Endocrinology Flashcards
Male vs female presentation of CAH
- Girl with virilization at birth +/- vomiting and dehydration
- Boy with vomiting, dehydration, hyponatremia, hyperkalemia
Electrolyte derangement in CAH
LOW sodium (think salt wasting form)
HIGH potassium
salt wasting happens around 1-2 weeks of life
Most common mutation in CAH
21-beta-hydroxylase deficiency
NMS test for CAH
measures 17 OHP
high in CAH
6 year old with vaginal bleeding, irregular hyperpigmented macules, bony dysostosis
Mccune Albright syndrome
look for hyperfunctioning polyendocrinopathy
CAH genetics
autosomal recessive
CAH physical exam findidngs neonate
ambiguous genitalia female
normal appearing male
timing for salt wasting in classic CAH
typically occurs at 7-14 days of life
stress dose steroids
moderate: 30-50mg/m2
severe: hydrocort 100mg/m2 (max 100mg) followed by 25mg/m2 q6h
Infant and Maternal Risk Factors for Rickets
Maternal: Vitamin D deficiency (dark skin pigmentation, full body clothing, high latitude, low Vit D diet), low Ca diet (poverty, malnutrition)
Infant: lack of Vit D supp, prolonged breastfeeding > 6mo without complementary feeding or supplementation PLUS same as maternal factors
Normal ages for puberty
Boys 9-14
Girls 8-13
Order of puberty for boys and girls (+ which SMR stage is peak growth potential for each?)
Girls: Boobs, Pubes, Grow, Flow
- thelarche is usually first sign of puberty (10-11y) -> pubic hair (pubarche) 6-12 months later -> menarche ~ 2.5 years after onset (breast tanner stage 4-5)
- Peak height velocity occurs breast stages II-III (typically 11-12y) and always precedes menarche
- 2cm growth potential after menses
Boys: the balls get hairy, the penis shoots up
- Growth of testes (> 4 ml in volume or 2.5cm in diameter) and thinning of scrotum are first signs of puberty (11-12y) -> pigmentation of scrotum and growth of the penis -> pubarche
- Acceleration of growth begins after puberty and is maximal at genital stages IV-V (13-14y)
SMR staging - breasts
Breast Development
I - Prepubertal; elevation of papilla only
II - Breast buds are noted or palpable with enlargement of the areola
III - Further enlargement of the breast and areola with no separation of the contour
IV - Projection of areola and papilla to form secondary mound above the breast level
V - Adult contour breast with projection of papilla only
SMR staging - pubic hair
I - Prepubertal; no pubic hair
II - Sparse growth of long, straight or slightly curly minimally pigmented hair
III - Considerably darker and coarser hair spreading over the mons pubis
IV - Thick adult-type hair that does not yet spread to the medial surface of the thighs
V - Hair is adult in type and is distributed in the classic inverse triangle for females and diamond for males
SMR staging - males
I - Prepubertal; testicular length < 2.5cm
II - Testes > 2.5cm; scrotum thinning and reddened
III - Penile growth in width and length and further testis growth
IV - Penis and testes further enlarged and scrotal skin darkens
V - Genitalia adult in size and shape
Bone age in constitutional growth delay
significant bone age delay (2 SDs below the mean, ~1.5-2 y delay as a teen)
Hypogonadotropic Hypogonadism DDx
Low FSH/LH + Low Testosterone/Estrogen
- CNS disorders (craniopharyngiomas, gliomas, prolactinomas, pituitary adenomas)
- Kallman syndrome (gonadotropin deficiency and cannot smell)
- Anorexia
- Hypothyroidism
- Prader Willi
- CHARGE syndrome
Hypergonadotrophic Hypogonadism (LH, FSH, T/E levels and common causes)
High LH/FSH, LOW Testosterone and Estrogen
- Turners Syndrome
- Premature Ovarian Failure
- Klinelfelter Syndrome
Workup for Delayed Puberty
Bone age (will be < chronological age if constitutional)
FSH/LH, and E or T to determine if gonadal failure vs. secondary to hypothalamic/pituitary
If gonadal do karyotype for Klinefelter in boys, Turner in girls
Prolactin
TSH in girls
Consider:
Cortisol, GH-IGF-1 axis assessment, cranial imaging if multiple deficiencies
AUS in girls for internal structures (androgen insufficiency, XY)
Central Precocious Puberty
Early maturation or HPA axis
Caused by CNS lesions, can be idiopathic
MR in all boys!
MR in girls <6yrs
Peripheral Precocious Puberty : LH, FSH, sex steroid levels?
