Endocrinology Flashcards
Define short stature
Height more than 2 standard deviations below the average for their age & sex/ height below the 2nd centile for their age & sex
(this is the same as being below the 2nd centile. Remember centile space is 2/3 of standard deviation so 3 centile spaces is 2 standard deviations. Centiles are 0.4th, 2nd, 9th, 25th, 50th, 75th, 91st and 99.6th. Average heigh tis the 50th centile so 2 standard deviations below is 3 centiles below the 50th centile which is the 2nd centile)
State some potential causes for short stature
- Familial short stature
- Constitutional delay in growth & development
- Malnutrition
- Chronic diseases e.g. coeliac disease, IBD, congential heart disease
- Endocrine disorders e.g. hypothyroidism, growth hormone deficiency
- Genetic conditions e.g. down syndrome
- Skeletal dysplasia e.g. achondroplasia
For constitutional delay in growth & puberty, discuss:
- What it is
- How it presents
- Key feature
- Diagnosis
- Management
- CDGP is a variation of normal development; puberty is delayed hence the pubertal growth spurt is delayed and lasts longer. It is the delay in puberty that causes the delay in the growth spurt. Final height & sexual development are reached at a later age.
- Presents with short stature in childhood but child evnetually reaches a normal height in adulthood
- Key feature= delayed bone age
- Diagnosis is by history, examination & x-ray of hand & wrist to assess bone age
- Managment= exclusion of other causes (it is a diagnosis of exlcusion), reassuring parents and child, monitoring overtime
When does puberty start in:
- Boys
- Girls
How long does it take to finish?
- Boys starts aged 9-15yrs
- Girls starts aged 8-14yrs
Puberty usually takes about 4yrs from start to finish
Discuss the order of puberty-related changes in girls
- Thelarche (development of breast buds)
- Pubic hair growth
- Growth spurt
- Menarche (about 2yrs from start of puberty)
- Pubic hair adult
- Breast adult
Discuss the order of puberty-related changes in boys
- Enlargement of testes
- Gradual darkening of scrotum
- Development of pubic hair, lengthening of penis and deepening of voice
- Growth spurt (including development of more muscular physique)
- Genitals conitnue to enlarge
- Adult pubic hair, growth of faical hair
What staging can be used to determine pubertal stage?
Tanner scale (based pm examination findings of sexual characteristics)
Discuss tanner staging for girls
For girls, look at both breast development & pubic hair. Stage 1-5:
Breast Development
1: No glandular breast tissue
2: Breeast bud
3: Breast tissue palpable outside areola
4: Areolar elevated forming ‘double scoop’ appearance
5: Areolar mound recedes back with areolar hyperpigmentation, papillae development & nipple protrusion
Pubic Hair
1: No hair
2: Initial growth of long, straight and lightly coloured hairs
3: Pubic hair is s becomes darker, coarser, curlier and spread scarcely over mons pubis
4: Abundant adult type pubic hair (terminal hair) over mons
5: Adult pubic hair distribution- classic traingle. Some may have hair that extends beyond inguinal crease onto medial thigh
Discuss tanner staging for boys
For boys, look at both male external genitalia and pubic hair. Stages 1-5:
Male external genitalia
1: Testicular volume <4ml or long axis <2.5cm
2: Enlargement of scrotum & testes so that testicular volume is >/= 4ml. Penis may have grown a little in length.
3: Testes continue to enlarge, penis grown in length
4: Testes continue to enlarge, penis grown in both length & width. Head of penis become larger.
