CAH, hypothyroidism and delayed puberty Flashcards
What is CAH?
Congenital adrenal hyperplasia - Inherited disorder of adrenal steroidogenesis
What is the aetiology of CAH?
AR genetic defect in p45 0 enzymes for steroidogenesis. This unbalances both the hormone in affected pathway and in the other steroid pathways. Buildup of precursor may also harm (i.e. 11-deoxycorticosterone has MC effects at high conc).
21a hydroxylase 90%, 11B hydroxylase 5% and 17a hydroxylase 5%.
Ganas involved CYP21A/CYP17A/CYP11B. Adrenal hyperplasia on histology
What is the epidemiology of CAH?
1/10k for 21, 1/100k for 11/17.
What would you find in history or exam of someone with CAH?
21:
· Male classic (total 21aHO deficiency): present at 1/12 with failure to thrive, severe vomiting, hyperkalaemia, hyponatraemia and dehydration. Death if untreated.
· Male non-classic (partial 21aHO deficiency) present at adolescence with early puberty and development of II Sex characteristics due to compansatory increase in testosterone
· Female classic: ambiguous genitalia, clitoromegaly, fused labia at birth.
· Female non classic: virilisation, hirtuitism, high skeletal growth.
11BHOXD: buildup deoxycorticosterone, which can act at MR in high concentrations. There fore salt losing crisis, and HTN.
17aHOXD: buildib 11deoxycorticosterone with strong MC effects, low androgens, therefore HTN and high K/low Na, ambiguous genitalia.
What investigations do you do for CAH?
Bloods: 17-OH progestrone (high in 12/11) testosteone, basal ACTH/FSH/LH
ACTH stimulation test: inappropriately elevated 17OH progestrone after test.
USS: presence of ovarian pathology. Genetic analysis and karyotype.
What is the management of CAH?
Acute salt losing crisis: IV fluid 0.9%NaCl, 20ml/kg over first hour and repeat if necessary, dextrose and hydrocortisone.
Medical: oral hydrocortisone and fludrocortisone. Increase dose when unwell May supplement NaCl.
Surgical for genitalia, genetic counselling.
What are the complications and prognosis of CAH?
Low female fertility. Ambiguous genitalia. Salt losing crisis.
Good if diagnosed early. If not, die form salt losing crisis.
What is congenital hypothyroidism?
Deficiency of T4 at birth which, if untreated, leads to severe delay.
What is the aetiology of Congenital hypothyroidism?
· Thyroid dysgenesis (85%) agenesis, ectopic thyroid, or hypoplasia
· Thyrod dysmorphogenesis (10%) genetic defects in active I transport, hormone synthesis or secretion. Pendred syndrome (thyroglobulin).
· Maternal transmission (5%) transplacental passage of antithyroid drugs or AI disease Abs, or radio iodine.
· Central hypothyroidism: failure of TSH production, hypothalamic or pitiutary defect.
· Thyorid hormone resistanc: mutation in thyroid receptor B gene.
Associted with Syndromes (diGeorge?)
What is the epidemiology of congenital hypothyroidism?
1/3500 births.
What would you find in the history of a patient with congenital hypothyroidism?
Neonatal: asymptomatic due to transplacental T3/4 passage. Increasingly poor feeding, constipation, lethargic, jaundice, thick skin, hypothermia, bradycardia.
Infant: first sign is prolonged neonatal jaundice. Then have other hypothyroid symptoms and severe delay.
What is found in the examination of someone with congenital hypothyroidism?
Coarse dry hair, flat nasal bridge, portruding tongue, slow waxing reflexes. Slow pulse. Developmental delay then ensues if untreated, global, delayed puberty and dentition, short stature, sensorineural hearing loss.
What investigations would you do for congenital hypothyroidism?
Neonatal screening: heel prick test at 5-7/7. Guthrie for TSH level (>50ug/l is diagnostic).
Bloods: low T4, high TSH, low Hb, unconjugated BR high.
Wrist and hand XR: bone age lower than chronological age. ECHO for cardiomegaly.
Radioactive Tc scan: detects functional thyroid tissue (ectopic/dysgenesis/resistance?).
What is the management of congenital hypothyroidism?
Thyroxine replacement: PO sodiumLthyrozine (10-15ug/d).
Regular follow up to monitor TSH/T4 levels to adjust dose, monitor bone growth and development.
What are the complications/ Prognosis of congenital hypothyroidism?
Excessive tx leads to hyperthyroid, advance bone age and therefore fuse epiphyses -> short. Too little tx leads to neuro delay. Pgx good with early deteciton and adequate tx. May have some loss of intelligence but very mild.
