ENDOCRINOLOGY Flashcards
1
Q
What are the clinical features of McCune-Albright Syndrome?
A
BONES AND ENDOCRINE:
- Polyostic fibrous dysplasia
- Cafe au lait spots (jagged edge “Coast of Maine” appearance)
- Hyperthyroidism
- Precocious puberty
2
Q
What are the 3 Es of Diencephalic syndrome?
A
- Emesis
- Emaciation
- Euphoria
Results from hypothalamic tumor
Body is in catabolic state
Child will want to eat a lot
3
Q
What hormones influence growth? (6)
A
- Growth hormone
- Insulin
- Insulin Growth Factor -1
- Cortisol
- TSH
- Androgens/estrogen
4
Q
Which hormone controls prenatal growth? Postnatal growth?
A
Pre-natal growth: insulin
Postnatal growth: GH
5
Q
What is the most accurate way of predicting adult height? What is the least accurate way?
A
Most accurate - bone age
Least accurate - mid parental height
6
Q
3 causes of delayed bone age:
A
- Constitutional delay
- Chronic disease
- Endocrine disease
7
Q
What is the most common cause of endocrine-related growth failure?
A
Primary hypothyroidism (causes growth arrest)
8
Q
What is the most common cause of hypoglycemia in patients over 18 months old?
A
Ketotic hypoglycemia: substrate (glucose) deficiency
9
Q
What is the management of a newborn found to have increased TSH and decreased thyroid hormone (T4) on newborn screening and confirmed again on bloodwork?
A
IMMEDIATE initiation of thyroid hormone replacement (levothyroxine)
-delay in therapy greater than 2 weeks of age can result in cognitive impairment
10
Q
What are the Tanner/sexual maturity rating stages in girls?
- pubic hair
- breasts
A
SMR stages:
- Preadolescent
- Sparse pubic hair, small mound of breast and papilla
- Darker, increased pubic hair; enlarged breast and areola
- Coarse, abundant pubic hair; areola and papilla form double mound
- Adult feminine triangle, spread to medial surface of thighs; mature breasts, nipple projects
11
Q
At what Tanner/SMR stage does menstruation occur?
A
30% in stage 3, 90% by stage 4
12
Q
At what Tanner/SMR stage does axillary hair production occur for:
- boys
- girls
A
Boys: stage 4
Girls: stage 3
**Remember that girls mature more quickly than boys!
13
Q
What are the Tanner/sexual maturity rating stages in boys?
- pubic hair
- penis
- testes
A
- No pubic hair, preadolescent penis and testes
- Sparse pubic hair; minimal change in penis size, enlarged scrotum
- Darker pubic hair, lengthening of penis, testes grow larger
- Coarse, abundant pubic hair; glans and breadth of penis increase, increased size and darkening of scrotum
- Adult distribution of pubic hair with spread to medial surface of thighs, adult size penis and testes
14
Q
What is the cycle of menses?
- follicular phase
- luteal phase
A
- Follicular phase: begins with onset of menses –> results in mid cycle LH surge which induces ovulation from the follicle. Empty follicle then forms the corpus luteum initiating the luteal phase
- Luteal phase: progesterone and estradiol are secreted from the corpus luteum maintaining the endometrial layer of the uterus. If pregnancy does not occur and there is no HCG to maintain the corpus luteum, it dies which results in withdrawal of progesterone and thus endometrium sloughs, giving you a period
15
Q
What are the stages of puberty in females?
-what age does puberty start?
A
Onset of puberty: 8-13 yo
- Thelarche: onset of breast development (precedes pubarche by 6-12 mo)
- Adrenarche –> Pubarche: onset of adrenal androgen production which leads to onset of sexual hair growth
- Menarche: follows thelarche by 2-3 years
Remember boobs, pubes, grow, flow
**Growth spurt starts with early puberty and occurs over 2-3 years with peak height velocity achieved about 1 year before menarche
16
Q
Growth spurt is completed by what age in females?
A
99% of growth is complete by 15 yo
17
Q
What are the stages of puberty in males?
-what age does puberty start?
A
Avg age of onset: 9-14 yo
- Testicular enlargement: 1 yr before pubarche
- Adrenarche/pubarche: from adrenocortical androgen production and gonadal activity
- Pubertal growth spurt: occurs 2 years later in boys than girls and occurs during SMR pubic hair stages 3 and 4
- Facial hair/voice change during SMR stage 4
18
Q
Growth spurt is completed by what age in males?
A
99% of growth is complete by 17 yo
19
Q
What does the adrenal medulla secrete?
What does the adrenal cortex secrete?
- glomerulosa
- fasciculata
- reticularis
A
Adrenal medulla:
-catecholamines
Adrenal cortex:
- zona glomerulosa: mineralocorticoids aka aldosterone (think glomerulus in kidney)
- zona fasciculata: glucocorticoids
- zona reticularis: sex hormones + small amt glucocorticoids (“I had sex with reticularis”)
20
Q
After the onset of menarche, how much more will girls typically grow?
A
7 cm after menarche
-but need to get bone age xray to know for sure
21
Q
What are the effects of cortisol?
- metabolic
- CVS
- growth
- immune
- skin/bone/calcium
- CNS
A
- Metabolic: increases serum glucose by increasing hepatic gluconeogenesis and glycolysis
- CVS: positive inotropic effect on the heart
- Growth: inhibit linear growth and skeletal maturation by decreasing GH and IGF1
- Immune: decreases inflammation and immune response
- Skin/bone/calcium: inhibits fibroblasts leading to poor wound healing, decreases serum Ca and decreases osteoblastic activity –> osteoporosis
- CNS: crosses BBB and has direct effects on brain metabolism –> stimulates appetite, insomnia, irritability, emotional lability
22
Q
What are the 3 urine catecholamines you test for in cases of possible adrenal medulla tumors?
A
- VMA
- Metanephrine
- Normetanephrine
23
Q
What are the steps of sex differentiation in utero?
A
- If there is a Y chromosome, then the bipotential gonads can differentiate into testes between 6-8 wks.
