Endocrinology Flashcards
Rickets - physical exam
- Bowed legs + arms
- Widened ankle/wrist
- Frontal bossing
- Delayed closure of fontanelle
- Craniotapes
- Pigeon chest
- Rachitic rosary
- Kyphosis or kyphoscoliosis
- Poor dentition: enamel hypoplasia, delayed tooth eruption
When does cerebral edema and osmotic demyelination syndrome occur?
CE = rapid correction of hyperNa ODS = rapid correction of hypoNa
4 hormones (and their mechanism) involved in sodium hemostasis
- ADH - stimulated by osmolarity receptors in hypothalamus (volume depletion or hyperNa), increased reabsorption and retainment by kidneys of H20
- Aldosterone - released from adrenal cortex followed by decreased renal blood flow, increased reabsorption of Na by the kidneys
- GC’s - some mineralocorticoid
- Natriuretic peptide - cardiac wall stretch, increased Na renal excretion
DDx for primary and secondary (most common) adrenal insufficiency
Primary:
- Steroidogenesis: CAH
- Damage: trauma, tumor, infection, autoimmune (Addison disease)
- Adrenal hypoplasia
- Peroxismal disorders: Adrenoleukodystrophy
Secondary:
- Infection
- CNS surgery or irradiation
- Trauma
- Exogenous steroids
Mid-parental height calculation
F = (pat ht + mat ht - 12.5cm) / 2 M = (pat ht + mat ht + 12.5cm) / 2
Most common cause and presentation for acquired hypothyroidism
Autoimmune thyroiditis - Hashimoto Disease
- Presentation: asx, goiter, dec energy/growth, poor school performance, constipation, cold intolerance, irregular menstrual periods, associated autoimmune conditions
Most common cause of hyperthyroidism + pathophysiology
Graves disease –> TSH receptor Ab binds + stimulates the thyroid
Congenital hypothyroidism - symptoms + signs
Symptoms: Lethargy, poor feeding + weight gain, constipation, cold, hoarse cry
Signs: Acrocyanosis + mottling, extended belly, coarse features, prolonged jaundice, large fontanelle, hypotonia, slow reflexes
Causes of congenital hypothyroidism - primary, secondary, other
Primary: Dysgenesis, agenesis, ectopic, dyshormonogenesis
Secondary: Hypopit, hypothalamic abnormality
Other: Maternal iodine deficiency, transient
Initial work-up for a goiter
TSH, T4, anti-thyroidal Abs, US
Mimics of thyroid goiter (x2)
Lymphoma, parathyroid enlargement
Name main categories for short stature ddx
- Constitutional growth delay
- Familial
- Endocrinopathy
- Genetic syndrome
- Iatrogenic/medications
- Nutritional
- Chronic disease
- Psychosocial
Definition of gonadarche
Sex hormone production from gonads - triggered by LH and FSH from pituitary
Definition of adrenarche
Increase in adrenal androgen production –> pubarche, acne, sweat/body odour, axillary hair
DDx categories for precocious puberty
- Central = early onset of HPA activation
- Peripheral = hormones not coming from the brain
- Benign/non-progressive = pubertal variants
Widened wrists - what is the endo related dx?
Rickets
Bony findings of rickets
Delayed closure of fontanelle, craniotabes, frontal bossing, leg bowing, widened wrists, rachitic rosary
What SMR for breast development would you think of precocious puberty?
3 or higher - bilateral
What test would you do for adrenoleukodystrophy?
VLCFA
Target for HbA1c for T1DM?
Less than 7.0%
NMS cut off for normal TSH filter paper blood spot
> 30
How to definitively confirm Addison disease?
ACTH stim test
What should you test and treat for before treating GH deficiency?
Hypothyroidism
Classic triad for pheo
Headache, sweating, tachycardia
Associated disorders with pheo (x3)
NF 1, MEN2, von hipple lindhau
Why should you monitor children with ?pheo closely during ultrasound?
Can increase metanephrine release
Phytoestrogen cannot be given to…
Congenital hypothyroidism
What test to do to distinguish rickets?
