Endo Topic Reviews Flashcards
(293 cards)
1
Q
Inheritance of NF1?
A
Mutations on NF 1 gene on chromosome 17
AD (50% de novo)
2
Q
MODY (Monogenic diabetes) typical presentation and inheritance pattern
A
MODY - genetic enzyme deficiency
Autosomal dominant
Asymptomatic and lean
NO DKA
Often have lower insulin requirements
Managed with sulfonylureas
3
Q
List criteria for dx of PCOS in adolescents:
A
PCOS is characterized by:
1) Oligoovulation or anovulation (eg amenorrhea, oligomenorrhea)
2) Hyperandrogenism: acne, hirsutism, male pattern hair loss, elevated testosterone, androstenedione, elevated LH/FSH ratio
4
Q
List 4 clinical symptoms of excess androgen:
A
Hirsutism
Acne
Male pattern baldness
Alopecia
5
Q
During what phase of the cycle should tests for PCOS be completed in a non-amenorrheic patient?
A
day 2-4
6
Q
LH:FSH ratio in PCOS?
A
Typically elevated
LH typically elevated, FSH is low/normal which causes elevated ratio
7
Q
1st line therapy for PCOS?
A
Combined hormonal contraceptives
Progestin inhibits endometrial proliferation
Estrogen elevates circulating sex hormone binding globulin
8
Q
What is a second medication that is used if evidence of insulin resistance in PCOS?
A
Metformin –> reduces insulin resistance and levels of androgens
9
Q
What medication can be used for relief of hirsutism in PCOS? Name two potential side effects of this medication
A
Spironolactone
- can lead to irregular menses and be teratogenic
10
Q
List a differential diagnosis for PCOS:
A
- Pregnancy
- Hyperprolactinemia
- Thyroid disorder
- Congenital adrenal hyperplasia
- Androgen producing adrenal or ovarian tumor
- Cushing’s syndrome
- Hypothalamic amenorrhea
11
Q
What are the 5 “I” precipitating factors for DKA?
A
Infection
Infarction
Infant (pregnancy)
Indiscretion (dietary noncomplicance)
Insulin deficiency
12
Q
Differences between HHS and DKA?
A
HHS
- glucose > 33
- profound dehydration
- lethargy/coma
- little to no ketosis
- more common in type 2
13
Q
CPS classification of mild / mod / severe DKA ? pH and bicarb values
A
Mild = pH 7.2-7.29, bicarb 10- <18
Mod = pH 7.1-7.19, bicarb 5-9
Severe = pH < 7.1, bicarb < 5
14
Q
Risk factors for cerebral edema in DKA?
A
*New-onset diabetes
*Longer duration of symptoms
*Young age (<5 years)
*Severe acidosis (pH <7.1 or HCO3 <5)
*Laboratory evidence of severe dehydration (elevated urea, hematocrit)
*Hypocapnia (pCO2 <21)
*Insulin therapy in first hour of management and/or insulin bolus
*Rapid administration of hypotonic fluids
*Use of sodium bicarbonate
*Failure of measured sodium to rise during treatment
15
Q
Calculate corrected Na in DKA?
A
Na +[( glucose – 5) x 0.3]
16
Q
Anion gap calculation?
A
Anion gap = Na – (Cl + H3O)
normal = 12±2
17
Q
If acidosis not correcting in DKA, what are some things to consider:
A
Insulin mixed correctly?
Being given appropriately?
Making sure line is flushed after giving insulin
Source control of infection?
Malperfusion or lactic acidosis
Hyperchloremia causing non anion gap acidosis
Getting more dehydrated
Exogenous sources for acidosis like toxins
18
Q
Emergency steps in responding to suspected cerebral edema in DKA?
A
- Elevate head of bed to 30°; keep head midline
- After initial fluid resuscitation, run IV fluids at 75% of rate outlined
in Rehydration Table below - Monitor BP and perfusion closely to avoid hypotension and prevent
further cerebral injury - Administer 3% NaCl 5 mL/kg (MAX 250 mL) IV over 10 min OR
mannitol 0.5-1 g/kg (MAX 100 g) IV over 15 min - Update Pediatric Referral Centre
- May repeat hyperosmolar agent dose x 1 after 30 min if no
improvement or use alternate agent - Head CT not required prior to treatment or transport
19
Q
Differences between presentation of precocious puberty in NF 1 vs McCune Albright?
A
NF 1 –> would present as CENTRAL precocious puberty due to optic glioma
Stages of puberty should still occur in order
McCune Albright –> presents as PERIPHERAL precocious puberty
Stages of puberty occur out of order
20
Q
Classic triad of McCune Albright?
A
1) Polyostotic Fibrous Dysplasia of bone (common facial – painful facial asymmetry; thin cortex, intramedullary ground glass - can present as a “bump” on a bone)
2) Autonomous Endocrine Hyperfunction - Peripheral Precocious puberty (vaginal bleeding precedes breast development), Hyperthyroidism, Cushing syndrome, Acromegaly/gigantism, Hypophosphatemic Rickets
3) Café au lait macules (Coast of Maine - jagged border (vs coast of california which is smooth)
21
Q
What is the signal for the gonadotroph cell in the pituitary to release gonadotropins LH and FSH at the start of puberty?
A
Hypothalamus starts secreting PULSATILE GnRH
22
Q
Progression of normal puberty in females?
A
Boobs, pubes, growth (height), flow (menses)
Peak height velocity occurs breast stages II-III (typically 11-12y) and always precedes menarche
23
Q
Progression of normal puberty in males?
A
Balls, pubes (pubic hair), growth (penile length), flow (ejaculation)
Acceleration of growth in height begins AFTER puberty and is maximal at genital stages 4-5 (13-14 yo)
24
Q
What volume do testes have to be to indicate that puberty has started in males?
A
4ml or greater
25
What is the role of FSH in the female vs male?
Female - along with LH, promotes growth of ovarian follicles and signals ovary to make estradiol during follicular phase and progesterone during luteal phase
Male - Stimulates the development of the seminiferous tubules, stimulates spermatogenesis
26
What is the role of LH in females vs males?
Male - stimulates Leydig cells to produce testosterone
Females - surge at mid cycle triggers ovulation
27
Differences in elevated serum lipids between familial hypercholesterolemia and familial combined dyslipidemia?
FH -- isolated elevated LDL
FCD -- mixed pattern of abnormalities: high LDL-C, high Tg, low HDL-C
28
Dx of definite Familial Hypercholesterolemia?
Need:
LDL 4.0 mmol/L or greater
PLUS
DNA mutation OR tendon xanthomas OR LDL-C 8.5 or greater
29
Treatment for familial hypercholesterolemia?
Diet, lifestyle
Statins - recommended to start between 8-10 years of age if LDL-C remains >/= 4.9 mmol/L or >/= 4.1mmol/L with a family history of premature ASCVD or other cardiovascular risk factors
secondary agents as required - highest evidence for ezetimibe
Target LDL-C < 2.0 mmol/L and non-HDL-C < 2.6mmol/L
30
Dx of Probable Familial Hypercholesterolemia?
LDL-C 4.0 mmol /L or greater
PLUS
1st degree relative with high LDL
OR Proband or 1st degree relative with early atherosclerotic cardiovascular disease ( <55 men, < 65 women)
31
Why do patients sometimes get mild hirsutism with functional hypothalamic amenorrhea?
When estrogen levels are low, androgens have a more pronounced effect, potentially leading to mild hirsutism.
32
Diagnostic criteria for NF1? Need 2 or more of these 7:
2 or more of 7:
C: > 6 or more Café-au-lait macules
>5mm pre-pubertal >15mm post-pubertal
R: Affected 1st degree Relative
O: Optic nerve glioma
Importantly, they can also cause precocious puberty, as these tumors may affect the hypothalamic-pituitary-gonadal axis.
P: Pseudoarthrosis (distinctive osseous lesions can be sphenoid dysplasia or tibial pseudoarthrosis)
L: > 2 or more Lisch nodules
A: Axillary or inguinal freckling
N: > 2 neurofibromas OR 1 plexiform neurofibroma
Cutaneous neurofibromas are soft, benign tumors that develop on or under the skin
Plexiform neurofibromas can grow along nerve pathways and can be more complicated, sometimes causing deformities or functional impairment
D: Dysplasia of the sphenoid
33
What is the DDX for short stature?
Familial (short family)
**Constitutional (late bloomer)
**Growth Hormone Deficiency (may have midline defects)
**Hypothyroidism - short stature may be only symptom
**Cushings (steroid excess)
Malnutrition, chronic GI disorders
SGA baby with insufficient catchup growth
**Syndromes: Turner, Tris 21, prader willi, russel-silver
34
What underlying cause is most in keeping with this growth chart?
Familial Short Stature
35
how does constitutional growth delay present?
