs

Answer 5

Insulin-like growth factor binding proteins
—7 types
—regulate [IGF-I]
—appear to have effects independent of IGFs
—IGFBP-3 is GH-dependent and is used to measure [GH]

Question 6

Somatostatin

Answer 6

—pulsatile

—suppresses GH release @ pituitary

Question 7

Thyroid Hormone
—Hypothyroidism effect on growth?
—Hyper “ effect on growth?

Answer 7

—important for skeletal growth
—Hypo: impaired GH release, delays bone maturation and limits linear growth
—Hyper: accelerates linear growth and bone maturation

Question 8

Gonadal Steroids

Answer 8

—both accelerate linear growth in puberty by working synergistically w/ growth hormone
—estrogen is responsible for bone maturation in BOTH ♀ & ♂ (aromatase)
EXAMPLE: 1994 NEJM case study of ♂ w/o estrogen receptor → still growing but young bone age and profound osteoporosis; high [T]

Question 9

Growth rate over time
—fetal
—infant
—child
—puberty
—adult

Answer 9

fetal: wicked fast, IGF-II-mediated
infant: a little slower, ∆ to IGF-II (we think)
child: slower still
puberty: faster growth thanks to sex steroids (acromegalic [GH] if you were to check!)
adult: no more growth but still fxn of GH

Question 10

How to predict height?

Answer 10

ESTIMATE
♀: (Dad - 5” + Mom)/2
♂: (Mom + 5” + Dad)/2
Result should be +/- 3.5” of adult height

RADIOLOGICALLY
—Use x-rays to estimate bone age

Question 11

DDx for Growth Disorders

Answer 11

GH def
IGF-I def
Hypothyroidism
Hypogonadism
Precocious puberty
GH def (actually least likely cause of short stature)

Question 12

GH/GHRH Deficiency: Clinical presentation

Answer 12

—hypoglycemia in infancy is often presenting sx
—decreased BMD & linear growth = younger bone age
—increased adiposity (ripply abdominal fat, cherubic facies); usually wt is nl for age

Question 13

GH/GHRH Deficiency: Etiologies

Answer 13

—idiopathic
—tumors (esp craniopharyngioma)
—radiation
—genetic syndromes (e.g. Prop-1 mutation have been implicated in ~50% of GH def)

Question 14

How do you dx GH/GHRH Deficiency?

Answer 14

—Document low growth velocity & bone age
—R/o anything else? (nutrition, illness, meds, almost anything!)
—Check thyroid
—Measure IGF-I and IGFBP-3 (allegory for GH; better to measure because unlike GH it is no pulsatile)
—Provocative GH test:
—1. insulin-induced hypoglycemia (gold-standard)
—2. arginine infusion
—3. L-dopa, clonidine, glucagon
—4. GHRH

—Head MRI

Question 15

GH Deficiency in Adults
—PRESENTATION
—DX

Answer 15

PRESENTATION
—does exists
—lower QOL
—body comp ∆s
—incr CV risk factors
—reduced exercise capacity

DX
—IGF-1/IGFBP-3 assays less helpful; jump to insulin or GHRH/arginine provocative tests

TX
—FDA-approved but; controversy persists
—lower dose than w/ peds

Question 16

Development of pituitary cells from precursor #1

Answer 16

Pre#1 (ACTH) —PROP-1→ Pre#2 (FSH,LH) —Pit-1 → Pre#3(TSH, GH→Prl)

Question 17

IGF-I Deficiency
—Etiology
—Labs
—Tx

Answer 17

ETIOLOGY
—one example: Laron Dwarfism = defects in GH-receptor

LABS
—High GH
—Low IGF-1

TX
—Resistance to GH tx but responsive to IGF-1

Question 18

Growth d/o w/ hypothyroidism
—Frequency
—Presentation

Answer 18

FREQUENCY
—much more common than GH def

PRESENTATION
—Typical hypothyroid sx
—Marked decrease in growth velocities
—Delayed epiphyseal plate closure, preserving some growth potential
—Wt well-preserved or obese

Question 19

Growth d/o w/ Gonadal hormones

Answer 19

HYPO
—growth spurt is blunted, but epiphyseal plates don’t close so growth continues past puberty
—Eunuchoid body habitus (arms and legs disproportionately long)

HYPER (Precocious Puberty)
—Growth is super fast and then stops short before reaching ideal height b/c growth plates fuse