Endocrinology Flashcards
1
Q
What is the main hormone that triggers puberty?
A
LH
~1- 3 yr before onset clinically evident puberty, LH levels become detectable during sleep in pulsatile pattern
2
Q
What are the cut offs for precocious puberty in boys and girls?
A
Boys <9 years (early puberty is more pathologic)
-NOTE: Onset of puberty= testicular enlargement
Girls <8 years (THELARCHE)
-NOTE: Onset of puberty=thelarche
3
Q
What are the cut offs for delayed puberty in boys and girls?
A
Girls > 13 (thelarche), >15 (menses)
NOTE: Late puberty rare in girls, commonly organic
Boys > 14
4
Q
What is the first clinical sign indicative of hypothalamic-pituitary-gonadal activation in girls and boys?
A
Girls-breast buds
Boys-testes volume (>4ml) or length >2.5 cm
5
Q
Describe SMR staging for girls (breasts)?
A
Stage 1: Prepubertal, with no palpable breast tissue
Stage 2: Breast bud, with elevation of the papilla and enlargement of areolar diameter
Stage 3: Enlargement of breast, without separation of areolar contour from breast
Stage 4: Areola and papilla project above the breast, forming a secondary mound.
Stage 5: Recession of the areola to match contour of breast, with papilla projecting beyond contour
6
Q
Describe SMR staging for boys (genitals)?
A
Stage 1: Prepubertal. Testicular volume <1.5ml, penis <3 cm
Stage 2: Enlargement of scrotum and testes (testicular volume 1.6-6ml); scrotal skin reddens and changes in texture
Stage 3: Enlargement of penis (to about 6 cm); further growth of testes (6-12 ml)
Stage 4: Increased size of penis (10cm) with growth in breadth and development of glans; testes (12-20 ml) and scrotum larger, scrotal skin darker
Stage 5: Adult genitalia (testicular volume 20 ml), penis 15 cm
7
Q
What is a differential diagnosis of precious puberty?
A
Central:
- Idiopathic (95% in girls, only 50% in males)
- CNS lesions-hypothalamic hamartomas, brain tumour
Peripheral: A. Girls -Ovarian cyst -Ovarian tumor -McCune Albright -Prolonged untreated hypothyroidism) -Exogenous estrogen/testosterone -Severe longstanding hypothyroidism -CAH -Estrogen-secreting adrenal tumour -McCune Albright
B. Boys
- Leydig cell tumour
- Adrenal (CAH, adrenocortical tumor)
- hCG secreting tumour
- Familial male precocious puberty
- Severe longstanding hypothyroidism
- Exogenous testosterone
- CAH
- Androgen-secreting adrenal tumour
8
Q
What is premature adrenarche?
A
Due to early maturation of adrenal androgen production
Benign, non-progressive pubertal variant
9
Q
What bloodwork might you do for premature adrenarche?
A
- Bone age: (mild to moderate increase, but should NOT be >2 years)
- DHEAS normal or mildly increased
- LH, FSH-prepubertal
- Consider 17-OHP and testosterone to r/o ddx (adrenal/ovarian tumours, CAH, exogenous androgens)
10
Q
How do you differentiate premature adrenarche from peripheral precocity?
A
Premature adrenarche:
Associated with increased weight
True puberty at normal age
Normal penile length
Precocity:
Bone age >2 years advanced
Marked hyperadrogenism (e.g. clitoromegaly)
Can have longer penile length (because of excess testosterone)
11
Q
What is premature thelarche?
A
Onset 6-24 mo
Isolated to breast development
Benign non-progressive pubertal variant
12
Q
How do you differentiate premature thelarche from precocious puberty?
A
Premature thelarche:
- No height acceleration
- Most will regress
- True puberty at normal age
- SMR <2
Preciocious puberty:
- SMR >3 breasts
- Advanced bone age
13
Q
Does premature adrenarche increase the risk of PCOS?
A
YES
14
Q
What investigations should you order for premature thelarche?
A
Bone age
Continued observation for GV and secondary sexual characteristics
15
Q
How do you test for familial male limited precocious puberty?
A
Genetic testing LHCGR
16
Q
If you see discrepancy and penis size/pubic hair and testicular growth, is this more indicative of central or peripheral precocity?
A
Peripheral
Excess androgen causes penis to enlarge, pubic hair
However, FSH is supressed so there is no stimulation of Sertli cells to cause testicular enlargement
17
Q
What are the clinical manifestations of McCune Albright?
A
- Usually girls
- Precocity (ovaries/testes are autonomously producing hormones)
- Patchy hyperpigmentation
- Polyostotic fibrous dysplasia
- Other endocrinopathies (hyperthyroidism, GH excess, cushing’s syndrome)
- Renal phosphate wasting (leading to osteomalacia)
- Episodic puberty-cyclic breast enlargement and vaginal bleeding
18
Q
What initial tests do you order for peripheral precocity
A
Girls: bone age, TSH, LH, FSH, estradiol, GnRH stim testing → AUS for peripheral, MRI brain for central
Boys: bone age, TSH, LH, FSH, testosterone, GnRH stim, imaging essential MRI/CT brain
19
Q
When do you do an MRI for precocious puberty?
A
All boys with precocity
All girls <6 with precocity
20
Q
What is the most sensitive test to determine onset of puberty?
A
Basal LH > 0.3 IU/L
21
Q
What is a differential diagnosis of delayed puberty in girls?
A
Hypogonadotropic hypogonadism:
- CDGP***most common
- Chronic disease (e.g. anorexia, cystic fibrosis, IBD)
- Tumour
- Radiation
- Head injury
- Kallman syndrome
- CHARGE syndrome
Hypergonadotropic hypogonadism: Turner syndrome Ovarian radiation POF (Galactosemia Fragile X) Complete AIS Chemo
22
Q
What is the differential diagnosis of delayed puberty in boys?
A
Hypogonadotropic hypogonadism:
- CDGP ***most common
- Chronic disease (e.g. anorexia, cystic fibrosis, IBD, malnutrition)
- Kallman syndrome
- Pituitary tumour
- Head injury
- CHARGE syndrome
Hypergonadotropic hypogonadism:
- Klinefelter syndrome
- Testicular torsion/trauma
- Vanishing testes syndrome
- Chemo
- Gonadal infection
- Gonadal dysgenesis
23
Q
What test would you order if you were concerned about hypergonadotropic hypogonadism?
A
Chromosomes
To look for Klinefelter in boys, Turner in girls
24
Q
What are the goals of precocious puberty treatment?
A
Preserve adult height
Alleviate psychosocial concerns
25
How do you treat precocious puberty?
GnRH agonist (Lupron)-continuously given so downregulates LH, FSH
26
What is the definition of primary amenhorrhea?
Absence of menses by 15 years or >3 years after thelarche
27
What is the definition of secondary amenorrhea?
Absence of menses for 3+ months in women with regular cycles; 6 months in women with irregular cycles
28
What is the differential for primary amenorrhea?
Hypothalamic and pituitary disease
- Functional hypothalamic amenorrhea
- Isolated GnRH deficiency
- Constitutional delay of puberty
- Hyperprolactinemia
- Other
Gonadal dysgenesis/POI
- Turner syndrome
- 46,XY gonadal dysgenesis
- Primary ovarian insufficiency (POI)
Polycystic ovary syndrome
Outflow tract disorders
- Imperforate hymen
- Transverse vaginal septum
- Müllerian agenesis
Receptor abnormalities and enzyme deficiencies
- Complete androgen insensitivity syndrome
- 5-alpha-reductase deficiency
- 17-alpha-hydroxylase deficiency
- P450 oxidoreductase deficiency
- Estrogen resistance
29
What tests would you order for McCune Albright?
