Endocrinology Flashcards
1
Q
What hormones are in the anterior pituitary and which are in the posterior pituitary?
A
anterior: growth hormone, prolactin, TSH, FSH, LH, ACTH
posterior: ADH, oxytocin
2
Q
What defects can occur with congenital hypopituitarism
A
usually growth hormone deficiency and one or more of the other 5 hormones made in the anterior pituitary
3
Q
What is septo optic dysplasia
A
abnormality of the optic nerve or chiasm (absence or hypoplasia) children are often blind or have very little vision
agenesis of the septum pellucidum and/or corpus callosum
hypothalamic insufficiency affecting both the anterior and posterior pituitary
4
Q
What is associated with midface anomalies particularly a solitary maxillary central incisor
A
growth hormone deficiency
5
Q
What is the most common tumor in children that affects the pituitary
A
crainiopharyngioma
6
Q
What are the effects of an ectopic posterior pituitary gland
A
failure of the posterior pituitary to migrate toward the anterior pituitary and form the infundibulum causes problems with the portal vessels and communication between the hypothalamus and the anterior pituitary:
thus leads to anterior pituitary problems: growth hormone deficiency to panhypopituitariam
7
Q
What is an indicator of the degree of problems in those with an ectopic posterior pituitary gland?
A
presence of pituitary stalk
if present: isolated growth hormone deficiency
if abnormal: multiple hormone deficiencies
8
Q
What are some clinical manifestations of growth hormone deficiency
A
normal size at birth
fall off of growth curve by more than 4 SD by 1 year of age
microphallus in males
hypoglycemia and direct hyperbilirubinemia in neonate
characteristic facies over time: round head, short broad face with prominent frontal bone and depressed saddle shaped nose
high pitched voice
small gonads, sparse secondary hair
normal intelligence
9
Q
How is growth hormone deficiency diagnosed
A
suspect when there is post natal growth failure (more than 3 SD below the curve by age 3)
Serum IGF-1 and IGH BP-3: if in the upper range of normal GH deficiency is ruled out
definitive diagnosis with lack of response to stimulation of GH production (exercise, insulin, glucagon, L-dopa, arginine, clonidine)
10
Q
What is idiopathic short stature?
A
more than 2.25 SD below the mean
with normal GH levels
unlikely to reach a normal adult height
can now be treated with GH
11
Q
What is Laron syndrome
A
short stature with normal GH levels
problem is at the receptor
low levels of IGF-1
treated with IGF-1
12
Q
What is seen in constitutional growth delay
A
variant of normal growth, with slower growth rate, but after age 3 normal growth velocity
bone age is delayed
family history of growth delay is common
often have delayed puberty
will reach normal adult height with no intervention
13
Q
What is seen in familial short stature
A
normal growth velocity
normal bone age
family history of short stature
14
Q
What is seen in hormone deficiency
A
decrease in growth velocity
delayed bone age
sometimes family history
15
Q
How is mid parental height calculated?
A
boys: {mom height + dad height + 13 cm }/2
girls {mom height + dad height-13 cm} /2
16
Q
What are some other causes of short stature
A
hypothyroidism
psychosocial dwarfism
Silver-Russell: short stature, SGA, frontal bossing, triangular facies, short and incurved 5th digits and asymmetry
17
Q
What are some of the side effects to growth hormone
A
SCFE, pseudotumor cerebri, transient carbohydrate intolerance, transient hypothyroidism, scoliosis
18
Q
What causes diabetes insipidus
A
ADH deficiency from the posterior pituitary
or kidney unresponsive to ADH
ADH works on kidney to conserve water and make urine hyperosmolar
19
Q
What causes increase in ADH
A
elevated osmolality, hypervolemia sodium is the strongest stimulus thirst begins with osmolality is > 295 nausea is a potent stimulus angiotensin II, insulin-induced hypoglycemia, acute hypoxia and acute hypercapnia
20
Q
What are some causes of central DI
A
primary inherited (rare): AD wolfram syndrome and septooptic dysplasia Acquired: tumors (craniopharyngioma, optic glioma, germinomas) head injury Systemic disease: sarcoidosis, encephalitis, histiocytosis, tuberculosis
21
Q
What causes nephrogenic DI
A
x linked inherited form lithium polycystic kidney disorder sickle cell anemia chronic pyelonephritis sarcoidosis, amyloidosis
22
Q
What are the clinic findings of diabetes insipidus
A
polyuria and polydipsia
infants: poor feeding, poor growth, irritability, high fevers
new onset enuresis in older children
23
Q
What is the diagnosis and treatment of diabetes insipidus
A
hyperosmolar serum dilute urine low or absent ADH suggests central DI give desmopressin DDAVP: if central DI: urine will become more concentrated and osmolality will decrease if nephrogenic: no change
Central DI: DDAVP
nephrogenic DI: low sodium with adequate protein and lots of water ) 300-400 ml/kg/day, can use thiazide, indomethacin
24
Q
What are the symptoms of SIADH
A
hyponatremia, low serum osmolality
high urine osmolality
fluid overload with low urine output
25
What are some causes of SIADH
pneumonia, tumors, TB, CF, meningitis, encephalitis, head trauma, post neurosurgery
26
What is the treatment for SIADH
fluid restrict
| treat underlying problem
27
What is seen with cerebral salt wasting and what is the treatment
hyponatremia
hypersecretion of atrial natriuretic peptide
increased urine output, hypovolemia
high urinary sodium excretion
low ADH
treatment: replace urine output with IV solution normal saline to 3% depending, may need oral salt replacement
28
What happens if there is growth hormone excess and how is that tested for?