LH and FSH low, estrogen and testosterone HIGH
- Can be either production from gonads or adrenals, or exogenous source
DDx Peripheral Precocious Puberty
Girls:
- ovarian cysts or ovarian tumors
- McCune Albright (coast of maine cafe au lait spot, precocious puberty and polyostic fibrous dysplasia)
- estrogen secreting adrenal tumours
- late onset CAH (early adrenarche with PCOS like picture)
Boys:
- Leydig cell tumors
- hCG-secreting germ cell tumors
- familial male precocious puberty (due to changes in LH receptor – genetic cause)
Both girls & boys:
- primary hypothyroidism (high levels of TSH directly stimulate FSH receptors)
- exogenous sex steroids
- adrenal pathology ( w/u would include raised DHEAS or adrenal CT)
Essential investigation for boys with central precocious puberty?
Head MR!!
(consider head MR in girls with central precocious puberty if <6)
Triad of McCune Albright Syndrome
Triad (need 2/3 to make Dx):
- Café au lait macules (coast of Maine vs. smooth border NF-1 coast of California)
- Peripheral precocious puberty ( May also have thyroid and adrenal gland involvement w/ hyperthyroid and cushings)
- Fibrous dysplasia of multiple bones -> rickets/osteomalacia + phosphaturia
Premature Thelarche
SMR II-III breasts
NO workup needed
Gynecomastia
Incidence peak at age 14y, Tanner stage 3-4 and testicular volume 5-10ml
May involve only 1 breast or both breasts at different times
Rarely persists >2yrs
No workup needed
Androgen Insensitivity
XY
Phenotypically female. if complete, will have start of vagina
Will develop breasts, but not responsive to androgens so likely no pubic hair
Will not have a period -> because internal organs are male!
5- alpha reductase deficiency
XY
Phenotypically female, with internal testes + vas deferens (empty into blind pouch/vaginal canal)
Will experience voice deepening, male puberty
don’thave DHT so not as much pubic hair/axillary hair/sweat/deep voice
When to start evaluating for comorbidities with obesity (BMI)? What conditions do you need to screen for?
> 85th% workup for:
Dysglycemia (OGTT (preferred), Fasting glucose, HbA1c)
Dyslipidemia
Hypertension
NAFLD (ALT)
OSA
Psychiatric/Mood
Ages for Hyperlipidemia Screening? RF that require screening?
If increased risk start screening at age 2
For patients who are >85th% age 9-11, again at age 17-21
Children at increased risk:
- Family history of premature CVD (male relative < 55y; female relative < 65 y)
- Child with other CV risk factors (obesity, HTN, smoking)
- Child with high-risk condition: ex. Diabetes, CKD, post stem cell or heart transplant etc
Treatment for Hyperlipidemia
- Diet and lifestyle x 6 mo
- If LDL remains >4.9 (no RF), >4.1 (w/ fam hx or 1RF), or >3.4 (2RF) start statin treatment
PCOS Diagnostic Criteria in Teens
- Abnormal menstrual pattern (persistant x 1-2yrs)
- Clinical/biochemical evidence of yperandrogenism (hirsutism, elevated testosterone)
Laboratory findings in PCOS
Increased LH
Low or normal FSH
High LH:FSH ratio (not diagnostic)
Elevated free and total testosterone
Normal DHEAS, 17-OHP (if high, image for adrenal tumor as alternate cause for presentation)
Management of PCOS
OCPs are first line therapy
Congenital Hypothyroidism Clinical Manifestations
- prolonged neonatal jaundice (indirect)
- feeding difficulties, poor appetite
- apneic episodes
- sleepy
- constipated
- large umbilical hernias
- USUALLY ASYMPTOMATIC AT BIRTH BECAUSE OF TRANSPLACENTAL PASSAGE OF MATERNAL T4
Interpretation of TSH values in Newborns
TSH > 17 is elevated
If TSH 17-40, repeat TSH with free T4 (because its most often a false positive)
If TSH > 40, repeat labs, start thyroxine immediately and imaging (nuclear scan/ultrasound) for diagnosis
Treatment of Congenital Hypothyroidism
- Start therapy within 7-14d
- Tx with Levothyroxine 10-14mcg/kg
- DO NOT GIVE SOY FORMULA
Frequency of TSH/T4 monitoring in Congenital Hypothyroidism?
TSH and Free T4 should be done q1-2 months in the first 6 months of life then q2-4 months until age 3
What is the most common cause of goiter in kids?