Screen for other endocrinopathies
30
When is anovulation most common?
Within first 2 years of menses
31
List 5 conditions causing DELAYED bone age
```
Constitutional growth delay
GH deficiency
Hypothyroidism
GI disease (celiac, crohns)
Rheumatologic disease (JIA)
Renal disease (CKD, RTA)
Cancer
Immunodeficiency
Pulmonary disease
Malnutrition
```
32
List 3 conditions causing with ADVANCED bone age
Precocious puberty
Excessive androgen production
Hyperthyroidism
CAH
33
Describe the features of Androgen Insensitivity Syndrome?
Overall- normal appearing female with brests, no menses, no pubic hair, with internal male genitalia
- Female phenotype, but 46 XY karyotype
- Normal breast development (from peripheral conversion of T)
- Primary amenorrhea
- Little or no axillary or pubic hair
- Absent uterus, but testes present
- Blind vaginal pouch on exam (no upper 1/3)
- Male height
34
How many years after thelarche do you normally get menses?
2 years
35
Describe normal sex development in males
1. Bipotential gonad
2. Y chromosome-SRY
3. Testis development
4. Sertoli cells produce AMH, which degrades Mullerian duct, resulting in no uterus
5. Leydig cells produce testosterone, which develops Wolffian duct, resulting in male internal genitalia
6. Testosterone also converted to DHT to create male external genitalia
36
Describe normal sex development in females
1. Bipotential gonad
2. No Y chromosome
3. Gonad becomes ovary (produce estrogen and progesterone)
3. No AMH or Testosterone produced
4. Mullerian duct turns into internal female genitalia and wolffian duct degenerates
37
What does DSD look like in males?
Bilateral UDT
Bifid scrotum
Hypospadius
38
What does DSD look like in females?
Clitoromegaly
Single genitourinary opening
Inguinal hernia
39
What are the different categories of DSDs?
1) Sex chromosome DSD
2) 46 XY DSD
3) 46 XX DSD
40
What are the sex chromosome DSDs?
1. Turners (45,X)
2. Klinefelter (47, XXY)
3. Mixed gonadal dysgenesis/ovotesticular DSD (45, X/46, XY)
4. Chimeric ovotesticular DSD
(46,XX/46,XY)-BOTH ovaries and testes tissue are present.
41
When would you think about a mixed gonadal dysgenesis?
When there are asymmetric findings (unilateral ovary/testes, half a uterus)
42
What are the most common 46 XY DSDs?
The ones you need to know:
1. 5 alpha reductase
2. AIS
Comprehensive differential:
1. Disorders of gonadal development
- Complete gonadal dysgenesis (female phenotype)/Swyer syndrome
- Partial gonadal dysgenesis
- Vanishing testes syndrome
- Ovotesticular DSD
- Others: WAGR, campomelic
2. Disorders in androgen synthesis
- Androgen biosynthesis defect (e.g. 17 hydroxysteroid dehydrogenase deficiency, 5alpha reductase deficiency, StAR mutation)
3. Defect in androgen action (e.g. PAIS, CAIS)
4. LH receptor defects (e.g. Leydig cell hypoplasia)
5. Disorders of AMH and AMH receptor (e.g. Persistent Mullerian Duct syndrome)
Other
e.g. severe hypospadius, cloacal extrophy
43
What are the clinical features of complete gonadal dysgenesis (46,XY)?
Infertile phenotypic female (normal external and internal female structures) with streak gonads
44
What is the genetics of AIS?
X-linked
45
What is the phenotype of 5-alpha reductase deficiency?
Internal genital male
External genitalia female
```
Most common phenotype: -Small phallus
Bifid scrotum
Urogenital sinus with perineal Hypospadias
Blind vaginal pouch
Testes present
```
46
What is the most common 46, XX DSD?
Most common:
-Virilizing CAH (usually 21-hydroxylase and 11-hydroxylase)
Comprehensive differential:
Disorders of gonadal development
- Ovotesticular DSD
- Testicular DSD (e.g. SRY+)
- Gonadal dysgenesis
Androgen excess
- CAH-21 hydroxylase deficiency, 11-hydroxylase deficiency
- Aromatase deficiency
Other
- Cloacal extrophy
- Vaginal atresia
- MURCS
- Maternal androgenic medications during pregnancy
- Virilizing maternal tumours
47
What investigations should you order for DSDs?
1. Karyotype with rapid determination of sex chromosomes within 24-48h
2. Screen for CAH → 17-OHP, androstenedione
3. Screen for androgens and precursors
4. Screen for gonadal response to gonadotropin if suspected to have testes (inject HCG and measure androgens before/after)
5. Genetic analysis for SRY
6. Gonadotropin levels
7. Imaging of internal anatomy starting with pelvic U/S
o Presence of a uterus and absence of palpable gonads usually suggests a virilized XX female
o Absence of a uterus, with or without palpable gonads, almost always indicates an under virilized male and an XY karyotype
o Also consider VCUG, endoscopy, renal/adrenal ultrasound, pelvic CT or MRI if needed
48
If gonads are palpable, what is the most likely type of DSD?
46 XY
49
If gonads not palpable, what is the most likely type of DSD?
46 XX (CAH)
50
What are the types of CAH?
1) Salt wasting 70%
2) Simple virilizing (glucocorticoid deficiency)
3) Non-classical (late onset)
51
What are the factors that affect gender assignment?
```
Diagnosis
Genital appearance
Surgical options
Need for life long replacement therapy
Potential for good sexual function
Views of the family
Potential for fertility
```
52
Baby with ambiguous genitalia and palpable gonads most likely has....
Partial AIS (vs. 5 alpha reductase)
53
Child with hypospadius, enlarged phallus and non-palpable testes?
Think 46, XX
| CAH
54
In the first year of life, what is the main factor affecting growth?
Nutrition
| GH independent
55
When do IUGR babies have catch up growth?
Weight by 2 years
| Height by 2.5 years
56
How do you calculate mid parental height
Boys: (father’s height + mother’s height) / 2 + 6.5 cm +/- 8.5 cm
Girls: (father’s height + mother’s height) / 2 - 6.5 cm +/- 8.5 cm
57
What are 4 key questions to ask in short stature?
1) Is the child short?
- If ≤2.3% should have evaluation
- If >2.3% no further workup unless dropping %iles, dysmorphic features, or evidence of systemic disease
2) Is height velocity impaired?
- Growing < 5 cm/yr age 2-6, <4 cm/yr from age 6 to puberty
- Normal HV: usually nonpathologic SS (FSS, CSS),
- Abnormal HV: more likely to have pathologic SS (malnutrition, GH deficiency, cortisol excess, hypopit)
3) What is projected adult height (MPH), i.e. is growth in range for the family?
- If projected height ≤ 8.5 cm below MPH, then considered within range for family
4) What is the bone age? i.e. is there evidence of delayed or accelerated growth?