gigantism if epiphyses are open and acromegaly if the epiphyses are closed
rapid growth, coarse facies, big hands and feet with hypogonadism
high growth hormone levels that do not suppress with glucose administration
29
what is sotos syndrome or cerebral gigantism
rapid growth early in childhood with no evidence of endocrine disorder
infants are > 90th percentile and grow to be > 97th percentile by 1 year of age
accelerated growth persists till age 4 or 5
puberty is at the normal time with normal adult height
big hands and feet and clumsy
poor coordination
some degree of intellectual disability
long narrow face with high forehead and small pointed chin
30
What are the symptoms of a prolactinoma and how is it diagnosed
amenorrhea, headache, galactorrhea
visual field defects
diagnose with MRI
usually due to an adenoma that can be resected or managed with bromocriptine
31
Describe beckwith-wiedemann syndrome and what screening is needed for these patients
overgrowth syndrome
hypertrophy of organs, macroglossia, hepatosplenomegaly, nephromegaly and beta cell hyperplasia resulting in hypoglycemia
at risk for wilms tumor, adrenocortical carcinoma and hepatoblastoma
need abdominal US q 3 months until 8 years old
need AFP q 6 weeks until 6 years old
32
What hormone starts puberty
LH begins being secreted at night 1-3 years prior to the onset of puberty
33
What hormone closes the epiphyses
estrogen
34
What is the first sign of puberty in a girl
| in a boy
breast bud development
| testes enlargement and scrotal thinning
35
How long is it from the beginning of breast buds to menarche for most girls?
2-2.5 years though it can be as long as 6 years
36
When does peak height velocity occur for girls, and for boys
breast stage 2-3, usually between 11-12 years old
| tanner stage IV-V, usually between 13-14 years old
37
At what breast stage does menarche usually occur?
breast stage 4, if it occurs earlier, must work up a cause
38
What is the definition of late puberty for girls and for boys
delayed male puberty: no secondary sexual characteristics by 14 or if > 5 years from beginning to completion
delayed female puberty: no secondary sexual characteristics by 13 or if > 5 years have passed between the beginning and completion of puberty
39
What are signs of true precocious puberty in girls, in boys?
Girls: breast development and pubic hair (tumor 10% of the time)
Boys: testes > 3 ml and pubic hair (source is testes) brain tumor 50% of the time
40
What is the most common brain lesion that causes true precocious puberty and what is the management
hypothalamic hamartoma
ectopic neural tissue that functions as an accessory GnRH pulsatile generator
usually surgery is not done and instead treated with medication
41
What are some causes of central precocious puberty
idiopathic (girls)
congenital defects septo-optic dysplasia
brain tumor (craniopharyngioma, dysgerminoma, ependymoma, ganglioneuroma, optic glioma)
Other lesions (arachnoid cyst, suprasellar cyst)
Infection or inflammation: brain abscesses, encephalitis, granuloma, meningitis
Injury: head trauma, irradiation
hereditary conditions: neurofibromatosis, tuberous sclerosis
42
How is central precocious puberty treated
GnRH agonists:
leuprolide injection
constant infusion decreases pituitary response to GnRH and leads to decreased gonadotropin secretion
43
What are the symptoms of McCune Albright syndrome
café au lait spots
fibrous dysplasia of the skeleton
hyperfunctioning endocrine organs, often presents as peripheral precocious puberty
more common in girls with ovarian cyst and vaginal bleeding
44
What tumors can cause peripheral precocious puberty
HCG, human chorionic gonadotropin secreting tumors
see penile enlargement and pubic hair without testicular enlargement
could be in the gonad, adrenal gland or the brain
45
What is premature thelarche and how should it be monitored
isolated breast development and is a diagnosis of exclusion
occurs first 2 years of life
no adrenal gland involvement
rule out excessive exposure to estrogen from cosmetics or soy products
order estradiol, LH and FSH and a bone age (these should all be normal for age)
monitor that it is not the first sign of precocious puberty
46
What is premature adrenarche
variant of normal but diagnosis of exclusion
signs of isolated pubic hair, body odor, acne before 8 years of age in girls and 9 in boys with no other involvement of gonads, breast development
47
What tests should be done if there is premature adrenarche?
must rule out exogenous exposure and adrenal tumors and late onset CAH
DHEAS, testosterone, androstenedione, 17-hydroxy-porgesterone and bone age
These should be normal, with only DHEAs being mildly elevated.
