Endo Flashcards
Define Familial short stature and Constitutional Delay
Familial Short Stature:
- normal growth velocity
- Boen age = chronological age
- Predicated Adult height appropriate for midparental height
Constitutional Delay of Growth
- normal growth velocity
- BA < CA
- delayed entry into puberty
- often positive family history
- Predicated Adult height appropriate for Mid-parental Height
When can children cross percentile lines
- During first 2 - 3 yrs of life, child may cross % iles
- During puberty child can cross % iles
- From 3 yrs until puberty , well children do not cross %ils
What is the definition of GH deficiency in Canada?
Low response to 2 GH stim tests ( < 8 ug/L)
In neonates its (< 15)
What is the classic definition of Precocious Puberty
What are some Red Flags
Pubertal signs prior to 8 yrs in girls, 9 yrs in boys
Red flags:
- rapid progression, BA advanced > 2 yrs
- Predicted Adult Heigh < 150 cm or > 2 SD below mid-parental height
- CNS symptoms/signs
How do you differentiate central from peripheral precocious puberty
- normal puberty follows a specific sequence, age at which individual steps occurs differs
- if it is precocious puberty - differs from normal sequence
- in girls: estrogen dependent effects usually predominate
- in boys: testes are inappropriately small in size or asymmetric
What are 2 common benign conditions often confused with precocious puberty
Premature thelarche
- isolated breast development
- 6 - 24 mon of age
- does not exceed SMR III
- no change in growth %ile
Premature adrenarche
- public hair +/- axillary hair
- body odor
- acne
- no thelarche
- early secretion of adrenal androgens (DHEA)
- no change in growth %ile
- bone age = bone height
Define Delayed Puberty
Absence of secondary sexual characteristics after 13 yrs in girls and 14 yrs in boys
Increase LH and FSH with low testosterone/estrogen = primary gonadal failure
Low LH and FSH with low testosterone/estrogen = permanent or functional pituitary or hypothalamic disregulation
What is McCune-Albright Syndrome
-rare disorder defined as the triad of peripheral precocious puberty, irregular cafe-au-lait skin pigmentation and fibrous dysplasia of bone
When is MRI indicated for precocious puberty
- boys of any age
- anyone with CNS symptoms
- Girls with PP < 5 yrs of age
What is the criteria for diagnosis of T1DM
FBG > 7 mmol or RBG >/ 11.1 mmol
or 2 hour OGT glucose >/ 11.1 mmol
HgA1c is not in dx as it is in adults
How to you calculate Insulin Sensitivity Factor (ISF)
The amount of BG that will drop for every unit of rapid insulin given
100/TDD (total daily dose)
Generally doubling the basal insulin total = TDD
Screening for T2DM should be preformed every 2 yrs using a FPG in youth with
BMI > 95%, acanthosis nigricans and dyslipidemia
Risk factors of T2DM
- family hx
- exposure to GDM in utero
- ethic group
- signs of insulin resistance including AC, HTN, fatty liver, dyslipidemia
- BMI > 95%
What are the counter-regulatory hormones to insulin?
- cortisol
- GH
- glucagon
- epinephrine
Adaptions to avoid hypoglycaemia
- regular ingestion of food with storage of excess as glycogen and fat
- glycogenolysis and gluconeogensis
- decreased utilization of glucose by substitution of ketones as primary energy source
During hypogylcemic even should you insulin be low or high?