- Delayed BA: CS, nutritional deficiency, underlying systemic disease (e.g. IBD), and endo SS
- Differentiate based on HV
- Kids with CSS, have low-normal HV appropriate for BA, until reach pubertal BA, when speeds up
- Kids with systemic or endocrine disease have progressive ↓s in HV
- Normal BA: FSS, Turner, skeletal dysplasia, early systemic disease
- Advanced BA: Precocious puberty, hyperthyroidism; usually have accelerated early growth but epiphysial closure results in SS as adult
Additional questions:
1) Was the growth retardation prenatal or postnatal in onset?
- If IUGR, unlikely to be GH, T4
- Consider chromosomal, genetic, TORCH
2) Is the child proportionate or disproprtionate?
- Disproportionate:
- Short limbs: Rickets, epiphyseal dysplasias, achondroplasia
- Short trunk: kyphoscoliosis, spinal irradiation
58
What is normal growth velocity?
Age 3-Pubertal
>5 cm/year=normal
<4 cm/year=abnormal
Puberty
8-10 cm/year
59
How do you differentiate between familial short stature and constitutional delay?
FSS
- Normal growth velocity
- Parents short
- Bone age normal
- Normal puberty
- Short final height
CDGP
- Delayed growth velocity 6-36 months, then normal through prepubertal childhood, then catch up at puberty
- Height is normal for bone age (not chronologic age)
- Family hx delayed growth/puberty
- Bone age delayed
- Puberty delayed
- Normal final height
60
What are some red flags for endocrine disorder causing short stature?
Decline in growth velocity with preservation of weight
Delayed bone age
Delayed puberty
61
What investigations should you order for short stature if child has decreased height velocity or height >2.5 SD below mean?
Bone age
CBC, ESR
Creatinine, lytes, bicarb, Ca, PO4,ALP, albumin
TSH, fT4
Karyotype in females
IGF-1 and IGFBP-3 (IGFBP-3 has higher sensitivity in children <10 years)
Anti-TTG+IgA
Others:
Morning LH, FSH (if precocious puberty)
MRI+gad (for children with established GH deficiency, signs of HPA dysfunction, or midline defects)
62
How do you diagnose GH deficiency?
```
Slow height velocity
Delayed bone age
Low IGF-1
GH stimulation test
Exclude hypothyroidism (because GH secretion requires intact thyroid function!)
```
63
What are red flags for short stature?
```
Cross percentiles
Decreased GV
Short for family heights
Disproportionate
Dysmorphic
Lower height than weight percentile
```
64
List 5 indications for growth hormone therapy
```
GH deficiency
Growth failure in CKD
SGA with failure of catch up growth
Turner's syndrome
Idiopathic short stature with ht <2.25 SD
```
65
Before puberty what is the growth velocity?
Slows down (4-6 cm/year)
66
Describe the mechanisms of calcium regulation
1) Calcium in diet
2) Calcium sensing receptor in parathyroid gland will release PTH if Ca low
3) PTH's job is to keep Ca normal at the expense of everything else (PO4, bone); main action is to activate Vitamin D
4) Vitamin D is stored as 25--Vitamin D. It is activated to 1, 25 Vitamin D by 1-alpha hydroxylase in kidney (activated by PTH)
5) Vitamin D increases gut absorption of Calcium
67
What do Vitamin D and PTH do to Ca and PO4?
PTH increases Ca and decreases PO4
| Vitamin D increases Ca and PO4
68
In vitamin D deficiency, what happens to Ca, PO4 and PTH?
Low/normal Ca (because of secondary hypoparathyroidism)
Low phosphate
High PTH
69
What are the causes of hypoparathyroidism?
Parathyroid hypoplasia/aplasia
- DiGeorge
- Maternal DM
Autoimmune parathyroiditis
-Isolated or with type 1 autoimmune polyendocrinopathy
Infiltrative lesions
- Hemosiderosis
- Wilson's
Post-surgical/post radioactive ablation
PTH receptor defects
-Pseudohypoparathyroidism
70
Causes of hypocalcemia
Vitamin D deficiency
Hypoparathyroidism
Rare causes:
Inadequate dietary intake
Redistribution (hungry bone syndrome, TLS, acute pancreatitis, osteopetrosis)
71
Causes of vitamin D deficiency
```
Poor dietary intake
Lack of sunlight
Malabsorption (CF, celiac, IBD)
Maternal vit D deficiency
Severe liver disease
Renal failure
Increased catabolism of VitD (AEDs-phenobarb, phenytoin)
Hereditary 1, 25 OH resistance
1-a-hydroxylase deficiency
```
72
What doses of Vitamin D are recommended?
0-1 year-400 IU
1-3 years-600 IU
4-18 years- 600-1000IU
73
What formulation of vitamin D do you give in vitamin D deficiency and hypoparathyroidism?
Vitamin D deficiency-25-OH D (cholcalcefirol)
| Hypoparathyroidism-1,25(OH)D (alfacalcidiol)
74
What is an appropriate dose of calcium supplement?
50-100 mg/kg/day
75
What are causes of hypercalcemia?
Hyperparathyroidism
- Parathyroid Adenoma/Hyperplasia
- MEN1
Excess vitamin 1, 25 D
- Subcutaneous fat necrosis
- Granulomatous disease (activated macrophages secrete 1-alpha hydroxylase)
- Vitamin D intoxication
- Sarcoidosis
- TB
Increased bone turn over
- Immobilization
- Hyperthyroidism
- Tumours
Other
- Familial Hypocalciuric Hypercalcemia
- William's syndrome
76
What are causes of hyperparathyroidism?
Primary
- Parathyroid Adenoma/Hyperplasia
- Genetic syndromes like MEN1
Secondary
Tertiary
-Longstanding hyperparathyroidism progresses to autonomous secretion of parathyroid
PTHrP tumours
77
What are the features of William's syndrome?
```
Cocktail personality
Supravalvular aortic stenosis
Short stature
Recurrent ear infections, hearing loss
Increased laxity, low msucle tone
Hypercalcemia
```
78
How do you treat hypercalcemia?
Hyperhydration
DO NOT give lasix
Low calcium diet
Bisphosphanates
- Decreases osteoclast acivity
- Takes 48-72 hours to see effect
Calcitonin
- Only works for short time
- Decreases bone resportion
- Mild increase in urinary Ca
Steroids
- If excess 1, 25 Vit D
- Inhibits conversion of 25 to 1, 25 Vit D
79
What is difference between osteomalacia and ricket's?
- Osteomalacia=undermineralization of bone osteoid
- Requires adequate Ca and PO4
-Rickets=Disease of growing bone that is due to poorly mineralized matrix at the growth plates
80
List 5 clinical features of Rickets
- Craniotabes
- Delayed closure of fontanelles
- Frontal bossing
- Delayed dentition; caries
- Craniosynostosis
- Rachitic rosary (widening of costochondral junctions)
- Harrison groove (depression of lower anterior chest from diaphragm pulling softened ribs)
- Respiratory infections and atelectasis (soft ribs impairs air movement)
- Enlargement of wrists and ankles (large growth plates)
- Valgus or varus deformities
- Windswept deformities
- Fractures
- Delayed motor milestones
81
What are the two types of rickets?
Calcipenic rickets
| Phosphopenic rickets
82
Radiographic features of rickets?
