Which type of adrenal insufficiency more likely to have mineralocorticoid deficiency, primary or secondary?
primary more likely to have mineralocorticoid deficiency
Primary also have increased ACTH level (and remember how it leads to hyper pigmentation) , abnormality is of the adrenal gland
secondary - hypothalamic or pituitary dysfunction, low cortisol with inappropriately normal or low ACTH, normal mineralocorticoid production (therefore less likely to have electrolyte abnormalities and hypovolemia)
Ddx of primary adrenal insufficiency
- enzymatic defects: CAH, congenital adrenal hypoplasia
- autoimmune disease - autoimmune polyendocrinopathy syndromes (APS I and II), Schmidt
- infectius disease: TB, meningococcemia, disseminated fungal infections
- trauma: bilteral adrenal hemorrhage
- adrenal hypoplasia
- iatrogenic - exogenous steroids
Most common causes of secondary adrenal insufficiency?
hypothalamic/pituitary poor development - timor, CNS trauma, irradiation, infection or surgery
congenital adrenal hyperplasia - most common mutation
21 hydroxylase deficiency most common and partial forms
equal in males and females
late onset form - in teens with hirsutism and menstrual irregularities
girls more likely to be diagnosed early since they will have ambiguous genitalia (whereas male will have normal male genitalia)
What is the recommended physiologic and stress dosing of oral hydrocortisone?
physiologic: 12-15 mg/m2/24 hours
stress dosing: 50-100 mg/m2 /24 horus of hydrocortisone
doses >50 mg/m2/24 hours are generally pharmacologic doses (not used for adrenal replacement or stress dosing
How long of using steroids is likely to cause adrenal insufficiency?
> 30 days high risk of prolonged or permanent adrenal suppression
vs <10 days relatively low risk
Causes of hypercalcemia
high 5 Is
- H- hyperparathyroidism - familial, isolated, syndromic
- Idiopathic - Williams syndrome (also have SV AS and pulmonary artery stenosis)
- Infantile - subcutaneous fat necrosis, maternal hypoPTH
- Infection - TB
- Infiltration - malignancy, sarcoidosis
- Ingestion - milk-alkali, thiazide diuretics, vitamin A, vitamin D
- S - skeletal disorders - hypophosphatasia, immobilization, skeletal dysplasia
menarchal 9 year old, parents are concerned about her height, which investigation to do?
bone age will help predict adult height (but we know it is likely advanced if she has her period)
once people have their period we tell them they will grow another 5 cm and you will grow for another 2 years
Short stature
decide if normal variant or pathologic (based on growth velocity and target height) normal growth velocity is 5 cm/year
if normal - then familial short stature or constitutional delay (should have delayed bone age for constitutional)
pathologic: proportionate (prenatal (IUGR, dysmorphic syndromes, chromosomal disorders) /postnatal (meds)and disporportionate
how to do upper and lower segment to see if proportionate
lower is symphysis pubis to ground, subtract this from height
check for scoliosis
can also do sitting height (takes the legs out of the equation)
if disproportionate then think of skeletal dysplasia
Shown a growth curve of kid tracking along the 3rd percentile, what is it? target mid parental height is at that percentile
normal growth velocity
tracking towards the mid parental height
familial short stature
Shown kid who is older than his little sister, way below the curve, velocity is low, way below target height?
abnormal
had micropenis, was treated with testosterone (known to stunt height)
IGF1 level was low, got a GH stim test
good response to growth hormone
Any time you diagnose growth hormone deficiency, need to do MRI of the head!!!