25-OHD
What thyroid diseases are TPO, TRAB, and TgAB antibodies associated with?
TPO - Hahimotos
TRAB - Graves’ disease
TgAB - Monitoring for thyroid cancer
Definition for precocious puberty (age)
Girls < 8 years and boys < 9 years
If you have an exaggerated response to glucagon what are you thinking is the dx?
Hyperinsulinism
Two best tests for ?cushing syndrome
Urine 24 cortisol collection
Dexamethasome suppression test
Canadian guidelines for target HbA1c for T1DM
<7.5%
When to check urine ketones for T1DM?
If glucose >14
If child with T1DM is having lots of lows what test would you double check?
Celiac
How many days of supraphysiogic dosing of steroids do you consider risk for AI?
Greater than 14 days
Dx criteria for PCOS
Two of three - hyperandrogenism, amenorrhea or oligo, and US changes
x2 normal growth variants
Constitutional delay, familial short stature
What syndrome is important to screen for in all females with short stature?
Turner Syndrome
What size of testicle is pre-pubertal?
2.5cm or 4mL
Age for M and F when you consider delayed puberty?
M >14
F >13
In setting of delayed puberty, what does elevated LH/FSH with low testosterone indicate?
Hypergonadotropic hypogonadism
Age and SMR stage for premature thelarche?
- Birth to 2 years
- Equal to or less than SMR III
Age range for premature adrenarche
Typically 4-8 years
What would bone age, adrenal androgens, and LH/FSH show for premature adrenarche?
- BA = mild to moderate increase
- Androgens = normal or mild increase
- LH/FSH = pre-pubertal
Age for precocious puberty for M and F?
M <9 years
F <8 years
x2 methods for correcting hyperglycemia in DM
- TDD x 10-20% as rapid insulin by subcutaneous injection or insulin pump bolus
- Insulin Sensitivity Factor (ISF) = 100/TDD
1 unit of insulin will drop glucose by this much - given enough rapid insulin to drop BG to target 6-8 mmol/L
What factor best correlates with future cardio-metabolic risk?
Waist circumference
What x4 components need to be considered for metabolic syndrome?
- Abdominal obesity (waist circumference)*
- Dyslipidemia
- Hypertension
- Fasting glucose/T2DM
Critical sample for hypoglycemia
- Glucose
- Insulin, C-peptide
- Ketones: BHB
- FFA
- Growth hormone, cortisol
- Lactate
- Additional: ammonia, IGF-1, LFTs, thyroid, plasma a.a.’s, total/free carnitine/acylcarnitine, urea/lytes, urine (toxicology, ketones, urine reducing substances, organic acids)
When should we consider a critical sample in a neonate?
If hypoglycemia (BG <2.8) persisting >72 hours
After dx of DI is made, what is the next step to determine where the problem is?
Trial of ADH to differentiate between central vs nephrogenic DI
Dx if after fluid deprivation urine osm <300 and after desmopressin >750?
Central DI
Dx if after fluid deprivation urine osm <300 and after desmopressin <300?
Nephrogenic DI
Dx if after fluid deprivation urine osm >750 and after desmopressin >750?
Primary polydipsia
Cut off measurement for micropenis?
<2.5 cm
Cut off measurement of clitoris?
> 9mm
DDx for 46 XX DSD?
- Disorders of gonadal/ovarian development: ovotesticular DSD, gonadal DSD, gonadal dysgenesis
- Androgen excess: CAH, maternal virilizing disease, maternal androgen use
Basic lab work-up for 46 XX DSD
- 17-OHP
- Glucose, lytes
- Renin
- ACTH
- LH/FSH
- Testosterone
When do you expect Classic Salt Wasting CAH to present?
7-14 days of life
Types of CAH - what hormones are affected?