If abnormal need to rule out late onset CAH
48
What increased thyroid binding globulin and thus increases total T4?
pregnancy, OCPs,
tamoxifen, clofibrate, narcotics,
hepatitis, biliary cirrhosis
49
What decreases thyroid binding globulin and thus decreases total T4?
androgens
glucocorticoids
nephrotic syndrome
inherited TBG deficiency
50
What is radioiodine uptake used for? What diseases are associated with elevated vs decreased findings?
differentiating non-pituitary thyrotoxic states
get a number that tells the percentage of the dose taken up into the thyroid
increased:
graves, hot nodule (multinodular goiter, toxic solitary nodule, hCG-secreting tumor)
decreased:
self limited thyroiditis
thyroiditis factitia
amiodarone
51
What is a thyroid scan used for?
give a dose of technetium 99 and scan to get a picture
| for nodular disease, if a nodule is hot or cold
52
What are causes of congenital hypothyroidism
thyroid dysgenesis or defective thyroid embryogenesis
maternal antibodies if mom has graves disease
transient congenital hypothyroidism due to iodine deficiency in mom
53
What are the symptoms of congenital hypothyroidism
```
asymptomatic at birth
then develop feeding problems, constipation, sluggishness, lack of interest, choking spells and somnolence, large tongue, hypothermia
umbilical hernia
genital and extremity edema
bradycardia, cardiomegaly
anemia
wide open posterior fontanelle
slow bone maturation absent distal femoral epiphysis
```
54
How is low TBG tested for and what is the management
infant will have low total T4 and normal TSH and free T4
obtain TBG level
do not treat infant
55
what is often seen in infants with central hypothyroidism
TSH is low, due to a deficiency in TRH
often infant presents with signs of other pituitary defects with hypoglycemia, hyperbilirubinemia and micropenis with midface anomalies
56
How is hypothyroidism treated
levothyroxine 10-15 micrograms/kg/day in a crushed tab
do not give with soy or iron
start with in the first two weeks to prevent developmental delay
57
What are symptoms seen with hypothyroidism in older children?
```
greater weight for age than height
delayed bone age
slow tendon reflexes
constipation
somnolence, behavior changes
growth failure
SCFE
```
58
Who should be screened frequently for hypothyroidism
those with type 1 diabetes, down syndrome, turner, kleinfelter
59
What antibodies are positive with hashimoto's thyroiditis. What is the treatment?
antithyroglobulin
anti-thyroperoxidase
can be present in normal individuals but are indicative especially if there is a family history
60
What should be done for the patient who is euthyroid but has antibodies
check thyroid levels every 6 months and treat if they become hypothyroid
61
What is subacute of de Quervain Thyroiditis and how does it present
self limited inflammation of the thyroid often after an upper respiratory infection
fever, thyroid tenderness, and pain
initially symptoms of hyperthyroidism followed by hypothyroidism
lasts 2-9 months
controlled with analgesics or if severe prednisone
62
What is suppurative thyroiditis and how is it treated
bacterial infection of the thyroid usually the left lobe
if it occurs there is usually an embryologic remnant
fever, thyroid enlargement, pain and local tenderness
thyroid function is normal
treat with appropriate antibiotics (can do fine needle aspiration for culture)
usually staph, strep pyogenes or pneumoniae
63
What is graves disease and how does it present
most common cause of hyperthyroidism in children
diffuse thyroid hyperplasia due to thyroid-stimulating immunoglobulin
muscle weakness, anxiety, palpitations, increase appetite, weight loss or weight gain
behavior problems
hypertension, tachycardia, cardiomegaly
tremor, excessive perspiration, widened pulse pressure
thyroid bruit
64
How is graves disease treated
B blockers for controlling manifestations
three ways to stop increased production:
Radioactive iodine ablation: still a chance of relapse, use to have concerns for leukemia and thyroid cancer after treatment, but these concerns have not panned out
Surgical removal: risk of hypoparathyroidism, damage to recurrent laryngeal nerve
Medical management: methimazole (PTU can be used but less recommended in children due to hepatotoxicity)
65
What are the side effects of PTU and methimazole
skin rashes
| agranulocytosis (sore throat, mouth ulcers)
66
What is neonatal thyrotoxicosis
mom's thyroid antibodies cross the placenta and affect baby
| Mom may be treated for hypo or hypothyroidism but, antibodies are still present
67
How does neonatal thyrotoxicosis present
irritability, flushing, tachycardia, hypertension, thyroid enlargement and exophthalmos some with arrhythmias and high output cardiac failure (most common cause of death)
treat with sedatives, digitalis
lugol solution (iodine and potassium iodine) response in 24-36 hours
can use propranolol
68
How can thyroid cancer present
solitary thyroid mass with a consistency different than the rest of the thyroid
solitary nodule prior to 20 years of age is likely to be malignant 26%
may have cervical adenopathy and hypocalcemia with hyperphosphatemia
69
What are risk factors for thyroid cancer
```
history of radiation to the neck or head
a solitary nodule > 1 cm with fixed, hard or irregular borders
solitary nodule with calcifications
family history of MEN
rapidly growing nodule that is firm or hard
satellite lymph nodes
hoarseness or dysphagia
evidence of distant metastasis
```
70
What are the guidelines to evaluate a thyroid nodule
1. check TSH
if TSH is low likely hot nodule and should do thyroid uptake scan
if TSH is high or normal do ultrasound to confirm if there is a nodule
2. If nodule is present, do FNA
3. If FNA is indeterminate, shows malignancy or is suspicious for malignancy do surgery
if FNA is benign, follow
if FNA is non diagnostic either follow or do surgery
if FNA is not available, surgery to determine if there is malignancy
71
what can be used to follow as a tumor marker after removal of thyroid cancer
thyroid binding globulin
72
What are the majority of childhood thyroid cancers and what is the one cancer type that can also secrete other hormones?