MRI head - can show ectopic posterior pituitary, anterior pituitary and stalk not seen
sella turcica is where the posterior pituitary gland sits
don’t start growth hormone if you think of mass (high suspicion)
Side effects of growth hormone treatment
- SCFE
2. headaches - can get pseudotumor
Investigations for short stature - if doesn’t look like normal variant, then what endo does:
poor growth velocity and short stature endocrine screen: TSH, free t4 (to rule out central cause - remember that you are not ruling out central cause with TSH) Growth hormone - IGF1 (have to pay in outside lab) o Find: FSH/LH The : TSH Adenoma: ACTH - likely will do cortisol Prolactin
Posterior pituitary: ADH and oxytocin
check sodium
Chronic disease work up also: CBC diff, lytes, BUN/Cr, ALT, bill, ESR (controversial)
Approach to delayed puberty - 1st test to do
FSH/LH - tells you if central vs. peripheral
if peripheral then looks almost menopausal, the FSH/LH is trying to catch up
low (central) - constitutional delay of growth and puberty, hypothalamic or pituitary cause
high (peripheral) - gonadal failure
14 year old girl without any signs of puberty
definition of normal puberty -
girls: age 8-13 is normal time to have puberty
boys: 9-14 is normal time
growth - started off at 50th percentile now is falling off , growth velocity is abnormal
way below the mid parental height , bone age is delayed
whenever you have a short girl with no puberty - think of Turners
follows the Turner curve perfectly
normal pre-pubertal growth velocity
5 cm /year
post puberty it gets way more complicated
turner’s bone age is only delayed in puberty (not in pre-puberty)
hypothyroidism should have delayed bone age
features of turner
shot stature epicanthic folds, ptosis high arched palate micrognathia lowest ears, malformed ear lobes recurrent OM, auditory problems low posterio hairline short, webbed neck shield chest, widely spaced nipples renal malformations streak ovaries, primary amenorrhea cubitus valgus lymphedema at birth short fourth metacarpal pigmental nevi
If waiting for Turner’s and waiting for karyotype, then what test can you do?
FSH is often very high even when young (i.e. 8 or something)
15 year old boy, no puberty (just a bit of pubic hair)
FSH/LH is high
gonadal problem
#1- Klinefelter most common - do karyotype XXY
other: mumps, testicular torsion, leukaemia treatment etc
15 year old boy, no puberty (just a bit of pubic hair)
FSH/LH are low, what should you ask ? sense of smell
Kallman’s
don’t have sense of smell, so need to ask about it
has to do with the migration of the neurons
LH/RH stimulation test - GnRH stimulation test - try to give GnRH if body hasn’t seen it before it will be a flat response, LH/FSH won’t go up
treat with testosterone
testes won’t grow, HCG can help them grow a bit, but they work
14 year old boy, no puberty, strong family history of constitutional delay, gonadotropins are low, delayed bone age
exaggerated constitutional delay
can sometimes do testosterone injections, give them some of the early features of puberty (including a growth spurt), give for 6 months (low dose), then stop it, take over where you left off
does not impact final adult height
Precocious puberty approach - benign variant or real thing
normal growth velocity and bone age - normal variant
estrogen - breasts and uterine lining changes ->thelarche
androgen - acne, hair, body odor ->premature adrenarche
increased growth velocity - pathological
advanced bone age - pathological
premature thelarche what age
usually around 18 months - can stay till age 3
need to make sure have normal growth velocity and normal bone age and don’t need to refer if these are okay
if have increased growth velocity or advanced bone age then:
GnRH stim test - to see what the deal with LH/FSH is (is it central or peripheral) ; pubertal response or pre-pubertal response - if LH is >10 then pubertal response (true central puberty), if flat (LH 1-2) then need to look elsewhere to look for where the estrogen is coming from
premature adrenarche
usually around age 5
in some kids, can get adrenarche first (before age 8) even though in most girls boobs are first
if going to do some investigations:
17OHP for non classic CAH, testosterone (DHEAS)
(FSH/LH not that useful for premature adrenarche)
tanner 2 pubic hair - DHEAS will be that level, the others should be normal
fsh/lh levels useful when?