5. Adult sized & shaped penis & testes
Pubic hair
1: No hair
2: Initial growth of long, straight and lightly coloured hairs at root of penis
3: Pubic hair is s becomes darker, coarser- mostly at the root of penis
4: Abundant adult type pubic hair (terminal hair) which reaches thights
5: Adult pubic hair distribution with hair extending up towards umbilicus & may spread to medial thighs
Hypogonadism can cause a delay in puberty; define hypogonadism
Lack of sex hormones, oestrogen & testosterone/decreased functional activity of gonads
Hypogonadism can be:
- Hypogonadotrophic hypogonadism
- Hypergonadotrophic hypogonadism
… describe each
- Hypogonadotrophic (secondary) hypogonadism: deficiency of LH & FSH
- Hypergonadotrophic (primary) hypogonadism: lakc of response to LH & FSH by the gonads (ovaries & testes)
For hypogonadotrophic hypogonadism, discuss:
- How it leads to hypogonadism
- Some potential causes of hypogonadotrophic hypogonadism
GnRH (gonadotrophin releasing hormone) is release by hypothalamus and stimulates the anterior pituitary to release LSH and FSH. LH and FSH are gonadotrophins which stimulate the gonads to produce sex hormones. Deficiency of either GnRH or LH and FSH can lead to decreased sex hormones.
Occurs due to either abnormal functioning of the hypothalamus or the pituitary:
- Damage to hypothalamus or pituitary (e.g. radiotherapy for cancer, injury,. tumour)
- Growth hormone deficiency
- Hypothyroidism
- Hyperprolactinaemia
- Congenital e.g. Kallman syndrome
- Chronic disease e.g. cystic fibrosis, IBD
- Functional e.g. inadequate nutrition/rapid weight loss/eating disorders
For hypergonadotrophic hypogonadism, discuss:
- How it leads to hypogonadism
- Some potential causes of hypergonadotrophic hypogonadism
GnRH, LH and FSH are released as they should be but the gonads show a lack of response to the gonadotrophins LH & FSH. There is no negative feedback from the sex hormones hence anterior pituitary produces increasing amounts of LH & FSH in attempt to stimulte the gonads hence you get high levels of gonadotrophins (hypergonadotrophic).
Occurs due to abnormally functioning gonads:
- Damage to gonads (e.g. testicular torsion, cancer, infections such as mumps)
- Congenital absence of testes or ovaries
- Kleinfelters syndrome (XXY)
- Turner’s syndrome (XO)
Remind yourself what Kallman syndrome is
Genetic syndrome causing hypogonadotrophic hypogonadism and an impaired (reduced or absent) sense of smell
Remind yourself what Turner’s syndrome is
Female only genetic disorder in which child only has 1 X chromosome (as opposed to 2); hence karyotype is XO. Ovaries do not complete normal development and hence there is a lack of oestrogen resulting in hypergonadotropic hypogonadism. Treat with HRT. See image for characteristics.
Remind yourself what Kleinfelter’s sydnrome is
Boys are born with extra X chromosome so have karotype XXY. Symptoms & signs:
- History of delayed early development
- Delayed puberty
- Tiredness
- Reduced muscle tone
- Gynaecomastia
- Taller than expected with long arms & legs
- Broad hips
- Reduced facial & body hair
- Small penis & testicles
- Subfertility
At what age would you be concerned an start investigations for delayed puberty in:
- Girls
- Boys
- Girls: 13yrs
- Boys: 14yrs
Discuss what investigations you may consider if you suspect delayed puberty; for each state why
Blood Tests
- FBC & ferritin: assess for anaemia (severe chronic anaemia can lead to delayed growth)
- U&E: asses for CKD (can delay and blunt affects of puberty)
- Anti TTG or anti EMA: assess for coeliac disease as can delay puberty
- Early morning FSH & LH:asses if hypergonadotropic or hypogonadotropic
- TFTs: hypothyroidism can delay puberty
- Prolactin: prolactin inhibits GnRH release so can cause hypogonadotropic hypogonadism
- Insulin-like growth factor: assess for GH deficiency as can delay puberty
Imaging
- X-ray of wrist: asses bone age to make diagnosis of CDGD
- Pelvic ultrasound: asses ovaries in females
- MRI brain: asses for pituitary pathology & olfactory bulbs (in possible Kallman syndrome)
Genetic testing
- E.g. for Turner’s syndrome (XO), Kleinfelter’s syndrome (XXY)
Briefly discuss the management of delayed puberty
Depends on cause but may include:
- Treat the underlying condition (if present)
- If CDGP, reassure and monitor
- Replacement sex hormones under expert guidance
- Growth hormone supplementation in some conditions such as Turner’s syndrome
State some examples of developmental screening/assessment tools
- Ages & Stages questionnaire
- Denver developmental assessment and schedule of growing skills
- Bayley and Griffiths
What is the role of growth hormone in children?
