Endo Flashcards
1
Q
Mode of inheritance for 5 alpha reductase
A
autosomal recessive
2
Q
Mode of inheritance for androgen insensitivity
A
x linked recessive
3
Q
Findings Kallman syndrome
A
isolated gonadotropin RH def and anosmia (embryo: failure of cells to migrate from olfactory bulb)
4
Q
Until when to expect spontaneous descent of testes
A
6 mons
5
Q
How does lugols solution work
A
Wolff chaikoff effect
- inhibit organification in thyroid gland
- Effective for 10 days
6
Q
Half life of thyroid antibodies
A
12 days (hyperthyroidism from antibodies- up to 3 weeks)
7
Q
Treatment of choice for neonatal hyperthyroid
A
methimazole
8
Q
Findings in thyroxemia of prematurity
A
Dec TBG- dec T4, T3
9
Q
Most common cause of congenital hypothyroidism
A
thyroid dysgenesis (agenesis, partial dysgenesis, extopic)
10
Q
Time to normalize TFT with treatment
A
FT4- 3 days; TSH- 2 weeks
11
Q
Treatment for hyperinsulinism
A
- Diazoxide (KATP antagonist)
- Octreotide
- Ca channel blocker
- Pancreatectomy
12
Q
Function of Mg in relation of Ca
A
- PTH release
- Calcitriol synthesis
- significant at Mg 1.5 mg/dl
13
Q
Signs of HypoCa secondary to HypoMg
A
- Tetany
- Seizure
- Weakness
- Prolonged QT
14
Q
Biochemical features of Osteopenia of prematurity
A
- hypophosphatemia (<3.5mg/dl)
- Hyperphosphatsia (>800 IU/L)
15
Q
Treatment for 21-hydroxylase deficiency
A
mineralocorticoid
glucocorticoid
genital reconstruction
16
Q
treatment for 11-betahydroxylase
A
glucocorticoid
genital reconstruction
17
Q
Findings in Vit D Rickets
A
pathologic fracture
rachitic rosary
moth eaten metaphases
18
Q
Lab findings in infant of diabetic mother
A
- Hypoglycemia (fetal hyperinsulinism)
- Low Mg
- low Ca
19
Q
Signs of hypoMg
A
- seizure
- muscle weakness
- decreased DTR
- irritability
- inc QT interval
20
Q
incidence of infant affected by mat graves
A
1%
21
Q
Timing of passing maternal Ab
A
2nd half of pregnancy
22
Q
Intrauterine sx of fetal hyperthyroidism
A
- fetal tachy
- iugr
- hydrops
- goiter
23
Q
Duration of infantile hyperthyroid from maternal thyroid Ab
A
4-6 weeks
24
Q
Embryology of thyroid
A
4wk- endoderm (pharyngeal floor), four pharyngeal pouch (calcitonin)
8 wk- fetal hypothalamus- TRH but TSH low
10-12 wk- thyroid complete
18-20 wk- thyroid gland func matures, response to TSH, inc T4 only
30 wk- T3 rises
-no fetal inhibition on TSH by T4
- hpt axis func abt 1-2 mos after birth
25
maternal T4 in cord blood at birth
30-50%
26
Medication of hypothyroid before and during pregnancy (should be done before the 3rd TM)
Levothyroxine
27
Effect for hypothyroid in pregnant women to infant
1. lower IQ
2. Expressive and nonverbal delays
28
increase in thyroid hormone in pregnancy
20-50%, inc TBG
29
Timing of TSH surge in neonate
30 mins after birth then normal 3-5 days
30
Stimuli for TSH surge
cool extrauterine environment
31
peak of neonatal T4
48 hours after birth
32
Pitfall of NBS using TSH
1. false pos- ideally 2-4 DOL
2. fail to detect TBG def and central hypothyroid
33
Pitfall of NBS using T4
miss primary hypothyroidism
34
What is hypothyroxinemia of prematurity
Lower total and FT4 in preterm infant due to:
1. abrupt discontinuation of maternal thyroid hormone
2. immature HPT axis (dec or absent inc T4 from TSH surge)
3. Low TBG
35
What is sick euthyroid
Low T3 and T4 (T3 more affected) due to inhibition of conversion enzyme
- Mortality assoc with low both TSH, T4 and T3
36
Complications of maternal Graves disease
