Which antibodies are most commonly seen in Hashimoto thyroiditis?
Thyroid antiperoxidase antibody (anti-TPO) and antithyroglobulin antibody seen in 90% of patients
What should you consider in a patient with hypoparathyroidism, Addison's, recurrent candidiasis and skin changes?
APCED Auto-immune polyendocrinopathy ectodermal dysplasia - autoimmune polyendocrinopathy, candidiasis, ectodermal dysplasia
With nephrogenic DI, what is the most common inheritance pattern? Name 4 acquired causes of nephrogenic DI.
X-linked, some forms can be AD or AR Acquired causes: hypercalcemia hypokalemia lithium rifampin methicillin kidney disease
In physiologic adrenarche, describe: - age at which acceptable - what blood / urine markers are seen - bone age findings - long-term prognosis - tests to perform if unsure if physiologic
Adrenarche (increase in adrenal steroids) resulting in hair, body odour and skin changes and maybe slight growth acceleration but no other signs of puberty - 6 years of age in boys and girls - rise in DHEAS, urine 17-ketosteroids (hydroxysteroids normal) - bone age on upper end of normal - more likely to develop PCOS or hyperandrogenism - ACTH stim test with 17-OHP (rule out atypical CAH)
What is Russel-Silver syndrome?
A growth disorder from before and after birth: LBW & FTT, normal head size Low appetites and at risk of hypoglycemia Small triangular face, prominent forehead, downturned corners of mouth Delayed development, learning disabilities
What type of growth are these curves showing?
Constitutional delay of growth and adolescence
What form of growth?
Familial or genetic short stature
What form of growth?
Primary nutritional or severe chronic illness
What form of growth?
Congenital GH deficiency :)
Name a possible syndrome associated with this type of growth
What is the calculation for expected height range in kids?
(based on parents)
(Mum's height + dad's height) +/- 13cm if boy/girl
divided by 2
Range calculated as +/- 10cm
What is the rate of growth in both sexes?
When are kids 'allowed' to cross percentile lines on the growth chart?
1- within first three years of life while finding their fit (ie: small infants to large parents and vice versa)
2- at puberty (accounting to different start times of growth spurts)
What is IGF1?
Insulin like Growth Factor 1
factor produced by growth hormone's effect on the liver
What is the significance of bone age?
Where to measure?
Most conditions that cause poor linear growth also cause a delay in skeletal maturation and retarded bone age, it indicates that the short stature is to some extent reversible.
A bone age that is NOT delayed is of greater concern and can be diagnostic ie: syndromes, achondroplasia, rickets
Measure at hand and wrist epiphyseal maturation centers
What investigations to consider in a well nourished child with a deceleration in linear growth?
karyotype if female
(if considering glucocorticoid excess: 24h urinary free cortisol & creatinine)
Approach to decelerating linear growth in a thin child?
Consider primary GI, nutritional, renal or other systemic chronic disease:
CBC w/ ESR
first morning void
What findings suggest growth hormone deficiency:
in the neonate? (try 4)
in the child? (try 3)
neonate: 1- hypoglycemia, 2- prolonged jaundice, 3- hepatitis, 4- microphallus, 5- traumatic delivery
child: 1- cranial irradiation, 2- head trauma or CNS infection, 3- cosanguinity or affected family member, 4- craniofacial midline abnormalities
What growth findings would suggest GH deficiency?
severe short stature (< 3 SD below)
height < 2 SD and height velocity <1 SD
Indications for GH treatment approved by FDA
Chronic Renal Failure
Idiopathic short stature
SGA with short stature
Define central precocious puberty & tests to investigate
Onset of secondary sexual characteristics:
development on breasts before the age of 8 in girls
development of testicular volume >4mL before the age of 9 in boys
Order bone age, FSH/LH/estradiol/testosterone
If +ve, consider GnRH stim test and cranial imaging in boys or girls <6yo
Who do you worry more about with precocious puberty, girls or boys?