Family history of delayed growth and puberty
slow growth velocity and slow entry to puberty then should be normal
**Delayed bone age**
Predicted adult height appropriate for mid-parental height
36
What underlying cause is most in keeping with this growth chart?
Constitutional Delay of Growth and Puberty
37
Presentation of growth hormone deficiency?
Poor growth velocity
Delayed bone age
May have neonatal hypoglycemia, hyperbili
May have midline defects: *micropenis*, "cherubic" features, midface hypoplasia, cardiac defects
low IGF-1 (more stable surrogate for growth hormone)
38
What underlying cause is most in keeping with this growth chart?
Growth Hormone Deficiency
39
gold standard for diagnosis of Growth Hormone Insufficiency?
Growth hormone stimulation test
(low response on 2 tests)
attempt to stimulate GH response using arginine, clonidine, L-dopa or propranolol, but GH doesn't rise
40
Treatment of growth hormone insufficiency is daily subcutaneous injections of growth hormone analogue. What are the side effects?
SCFE, Idiopathic Intracranial Hypertension, hyperglycemia, growth of nevi, carpal tunnel, injection site reactions, sudden death in patients with OSA
FYI Other indications for GH therapy – Turner syndrome, chronic renal failure, SGA with inadequate catch-up growth, ISS (<-2.25SD), SHOX mutation, Prader-Willi Syndrome, Noonan Syndrome
41
What is the definition of precocious puberty?
Girls: Thelarche (breast development) before age 8
Boys: Testicular enlargement before 9
prec puberty is 10x more common in females!
42
Will LH, FSH and estrogen levels be low / normal / high in functional hypothalamic amenorrhea?
LH, FSH, and estrogen all likely to be low
However FSH will typically be higher than LH
This is the pattern typically seen in pre-pubescent girls
43
what size of testicle is indicative of pre-pubertal
≤4ml per Prader bead
44
what is the sequence of puberty?
females: breasts, height, menses
males: testicle enlargement, pubic hair, growth spurt
45
What is the antibody associated with Grave's disease?
Thyroid receptor binding inhibitor immunoglobulins (TRAbs)
Thyroid stimulating immunoglobulin (TSI-Ab)
Can also have positive anti-TPO and anti Tg antibodies
46
What is the differential for precocious puberty?
**All Boys with PP MUST get Head MRI, girls should have one if PP occurs <6yrs**
CENTRAL PRECOCIOUS PUBERTY (GnRH dependent):
**Steps of puberty occur in order**
- Idiopathic (80-90% of girls)
- CNS tumour (Eg. optic glioma - presents with precocious puberty due to hypothalamic involvement)
- Neurofibromatosis-1
- Hydrocephalus, CP
- Radiation
-----------
PERIPHERAL PRECOCIOUS PUBERTY (GnRH independent):
**Steps of puberty occur out of order**
- Ovarian/Testicular cyst or tumor
- Congenital Adrenal Hyperplasia
- Adrenal Tumour
- hCG-producing tumour
- McCune Albright Syndrome
- Hypothyroidism
- Exogenous Estrogen/Testoserone
47
neurofibromatosis inheritance pattern
autosomal dominant loss-of-function mutations in NF1 gene
48
Conditions associated with Grave's disease?
DM, celiac, primary adrenal insufficiency
SLE, vitiligo, RA, myasthenia gravis
Turner syndrome and T21
49
How does complete androgen insensitivity syndrome (CAIS) present?
CAIS =genetic mutation in androgen receptor
●Female phenotype with normal breast development
●Primary amenorrhea
●Little or no axillary or pubic hair
●Absent uterus, but testes present (usually in abdomen)
●46,XY karyotype
Dx = genetic sequencing (x-linked recessive)
50
What does pelvic ultrasound show in Complete androgen insensitivity syndrome?
Pelvic ultrasound shows absent Mullerian structures due to the action of AMH. Wolffian duct derivatives (vas deferens, epididymis, seminal vesicle) are absent due to androgen resistance
51
Name several causes of hyperthyroidism that are due to increased TSH secretion:
TSH-secreting pituitary adenomas
Pituitary thyroid hormone resistance
hCG-induced (TSH-like action)
Others that are rare in children
All would have negative antibodies and diffusely increased radioactive iodine or technetium uptake
52
What is the pathophysiology of Grave's disease?
Autoimmune disease
Auto-antibodies stimulate the TSH-receptor
53
What is the definition of delayed puberty?
Girls:
-No breasts by 13yrs old
-No menses by 16 yrs old
Boys
- No testicular enlargement by 14 yrs
(or > 5 Years from onset of puberty to completion for either)
54
what is the DDX for delayed puberty?
Hypogonadotropic Hypogonadism (LOW LH/FSH):
- constitutional (late bloomer, delayed bone age)
- hypopituitarism
- Kallman syndrome (*anosmia*, microphallus)
- Prader-Willi
- Chronic disorders affecting pituitary fxn (anorexia, malnutrition, IBD, celiac, CNS radiation or trauma etc)
Hypergonadotropic Hypogonadism (HIGH LH/FSH):
- Turner syndrome
- Klinefelter
- Acquired causes of gonadal dysfunction (ovary or testicle surgery/infection/trauma, systemic chemo)
55
Radioactive iodine or technetium 99 uptake in Grave's disease?
Diffusely increased
56
How would subclinical hyperthyroidism present?
Normal FT4 with suppressed TSH
57
List 3 causes of high radioactive iodine uptake in the thyroid:
Graves' Disease: Diffuse high uptake across the entire thyroid gland due to overproduction of thyroid hormones.
Toxic Multinodular Goiter (Plummer's Disease): Patchy, irregular uptake due to the presence of autonomous hyperfunctioning nodules.
Thyroiditis (early phase): The thyroid may take up increased iodine if there’s a transient increase in thyroid hormone production.
58
List 3 causes of low radioactive iodine uptake:
Common in conditions causing thyroid hormone excess without thyroid gland activity:
- intake of thyroid hormone
- thyrotoxic phase of chronic lymphocytic thyroiditis (Hashitoxicosis)
- subacute thyroiditis (painful, postviral, granulomatous, de Quervain)
59
What is the presentation of Cushing's Syndrome?
Short stature
Abdominal (truncal) obesity with thin limbs
Round ("moon") facies
Buffalo hump (dorsocervical fat pad)
*Hypertension
*Red/purple striae (not pale striae seen with rapid weight gain)
decreased muscle mass
delayed puberty
easy bruising
60
what is the presentation of premature thelarche?
*Isolated breast development in pre-pubertal girl (usually first 2 yrs of life)
*unilateral or bilateral breasts (tanner 2-3)
Normal bone age
Normal growth velocity
61
treatment for premature thelarche?
Reassure and follow up in 3-6 mos, most will regress
62
Presentation of X-linked adrenoleukodystrophy?
= accumulation of very long chain fatty acids (VCLA)
~7yr old boy
*ataxia
*attentional problems
*hyperpigmented skin (increased ACTH secretion)
Adrenal insufficiency: fatigue, GI sx, weakness, AM headaches
(accumulation of fatty acids in the adrenals causes adrenal dysfxn)
63
Diagnosis of X-linked adrenoleukodystrophy?
Very Long Chain Fatty Acids (VLCFA) will be elevated
(they accumulate bc they can't get broken down - and the accumulation causes the organ dysfunction --> Ataxia, poor attention, adrenal insufficiency)
FYI tx is stem cell transplant (HSCT) and hydrocortisone for adrenal insufficiency
64
Presentation of diabetes insipidus?
polydipsia and polyuria with a dilute urine
hypernatremia
dehydration
65
Diagnosis of central vs nephrogenic diabetes insipidus?
Water deprivation test - pt continues to have polyuria with poorly concentrated urine (= dx of diabetes insipidus)
While water deprived, give DDAVP
if urine becomes more concentrated = dx of central DI (where problem is the lack of secretion of ADH)
if no change = dx of nephrogenic DI (kidneys are unresponsive to ADH)
66
Treatment of diabetes insipidus?
Nephrogenic DI = managed by nephro, usually thiazide diuretic and other meds to reduce urine output
Central DI = oral DDAVP q8-12h (side effect of hyponatremia + water intoxication)
(Central DI pts should be screened for other deficits in anterior pituitary hormones, including thyrotropin, adrenocorticotropic hormone, and growth hormone, and for hypogonadotropic hypogonadism)
67
What is a "cold" thyroid nodule
Does not take up iodine on RAI test --> may be nonfunctional or possibly malignant
May need fine needle biopsy
68
First line medication for Grave's?
List what bloodwork monitoring is necessary.
What side effects can be associated?