1. gHTN
2. Pre ec
3. IUGR
4. Preterm birth
37
Meds affecting TFT
1. phenytoin: dec TBG affinity
2. dopa: dec TSH
38
Normal male sexual differentiation
39
Normal Female Differentiation
* No SRY- ovarian granulosa/ theca cells
* No AMH- mullarian (Cloaca) then into internal female (uterus, fallopian, upper 1/3 vagina), no wolfian
* No testosteron/DHT- clitoris (genital), labia minora (urethral), labia majora (labioscrotal)
40
Most common cause of genital ambiguity
In 46 XX: CAH
41
Most common cause of CAH (3)
21-hydroxylase deficiency
11 hydroxylase decificency
3B-hydroxysteroid dehydrogenase
42
Presentation of 21 hydroxylase def
salt wasting (hyponatremia, hyperkalemia)
hypoglycemia
hypovolemia
shock
43
Presents as virilization of the mother and the fetus
Aromatase deficiency
* cannot convert androgren precursor to estrogen
44
Maternal causes of Androgen excess
* ingestion of androgen or progestin
* virilizing adrenocortical tumors
* ovarian tumor
* luteomas
45
Presentation of vanishing testes or testicular regression
* Before 8 weeks: phenotypic female
* 8-10 weeks: ambigious genitalia
* after 12 weeks: normal male
46
Presentation of complete androgen insensitivity
Female external genitalia with a blind vaginal pouch
Presents with primary amenorrhea
47
Initial lab test for all ambigious genitalia
Routine chromosome analysis
-Should be obtained within the 1st 24 hrs after birth
48
Definition of clitoromegaly
clitoral length \>9 mm or width \> 6mm
49
Interpretation of AMH
- reliable marker of testicular function
## Footnote
- Low: vanishing testes, XY gonadal dysgenesis
- Elevated: androgen insensitivity, hypogonadotrophic hypogonadism
50
Hormones of anterior pituitary gland
1. Corticotroph: ACTH
2. Thyrotroph: TSH
3. Somototroph: GH
4. Gonadotroph: LH, FSH
5. Lactotroph: Prolactin
- in order of cell differentiation
51
Embryology of Pituitary Gland
Adenohypophysis: primitive oropharynx (Rathke pouch
Neurohypophysis: Neural ectoderm
Hypothalamus: Diencephalon
* Functional: 12 weeks
* HPA axis: 18-20 weeks
52
Findings of septo-optic dysplasia
1. Optic nerve dysplasia: wandering nystagmus
2. midline abnormalities (agenesis of corpus callosum, absence of septum pellucidum
3. Pituitary hypoplasia: GH deficiency most common
- 2 of the 3 is needed for Dx
53
Findings in Pituitary Stalk Interuption
1. Thins or interupted pituitary stalk
2. absent or ectopic post pit
3. small or absent ant pit
* hypoglycemia
* Jaundice
* micropenis
* short fifth digit
* unilateral ptosis
* congenital alopecia
54
CHARGE syndrome
* Autosomal dominant
* **C**oloboma
**H**eart defect
**A**tresia coanal
**R**etardation growth
**G**enital abnormality
**E**ar abnormality with sensorial-neural hearing loss
* Mutation with CHD7
55
Most affected pit hormone in childhood
GH defiency
* hypoglycemia
* +/- micropenis
* does not cause IUGR
* Postnatal linear growth not affected until 6-9 mos
56
Definition of micropenis
* Term: \<2.5 cm
* 34 weeks: \<2 cm
* 30 weeks: \<1.5 cm
57
Test for GH def
* random GH: \> 10 ng/ml adequate
* \<5 ng/ml with other of pit defiency findings- GH def
- Done within 1st 7 days
* IGF-1 cannot be used for the 1st 15-18 mos
58
Findings ACTH deficiency
* hypoglycemina
* hyponatremia without hyperkalemia- cortisol req for water excretion
* cholestasis- def cortisol -\> poor bile flow
* failure to thrive
59
Testing for ACTH def
ACTH or CRH stim test: 3-4 weeks