- Salt wasting = GC and MC deficiency
- Simple virilizing = GC deficiency
- Non-classical
Basic lab work-up for 46 XY DSD
- Testosterone
- DHEAS
- Androstenedoine
- LH/FSH
- Mullerian inhibiting substance
- Lytes, glucose
Hashimoto Thyroiditis Ab’s
- Anti-thyroid peroxidase
- Anti-thyroglobulin
1st and 2nd line treatments for Graves Disease
- 1st line: methimazole
- 2nd line: PTU, radioactive iodine, thyroidectomy
What kind of thyroid disease would a NMS miss?
Central hypothyroidism
x2 screening tests that can be considered for query cushing syndrome?
- 24 hour urine cortisol collection
- low dose dexamethasone suppression test
Once cushing syndrome is confirmed, what is the next step in investigation?
High dose dexamethasone suppression test - determine if ACTH-dependent (ACTH elevated) vs ACTH-independent (ACTH depressed)
Difference between Cushing syndrome + Cushing disease?
- Cushing syndrome = constellation of symptoms/signs in keeping with excess glucocorticoids
- Cushing disease = secondary to pituitary pathology
Most likely pathology to cause Cushing Syndrome in (a) <5 years of age and (b) >5 years of age?
(a) Adrenal pathology - McCune Albright Disease
(b) Pituitary disease
Clinical signs/symptoms of Cushing Syndrome
- Weight gain
- Striae
- Osteopenia
- Growth retardation
- Hypertension
- Hyperglycemia
- Proximal muscle weakness
- Behavioural change
Causes for adrenal insufficiency
- Primary = adrenal: Congenital (CAH, adrenal hypoplasia) vs acquired (autoimmune - Addison, autoimmune polyglandular syndrome, infectious, hemorrhage)
- Secondary = pituitary/hypothalamic/exogenous: Congenital (hypopituitarism) vs acquired (exogenous steroids, trauma, surgery, radiation, tumor)
Additional features with Primary Adrenal Insufficiency
- Hyperpigmentation
- Lyte disturbance (hypoNa, hyperK)
- Salt craving
Screening (what is cut off that you are concerned about) + diagnostic tests to consider for Adrenal Insufficiency
- Screening = AM cortisol, <100-140 = concerning
- Diagnostic = ACTH stimulation test
If you tested renin level in primary adrenal insufficiency, would it be elevated or depressed?
Elevated
Stress dosing for moderate + severe illness for adrenal insufficiency?
- Moderate illness = 30-50 mg/m2/day
- Severe illness = 100 mg/m2 x1 dose then same dose divided q6h
DiGeorge Ca disorder
Hypoparathyroidism + HypoCa
Criteria for osteoporosis in children
- Low bone mass by DXA Z-score
- Clinically significant fracture history
What would count as a clinically significant fracture history?
- 2 or more long bone #’s by 10 years old
- 3 or more long bone #’s by 19 years old
- 1 or more vertebral compression #’s at any age
3 stages of vitamin D deficiency
- Relative PTH resistance, low Ca
- Higher Ca levels at expense of HypoPO4
- HypoCa + hypoPO4 with rising PTH + ALP
Physiology pathway in setting of hypoCa
- Low Ca –> high PTH from parathyroid
- Activates: (a) bone resorption, (b) kidney to resorb Ca + excrete PO4, (c) activate enzyme to convert vitamin D to calcitriol –> increase Ca absorption from GI
What x2 processes regulate free ionized Ca
- pH
- Protein binding
What happens to Ca in setting of increasing pH?
Increase pH = less H+ to bind to proteins so increased binding to Ca = hypoCa + compensatory increase in PTH
What is the threshold for normal growth velocity in children age 3 to puberty?
> 5 cm/year
Work-up for short stature
- Bone age XR
- Labs: CBC, lytes, renal function, CRP/ESR, UA, celiac screen, TSH, IGF-1, karyotype
What is prepubertal testicular volume and size?
<4mL and <2.5cm
What typically comes first axillary or pubic hair?
Pubic hair
Sequence of puberty in M and F
M = berry, hairy, twig, big F = boobs, pubes, grow, flow
What diagnosis to consider in patient with delayed puberty, normal growth without a growth spurt, and anosmia?