> 90% are well differentiated follicular carcinomas
medullary carcinoma makes calcitonin it can also make ACTH, melanocyte stimulating hormone, serotonin, prostaglandins, somatostatin
73
What does PTH do
PTH causes release of calcium from bones, increases renal resorption of calcium and wasting of phosphorus, it increases hydroxylation of vit D in the kidney
increased vitamin D results in increased calcium and phos absorption from the gut
74
What are causes of early onset, first 72 hours of life, hypocalcemia
prematurity
maternal factors: toxemia, diabetes, hyperparathyroidism
infant issues: sepsis, IUGR, hypomagnesemia, RDS
75
What congenital syndrome is associated with aplasia/hypoplasia of the parathyroid glands
DiGeorge syndrome
76
What autoimmune syndromes are associated with hypoparathyroidism?
autoimmune polyglandular syndrome type 1:
hypoparathyroidism, Addison disease and chronic mucocutaneous candidiasis, need 2/3
AR
remember autoimmune polyglandular syndrome type 2 is type 1 diabetes, thyroid disease and Addison's disease
77
How does hypoparathyroidism present and what labs are noted
signs of hypocalcemia:
seizure, tetany, numbness, tingling positive Chvostek or trousseau sign
muscle pain and cramps most common
hypocalcemia, hyperphosphatemia and low PTH, D 1-25 is low, alk phos is low to normal
ECG can show prolonged QT interval
78
What is seen in type 1 a psuedohypoparathyroidism
AD
PTH can't bind to receptor so....hypocalcemia, hyperphosphatemia and high PTH
patients present with tetany, found faces, short stocky builds and short fingers with short 4th and 5th metacarpal bone
knuckle, knuckle dimple dimple
79
What is seen in pseudo pseudohypoparathyroidism
so...same phenotype as pseudohypoparathyroidism but...labs are normal
80
What is ricketts
bony malformation due to abnormality of calcium and phosphorus
under mineralization of the growth plate
and only occurs in those with an open growth plate
81
What are the symptoms / signs of rickets
irritability, weakness, fractures and growth retardation
infant with frontal bossing, craniotabes, widened sutures, rachitic rosary (nodules on the ribs) and flared wrists
older child with flared wrists or ankles with genu valgum or genu varum
82
What is seen in hypophosphatemic rickets
extremely low serum phosphorus, high urinary phosphorus, elevated alk phos and normal PTH
Kidney wastes phosphorus
x linked
treatment: phosphorus replacement and calcitriol
83
What is found with MEN Type 1
```
AD
associated with hyperplasia or neoplasia of
pancreas
pituitary
parathyroid (hyperparathyroidism)
```
84
What is found with MEN Type 2a
pheochromocytoma
medullary thyroid carcinoma
hyperparathyroidism
85
What is found with MEN Type 2 b
pheochromocytoma
medullary thyroid carcinoma
mucosal neuromas
86
How does hyperparathyroidism present
as hypercalcemia
muscular weakness, nausea, emesis, abdominal pain constipation, fever
bed wetting with polyuria, bone pain, kidney stones
elevated PTH, elevated Calcium low phos
87
What is a symptom that should make you suspect adrenocortical insufficiency?
hyperpigmentation, due to increased ACTH, the pro-protein also makes melanocyte stimulating hormone
This does not happen if the issue is central and no or low ACTH is being made.
88
What are the symptoms of congenital adrenal hypoplasia
increased pigmentation, salt wasting and low levels of adrenal steroids, cryptorchidism is common
89
What is Addison's disease and how does it present
most common cause of acquired forms of adrenal insufficiency
autoimmune destruction by anti-adrenal antibodies
muscle weakness, anorexia, weight loss, wasting, low blood pressure, abdominal pain and salt craving
exam may comment on the child's TAN
90
What is seen in adrenoleukodystrophy
can not break down very long chain fatty acids
X linked
degenerative neurologic disease, progresses to dementia, loss of vision and hearing speech and gait
adrenocortical deficiency can precede or follow the neurologic changes
should test for long chain fatty acids in any boy with new onset adrenal insufficiency
91
What are some circumstances when there is adrenal hemorrhage that leads to adrenal insufficiency
neonatal: in difficult labor/delivery, with scrotal hematoma sometimes only picked up with calcifications on adrenals on imaging
waterhouse-friderichsen syndrome, adrenal hemorrhage with meningococcemia
92
What drugs can induce a state of corticosteroid deficiency
ketoconazole, rifampin, phenytoin and phenobarbital
93
What lab tests are indicative of adrenal insufficiency
if salt wasting: low serum sodium and chloride, increased potassium and renin
hypoglycemia
calcification on adrenals on imaging if due to hemorrhage
definitive testing is ACTH stim test, with cortisol level before and after ACTH
aldosterone-low in Addison's, salt wasting CAH and adrenal hypoplasia
94
What is the treatment for adrenal insufficiency
fluids with sugar, 5% NS
stress dose of hydrocortisone
maintained on fludrocortisone
95
What does a patient need who has ACTH deficiency or has familial glucocorticoid deficiency
just cortisol replacement since aldosterone is still made as it is not ACTH dependent
96
What does GFR stand for, in the adrenal gland and what is made in each area
Glomerulosa: Salt: Aldosterone
fasciculata: Sugar: cortisol
reticularis: sex: Androgens
97
What are the symptoms of an adrenocortical tumor
virilization: boys: accelerated growth, increased penile size, pubic hair and no testicular growth
Girls: masculinization with clitoral enlargement, increased growth, acne, deep voice, and pubic hair
some will also present with cushing syndrome
98
What are the tests and treatment for adrenocortical tumors?