Growth plate thickening
Edge of metaphyseal border loses sharpness (fraying)
Concave surface of growth plate (cupping)
Widening of metaphysis.
http://www.learningradiology.com/archives04/COW%20088-Rickets/ricketscorrect.htm
83
What are the causes of calcipenic rickets?
Vitamin D deficiency
- Inadequate intake/sun exposure
- Malabsorption
- Increased catabolism
- 1-alpha hydroxylase deficiency
- Vitamin D receptor problem
Calcium deficiency
- Inadequate intake
- Increased urinary losses
84
What are the causes of phosphopenic rickets?
1. Inadequate intake
2. Malabsorption
3. Renal phosphate wasting
- Fanconi
- Dents
- Antiseizure meds
4. Genetic hypophosphopenic rickets (X-linked, AD, AR)
5. Overproduction of phosphatonin
- Tumor-induced rickets
- McCune-Albright syndrome
- Epidermal nevus syndrome
- Neurofibromatosis
85
How do you differentiate calcipenic vs phosphopenic rickets?
Main differentiating factor is PTH. Elevated in calcipenic rickets, low/normal in phosphopenic rickets
Phosphate not helpful in differentiating (in calcipenic because of secondary hypoparathyroidism)
Calcipenic rickets
Vitamin D deficiency: ++ALP, -/N Ca, -/N PO4, +PTH, -25OHD
Calcium deficiency: ++ALP, -/N Ca, -/N PO4, +PTH, N 25 OHD
Phosphopenic rickets
Nutritional deficiency: +ALP, N Ca, -PO4, -/NPTH, N 25OHD
Renal tubular PO4 wasting: +ALP, N Ca, -PO4, -/NPTH, N 25OHD
Genetic hypoPO4 rickets:
+ALP, N Ca, --PO4, +/NPTH, N 25OHD
86
What is the biochemical marker of rickets?
ALP=increased bone turnover of undermineralized bones
87
What is the best test for nutritional vitamin D deficiency?
25 Vit D
| 1, 25 Vit D is activated form--rarely need to test
88
What 4 investigations would you order for rickets?
Ca, PO4, ALP, PTH, 25-OHD
Rickets survey (hands and knees)
NOTE: best test for rickets is 25-OHD
89
```
All are seen in hyperparathyroidism except:
Hyporeflexia
Increased ICP
Carpopedal spasm
Candidiasis
Nonspecific EEG changes
```
Hyporeflexia
90
```
Hyperparathyroidism can be seen in all except:
Primary proximal renal tubular acidosis
Vitamin D deficient rickets
Rickets with liver failure
Rickets with anticonvulsants
```
Primary proximal renal tubular acidosis-PTH is normal/low
With liver failure and anticonvulsants, you get vitamin D deficiency, which results in secondary hyperparathyroidism
91
What is the active form of thyroid?
T3
92
For primary thyroid disorder, what is the best thyroid function test to use?
TSH
| Doing just a fT4 would miss a compensated hypothyroidism
93
For central hypothyroidism, what is the best thyroid function test to use?
fT4
94
What are causes of congenital hypothyroidism (3 categories)?
1) Dysgenesis-85%, abnormal development (e.g. ectopic thyroid, aplasia, hypoplasia)
2) Inborn errors of metabolism (dyshormonogenesis)-15%
3) Maternal antibiodies-2% transplacental maternal thyrotropin-receptor blocking antibody (TRBAb)
4) Maternal drugs: Iodides, Amiodarone, Propylthiouracil, Methimazole Radioiodine
95
When do you need to start treatment for congenital hypothyroidism?
Within first 7-14 days of life
96
When do you screen for congenital hypothyroidism?
DOL 3
97
What is an elevated TSH on newborn screening?
TSH >17
| TSH>40=critical (start meds now and order nuclear sign!)
98
What do you do with an elevate d TSH 17-40 on newborn screening?
repeat TSH, fT4
99
What do you do with an elevate d TSH >40 on newborn screening?
Repeat labs and start levothyroxine
| Thryoid nuclear scan
100
What are normal ranges for TSH and fT4 in 1st month of life?
T4 11-40
| TSH 1.7-9.1
101
What is the cause of neonatal hyperthyroidism?
1. Neonatal graves-Transplacental passage of thyroid stimulating antibodies (TBII)
2. Genetic defects of TSH
receptors
102
List 4 causes of acquired hypothyroidism
1. Hashimotos thyroiditis***most common
2. Polyglandular autoimmune syndrome type I and II
3. Iatrogenic (antithyroid drugs, radiation, thyroidectomy)
4. Systemic disease (LCH, cystinosis)
5. Hypothalamic/pituitary disease (craniopharyngioma, head trauma, LCH)
103
What should you do with subclinical hypothyroidism?
Repeat test
Check antibodies
Follow up in 3-6 months
Treat if TSH rising and staying >10
104
What are the causes of hyperthyroidism?
```
Grave's disease
Subacute thyroiditis
Acute suppurative thyroiditis
Toxic multinodular goiter
Toxic solitary adenoma
McCune Albright
Hyperfunctioning thyroid carcinoma
```
105
How do you treat hyperthyroidism?
Methimazole (first line)
Propanolol for symptoms
RAI
Subtotal thyroidectomy
106
What is sick euthyroid syndrome?
Abnormal TSH in sick patients
Normal adaption to critical illness state in which body is trying to slow down metabolism
DO NOT TREAT
107
Types of thyroid cancer
Papillary-most common
Follicular
Medullary-with ret mutations
108
Risk factors for thyroid cancer
Irradiation to head and neck
| Family history of medullary thyroid cancer, MEN2
109
Treatment of thyroid cancer
Near total thyroidectomy+
| Radioactive iodine ablation
110
What is the best way to monitor effectiveness of thyroid replacement in autoimmune thyroiditis?
TSH
111
What is most common cause of asymptomatic enlarged thyroid gland?
Hashimoto's
112
What are the diagnostic crtieria for diabetes?
```
FPG ≥7.0 mmol/L x2
or
A1C ≥6.5% (in adults) x 2
or
2hPG in a 75 g OGTT ≥11.1 mmol/L x2
or
Random PG ≥11.1 mmol/L + symptoms x1
```
113
What are the 4 principles of DKA management?
1. Treat shock
2. Slow Rehydration with electrolyte replacement
3. Correct hyperglycemia and acidosis with low dose insulin
4. Avoid complications
Hypoglycemia
Hypokalemia
Cerebral edema
114
At what rate should you rehydrate in DKA?
NS with 40 KCl (If K <5.5 and no evidence of renal failure)
| 7 ml/kg/h for first hour, then decrease to 3.5-5 ml/kg/h
115
When should you start insulin in DKA?
1 hour after IV fluids
116
What should you monitor during DKA management?
1. Hourly vital signs
2. Accurate fluid balance
3. Hourly glucose
4. Q2hr gas – venous
5. Q4hr electrolytes
117
By how much should the glucose drop / hour in DKA management?
<5 mmol/h
118
When do you switch to D5NS in DKA management?
When glucose <15
119
How do you calculate corrected sodium in DKA?
measured Na + 2 x [(glucose-5.5)÷5.5
120
Risk factors for cerebral edema
```
Younger age (<5 years)
New-onset diabetes
High initial serum urea
Low initial pCO2
Rapid administration of hypotonic fluids
IV bolus of insulin
Early IV insulin infusion (within 1st hour of fluids)
Failure of serum sodium to rise during treatment
Use of bicarbonate
```
121
What are the glycemic targets for diabetes?