* Due to placental CRH stim: false normal if done early
60
Findings TSH deficiency/ hypothyroidism
* **Asymptomatic**
****
* Prolonged jaundice
* Feeding difficulty
* Constipation
* Umbilical hernia
* Macroglossia
* Hypotonia
* delayed reflexes
* Widen ant fontanelle
* Dry skin
61
Diagnosis of central hypothyroidism
Low FT4 (\<0.8 ng/dl) with low or normal TSH
Differential: Sick euthyrodism, Dopamine infusion
62
Treatment consideration in TSH deficiency
* assess for adrenal deficiency (inc cortisol clearance with thyroid replacement)
* should be treat 48-72 hrs prior to thyroid tx
* with cholestasis: higher doses of levothyrox and hydrocort due to dec absorption
* Discontinue thyroid tx before 3 y/o not recommended
63
How to administer levothyroxine
* Administer 30 mins before feeds
* absorption inhibited by food and products with soy, iron, calcium, aluminum
* Crushed tablet with 1-2 ml breastmilk, formula or water
* Placed in cheek pad
64
Pathway for insulin release
65
Action of insulin
1. inc cell glucose uptake
2. deposition of glucose as glycogen
3. lipogenesis
4. inhibition of breakdown of TG (lipolysis), FA (ketogenesis)
5. Fetal growth factor
66
Maintenance of glucose in newborn prior to establish feeds
1. glycogenolysis via inc glucagon and epinephrine
2. Supress insulin (4-48 hrs)
67
True or false
gluconeogenesis and ketogenesis is established after birth
False
68
Rationale for hypoglycemia in
1. LBW and IUGR
2. IDM/Macrosomia
1. decreased glycogen store and low fat stores
2. high insulin level, delay glucagon increase
Ideal: with establishment of feeds- normal levels in 48 to 72 hours
69
counter regulatory hormones of insulin
**glucagon**- promote glycogenolysis, formation ketone bodies
**GH**- promotes lipolysis (inc FFA for skeletal and cardiac muscle)
**catecholamines**- inhibits insulin release and promotes glucagon release
**cortisol-** inc gluconeogenesis from nin car source: alanine, lactate, glycerol
70
Outcome for severe/ frequent hypoglycemia
worse executive and visual-motor integration
71
Etiology of hypoglycemia after 48 hours
1. Maternal diabetes (most common transient cause)
2. Hyperinsulinism- most common cause of persistent nonketotic hypoglycemia
* transient: stress
* permanent: channelopathies
3. hypocortisolism- midline defect
4. GH defieciency- midline defect, signs of panhypopituarism
72
Newborn with persistent hypoglycemia- differential pathway
73
Most accepted definition of hyperglycemia
Plasma glucose 125 mg/dl
74
consequences of hyperglycemia
Immediate:
* dehydration
* ketosis
* DKA
* poor growth
* weight loss
* poor pefusion
* susceptibility to infection
Long Term: Neurodevelopment
75
rationale for consequence of hyperglycemia
* changes in osmolality and blood flow
* endothelial injury
* intracellular acidosis
* inc oxidative stress
76
Etiology of hyperglycemia
1. critical illness
2. infection
3. stress
4. meds (GIR fluids)
5. inadeq insulin
Rationale:
inc cytokines, dec glucose utilization, inc gluconeogenesis
77
Most common defect of permanent DM
KCNJ11 and ABCC8 gene (encode beta-cell subunits of K-ATP channel)
## Footnote
associated with parental consanguinity
78
Management of hyperglycemia
1. Dec GIR
2. Correct dehydration
3. establish eneteral feeds- inc incretin
4. dec IL infusion- dec gluconeogenesis and insulin resistance
5. Insulin
79
ketogenic AA
Leucine
Alanine
Glutamine
80
What is the mechanism for maternal diabetes teratogenecity