Methimazole (MMI)
MOA: Inhibits thyroid hormone synthesis by decreasing oxidation of iodide and iodination of tyrosine
Bloodwork / Monitoring:
Pre-medication starting - children should be tested for LFTs, CBC (neutrophil count) → repeat at 8 weeks after medication is started or after a dose increase
Common Adverse effects: Rashes, Myalgias, arthralgias, Nausea
Major adverse effects: Vasculitis with Lupus-like syndrome; Hepatitis, jaundice, liver failure; Agranulocytosis
69
What pre-medication is needed before radioactive iodine therapy (ablation) or surgery (thyroidectomy) in Grave's disease?
Both beta-blocker and MMI to reduce the risk of thyroid storm
70
In central (secondary) adrenal insufficiency, what is the impact on mineralocorticoid production?
Not impacted as it is a deficiency in CRH or ACTH, not at the level of the adrenal gland
71
Symptoms of secondary adrenal suppression?
Poor linear growth * (50% of cases)
Poor weight gain
Anorexia
N/V
Malaise
Weakness/fatigue
Headache
Abdominal pain
Myalgia/arthralgia
Psychiatric symptoms
Cushingoid features
72
When is a child at risk of adrenal insufficiency on systemic steroids?
Children at risk of AS when GC tapered below physiologic GC dose – 8mg/m2/day
Consider screening for AS w/ AM cortisol before discontinuing or tapering GC below physiologic dose threshold
73
What is the approach to glucocorticoid taper in secondary adrenal insufficiency?
<1month – no taper
1-3 months – 1-2 week taper
3-6 months – 2-3 week taper
>6 month exposure – 3-4 week taper
74
75
Definition of central vs nephrogenic diabetes insipidus?
Central: No ADH (pituitary does not secrete ADH)
Nephrogenic: Kidneys don't respond to ADH
76
What is the most common cause of ambiguous genitalia?
Congenital Adrenal Hypoplasia
77
What is the most common enzymatic defect in CAH?
21-hydroxylase deficiency (results in decreased cortisol synthesis, loss of negative feedback and increased ACTH secretion, increased production of androgens)
78
What are the classic investigations seen in CAH and what is the gold standard test?
Hyponatremia
Hyperkalemia
Hypoglycemia
Hypotension (in crisis)
High 17-OHP
ACTH stimulation test gold standard
79
How does a 46XX vs 46XY presentation of CAH differ?
46 XX will present in adrenal crisis often, with virilized genitalia (i.e. clitoromegaly)
46XY will present with normal male genitalia, adrenal crisis, and precocious pseudopuberty
80
What are the 3 types of CAH?
1.) Classic salt wasting
Atypical genitalia in females.
Salt wasting at 7-14days
2.) Classic non salt wasting (simple virilizing)
Early virilization age 2-4 years
3.) Non classic (late onset)
Early pubarche or precocity in school age children, PCOS-like picture
81
Treatment of CAH
Treatment
Acute setting (salt wasting crisis): FLUIDS, correct electrolyte abnormalities
Glucocorticoid replacement 100mg/m2/d (stress dosing)
Mineralocorticoid replacement (Florinef) when weaning HC
Doses of steroids should be high enough to suppress CRH/ACTH secretion and therefore minimize virilization
82
Glucocorticoid replacement and stress dosing in minor, moderate and major surgical procedure
Minor or moderate - 30 mg/m2/day hydrocortisone equivalent divided x 3 until symptoms resolve
Major surgery -
Hydrocortisone 50 mg/m2 to 100 mg/m2 IV (maximum 100 mg) pre-op, then 100 mg/m2/24 h IV (maximum 200 mg) divided every 6 h or by continuous infusion
83
List at least 5 causes of primary (peripheral) adrenal insufficiency?
Imparied steroid hormone biosynthesis (eg CAH)
Adrenal destruction or dysfunction (eg mitochondrial defects)
Impaired adrenal development or hypoplasia
Infection (TB, HIV, CMV), hemorrhage, infarction of the gland
Drug side effects (ketoconazole, rifampin)
Autoimmune adrenalitis (Addison's disease)
84
What is primary adrenal insufficiency?
Disease intrinsic to adrenal cortex, causing HIGH ACTH and low cortisol.
At risk of mineralocorticoid def (low aldosterone, elevated renin and hyponatremia and hyperkalemia)
85
Clinical manifestations of Primary adrenal insufficiency
Skin and mucous membrane hyperpigmentation
Morning headache
Fasting hypoglycemia
Nausea, vomiting, abdominal pain, poor appetite
Anorexia, weight loss
Slowing of linear growth
Muscular weakness, fatigue
Hypotension, dizziness; salt craving
Adrenal crisis (acute onset or exacerbation of insufficiency with electrolyte abnormalities, metabolic acidosis, and shock)
Orthostatic hypotension
86
List at least 5 causes of secondary (central) adrenal insufficiency
Suppression of ACTH due to long-term exogenous glucocorticoid usage
Panhypopit
Infiltrative process (eg craniopharyngioma)
Radiation therapy
Multiple anterior pituitary hormone deficiency
Hypothalamic dysfunction
87
What are the 3 zones of the adrenal cortex and what hormones do they release?
The zona glomerulosa produces mineralocorticoids, the zona fasciculata produces glucocorticoids, and the zona reticularis produces androgen precursors (mostly DHEA with some androstenedione)
88
How to interpret morning cortisol levels?
First morning cortisol (at 7-9 AM)
Normal: 350-500 nmol/L
Screening threshold: <275 nmol/L
ACTH stim test is gold standard for diagnosing AI
89
How to do an interpret ACTH stimulation test?
Measure serum cortisol at time 0
Administer cosyntropin 250 micrograms IM/IM (15 microgram/kg)
Measure serum cortisol in 60 min
Normal response is a doubling of baseline cortisol in 60 min with peak > 500nmol/L (this is in the CPS statement)
With primary adrenal insufficiency: there is a suboptimal cortisol response b/c adrenal gland isn’t working properly and responding properly to signal from ACTH
90
Daily physiological hydrocortisone dosing?
8 mg/m2/day hydrocortisone equivalent daily
91
Management of adrenal crisis?
0.9% NS 20ml/kg bolus for resuscitation
Hydrocortisone 100mg/m2 IV bolus, then 100mg/m2/d divided 6h
Treat underlying illness
92
Which patients with precocious puberty always require an MRI?
ALL males
All girls < 6
93
What would LH/ FSH and estrogen be in Turner syndrome?
LH/FSH high
Estrogen low
Premature ovarian failure
94
List 5 cardiovascular anomalies that can occur with Turner syndrome
Bicuspid aortic valve (most common), coarctation, aortic stenosis, MVP, PAPVD (partial anomalous pulm venous drainage), HLHS; also aortic root dilatation, HTN (idiopathic vs CoA)
95
What is the most common renal anomaly in Turner syndrome?
Horseshoe kidney
96
What are at least 5 endocrine abnormalities in Turner syndrome?
short stature
lack of spontaneous puberty (gonadal dysgenesis (with streaks of fibrous tissue)
premature ovarian failure (high FSH/LH, low estrogen)
primary amenorrhea
lack of secondary sexual characteristics
hypothyroid
T2DM and glucose intolerance
hyperlipidemia
97
Name at least three MSK abnormalities in Turner syndrome
DDH, scoliosis, kyphosis, lordosis, cubitus valgus, short 4th metacarpals, tibial exostosis
98
Name two most common HEENT abnormalities in Turner syndrome
Recurrent AOM
SNHL
99
What test do you need to diagnose Turner syndrome
Karyotype
100
How early can you start GH therapy in girls with Turner syndrome?
As early as 2 years old
Start when height begins to fall off percentile
Considered standard of care
101
What age is the onset of puberty considered precocious puberty?
< 8 in girls
< 9 in boys
102
At what age is puberty considered delayed
Puberty is considered delayed if it has not started by age 13 in girls and 14 in boys
103
Differential for hypocalcemia
PTH low / inappropriately normal
-genetic (DiGeorge, mutation in CaSr, PTH Gene mutation, mitochondrial disorders, Kenny-Caffey syndrome)
- autoimmune (autoimmune polyglandular syndrome - hypoparathyroidism, candidiasis, adrenal insufficiency)
- post surgery, radiation etc
PTH high
- Abnormal Vitamin D metabolism (low Vitamin D
- pseudohypoparathyroidism
- renal insufficiency
- nutrition
-low magnesium
- sepsis
-drugs
Magnesium low
- GI losses
- renal wasting
- alcoholism
- malnutrition
- drug induced
104
Signs and symptoms of hypocalcemia
Tetany: neuromuscular irritability
Perioral and acral paresthesia
Muscle cramps
Laryngospasm
Trousseau sign
Chvostek sign
Seizures
CVS: Hypotension, decreased cardiac contractility, long QT
Papilledema
Psych: emotional instability, anxiety, depression
105
How can you determine with Calcium and phosphate levels if underlying etiology is related to PTH versus Vitamin D?
If your calcium and phos are in the same direction (eg low calcium low phosphate), it is a vit D problem
If your calcium and phos are in different directions, it is a PTH problem
106
What is the best measure of vitamin D stores in the body?
