Endo Flashcards
What is CAH and how is it inherited? How may a child with CAH present?
CAH = Congenital Adrenal Hyperplasia
- -> autosomal recessive
- -> many forms, most common cause (90%) due to 21-hydroxylase enzyme deficiency
- -> most common non-iatrogenic cause of low cortisol and aldosterone secretion
Sx:
- Virilisation [more obvious in females - clitoromegaly, fusion of labia; males = enlarged penis and scrotum pigmented]
- Salt-losing crisis [often 1st sign in boys in week 1-3 of age; vomiting, weight loss, hypotonia, circulatory collapse]
- Tall stature (occurs in 20% of ‘non-salt’ losers)
- Excess androgens (muscular, adult BO, pubic hair, acne)
What are some other differentials for CAH?
DDx:
- 5-alpha reductase deficiency (XY) –> ambiguous genetalia but internal male organs present - increased testosterone at puberty virilises them (‘Penis at 12 syndrome)
- Androgen insensitivity syndrome (XY but phenotype XX) - feminisation with no internal male or female organs (often have 2 groin swellings/hernias that are undescended testes), delayed puberty
- CAH/21-OH deficiency (XX) - ambitious genetalia, salt losing crisis
- CAH/17-OH deficiency (XY) - feminisation, hypertensive (as this enzyme needed for testosterone synthesis but not cortisol/MR)
What Ix would you do for suspected baby with CAH?
Ix:
- Initially –> examine for ambiguous external genetalia and USS to examine internal genetalia
- Diagnostic = raised plasma 17a-OH progesterone [but cannot do in a newborn as influence by mothers levels]
- Bloods (show biochemical abnormalities e.g. low Na, high K, low HCO3 if metabolic acidosis, low glucose from low cortisol)
- Other confirming tests = karyotyping, high urea (dehydration), beta-HCG
How would you manage a child with CAH?
Mx:
- Corrective surgery for females (raised as girls as have uterus and ovaries but surgery often delayed until early puberty)
- Salt-losing crisis = IV hydrocortisone, IV saline, IV dextrose
Long term management:
- lifelong glucocorticoids (hydrocortisone to suppress ACTH and testosterone levels)
- MR (fludrocortisone) if salt-loss
- Monitoring of growth, skeletal maturity, plasma androgens and 17aOH progesterone levels
- Additional hormone replacement at times of illness/surgery (i.e. 2x hydrocortisone dose)
What is delayed puberty and who is it most commonly seen in?
When would you refer for faltering growth?
Delayed puberty -> absence of pubertal development by age 14 in males (lack of testicular development; <3/4ml) and lack of breast development by age 13/no menstruation by age 15
Most common cause in boys due to constitutional delay of growth and puberty (CDGP)
If faltering:
- if on 75th centile/+ then refer once centile downs by 3/+
- if between 25-75th then refer after 2/+ centile drops
- if <25th then refer after 1/+ drop in centile
What are some causes of delayed puberty?
Aetiology:
- > Functional (most common)
- e.g. CDGP (low bone age, no puberty signs and no organic causes, MALES»>females, usually a FHx
- chronic disease, malnutrition
- psychiatric - excessive exercise, depression, anorexia
- > Hypogonadotrophic (low FSH and LH)
- hypothalamo-pituitary disorders e.g. panhypopituitarism, Kallmann’s syndrome (LHRH deficiency + anosmia), Prader-Willi, hypothyroidism
- > Hypergonadotrophic (high LH and FSH)
- Congenital e.g cryptorchidism, Klinefelters, Turners
- Acquired - torsion, chemotherapy, AI, infection, trauma
What Ix would you do in delayed puberty?
Ix:
- Initial examination –> dysmorphic features, Tanner’s staging for girls, Prader’s orchidometer for boys and signs of disease
- Growth charting with height and weight, and plotting mid-parental height
- Bloods –> Gn dependent vs independent (LH, FSH) - GnRH stimulation given if under 12y; + TSH, Prolactin, testosterone
- Imaging - bone age from wrist XR, MRI brain,
How would you manage a child with delayed puberty?
Mx:
- CDGP = most don’t need treatment, 1st line is to reassure and offer observation, 2nd line = short course of sex hormone therapy (boys = IM Testosterone every 6w for 3-6 months; girls = 3-6mo oral estradiol (transdermal/oral-BMJ)
- Primary testicular/ovarian failure = boys require regular testosterone injections, girls get oestrogen replacment and cyclical progesterone once established cycles
- ++ Address psychosocial concerns ! (Referral to specialist also)
What is the difference between early normal puberty and precocious puberty?
