Endo & Growth Flashcards
what is the MOST common cause of precocious puberty in girls?
Idiopathic
presents just like normal puberty
what is the staging for puberty?
Tanner staging
What are the outcomes of premature therlache?
Persists
Regresses
Does NOT progress to precocious puberty (eg secondary sexual characteristics)
what is the best immediate diagnostic measure to test for CAH?
17aOH progesterone levels (though this condition itself is a defficiency of 21 alpha hydroxylase)
random level AND 72hour levels
Why is CAH called CAH?
deficiency of end hormones leads to overstimulation of adrenal gland by ACTH = hyperplasia of the adrenal glands! (+ excess androgens)
what is CAH?
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis.
It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex.
Most of these disorders involve excessive or deficient production of such hormones as glucocorticoids, mineralocorticoids, or sex steroids, and can alter development of primary or secondary sex characteristics in some affected infants, children or adults.
It is one of the most common autosomal recessive disorders in humans
what is the most common cause of a disorder of sexual development?
CAH
which are the most deficient hormones in CAH?
More than 90% show a deficiency of 21-hydroxylase – needed for cortisol
- 80% are unable to produce aldosterone – leading to decreased Na and increased K (hyperkalaemia)
- Cortisol deficiency stimulates pituitary to increase ACTH → overproduction of adrenal ANDROGENS
How does CAH present?
Classic forms:
- Simple-virilising 25%: Virilization (masculinisation) of external genitalia in female infants → clitoromegaly and variable fusion of labia ( +ambiguous gentialia)
• In males → enlarged penis, pigmented scrotum
-> if not identified and treated they will grow rapidly and have more virilisation:
present tall, muscular, pubic hair, acne, precocious puberty
• Boys - enlarged penis, small testes
• Girls - abnormal or absent periods, facial hair
2• Salt-wasting: in 75% of cases of severe enzyme deficiency, insufficient aldosterone production can lead to salt wasting, failure to thrive, and potentially fatal hypovolemia and shock.
The missed diagnosis of salt-loss CAH is related to the increased risk of early neonatal morbidity and death.
Non-classic:
1. The non-classic form is characterized by mild subclinical impairment of cortisol synthesis; serum cortisol concentration is usually normal.
presentation : late in childhood, accelerated growth, premature sexual maturation
what causes the hypoglycaemia in CAH?
cortisol deficiency
what ivx do we conduct for CAH and what are the findings?
In classic 21-hydroxylase deficiency, laboratory studies will show:
Increased 17α-hydroxyprogesterone in blood (precursor for deoxycortisol so cortisol)
- random and 72 hour levels
• ↑ testosterone, progesterone, adrenal androgen precursors
U&Es -> • In salt losers → low Na, high K, metabolic acidosis, (as aldosterone is low),
Blood glucose - > hypoglycaemia
If virilisation:
Karyotype with fluorescent in situ hybridization (FISH) for sex-determining region of the Y chromosome
how does a Salt losing adrenal crisis present?
→ aged 1-3w MALE
-> salt losers
→ vomiting, weight loss, floppiness, circulatory collapse ± arrhythmias, dehydration and hypoglycemia
what is the mx AND follow up of CAH?
Mx:
• MDT involving endocrinologists, urologists and paeds
• Female
o Corrective surgery to external genitalia if required
- there is a debate surrounding gender assignment
- Lifelong glucocorticoids (hydrocortisone) to suppress ACTH and testosterone
- Mineralocorticoids (fludrocortisone) if there is salt loss
Regular blood tests → monitoring of growth, skeletal maturity, plasma androgens, 17α-hydroxyprogesterone to allow adjustment of steroid replacement doses
- Additional hydrocortisone to cover periods of illness or surgery
- Child may have short stature so may benefit from GH replacement
- Males usually have normal fertility but females may have problems conceiving so may need additional help
what is the mx of a salt losing crisis?
• Male
o Salt losing adrenal crisis → saline, dextrose, IV hydrocortisone
what is the 2nd most common enzyme deficiency in CAH?
what would ivx show?
11β-Hydroxylase CAH (5%)
ivx would show increased 11-Deoxycortisol as it catalyses the conversion of 11-Deoxycortisol→DOC
define delayed puberty?
the lack of any pubertal signs by 14 years in boys (m = no testicular development)
and 13 years (f = no breast development) or 15 (no periods).
what are the CAUSES OF DELAYED PUBERTY?
- Constitutional delay – commonest
short stauture because of a delay in the onset
of puberty - LOW Gonadotrophin secretion = Hypogonadotrophic hypogonadism
a. Systemic disease – CF, severe asthma, Crohn’s, organ failure, anorexia nervosa, starvation, XS exercise
b. Hypothalamo-pituitary disorders – panhypopituitarism, intercranial tumours, Kallmann syndrome (LHRH deficiency and anosmia), isolated gonadotrophin or GH deficiency
c. Acquired hypothyroidism
- Failure of end organ with HIGH Gonadotrophin secretion = Hypergonadotrophic hypogonadism
a. Chromosomal abnormalities – Klinefelter’s 47XXY, Turner’s 45 XO
b. Steroid hormone enzyme deficiencies
c. Acquired gonadal damage – post-surgery, chemo, radio, trauma, torsion of testes, AI disease
what is the aetiology of Constitutional delay?