- The testes produce testosterone (Leydig cells) and anti-Mullerian hormone (Sertoli cells) –> testerone directs formation of the internal male reproductive organs from Wolffian ducts and AMH suppresses development of the Mullerian ducts (ie. preventing female internal reproductive organ formation)
- At 8-12 wks, the testosterone made by testes is changed to DHT (by 5 alpha reductase). DHT causes formation of male external genitalia. If there is no DHT, then female external genitalia develops.
**In infants with CAH, there is an excess of DHT due to build up of intermediate metabolites and thus female babies can have virilization (formation of male external genitalia) while still having normal female internal reproductive organs
24
Q
What is the most common cause of congenital adrenal hyperplasia?
A
21-hydroxylase deficiency (90% of cases)
-two types: classic (severe form, 75% have salt wasting) and non-classic (milder)
25
In non-classic CAH, what are most common presenting features (2)?
Androgen excess manifests later in life as:
1. Premature adrenarche
2. Advanced bone age
* *genital ambiguity is not present at birth
- no salt-wasting (mineralocorticoid deficiency)
26
What is the differential diagnosis for short stature with:
- normal growth velocity (aka following growth curve) (3)
- abnormal growth velocity (aka droppping off growth curve)? (5)
Normal growth velocity:
1. Constitutional growth delay (bone age < chronological age)
2. Familial short stature (bone age = chronological age)
3. Idiopathic short stature (height < 2 SD of mean for age with no other medical abnormalities found on investigations)
Abnormal growth velocity
1. Chronic disease
2. Malnutrition
3. Endocrinopathies (hypothyroidism, GH deficiency, excess glucocorticoid)
4. Psychosocial
5. Drugs (glucocorticoids)
27
What is the classic triad of septo-optic dysplasia?
| -diagnostic criteria?
Triad:
1. Optic nerve hypoplasia (manifests as nystagmus)
2. Pituitary hormone abnormalities: growth failure, hypothyroidism, adrenal insufficiency, diabetes insipidus (varying degrees)
3. Midline brain defects: agenesis of septum pellucidum and/or corpus callosum
- need 2/3 of features for diagnosis (this is up for debate)
28
What are the two common presenting symptoms of septo-optic dysplasia in neonates?
1. Hypoglycemia
| 2. Seizures secondary to underlying structural brain abnormalities
29
What investigations should be ordered in a suspected case of septo-optic dysplasia?
1. Brain MRI to rule out midline brain abnormalities
2. Ophtho consult
3. Pituitary function: TSH, cortisol (random in a neonate is fine), growth hormone, IGF-1
* **when child is older, consider LH and FSH levels to monitor for delayed puberty
30
What is the normal growth velocity for children:
- < 1 yo
- 1-2 yo
- 2-3 yo
- childhood
- adolescence
- < 1 yo: 18-25 cm/y
- 1-2 yo: 10-12 cm/y
- 2-3 yo: 8-10 cm/y
- childhood: 5 cm/y (small deceleration before onset of puberty)
- adolescence: 6-9 cm/y (but this is variable)
31
What is the best way to monitor effectiveness of thyroid replacement in autoimmune thyroiditis?
Monitor TSH
| -autoimmune thyroiditis: lymphocytic infiltration of thyroid gland
32
What is the most common form of inheritance of primary nephrogenic DI?
X-linked inheritance
- more common in males (90%)
- mutation in AVPR2 gene
33
What is the most common cause of thyroid disease in children?
-what is the most common antibodies seen in this condition (3 in total)?
Hashimoto's aka lymphocytic thyroiditis aka autoimmune thyroiditis
- MOST COMMON cause of thyroid disease in children
- T cell lymphocytes infiltrating thyroid gland
- hyperplasia first (can get hyperthyroidism) and then follicular cells die (hypothyroidism)
- anti-thyroperoxidase antibodies most common (90%); can also have anti-thyroglobulin antibodies (10%) and anti-thyroid receptor antibodies
34
What is the treatment for Hashimoto's thyroiditis?
- If hypothyroid: levothyroxine
| - If euthyroid: monitor with no treatment
35
What are the indications for growth hormone (6)?
1. Turner's syndrome
2. Idiopathic short stature with severe functional impairment secondary to short stature
3. Prader Willi
4. Growth hormone deficiency
5. Chronic renal failure
6. SGA with short stature
36
What are the possible side effects of growth hormone (4)?
| think what obese people are at risk of getting
1. SCFE
2. Pseudotumor cerebri
3. Gynecomastia
4. Worsening scoliosis
37
Is precocious puberty more common in boys or girls?
| -what is the most common etiology in this group?
Girls!
| -most common etiology is idiopathic
38
What is the differential diagnosis for virilized female baby?
1. 3-B-hydroxysteroid-dehydrogenase deficiency
2. CAH (21 hydroxylase deficiency
3. Maternal androgen exposure (maternal adrenal tumor)
39
What is the differential diagnosis for an undervirilized male?
1. Defect in androgen synthesis (3-B-hydroxysteroid-dehydrogenase or 5-alpha reductase deficiency)
2. Androgen insensitivity syndromes (receptors do not respond to testosterone)
3. Syndromes with defect in testicular malformation
- Deny-Drash: nephropathy, bilateral Wilm's and ambiguous genitalia
- WAGR
40
What are the clinical features of hypoparathyroidism (5)?
1. Hypocalcemia
2. Delayed teeth eruption/strength
3. Scaly skin
4. ***Mucocutaneous candidiasis
5. Cataracts
* **All from hypocalcemia
41
What are the exam findings of hypocalcemia (6)?
1. Muscle spasms
2. Chovstek's sign: facial nerve spasm on tapping
3. Trousseau's: hand spasm with blood pressure cuff inflated
4. Seizures
5. Tetany
6. Hyperreflexia
42
What hormones is secreted by the anterior pituitary gland?
```
FATPIG
F - FSH/LH
A - ACTH
T - TSH
PI - prolactin
G - GH
```
43
What are the two hormones secreted by the posterior pituitary gland?
1. Oxytocin
| 2. ADH
44
How do you distinguish between primary and secondary adrenal insufficiency on clinical features and labwork?