<6 years:
HbA1C <8
FPG 6-10
6-12 years
HbA1C <7.5
FPG 4-10
13-18 years
HbA1C<7.0
FPG 4-7
2-hour pc 5-10
122
What are typical daily insulin requirements?
Pre and post pubertal: 0.8 to 1 units/kg/day
| Mid-pubertal: 1 to 1.2 units/kg/day
123
Explain how you divide insulin for a TID regimen
2/3 TDD in AM
- 2/3 intermediate @ breakfast
- 1/3 rapid @ breakfast
1/3 TDD in PM
- 1/3 rapid @ dinner
- 2/3 bedtime
124
Explain how you divide insulin for a MDI regimen
50% TDD basal
| 50% TDD boluses
125
What advice do you give T1DM for sick day management
-Maintain blood glucose between 4-11
-Check ketones
-If elevated (with elevated BG) give 10% TDD insulin and recheck in 4 hours
-If low, reduce by 20% TDD
Do not stop insulin
126
How frequently do you screen for associated conditions in T1DM?
Autoimmune thyroid disease:
-TSH, TPO Ab at diagnosis and every 2 years
Celiac:
-If clinically indicatetd; GI sx, poor growth, unexpected hypoglycemia
Addison's
-If clinically indicated: unexplained recurrent hypoglycemia, decreased insulin requirements
127
When do you screen for complications of T1DM ?
Nephropathy-first morning urine ACR yearly starting at 12 years in those with T1DM >5 years
Retinopathy-yearly at 15 years in those with T1DM >5 years
Neuropathy-postpubertal adolescents yearly after 5 years duration T1DM
Dyslipidemia-Screen at 12 and 17 years, <12 if BMI>95th percentile, family history of hyperlipidemia or premature cardiovascular disease
Hypertension-Twice a year
128
When and how do you screen for T2DM in at risk children?
Screening for T2DM should be performed every 2 years using an FPG test in children with any of the following:
I. ≥3 risk factors in nonpubertal or ≥2 risk factors in pubertal children
Risk factors:
a) Obesity (BMI ≥95th percentile for age and gender)
b) Member of a high-risk ethnic group (e.g. Aboriginal, African, Asian, Hispanic or South Asian descent)
c) Family history of type 2 diabetes and/or exposure to hyperglycemia in utero
d) Signs or symptoms of insulin resistance (including acanthosis nigricans, hypertension, dyslipidemia, NAFLD [ALT >3X upper limit of normal or fatty liver on ultrasound], PCOS)
II. Impaired fasting glucose or impaired glucose tolerance
III. Use of atypical antipsychotic medications
129
When do you screen for complications of T2DM?
Nephropathy-yearly at diagnosis
Retinopathy-yearly at diagnosis
Neuropathy-yearly at diagnosis
Dyslipidemia-At diagnosis, then every 1-3 years
HTN-at least twice annually
PCOS-yearly in pubertal females (hx/PE for oligo/amenorrhea, acne and/or hirsutism)
NAFLD-yearly with ALT
130
What orders would you put in for NPO in a T1DM patient?
Hold R, give 50% of N
| Blood glucose monitoring should be performed every one to two hours
131
When does neonatal hyperthyroidism from maternal antibodies remit?
6-12 weeks
| Antibodies can remain up to 6 months
132
List 3 symptoms of neonatal hyperthyroidism
```
Low birth weight
Preterm delivery
Microcephaly
(premature fusion of cranial bones), Irritability
Tachycardia/arrhythmias/hydrops, Hyperphagia
Diarrhea,
Goitre
Advanced bone age
Hepatosplenomegaly
Exophthalmos
```
133
Until when should corrected age be used when plotting premature infants on growth curves? (CPS)
Corrected age should be used at least until 24 to 36 months of age
134
Above what age should BMI be measured to screen for thinness, wasting, overweight and obesity?
>2 years
NOTE:
<2 years-use weight for length OR % Ideal Birth Weight
135
What is the definition of obesity based on BMI in the following age groups (CPS):
i) <2 years
ii) 2-5 years
iii) 5-19 years
```
i) <2 years
Weight for length >99.9%ile
ii) 2-5 years
BMI >99.9%ile
iii) 5-19 years
BMI >97th%ile
```
136
What is the definition of underweight using weight for length in the following age groups (CPS):
i) <2 years
ii) 2-5 years
iii) 5-19 years
```
i) <2 years
Weight <3rd%ile
ii) 2-5 years
Weight for length<3rd%ile
iii) 5-19 years
Weight for length<3rd%ile
```
137
Why are less children identified as FTT in the 1st 6 months based on WHO growth curves (compared to CDC)?
WHO curves are based on the growth of healthy breastfed infants
Breastfed infants grow more quickly in first 6 mo, more slowly 6-12 mo
Non-BF infants will thus appear to grow slowly first 6 mo, quickly 6-12 mo
Therefore, FTT is diagnosed less <6 months of age, and may be OVERDIAGNOSED in 6-12 months
138
At what age will most children's growth correlate with their genetic potential (mid parental height)?
By 2 years!
NOTE:
Baby's size from 6-24 months initially reflects uterine environment
By 2 years of age, usually closer to genetic potential
139
What is the definition of delayed/advanced bone age?
```
Delayed/advanced bone age defined as ≥ 2 SD from the mean
Number of months for 2SD ↑s with age
~12 mo age 2-4
~18 mo age 4-12
~2 yr age 12+
```
140
List 4 genetic causes of short stature
```
Turner syndrome
SHOX mutation
Noonan's syndrome
Russell Silver
Achondroplasia
```
141
What workup should you do for a child with short stature, but normal growth velocity?
History
Physical
Bone age
Unlikely to be pathologic SS
142
List 2 side effects of growth hormone therapy
↑ pseudotumor cerebri
Raised IOP
SCFE
↑ existing scoliosis
143
List 3 things that increase physiologic GH secretion
Exercise
Sleep (stage 3/4)
Sex steroids
Puberty
144
What percentage of SGA infants do not have catch up growth by 2 years?
10%
Consider GH therapy for these kids!
145
Differential diagnosis of short stature
1. Normal variants of growth
- Familial short stature
- CDGP
- SGA with catch up growth
2. Pathologic causes of growth failure
A) Systemic diseases
- Undernutrition
- Glucocorticoid therapy
- GI disease (celiac, crohns)
- Rheumatologic (sJIA)
- Renal disease (CKD, RTA)
- Malignancy
- Pulmonary disease (cystic fibrosis, severe asthma)
- Immunodeficiency
B) Endocrine
- Hypothyroidism
- Cushing syndrome
- GH deficiency
- Precocious puberty
C) Genetic
- Turner syndrome
- SHOX mutation
- Noonan
- Russell Silver
D) Skeletal dysplasias
- OI
- Spondylepiphyseal dysplasia
- Achondroplasia
146
List 3 conditions causing short stature with NORMAL bone age
```
FSS
SGA with catch up growth
Turners
SHOX
Russell Silver
Noonans
Skeletal dysplasias (OI, Spondylepiphyseal dysplasia
Achondroplasia)
Early systemic disease
```
147
List 4 causes of fetal overgrowth
```
Maternal DM
Sotos syndrome
Weaver syndrome
Beckwith wiedmann
IGF-1 excess syndromes
```
148
How do you determine the expected adult height of a child with CDGP?