Majority simple constitutional delay - late bloomers - not requiring detailed investigation
- More common in males
- Often familial – usually FHx of same in parent of same sex
• Also associated with dieting and XS exercise
• Children are short during childhood, delay in sexual maturation and delayed skeletal maturity
delayed bone age
• Legs are long in comparison to back
how do we ivx constitutional delay or delayed puberty?
- Height and weight of child - plot on growth curve
- Compare to mid-parental heights
- Assess for features of malnutrition
- Assess for features of disproportion eg webbed neck, longer legs (kleinfelter)
- Cranial nerve and neuro exams - identify brain tumours, anosmia - kallmans
Boys → pubertal staging - Tanners (testicular volume), Karyotype (Kleinfelters)
• Girls → Karyotype (Turner’s), thyroid and sex steroid hormone levels
Also:
- Non dominant wrist xray: delayed bone age
- Blood - basal FSH,LH (low in HypoHypo, High in gonad disease)
- LHRH stimulation test
• Use LHRH to stimulate gonadotrophins then measure LH and FSH
TFTs → if hypo
• Also ask for prolactin
Consider MRI brain for structural causes eg tumours
- Look for signs of chronic disease, dysmorphia, plot height and weight, calculate mid-parental height
- Can only diagnose once other causes have been eliminated
how do we mx constitutional delay?
- Reassurance as treatment not usually required
- They will eventually reach their target height
Boys:
• Oral oxandrolone can be used (3-6 months) for catch up growth - but not secondary sexual characteristics.
- ONLY give if psychosocial distress present
- Can give testosterone - get 2ndary characteristics
- Females can be treated with oestradiol for same reason
- Consider need for psych input regarding bullying, body image, social etc
Pubertal development and progress are best assessed by ______ ?
Tanner staging
what are the signs of puberty in BOYS in order?
- The first sign of puberty in boys is an increase in the size of the testes. enlargement to over 4-mL volume
measured - This is followed by penile and scrotal changes.
- Growth of axillary + pubic hair and other changes, such as changes of the voice
Rapid height growth is next, occur in mid- to late puberty - (12 mL to 15 mL testicular volume) - 18 months post first sign of puberty
- Facial hair does not appear until late puberty.
Testicular size is documented as a measurement of the longest axis or by the testicular volume using the Prader orchidometer.
what are the signs of puberty in GIRLS in order?
The first demonstrable sign of puberty in girls is breast development (palpable breast disc).
Pubic and axillary hair, acne, and body odour develop as a result of androgens secreted from the adrenal gland. occur almost immediately after breast development
The peak growth spurt occurs in Tanner stage 3 breast development,
and menarche occurs in Tanner stage 4 breast development . Menarche occurs 2.5 years after the
start of puberty and signals that growth is coming
to an end, with only around 5-cm height gain
remaining
Caution must be exercised in examination of breast tissue in obese girls, as simple fat may be mistaken for breast tissue.
define puberty
Puberty = interval characterized by the acquisition of secondary sexual characteristics, accelerated linear growth, increase in secretion of sex hormones, maturation of gonads (testes in boys and ovaries in girls), potential for reproduction.
how do we treat delayed puberty of organic/permanent cause?
• Girls - Organic cause:
▪ Pubertal induction with oestrogen –
weekly transdermal patch of gradually increasing dose over 6 months to adult dose
- note : do NOT give COCPs instead!
▪ Cyclical progesterone after breakthrough bleeding or adequate oestrogenisation
o If Turners → give GH subcut daily ± oxandrolone
(until 12-14 y/o)
- If the diagnosis is made late, oxandrolone added to promote linear growth.
• Boys – organic cause
o Pubertal induction with testosterone – IM every 6 weeks for 6 months then increase dose and increase frequency until adult dose reached
-> side effects: hyper aggression and hyper sexuality for a few days post dose.
define precocious puberty
Premature sexual development is the development of secondary sexual characteristics before 8y in females and 9y in males
• Precocious puberty is when its accompanied by a growth spurt
what are the forms of precocious puberty?
Gonadotrophin dependent – central – from premature activation of HPA
o Gonadotrophin independent – pseudo – from autonomous excess sex steroid secretion
what is the aetiology of precocious puberty?
red flags?
FEMALES
• Most commonly due to premature onset of normal puberty - Idiopathic
- Abnormal or organic cause when there is dissonance (sequence of pubertal changes is abnormal - if the sequence is normal then should be normal)
- Red flags: Rapid onset, neuro symptoms or signs
MALES
• Most commonly has an organic cause eg abnormal
how do we ivx precocious puberty?