Primary adrenal insufficiency: adrenal gland dysfunction
- elevated ACTH
- low cortisol or low mineralcorticoid (hyponatremia/hyperkalemia)
- will see hyperpigmentation (due to pituitary gland trying to stimulate the adrenals and also secreting MSH)
Secondary adrenal insufficiency:
hypothalamic or pituitary dysfunction
-low ACTH
-low cortisol, normal mineralocorticoid (controlled by RAAS system, not hypothalamus or pituitary; thus no hyponatremia/hyperkalemia)
45
What is the differential diagnosis for primary adrenal insufficiency (5)
1. Autoimmune: isolated, autoimmune polyendocrinopathy syndromes
2. Infectious: meningococcemia, disseminated fungal infections, TB
3. Trauma: bilateral adrenal hemorrhage
4. Inherited enzymatic defects: CAH
5. Iatrogenic: exogenous steroids
46
What conditions should be screened for in obese patients? (8)
1. Hyperlipidemia
2. Obstructive sleep apnea
3. Type 2 DM
4. Hypothyroidism
5. SCFE
6. Intracranial hypertension
7. PCOS
8. Accelerated growth secondary to increased estrogen
47
What is the diagnostic criteria for PCOS?
1. Anovulation or oligoovulation
2. Hyperandrogenism
3. Polycystic ovaries on U/S (not required to make the diagnosis)
48
What are clinical features of rickets?
General:
1. FTT
2. Fractures
3. Frontal bossing
4. Delayed anterior fontanelle closure
5. Delayed eruption of teeth
6. Craniotabes (soft, thin skull)
Chest:
1. Ricketic rosary: prominent knobs of bones at costochondral joints
2. Harrison's groove: diaphragm pulls weakened bones downward
3. Atelectasis
Wrist:
1. Widening of wrist
49
How do you calculate mid parental height?
Girl: [(mom's ht in cm + dad's ht in cm) - 13 cm] / 2
Boy: [(mom's ht in cm + dad's ht in cm) + 13 cm] / 2
50
Which is the only pituitary hormone that is suppressed by a hypothalamic factor?
Prolactin - inhibited by hypothalamic release of dopamine
-thus, in hypothalamic deficiency, you get a decrease in most pituitary hormone secretions but can have increase in prolactin secretion
51
In a baby born with ambiguous genitalia, what is the most important thing to do on exam?
Establish whether there are palpable gonads in the scrotum or inguinal canal
-if you feel testicles, Y chromosome is more likely
52
Broadly, what are the 3 causes of ambiguous genitalia in a male patient (XY chromosome on karyotype)?
-useful investigations?
1. Defective adrenal production of androgens
2. Lack of proper testicular testosterone synthesis
- ie: 5 alpha reductase deficiency = inadequate conversion of testosterone to DHT leaing to ambiguous external genitalia but normal internal genitalia
3. Failure of target tissues to respond to androgens
- complete vs. partial androgen insensitivity
- complete: presents in adolescence since child appears phenotypically female and when reaches adolescence, amenorrhea is noted
- partial: has ambiguous genitalia thus is diagnosed at birth
- useful investigations: testosterone and DHT (dihydrotestosterone) levels
53
What are the 2 most common causes of ambiguous genitalia in a female patient (XX chromosome on karyotype)?
Virilization occurs when the female fetus is exposed to excessive androgens; since mullerian inhibiting substance is not present however (secreted only by testicles which only develop when there is a Y chromsoome), female internal reproductive organs are normal
1. Congenital adrenal hyperplasia
2. Maternal exposure to exogenous androgens
54
What are potential sources of maternal androgens that could contribute to virilization of a female baby?
1. Use of progestins during pregnancy
2. Ovarian or adrenal tumors
3. Maternal CAH
55
What syndromes are associated with tall stature (ie. height 2 SD above mean)?
1. Marfan syndrome
2. Klinefelter
3. XYY
4. Homocystinuria
5. Growth hormone excess (cerebral gigantism from pituitary GH-producing tumor or GH-releasing factor producing tumor in hypothalamus)
56
What is the definition of precocious puberty?
| -in girls vs. boys?
- Girls: Onset of puberty prior to age 6 in African American girls and prior to age 8 in all other races
- Boys: onset of puberty prior to age 9
57
What are the 2 broad categories for classifying etiologies of precocious puberty?
- main causes for each?
- clinical features of each?
- treatment for each?
1. Gonadotropin-dependent (ie. central) precocious puberty
- will see HIGH LH & FSH due to increased pituitary gland production
- early hypothalamic GnRH secretion occurs = usually idiopathic in females but more likely to be secondary to another process in males
- clinical features: accelerated linear growth with advanced bone age (but this means earlier fusion of epiphysis which leads to adult short stature), pubertal levels of LH, FSH, estradiol, testosterone, in boys will see bilaterally enlarged testes
- diagnose with GnRH stim test
- treatment: GnRH agonists, ie. lupron (remember that pituitary gland releases FSH & LH based on pulsatile release of GnRH by hypothalamus; thus with GnRH agonist acting at the pituitary GnRH receptors at all times, will actually have decreased FSH & LH production due to desensitization)
- Causes (think CNS lesion):
1) Hypothalamic hamartoma
2) Gliomas
3) Trauma
4) Postinfectious changes
5) Hydrocephalus
2. Gonadotropin-independent precocious puberty:
- will see LOW FSH/LH due to excess androgens causing negative feedback loop
- Causes (think tumor):
* girls: 1) Exogenous estrogens (pills/creams)
2) estrogen-producing tumors of the ovary or adrenal gland
3) ovarian cysts
4) McCune-Albright syndrome
* boys: 1) topical androgens
2) adrenal enzymatic deficiencies
3) testicular tumor
4) Leydig cell hyperplasia
5) HCG-producing tumors
6) adrenal tumors
- clinical features: virilization, increased linear growth, usually normal sized testes for age
- treatment: remove the source of excess androgen
58
In what age group does premature thelarche commonly occur?