useful in delayed puberty
almost useless in precocious puberty
6 year old girl with breast development and pubic hair
more likely central because both thelarche and adrenarche
has growth acceleration
not typical age for premature thelarche
advanced bone age - follow bone age to figure out the predicted height
will do a LH/RH (GnRH) stim test to confirm that it is central
also will do the pituitary hormone screens
do head imaging next - won’t often find abnormality but need to look
Treatment is Lupron - blocks the pulsatility
Side effects of lupron
reasons to treat with Lupron
height and psych
give it monthly or triple dose every 3 months
keep going until 11 year old and then take off on their own
sterile abscess - at injection site - can’t give it to them will be worse if you give more, then need to give sc daily
some weight gain
treat girls before age 6 for sure for precocious puberty, not as clear for 6-8 year old
6 year old boy with precocious puberty
most important is testicular size
look for peripheral cause
do testosterone, DHEAS, 17OHP, androstenedione
growth acceleration
Most common CAH
21 hydroxylase deficiency
remember that it is a spectrum of disease
get shunting of the hormones to the testosterone (androgen pathway)
done as a newborn screen - saves the boys
Should always check testes in newborn girls because
CAH won’t have testes but otherwise might look like a boy
Disorders of Sex Differentiation
congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical
46 XY DSD
chromosomes are male
something about the individual is not male
undervirilized male (so not as much androgen effect)
46 XX DSD
overvirilized XX female (old language)
ovotesticular DSD (usually XX)
not just your chromosomes determine what sex you are
term to use
genital tubercle
labiascrotal folds
website for families
www.sickkids.ca/childphysiology/cpwp/genital/genitaldevelopment
What is DHT
the potent androgen in fetal development, if issue with the conversion to DHT can cause lots of problems
Approach to ambiguous genitalia
are gonads palpable or not?
No
- probable 46 XXDSD (ie CAH) or maternal/fetoplacental issues (in utero)
Unilateral - hypospadias, ovotesticular DSD, mixed gonadal dysenesis
Bilateral - 46 XYDSD -
hormonal - not making enough testosterone, not respond (androgen insensitivity), enzyme problem (5alpha reductase)
or hypospadias
**if you can feel testes most likely XY
46 XY DSD - can they make testosterone - do a hCG stim test to find out
if hcg stim test positive then ratio of T/DHT - if normal then AIS if >30 then 5 alpha reductase def
if they don’t respond to the hcg stim test then testosterone synthesis defect
there is complete AIS and partial
if undervirilized then may not produce anything unless you stimulate
factors that affect gender assignment
diagnosis genital appearance surgical options need for life long replacement potential for fertility view of the family and cultural practices
- Child with micropenis. Best test to determine sex of rearing
a. Y chromosome
b. testosterone level
c. hypospadias
d. palpable gonads
e. size of phallus
dr. gold bloom says palpable gonads is the best answer
hypocalcemia with PTH high
vitamin D related - 7 dehydrocholesterol - vitamin D-25 OH vitamin D - 1,25 OH D3 - receptor
liver, renal, 1 alpha OH deficiency, resistance
not vitamin D - GI/Renal losses ( urine Ca)
hypocalcemia with PTH low (high PO4)
hypoparathyroidism (inappropriate)
hypocalcemia
ALP, urine calcium
remember that nomal PTH may be inappropriately normal in the face of hypocalcemia
hypocalcemia treatment - depends on where the problem was
PTH deficiency - treat with calcium, calcitriol (activated vitamin D) and possibly Mg
vitamin D deficiency - give them vitamin D plus enough Ca in diet
if problem with 1 alpha OH deficiency then need to give 1,25 OH (calcitriol) since they can’t convert it themselves
if ionized calcium is low (<0.8 mmil)
or patient is symptomatic, patient needs IV calcium infusion as follow
9 month old presents to ER with choking vs seizure
calcium is 0.7 mmol/L
hypocalcemic seizures
Ddx of hypoglycaemia
- endocrine cause
- inborn error or metabolism - carb metabolism, FA metabolism, AA metabolism/organic academies
- Acquired Disorders
4.
Endocrine causes of hypoglycaemia
- hyperinsulinism
- not enough cortisol - adrenal insufficiency (primary or secondary)
- GH deficiency
If hypoglycaemic should make ketones
if don’t make ketones:
- fatty acid oxidation defect
- hyperinsulinism
GH only at time of hypoglycaemia - do critical sample
things to help
ketones? (see above)
glucose requirements (if very high then think of hyperinsulinism)
hepatomegaly - glycogen storage
timing of the hypoglycaemia - fasting or non fasting - FAO more when starving, vs. insulin right after)
growth - GH deficiency
most common cause of hypoglycaemia in child >18 months
benign ketotic hypoglycemia
treatment of hypoglycaemia
if alert, treat orally if not work then treat with IV
Adrenal insufficiency presentation
primary (at the level of the organ) vs secondary (above the organ)
don’t have bronzing with secondary (since won’t have high ACTH)
if at the level of the adrenal gland then won’t have aldo involvement (controlled by RAS), will have more severe hypotension and hyponatremia if primary
Critical sample for adrenal insufficiency
cortisol, ACTH, lytes, glucose (can get hypoglycaemia)
renin
Treatment of adrenal insufficiency
- steroids - hydrocortisone 50-100/m2 has some mineralocorticoid and glucocorticoid effect so don’t need fluorine yet *want to give enough to replace but not so much that it messes up growth
- fluid - restore volume and Na appropriately
- sugar
- support
- search - for aetiology of crisis
- Stress coverage - mild illness double, fever/vomiting - triple dose, unable to tolerate orally - solucortef IM or IV
What is used to determine the initial dose of thyroid hormone replacement in lymphocytic thyroiditis?
