Abnormal Growth Flashcards
What is the difference between hypergonadotrophic hypogonadism and hypogonadotrophic hypogonadism?
- hypogonadotrophic hypogonadism: impaired secretion of gonadotropins, including FSH and LH by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.(Kallman, tumors, head trauma, drugs, malnutrition)
- Hypergonadotrophich hypogonadism: hypogonadism due to an i_mpaired response of the gonads_ to FSH and LH and in turn a lack of sex steroid production and elevated gonadotropin levels (as an attempt of compensation by the body) (e.g., Turner’s, Klinefelter’s, trauma, radiation, STIs, drugs)
Abnormal growth: What questions do you want to ask during the interview to help define the problem?
- Parental heights: so you can plot on growth curve
- Puberty questions: are they on track? Tanner stages? If on track with puberty, less worrisome.
- If no puberty in female - think of Turners. Early puberty not so worrisome.
- Early puberty in males: worry
- Diet and exercise: are they malnourished? Could be tied to puberty delay as well.
- GI complaints: IBD / Celiac - malnourished
- Other sx suggestive of thyroid - e.g., temp intolerance (anorexia too)
- Sense of smell? none = Kallman
Abnormal growth: What do you look for on exam?
- Height and weight
- Arm span and upper-to-lower (U/L) body-segment ratio
- Sexual maturity ratings (SMRs) - orchidometer (blue beads = prepubertal; yellow = puberty)
- A general physical examination, with special attention to the thyroid gland, ophthalmological examination, neurological examination, and stigmata of congenital syndromes (e.g., gynecomastia Klinefelter’s, webbed neck of Turner, etc)
Abnormal growth: What diagnostic studies should be ordered?
- Bone age
- BUN, creat
- CBC, ESR
- Total IgA, tTG IgA (Celiac Dz IGA 30-300)
- Thyroid indices, TSH
- IGF-1, IGFBP-3
- FSH, LH, Testosterone
- Karyotype
- Head MRI
- Midparental height calculation
whether to reassure parents or b/c a possible abnormality. Karyotype specifically in girls, rarely in boys – girls looking for Turner. (more explanations given)
Abnormal growth: When should you evaluate a patient for short stature?
- Linear growth rate is<4 to 5 cm/year during the years prior to the normal age for peak linear growth velocity
- No evidence of a peak linear growth velocity by age 16 years in boys and 14 years in girls.
- Deceleration below an individual’s established growth velocity occurs.
- The adolescent’s height is more than 2 standard deviations (SDs) below the calculated midparental height
- The adolescent’s height is more than 3 SDs below the mean. Consideration should be given to carrying out a full evaluation if an adolescent’s height is between 2 to 3 SDs below the mean; at a minimum, a careful history and physical examination, screening laboratory tests and observation of growth for 6 months is warranted.
When should you evaluate a patient for delayed puberty?
- absence of breast budding by age 13 in girls, PH1 beyond 14yo, no menstruation beyond 16yo OR 5y between initiation of breast growth and menarche
- lack of testicular enlargement by age 14 in boys, PH1 beyond 15yo, phallic enlargement in absence of testicular enlargement, >5y btwn initation to completion of genital growth
How do you calculate estimates of mature height?
Mid-Parental Percentile
M: Fa HT + Mo HT + 5”
2
F: Mo HT + Fa HT – 5”
2
What would the growth curve of a child with familial short stature look like?
Progress “normally” at a lower percentile.
Birth weight and length that are often below the 3rd percentile for gestational age, Growth curve that generally parallels the 3rd percentile
What would the growth curve of a child with growth hormone deficiency look like?
height percentile drops off more precipitously than weight (which also drops)
What would the growth curve of a child with constitutional delay of growth look like?
- often slow growers throughout childhood, may slow even further when they reach age when puberty normally occurs.
- GV increases into normal range when finally enter puberty
- Tend to have a less exuberant growth spurt and thus final height often shorter than predicted
What would bone ages be for familial short stature?
BA=Chronologic Age
What would bone ages be for growth hormone deficiency?
BA<ca>
</ca>
What would bone ages be for constitutional delay of growth?
BA < CA
(equal delay of bone and height age)
A patient with primary amenorrhea has serum gonadotropins checked. Her FSH is 102 MIU/ml, and LH is 94.5 MIU/ml. What other labs should be checked?
hypergonadotrophic hypogonadism
17 hydroxyprogesterone, karyotype, head CT/MRI, serum progesterone, serum testosterone
What is BMI and why might it be useful in the evaluation of patients with primary amenorrhea?
Mass (kg)/height (m2)
Very low BMI (due to anorexia or malabsorption like Celiac or IBD) can cause primary amenorrhea
What are some counseling issues and strategies for adolescents who experience delays in physical growth and/or sexual development.