90% of girls have the idiopathic form
75% of boys will have a structural CNS abnormality
How do you treat central precocious puberty?
(assuming work-up negative)
GnRH agonist in order to disrupt pulsatility
ie: Leuprolide acetate (Lupron)
Actual adult height of patients followed is 1 SD less than mid-parental height
What is the most common form of congenital adrenal hyperplasia?
What lab findings?
'Salt-losing form' 70% of CAH
21-hydroxylase deficiency (90% of CAH cases) therefore accumulation of 17-OHP as it can't be converted to 11-deoxycorticosterone and 11-deoxycortisol (aldosterone and cortisol precursors)
Presents with hyponatremia, hyperkalemia, hypoglycemia, metabolic acidosis, vomiting, lethargy, shock at 10-14 days of age
When do virilized females with CAH get operated?
What to do with subsequent pregnancy in mum?
They get operated at 2-6 months.
Subsequent pregnancies can be treated with dexamethasone in order to suppress fetal androgen production and lessen external genitalia virilization. Once CVS can be done, continue treatment only if the fetus is a female.
When do boys with 'simple virilizing' CAH generally present, and with what?
'Simple virilizing' form 30% of CAH
Often not diagnosed until 3-7 years of age when excess androgens have already caused accelerated linear growth +/- excessive muscular development, pubic and axillary hair, acne and deep voice, prepubertal testes (skeletal maturation up to 5 years in advance of chronological age, ends up with shorter adult height because of premature closure).
Name the most common disorders of sexual differentiation
virilizing CAH (14%)
androgen insensitivity syndrome (10%)
mixed gonadal dysgenesis (8%)
clitoral / labial anomalies (7%)
hypogonadotropic hypogonadism (6%)
46 XY SGA with hypospadias (6%)
Suggested approach to abnormal sexual differentiation?
1) history and physical, ***palpable gonads
b) blood tests: 17OHP, androstenedione, gonadotropin levels, molecular testing for SRY
c) internal anatomy evaluation with US, endoscopic GU exam, VCUG, CT or MRI
Describe the pathophysiology, physical and lab findings of androgen insensitivity syndrome
mutation in androgen receptor gene, X-linked recessive, most common male DSD
phenotypic spectrum with complete AIS presenting as phenotypic females and normal appearing males with simply infertility
46X-Y, testes, normal or elevated LH and testosterone (&DHT) levels, vagina ends in blind pouch (no other female internal organs). At puberty breast development but no menstruation and no sexual hair. Adult height that of male XY.
Replacement therapy with estrogens indicated at puberty.
What are the features of Denys Drash syndrome?
WT1 gene mutation
Nephropathy, bilateral Wilms tumour, ambiguous genitalia in XY with undescended testes
What are parathyroid hormone's effects?
Symptoms of hypoparathyroidism?
In response to low serum calcium and high phosphate: PTH turns on and increases calcium, decreases phosphate.
Symptoms related to hypocalcemia: MSK cramps and pain, numbness, Chvostek & Trousseau, convulsions, ICP/headache/papilledema, cataracts
When might you consider testosterone therapy in short boys?
Constitutional delay of growth and adolescence consider show term (4-8mo) low dose testosterone
- delayed onset of puberty, bone age >2 SD below mean
- weight and height decrease near the end of infancy, parallel the norm throughout childhood and accelerate towards the end of adolescence
- parents height in normal and patient's expected adult height is normal
How can you distinguish between constitutional delay of growth and adolescence and familial short stature?
Bone age is normal in familial short stature whereas it is delayed in CDGA
95% of kids greater than two years of age have at least this growth velocity
What features should be present before diagnosing benign premature thelarche in a toddler?
What findings on investigation?
1) Age <3y 2) Normal or slightly advanced bone age (with 2-3 years) 3) No other signs of precocious puberty (no estrogen changes in genitalia) 4) Persists for 3-5 years, not progressive
Detailed history reassuring, bone age with 2-3 yrs
LH/FSH/estradiol normal, no pelvic US necessary
What tests to order if you suspect peripheral precocious puberty?