TSH is the best likely
although often do do a weight based dosing initially
primary problem at the level of the thyroid gland therefore the other ones aren’t reliable - need to depend on TSH
- Which is an indication of delayed puberty?
a. 15 yo girl with amenorrhea
b. 12 yo girl with no axillary hair
c. 13 yo boy with no public hair
d. 15 yo boy with no voice change
voice change?
they are all wrong
types of diabetes
1 2 3 mody - autosomal dominant 4 CF related diabetes 5. secondary diabetes
3 generations of diabetes without classic features of type i or 2 then reasonable to test for MODY, advantage they can sometimes be managed with sulfonylurea
Diabetes development
much quicker in kids, can end up on insulin very quickly
doses of insulin go way up in puberty
health of the beta cells determines what happens
consider T2Dm when
BMI >85, high risk ethnic, exposure to diabetes in utero, fhb of type 2, clinical features of insulin resistance, children on psychotropic meds
insulin resistance
waist circumference (measure in oske at umbilicus) acanthosis nigricans
PCOS
irregular menses
clinical or biochemical signs of increased androgen
30% of women with PCOS will have IGT or T2DM by the 3rd decade of life
don’t use U/S for PCOS diagnosis
DM
family history more in type 2
ethnic more likely type 2
acanthosis type 2
age older Type 2 (13-15) 8-19 for type 1
to tell between type 1 and 2
c peptide (high or normal in type 2) and antibodies (present in type 1)
classification of diabetes
fasting blood sugar 6-7, but 2 hour is normal (<7.8) - impaired fasting glucose
fasting blood sugar is normal, but 2 hour between 7.8-11 : impaired glucose tolerance
everything else is diabetes !!
kids with fasting blood sugar every 2 years
> 3 risk factors in no pubertal or 2 risk factors in pubertal
obesity, member of high risk ethnic group, FHx of T2Dm and/or exposure to diabetes in utero, signs/symptoms of insulin resistance , IFG or IGt or use of anti-psychotic medications/atypical neuroleptics
OGTT if BMI>99th or multiple risk factors
based on HgA1c treatment
M9% metformin, >9% insulin
metformin start at 250 then increase
insulin can likely get by with once/day insulin, also some pre mixed options
type 2 - start to monitor for complications right away, more likely to have them early on
CDI guidelines - read them
type 1 diabetes
prevalence 0.4% of individuals <18 years
increased risk with family members sibling 5% father 6-8% mother 2-3 % identical twin 30-50%
Etiology
viral, mild protein, others
beta cells die over time
target ranges of sugar for different ages
age <5 year old - pre meal 6-10
6-12 4-10
13-18 4-7
DKA
decreased by 2-3 mmol/H for Na
hyperglycemic hypoerosmolar syndrome
severe hyperglycemia
high osmoses
absence of ketones - HCO3 >15 mmol/L, urine ketones negative or trace
mostly a fluid deficit - this is how the treatment differs
wait several hours before insulin
start insulin at lower rate
type 1 diabetes
when you are sick don’t stop insulin
how much extra they need depends on total daily insulin
blood glucose 2-4 hours, urine/blood ketones q2-4 hours (if sugar >14), never omit insulin
reduce the doses if they are not eating much
if high then give extra depending on ketones
TDD - add all the types up
TDD 12+ +4+8 - 30 units
therefore need an extra 20% at that moment
surgical abdomen T1DM what to do
emergenc surgery
check glucose, acid base status, correct hyperglycaemia
IV fluids with dextrose and insulin infusion is generally what we do (0.02 units/kg/hour)
titrate it downward)
diabetes
exercise - either need to cut down on insulin or increase food
depends on timing