Ages 1-4 yo
| -average: 18 months
59
What is the differential diagnosis for gynecomastia?
| -distinguishing features between the 2 broad categories?
Physiologic vs. pathologic
- Physiologic: occurs in 40% of boys, breast enlargement starts at tanner stage 2-3, lasts ~ 2 yrs, can be unilateral or symmetric
- pathologic: onset before or after puberty, rapid progression, nipple discharge, drug use, >4 cm of breast tissue, small testicles, testicular mass, abnormal neurologic exam, tall & slim body habitus (eunuchoid body habitus = Klinefelter)
- ddx for pathologic gynecomastia:
1. Klinefelter syndrome
2. Partial androgen insensitivity
3. Hyperthryoidism
4. Marijuana
5. Liver disease or tumor
6. Adrenal or testicular tumor
60
What are the 2 broad categories of delayed puberty?
| -ddx for each?
Primary gonadal delayed puberty (problem with the ovary/testes) vs. secondary gonadal delayed puberty (problem with the CNS axis)
Primary gonadal delayed puberty:
- will see INCREASED LH/FSH since the pituitary gland is trying to stimulate the gonad to produce androgens and is getting nothing back
- ddx (common):
1. Chemotherapy/radiation therapy
2. Autoimmune destruction
3. Androgen insensitivity syndrome (XY karyotype but phenotypically female = develop breasts but never grow sexual hair or have menarche)
4. Complete 17 alpha hydroxylase deficiency: cannot make any sex steroids
5. Turner syndrome: no breast development since ovaries fail prior to puberty, still develop sexual hair since adrenals are still making androgens
6. Klinefelter syndrome:
- will see DECREASED LH/FSH since there is either a problem with the hypothalamus not making GnRH or pituitary gland not making LH/FSH and thus nothing is stimulating the gonads to secrete sex hormones
- treatment: replacement of sex steroids (ie. testosterone injections or conjugated estrogens, OCP to induce menses)
Secondary delayed puberty (hypogonadotropic):
- ddx:
1. Constitutional delay (most common)
2. Kallmann syndrome: Failure of GnRH neurons to migrate to the hypothalamus during embryogenesis and thus lack of cells that secrete GnRH = thus have hypogonadotropic hypogonadism. Patients also have anosmia or hyposmia (altered sense of smell)
3. Pituitary adenoma: secretes prolactin which acts on negative feedback loop and decreases LH/FSH release
4. Hypothyroidism
5. Chronic illness/malnutrition
- investigation: do GnRH stim test to differentiate between these two (Kallmann will have low or absent GnRH), CNS imaging to r/o tumor
- treatment: replacement of sex steroids
61
What is the screening test for growth hormone deficiency?
IGF-1
| -if this is abnormal, then do growth hormone stim test
62
What is the workup for someone with short stature and poor growth velocity?
1. Endocrine screen: *For anterior pituitary:
Go find the adenoma please
-Go = growth hormone (measure surrogate which is IGF-1)
-Find = FSH and LH (no point in
-The = TSH and FT4
-Adenoma = ACTH = do cortisol level
-Prolactin = rules out mass
* For posterior pituitary problems:
- lytes to rule out ADH abnormalities
- oxytocin is not going to be super helpful
Include CBC + diff, BUn, Cr, ALT, Bili as well
63
What is normal puberty?
- Girls: NORMAL to start between 8-13 years old
| - Boys: NORMAL to start between 9-14 years old
64
What are the clinical features of Turner syndrome?
1. Short stature
2. Lowset ears
3. Cystic hygroma
4. High arched palate
5. Short, webbed neck
6. Shield chest with widely spaced nipples
7. Low posterior hairline
8. Primary amenorrhea
9. Cubitus valgus
10. Bicuspid aortic valve (most common cardiac issue)
11. Coarctation of aorta
65
How big do testes have to qualify as puberty?
4 ml or 2.5 cm
66
In a patient with precocious puberty, what are the first two investigations you should do?
1. Look at growth velocity
2. Order bone age
* ***if there is increased growth velocity and advanced bone age, then there is a pathological cause of precocious puberty
* ***Baseline FSH and LH levels are useful in delayed puberty but USELESS in precocious puberty because it doesn't really tell us anything!!!! Do NOT order it!
67
What is a complication of lupron?
Sterile abscesses at IM injection site
68
When do you treat precocious puberty?
Depends on age (usually treat for girls < 6 yo and all boys with progressive central precocious puberty) and how much of an effect it is having on their psyche
- treatment with lupron in girls < 6 yo resulted in improvement by ~10 cm in final adult height
- treatment in girls 6-8 yo showed ~5 cm improvement in final adult height
- treatment in girls after 8 yo = no final adult height improvement
69
What are the androgens we measure in precocious puberty? (4)
1. DHEAS
2. Testosterone
3. 17 OH P
4. Androstenedione
70
What is the definition of premature thelarche?
| -what are the mandatory requirements to make this diagnosis?
Premature thelarche = breast enlargement WITHOUT development of nipples or areola
- can occur in girls 1-4 yo and may be unilateral
- In order to make this diagnosis: need NORMAL growth velocity (ie. there is no acceleration of linear growth) and NORMAL bone age (ie. no advanced bone age)
- this is what differentiates this from precocious puberty
71
What are the calcium and phosphate levels seen in hypoparathyroidism?
-what about vitamin D deficiency?
Low calcium and high phosphate
| -vitamin D deficiency: low calcium and low phosphate
72
What are possible diagnoses if you see calcium low, phosphate low, magnesium low? (2)
1. Malabsorption
| 2. Renal losses
73
What is the role of PTH in hypocalcemia?
****remember that the KEY in hypocalcemia is getting a PO4 level to see if it is related to hypoparathyroidism or not
Calcium is tightly controlled by PTH (released by parathyroid glands)
-calcium sensing receptors in parathyroid gland. If Ca low, PTH release occurs
-PTH has direct and indirect effects to try to increase serum calcium
-bone resorption and causes release of calcium
-in kidneys, PTH causes calcium reabsorption and increases calcitriol production (1,25-OH2D = activated form of vitamin D)
-1,25-OH-2D = acts on gut to increase calcium absorption
***need a normal magnesium level for PTH to function normally (ie. hypomagnesemia can lead to hypoparathryroidism)
74
Vitamin D synthesis in body: what is the pathway?