Find %ile of current height for BONE AGE
| Extrapolate to age 18-20 on growth curve
149
What is expected progression of puberty in girls with respect to the following:
i) Pubarche
ii) Thelarche
iii) Growth spurt
iv) Menses
Normal order:
BOONS, PUBES, GROW, FLOW
1) Thelarche (age 10-11)
2) Pubarche: 6-12 months after thelarche
Pubic hair THEN axillary hair
3) Growth spurt
- Peak GV at SMR breast stage 2-3
4) Menses
- Usually 2 years after thelarche
150
What is expected progression of puberty in boys with respect to the following
i) Testicular enlargement
ii) Pubarche
iii) Growth spurt
Normal order:
1) Testicular enlargement
2) Pigmentation of scrotum, growth of penis
3) Pubarche
4) Growth spurt
- Typically 2 years after puberty
- Peak GV at genital SMR 4-5 ~13-14 yr
151
When is the peak growth velocity for boys and girls?
Boys-Genital SMR 4-5, 2 years after puberty, typically age 13-14
Girls-SMR stage 2-3, before menses
152
SMR staging for pubic hair
Stage 1: Prepubertal with no pubic hair.
Stage 2: Sparse, straight hair along lateral vulva.
Stage 3: Hair is darker, coarser, and curlier, extending over mid-pubis.
Stage 4: Hair is adult-like, but does not extend to thighs.
Stage 5: Hair extending from thigh to thigh.
153
Where can you find hCG secreting tumours?
Hepatoblastomas
| Choriocarcinomas/teratomas in CNS, mediastinum, gonads or adrenal glands
154
What is familial male limited precocious puberty?
Autosomal dominant genetic disorder
Constitutive activation of LH receptor
Causes puberty at 2-3 yo with mature leydig cells and ↑ testosterone
155
What are the clinical features suggestive of premature adrenarche?
```
Pubic hair <8 years in girls, <9 Adult odour
Mild accelerated growth velocity
Slightly advanced BA
Mildly elevated DHEAS
Increased risk of PCOS
```
156
How long does it take for premature thelarche to resolve?
Up to 3-5 years
157
Work up for delayed puberty
- Bone age
- FSH/LH and estrogen or testosterone to determine if gonadal failure vs. secondary to hypothalamic/pituitary
- Karyotype if hypergonadotropic hypogonadism
- Prolactin, TSH in girls
- Cranial imaging if multiple deficiencies
- AUS in girls for internal structures
158
Describe the genetics of familial hypercholesterolemia
Mutation in LDL receptor
Monogenic
Autosomal dominant
159
List 3 clinical features of homozygous familial hypercholesterolemia
- Severe atherosclerosis at aortic root and CA by early to mid childhood
- Xanthomas over Achilles tendon, extensor tendons of hands, cutaneous, corneal arcus
- At risk of sudden death
160
Which children should be screened for hyperlipidemia and at what age?
```
Screen children between age 2-10
Screen if following risk factors:
-Family history of CAD <55 years
-Family history of obesity, HTN, DM
-Parent cholesterol >13.3
```
161
What lifestyle recommendations would you make to treat hyperlipidemia?
1. Low fat diet
2. Decrease saturated fat, trans fat, total cholesterol intake
3. Exercise
4. Omega-3 fish oil
162
List 3 high risk conditions and 3 medium risk conditions for coronary artery disease
High risk:
- Homozygous FH
- Severe heterozygous FH
- Type 1 and 2 diabetes mellitus
- Chronic kidney disease
- Heart transplant recipients
- Kawasaki disease with current coronary aneurysms
Moderate risk:
- KD with regressed aneurysm
- Chronic inflammatory disorders
- HIV
- Nephrotic syndrome
163
When should pharmacotherapy be used to treat hyperlipidemia in children?
Only in children >10 years
Failure of dietary measures x 6 months AND:
- LDL-C ≥4.9 mmol/L with risk factors
- LDL-C 4.1 mmol/L- 4.9 mmol/L and one of the following conditions:
(1) a family history of premature CVD
(2) one high-level CVD risk factor or condition
(3) two moderate-level risk factors or conditions.
- LDL-C is 3.4 mmol/L - 4.1 mmol/L and:
(1) Two high-risk CVD factors or conditions
(2) One high-risk and two moderate-risk CVD factors or conditions
164
List 3 side effects of statins
Liver dysfunction
Rhabdomylosis
Rash
Lupus like syndrome
165
How do you treat hypertriglyceridemia?
Fibrates
166
List 5 complications of obesity
- Dyslipidemia
- Hypertension
- Type 2 DM
- PCOS
- Cholelithiasis
- NALFLD
- Pseudotumourcerebri
- Blount disease (tibia vara)
- SCFE
- Behavioral problems (anxiety, depression, eating disorders)
- OSA
167
What is safe weight loss in obesity management?
- 2-11 yrs: up to one pound per month
| - Adolescents: up to two pounds per week
168
List 5 interventions to prevent obesity
- Breastfeeding
- Establishing a healthy feeding relationship early in life (avoiding overly restrictive and overly permissive feeding patterns)
- Encouraging a family to eat meals together.
- Limiting consumption of sugar-sweetened beverages, including juice
- Encouraging a diet with ample servings of vegetables and fruits
- Limiting eating at restaurants, particularly fast-food restaurants
- Limiting portion size
- Encouraging moderate to vigorous physical activity for >1 hour daily
- Limiting television and other screen time – no screen time for children under 2 years of age; less than 2 hours daily after age two
169
List 6 causes of secondary ammenorrhea (past SAQ)
```
Pregnancy
Prolactinoma
PCOS
Primary Ovarian Failure
Anorexia Nervosa
Craniopharyngioma
Thyroid
```
Below is a more comprehensive differential:
1. Pregnancy
2. Hypothalamic dysfunction
- Functional hypothalamic amenorrhea
- Hypothalamic tumors and infiltrative lesions (e.g. cranipharyngioma, hamartoma, LCH)
- Systemic illness (e.g. Type 1 DM, Celiac disease)
3. Pituitary disease
- Hyperprolactinemia
- Other sellar masses (pituitary adenoma, craniopharyngioma, meningioma)
- Other diseases of the pituitary (radiation, infarction, and infiltrative lesions of the pituitary gland, such as hemochromatosis )
4. Thyroid disease
5. Polycystic ovary syndrome
- Other hyperandrogenic disorders (CAH, androgen-secreting tumours)
6. Ovarian disorders
- Primary ovarian insufficiency (premature ovarian failure)
- Ovarian tumors
7. Uterine disorders
- Asherman syndrome
170
List 4 investigations for secondary amenorrhea
```
Beta HCG
LH/FSH
TSH
PRL
Consider MRI if elevated PRL or central causes
Progesterone withdrawal test
```
171
How do you interpret a progesterone withdrawal test?