LH, FSH levels
DHEAS, testosterone, 17-OHP, estradiol
Abdominal US, testicular US
What is premature pubarche?
Appearance of sexual hair before 8y in girls or 9y in boys without other evidence of sexual maturation
What random gluose threshold is used to diagnose diabetes?
When, how and how often should you test for type 2 diabetes?
Do a fasting plasma glucose every 2 years
1) if >3 in prepubertal or >2 in pubertal children:
a) Overweight (BMI >95%)
b) High risk race (native, black, hispanic, asian, pacific islander)
c) Family history of DMII or hyperglycemia in utero
d) Signs or symptoms of insulin resistance (PCOS, HTN, acanthosis, dyslipidemia)
2) Use of an atypical antipsychotic
3) Impaired fasting glucose or impaired GTT
How to differentiate between type 1 and type 2 DM?
1) Clinical presentation
3) Lab studies
DM II are generally overweight, after puberty, signs of insulin resistance, family history, level of sugar in true DKA >50, ketoacids +++,
What is the threshold for fasting blood glucose to diagnose diabetes?
What A1C is considered a threshold for diagnosis diabetes?
What is first line treatment for DMII?
2) normal renal function (potentially fatal lactic adidosis reported) and normal hepatic function
3) common side effects related to GI
What are typical insulin orders when a patient is NPO for surgery?
50% of usual NPH/Lente dose
D5NS IVF at maintenance
What is the usual progression of puberty in girls and boys?
Girls: thelarche -> pubarche -> increased growth velocity -> menarche
Boys: testicular enlargement -> phallus enlargement -> adrenarche -> growth spurt
What tests should be ordered for a scrotal mass?
What is considered delayed sexual development?
When is it considered primary amenorrhea?
Delayed sexual development: girls 13 or boys 14 years
Periods should come by 5 years since the beginning or puberty, or by 16 years.
MALE Pubertal gynecomastia, describe the following:
- peak age or Tanner stage?
- 0.5cm in diameter
- 14 yrs or Tanner 3-4 (testes 5-10mL)
- tenderness common
- spontaneous regression months-years (2 max)
Name 5 causes of pathological gynecomastia
1) Familial x-linked or AD gynecomastia
2) exogenous sources of estrogens ie meds like spironolactone
4) Male undervirilization ie AIS
6) Leydig cell tumours
What are the diagnostic criteria of PCOS?
2 of the following:
In who is soy formula especially contraindicated?
Congenital hypothyroidism, the phytoestrogens can inhibit thyroid peroxidase so thyroxine levels should be monitored more closely
What are features of Klinefelters?
psychiatric (LDs, anxiety)
tall & slim with legs>>arms
failure of testicular growth, small phallus (hypergonadotropic hypogonadism)
increased risk breast cancer, germ cell tumours, leukemia, lymphoma
Major etiologies of congenital hypothyroidism?
Thyroid dysgenesis (aplasia, hypoplasia, ectopic gland) 80-85%
Inborn error of thyroxine synthesis (dyshormonogenesis) 15%
Maternal thyrotropin-receptor blocking antibodies 2%
mostly sporadic cases, rarely familial but has been described
Clinical findings in congenital hypothyroidism
prolonged physiologic jaundice
sluggish, poor appetite, increased sleep
cold and mottled
edema of genitals and extremities
pulse slow, cardiomegaly, pericardial effusion
widely open anterior and posterior fontanelles
retardation of osseous development on x-rays
What are clinical manifestations of neonatal graves? Early and late
Early: restless, irritable, hyperactive, exophthalmos, tachycardia, tachypnea, temperature elevation
Later: weight loss, ravenous appetite, HSM, jaundice, HTN, cardiac decompensation
Late: advanced bone age, frontal bossing, craniosynostosis
Treatment of neonatal Graves?
How to confirm diabetes insipidus on labs?
Serum osm >290 mOsm/kg
Urine osm <290 mOsm/kg
Unlikely if SOsm <270 or UOsm >600
What are the features of McCune Albright?