Kallman Syndrome
What two genetic syndromes would you consider for M and F with delayed puberty?
Klinefelter + Turner’s Syndrome
Categories on the differential for delayed puberty?
- Hypogonatropic hypogonadism - functional + permanent
- Hypergonadotropic hypogonadism
- Constitutional delay in growth + puberty
DDx for precocious puberty
- Central: CNS lesion/tumor, idiopathic
- Peripheral: CAH, adrenal lesion, ovarian/testicular lesion, McCune Albright, hypothyroidism (through FSH), benign variants (benign thelarche + adrenarche)
Work-up for Central Precocious Puberty (x2)
- MRI for ALL boys and for all girls <6 years
- LH level = ensure it is prepubertal
Premature adrenarche - age range, what investigations show
- 4-8 years old
- BA+ = chronological age
- LH/FSH = prepubertal
- DHEAS/testosterone normal to mildly increased
Premature thelarche - age range
birth - 2 years
What genetic condition to think of with precocious puberty?
McCune Albright
When is glucagon effective for hypoglycemia?
Insulin-mediated hypoglycemia
DDx for hypoglycemia
Non-acidemia:
(a) High FFA/low ketones = FAOD
(b) Low FFA/low ketones = hyperinsulin
Acidemia:
(a) High lactate = gluconeogenesis defects, GSD
(b) High ketones = ketotic hypoglycemia, hormone defects (GH or cortisol deficiency), GSD
Other = ingestions, illness, liver failure, malnutrition
Why do you not make ketones in FAOD?
Need fatty acids to enter metabolism cycle at level of Acetyl CoA to then make ketones
In acute management, what should you glucose infusion rate be?
6-8 mg/kg/min
How to calculate water deficit in setting of hyperNa?
Water deficit = (0.6 x wt) x (current Na - ideal Na/ideal Na)
How fast to correct hyperNa or hypoNa?
No faster than 10-12 mEq/L in 24 hours (no more than 1 mEq/L per hour)
- Replace over 48 hours in moderate
- Replace over 72 hours in severe
DDx for hyperNa
- Water deficit: Renal losses (DI), GI losses, insensible losses, decreased intake (including midline defect to cause impaired thirst)
- Excessive Na: Increased intake, hyperaldosteronism
Most important investigation in hyperNa
Urine osm
DDx for low serum osmolality hypoNa
- Hypovolemic: High urine Na (renal losses = diuretics, renal dysfunction, RTA, AI), low urine Na (extra renal losses = GI, insensible)
- Euvolemic: SIADH, DI, hypothyroidism, AI
- Hypervolemic: High urine Na (renal failure), low urine Na (CHF, cirrhosis)
x4 most important points in assessment in disorders of sexual development
- Gonads - palpable?
- Phallic length - clitoris (<9mm) + penis (>2.5cm)
- Posterior labial fusion - # and location of urogenital openings
- Other dysmorphic features or malformations
x2 initial investigations for DSD
- US to visualize gonads
- Karyotype
Most likely group of diagnoses if (a) gonads are palpable and (b) if gonads are NOT palpable
(a) XY DSD
(b) XX DSD
Work-up if you are thinking XY DSD
- Testosterone, androstendione, DHEAS, LH/FSH, MIS
- US
- Karyotype
Work-up if you are thinking XX DSD
- 17-OH progesterone, cortisol, lytes
- Testosterone
- Karyotype
- US
Main categories of DDx for XY DSD
- Disorders of gonadal/testicular development
- Disorders of androgen synthesis or action
Main categories of DDx for XX DSD
- Disorders of gonadal/ovarian development
- Disorders of androgen excess
CAIS vs PAIS
CAIS = complete, feminized PAIS = partial, variably virilized
Chronic AI therapy - CC dose + other addition
- HCT 6-8 mg/kg2/day divided TID
- For primary AI = mineralocorticoid with fludracortisone
HypoCa ddx
- Low PTH/hypoparathyroidism = impaired synthesis or secretion of PTH (DiGeorge, autoimmune, infiltration of gland)
- High PTH = deficient Ca intake/intestinal absorption, vitamin D deficiency, defects in vitamin D metabolism (renal dysfunction, hepatic dysfunction), defects in vitamin D action, end organ resistance to PTH (pseudohypoparathyroidism)
Acute manifestations of hypoCa
- Neuromuscular excitability = muscle contractions, tetany, seizures, broncho/larygnospasm, Trousseau’s (BP), Chvostek (facial nerve)
- CVS = prolong QT, hypotension, arrhythmia
- Papilledema
What electrolyte should you also correct in hypoCa?