High glucose concentration
* HbA1C- correlate with rate of congenital anomalies
* timing: 2-8 weeks of gestation
* Alteration of DNA methylation
* Inc reactive oxygen species, disordered antioxidant defense
* Inc apoptosis (from distubrance of Ca homeostasis)
81
Maternal DM and CNS
| (most common anomalies)
neural tube defect
holoprosenecephaly hydrocephaly
82
Maternal DM and Cardiac
| (most common defect)
truncus arteriosus
AVSD
heterotaxy
single ventricle
83
Maternal DM and Craniofacial area
| (common affected)
Oculo-Auriculo-Vertebral disorder
* involves abnormalities from the 1st and 2nd pharyngeal arch: ears, eye, vertebral column
orofacial cleft
84
Maternal DM and GI
| (most common associated)
Atresia
Imporforate anus
Ventral wall defect (gastroschisis and omphalocele)
85
Maternal DM and GU
Hypospadias
renal agenesis/hypoplasia
bladder extrophy
86
Maternal DM and Musculoskeletal
Caudal regression syndrome
| (highest odd ratio)
87
Prevention of fetal and maternal complication of DM
1. HbA1C- \< 6.5% pregestation, \<6% in gestation
2. Closer monitoring: detail anatomy scan at 18 to 20 weeks
3. Fetal echo to consider
88
Definition of metabolic bone disease
reduction of bone mineralization below expected
Characterized by:
1. Biochemical:
* Ca \<8.5 mg/dl (inadequate intake)
* Phos \<3.6 mg/dl
* Alk phos
* \<33 wks: \> 900 IU/L plus phos \<5.6 mg/dl
* \<30 wks: \>500 IU/L
2. Radiographic
* reduced bone mineralization on xray: 20-40%
* Normal: normal bone denisty, normal dense white line
* Grade 1 loss of dense whie line at metaphysis and thining cortex
* Grade 2: fraying metaphysis with splaying (metaphyseal widening) and cupping (rachitic changes)
* Grade 3: fractures
89
Incidence of MBD
23% VLBW
55% ELBW
Detected at 10-16 weeks postnatal age
90
Embryology of skeleton
* Begins at 6 weeks
* Pathway:
1. craniofacial: cranial neural crest
2. axial: paraxial mesoderm
3. Limb: lateral plate mesoderm
* Differentiate:
1. chondrocyte: cartilage then turns to bone (carilage frame work done by 8 weeks)
2. osteoblast: osteoid bone matrix (mineralization majority at 3rd TM)
91
Function of osteoblast and osteoclast
Osteo**b**last:
* secrete osteoid bone matrix (unmineralized bone matrix) forms organic **b**one after binding with calcium
* differntiate in osteo**cytes**: signal and mechanoreceptor regulate osteoblast and osteoclast (**oversight** the two cells)
Osteoclast: from hematopoetic stem cell, bone resorption
92
timing of skeletal mineralization
Majority 3rd trimester
93
Hormones regulating Mineralization
1. Parathyroid
2. Vitamin D
3. PTH related peptide
4. Calcitonin
94
Effects of PTH
* Affected by dec serum Ca level
* Bone:
1. inc osteoclast activity: inc calcium in blood (by upregulate RANKL expression)
* Kidney:
1. Inc Ca reaborsption in distal tubule (inc TRPV5 transport)
2. Dec phos reabsorption
3. Inc active Vit D (1,25 dihydroxy Vit D/ Calcitriol)
95
What is Vit D
* Active: 1, 25 dihydroxyvitamin D (Calcitriol)
* D2- enteral
* D3- sunlight exposure
* Inc Ca absoprtion
96
What is PTH related peptide
Inc Ca transfer from placenta
Involved in proper chondrocyte dev endochondral bone formation
Produced by: placenta, parathyroid, muscles
97
What is Calcitonin
* secreted from thyroid and placenta
* inc calcitriol (Vit D)
* dec osteoclast activity
98
True or false
Calcium, magnesium and phosphorus is higher in the fetus than the mom
true
99
Intake of fetus per day of