- insulin should be not measurable during hypoglycemic event
- if it is measurable - suggests that it is hyperinsulinsim
Diabetes Insipidus
- loss of vasopressin production (Central) or action (nephrogenic)
- continued production of dilute urine (<300 mosmols) despite increasing serum osmolality (> 300 mosmol) and increasing serum sodium, decreased body weight and signs of dehydration
Causes of SIADH
- CNS injury/tumor
- resp illness
- drugs
- hypothyroid
- adrenal insufficiency
Other stresses:
- Nausea
- surgery
- pain
- psychological stress
Definition of Micropenis and Clitoromegaly
Micropenis: stretch penile length < 2.5 cm in a term infant
Clitoromegaly: lenght of clitoris > 9 mm in a term infant
Posterior labial fusion: AG ratio > 0.5 (distance from anus to posterior fourchette, divided by distance from anus to base of phallus
Causes of 46 XX DSD
- CAH - most common cause
- Virilizing maternal disease
- Maternal androgen use
- Ovotesticular DSD, XX testicular DSD, gonadal dysgensis
Basic labs: 17OH serum lytes glucose ACTH Renin testosterone LH/FSH
Cause of 46 XY DSD
- Leydig cell failure
- Testosterone biosynthetic defect
- 5 alpha reductase deficiency
- Androgen receptor disorder
- Gonadal dysgenesis
- rare forms of CAH (3 B hydroxysteroid dehydrogenase deficiency)
Basic Labs: Testosterone Dihydrotestosterone (hCG stimulation) LH/FSH Mullerian inhibition substance Electrolytes Glucose
How do you stress dose hydrocortisone in an Adrenal Crisis?
minor stress: 2 - 3 x replacement oral
major stress: 50 - 100 mg/m2 IM/IV stat and continued as divided dose q 6 - 8 hours
< 3 = 25 mg
3 - 12 = 50 mg
12 + = 100 mg
Causes of Congenital Hypothyroidism
Permanent:
- Thyroid dysgenesis (80%)
- Dyshormonogenesis (10%)
- hypothalamic/pituitary (5%)
Transient (5%)
- intrauterine antithyroid meds
- maternal blocking antibody
- iodine deficiency
What is the Antibody in Graves Disease
-Thyrotropin receptor stimulating antibody
Pheochromocytoma
- rare neuroendocrine tumor
- synthesize and secrete catecholamines (dopamine, norepinephrine, epinephrine) and metabolites
- may occur as part of hereditary tumor syndrome: VHL, MEN, NF1
- sustained hypertension, classic triad: headache, palpitations, diaphoresis
Adrenal Insufficiency
- primary (addison’s disease) or central AI
- therapeutic glucocorticoid administration most common cause of secondary AI
- main presenting symptoms nonspecific: weight loss, fatigue, hypotension, vague abdo pain
- hyponatremia in Primary and Central AI
- hyperkalemia and hyperpigmentation in Primary AI
What makes up Autoimmune Polyglandular Syndromes 1 and 2
APS1
chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency
AIRE gene mutations 21q22.3
APS2:
T1DM, Celiac, thyroid disease, AI, vitiligo HLA-DR3, CTLA-4
What is the difference between Cushing Syndrome and Cushing’s Disease
Cushing Syndrome:
-constellation of clinical findings causing excess glucocorticoids
hypothalamic, pituitary, primary adrenal, ectopic ACTH, iatrogenic
< 5 ys- adrenal pathology most likely e.g. McCune Albright Disease
> 5 yrs = pituitary disease most common
Cushing Disease
excess pituitary ACTH production e.g. pituitary adenoma
What are Clinically Significant Fractures
- 2 or more long bone fractures by 10 yrs
- 3 or more long bone fractures by 19 yrs
- 1 or more vertebral compression fracture (loss of > 20% of vertebral body height at any age)
Causes of High TSH but normal or low FT4 levels in pts receiving LT4 therapy
- poor compliance
- administration with meds, food (iron or calcium can interfere with the binding)
- change in LT4 preparation (should keep pt on the same brand, prep can affect absorption)
- malabsorption
- increased thyroxin binding globulin capacity
Causes of Low TSH, high FT4
-Graves (including neonatal graves)
-excess thyroxine administration
-thyroiditis (post viral)
-toxic multinodular goitre
-toxic adenoma
-exces iodine intake
-
Causes of High TSH, Low T4
- Lymphocytic (hashimoto) thyroiditis
- thyroidectomy
- Post radioiodine ablation
- Iodine deficiency (or excess)
- hypothryoid phase of thyroiditis
Causes of inappropriately normal or low TSH, low FT4
- non-thyroidal illness (sick euthyroid, seen in critical care cases)
- central hypothyroidism (isolated or part of generalized hypopituitarism)
Hypercalcemia
normal or elevated PTH:
- primary hyperparathyroidism (including MEN)
- familial hypocalciuric hypercalcemia (don’t get stones)
Low PTH:
- Immobilization
- Williams syndrome
- malignancy (PTHrP)
- subcutaneous fat necrosis in neonate
Which children are most at risk for Rickets?