urinary 17-ketosteroids, serum DHEA, serum DHEAS and serum androstenedione, testosterone are elevated
CT/ MRI to locate tumor which must be surgically removed
99
What is cushing syndrome and how does it present
either exogenous or endogenous excess of glucocorticoids
obesity, poor height velocity, buffalo hump, purple striae, hypertension, round face (moon facies), hirsutism, abnormal masculinization
100
What are some causes of Cushing syndrome
ACTH- independent (cushing syndrome): in infancy is usually an adrenocortical tumor, usually malignant
McCune Albright syndrome
Carney complex
ACTH dependent: bilateral adrenal hyperplasia usually due to a pituitary microadenoma
101
What is Carney complex
AD
blue nevi
cardiac myxomas
skin myxomas
thyroid and pituitary tumors
primary pigmented nodular adrenocortical disease: results in ACTH independent cushings
abnormal pigmentation with freckles around the lips, eyes and genitalia
102
How do you confirm cushing disease / syndrome
could order an afternoon cortisol and it would be high
best screen is a 24 hour urinary free cortisol, which will be elevated
dexamethasone suppression test: give dexamethasone at 11pm and test cortisol at 8 am. If cortisol is not < 5 microg/dl, cushing is confirmed
To determine if ACTH independent or dependent:
2 step dexamethasone test: give a low dose followed by a high dose of dexamethasone for two consecutive days. If it is ACTH dependent the larger dose but not the smaller dose will suppress urinary free cortisol levels
103
What do you do if MRI does not show an adenoma but, one is suspected?
bilateral inferior petrosal blood sampling to measure ACTH before and after giving CRH to localize the tumor
104
What are the symptoms and what lab values are seen in hyperaldosteronism
hypertension (can have headaches and dizziness, visual changes)
enuresis, polyuria, polydipsia,
from hypokalemia:growth failure, intermittent paralysis, fatigue, tetany
labs will show hypokalemia, low renin with elevated plasma and urine aldosterone
105
What are some causes of primary hyperaldosteronism
aldosterone secreting adenoma
| glucocorticoid suppressible aldosteronism, ACTH dependent AD form
106
How is hyperaldosteronism diagnosed and treated
hypertension, hypokalemia, low renin and high aldosterone .
Give dexamethasone to see if abnormalities are corrected, if they are it is glucocorticoid suppressible form
If not, do CT to look for adenoma or bilateral micronodular hyperplasia
if negative do adrenal vein catheterization looking for adenoma
treat with steroids if glucocorticoid responsive, remove adenoma, treat bilateral hyperplasia with spironolactone
107
What is Liddle syndrome
```
AD
hypokalemia
hypertension
low renin
but low aldosterone
treat with sodium restriction and triamterene (K sparing diuretic)
```
108
What is a pheochromocytoma
catecholamine-secreting tumor in the chromaffin cells
| in children it is most often norepinephrine
109
What are the manifestations and laboratory findings
hypertension (can be fluctuating like in adults but often not)
vomiting, sweating or seizures if hypertension is very high
trouble gaining weight and growth failure
eye exam will papilledema, exudates and hemorrhages
urine with protein and a few casts, glucose
elevated blood and urine levels of catecholamines
with 24 hour urine > 300 micro grams in 24 hours
elevated vanillylmandelic acid and metanephrine
find them via CT or MRI
110
What is the treatment for pheochromocytoma
careful surgery, using alpha and beta blocker prior to surgery
111
What is primary hypergonadotropic hypogonadism in males, how does it present and how is it diagnosed
normal external genitalia suggest that cause is damage after sexual differentiation occurred
testicles have a defect a do not make testosterone
so high LH and FSH and low testosterone, but have to get labs when one would expect puberty
suspect if penis and testicles are abnormally small often not recognized until age of puberty and sexual characteristics don't happen, no testicle or penile enlargement, hair does not develop fully
epiphyses close but later so limbs are long
112
What are the manifestations of Noonan Syndrome
AD with variable expression
look like turners: short, webbed neck
but have pectus deformity, cubitus valgus
right sided heart disease (pulmonic stenosis, ASD, hypertrophic cardiomyopathy)
25% have intellectual disability
high frequency sensorineural hearing loss
at risk for ALL and CML
boys with cryptorchisim and can be hypogonadal or normal
113
What is seen in Klinefelter Syndrome
usually 47 XXY but can be mosaic
usually not diagnosed until puberty
some have intellectual disability or psychiatric problems (particularly fire setting?!)