Chronic Lymphocytic thyroiditis (Hashimotos)
Chronic Lymphocytic Thyroiditis
- clinical presentation
Growth failure
Weight preservation/gain (does not cause obesity)
Dry skin and hair
Diffuse goiter
Bradycardia
Cold intolerance
Delayed or precocious puberty
Decline in school performance
Muscle hypertrophy and weakness; delayed relaxation phase of deep tendon reflexes
Myxedema
Goiter (euthyroid goiter is more common than hypothyroidism)
Chronic Lymphocytic Thyroiditis: Workup + Treatment
Elevated TSH, Low free T4 (primary hypothyroidism)
Antithyroid perixodase antibidodes (TPOAb), TgAb
Imaging needed only if nodule or asymmetric goiter
Tx: treat if TSH >10 with Levothyroxine
Conditions associated with Graves Disease
DM, celiac, primary adrenal insufficiency
SLE, vitiligo, RA, myasthenia gravis
Turner syndrome and T21
Clinical presentation of Graves Disease
Weight loss despite large appetite
Heat intolerance, sweating
Tremor
Proptosis and periorbital edema, lid lag - results from Abs against TSHR-like protein in retro-orbital connective tissue
Exophthalmos (antibodies against a TSHR-like protein in retro orbital connective tissue) – less common in children
Poor concentration, fidgety, hyper
Increased frequency of bowel movements
Palpitations, tachycardia
*Fatigue
Diffuse Goiter- usually without palpable nodules
Labwork in Graves
TSH low
Free T3/T4 high
ALP high
Thyrotropin receptor stimulating Ab high
Maternal/Neonatal Graves
Cord blood: diagnosis with high TRAb titres. Infants may be asymptomatic at the time of delivery.
At 48 hours of age, or sooner if symptomatic or discharged, Infant blood may be sent for:
TSH
FT4, FT3
These levels may be repeated at 5-7 days post delivery as an outpatient
Elevated FT4, FT3 and a suppressed TSH level indicate hyperthyroidism
If hyperthyroid-> treat with methimazole! 0.2-0.5mg/kg/d
If hypothyroid-> continue to monitor labs
First line treatment for Graves
Methimazole
Causes of Congenital Goiter
Maternal:
- Maternal methimazole or propylthiouracil
Neonatal graves:
- Transplacental passage of maternal TSH receptor stimulating ab
- Usually infant has symptoms of hyperthyroidism with small goiter
Congenital hypothyroidism
- Intrinsic defect in synthesis of thyroid hormone
- Newborn metabolic screen
- Treatment with thyroid hormone to start immediately
Pendred syndrome
- Familial goiter + neurosensory deafness
Iodine deficiency
- Rare cause of congenital goiter but still seen in developing countries
- Severe iodine deficiency in early pregnancy can cause neurologic damage during fetal development
Teratoma
- Consider if the goiter is lobulated, asymmetric, firm, or unusually large
Causes of Acquired Goitre
Chronic Lymphocytic thyroiditis (Hashimotos)
Graves
Amiodarone
Lithium
Tests for Cushings Syndrome
Midnight Salivary Cortisol
Dexamethasone suppression test (1mg Dex at midnight and then test serum cortisol at 8AM)
- If <50 = normal/ NOT cushings
Test for X linked adrenoleukodystrophy
Serum VLCFA
All males need MR at time of diagnosis
HC dosing for AI:
- Mild illness
- Severe illness/surgery
Mild: 30-50mg/m2/d
Severe/Surg: 100mg/m2 dose x 1 then 100mg/m2/day divided q6hrly
Who is at risk of AI from steroid use?
Systemic use >14d
ICS >3mo (high dose, fluticasone)
Swallowed ICS >1mo
Those on CYP3A4 inhibs (antifungals, clarithromycin)
Kid has bad eczema refractory to treatment on his scalp, petechiae noted in the area, and has DI - what is the underlying condition?
LCH (pituitary stalk thickening causes DI in these kids)
Treatment of Central DI
DDVAP
Treatment of Nephrogenic DI
Thiazide diuretics
________serum osmolality with ______-osmolar urine suggests Central or Nephrogenic DI
______ serum osmolality with _____-osmolar urine suggests compulsive water drinking
High serum osmolality with hypo-osmolar urine suggests Central or Nephrogenic DI
Low serum osmolality with hypo-osmolar urine suggests compulsive water drinking
Water Deprivation Test
First, the patient is deprived of all fluids for up to 8 hours and urine osmolality is measured after each void
- If the patient fails to concentrate urine during the water deprivation, DI can be diagnosed
- If the patient is able to concentrate urine, compulsive water drinking can be diagnosed
Following this deprivation, synthetic ADH (DDAVP) is administered
- If the patient responds and begins concentrating urine, central DI is confirmed
- Alternatively, if there is no response to ADH, nephrogenic DI is diagnosed
Diagnostic Criteria for T1DM
FBG >7
OR
A1C >6.5
OR
2hBG in a 75g OGTT >11.1
OR
Random BG >11.1
A1c targets for T1DM
7.5
A1C targets for T2DM
7
Starting outpatient Insulin Therapy
Initial daily insulin dose: 0.4-0.6 units/kg/d
Intermediate & Rapid-acting regimen:
Divided 2/3 before breakfast and 1/3 before supper
Each dose divided 2/3 IAI, 1/3 RAI
For example, for a child who weighs 30 kg, the total initial daily insulin dose based on 0.5units/kg/day would be 15 units; 10 units given before breakfast, divided as 7 units IAI and 3 units RAI; 5 units total before dinner, divided as 3 units IAI and 2 units RAI
For basal/bolus regimen: total daily dose is divided 50% LAI, 50% RAI
DKA Lab Findings
hyperglycemia (glucose > 11.1)
metabolic acidosis (pH < 7.3 OR serum bicarb HCO3 < 15)
ketonuria
Risk Factors for Cerebral Edema in DKA
- Young age
- First presentation
- More severe acidosis
- Insulin prior to 1hr of fluids
Monitoring in DKA
Follow glucose, fluids, neuro-vitals, HR, BP Q1H
Follow lytes, and gases q2-4h, corrected Na, osmolality, anion gap
Want glu to fall <5 mmol/hr after the first hour
When to add glucose to IVF in DKA
Once glucose < 17, change fluids to D10NS OR glucose is < 25 and is decreasing by > 5mmol/hr
Per CPS, screening criteria for T2DM in Indigenous populations?