- GHRH stimulates GH release from anterior pituitary, GHIH/somatostatin inhibits GH release from anterior pituitary
- Exerts direct effects as GH; exerts indirect effects as it stimulates production of insulin-like growth factor (also called somatomedins, IGF1 & IGF2) in liver
- GH & IGF stimulates cell production and growth of organs, bones & muscles in children.
*NOTE: in adults GH is important for maintaining muscle & bone mass, healing & repair and modulating metabolism and body composition
State some congenital causes of GH deficiency
State some acquired causes of GH deficiency
Congenital
- Genetic mutation in GH1 (growth hormone 1) gene
- Genetic mutation in GHRHR (growth hormone releasing hormone receptor) gene
- Empty Sella syndrome (pituitary gland is under-developed or damaged)
Acquired
- Infection
- Trauma
- Surgery
GH deficiency can occur in isolation or in combination with other pituitary hormone deficiencies e.g. hypothyroidism, adrenal insufficiency, gonadotrophin deficiencies; what is it called when pituitary does not produce a number of pituitary hormones?
Hypopituitarism
Describe presentation of GH deficiency in:
- Neonates/at birth
- Infants & children
Neonates/at birth
- Micropenis (males)
- Hypoglycaemia
- Severe jaundice
Infants/children
- Poor growth (usually stopping or severely slowing from ages 2-3)
- Short stature
- Slow development of movement & strength
- Delayed puberty
Explain why GH deficiency can cause hypoglycaemia in neonates/at birth
GH stimulates glycogenolysis and lipolysis hence deficiency can result in hypoglycaemia
What investigations could you do to confirm GH deficiency?
What other investigations may you do aswell?
To diagnose GH deficiency:
- Serum IGF-1
- Growth hormone stimulation tests (measure the response to medications that normally stimulate the release of growth hormone e.g. glucagon, insulin, arginine and clonidine. GH levels are monitored regularly for 2-4 hours after to assess the hormonal response. In GH deficiency there will be a poor response to stimulation. Insulin tolerance test is definitive test for GH-IGF1 axis.
Others:
- Test other deficiencies e.g. TFTs, cortisol
- MRI brain (structural abnormalities of pituitary or hypothalamus)
- X-ray of wrist to determine bone age & predict final height
- Genetic testing for associated conditions e.g. Turner syndrome, Prader-Willi syndrome
Discuss the management of GH deficiency
Managed by paediatric endocrinologist:
- Daily SC injections of GH hormone (somatropin) at bedtine
- Treatment of other associated hormone deficiencies
- Treatment of underlying cause (e.g. if a tumour)
- Close monitoring of height & development
What is gigantism?
Condition due to excess growth hormone in children (before epiphyseal growth plates have fused) which causes excessive growth in height, muscles & organs making child large for their age.
State some signs & symptoms of gigantism
- Tall stature
- Generally large for their age
- Delayed puberty
- Prominent forehead
- Prominent jaw
- Large hands and feet with thick fingers & toes
- Headaches
- Sweating
- Weakness
- Visual disturbances (e.g. double vision or reduced peripheral vision)
State some potential causes of gigantism- highlighting most common one
- Benign pituitary tumour
- Caused by conditions that may cause pituitary tumour:
- MEN-1
- Carney complex
- McCune-Albright syndrome
- Neurofibromatosis
What investigations would you do for gigantism?
- Plasma IGF1 levels: high
- Oral glucose tolerance test (glucose ingestion should lower GH levels): GH levels not lowered in gigantism
Discuss the management of gigantism in children
- Surgery to remove tumour
- Medications
- Somatostatin analogues e.g. ocreotide
- GH receptor antagonist e.g. pegvisomant
- Dopamine agonists to block GH release e.g. bromocriptine
- Radiation therapy
State some potential complications of gigantism
- Delayed puberty
- Diabetes
- Sleep apnoea
- Hypertension
Why is it so important to recognise and treat hypothyroidism in neonates, infants & children?