puberty starts normally with enlargement of the testes and then stalls with decrease in testicular size due to seminiferous tubules dysgenesis
penile size is small due to decreased testosterone
gynecomastia (same risk of breast cancer as women)
long legs and above normal height
testicular lesions with spermatogenic arrest with azoospermia and infertility
114
What laboratory values are seen in Klinefelter syndrome and what is the treatment
decreased testosterone and increased LH and FSH during mid puberty
confirm with karyotype
treat with testosterone, most effective with early diagnosis
115
What is seen in XX males
male phenotype likely because the SRY gene is on one of the X chromosomes
small testicles, small penis with no evidence of ovarian or Mullerian duct tissue
look like Klinefelter boys but are shorter
116
What is seen in XYY males
tend to be tall
severe nodular cystic acne
developmental delay and behavior problems are common
117
What are some causes of secondary or hypogonadotropic hypogonadism?
hypopituitary: infant with penile length < 2.5 cm, with undescended testes: possible gonadotropin deficiency
isolated GnRH deficiency: kallmann syndrome: anosmia or hyposmia and hypogonadism. X-linked
118
how is hypogonadotropic hypogonadism diagnosed and treated?
LH and FSH are low as are testosterone
this can also been seen in constitutional delay, often there will be other defects that suggest pituitary like GH deficiency or ACTH deficiency
treat with testosterone
119
What are some other syndromes with hypogonadal symptoms
Laurence-moon-bidelo or bardet-biedl syndrome: retinitis pigmentosa, obesity intellectual disability, genital hypoplasia and hypogonadism
prader willi:
120
When is gynecomastia normal and when should additional work up be done.
physiologic pubertal gynecomastia: tenderness, size reduces in a few months. provide reassurance
must be tanner 2, 3 or 4
if tanner 1 or 5 = it's abnormal
121
When and what work up should be done for gynecomastia
tanner 1 or 5
younger than 10 or older than 16
chronic illness, liver, thyroid, renal, abnormal pubertal progression, patient wants surgery or macrogynecomastia (> tanner 3)
Due to an imbalance of estrogen : testosterone
check LFTs, TFTs, Cr, testosterone, estradiol, hCG, LH, DHEAS, karyotype if concerned about Klinefelter
in prepubertal children look for exogenous estrogen sources
galactorrhea signals prolactinoma
122
What happens to oocytes in girls with turner syndrome
In normal girls the number of oocytes slowly declines during childhood. In turner syndrome this process is faster with all oocytes depleted by age 2
123
What are the clinical manifestations of Turner syndrome
at birth:
marked edema of the dorsum of the hands and feet
loose skin at the nape of the neck
Childhood:
short
webbed neck with low hairline
high arched palate, small mandible and prominent ears
broad chest with widely spaced nipples
cubitus valgus
hyperconvexity of the fingernails
no breast development, no estrogen but will have adrenarche
124
What are the cardiac findings in Turner Syndrome
```
bicuspid aortic valve (most common)
coarctation of the aorta
aortic stenosis
mitral valve prolapse
due to risk for aortic dissection, followed with ECHO every 5-10 years
```
125
What are the common renal findings in turner syndrome
pelvic kidney
horseshoe kidney
double collecting duct or complete absence of one kidney
all girls should have renal US at diagnosis
126
What thyroid abnormalities can occur in Turner Syndrome
Many have anti thyroid antibodies
| should be screened for thyroid disease annually
127
What are the skeletal abnormalities in Turner syndrome
shortening of the 4th metacarpal bone
scoliosis
epiphyseal dysgenesis in the joints of knees and elbows
madelung deformity, subluxation of the distal radius/ulna
128
What developmental abnormalities are associated with Turner syndrome
slightly delayed gross and fine motor skills
normal intelligence
have difficulty with spatial relationships, which makes math difficult
129
How is Turner syndrome confirmed and how is it treated
GH for height
estrogen
monitor for glucose intolerance
130
What is XX gonadal dysgenesis
normal external genitalia and otherwise normal however, at puberty sexual maturation does not occur as there are only streak gonads
long arms and legs as epiphyseal fusion does not happen
gonadotropin levels are elevated
Perrault syndrome: ovarian dysgenesis and sensorineural hearing loss
Treat with estrogen replacement
131
What is mixed gonadal dysgenesis or 45X/ 46 XY gonadal dysgenesis
can range from turner syndrome to being male in appearance to ambiguous genitalia to female parts with mild virilization
gonadal tumors, gonadoblastoma occur in about 25%
132
What is seen if there are many X chromosome like XXX, XXXX or XXXXX?
47 XXX tend to have speech and language delays with poor coordination, poor academic performance and immature behavior
Tall
Those with more Xs have intellectual disability usually with more Xs the more severe the disability
133
What are the symptoms of Polycystic ovary syndrome or Stein-Leventhal Syndrome?
obesity, hirsutism, secondary amenorrhea and bilaterally enlarged polycystic ovaries
unknown cause but seen with elevated levels of testosterone and LH: FSH ratio, many also have insulin resistance
134
How is Polycystic ovary syndrome or Stein-Leventhal Syndrome diagnosed and treated?
elevated testosterone with elevated LH:FSH ratio
perform US to look for polycystic ovaries
DHEAS, 17-OH progesterone and androstenedione to screen for possible adrenal causes
OCPs, spironolactone for hirsutism and in obese patients loosing weight and oral diabetic medications if insulin resistant
135
What determines "maleness" and what is the usual sequence of events during development. What is the usual sequence for girls?