Vitamin D3 is from the skin
Liver --> 25 OH D
Kidney --> 1,25 OH2 D (active form!)
75
A patient with hypocalcemia also has alopecia. What is the most likely diagnosis?
-what is the inheritance pattern of this condition?
Vitamin D resistant rickets = 50% can be associated with alopecia
- this is caused by inability to reabsorb phosphate so will get LOW PO4 and normal or low calcium
- inheritance pattern: X-linked dominant
76
What tests should be included in a critical sample for hypocalcemia? (10)
* ***Most important:
1. PO4****
2. PTH****
3. Calcium****
4. 25-OH-D
5. 1,25-OH2-D
6. ALP
7. Mg****
8. Consider liver function/enzymes
9. Consider renal function
10. Urine calcium:Cr ratio****
****2 lavendar + 2 green tubes
77
What is the treatment of hypocalcemia secondary to hypoparathyroidism?
-what if the hypocalcemia is secondary to GI/renal losses?
How you treat will depend where the problem is! If hypomagnesmia, need to replace Mg
1. Calcium
2. Calcitriol (aka 1,25-OH2-D) since without PTH, you will not be able to convert 25 OH vitamin D to 1,25 OH2 D and thus not have adequate GI absorption of calcium
If hypocalcemia is secondary to GI/renal losses:
1. Vitamin D2 (vitamin D drops, ergocalciferol)) and then this can be converted to subsequent types of vitamin D active forms
2. Calcium
78
What are the steps of glucose production in a fasting state based on timing after last meal?
1. Glycogenoloysis happens in first 4-8 hrs
- if you can't do this, glycogen storage disorders
2. Gluconeogenesis from amino acids in 8-12 hours
3. Fatty acid oxidation at 12-18 hours in infants or 18-24 hours in children
79
If hypoglycemia occurs secondary to hyperinsulinism, when is the timing of hypoglycemia?
-hyperinsulin states = hypoglycemia happens immediately after feed because bolus of glucose causes bolus of insulin release
80
Important clues to diagnosis cause of hypoglycemia?
1. Ketones?
2. Timing?
3. Hypoglycemia meds in the family (ie. ingestion)?
4. Acute illness?
5. Prolonged fasting?
6. Salt craving? = primary adrenal insufficiency (deficiency of mineralcorticoid)
7. Headaches/visual changes = secondary adrenal insufficiency due to brain tumor
8. Growth?
9. Acidotic?
81
What are the free fatty acid/glucose/ketone levels in:
- MCAD
- hyperinsulinism
MCAD = high free fatty acid and normal glucose requirements, ketones are low
Hyperinsulinism: glucose requirements are high and free fatty acids are low, ketones are low
82
How do you calculate glucose infusion rate?
(%glucose in solution)(TFI)/144
83
How do you calculate corrected Na?
Take blood sugar, substract 5.6 (this is a normal blood sugar) and divide by 3.5 = then add this to measured sodium!
-ex. BG 25? (25 - 5.6)/3.5 = add this to the measured Na level
84
What are risk factors for cerebral edema in patients with DKA?
-how to avoid cerebral edema in DKA treatment?
1. New onset presentation
2. Hypernatremia (severe dehydration): Na > 145
3. Age < 5 yo
4. High urea
5. Headache
6. Severe acidosis pH < 7.1
7. Failure of measured serum sodium to rise
* **This is why we avoid rapid changes in osmolality
- lower fluid rate and lower insulin infusion rate if concerned re: cerebral edema
* **Aim to decrease serum osmolality by 2-3 mmol/h MAX, bolus only if hypotensive (10 cc/kg), use NS + 40 mEq/L, add glucose to IV fluids once BG < 15
- once acidosis is corrected (HCO3 > 18), titrate insulin to maintain BG 6-10
- start SC insulin once acidosis corrected at breakfast or supper (to avoid hyperchloremic metabolic acidosis)
85
What are the major and minor criteria for cerebral edema?
| -management?
Major criteria:
- altered mentation/fluctuating LOC
- sustained heart rate deceleration
- age appropriate incontinence
```
Minor criteria:
Vomiting
headache
lethargy/not easily aroused
diastolic pressure > 90
Age
```
86
What are the diagnostic criteria for hyperglycemic hyperosmolar syndrome?
1. Severe hyperglycemia (BG > 33)
2. Serum osmolality > 330 mmol/L
3. Absence of significant ketosis: HCO3 > 15, urine ketones negative or trace
87
What is the management of hyperglycemic hyperosmolar syndrome?
1. Bolus NS 20 ml/kg
- assume 12-15% fluid deficit
- calculate this and correct deficit over 24-48 hrs!
- don't be afraid to bolus!!!
- begin insulin when glucose concentration no longer declining with fluid alone
- 0.025-0.05 U/kg/h
- aim to decrease BG by 3-4 mmol/L/h
- tend to have higher fluid requirements than DKA
- consider lower dose and later initiation of insulin infusion
88
When would you start insulin in a T2DM patient?
If HgA1C > 9%, will need subq insulin!
- this is because in severe hyperglycemia, even if pancreas is ABLE to make insulin such as in T2DM, the beta islet cells are shocked by the hyperglycemia and will stop producing insulin
- give them insulin until the BGs are coming down, then may be able to wean off insulin
89
A child with T1Dm comes in with V/D and other people in her family have gastro. Her blood glucose is 18. Urine 3+ ketones, pH 7.35. What do you do?
-what advice do you give parents on discharge?
She needs insulin! Need 20% of total daily dose of insulin! Give this in NR!
-ie. total daily insulin dose = 30 units. So give 6 units NR right away.
Advice for parents:
1. BG checks q2-4h
2. urine/blood ketones q2-4h, if BG > 14 at any time
3. Never ever ever omit insulin even if the child is refusing to eat.
90
What are the insulin dose adjustments during illness?