Mg
Management strategies for hyperCa
- Stop Ca + vit D
- Increase excretion = IV fluids, avoid diuretics, dialysis
- Stop bone resorption = calcitonin, bisphosphonates, GC’s
DDx for hyperCa
- Increased intestinal absorption = increased intake, vitamin D mediated/intoxication (increased intake, granulomatous disease, chronic inflammatory d/o)
- Increased bone resorption = malignancy, hyperparathyroidism (adenoma, secondary/tertiary from chronic renal disease)
- Diminished excretion = diuretics
- Familial hypoCa-uria hyperCa
- Hyperthyroidism, thyrotoxicosis
- HypoPO4
- Other: subcutaneous fat necrosis, AI, pheo, William’s syndrome, RTA, IEM
Where is vitamin D activated?
Liver
Extra-skeletal effects of vitamin D
- Skin (tx for psoriasis)
- Immune effects (for B+T cell function)
- Cancer
- Psychiatric conditions
x2 most important minerals for bone mineralization
- Ca
- PO4
What does CPS recommend for GC taper?
- <1 month = no taper
- 1-3 months = 1-2 week taper
- 3-6 months = 2-3 week taper
- > 6 months = 3-4 week taper
What range for AM cortisol would be suspicious for (a) AI vs (b) AS?
(a) <100
(b) 100-275
What children are considered higher risk for AS and should be considered for screening?
- High dose ICS (flut >500mcg/d) for >3 months
- Systemic CC’s for >2 weeks
- Swallowed ICS for >1 month
- Concomitant use of nasal steroids
- ICS for >3 months in conjunction with CYP3A4 inhibitors
What medications can prolong GC half-life?
CYP3A4 = antiretrovirals, antifungal agents, some Abx
What time of day is it better to dose GC’s?
Morning - to not interfere with HPA axis
Symptoms/signs of possible AS
- Poor linear growth + weight gain
- Anorexia
- Fatigue + weakness
- Abdo pain, N/V
- Headaches
- Myalgia/arthralgia
- Psychiatric symptoms
x2 types of rickets
Hypophosphatemic and hypocalcemic
In hypophosphatemic rickets, what would PTH, PO4, and Ca look like?
- PTH normal/mildly high
- PO4 low
- Ca normal
In hypocalcemic rickets, what would PTH, PO4, and Ca look like?
- PTH high
- PO4 normal/low
- Ca normal/low
Best test for Cushing Syndrome
Dexamethasone supression test
If the dexamethasone suppression test is positive, what does this mean for Cushing Syndrome?
- Means that the AM cortisol following dose of dexamethasone remains elevated
- Must be another source for steroid
What to think about for a teenage girl with advanced breast development but no adrenarche?
Androgen sensitivity syndrome
6 year old boy with pubic hair but testes <2mL - what is the most likely cause?
Benign premature adrenarche
Initial screening investigations for patient who is 3rd%tile for height while MPH is 75th%tile
- CBC
- ESR
- Bone age
- Cr, electrolytes, extended lytes
- Karyotype (for all girls)
- TSH
- Celiac screen
- IGF-1 (if GV off)
What do you see in the serum at the end of a water-deprivation test if central DI?
Increased serum osmolarity
When do you screen for T2DM?