If withdrawal bleeding-normal endometrium
| If no withdrawal bleeding-hypoestrogenism, outflow obstruction
172
List 3 causes of menorrhagia
1) Dysfunctional uterine bleeding
2) Hematologic (ITP, VWF)
3) PID
4) Hypothyroidism
5) Ectopic pregnancy/spontaneous abortion
173
List 3 tests you would do for menorrhagia
```
CBC, ferritin
INR/PTT
TFTS
vWF antigen and ristocetin cofactor
If sexually active then test for STI’s, HCG
```
174
What is the most common cause of menmetorrhagia in a girl who started menstruating recently? (Past SAQ)
Dysfunctional uterine bleeding from anovulatory cycles
175
List 2 steps in management of dysfunctional uterine bleeding from anovulatory cycles
1. Iron supplementation
| 2. OCP
176
Describe the pathophysiology of PCOS
Increased LH pulsatility
High LH: FSH ratio
Increased ovarian production of androgens
Impaired folliculogenesis from low FSH
177
List 4 clinical features of PCOS
```
Metorrhagia
Hirsutism
Acne
Obesity
Polycystic ovaries on US
```
178
List 3 conditions you should exclude in a patient with suspected PCOS
Non classical CAH
Cushings (if HTN and muscle wasting)
Androgen secreting ovarian/adrenal tumour
Thyroid disease
179
Treatment of PCOS
Weight loss
Combined OCP
Metformin
180
List 2 complications of PCOS
- Infertility
- Endometrial cancer
- Metabolic disease (IGT, Type 2 DM)
181
What is the best test to detect PCOS (past MCQ)?
Increased LH/FSH ratio
182
What laboratory findings are in keeping with AIS?
- 46,XY karyotype
| - Serum testosterone concentrations in the normal adult male range
183
What is the difference between osteoporosis and osteomalacia?
Osteomalacia=undermineralized bone
| Osteoporosis=normal mineralization, but decreased bone volume
184
When is peak bone mass achieved?
20-35 yr of age
185
List 3 things that affect bone mass
- Vitamin D
- Calcium intake
- Weight-bearing exercise throughout childhood
- Alcohol and tobacco reduce bone mass accretion
186
How do you treat hypoglycaemia in T1DM?
1. Severe-glucagon 1m IM (0.5 mg if <=5 years)
2. Mild-mini dose glucagon
3. In hospital -IV dextrose
187
List 3 counselling points for T1DM in adolescence
1. Smoking cessation
2. Sexual health and contraception-unplanned pregnancies should be avoided
3. Screen for depression, anxiety, EATING DISORDERS
4. Transition to adult care
188
How do you screen peripheral neuropathy in diabetes?
History: numbness, pain and paresthesia
Physical exam: sensation, vibration, light touch and ankle reflexes
Monofilament testing suboptimal sens and spec in adolescents!
189
What are the goals of surgery management in T1DM?
Minimize hyperglycaemia-poor wound healing, decreased immunity
Target BG 5-10
Give 50% long acting and no short acting if NPO
Consider IV insulin if critical ill or not eating
190
What is the best way of screening for diabetic nephropathy?
First AM urine ACR
191
Criteria for DKA
Hyperglycemia (gluc>11)
Metabolic acidosis (pH<7.3, serum bicarb<18)
Ketonuria
192
Management of cerebral edema in DKA
1. Exclude hypoglycaemia
2. Raise head of bed
3. Mannitol
4. Protect airway
5. Decrease insulin to 0.05 U/kg/h
6. Arrange for ICU
193
How long after switching to subcutaneous insulin should you continue IV insulin?
1 hour
194
What is nonketonic hyperosmolar coma?
```
More common in T2DM
Severe hyperglycemia
No/mild ketosis
Severe dehydration
Altered sensorium and other neuro signs
```
195
What is maturity onset diabetes of the young?
```
Monogenic diabetes
Non-insulin dependent diabetes
Diagnosed <25 years of age
Autosomal dominant transmission
No antibodies
```
196
Which Aboriginal children be screened for T2DM according to CPS?
All of the following:
- Aboriginal descent*
- BMI >85th%ile
- Age >10 years old
And any one of the following:
- Sedentary lifestyle
- Children born to mothers who had gestational diabetes
- First- or second-degree relative† with type 2 diabetes
- Acanthosisnigricans
- Dyslipidemia
- Hypertension
- Polycystic ovarian syndrome
197
What is the target HbA1C for children with T2DM?
HbA1C <=7.0%
198
When should oral antihyperglycemic agents (metformin) be considered in the treatment of T2DM?
1. If glycemic targets are not achieved within 3–6 months using lifestyle modifications
2. If presenting HbA1C >7.0%
199
Differential diagnosis of hypoglycaemia in infants/children
1) Disorders of Carbohydrate Metabolism
- Disorders of glycogenolysis (e.g. GSDs)
- Disorders of glycosylation
- Disorders of gluconeogenesis (Fructose 1,6, bisphosphatase, pyruvate carboxylase)
- Galactosemia
- Hereditary Fructose Intolerance
2) Disorders of Amino Acid Metabolism
- e.g. MSUD, propionic acidemia
3) Disorders of Fatty Acid Metabolism
- e.g. MCAD
4) Hyperinsulinism
- Congenital hyperinsulinism
- Oral hypoglycemic agents
- DM
5) Ketotic Hypoglycemia***most common
6) Hormone Deficiencies
- Panhypopit
- Growth Hormone deficiency
- Cortisol Deficiency (Addison’s, CAH or ACTH Deficiency)
7) Ingestions
- Ethanol
- Salicylates
- Beta-Blockers
- Pentamidine
200
What are the features of ketotic hypoglycaemia?
- Most common form of childhood hypoglycemia
- Typically presents in children between 18 months and 5 years and spontaneously remits by 8-9 years of age
- Hypoglycemic episodes tend to occur during intercurrent illness when food intake is limited
- Pathogenesis is not well understood
- Requires exclusion of other causes of hypoglycemia
201
Laboratory features suggestive of ketotic hypoglycaemia
- Appropriately decreased insulin levels
- Normal lactate and pyruvate
- Elevated GH, cortisol, FFA, and ketones
- Decreased alanine on quantitative plasma amino acids
- Normal thyroxine (excludes hypopituitarism)
- Normal free and total carnitine, normal distribution of the fatty acid length in the acylcarnitines
- No response to administration of glucagon at time of hypoglycemia
- Negative urine reducing substances
202
Most important counselling for ketotic hypoglycemia
Monitor urine ketones
Ketonuria often precedes hypoglycaemia
If urine ketones high, give carbs!
203
List 10 tests to order for critical labs
```
Blood glucose
Insulin
C-peptide
Cortisol
Growth hormone
Lactate
Venous blood gas
Free fatty acids
Total and free carnitine
Beta hydroxybutyrate
Ammonia
Pyruvate
Urine reducing susbtances and ketones
T4, TSH
IGFBP-1
```
204
A robust response to glucagon (glucose up 1-2mmol/L) suggests what underlying aetiology of hypoglycemia?
Hyperinsulinism
Minimal response in FAO, GSD, gluconeogenesis disorders
205
What brain tumour is commonly associated with hypopituitarism?
Craniopharyngioma
206
List 4 clinical features of sept-optic dysplasia
1. Optic nerve hypoplasia
2. Agenesis of corpus callosum/septum pellucidum
3. Panhypopituitarism/isolated hormone deficits
4. Developmental delay
207
What physical exam finding is seen in most patients with thyroid dyshormonogenesis?
Goiter
208
In a patient with goitre and SNHL, what condition should you suspect?