This is for EACH PRE MEAL:
BG < 5 +/- ketones: reduce N and NR/H by 20%
BG 5-14 +/- ketones: usual dose of insulin
BG > 14, negative or trace ketones: give 10% of TDD as NR
BG > 14, moderate ketones: give 15% of TDD as NR
BG > 14, large ketones: give 20% of TDD
91
What type of insulin is in an insulin pump?
Novorapid only!
| -gives continuous basal insulin and then the child boluses the NR pre meals
92
What is your management for T1DM patient who is fasting for surgery and they're in hospital?
Normally: 50% of insulin as basal and 50% of insulin is for when you eat (boluses)
Safest thing to do:
1. IV fluids with dextrose D5W
2. Insulin infusion 0.02 U/kg/hr and titrate insulin to maintain BG 6-12
3. BG monitoring 1h after starting infusion and after any change in infusion rate, then
93
Definition of hypoglycemia?
- definition of severe hypoglycemia?
- what BG must a person be at before they should drive?
BG < 3.5 mmol/L with or without symptoms
- severe hypoglycemia = hypoglycemic event that required assistance to treat (ie. they couldn't treat themselves) = loss of consciousness, seizure, confusional episode
- BG for person to drive safely: ABOVE 5! "You need to be above 5 to drive!"
94
Treatment for hypoglycemia?
>20 kg: 15 g carbs
< 20 kg: 10 g carbs
Or D10W 5 cc/kg boluse, then continue IV fluids with dextrose
Glucagon: 5 yo: 1 mg IM
-note: can cause nausea and vomiting
95
8 yo girl with T1Dm vomiting all night, refusing breakfast, blood glucose in ER 4.3. Urine small ketones. What is your management?
Hold rapid since she's not eating. Decrease her NPH for as long as she is not eating.
96
What is a red flag for delayed bone age compared to chronological age to make you say "hmm...this definitely can not be just constitutional growth delay, there must be a pathological cause!"?
Once bone age is > 2 yrs behind chronological age, this is most likely due to a pathological cause and is NOT constitutional growth delay
97
What is the differential diagnosis for decreased IGF-1 levels? (4)
1. Growth hormone deficiency
2. Hypothyroidism
3. Malnutrition
4. Liver disease
98
When is it acceptable for a child to cross percentile lines on the growth curve? (2)
-thus, when is it NOT acceptable and thus investigations should be pursued?
1. During first 2-3 yrs of life since birth weight means nothing in terms of predicting postnatal growth
2. During puberty since there is variation between children in timing of puberty
****Thus, in between 3 yo and puberty, children should definitely be following their growth curve and not crossing percentile lines!
99
A 2 yo presents with breast development x 6 months. There is no increased growth velocity. There is no pubic hair, axillary hair or acne. What is the best investigation most likely to confirm the suspected diagnosis?
BONE AGE!!!!
-if bone age = chronological age, then this is premature thelarche since there are no other signs of puberty and no increased growth velocity!
100
When would you consider ordering head imaging for a girl presenting with true precocious puberty?
MOST cases of precocious puberty in girls is idiopathic...however, if there are neurologic s/s OR if she is < 5 yo, then need to get head imaging to r/o CNS tumor (hypothalamic hamartoma, glioma, etc.)
101
A patient presents with precocious puberty. What is a clue on history that will tell you whether the precocious puberty is from a CENTRAL vs. PERIPHERAL cause?
If the precocious puberty follows the normal, expected sequence of puberty, then most likely it is CENTRAL!
If the precocious puberty does NOT follow the normal, expected sequence of puberty, the most likely it is PERIPHERAL!
- ie. in girls: if adrenarche occurs prior to thelarche
- ie. in boysL if adrenarche/pubarche occurs but they have tiny testes still (remember that testicular enlargement is the FIRST STAGE in normal puberty!)
102
A 16 yo girl presents with primary amenorrhea. On exam, she has SMR 5 breast development and SMR 1 pubic hair with no axillary hair. What is the best investigation most likely to reveal the diagnosis?
Testosterone level = most likely androgen insensitivity syndrome
- think this if you see breast development with NO periods and NO adrenarche!
- Has breasts because with the XY karyotype, she is making testosterone but the tissues' receptors aren't responding...thus the testosterone that is kicking around gets aromatized by adipose tissue into estrogen which stimulates the breast development
103
What are the recommended glycemic targets for pediatric patients with T1DM? What about HgbA1C targets?
- 0-5 yo
- 6-12 yo
- >12 yo
0-5 yo: 6-10, HgbA1C < 8.0%
6-12 yo: 4-10, HgbA1C < 7.5%
>12 yo: 4-7, HgbA1C < 7.0%
104
You have diagnosed a child with diabetes insipidus and would like to figure out if it's central vs. nephrogenic (ie. is the posterior pituitary gland not making any ADH or is the kidney unable to respond to ADH?). What is your next best test?
Trial dose of DDAVP (desmopressin), then measure lytes, serum osmolality, urine lytes and urine osmolality.
- if there is a response to the DDAVP and the kidneys are able to concentrate the urine, then this means the post pit is not making ADH! Next step would then be MRI head to r/o tumor
- if there is NO response to the DDAVP, then you've made the diagnosis of nephrogenic DI
105
What are possible causes of central diabetes insipidus? (5)
1. Post head trauma (ie. basal skull fracture)
2. Post neurosurgery
3. Post radiation
4. CNS tumor of the pituitary gland (germinoma)
5. Septooptic dysplasia
106
A child presents with polyuria and polydipsia. Their blood glucose and serum lytes are normal. What is your next step?
Order serum and urine lytes and osmolality to see if the urine is dilute! This MAY be diabetes insipidus! Remember that a normal electrolyte profile does NOT rule out DI if the patient's thirst mechanism is intact and they have access to free water!
107
What are causes of congenital hypothyroidism? (6)
Permanent:
1. thyroid dysgenesis (80%)
2. dyshormonogenesis (10%) = cannot make thyroid hormone
3. Hypothalamic/pituitary dysfunction (5%) = no TSH
Transient (5%):
4. Intrauterine antithyroid meds
5. Maternal antibodies against baby's thyroid
6. Iodine deficiency
108
What is the classic triad of pheochromocytoma?