Females:
• IX → US of ovaries and uterus
o In premature onset of NORMAL puberty, multicystic ovaries and enlarging uterus will be identified (most common)
• Rule out gonadal tumour, cysts
Male:
• Examination of testes
o Bilateral enlargement → gonadotrophin release – usually intercranial lesion
o Small testes → adrenal cause → tumour or CAH
o Unilateral → gonadal tumour
• MRI for suspected intercranial tumour
- Non-dominant wrist x-ray to assess skeletal age
- Check basal LH/FSH, serum testosterone and oestrogen
- LHRH stimulation test – (suppressed LH/FSH if G-independent)
Gonadotrophin-dependent (↑LH > ↑FSH) Gonadotrophin-independent (↓FSH, ↓LH, Rare)
how do we mx precocious puberty?
- Gonadotrophin dependent disease
o Give GNRH analogues
o Only pulsatile exposure triggers pubertal progression, continuous exposure suppresses
o ± growth hormone if required
- Gonadotrophin independent
o Identify source of excess sex steroids and give androgen or oestrogen inhibitors
- Increased testosterone or McCune Albright → ketoconazole as inhibitor of steroid synthesis
- CAH → hydrocortisone + GNRH analogue
- Tumours → surgery
what is premature Adrenarche/Pubarche?
aetiology?
Ivx?
mx?
main differential?
- Pubic OR Axillary hair before 8y in females and 9y in males
- Along with NO other signs of sexual development
- May be slight increase in growth rate
An adult-type axillary body odor is the other major clinical finding.
Aetiology: weak androgens secreted by adrenals (this is NOT the usual steroids)
- Most commonly due to accentuation of normal maturation of androgen production by adrenal gland
- More common in Asian or Afro-C
• Usually self-limiting
Ivx:
Obtaining a urinary steroid profile,
Blood androgens levels
Bone age
• If more aggressive virilization – consider non-classical congenital adrenal hyperplasia or adrenal tumour (virilising tumour)
main differential - non-classical CAH, virilising tumour
what are the recognized patterns of premature
sexual development ?
• precocious puberty
• premature breast development (thelarche)
• premature pubic hair development (pubarche or
adrenarche)
• isolated premature menarche.
what are the complications of premature Adrenarche/Pubarche?
Girls who develop premature pubarche are
at an increased risk of developing polycystic ovarian
syndrome in later life.
how does premature thelarche present?
ivx and mx?
This usually affects females between 6 months
and 2 years of age.
The breast enlargement may be asymmetrical and fluctuate in size, rarely progressing beyond stage 3 of puberty.
It is differentiated from gonadotrophin-dependent precocious puberty by the absence of axillary and pubic hair and of a significant growth spurt.
It is nonprogressive and self-limiting. Investigations are not usually requiredq
what is the aetiology and clinical presentation of Achondroplasia?
- Most common type of skeletal dysplasia
- Auto dom but 80% sporadic mutations
- Caused by mutation in fibroblast growth factor receptor 3 – FGFR3
Clinically: • Short stature, shortening of limbs • Large head, frontal bossing, depression of nasal bridge • Short, broad hands • Marked lumbar lordosis • ± hydrocephalus
what is the ivx and mx of Achondroplasia?
Not apparent until more than 22w GA so may be missed
• Diagnosis made by clinical features and XR findings;
o Metaphyseal irregularity, flaring in long bones, late-appearing irregular epiphyses
• Full skeletal survey ± confirmatory molecular analysis
identifying disproportionate short stature
• sitting height – base of spine to top of head
• subischial leg length – subtraction of sitting height
from total height
Management:
- Regular follow up to detect complictions;
- Gross motor skill delay, kyphosis, early osteoarthritis, risks from hydrocephalus, obesity, ENT issues
- No evidence of benefit from growth hormones
- Final height varies from 80cm to 150cm
• use Condition specific centile charts
what is Prepubertal vaginal bleeding / “premature menarche”?
Aetiology?
Ivx and mx?
When a girl with little or no breast development has vaginal bleeding, this causes great concern for parents and providers.
This condition, sometimes referred to as “premature menarche,” has been well-described in the literature, although its cause is unknown.
Studies show that hormonal levels are prepubertal, and pelvic ultrasonography shows a prepubertal uterus and ovaries.
The bleeding can occur monthly but resolves in a few months, so reassurance and watchful waiting are often the best course. In persistent cases, a foreign body such as toilet paper may be found on pelvic exam.
when bone age < constitutional age but
growth velocity is normal
what is the cause?
constitutional delay aka late bloomers
when bone age < constitutional age but
growth velocity is ABnormal
what is the cause?
chronic illness
malnutrition
endocrine
when bone age = constitutional age but
growth velocity is ABnormal
what is the cause?
genetic
person is short
when bone age = constitutional age but
growth velocity is normal
what is the cause?
familial short stature - ALL family members are short
=
be sure to rule out skeletal dysplasia