1. Calcium
2. Phosphorus
Calcium: 100-120 mg/kg
Phosphorous: 50-65 mg/kg/day
100
Main source of calcium in the fetus
via active transport across the placenta
101
Reason for relative hypercalcemia in the fetus (3)
1. Low PTH
2. Low Calcitriol
3. High PTH related peptide
102
Absorption of Ca in the newborn is by
* Initial passive
* GI matures: active transport via calbindins (Vit-D dependent)
103
Risk factors for metabolic bone disease (prenatal and post natal)
* Prenatal
1. Uteroplacental deficiency ( preeclampsia, IUGR)
2. Chorioamnionitis
3. Maternal Vit D def
4. Male
* Postnatal
1. Prematurity- Ca accretion in 3rd TM
2. Feeding intolerance
3. Vit D def
4. Meds (inc excretion): loop diuretics, steroids, caffeine, NaHCO3
5. Sepsis
6. acidosis
7. renal disease
8. liver disease
9. GI
10. Immobility
104
Monitor sked for MBD
Biochemical at 4 weeks: alk phos and phos then every 2 weeks
Can d/c if: Alk phos \<500-600, phos \>4 on full feeds
Xray for changes if alk phos \>800
105
What is normal accepted mean blood pressure in preterm infant
2-3 mmHg above the infant post menstrual age
106
What are the cell origin for the adrenal glands
Adrenal **c**ortex: **c**oelmic epithelium
Adrenal medulla: neural crest
107
1. Components of the mature adrenal gland and early counter part and hormone produced
2. Which early counter part contributes most to the size of the mature adrenal at birth
Zona reticularis: fetal zone: androgen
Zona fasiculata: transitional zone: cortisol
Zona glomerulosa: definitive zone: aldosterone
Fetal zone contributes to size at birth
108
Components of the development of the fetal HPA axis
Pregnant woman
Placenta
Fetus
Early gestation (less than 30 weeks): mom provides the steroids; placenta provides progrestrone
Late gestation (after 30 weeks): inc 11B-HSD in placenta to inactive maternal cortisone; fetus produce own ACTH and cotisol
109
What is the action of cortisol
metab, stress response, immune and inflam response
Results in: Inc BS, Inc glucagon, Inc catecholamine (via inhibit B receptor breakdown)
Deficiency results in: CLD, cardiovacular instability
110
Role of Aldosterone
Absorb Na, excrete K
Control BP (inc extracellular fluid volume) via distal collecting tubule
Results in alkalosis (Inc H excretion to balance K absorption)
111
Role of DHEA and androgenic steroids
Precurssor to estrogen and androgen
DHEA: reduce inflam inc blood flow, immunity, insulin sensitivity, bone metab;
Encourage fetal cortisol production: additional 11B-HSD2 in the placenta
## Footnote
Produced by the fetal zone whihc disappears by 6-12 mons of age
112
Presentation of adrenal insuffiency
Vasopressor resistant hypotension
113
Duration of neonatal graves disease
3 to 5 months
self-limited condition resolves with the clearance of the thyroid receptor antibodies.
114
When and what to treat with abnormal TFT
Treat ASAP
1. Hyperthyroid
* Asymptomatic: methimazole
* Symptomatic methimazole + propanolol
2. Hypothyroid
* Levothyroxine
115
what is the main treatment of choice for diabetes insipidus
thiazide diuretic
think of DI- hypernatremia, polyuria with diluted urine
116
Mechanism to achieve normothermia in newborns
Nonshivering thermogenesis by oxidation of brown adipose tissue
## Footnote
- has sympathetic innervation, very rich vascularization, and an increased number of mitochondria
- located in the interscapular area, axilla, around the great vessels and kidneys