All 3 of the following:
- indigenous patients
- BMI > 85% expected for age
- Age > 10 years old
AND any one of the following:
- Sedentary lifestyle
- Children born to mothers who had gestational diabetes
- 1st or 2nd degree relative with type 2 diabetes
- Acanthosis nigricans
- Dyslipidemia
- Hypertension
- PCOS
Screening test for T2DM
Fasting blood glucose (>7 = diagnostic)
Diabetes Canada Guidelines for Screening for T2DM
> 3 risk factors in non pubertal children beginning at 8 years of age OR > 2 risk factors in pubertal children.
Risk factors include:
-Obesity (BMI > 95% for age and gender)
- Member of a high-risk ethnic group (e.g. African, Arab, Asian, Hispanic, Indigenous or South Asian descent)
- 1st degree relative with T2DM and/or exposure to hyperglycemia in utero
- Signs or symptoms of insulin resistance: acanthosis nigricans, hypertension, dyslipidemia, NAFLD (ALT >3x ULN or fatty liver on U/S)
Also consider screening in children with any of the following conditions: PCOS, impaired fasting glucose, use of atypical antipsychotic medications
SCREEN WITH A1C and FPG
APS 1 Triad
Addisons
Chronic mucocutateous candidiasis
Hypoparathyroidism
APS 2 Triad
Addisons
T1DM
Thyroid (autoimmune-hypo or hyper)
MEN1
Pituitary adenoma
Parathyroid hyperplasia
Pancreas tumors
MEN2
Thyroid Cancer
Pheochromocytoma (Too Excited)
Parathyroid hyperplasia
Marfanoid (Too Tall)
When to worry about growth velocity?
<5cm/yr in patient >4yrs
Bone age in GHD
Delayed
Bone age in Turners
Normal until puberty, then delayed
What are the indications for GH therapy in short stature?
GHD
Turner syndrome
Chronic renal failure
SGA with failure of catch up growth
Idiopathic short stature (height < 2.25 SD)
Constitutional delay: growth velocity and bone age?
Growth velocity: normal
Bone age: delayed
Familial Short stature: growth velocity and bone age?
Growth velocity: normal
Bone age: normal
Growth Hormone Deficiency: growth velocity and bone age?
Growth velocity: slow
Bone age: delayed
Albright Hereditary Osteodystrophy
PTH insensitivity:
Hypocalcemia
Hyperphosphatemia
Psuedo-Hyperparathryoidism
Hypocalcemia Symptoms and Treatment
Symptoms:
Muscle Cramps, Tetany
Chvosstek Sign (Facial Tap), Trousseaus Sign (BP cuff and hand tetany)
Abdominal Pain
Seizure
QTc prolongation
Treatment (Severe or Symptomatic)
1. IV Calcium Gluconate
2. Calcitriol
Discharge on PO elemental calcium and PO Calcitriol
Hypercalcemia Symptoms and Treatment
Symptoms: “Bones, Stones, Groans, Psychiatric Overtones”
Increased fracture risk
Nephrolithiasis
Abdominal cramping, nausea, illeus, constipation
Psychosis, Lethargy, Mood changes
ECG = Short QTc
Treatment:
1. Stop exogenous calcium
2. Hyperhydration: NS @ 2x maintenance
3. Lasix
+/- Bisphosphonates to force calcium into bones
Rickets X Ray Findings
Cupping and Fraying of Metaphases
Physeal Widening (Splaying) b
Bowing of Long bones
Decreased Bone mineralization
Rachitic rosary.