–Juvenilization (Sandberg 1999)
–Teasing, Bullying (Voss and Mulligan 2000)
–Exclusion (Zimet 1997)
–Loss of independence, overprotection (Zimet 1997)
–Physical limitations
- heightism in language, job, marriage/partnership
- discuss w/ado. Find out if they perceive a problem - consider that over focusing on getting them taller may send the opposite message we want
What are the clinical characteristics specific to Turner syndrome?
- 45,X (or mosaic 45,X/46,XX, etc)
- Short stature
- Streak gonads
- Absent pubertal growth spurt
- Poor development of secondary sexual characteristics, with less breast development than pubic hair development
- Lymphedema
- Nail dysplasia
- High arched palate
- Strabismus
- Hearing deficit due to chronic otitis
- Cubitus valgus
- Webbing of the neck
- Low hairline
- Shield-shaped chest
- Coarctation of the aorta
- Horseshoe kidneys
- Short fourth metacarpal
- Multiple pigmented nevi
- Normal vagina, cervix, and uterus
- Poor space-form perception with normal overall intelligence
*
What tests would aid in the diagnosis of Turner syndrome?
Karyotype
FSH and LH levels
What is an appropriate management plan for Turner syndrome?
Refer to Endocrine, consider further tests to investigate complications.
- GH helps - higher dose than GH deficiency
- monitor IGF-1, TSH, bone age during Tx
- baseline renal U/S, periodic ECHO
- Delay estrogen replacement to 12 to 14 to maximize height gain
What are the clinical characteristics specific to Klinefelter syndrome?
- 47, XXY (more Xs = more severe)
- small, firm testes
- tall, slender body habitus w/long legs and shorter torso (growth plates not closing, low testosterone)
- gynecomastia (higher estrogen)
- feminine hips
- high pitched voice
- sparse facial and pubic hair
- infertility
- hypergonadotrophich hypogonadism
- motor delay or dysfunction
- speech and language difficulties
- attention deficits
- learning disabilities
- dyslexia or reading dysfunction
- psychosocial or behavioral problems
What tests would aid in the diagnosis of Klinefelter syndrome?
karyotype
FSH & LH levels
What is an appropriate management plan for Klinefelter syndrome?
Refer to Endocrine
Rx: testosterone, Ca++, Vit D
Manage comorbidities, learning issues, etc
What are the clinical characteristics specific to Androgen Insensitivity?
- 46, XY (genetically male but resistant to androgens)
- previously referred to as “testicular feminization”
- phenotypic female with tall stature, absence of sexual hair, normal breast development and timing of puberty, but absence of menarche.
- Vagina is a short pouch and there is no uterus.
What tests would aid in the diagnosis of androgen insensitivity?
The karyotype is 46,XY, and testosterone levels are elevated.
What is an appropriate management plan for androgen insensitivity?
- Refer to Endocrine
- Gender assignment question - may inform tx plan
- Remove testes d/t risk of cancer
- psychological support
Explain Turner syndrome to an adolescent in a developmentally appropriate manner.
When we’re all being formed in our mother’s womb, each of us has the genetic material from our parents rearranged in a different way - and those differences produce our physical characteristics. The genetic material is kept in chromosomes - typically, women have 46 chromosomes and two of those are X (or female). You have 45, and only one of yours is an X. Having one X instead of two means that your hormones and genes have worked a little diffently in your body, and that’s why, as you’ve noticed (e.g., you’re shorter than your classmates, you don’t have breasts yet). So we can give you some of the hormones that you’re body has been missing. This will allow you to grow taller and develop breasts… etc
Explain Klinefelter syndrome to an adolescent in a developmentally appropriate manner.
When we’re all being formed in our mother’s womb, each of us has the genetic material from our parents rearranged in a different way - and those differences produce our physical characteristics. The genetic material is kept in chromosomes - typically, men have 46 chromosomes and two of those are sex hormones - X and Y. You have (47), 2 x and one Y. Having one extra X means that your hormones and genes have worked a little diffently in your body, and that’s why, as you’ve noticed (e.g., you’re taller and slimmer, your testes are smaller, you have this extra breast tissue). So we can give you some of the hormones that you’re body has been missing. … etc
Explain Androgen Insensitivity to an adolescent in a developmentally appropriate manner.
Very carefully gauge how teen feels in order to craft this – one script probably wouldn’t work
When we’re all being formed in our mother’s womb, each of us has the genetic material from our parents rearranged in a different way - and those differences produce our physical characteristics. The genetic material is kept in chromosomes - typically, we think of men having 46 chromosomes and two of those are sex hormones - X and Y. And women, we think of as having 46 chromosomes with two Xs. Having XX or XY tells our body what hormones to send out to develop, for example, a penis or a vagina. In your mother’s womb, your genetic material was rearraranged to be 46XY, so hormones were sent out to tell your body to start forming “male” sex characteristics. But because your body is resistant to those hormones, it didn’t completely listen. This means that you developed the female sex characteristics. But since you are XY and not XX, you also produced some male characteristics that we can’t see on the outside. Now you have a choice. – gauge how they feel about their gender – and counsel – e.g., You have grown up as a female and this information does not make you any less of a girl. OR choosing to identify as a boy - will inform how we treat.