25-OH Vitamin D
107
If underlying diagnosis is primary hypoparathyroidism, how do you treat?
If due to primary hypoparathyroidism, need to supplement with oral calcium AND calcitriol (active vitamin D)
If nutritional, supplement with calcium and vitamin D
If symptomatic: IV calcium gluconate
108
Above what TSH value is immediate treatment in an infant warranted?
If TSH > 40, repeat labs but start levothyroxine immediately
109
What is the dose of levothyroxine in congenital hypothyroidism
10-15mcg/kg daily
110
Most common cause of congenital hypothyroidism
Abnormal thyroid gland development - aplasia, hypoplasia, or an ectopic gland
111
Why is it important to treat congenital hypothyroidism early?
If delay in treatment can lead to
- poor growth
- significant developmental delays
- jaundice, bradycardia, poor feeding, delayed closure of the fontanelles, constipation, floppy
112
What kind of formula should be avoided for infants with congenital hypothyroidism?
AVOID soy formula
113
What is the best measure of adiposity specifically for predicting metabolic syndrome?
Waist circumference
114
Inheritance pattern of of all Multiple Endocrine Neoplasia (MEN1, MEN2A, MEN2B) syndromes?
Autosomal Dominant
115
Diagnostic criteria for MEN1 (Multiple Endocrine Neoplasia 1)?
≥ 2 classic endocrine tumours (Hyperparathyroidism, Pituitary Tumours (PRL, GH, ACTH), Insulinoma*)
OR a classic endocrine tumour types + known 1st degree relative with MEN1
116
what is the most common cause of acquired hypothyroidism in children?
Autoimmune Thyroiditis = Hashimoto's = Chronic Lymphocytic Thyroiditis
2:1 F:M
higher risk in tris 21, Klinefelter, celiac, T1DM, Turner
117
Presentation of autoimmune thyroiditis?
Primary Hypothyroidism features:
- diffuse goiter (most common cause of goiter)
-short (normal weight)
- dry skin/hair
- cold intolerance
- decline in school performance
118
Investigations for autoimmune thyroiditis?
High TSH (>10)
Low T4 (<10)
high antithyroid peroxidase antibodies (TPOAb) - 90% of kids
high antithyroglobulin antibodies (TgAB) - 50% of kids
Thyroid ultrasound only if
- goiter and negative antithyroid antibodies
-nodule or asymmetric goiter
-suspicious cervical adenopathy
(may also see hyperlipidemia, anemia)
119
Treatment and monitoring for autoimmune thyroiditis?
levothyroxine (T4)
and check TSH and T4 4-6 wks after changing dose
monitor TSH and free T4 q4-6 mo
side effects if dose of levo too high: poor sleep, short attention span, behavioral problems
risk of idiopathic intracranial hypertension (headache, vision changes)
120
What is the management of gender dysphoria for individuals assigned female at birth?
Step 1 = Hormone Blockers
Gonadotropin-releasing hormone agonist (GnRHa; leuprolide acetate for depot suspension) IM q4-12 wks
OCP/Depot/IUD
weight-bearing exercise, calcium + vit D intake to promote bone health
Step 2 = Gender affirming care
17B-estradiol
121
Management of gender dysphoria for individuals assigned male at birth?
Step 1 = Hormone Blockers
Gonadotropin-releasing hormone agonist (GnRHa; leuprolide acetate for depot suspension) IM q4-12 wks
Spironolactone or Cyproterone acetate
Step 2 = Gender affirming care
Testosterone esters (may permanently decrease fertility)
122
Risks and benefits of Gonadotropin-releasing hormone agonists (GnRHa) (aka Hormone Blockers) in gender dysphoria?
Risks: lower bone mineral density (partially reverses with cessation)
Benefits: more time for gender exploration, prevents further development of secondary sex characteristics, lowers dose of gender affirming hormone therapy, reduces risk of suicidal ideation
123
How to prescribe Gonadotropin-releasing hormone agonists (GnRHa) (Hormone Blockers) in gender dysphoria?
IM q4-12 wks
Should NOT not be prescribed before the onset of puberty (i.e., Tanner stage 2)
124
Presentation of septo-optic dysplasia?
panhypopituitarism symptoms (ex: neonatal hypoglycemia, micropenis)
*midline defects (eg. cleft palate, absent septum pellucidum or CC)
*Hypopituitarism (GH deficiency, Hypothyroidism, ACTH def, GnRH deficiency, DI)
*Optic nerve hypoplasia (visual impairment)
* = diagnostic criteria, need 2/3
125
Investigations for septo-optic dysplasia?
Head MRI and pituitary function testing (and ongoing, as they can develop over time)
126
what is Grave's disease?
Hyperthyroidism
autoantibodies that bind the thyrotropin receptor (TSHR-Ab) on the thyroid (mimics action of TSH) --> overproduction of T3 and T4
5:1 F:M, peaks 11-15 yrs old
127
Presentation of Grave's disease?
Diffuse goiter
Warm moist skin, heat intolerance, fatigue
fine, friable hair/nails, hair loss
Tall, weight loss despite large appetite
delayed puberty, oligo-/amenorrhea
nervous/fidgety, tremor, emotional lability, tachy, palpitations, HTN
Exophthalmos
128
Investigations for Grave's disease?
High T3/T4
Low TSH (suppressed)
Positive Thyrotropin receptor antibodies (TSHR-Ab) (= thyroid-stimulating immunoglobulins (TSI))
99-technetium scan - indication? purpose?
129
Treatment for Grave's disease?
Methimazole (MMI)
= inhibits thyroid hormone synthesis
Radioactive Iodine therapy (ablation) if >5 yrs and not in remission by 1-2 yrs on MMI (end result = hypothyroidism)
Thyroidectomy if severe eye disease, very large thyroid goiter, failed prev 2 treatments (risk of hypoparathyroidism, recurrent laryngeal nerve palsy)
130
Consider which diagnosis in a phenotypic female with bilateral inguinal hernia and primary amenorrhea and secondary sexual characteristics?
Complete androgen insensitivty
131
Which medications are most commonly associated with gynecomastica
Ketoconazole
Spironolactone
Exogenous hormones (andogens, anabolic steroids, estrogens, growth hormone, gonadotropins)
Soy
Marijuana
Cimetidine
CCBs
First gen antipsychotics
132
Lack of menarche by what age constitutes primary amenorrhea?
15
133
Which syndrome is the most common cause of testicular failure?
Klinefelter syndrome
47, XXY
Testosterone level may be close to normal because Leydig cell function may be retained, however seminiferous tubules are lost and lead to infertility
LH levels are normal to elevated, FSH levels are HIGH
134
Which endocrine glands can be affected in McCune Albright?
Autonomous hyperfunction of 1 or more endocrine glands which may include pituitary, thyroid, adrenal, ovarian/testicular
135
Initial treatment for familial hypercholesterolemia?
Lifestyle - exercise, low fat diet
Statins - recommended to start between 8-10 years of age if despite lifestyle modifications LDL-C remains >/= 4.9 mmol/L or >/= 4.1mmol/L with a family history of premature ASCVD or other cardiovascular risk factors
136
If palpable gonads in an infant with ambiguous genitalia, what is the likely sex?
XY
Likely undervirilized male
If no palpable gonads, more likely XX overvirilized female
137
Which patients should be screened for T2DM?
q2yr with A1C or fasting BG if 2 risk factors (or 3 for younger pts between 8yrs and puberty)
Risk factors include:
Obesity (BMI > 95%)
African, Arab, Asian, Hispanic, Indigenous or South Asian descent
1st degree relative with T2DM
Mom had gestational diabetes
Acanthosis nigricans, hypertension, dyslipidemia, NAFLD (ALT >3x ULN or fatty liver on U/S)
PCOS
impaired fasting glucose
impaired glucose tolerance
Use of atypical antipsychotic
138
What is the median age of onset of T1DM?
bimodal age presentation
4-6y and adolescence
139
What autoimmune diseases are associated with T1DM?
Autoimmune thyroiditis
Celiac disease
Addison disease (primary adrenal insufficiency)
140
Clinical presentation of Celiac disease with history of T1DM
60-70% asymptomatic
Intestinal symptoms are more common in children whose disease is diagnosed within the first 2 yr of life
others - failure to thrive, chronic diarrhea, vomiting, abdominal distention, muscle wasting, anorexia, and irritability.
Extra-intestinal manifestations = IRON deficiency anemia (unresponsive to iron therapy)
141
What is the genetic risk for T1DM in monozygotic twins and what is the rate of increase in first degree relatives with T1DM?
50% of monozygotic twins are discordant for T1DM
Risk increases with family history for T1DM by 5% for 1st degree relative
142
Clinical presentation of T1DM
Polyuria (nocturia), polydipsia, weight loss, fatigue
Hyperglycemia, glucosuria
Hypovolemial
Symptoms of ketoacidosis: additionally nausea, vomiting, kussmaul respiration, somnolent, dehydration, fruity smelling breath
143
What viral infections are most common to trigger B-cell autoimmunity and presentation of T1DM?