Early normal:
- > Girls = 8-10y
- > Boys = 9-12y
Precocious:
- > Girls = <8y
- > Boys = <9y
What is puberty defined as in i) girls and ii) boys? What are the Tanner stages?
note: girls order = boobs, pubes, grow, flow
i) Girls:
Breast development - Tanner’s staging
1 = flat chested
2 = buds appear
3 = breast elevation, conical -> rounder shape
4 = areolar mound, menstruation within 2y of this age
5 = adult breast development
ii) Boys:
Testicular development >4ml (Prader’s orchidometer)
What are some causes of precocious puberty?
Causes:
- > Gonadotrophin-dependent (GDPP)
- premature activation of the HPG axis
- idiopathic, CNS disorders (tumours/trauma/congenital causes)
- > Gonadotrophin-independent (GIPP) - 20% of PP
- early puberty from increased gonadal activation independent of HPG
- Ovarian = follicular cyst, granulose cell tumour, leydig cell tumour, gonadoblastoma
- Testicular = leydig cell tumour, familial testoxicosis (defective LH-R function)
- Adrenal = CAH, Cushing’s
- Tumours = bHCG secreting of the liver, ovarian, testes, adrenal
- McCune-Albright syndrome (multiple endocrinopathy of thyrotoxicosis, bushings, acromegaly - Sx include cafe au last spots, ovarian cysts)
- Exogenous hormones (COCP, testosterone gels)
- > Benign isolated precocious puberty
- usually self-limiting
- e.g. premature thelarche (breast development before 8y; usually 6m-2yo), absent other pubertal signs and normal growth
- e.g. premature pubarche/adrenarche (isolated pubic hair development before 8yG/9yB) due to early adrenal androgen secretion in middle childhood, common in Asian/Afro-Caribbean
- e.g. premature menarche before 8y
What investigations would you do in a child with suspected precocious puberty?
Ix: > Females (normally not of concern) - Pelvic USS - showing multi cystic ovaries and enlarged uterus typical of premature onset of puberty - rule out gonadal tumour, cysts - Growth chart + examine
> Males (organic cause)
- examine testes
- MRI for cranial tumours
- GnRH-stimulated LH/FSH
GOLD STANDARD test = GnRH stimulation test (will show if GIPP or GDPP on whether LH/FSH is suppressed or not)
+++
-> WRIST XR
-> General hormone profile i.e. oestrogen, testosterone
-> Urinary 17-OH progesterone if CAH suspected
note:
- CAH = initial growth then premature bone fusion (tallest –> shortest in class), NORMAL LH/FSH
- GDPP = Bilateral enlargement of tests
- Gonadal tumour = Unilateral enlargement
- Small testes = adrenal tumour/CAH
How would you manage a child with precocious puberty?
Mx:
- Referral to paediatric endocrinologist
- If GDPP with no underlying pathology then often no treatment is required (90% females have no identifiable cause)
GDPP
- -> exclude neoplasms
- -> GnRH agonists e.g. leuprolide –> overstimulate pituitary and arrest puberty due to desensitisation
- -> GH therapy as GnRH agonists^ can stunt growth
- -> Cryptoterone, anti-androgen, can be given by specialists to suppress peripheral androgen action
GIPP
- -> exclude neoplasms
- -> CAH = hydrocortisone + GnRH agonist
- -> McCune-albright or Testotoxicosis = 1st line Ketoconozole or cryptoperone, 2nd line = aromatase inhibitors
What are skeletal dysplasias and what are its aetiologies/pathophysiology? How is it inherited/occuring?
Skeletal Dysplasia = 350+ disorders leading to various degrees of dwarfism. Most commonly due to achondroplasia (normal length thorax but small limbs) and hypochondroplasia (small stature, micromelia/small extremities and large head)
note: dwarfism = height <2.5 SD below mean
Aetiology:
-> Achondroplasia, Hypochondroplasia = FGFR3 mutations causing severe bone shortnening
Achondroplasia is the most common form of SD; autosomal dominant but 70% are sporadic mutations in FGFR3
- > Turners, Klinefelters = short stature homeobox gene defects (T=1 less SHOX=short, K=>2SHOX genes=tall) - risk factor is increasing parental age at conception
- > Osteogenesis imperfecta = blue sclera, short stature, loose joints, hearing loss, breathing problems. 7 forms; type 1 is most common due to abnormal pro-alpha 1/2 collagen polypeptides
How may a child with achondroplasia present?
Sx:
- Short stature, shortening of limbs +/- HYDROCEPHALUS
- depression of nasal bridge
- marked lumbar lordosis
- large head, frontal bossing
- trident hands