At least 2 or more risk factors once child is 10 years old or has reached puberty:
- Family history or of high ethnic group
- Obesity
- Evidence of impaired glucose tolerance
- Impaired glucose tolerance
- Use of psychotropic medications
Triad for McCune Albright
- Peripheral precocious puberty
- CALM
- Polyostotic fibrous dysplasia
What endocrinopathy can present similarly to PCOS?
Non-classical CAH = especially in certain ethnic groups (Mediterranean, Hispanics, and Eastern European Jews)
How to differentiate PCOS from non-classical CAH? (By labs)
- 17 OHP level
- ACTH stimulation test
What is androgen insensitivity syndrome?
- One of the most common XY DSD
- X-linked recessive
- Wide variation on presentation: phenotypic female (complete) to various forms of ambiguous genitalia to phenotypic male with infertility
What classification of disease is 5-alpha reductase deficiency? What does this enzyme typically do?
Abnormal androgen synthesis
-Impaired virilization secondary to inability to convert testosterone to DHT (typically converts 8% of testosterone to a stronger form = DHT)
What other XY DSD is difficult to differentiate with androgen insensitivity syndrome?
5-alpha reductase deficiency
At what age is it considered safe to start a statin?
> 10 years old
What maternal anti-arrhythmia medication causes a thyroid goiter in the child?
Amiodarone
Karyotype = 46, XY
(a) gonads/ducts
(b) gonadal cells
(c) gonadal hormones
(d) effect on ipsilateral ducts
(e) internal genitalia
(a) testis + mullerian
(b) leydig + sertoli
(c) testosterone + AMH
(d) +wolfian / -mullerian
(e) vas, epididymis, seminal vesicles
What is the M + F structure that is:
(a) genital tubercle
(b) urogenital folds
(c) labioscrotal swelling
(a) Penis / Clitoris
(b) Penile urethra / labia minora
(c) Scrotum / labia majora
What are the two most common types of DSD or ambiguous genitalia?
- 46, XX CAH
- 45X/46XY mixed gonadal dysgenesis
3 forms of 46 XX CAH
- Salt wasting (75%)
- Simple virilizing
- Late onset, non-classical
What are the x2 main functions of hydrocortisone in CAH?
- To restore cortisol
2. Suppress further virilization by providing a negative feedback to the hypothalamus + pituitary gland
Newborn exam: penis with incomplete foreskin + urethral meatus on underside of penis, testicles descended bilaterally
- what is this?
Isolated hypospadias
What would make you worry about DSD if there is hypospadias?
Undescended testes
What other x2 associations (specific to penis) can be found with hypospadias?
- Foreskin incomplete ventrally
- Erections curve downward (chordee)
Risk factors to consider screening for T2DM (+how many RF’s do you need to go ahead with screening)
- Obesity
- Family history
- Ethnicity
- Evidence of insulin resistance
- PCOS
- Impaired glucose tolerance
- Exposure to DM in-utero
- NAFLD
- HTN/dyslipidemia
- Need x3 if pre-pubertal
- Need x2 if post-pubertal
Most important investigation when query PCOS
testosterone
What is important to r/o for a query PCOS?
Other causes of hyperandrogenism - Cushing, exogenous, sex differentiation disorder (e.g., late onset CAH)
Once you have the mid-parental height = then how do you decide the expected adult height for this child?
+/- 8.5
When do you start screening for (a) retinopathy and (b) nephropathy (including test) and (c) dyslipidemia for patient with T1DM?
(a) 15 years old or >5 years since dx
(b) 12 years old or >5 years since dx
- Urine PCR
(c) 12 and 17 years old
Dx for 14 years old M with 3-6 month history of gynecomastia (SMR 3) - counselling?
- Physiological/pubertal gynecomastia
- Should not be greater than SMR 3 and should resolve after 2 years
What should you look out for in a boy with Physiological/pubertal gynecomastia?
?Klinefelter’s
?Prolactin level if galactorrhea or anti-psychotic
What is stage 4 neuroblastoma?
Good prognosis - involvement of skin
Once confirm dx of neuroblastoma - what are investigations to consider for staging?
- MRI: chest, pelvis, abdo
- BMA