Need an SRY gene to be "male"
For males Sertoli cells make Mullerian inhibit substance at 6-7 weeks causing Mullerian ducts to regress
at 8 weeks leydig cells make testosterone this makes Wolffian duct to virilize into the epididymis, vas deference and seminal vesicle
external characteristics require dihydrotestosterone
Girls: default pathway if the above does not happen, estrogen is not necessary for sexual differentiation
136
What are some causes of XX 46 DSD?
```
infant has normal female internal structures but external genitalia are virilized
too many androgens
Congenital adrenal hyperplasia
maternal androgen producing tumor
medication mom is taking like danazol
```
137
What will happen to baby is mom is exposed to androgens and what is the time frame
Mom exposed during 13-18 weeks: labial fusion
Mom exposed after 18 weeks: clitoral enlargement
If exposed the from 13 weeks on, baby will have both
138
What is Denys-Drash syndrome
46XY individual with nephropathy and ambiguous genitalia and wilm's tumor
total deficiency of testicular function so Mullerian ducts are present
renal failure often occurs at age 3
139
What is seen in WAGR syndrome?
Wilm's tumor
Aniridia
Genitourinary anomalies (cryptorchidism, lack of virilization, since Wilm's tumor suppressor gene is needed for testicular development, and they are missing this gene)
intellectual disability
140
What is seen in Swyer Syndrome or XY pure gonadal dysgenesis?
Individual is 46 XY
No Leydig cells, so no testosterone or Wolffian structures
No seritoli cells so Mullerian structures develop
normal stature and phenotypically female, inside and out
however, at puberty no breast development and no menses
have undifferentiated streak gonads that have a 25% risk for malignancy
141
What is seen with Leydig cell aplasia
female phenotype to mild virilization
Mullerian structures are inhibited so internal male structures are usually present but since Leydig cells do not make testosterone, external genitalia are female
Secondary changes do not happen at puberty and testosterone is low
142
What happens with 17 ketosteroid reductase deficiency and 5 alpha reductase deficiency?
17 ketosteroid reductase deficiency: AR defect in last enzyme to make testosterone. 46XY child with female external genitalia at birth, however no Mullerian or Wolffian structures. At puberty peripheral conversion of androstenedione produces male characteristics
5 alpha reductase deficiency: AR decreased production of dihydrotestosterone needed for external genitalia development. Present as female to under virilized male. Internal structures are male. At puberty due to testosterone virilization occurs.
143
What is persistent Mullerian Duct syndrome?
phenotypic males with all male structures
however seritoli cells did not inhibit Mullerian structures so they also have a uterus and fallopian tubes
They have an XY karyotype
often found incidentally during inguinal hernia repair
144
What is Androgen insensitivity syndrome
X linked disorder
receptor or testosterone does not work, so testosterone is elevated. Phenotype depends on how broken the receptor is.
present a completely female phenotype to ambiguous genitalia to male with infertility
There are no internal female organs
have a vagina with a blind pouch
at puberty will develop breasts due to the peripheral conversion of testosterone and estrogen receptor works
no menses
have abdominal testes and are at risk for becoming malignant
145
What is ovotesticular disorder of sexual differentiation
both ovarian and testicular tissue is present
can be male, female or ambiguous genitalia
most at 46 XX but some are 46 XY and others are mosaic
146
If an infant has ambiguous genitalia, a uterus and no gonads what does this indicate
virilized 46 xx infant
147
How is diabetes diagnosed?
1. fasting (8 hours) glucose > 126
2. symptoms of hyperglycemia and random glucose > 200
3. glucose > 200 on oral glucose tolerance test
4. A1c > 6.5
148
In what age groups are children most often diagnosed with Type 1 diabetes and what are some possible causes of the disease
peak incidence in 5-7 year olds and then at puberty
more diagnosis in autumn and winter
HLA such as DR3 and DR4 carry increased risk
149
How does Type 1 diabetes present?
polyuria, polydipsia, polyphagia and weight loss
enuresis in a child previously toilet trained
lethargy or weakness
skin or vaginal candidial infections
ketoacidosis presents as nausea, vomiting polyuria and dehydration
rapid kussmaul respirations due to the acidosis
150
What laboratory values define ketoacidosis
```
hyperglycemia usually > 300
acidosis < 7.3 or CO2 < 15
ketones in urine
75% are due to not taking enough insulin
some times infection can be a precipitating factor and this must be treated
```
151
How is DKA managed
1. 10 ml/kg of NS, more can be given if there is shock
2. 0.45 NS at 1.5 to 2 times maintenance
3. fluids need potassium, 1:1 potassium chloride to potassium acetate
4. After fluid bolus start insulin drip at 1u/Kg/hr
5. Once glucose is < 300 change fluids to 5% glucose in 0.45 NS, may need to increase glucose to continue insulin
6. monitor osmolality
7. give subcutaneous insulin once gap and acidosis is corrected. overlap subq an drip depending on half life of insulin
152
What is seen with cerebral edema due to DKA, what are some risk factors and what is the management?