Congenital rubella syndrome
Enteroviruses
Mumps
144
Pathophysiology of T1DM
Autoimmune destruction of insulin-producing Beta cells of pancreatic islets (autoantibodies to islet cell autoantigens) mediated by T lymphocytes
145
Which autoantibodies to islet cell antigens an we measure?
insulin antibody
GAD65 - Most common
Islet cell antibody (60-85% present)
ZnT8
146
What is the "honeymoon period" in T1DM?
After starting insulin, insulin levels may increase for weeks or months (remainder of function for beta cells after seeing insulin), followed by complete or near complete loss of Beta cell function.
147
Diagnostic criteria for T1DM
Fasting blood glucose ≥ 7.0 mmol/L
OR
2-hour plasma glucose level ≥11.1 mmol/L during a 75g OGTT
OR
Random plasma glucose ≥ 11.1 mmol/L in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis
OR
HbA1C >/= 6.5%
148
In what scenario are Hemoglobin A1C levels falsely low?
Hemolytic anemias
Pure red cell aplasia
Blood transfusions
Anemias associated with hemorrhage
Cirrhosis
Myelodysplasias
Renal disease treated with erythropoietin
149
How do you distinguish type 1DM between type 2 vs MODY vs neonatal diabetes
Basic phenotypic differences (metabolic picture DM2) All infants diagnosed with diabetes before 6 months need genetic testing - think about MODY (Auto dominant)
If you have ONE autoAb present - it does not distinguish type 1 from type 2, need TWO or more autoantibodies to confirm type 1 diabetes
150
Initial daily insulin dose in T1DM
0.4-0.6 units/kg/d
151
What is ISF and how do you calculate it?
Insulin Sensitivity Factor - amount that your blood glucose will decrease with one unit of insulin
ISF = 100/TDD
152
basal/bolus regimen for insulin in T1DM
total daily dose is divided 50% long acting insulin, 50% rapid acting insulin
153
intermediate and rapid acting regimen for insulin in T1DM
Divided 2/3 before breakfast and 1/3 before supper
Each dose divided 2/3 intermediate acting insulin and 1/3 rapid acting insulin
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 intermediate acting and 3 units rapid acting; 5 units total before dinner, divided as 3 units intermediate acting and 2 units rapid acting.
154
types of insulin preparations and onset/duration of action.
155
sick day management for insulin in T1DM
Goal: avoid DKA and hypoglycemia
Monitor BG and ketones every 2-4 hours around the clock
Do not stop insulin unless hypoglycemic, reduce 20%
If ketones AND blood glucose >14, take an 10-20% of TDD
156
Hypoglycemia presentation and management in T1DM
adrenergic: tremor, pallor, rapid HR, palpitations, diaphoresis;
neuroglycopenic: fatigue, lethargy, h/a, behavior changes, drowsiness, unconsciousness, seizures, coma; behavioral: irritability, agitation, erratic behavior, quietness, or tantrums
Treat BG <4 or 4-6 with symptoms: 10-15g CHO (e.g. 125mL juice or pop, 2-3 dextrose tablets, 250mL milk or 2tsp sugar)
Wait 10-15 min, recheck BG
157
screening recommendations for diabetes complications in type 1DM
Nephropathy - yearly at age 12 with duration >5 years (First morning or random urine ACR)
Retinopathy - yearly at age 15 with duration >5 years (Optho)
Neuropathy - yearly at age 15 with duration > 5 years (Neuro exam)
Dyslipidemia - screen at 12 and 17 years of age. <12yo only if BMI >97th percentile or history of familial dyslipidemia. Fasting or non-fasting TC, HDL-C, TG)
Hypertension - all children TWICE a year
158
How can schools support students with T1DM in school?
An individual care plan (ICP) must be developed for each student with diabetes and discussed with parents, principal and teacher. ICP should clearly outline roles and responsibilities of school personnel, parents, and child.
Each teacher of a child with diabetes must know how to recognize and treat hypoglycemia. Giving IM glucagon is optimal treatment. Need 2 personnel who are trained to provide support.
give kids 30-60min for cognitive recovery from hypoglycemia before returning to an exam
159
Which test for T2DM is predictive of future DM -related complications?
A1C
160
Best test to screen for T2DM?
DM Canada BEST recommendation: Use a combination of A1C and fasting or random blood glucose to screen for T2DM in children/adolescents with risk factors
FPG generally considered highest reproducibility and easier for children to do
OGTT has high detection rate but poor reproducibility
A1C should be used in conjunction with FPG or OGTT, not in isolation
161
Which youth are at higher risk of developing earlier and severe microvascular and cardiovascular complications - type 1 or type 2 DM?
Type 2 DM
162
How/when should neuropathy be screened for in youth with T2DM?
Yearly screening commencing at diagnosis of DM
Symptom history - numbeness, pain, cramps, paresthesia
Vibration sense
Light touch
Ankle reflexes
163
How/when should retinopathy be screened for in youth with T2DM?
Yearly screening commencing at diagnosis of DM
7-standard field, stereoscopic-colour fundus photography with interpretation by a trained reader (gold standard); OR
Direct ophthalmoscopy or indirect slit-lamp fundoscopy through dilated pupil; OR
Digital fundus photography
164
How/when should nephropathy be screened for in youth with T2DM?
Yearly screening commencing at dx of DM
First morning (preferred) OR random ACR
Abnormal ACR requires confirmation at least 1 month later with either a first morning ACR or timed overnight urine collection for ACR
Repeated sampling should be done every 3 to 4 months over a 6- to 12-month period to demonstrate persistence
165
Dyslipidemia screening in T2DM?
Yearly screening commencing at dx of T2DM
Fasting TC, HDL-C, TG, calculated LDL-C
166
HTN screening in T2DM?
At dx of diabetes and at every DM-related clinical encounter thereafter (at least 2x annually)
167
NAFLD screening in T2DM?
Yearly commencing at dx of DM
ALT and/or liver US
168
PCOS screening in T2DM?
Yearly screening commencing at dx of DM in pubertal females
Clinical assessment and exam
169
OSA screening in T2DM?
Yearly screening commencing at dx of T2DM
Clinical history and exam
170
Mental health screening in T2DM?
Depression - at dx and yearly thereafter
Binge eating - at dx and yearly thereafter
171
When should metformin be started in children with T2DM?
At diagnosis as long as A1C <9%, minimal symptoms, no acidosis
172
When should insulin be initiated in T2DM?
If patient metabolically unstable (A1C 9.0% or greater, acidosis present)
If patient metabolically stable (no signs/symptoms, no acidosis, A1C < 9.0%) then start basal insulin 3-6 months after diagnosis if glycemic targets have not been achieved
If targets still not achieved on a combination of metformin and basal insulin, start prandial insulin
173
Dx to consider in a patient who is young (under age 25), family history of diabetes < age 25, and nonobese?
MODY
Comprises a group of dominantly inherited forms of relatively mild diabetes
Diagnosed at a young age (<25 years) with an autosomal dominant transmission and lack of autoantibodies
MC form of monogenic diabetes (2-5% of diabetes)
Insulin resistance does not occur in these patients; instead the primary abnormality is an insufficient insulin secretory response to glycemic stimulation
Diagnose by genetic testing if high index of suspicion:
Familial diabetes with AD pattern of inheritance (>2 generations)
Onset <25 years
Nonobese
Negative islet autoantibodies
174
Causes of hypertonic hyponatremia? (serum osm > 285)
Severe hyperglycemia
Mannitol administration
Maltose (from IVIG)
Hypertonic contrast dye
175
Causes of pseudohyponatremia? (serum osm normal - 280-285)
Hypertriglyceridemia
Hyperproteinemia
Hypercholesterolemia
176
Causes of hypovolemic hyponatremia WITHOUT active renal sodium wasting (ADH turned on, urine osm > 100, urine sodium < 20-30)
GI loss:
Vomiting or gastric tube drainage (later stages).
Diarrhea.
Hemorrhage.
Sweating.
Poor oral intake.
Third space fluid sequestration:
Pancreatitis.
Bowel obstruction.
Peritonitis.
Burns.
Massive trauma.
177
Causes of hypovolemic hyponatremia WITH active renal sodium wasting (ADH turned on so urine osm > 100, urine sodium > 20-30)
Diuretics (especially thiazides).
Salt-wasting nephropathy (e.g., post-obstructive diuresis).
Hypoaldosteronism or adrenal insufficiency (mineralcorticoid deficiency)
Osmotic diuresis, e.g:
Glucosuria in uncontrolled diabetes, Urea, Mannitol.