1. Headache - ? from htn
2. Palpitations/tachycardia
3. Diaphoresis
* ***will have sustained hypertension so if you see palpitations/diaphoresis but you don't see hypertension, it's most likely not a pheo
* **spot urinary catecholamines are highly sensitive but NOT specific! Ie. lots of false positives
- best test: 24 hr urinary catecholamines
109
What is the differential diagnosis for hyperthyroidism? (4)
| -treatment options?
1. Graves disease = most common = thyroid gland stimulated by anti thyroid receptor antibodies
2. Subacute thyroiditis
3. Suppurative thyroiditis
4. Toxic uninodular goitre
Treatment options:
1. Surgery
2. Radioactive iodine
3. Methimazole: inhibits the enzyme thyroperoxidase which is needed to make thyroid hormone
110
You see a patient for a goiter. What is the most likely cause?
- what are possible cilnical features?
- what is your first diagnostic investigation and why?
Goiter = think Hashimoto thyroiditis = lymphocytic infiltation of thyroid gland
Possible clinical features:
- could be euthyroid = asymptomatic enlargement
- could have mild hypothyroidism
- overt hypothyroidism with enlarged or atrophic gland
First investigation: thyroid U/S! Need to rule out malignant nodules (thyroid cancer)
-if U/S shows solid mass, this is concerning for malignancy = would then proceed to FNA
111
A patient with Addison's disease comes to you in adrenal crisis. What is your definitive management after stabilizing ABCs?
Hydrocortisone 100 mg/m2 for stress dosing = has both mineralcorticoid and glucocorticoid effects!
- adolescent = give HC 100 mg total x 1
- infant = give 25 mg total x 1
112
You suspect a patient has Cushing syndrome. What is the BEST test to establish whether excess cortisol is present?
- what is the most likely cause of Cushing syndrome in a child 5 yo?
- You have made the diagnosis of Cushing syndrome. What are your next steps in investigation?
24 hour urinary free cortisol!
- 8 am cortisol is NOT helpful in Cushing syndrome! 8 am cortisol is helpful to see if a person has cortisol deficiency
- most likely cause of Cushing syndrome in child 5 yo: more likely to have pituitary adenoma (secretes ACTH)
Once you have confirmed Cushing syndrome: need to know, is this Cushing Disease (ie. ACTH-producing pituitary adenoma) or another cause?
- first order ACTH level! If ACTH level is low, then probably adrenals are secreting excess cortisol (tumors)
- if ACTH level is HIGH, then you need to figure out where the ACTH is coming from (ie. centrally from ACTH-producing pituitary adenoma or peripherally from ectopic ACTH-producing adrenal/lung/abdo tumor)
- thus, do a HIGH DOSE DEX SUPPRESSION TEST! = if you see no change in high cortisol, this is most likely ectopic ACTH-producing tumor. If you see a decrease in cortisol, this is most likely Cushing Disease
113
During what age group is the following most likely to present:
- complete androgen insensitivity
- partial androgen insensitivity
- complete androgen insensitivity: presents in adolescence since the patient is phenotypically female so no one will suspect the diagnosis until she presents with primary amenorrhea
- partial androgen insensitivity: presents at birth since the patient will have some virilization of external genitalia but not enough
114
A patient presents with a large, tender thyroid gland and is febrile. What is the most likely diagnosis?
Acute suppurative thyroiditis = rare cause of enlarged thyroid, most commonly caused by GAS, staph aureus or strep pneumo
-FNA would reveal purulent material
115
What is the most common type of thyroid malignancy in childhood?
Papillary adenocarcinoma
116
Why do you see hypocalcemia in patients with DiGeorge syndrome?
Hypoplasia or agenesis of parathyroid glands = thus no PTH to regulate serum calcium levels
117
What is pseudohypoparathyroidism and what will you see on lab findings?
-clinical features?
Bone and kidneys are resistant to PTH = see decreased Ca, increased PO4, INCREASED PTH because parathyroid glands are working hard to try to stimulate the bones and kidneys
- clinical features:
1. short stature
2. Mental disability
3. Brachydactyly (4th and 5th fingers)
4. increased bone density throughout body (especially in the skull)
5. Obesity with round facies and short neck
6. Subcapsular cataracts
7. Cutaneous and subcutaneous calcifications
8. Perivascular calcifications of the basal ganglia
118
You see a patient with hypocalcemia. Their PO4 levels are low and their PTH is high. What is the most likely diagnosis?
Vitamin D deficiency = can be from decreased dietary intake, decreased sunlight, malabsorption (CF, pancreatitis, celiac disease), liver or renal failure
119
What is an ACTH stim test used to diagnose?
| -how is it done?
Adrenal insufficiency = used to determine whether glucocorticoid insufficiency is due to primary or secondary cause
- steps:
1. measure cortisol level
2. give ACTH
3. re-measure cortisol level to see if it has risen! If it has, then this means that the adrenal gland is working fine and there is a central cause of adrenal insufficiency (hypothalamic or pituitary gland dysfunction). If there is no change, then it is a primary adrenal gland problem (most likely autoimmune)
120
What is Cushing Disease?
Excess glucocorticoid specifically from an ACTH-producing pituitary adenoma!
121
What is the most likely cause of a false positive on a congenital hypothyroidism newborn screen?
-false negatives?
False positive: newborn screen done within 24 hrs of birth = there is a normal TSH surge occurring after birth
False negatives: prematurity, maternal antithyroid drugs, maternal iodine deficiency
122
What are the criteria for screening for type 2 diabetes?
- when do you start screening?
- what is the screening test used?
All children who are overweight (BMI > 85th percentile) with at least 2/4 risk factors:
1. Family history of type 2 DM in 1st or 2nd degree relatives
2. First nations, African americans, hispanic, asian/pacific islander
3. Signs of insulin resistance or conditions assocaited with insulin resistance: acanthosis nigricans, hypertension, dyslipidemia, PCOS
4. Hx of gestational diabetes in mom
- start screening at 10 yrs or at onset of puberty if puberty occurs at younger age
- screening test: fasting plasma glucose q2y
123
WHat are the type of adrenal androgens?