- those exclusively breastfed
- children who’s mothers are vitamin D deficient
- those who are not exposed to enough sunlight
- those with darker skin
- those in northern community
- calcipenic or primary deficiency of phosphate
- inadequate dietary intake of Vit D
what are some genetic causes of delayed puberty?
1) Central
2) peripheral
central: Laurence Mood Biedl Prada willi Peripheral Turner Klinefelters
Investigations PP
BA 17 OHP testosterone/estradiol DHEA/DHEA-S LH, GnRH stim test MRI, U/S gonads Genetics (McCuneAlbright)
Investigations
delayed puberty
BA bHCG (r/o preg) karyotype, genetic LH, FSH, Prolactin, IGF1, cortisol GnRH stim test image - Head, pelvis functional - CBC, CRP, celiac, etc.
Screening for type 2 DM
Every 2 years using an FPG test in children with any of the following:
- > / 3 risk factors in nonpubertal or >/risk factors in pubertal children:
- obesity (BMI >/95th% for age and gender)
- member of a high-risk ethnic group (aboriginal, african, asian, hispanic or south asian descent)
- family history of type 2 DM and exposure to hyperglycemia in utero
- signs and symptoms of insulin resistance ( acanthosis nigricans, HTN, dyslipidemia, NAFLD (ALT > 3xULN or Fatty liver on u/s) PCOS) - Impaired fasting glucose or impaired glucose tolerance
- Use of atypical antipsychotic meds
Can HB A1C be used as part of the diagnostic criteria for T1DM
- No: Not recommended for diagnostic purposes in children, adolescents, pregnant women or those with suspected type 1 DM
- may be useful in DM2
- random BG will be useful enough. It is diagnostic
How do you correct BG?
BG - target/ISF
ISF = 100/TDD
Plus extra if ketones
What is normal growth velocity?
GV typically > 5-6 cm/yr in prepuberty
In puberty may increase to > 10 cm/yr
< 4 cm/yr abnormal
Suspect issues if crossing %iles or > 2 SDs
Who gets GH?
FDA approved indications: -GH deficiency -Turner syndrome SGA/IUGR with failure of catch-up -Renal insufficiency -PWS -Noonan syndrome SHOX haploinsufficiency -Idiopathic SS
No “formal approved” indications in Canada other than GH deficiency
- province by province
- most treat TS
- PWS, Idiopathic, IUGR
What is autoimmune/lymphocytic Thyroiditis (Hashimoto Disease)
- T cell lymphocyte destruction of thyroid tissue
- antibodies sensitive but not specific: Antimicrosomal/AntiTPO, Anti-thyroglobulin
- depending on phase, TSH may be elevated, suppressed or normal
- Goal of tx: normalization of TSH
What are the 3 treatment modalities for Autoimmune Thyroiditis and their side effects
- Antithyoid medications (methimazole/Tapazol of Propylthiouracil (PTU))
- agranulocytosis
- hepatotoxicity
- rash/serum sickness like
- teratogen
- hypothyroid (non-permanent) - RAI
- hypothyroid
- radioactive
- worsen eye disease - Surgery
- surgery
- hypothyroid
Tanner Key features
-menstruation at Tanner IV
-Max penile growth at Tanner III
-Ax Hair in Males at Tanner IV
Voice change in Males at Tanner IV - V
Double breast contour at Tanner III
Delayed puberty
Girls no secondary > 14 yrs
Girls amenorrhea > 16 yrs
Boys no secondary > 15 yrs
What degree of BA advancement is significant?
< 4 yrs: > 12 months significant
4 - 10 yrs: > 18 months significant
> 10 yrs: > 2 yrs significant
What is Premature thelarche?