Thyroxine important for brain growth & development therefore hypothyroidism can lead to problems with neurodevelopment and intellectual disability
What is congenital hypothyroidism?
State 2 potential causes
Born with underactive thyroid; can be due:
- Dysgenesis (an underdeveloped thyroid)
- Dyshormonogenesis (a fully developed thyroid gland that doesn’t produce enough hormone)
Hypothyroidism in neonates/infants/children can be congenital or acquired; what is congenital hypothyroidism and state two potential causes/reasons.
How many babies born with congenital hypothyroidism per year?
Born with underactive thyroid; can be due:
- Dysgenesis (an underdeveloped thyroid)
- Dyshormonogenesis (a fully developed thyroid gland that doesn’t produce enough hormone)
*around 1 in 3500 babies born with congenital hypothyroidism in UK
Congenital hypothyroidism is screened for on the newborn blood spot screening test; however, if it is not picked up at birth how may it present?
- Prolonged neonatal jaundice
- Poor feeding
- Constipation
- Increased sleeping
- Reduced activity
- Slow growth & development
**NOTE: test measures TSH and/or thyroxine (T4). If baby is born early may not make enough TSH to give an out of range result so may not be diagnosed on blood spot screening test
What is acquired hypothyroidism?
What is the most common cause? State some other causes.
- Child or adolescent develops underactive thyroid when it was previously functioning normally
- Most common cause= autoimmune hypothyroidism (Hashimoto’s thyroiditis). Other causes: iodine deficiency (developing world), post total-body irradiation (e.g. if treated for leukaemia)
*There is an association with other autoimmune disorders e.g. T1DM, coeliac
Describe typical presentation of hypothyroidism in children & adolescents
- Fatigue/low energy
- Poor growth
- Weight gain
- Constipation
- Dry skin
- Hair loss
- Poor school performance (impaired concentration)
Discuss the management of hypothyroidism in children
Levothyroxine once a day (doses titrated based on TFTs and symptoms). Managed by a paediatric endocrinologist.
State some potential consequences of untreated hypothyroidism in neonates/infants/children
- Can lead to cretinism
- Mental retardation
- Deafness
- Short stature
- Anaemia
- Heart failure
What is rickets?
What is it caused by?
- Rickets= condition affecting children that causes soft and deformed bones; deficient mineralisation at the growth plate of long bones results in growth retardation.
- Caused by vitamin D or calcium deficiency
Discuss the pathophysiology of rickets
- Activated vit D (calcitriol):
- Promotes absorption calcium & phosphate in intestinges
- Increases renal phosphate reabsorption
- Acts on bone to cause release of calcium & phosphate
- Hence, vit D deficiency results in calcium deficiency
- Calcium and phosphate are required for bone construction hence low levels result in defective bone mineralisation
- Low calcium also causes secondary hyperparathyroidism stimulating increased reabsorption of bone
- Leading to soft bones which can then become deformed
For insulin pumps, discuss:
- What they are
- How they work
- Who can qualify for one
- Advantages & disadvantages
- Two different types
- Small devices that continually infuse insulin at different rates to control blood sugars (alternative to basal bolus regime)
- Pump infuses insulin through SC cannula which is replaced every 2-3 days (site rotated to prevent lipodysrophy)
- To qualify: >12yrs and have difficulty controlling HbA1c
- Advantages: better glucose control, more flexibility with eating, less injections
- Disadvantages: have to learn to use pump, attached all time, blockages in infusion set, risk of infection
- Types:
- Tethered: devices with replaceable infusion sets & insulin. Control on pump
- Patch pumps: sit directly on skin without any visible tubes; when they run out of insulin who pump is disposed of and new one attached. Control on separate remote.
Remind yourself of pathophysiology of DKA
- Insulin usually drives K+ into cells so get hyperkalaemia.
What investigations would you do for diabetes insipidus?
- Plasma osmolarity: high
- Urine osmolarity: low
- Water deprivation test: pt should avoid fluids for 8hrs; then urine osmolarity is measured (would expect it to be high but in DI it is low). Then give desmopressin (synthetic ADH) and measure urine osmolarity again 8hrs later.