RTA
Ketonuria
Cerebral salt wasting (possibly a form of hypoaldosteronism)
178
Urine labs in SIADH?
Euvolemic but urine osm > 100 (should be < 100 when euvolemic)
FeNa > 0.5
179
serum / urine labs in psychogenic polydipsia or free water overload?
Urine osm < 100
Maximally dilute urine
180
Causes of hypervolemic hyponatremia with urine Na < 20 (RAAS turned on)
Heart failure
Cirrhosis
Nephrosis
Hypoalbuminemia
181
Causes of hypervolemic hyponatremia with urine Na > 20 (RAAS turned off)
Renal failure
May need dialysis
182
What 3 fluids are listed in the CPS statement on acute hyponatremia in hospitalized children as the best practice for standard maintenance IV solutions:
D5W Plasmalyte
D5W Ringer's Lactate
D5W 0.9% NS
183
If at risk for hyperchloremic metabolic acidosis, what is the best option for fluid:
Use a balanced solution such as Plasmalyte or RL rather than 0.45% NS because the acidosis is caused by the strong ion difference of the fluid, not by the chloride content itself
184
CPS definition of severe acute hyponatremia?
<130 within 48 h in child with normal baseline Na
185
Which children are at particular risk for hyponatremia while on IV fluids?
Children underoing surgery
Children with acute neurological or respiratory infections eg, meningitis, encephalitis, pneumonia and bronchiolitis
186
Factors to consider when prescribing IV fluids in children? per CPS statement
The approach to prescribing IV fluids should be as cautious as that for medications, with close attention paid to indications, monitoring, the type of fluid and the volume/rate of administration.
Children receiving IV fluid therapy should be reassessed at least daily, ideally more often, for having their IV fluids reduced or discontinued.
Oral fluids are generally very low in Na content (hypotonic). Where the total fluid intake (TFI) is a combination of oral and IV fluids, both need to be accounted for.
Because infants and young children have limited glycogen stores, dextrose should be part of the IV maintenance fluid prescription (eg, D5W 0.9%NaCl or D5W Ringer’s lactate or D5W Plasmalyte) if no other source of glucose is provided
Clinicians should be aware of the symptoms of hyponatremia, which may include headache, nausea and vomiting, irritability, decrease in level of consciousness, seizures and apnea.
Baseline serum electrolytes and renal function (Na, K, glucose, BUN, creatinine) should be measured when starting IV fluid therapy in hospitalized children.
Children receiving maintenance IV fluids should have their serum electrolytes checked regularly, with patients who may be at high risk of impaired renal water excretion checked daily if not more frequently.
All children receiving IV maintenance fluids should have their intake/output carefully monitored, as well as a daily weight measurement.
187
What is the recommended IV fluid to use when the serum sodium is 145-154?
Preference is an isotonic fluid unless the clinician wishes to use a hypotonic fluid to more aggressively replace the patient's free water deficit
188
What is the recommended IV fluid to use to correct hyponatremia
Isotonic solutions preferred
Unless needing 3% saline due to symptomatic hyponatremia eg seizures
189
What is a good "hyponatremia lab package" to order?
Repeat serum electrolytes (including extended lytes and glucose)
Serum osmolality
Serum random cortisol level
Urine osmolality and urine sodium
190
initial management of asymptomatic hyponatremia
Fluid restrict
Avoid fluid administration (unless needed for hypovolemia)
191
What laboratory features would be supportive of a diagnosis of PseudoHypoParathyroidism (aka Albright Hereditary Osteodystrophy)?
HINT: Include PTH, Ca, Phos, ALP, Bone age.
Lab Findings in PseudoHypoParathyroidism:
- PTH: High PTH
- Ca: HYPOcalcemia
- Phos: HYPERphosphatemia
- ALP: Normal ALP
- Bone Age: Advanced
192
Causes of dilute urine in hyponatremia? eg urine < 100 mOsm
[1] Hyponatremia due to {water intake > solute intake}.
[2] Patient is in the recovery phase (e.g., the patient initially had hypovolemic hyponatremia, received volume resuscitation prior to urinalysis, and is currently auto-correcting their own sodium levels.)
193
Causes of concentrated urine in hyponatremia (eg urine >100 mOsm, sp gravity > 1.003)
Physiological response of ADH to systemic hypoperfusion (hypovolemia, heart failure, cirrhosis)
SIADH
194
What does low urine sodium indicate
RAAS is turned on (aldosterone is retaining Na)
Causes:
- hypovolemic hyponatremia without renal sodium wasting
- hypervolemic hyponatreia - heart failure, cirrhosis, nephrotic syndrome
195
What does high urine sodium indicate:
RAAS is turned off
Causes:
- hypovolemic hyponatremia with active renal sodium wasting
- SIADH
- adrenal insufficiency
- renal failure (AKI, CKD)
196
Risk factors for seizures / herniation due to hyponatremia:
Severe hyponatremia
Massive water ingestion
MDMA (ecstasy)
Postop hyponatremia
Intracranial pathology
Known seizure disorder
197
Risk factors for osmotic demyelination syndrome:
Urine Na < 120 (ODS is rare if the initial sodium is > 120-125)
Hypokalemia
Cirrhosis
Alcohol use disorder
Malnutrition
More common in adults
198
what glycemic response to glucagon would be characteristic of hyperinsulinemic hypoglycemia?
>1.7 mmol/L after administration of glucagon
If LESS, and hypoketotic think about fatty acid oxidation defects
199
which syndromes are associated with hyperinsulinism?
Beckwith-Wiedemann syndrome
Kabuki syndrome (hyperinsulinism, short stature, short fifth finger)
200
how to treat hyperinsulinism?
glucagon! responds to glucagon (a "response" to glucagon is a BG rise of 1.7 or greater)
diazoxide only for refractory hypoglycemia
201
what is associated with insulinoma?
associated with MEN1
insulinoma = insulin secreting islet cell tumour
presents with recurrent hypoglycemia in adolescence
202
which features make fatty acid oxidation disorder the most likely etiology for hypoglycemia?
hypoglycemia triggered by FASTING
no ketones (can't break fatty acids into ketones)
rhabdomyolysis, hepatitis, arrhythmia, cardiomyopathy
NO response to glucagon challenge test (less than 1.7mmol rise in blood sugar after administering glucagon)
203
how does idiopathic ketotic hypoglycemia present?
hypoglycemia from insufficient energy stores
TODDLERS, young children
hypoglycemia triggered by
- 10-16 hr fasts (ie in the morning) or
- during illness (esp if vomiting, diarrhea)
Positive ketones (healthy response to low blood sugar)
204
treatment of idiopathic ketotic hypoglycemia?
treat hypoglycemia
long term:
no prolonged fasting
home glucose monitoring during illness
205
when do kids grow out of idiopathic ketotic hypoglycemia?
self-resolves by 6-8 yrs old
206
What causes Cushing's Syndrome? and how would you differentiate the underlying etiology?
Cushing's = Glucocorticoid Steroid Excess
ACTH-Dependent (High ACTH + High Cortisol):
1. Pituitary Oversecretion ("Cushings Disease" Adenoma)
2. Ectopic ACTH (Small Cell Lung ca, MEN1 Tumour, Pheochromocytoma, Medullary Thyroid ca)
ACTH-Independent (Low ACTH + High Cortisol):
1. Adrenal (Primary Adrenal Adenoma)
2. Exogenous (Oral/IV/Topical/Inhaled Corticosteroids)
207
Individual has a diagnosis of Cushings Syndrome. How do they present?
- FACIES: Round moon facies, prominent cheeks, flushed appearance
- GROWTH / DEV: Weight gain (truncal obesity with thin limbs). Linear growth failure
- MSK: Dorsocervical fat pad. Proximal muscle weakness. Decreased muscle mass. Osteoporosis and pathologic fractures.
- DERM: Purple striae (hips, abdo, thighs). Easy bruising.
- CNS: Emotional lability. Headache
- CVS: Hypertension.
- ENDO: Delayed puberty. Hyperglycemia. Glucose intolerance. Suppression of endogenous glucocorticoid production.
Note: these patients require increased doses of steroid with illness/stress
208
What investigations could you use to help diagnose Cushings Syndrome? (HINT: there are 3)
A. Salivary Cortisol Test (early morning and late night level)
B. 24-h Urine Free Cortisol (normal <275)
C. Dexamethasone Suppression Test
- Administer 20mcg/kg (max dose of 1mg) Dexamethasone the preceding night and measure early-morning cortisol level
- Abnormal: Inappropriately normal
- Normal: Suppressed (<50)
209
What would a growth chart (height and weight) consistent with Cushings Syndrome look like?
210
WHEN would pubertal gynecomastia present?
HINT:
- Peak AGE of onset: ***
- Puberty STAGE at onset: ***
Peak AGE of onset:
- 14yrs
Pubertal STAGE at onset:
- Tanner Stage 3-4
- Testicular volume 5-10ml
211
HOW would pubertal gynecomastia present?