Cutaneous pigmentation (Coast of Maine cafe au lait)
Name side effects anabolic steroids
boys: decreased sperm count, testicular atrophy
girls: menstrual irregularities, virilization
hepatic problems (transaminitis, cholestatic jaundice, hepatitis, HCC)
psychological effects (agression, anxiety, paranoia...)
What is the approach to congenital hypothyroidism?
Treat while awaiting result
What is the beta-HCG stimulation test used for?
Differentiating 5 alpha reductase deficiency, CAH and ovotesticular DSD:
if no testes: no rise in testosterone or DHT
if partial androgen insensitivity: rise in both testosterone and DHT
if 5 alpha reductase deficiency: rise in testosterone but not DHT (T:DHT ratio high! >12)
What is the most common form of childhood hypoglycemia?
ketotic hypoglycemia, usually related to substrate issue (with intercurrent illness and decreased food intake)
hypoglycemia + ketonemia + low plasma insulin concentrations
when sick screen for ketones, ensure high protein & high carbohydrate diet
What can cause a false positive neonatal thyroid screen?
test done too early (within 24-48h of birth)
What can cause false negative congenital hypothyroidism screen?
prematurity + low birth weight
What is the management of a positive neonatal hypothyroidism screen?
Call the patient in
History and physical exam
Repeat labs (TSH T4 TBG TRAbs)
Radionuclide uptake scan
What type of rickets?
low 25-OHD, hyperPTH
Vitamin D deficiency
What kind of rickets?
high PO4, hyperPTH, low1-25OH vitD
Chronic kidney disease
What regulates 1-alpha hydroxylase?
upregulated by PTH and hypophosphatemia
downregulated by hyperphosphatemia and 1-25D
What is the best method to screen for diabetic nephropathy?
What to do if it is positive?
Screen with spot urine albumin to creatinine ratio
Abnormal results should be confirmed at least 1 month later with FIRST morning albumin to creatinine ratio or timed, overnight urine collection for albumin excretion rate
When do you send diabetics for ophthalmology screening?
T1DM: if >/= 15, annually, starting 5 years after the onset of diabetes. Can stretch q2yrs if good control, sick <10yrs, no abN to follow up
screen for thyroid and celiac in T1DM at diagnosis!
T2DM: immediately after diagnosis
What are risk factors for cerebral edema in DKA?
1) <5 years old
2) newly diagnosed disease
3) severe acidosis (pH <7.1)
4) low pCO2
5) high BUN
6) bicarbonate treatment
7) administration of insulin in 1st hour
8) greater volumes of fluid given in first 4 hours
9) attenuated rises in serum sodium during therapy
How do you calculate an insulin sensitivity factor?
ISF: 100 divided by total daily insulin intake (long and short acting)
ie: if 13 units long active, 12 units short acting, ISF=100/25=4 so giving one unit of insulin would drop the blood sugar 4
Name three rapid insulins
Name three long acting insulins
What are the target HA1C in:
2) DM1 in <6yo
3) DM1 in 6-12yo
4) DM1 in >12yo
1) type 2 diabetes should be ≤7.0%
2) in <6yo A1C <8%
3) in 6-12yo A1C= 7.5%
4) in >12yo HA1C =7%
How do you manage a severely hypoglycemia child at home?
Glucagon 1mg IM
if in hospital dextrose 0.5-1g/kg IV over 1-3 minutes
In a patient in DKA with shock, describe management
IVF isotonic fluids just to correct circulatory inadequacy
IV infusion insulin 0.1 units/kg/hour minimum 1hr after fluid therapy begun
add glucose to IVF once plasma glucose 14-17mmol/L
avoid sodium bicarbonate
When do you start screening for microalbuminuria?
>/= 12 years old
Name infantile effects of maternal diabetes
1) sacral agenesis 2) congenital heart disease 3) small left colon syndrome 4) polycythemia (renal vein thrombosis) 5) hypoglycemia