DSA03 - Short Stature and Tall Stature

Familial Short Stature

Define Condition:

Dx of Exclusion

-Hx: (Nothing Remarkable)

> Short Height in Parents

-Sx/PE: Normal/Noncontributory, but consistently low height

-Dx:

> Growth Chart Abnormality

> Mid-Parental Height/MPH (confirm child's height to family height) + Bone Age Film (CONFIRM - Lets clinician know how much vertical growth is remaining (can help calculate final adult height = Predicted Adult Height, or PAH) ==> If PAH/Final Height Prediction falls within MPH range --> CONFIRMS

-Tx:

> Reassurance

> Serial exams w/ height measurements to ensure continued normal growth/consider alternative diagnoses

[(Mom's height + 5 inches) + (dad's height)]/2 +/- 2.5"

How do you calculate Mid-Parental Height/MPH (aka target height) Range for a BOY?

[(Mom's height) + (dad's height - 5 inches)]/2 +/- 2.5"

How do you calculate Mid-Parental Height/MPH (aka target height) for a GIRL?

Constitutional Delay of Growth and Puberty (CDGP) - aka "Late Bloomer"

Define Condition:

When vertical growth is "behind schedule"; NOT PATHOLOGIC (Normal growth variant)

-Hx:

> Initially shorter than expected/shorter than peers

> Often FHx (ask parents when they went thru puberty)

-Path: Vertical growth spurt occurs later that in their peers --> Continue growing after peers stop growing

-Sx/PE:

> Pubertal exam = LESS MATURE for chronologic age

> Final Height will be within normal range of MPH

-Dx:

> Growth Chart

>> Height is low in prepubertal years, BUT parallel to standard lines

> Bone Age Film = Delayed Bone Age relative to chronologic age

> PAH --> Compare to MPH (PAH should be w/n MPH range)

-Tx:

> Reassurance (maybe brief Testosterone trial for boys - one injection every 30 days for 6 months)

> Continue Monitoring

-CBCd

-CMP

-ESR

-Celiac Screen

-Thyroid Function Tests (TFTs)

-Growth Factors (IGF-1 and IGFBP-3)

-Karyotype (if pt is girl)

What are suggested screening tests to assess for other causes of short stature?

Growth Hormone Deficiency

Define Condition:

Poor ve rtical growth d/t low GH secretion

-Hx:

> Congenital = MCC IDIOPATHIC/SEVERE GENE MUTATIONS

>> Hx of Hypoglycemia in early newborn

>> Hx of Hyperbilirubinemia in early newborn

> Acquired

>> Trauma to Head

>> Radiation to brain

>> CNS Infex (Encephalitis, Meningitis)

>> Neurosurgical injury to pituitary

>> Sellar tumors

-Sx/PE:

> Normal + Short Stature

> Excess Adiposity (more lipolysis, more protein synthesis)

> Lack of Muscle Tissue (more lipolysis, more protein synthesis)

-Dx:

> Growth Chart

> Bone Age Film (DELAYED BONE AGE)

> PAH --> Compare to MPH (PAH BELOW MPH RANGE)

> PAH below <5th percentile

> Check IGF-1, IGFBP-3 (low levels)

> GH Stimulation Test

>> Usually via Arginine & Insulin

>> Levels drawn 8-10 times over time span of 2 hours after drug administration

>> GH peak > 10 ng/mL (Normal)

>> GH peak < 10 ng/mL --> DEFICIENCY

-Tx: Growth Hormone Injection (SQ)

> Nightly for years

> Continue visits to follow growth, assess compliance, optimize dose, and monitor S/Es

> D/C once vertical growth is nearly complete

-Stimulates linear growth by direct action on the epiphyseal plate

-Increases lipolysis

-Stimulates protein synthesis

-Antagonizes insulin action

What are the direct effects of GH on target tissues?

-Stimulates linear growth by action on the epiphyseal plate

-Balanced growth at other tissues

What are the indirect effects of GH (via IGF-1)?