HINT:
- SYMPTOMS: ***
- Time to REGRESSION: ***
SYMPTOMS =
- Subareolar hyperplasia with underlying rubbery firm mass.
- Unilateral or bilateral
- Transiently tender
- Normal testicular exam
- No features suggestive of underlying renal, hepatic, thyroid, or endocrinological issues.
Time to REGRESSION:
- Usually regresses spontaneously within a few months (rarely lasts longer than 2 yrs)
212
What is the workup & management of pubertal gynecomastia?
- Followup in 6mo (if story in keeping with pubertal gynecomastia then no further workup required)
213
Most cases of Physiologic Pubertal Gynecomastia are benign and self resolving (6mo FU but no workup).
What red flag features would prompt additional investigation?
Pathologic Gynecomastia Red Flags:
- In prepubertal boys with no other secondary sexual characteristics
- Rapid progression
- Enlargement >4cm in diameter
- Persistence for more than 1 year
- Galactorrhea
- Hx / Exam findings suggestive of underlying pathological conditions (medication use, endocrinopathies, malignancy)
214
A male child has gynecomastia.
In a situation where symptoms are less in keeping with Physiologic Pubertal Gynecomastia (persistent >12mo, moderate/severe gynecomastia) OR if red flags are present (prepubertal boys without other secondary sexual characteristics, rapid progression, enlargement >4cm, galactorrhea) then additional workup is required.
List the required workup:
Workup Includes:
- Endocrinology referral
- Bloodwork: 8AM fasting concentrations of LH, FSH, Testosterone, Estradiol, beta-hCG, DHEAS, LFTs +/- PRL +/- TFTs
- +/- Imaging
215
Management of pubertal gynecomastia in boys that have reached complete or near complete pubertal development
Poor evidence for androgens, aromatase inhibitors, and estrogen antagonists in pediatrics.
If breast development is excessive (Tanner stages 3-5), and causes significant psychological distress, and fails to regress in 18-24 mo, surgical removal of the enlarged breast tissue may be indicated.
216
What clinical features does PseudoHypoParathyroidism (AKA Albright Hereditary Osteodystrophy) present with?
PseudoHypoParathyroidism Clinical Features:
- Short stature
- Brachydactyly
- Obesity with round face
- Heterotopic Ossifications
- Advanced bone age
- NO nephrocalcinosis (as no excess Ca clearance)
- HyperPTH, Hyperphosphatemia, Hypocalcemia
217
A child is diagnosed with PseudoHypoParathyroidism (aka Albright Hereditary Osteodystrophy). What lab findings are consistent with this diagnosis?
HINT: PTH, Ca, Phos, ALP
PTH: High PTH
Ca: HYPO-Calcemia
Phos: HYPER-Phosphatemia
ALP: Normal
218
What is the inheritance and pathophysiology of Autoimmune Polyglandular Syndrome Type 1 (APS-1)?
Inheritance: AUTOSOMAL RECESSIVE
Pathophysiology: Caused by loss of function mutations in the Autoimmune Regulatory Gene (AIRE) which results in development of autoreactive T cells and autoantibodies directed at multiple tissues.
219
Name the classic 'Whitaker's triad' features associated with Autoimmune Polyglandular Syndrome Type 1 (APS-1)?
APS-1 is a clinical syndrome defined by the presence of ≥ 2 / 3 of classic features ('Whitaker Triad'):
1. CHRONIC MUCOCUTANEOUS CANDIDIASIS (Onset: age 5yrs)
2. HYPOPARATHYROIDISM
(Onset: age 10yrs)
3. PRIMARY ADRENAL INSUFFICIENCY
(Onset: age 15yrs)
+/- Most patients develop additional autoimmune manifestations over time (skin and gastrointestinal disorders typically emerging before age 20 and other endocrine disorders after the second decade)
220
What are the clinical features associated with Autoimmune Polyglandular Syndrome Type 2 (APS-2)?
APS-2 is a clinical syndrome defined by the presence of ≥ 2 syndrome-specific endocrinopathies:
1. AUTOIMMUNE PRIMARY ADRENAL INSUFFICIENCY
(Addison disease)
2. AUTOIMMUNE THYROID DISEASE
(Hashimoto thyroiditis or Graves disease)
3. TYPE 1 DM
+/- Some classifications can also include additional endocrine/gastrointestinal/systemic autoimmunity, primary gonadal insufficiency, vitiligo, alopecia, and chronic atrophic gastritis (with or without pernicious anemia).
221
what is the recommended A1C, fasting BG and 2-hr postprandial BG glycemic targets in T1DM?
A1C ≤7.5
Fasting BG 4 - 8 mmol/L
2hr postprandial BG 5-10
222
how to treat a low blood glucose in T1DM pts who are 5, 5-10 and >10 yrs old?
<5yrs = 5g
5-10 yrs = 10g
>10yrs = 15g
223
Subclincal Hypothyroid Etiologies (3)
1. Iodine Deficiency
2. Post surgical or post ablation
3. Medications (lithium, amioderone, tyrosine kinase inhibitor)
224
Management of Subclincal Hypothyroid
No benefit to treating, monitor thryoid function every 6-12 months
225
Indications for treatment of Subclincal Hypothyroid
elevated auto-antiboidies (anti-TPO), a goiter, and/or elevated cholesterol - levothyroxine is the medication of choice
226
Genetic abnormality in Prader Willi Syndrome
PWS is a disorder caused by sporadic deletion of paternal chromosome 15q11 - 15q13 (70% of cases).
Rarely can be caused by maternal UniParental Disomy (UPD) (25-30%) or imprinting defects (<5%)
227
Indication for Prader Willi Syndrome genetic testing < 2 years
significant hypotonia with poor such and difficulty gaining weight
228
Indication for Prader Willi Syndrome genetic testing 2-6 years
congenital hypotonia with history of poor suck and GDD
229
Indication for Prader Willi Syndrome genetic testing 6-12
congenital hypotonia with poor suck, GDD and excessive eating (hyperphagia) with central obesity if uncontrolled
230
Indication for Prader Willi Syndrome genetic testing 13+
cognitive impairment (mild-mod) + excessive eating (hyperphagia) + central obesity + hypothalamic hypogonadism
231
First line genetic testing for Prader Willi Syndrome
Methylation analysis
232
Frequency of hearing and vision screening for Prader Willi Syndrome
Annual hearing and vision screening before 3 years, annual vision assessment afterwards
233
Frequency of Thyroid screening for Prader Willi Syndrome
Thyroid screening every 2-3 years > 5 years
234
Definition of "Low Risk Neonate" born to mother with with Grave's Disease
Negative maternal TSH receptor antibody (TRAb) level in 2nd and 3rd trimester
235
Follow up for "Low Risk Neonate" born to mother with with Grave's Disease
No follow-up needed
236
Definition of "High Risk Neonate" born to mother with with Grave's Disease
Positive or unknown maternal TSH receptor antibody (TRAb) level in 2nd or 3rd trimester
237
Follow up for "High Risk Neonate" born to mother with with Grave's Disease
Determine TRAb in cord blood. If assay is unavailable or TRAb positive, check TRAb DOL1, TSH & FT4 and TRAb on DOL 3-5 and repeat again on DOL 10-14
238
Follow up for "High Risk Neonate" born to mother with with Grave's Disease with unknown or positive TRAb who is asymptomatic with normal thyroid function tests
Clinical follow up with a paediatrician at 4 weeks and at 2-3 months
239
Follow up for "High Risk Neonate" born to mother with with Grave's Disease with negative TRAb
no follow up required
240
Indications for admission or infant born to mother with with Grave's Disease (4)
1. Need for beta blockers
2. Hemodynamic instability
3. Arrhythmia/Heart Failure
4. Tracheal Compression due to Goiter
241
Treatment for infant born to mother with with Grave's Disease with abnormal thyroid function tests (hyperthyroidism)
Methimazole 0.2 - 0.5 mg/kg/day divided BID +/- Propanalol 2 mg/kg/day divided BID for 1-2 weeks - follow TSH & FT4 every 1-2 weeks. Average treatment duration is 1-2 months
242
Treatment for infant born to mother with with Grave's Disease with abnormal thyroid function tests (central or primary hypothyroidism)
Levothyroixide 10 ug/kg/day - follow TSH & FT4 every 2-3 weeks to titrate dose, usually transient
243
Describe Chvostek's sign and Trousseau's sign:
In hypocalcemia:
Chvostek's sign - muscle twitch at the ipsilateral corner of the mouth in response to a light tap over the facial nerve below the maxilla
Trousseau's sign is a carpal spasm in the hand caused by inflation of the blood pressure cuff around the ipsilateral arm approximately 15mmHg aove systolic BP
Both indicate increased neuromuscular excitability
244
ECG findings in hypocalcemia?