Pendred syndrome
209
List 3 clinical features of congenital hypothyroidism
```
Prolonged jaundice
Poor feeding
Large tongue
Wide fontanelle
Constipation
Cardiomegaly
Umbilical hernia
Macrocytic anemia
```
210
Name the disease that causes the following results on thyroid nuclear scan:
i) No uptake
ii) Uptake outside thyroid gland
iii) Increased uptake
i) No uptake
- Thyroid aplasia
- TRBab, iodine trapping defect
ii) Uptake outside thyroid gland
- Ectopic thyroid
iii) Increased uptake
Dyshormonogenesis
211
What is the pathophysiology of Hashimotos thyroiditis?
Lymphocytic infiltration of the thyroid. (60% Tcells, 30%Bcells)
Followed by atrophy of the follicles
212
What autoantibodies are associated with Hashimotos thyroiditis?
Autoantibodies found in 90%
Most common=Anti-TPO Ab
Less common=antithyroglobulin Ab, thyrotropin Rc-blocking Ab
213
What is Polyglandular autoimmune syndrome type I?
Hypoparathyoidism
Addisons
Mucocutaneous Candidiasis
214
What is Polyglandular autoimmune syndrome type I2?
```
Addison
TIDM
Thyroid diseas
Vitiligo
Alopecia
```
215
List 5 causes of congenital goitre
1. Thyroid dyshormonogenesis
2. Antithyroid drugs or iodides during pregnancy ( incl Amiodarone)
3. Neonatal Graves
4. Maternal iodine deficiency
5. Teratoma
216
What is the most common cause of asymptomatic acquired goitre?
Hashimotos thyroiditis
```
Other causes of acquired goitre:
Iodine deficiency
Toxic goitre (Graves, McCune Albright)
```
217
What is the natural history of neonatal graves?
```
Resolves within 6-12 weeks
If symptomatic (tachycardia, goitre, hyperthermic), can treat with methimazole, propranolol
```
218
What antibodies are associated with Graves disease?
Thyroid receptor stimuling antibodies (TRSAb)
219
List 2 side effects of methimazole
Agranulocytosis, cholestatic jaundice, hepatitis, polyarthritis
220
Treatment of thyroid storm
```
PTU Q8H by NG
Sodium iodide
Propnanol
Hydrocortisone IV
IV fluids
Cooling blankets, tylenol
```
221
Differential for thyroid nodule
```
Thyroid Ca
Benign adenoma
Colloid nodule
Thyroid abscess
Simple cyst
Thyroglossal duct cyst
```
222
What is the most common reason for a false positive screen for congenital hypothyroidism?
Newborn screen taken too early and caught post natal TSH surge
223
List 4 causes of central DI
1) Genetic
- Familial central DI (autosomal dominant)
2) Acquired:
- Idiopathic
- Trauma
- Neurosurgery
- Neoplasms (germinomas, pinealomas, craniopharyngioma, optic glioma)
- Infiltrative (LCH, AML)
224
List 4 causes of nephrogenic DI
1) Genetic
- Hereditary nephrogenic DI
2) Acquired:
- Lithium toxicity
- Hypercalcemia
- Renal disease (e.g. bilateral UTO, APCKD)
Other
- Hypokalemia
- Drugs
- Pregnancy
- Craniopharyngioma surgery
- Bardet-Biedl syndrome
- Bartter syndrome
225
What is the definition of DI?
Serum osmolality >300 mOsm/kg and urine osmolality is <300 mOsm/kg
*NOTE: serum osmolality can be normal with intact thirst; therefore urine osmolality is more definitive indicator
226
If serum and urine osmolality are suggestive of DI, what test can be used to distinguish between central and nephrogenic DI?
Water deprivation test
- During fluid deprivation, if patient has DI, serum osmolality will rise*** and urine osmolality will continue to be low (<300)
- When serum osmolality >295 or Na>150, give DDAVP
- If central, urine osmolality will increase (from <300 after fluid deprivation to >800 after DDAVP)
- If nephrogenic, urine osmolality will not change (from <300 after fluid deprivation to <300 after DDAVP)
227
How do you treat central DI?
1) Fluids
- If thirst intact, can maintain plasma osmolality
2) DDAVP
228
What is the urine osmolality typically in SIADH (with hyponatremia)
>100mOsm/kg
| Urine osm>serum osm
229
List 3 actions of PTH
PTH stimulates:
1. Activity of 1α-hydroxylase in the kidney, to activate vitamin D to 1,25 Vit D
2. Aborption of calcium from GI tract
3. Mobilizes calcium from bone
4. Renal absorption of Ca, excretion of PO4
230
What is the diagnostic test of choice in addison's disease?
ACTH stimulation test
231
What is the most common cause of CAH?
21-Hydroxylase Deficiency
232
What percentage of 21-hydroxylase deficiency is salt-wasting vs. simple virilizing?
Classical CAH: 70% = salt-wasting, 30% = simple virilizing
233
List 3 possible physical exam findings in females with classic CAH
- Affected females have masculinized external genitalia
- Enlargement of the clitoris – can resemble a penis
- Partial or complete labial fusion
- Urogenital Sinus - vagina has a common opening with the urethra
- No testes (internal genital organs are normal, because affected females have normal ovaries and not testes and thus do not secrete AMH)
234
List 3 laboratory abnormalities in salt-wasting CAH
```
Hyponatremia
Hyperkalemia
Metabolic acidosis Hypoglycemia
Elevated 17-OHP
Low AM cortisol
Elevated testosterone and androstenedione in females
```
235
How do you establish diagnosis of CAH?
Measure 17-OHP before and after ACTH stim
236
When does salt wasting occur in classical CAH
10-14 days after birth (or longer)
237
Treatment of CAH
1. Glucocorticoids
2. Mineralocorticoid replacement (fludrocortisone)
3. IV fluids with D5 to maintain sugars
4. Surgical management of ambiguous genitalia
- Virilized females usually have surgery 2-6 mo of age
238
List 3 causes of cushion's syndrome (high cortisol)
1. Cushing's disease (ACTH-secreting pituitary tumour)
2. Adrenocortical Tumours
3. Ectopic tumours (e.g. neuroblastoma)
4. Exogenous steroids
239
What test would you do for suspected Cushings syndrome?
1. Establish diagnosis:
- Single-dose dexamethasone suppression test
2. Find cause:
- ACTH stim testing, 2-step dexamethasone suppression, CRHstim testing, and CT/MRI
240
List 2 genetic syndromes with increased risk of pheochromocytoma
VHL
| MEN 2A/2B
241
Diagnostic test for pheochromocytoma
↑ Urine metanephrines
| CT/MRI or MIBG to locate the tumour
242
What medications must be given to patients with pheochromocytoma peri--operatively?
Need pre and post-op alpha and beta-blockade and fluid loading
243
What conditions cause complete XY males with complete feminization?
Swyer syndrome (complete gonadal dysgenesis)
Complete AIS
Lydia cell aplasia
244
In Smith-Lemli-Opitz syndrome , what does the external genitalia of newborn males look like?
Genotypic males usually have genital ambiguity
Genotypic females have normal genitalia
245
List 3 clinical features of Smith-Lemli-Opitz syndrome
1. FTT
2. Microcephaly
3. Ptosis
4. Anteverted nares
5. Broad alveolar ridges
6. Syndactyly of the 2nd-3rd toes
7, Severe mental retardation
8. Ambiguous genitalia
246
In a child with DSD, what on exam will help you most with your differential diagnosis?
Palpable gonads