Laron Syndrome (Not for Test, but BOARDS)

Define Condition:

Autosomal RECESSIVE Disorder d/t LOSS OF FUNCTION mutation of GH receptor

-Path: FUNCTIONALLY deficient response to GH, but making enough

-Sx/PE: Lifelong, severe vertical growth failure

> Facial Dysmorphisms

> Short Limb Length compared to trunk length

> Intellectual development NORMAL (or only MINIMALLY IMPAIRED)

> Short Stature

> Excess Adiposity (more lipolysis, more protein synthesis)

> Lack of Muscle Tissue (more lipolysis, more protein synthesis)

-Dx:

> Growth Chart

> Bone Age Film (DELAYED BONE AGE)

> PAH --> Compare to MPH (PAH BELOW MPH RANGE)

> PAH below <5th percentile

> Check IGF-1, IGFBP-3 (low levels)

> GH Stimulation Test

>> Usually via Arginine & Insulin

>> Levels drawn 8-10 times over time span of 2 hours after drug administration

>> GH peak > 10 ng/mL (Normal)

-Tx: Recombinant IGF-1 (Mecasermin)

Hypothyroidism

Define Condition:

-Sx/PE: Poor Growth Velocity

-Dx:

> Bone Age Film

>> Delayed Bone Age to relative to chronologic age

>> PAH may fall w/n MPP OR Below MPH

> Growth Chart

> TFTs

>> TSH & Free T4

-Tx: Thyroid Replacement Therapy

> Bone Age starts advancing

> May reach MPH target range

Cushing Syndrome

Define Condition:

Excess of glucocorticoids (for any reason - endogenous or exogenous) --> Impaired vertical growth

-Hx: Exposure to Glucocorticoid Therapy

> Asthma

> Inflammatory Diseases

> Transplant

> Leukemias

-Path: Vertical growth INHIBITION:

> Interfere w/ bone formation

> Disrupt collagen formation

> Nitrogen retention

> Impair GH secretion and action

-Sx/PE:

> Rapid Weight Gain

> Lower height for age group

-Dx:

> Growth chart

>> More striking plateau for vertical growth

>> MORE STRIKING INCREASE IN WEIGHT

> Cortisol Excess Stigmata

-Tx:

> Exogenous = Stop Offending agent (if possible)

> Endogenous (Cushing) = Tx Cushing

Undernutrition of Chronic Illness

Define Condition:

-Hx/Path:

> Inadequate nutrient intake (Swallowing dysfunction, Child neglect, Anorexia)

> Inadequate GI absorption (Celiac, IBD, CF)

> Increased metabolic demand (Chronic infex, Chronic Resp Fail)

> Inadequate metabolic utilization of nutrients (Inborn metabolism error, DM2)

-Dx:

> Growth Chart

>> Weight affected FIRST --> Vertical growth affected (less than weight)

>> Infant = Head circumference compromised

> Screening Labs for Systemic Illness

>> CBCd

>> CMP

>> ESR

>> Celiac

>> U/A

>> HbA1c

-Tx: Tx Underlying cause + Utilize other professionals (dietitians, social workers, therapists)

Genetic Syndromes causing SHORT STATURE

Define Cause of Stature Issue:

-Hx/Path:

> Conditions:

>> Trisomy 21

>> Turner Syndrome

>> Noonan Syndrome

>> Prader Willi Syndrome

> General Features:

>> Hx of delayed developmental milestones/intellectual disability

>> Multiple/unrelated health issues affecting disparate organ systems

-Sx/PE:

> Trisomy 21 = Epicanthal Folds

> Turner = Low posterior hairline

-Dx:

> Growth chart

> Check karyotypes in all girls (esp for TURNER)

> Focused genetic testing

-Tx:

> Turner = GH

> Noonan = GH

> Trisomy = None

Familial Tall Stature

Define Condition:

When pt is tall b/c parents are tall (normal growth pattern) - not pathologic

-Hx:

> Unremarkable Hx

> FHx of Tall Stature

-Sx/PE: Normal

-Dx:

> Growth Chart = Height AND Weight consistently elevated

> Bone Age FIlm

>> Calculate PAH ---> Compare to MPH (PAH should fall within MPH range)

-Tx:

> Reassurance

> Tall girls may get estrogen (facilitates closure on growth plates, but not common d/t S/Es)

Precocious Puberty

Define Condition:

When pt is tall d/t early puberty (natural vertical growth acceleration of puberty BEFORE other children) - normal growth variant (not pathologic)

-Sx/PE: Early Pubertal Features (more mature for chronologic age)

> Early Acne

> Axillary hair

> Pubic hair

> Breast development

> Menses

-Dx:

> Growth Chart = Increase in the speed of weight gain at the same time as the vertical growth acceleration

> Bone Age Film = PAH --> Compare to MPH

>> Bone age will be ADVANCED to chronologic age, but concordant w/ pubertal status

>> PAH is LOWER than MPH (Completes puberty EARLY --> cease vertical growth early)

> Labs

>> Boys = HIGH Testosterone

>> Girls = HIGH Estradiol

> Height Velocity Chart = Velocity INCREASES SIGNIFICANTLY in puberty (acceleration begins early)

-Prog: If appropriate Tx, PAH will be normal

Excessive caloric intake

Define Condition:

Children w/ too much intake have BRISK vertical growth

-Hx:

> High caloric Intake

> Inactivity

-Sx/PE: Unremarkable, besides tall stature & obesity

-Dx:

> Growth Chart

>> Weight Gain BEFORE brisk vertical growth

>> Rate/Magnitude of Weight Gain is MORE STRIKING than rate of vertical growth

-Tx:

> Reassurance

> Address intake

Pituitary Gigantism

Define Condition:

Pituitary adenoma secretes excessive GH when BEFORE growth plates have closed

-Sx/PE:

> Excessive Linear Growth

> Significant weight gain (begins with height acceleration)

-Dx:

> Growth Chart

>> Vertical Growth is MORE STRIKING than weight gain

> Check IGF-1 + GH Suppression:

>> First ELEVATED

>> THEN GH Suppression via 75 g Oral Glucose Load, then check after 2 hrs -->

>>> if < 1 ng/mL = Normal

>>> if > 1 ng/mL = GH Excess

> MRI (Pituitary) if GH Supression is Abnormal

-Tx:

> 1st = Transphenoidal Surgery (complete tumor resection)

> 2nd = Pharmacotherapy (if unfit for surgery, tumor too complicated, no relief from surgery)

>> Somatostatin Analog ("-tide")

>> GH receptor antagonist (Pegvisomant)

>> D2 Agonist (Cabergoline, Bromocriptine)

Acromegaly

Define Condition:

Pituitary adenoma secretes excessive GH when growth plates have closed - MC than pituitary gigantism

-Hx:

> Insidious onset (but slow progression)

> Dx in 40s

> A/w...

>> OSA

>> T2DM

>> Carpal Tunnel

>> Joint Pain

>> CVD

-Sx/PE:

> Macrognathia (enlarged hands/feet, coarse facial features, widened spaces btwn teeth, macroglossia)

> Secondary to Adenoma = HA, Visual Field Defects

-Dx:

> Check IGF-1 + GH Suppression:

>> First ELEVATED

>> THEN GH Suppression via 75 g Oral Glucose Load, then check after 2 hrs -->

>>> if < 1 ng/mL = Normal

>>> if > 1 ng/mL = GH Excess

> MRI (Pituitary) if GH Supression is Abnormal

-Tx:

> 1st = Transphenoidal Surgery (complete tumor resection)

> 2nd = Pharmacotherapy (if unfit for surgery, tumor too complicated, no relief from surgery)

>> Somatostatin Analog ("-tide")

>> GH receptor antagonist (Pegvisomant)

>> D2 Agonist (Cabergoline, Bromocriptine)

Genetic Syndromes causing TALL STATURE

Define Condition:

-Hx/Path:

> Marfan Syndrome

> Klinefelter Syndrome (47, XXY)

> Homocystinuria

-Sx/PE:

> Height OUT OF PROPORTION to family height

-Dx:

> Bone Age Film = PAH out of MPH range

> Labs:

>> Kline = Karyotype

-Tx: Genetics referral