```
DHEAS = weak androgen
Androstenedione = weak androgen
Testosterone = strong androgen
DHT = strong androgen
```
* **In adult males: adrenals produce 5% of androgens
* **In adult females: adrenals produce 50% of androgens
124
How can you tell the difference between primary vs. secondary adrenal insufficiency?
Primary adrenal insufficiency = will see mineralcorticoid deficiency! Also will see hyperpigmentation
-salt craving*****
Secondary adrenal insufficiency = will not see mineralcorticoid deficiency
125
Causes of primary adrenal insufficiency?
- how might an infant present with primary adrenal insufficiency compared to a child?
- labwork to draw?
Congenital
1. CAH
2. adrenoleukodystrophy (only treatment is bone marrow transplant)
3. ACTH resistance
Acquired:
1. Autoimmune adrenalitis = addison's
2. Hemorrhage/infection
Infants: greater requirement for aldosterone so without it, will become hyponatremic/hyperkalemic much faster! Also become ill super fast with hypoglycemia because they have less ketosis, also have less hyperpigmentation because get really sick before they have time to become hyperpigmented
Labwork: glucose, lytes, gas, cortisol, acth, aldosterone, renin BEFORE steroids given!
126
What is the management of acute adrenal crisis?
| -chronic?
BSA = square root of ht (cm) x wt (kg) / 3600
Acute:
1. Hydrocortisone: 100 mg/m2, then 25 mg/m2 q6h (can try 2 mg/kg if you don't know the dose)
2. Restore volume with boluses
3. Critical sample before steroids
4. Support: BP, BW, Endo, PICU
5. +/- vasopressors, more glucose
6. +/- EKG, calcium, HCO3, Kayexalate, glucose + insulin
Chronic:
1. Hydrocortisone 8-10 mg/m2/day div TID
2. Fludrocortisone 0.05 to 0.3 mg daily (if aldo def)
3. Education on Stress dosing
127
Stress dosing for adrenal insufficiency?
| -mild, moderate, emergent?
Emergent: hydrocortisone 100 mg/m2 IV then 25 mg/m2 IV q6h
Moderate (vomiting, fever > 38.5): hydrocortisone 30 mg/m2 PO/IV q8h (ie. triple normal home dose)
Mild illness (fever > 37.5): hydrocortisone 20 mg/m2 PO divided TID (ie. double normal home dose)
* **normal physiologic dose = 10 mg/m2/day
- children are usually on hydrocortisone at home if they have adrenal insufficiency
128
What are clinical features of transient pseudohypoaldosteronism?
-causes? (3)
Resistance to aldosterone but see high aldosterone and renin, normal cortisol. Will resolve as soon as the underlying condition is treated
- causes:
1. Obstructive uropathy
2. UTI
3. SCD
129
What investigations should be ordered for a baby with suspected CAH?
1. Lytes
2. Glucose
3. Gas
4. 17 OH P
5. DHEAS, androstenedione
6. Reinin
7. Aldosterone
8. Cortisol
130
What is the management for central DI?
1. Replace insensible losses: 400 ml/m2/day, replace with D5NW + 40 mEq/L KCl
2. Replace u/o 1:1 q2hrly = if urine Na > 150, can use D5NS, if urine Na 50-150, then use D50.45NS, urine Na < 50, then start D5W
- or start D5NS until your urine lytes become available
3. Replace fluid losses prn
4. Notify Endo
5. Consider DDAVP after Endo is notified
6. Monitor closely: risk is cerebral edema with too rapid calculation of hypernatremia
***be careful with giving boluses = only do it if they are hypotensive because
131
How do you replace fluid volume for hypernatremia?
TBW x (serum Na - 140)/140 ****don't want to decrease serum Na by more than 10 mmol/day...so if their initial Na is 170, then you wanna use 160 as your ideal instead of 140
- TBW = 0.6 x wt (kg)
- then give this volume over the next 24-48 hrs
- use dextrose D5W fluid = this is free water
***Then you add urine output replacement 1:1 q2hrly AND add insensible losses = 400 ml/m2/day but you have to use D5WNS + 40 KCl so need to get a second line. Do NOT use 4:2:1 rule!!! Because this takes into account his urine output which we are already doing!!!!
132
Treatment of SIADH?
| -how to correct hyponatremia?
1. Water restriction - only give insensibles (400 ml/m2) + 50-100% u/o (especially if you don't know what the cause of their SIADH is)
2. 3% NaCL 5 ml/kg only if symptomatic = max Na = 0.5 mEq/L/hr to prevent central pontine myelinolysis
3. Chronic treatment: 1000 ml/m2/day water
133
Clinical features of cerebral salt wasting?
| -treatment?
Loss of extra-cellular fluid = low serum sodium but HIGH urine output, may be secondary to atrionaturetic peptide causing increased urine output (osmotic diuresis)
-causes: brain tumors, post neurosurgery, traumatic brain injury
Treatment:
1. Insensibles NS + 40 KCl
2. Replace U/O 1:1 with NS
3. Replace losses
4. Avoid rapid increase in Na
134
What are the expected calcium levels and phosphate levels seen in vitamin D deficient rickets?
Ca can be normal or low
PO4 will be low!!!
-This is because without vitamin D, you get hypocalcemia and thus PTH secretion. PTH causes mobilization of calcium and phosphorus from bone and then subsequently resorption of calcium by kidneys and excretion of phosphate
135
A short 4 year old girl with cognitive impairment presents with brachydactyly of the 4th and 5th digits, obesity with round facies, short neck, subcapsular cataracts, cutaneous and subcutaneous calcifications, and perivascular calcifications of the basal ganglia. What is your diagnosis?
Pseudohypoparathyroidism!
- Will see low Ca, high PO4 but HIGH PTH!!!!!
- unresponsiveness of the renal tubules to parathyroid hormone
136
What is secreted by medullary carcinoma of the thyroid?
Calcitonin!
| -but usually see normal calcium and phosphorus levels