How is a bone age exam done and why?
X-ray of the left hand and wrist for bone age (since the bone age can determine if there is more potential for growth and be used to estimate predicted final height).
Growth velocity: average
Avg ~ 2-2.5”/yr
Minimum growth velocity
Minimum ~ 1.5”/yr * (~ 4 cm/yr)
*Late bloomers can slow to only ~1”/yr
SIgnificance of shifting percentiles in growth
can be normal even up to 0-3 year. Shift up early = likely to be tall. Shift down early = likely to be shorter.
Boys: approximately what age do testes enlarge?
11.5 yrs (9.5-13.5)
Boys: approximately what age does pubic hair come in?
12 yrs
What happens in terms of puberty at about 13-14 years in boys?
gynecomastia, axillary hair, voice change, acne, peak GV
When is tanner stage IV, approximately, in boys?
~14 years
When does facial hair come in for boys, approximately?
~15years
Progression of pubertal development in girls
Breast → Pubic Hair→ Menarche
When does breast and pubic hair development usually start in girls?
African Am: B and PH 810/12 yrs (7-11)
Caucasian: B 911/12 PH 106/12 yrs (8-12)
What is SHOX?
Short Stature Homeobox Gene
Pseudoautosomal
region of X and Y
What are IGF-1 and IGFBP-3? How are they regulated?
indirect measures of GH secretion
Regulated by GH and nutrition
Boys: Tanner 1
Boys: Tanner 2
-
(start of puberty): 11½ yrs (9.5 – 13.5)
- height at basal rate
- Testes enlarge to 4 ml or long axis 2.5 to 3.2 cm
- pubic hair develops at base of penis at 12 yrs
Boys: Tanner III
- ~13-14 yrs
- 7-8 cm/year growth
- gynecomastia, voice change, acne, muscle mass increases
- 12ml testes
Boys: Tanner IV
- **Peak GV 10 cm/year, ~14 yrs
- Axillary hair
Boys: Tanner V
- No further height increase
- Adult size penis, testes by 16.5 y/o
- ~ 15 yrs facial hair
Girls: Tanner 1
- 5-6 cm/year, not breast development or pubic hair
Girls: Tanner II
-
puberty starts
- 7-8cm/yr growth
- Thelarche: Breast buds age 10.9 (8.9-12.9)
- Pubarche: Public hair starts to grow (minimal), age 11.2 (9-13.4)
- African Am: B and PH 810/12 yrs (7-11)
- Caucasian: B 911/12 PH 106/12 yrs (8-12)
Girls: Tanner III
- **Height peak rate 8cm/yr (12.5)
- Breast: elevation of contour, areola enlarges age 11.9
- Courser, darker pubic hair age 11.9
- Axillary hair, acne
Girls: Tanner IV
- Height 7cm/year
- Areola 2ndry mound on breast 12.9 y/o
- Hair adult quality, not on thighs
Girls: Tanner V
- No further growth after 16 y/o, adult quality hair, spreads to thighs, adult breast, no 2ndry mound
Girls: when is menarche?
African Am: 121/12 yr; Caucasian: 128/12 yrs (12-13 avg)
Girls: how many years to complete development?
2-5 years
Girls: how many years after breast buts to menarche
2.5 years (6mo - 5 years)
How many years / inches growth after menarche?
2 years, 1-2”
Average growth velocity: after age 3
- Evaluate if child deviates from the norm:
- Avg 2-2.5”/yr = 5-6.6 cm/yr
- Minimum 1.5”/yr = 4 cm/yr
- Late bloomers can slow to only 1”/yr
Growth Hormone Rx SEs
- Na+/water retention
- Antibody formation
- Slipped capital femoral epiphyses
- Scoliosis
- Hyperinsulinemia
- Neoplasias
Rx for Constitutional Growth Delay
testosterone
Tx GH deficiency
GH
Tx for ISS
can try GH
What is ISS?
Idiopathic Short Stature:
- (No pathology. Normal short stature, familial short stature, genetic short stature, non-GHD short stature)
1. No identifiable pathology
2. Peak stimulated GH > 10 ng/ml
GH stimulation criteria
- > 2” below Mid Parental Percentile Height
- GV <25th %tile for age
- IGF-1/IGFBP-3 < -2 SDS
Why do a GH stimulation test?
To determine if body is not producing GH
- Clonidine
- Arginine
- Insulin-induced hypoglycemia
- L-Dopa
- Propanolol
- BW q30-90 min after 2 agents, and look at GH levels.
- “Normal”: peak GH > 5,6,7 or 10 ng/mL (arbitrary)