Can have short PR, narrow QRS, prolonged ST and ST depression, T wave flattening and inversion, prolonged QTc, prominent U wave
245
Adjusting calcium level for albumin level?
NO longer recommended
However exam might not be up to date on that per Elise
Corrected Calcium = (0.8 * (Normal Albumin - Pt's Albumin)) + Serum Ca
246
What is the cut off for rise in blood sugar after glucagon administration to diagnose hyperinsulinism ?
Rise of > 1.7 mmol
247
In neonatal hypoglycemia, when infusions fail to maintain blood glucose at appropriate levels or an especially high rate (eg 10mg/kg/min) of infusion is required, what is the next step (as well as calling Endo)?
IV glucagon
248
Endocrine manifestations of pituitary lesions (in order of appearance)?
GH deficiency
FSH /LH deficiency (hypogonadotropic hypogonadism)
TSH deficiency
ACTH deficiency
Prolactin
249
What size of prolactinoma causes no problems by mass effect / local extension?
< 1 cm
250
Which endocrine condition can be associated with prolactinoma
MEN 1
251
Visual impairment, panhypopit, and developmental delay?
Sepo-optic dysplasia
252
Risk factor for septo optic dysplasia?
Teenage pregnancies
253
Name the syndrome: recurrent otitis media, short stature, neonatal lymphedema
Turner syndrome
254
Name the syndrome: ambiguous genitalia, nephrotic syndrome, Wilms tumour
Denys Drash
255
Difference between primary, secondary and tertiary adrenal insufficiency
Primary: adrenal problem. Low cortisol, low DHEA, low aldosterone. High CRH, high ACTH.
Secondary: Pituitary problem. Low cortisol, low DHEA. Normal aldosterone because RAAS signals aldosterone and this is normal. Important because you will have no hyponatremia/hypokalemia. High CRH, low ACTH.
Tertiary: Hypothalamus problem. Low cortisol, low DHEA. Normal aldosterone (see above). Low CRH, low ACTH.
256
Boy with ADHD, evolves to have adrenal insufficiency - which diagnosis?
X linked adrenoleukodystrophy
257
Difference in dose of cosyntropin for ACTH stim tests between central and peripheral AI?
Low dose (1mcg cosyntropin) - used for central AI
High dose (250 mcg cosyntropin) - used for peripheral AI
Cortisol level drawn at 0, 30 and 60 minutes for both
Normal peak cortisol > 350
258
Name the syndrome - hyperinsulinism, short stature, short 5th finger
Kabuki
259
How to calculate mid-parental height?
[ Mother's height (cm) + father's height (cm) +/- 13 ] / 2
260
What is a delayed bone age?
1-2 year difference between bone age and chronological age
261
Name the syndrome! Intellectual impairment, short stature, hypogonadism, obesity, OCD, skin picking
Prader Willi
262
Differential diagnosis for diffuse thyroid enlargement
Most common:
Subacute or acute thyroiditis
Grave's disease
Colloid goiter
Congenital hypothyroidism
Less common:
- iodine deficiency
- infiltrative disorders
- chronic lymphocytic thyroiditis
- thyroid hormone resistance
- excessive iodine ingestion
263
What is a colloid goiter
Benign, causes diffuse neck swelling - goes away with time
Typically normal thyroid tests
More common in adolescent girls
264
Red flag features of goiter?
Hoarseness (compression on trachea)
Dysphagia (compression on esophagus)
Rapid growth
Firm or hard consistency
Pain
Increased WOB
Lymphadenopathy
Family history of thyroid cancer
265
Multinodular goiter
- presentation?
- labs?
Firm goiter with a lobulated surface and one or more palpable nodules
Areas of cystic change, hemorrhage, and fibrosis may be present
US --> multiple nonfunctioning nodules
Thyroid studies --> usually normal
266
US in hypothyroidism?
Only if you feel a nodule or red flag features of goiter
267
Monitoring lab used in central hypothyroidism due to central lesion?
free T4
TSH not useful - primary lesion is at the level of the CNS (hypothalamus or pituitary) --> TSH won't change over time
268
Monitoring test used in secondary / acquired hypothyroidism?
Screening done using TSH
Primary lesion is at the level of the thyroid
269
What is sick euthyroid (non-thyroidal illness)
Refers to changes in serum thyroid hormone levels observed in critically ill patients in the absence of hypothalamic-pituitary-thyroid primary dysfuntion
Classically - low T3, elevated rT3, inappropriately normal TSH levels (or mildly elevated)
Essentially, if someone is sick, probably not the best time to check their thyroid labs
270
If someone has hypocalcemia, what is the action of PTH
PTH should be high (secreted by parathyroid glands)
- Bones will increase osteoclast activity which will lead to both phosphate and calcium increasing
- 25 vitamin D --> converted to 1,25 vitamin D
- tells kidneys to excrete more phosphate
271
Living north of what latitude increases risk for vitamin D deficiency
55 degrees
272
Immediate management of acute hypocalcemia?
IV calcium gluconate - single dose but may continue as an infusion
Calcitriol (activated vitamin D - remember this is needed for intestinal absorption - if severe vitamin D deficiency or hypoparathyroidism suspected)
At discharge
- PO elemental calcium
- PO calcitriol
273
Name the syndrome: hypocalcemia, hyperphosphatemia, pseudohyperparathyroidism
Short stature, obesity, delayed puberty
Albright Hereditary Osteodystrophy
274
Differential diagnosis hypercalcemia?
Dietary - excess vitamin D, TPN
Primary hyperparathyroidism - MEN 1, 2A
Familial hypocalciuric hypercalcemia
Subcutaneous fat necrosis (infants - risk factor HIE and cooling)
Malignancy
Possible endocrine causes - AI, hyperthyroid, pheochromocytoma
275
What are the more common features of MEN 1?
PPP
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic tumours
276
What are the more common features of MEN 2A?
Parathyroid hyperplasia
Medullary thyroid carcinoma
Pheochromocytoma
277
What are the more common features of MEN 2B?
Mucosal neuromas
Marfanoid body habitus
Medullary thyroid carcinoma
Pheochromocytoma
278
Hypercalcemia symptoms?
Stones - kidney stones
Groans - nausea, constipation, ileus, abdominal pain
Bones - abnormal bone remodelling and fracture risk
Psychiatric overtones - lethargy, depressed mood, psychosis, cognitive dysfunction
279
Hypercalcemia immediate management
STOP any exogenous source of calcium and vitamin D
Hyperhydrate with noraml saline at 1.5-2x maintenance
ECG
Consider pharmacologic management:
- fluid and lasix
- bisphosphonates
- calcitonin
280
Rickets - classic imaging features?
Cupping and fraying of the metaphyses, physeal widening or splaying, bowing of long bones, decreased mineralization, rachitic "rosary"
281
Classic physical features of rickets
Short stature
FTT
Delayed closure of anterior fontanelle
Widened wrists
Genu valgum (can also be varum)
Delayed walking or waddling gait
Dental - variable
282
Endocrine features of Prader Willi?
GH deficiency
Hypothyroidism
Hypogonadism (central)
T2DM
Central adrenal insufficiency (unclear why, presumed hypothalamic dysfunction)
Osteoporosis
Obesity
283
Key features of Klinefelter syndrome
XXY
Small testes, gynecomastia, tall stature, delayed puberty, learning disabilities
284
Familial hypercholesterolemia inheritence?
AD
285
Lipid screening in children?
Not really a universal consensus or clear Canadian guideline
However in USA now recommending all children between 2-10 get lipids checked at least x1
286
Statins are approved at what age
8 years old and above
287
Features of premature adrenarche (pubarche)?
Appearance of sexual hair before the age of 8 in girls and 9 in males
Frequently have axillary body odour as well
Normal Bone Age
No other pubertal changes
288
Premature pubarche (adrenarche) can increase long term risk for which condition?
Which neonatal/infant condition increases risk for premature pubarche?
Increased long term risk for PCOS
Infants born SGA are more likely to develop premature pubarche
289
Treatment for premature pubarche?
Requires no treatment as long as isolated pubarche - no breast development, genital enlargement, growth acceleration, cystic acne, or advanced bone age
290
Name the syndrome: hypogonadotropic hypogonadism, anosmia, colour blindness, ASD, unilateral renal agenesis
Kallman syndrome
291
Labs (calcium, phosphate, PTH and ALP) in rickets?
Low calcium
Low phosphate
High ALP
High PTH
292
Symptoms of severe hypothyroidism?
Typical symptoms of hypothyroidism - may be more severe, PLUS can have
Delayed bone age
Goiter
Delayed relaxation of deep tendon reflexes
Pseudoprecocious puberty --> lack of androgen-mediated pubarche (eg penile and testicular enlargement in boys, menstruation and breast development in girls, but lacking pubarche)
293
What underlying cause is most in keeping with this growth chart?
Failure to Thrive or Chronic Disease