- isolated breast development
- typically b/w 6 - 24 months
- atypical > 4 yrs
- normal ht, velocity and BA
- 10% to true CPP
What is Premature Adrenarche
- isolated androgen effects (acne, hair, BO)
- BA normal or slightly advanced
- Elevated DHEA-S and Androstenedione (N testo and 17-OHP)
What is Pubertal Gynecomastia
- typically small (Turner 2), transient (< 3 yrs) and bilateral
- Klinefelter should go through your mind
DDX for Delayed Puberty
- Late bloomer
- Central:
- Panhypo Pit
- Isolated deficiency (kallman syndrome)
- Prolactinoma
- Cushing’s
- Hypothalamic (AN, athlete) - Primary gonadal failure
- chemo/rad/surgery/trauma
- don’t forget turner’s/klinefelters - In girls:
- pelvic abnormality/DSD
- pregnancy
What is the best test to detect PCOS
**Testosterone = increased in approx 70%
LH/FSH ratio elevated (>3) in 35 - 45%
Which DSD have non palpable testes
CAH and Partial androgen insensitivity (depending on the degree)
CAH over virilized female
Partial androgen insensitivity is underviralized male
CAH is more common than PAI
How do you treat Adrenal Insufficiency
Replace corticosteriods:
-6 - 8 mg/m2/day of hydrocortisone (or equivalent)
Stress dosing for illness
- 20 - 30 mg/m2/day for mild illness
- 50 mg/m2/day for moderate
- 100 mg/m2/day for severe illness
- medic alert bracelet
-replace mineralocorticoid in primary AI
Approach to HypoCa
- Is it real? check albumin or iCa
- Low Ca and Low PO4
- vit D problems: low vit D or poor vit D metabolism - Low Ca and N/Increased PO4
- Low PTH => Hypoparathyroidism, Digeroge, Post surgery, Polyglandular AI
- High PTH => Pseudohypoparathyroidism, Albright’s hereditary osteodystrophy - Low Mg => hypoMg causing HypoCa
What are the features of HypoCa
- weakness, twitching, seizures
- laryngospasm
- prolong QT
- Chvostek’s
- Trousseau - carpal spasm
Approach to Hyper Ca
- Is it real?
- Rule out William’s, immobilization, hyper thyroid, iatrogenic (Lithium, Thiazide, VitA, Aluminum), Alkalosis, AI, Renal Failure
- Low Urinary Ca => Familial HypoCa-uric, Hyper Ca (FHH)
- Low PO4 => PTH or PTH rp mediated
- Elevated PO4 => Vit D intox, granulomatous disease
Hyper Ca manifestations
moans, groans, stones, bones and psychiatric overtones
Treatment for Hyper Ca
- fluids
- bisphosphonates
- loop diuretics
- steroids
If you suspect vit D deficient rickets but it’s not responding to treatment with Vit D, what should you consider?
- Alpha hydroxylase deficiency, Vit D resistance
When treating Vit D deficient rickets, how fast you you see and increase in Ca/PO4, Xray changes, Vit D levels and physical exam?
- Increased Ca/PO4 in 1 week
- Radiological improvement in 1 week
- Vit D levels in 3 months
- Physical exam in 6 months
How you you treat vit D deficient rickets?
- Vit D > 1000 U
- follow up in 2 weeks
- follow 25-OH Vit D, AlP, Ca
What are signs of rickets?
- bowing of the legs
- bowing of the arms
- rachitic rosary
- craniotabies
- widened risks
- flared ribs at diaphragm (Harrison’s sign)
- delayed fontanelle closure
- dental abnormalities
- fractures
xray finding:
-cupping and frying of the diaphysis
What are physical features suggestive of OI
- blue sclera
- multiple fractures
- pectus
- curving of the long bones
- delayed fontanelle colsure
- large head size
- osteopenia on XR
- wormian bones on head XR
- triangular face
- joint laxity
- easy bruising
- dentinogensis imperfecta
Features of Congenital hypothyroidism
- umbilical hernia
- macroglossia
- rough/dry skin
- inactive defecation
- birth weight > 3500g
- coldness, pallor, hypothermia
- edematous facies
- prolonged jaundice
- open posterior fontanelle
- hoarse cry