cerebral edema: headache, vomiting, changes in level of alertness, fixed or unequal pupils, seizures
risk factors:
young age < 5
new onset diabetes
low PCO2 or high BUN
treatment with bicarb
decrease in corrected sodium with therapy (fluid overload)
give mannitol or 3% saline before CT scan
153
What is another complication of DKA
hypokalemia: u waves on EKG
hyperkalemia: peaked T waves on EKG
154
What is seen in hyperglycemic hyperosmolar syndrome
```
severe hypoglycemia, often > 600
hyperosmolar, > 330
no ketosis
non ketotic acidosis
dehydration
neurologic complications, seizures, hemiparesis, Babinski present
```
155
How is hyperglycemia hyperosmolar syndrome treated
admit to PICU
rapid correction of dehydration and careful correction of osmolality
initial 20 ml/kg NS bolus
0.45% NS at a rate to replace 50% of deficit in first 8-12 hours, remaining over next 24 hours
start insulin drip at 0.25 to .5 u/mg/hr once glucose stops dropping due to IV fluids
156
What is the total insulin daily dose for newly diagnosed patient with diabetes?
0.7-1 u/kg/day
157
How is the dose for basal insulin calculated, the carbohydrate to insulin ratio and the correction factor calculated?
basal insulin= 1/2 of the total daily dose, 1/2 or 0.7-1 u/kg
carbohydrate to insulin ratio : 500 / total daily dose = g of carbs per 1 u or insulin
correction factor: 1800/total daily dose= number of point glucose should decrease for 1 unit of insulin
158
How is the insulin regimen calculated if the child is using mixed insulin?
calculate total daily dose
divide total dose for 2/3 to be given in the morning and 1/3 in the evening
of this, 2/3 is intermediate acting and 1/3 is short acting
at supper the short acting dose is often given with the NPH dose being given at bed time
used when patients are having difficulty with carbohydrate counting or cost is prohibitive of other regimen
159
What are the blood glucose goals by age?
< 6 years: premeal 100-180, overnight: 110-200, A1c < 8.5
6-12 years premeal 90-180, overnight 100-180, A1c < 8
young adults: premeal 90-130, overnight: 90-150 A1c < 7.5
160
What is the honeymoon period in type 1 diabetes
there is still residual beta cell function in the early months after diagnosis
recurrent hypoglycemia is common during this time
161
What is Somogyi phenomenon and and how do you tell the difference?
Somogyi phenomenon: hypoglycemic episode with early morning sweating, night terrors or headaches alternating with hyperglycemia, ketonuria thought to be due to counter regulatory hormones responding to hypoglycemia
162
what is dawn phenomenon
Dawn phenomenon: normal event with glucose eleates between 5 and 9 am due to waning effects of insulin and GH release which antagonizes glucose
163
How do you tell the difference between Somogyi phenomenon and dawn phenomenon?
Obtain glucose at 3, 4 and 7 am
If normal night glucose with rise at 7 am: dawn phenomenon and can increase evening insulin dose
if 3 or 4 am blood sugar is low, < 60 followed by rebound hyperglycemia at 7 am, somogyi phenomenon and insulin dose should be decreased
164
What should be monitored in those with Type 1 diabetes
5 years after diagnosis:
urine albumin yearly (nephropathy)
ophthalmic exam yearly is age > 10 (retinopathy)
fasting lipids: if abnormal yearly, if normal every 5 years
check starting at age 10 unless concerning family history, then start at diagnosis or age two.
celiac disease at diagnosis then any other time with symptoms
thyroid at diagnosis and then annually
165
What should be done if a patient with diabetes has microalbuminuria or macroalbuminuria?
treated with ace inhibitor
problematic in teenage girls who are of child bearing age
slow progression of renal disease even in absence of hypertension
166
Is there a genetic predisposition to type 2 diabetes
yes though not HLA
167
Who should be screened for Type 2 diabetes
overweight with BMI > 85th percentile for age, sex or weight for height > 85th percentile or weight > 120 % for ideal body weight
AND 2 of the following risk factors
Family history of Type 2 diabetes in 1st or second degree relative
Race: African American, native American, latino, Asian-American or pacific islander
Signs of insulin resistance or associated conditions: acanthosis, PCOS, hypertension, dyslipidemia or SGA
Maternal history of diabetes or gestational diabetes during pregnancy
168
When does screening start for diabetes and how often. How should screening be done.
For those who meet the criteria, start at 10 and every 3 years if normal.
fasting glucose
oral glucose tolerance test in those with impaired fasting glucose or normal but the suspicion is high
169
How is type 2 diabetes treated in children
if metabolically decompensated at presentation, with ketosis and glucose > 300 = insulin until stable and can be weaned later
if metabolically stable = metformin, diet, exercise
these are the only two medications approved for Type 2 diabetes
170
What screening tests should be done in those with Type 2 diabetes?
```
testing should be done at diagnosis
urine for microalbumin, yearly
ophthalmology, yearly
Blood pressure at every visit
serum lipids, yearly
screening for NASH and then yearly
```
171
What is Donohue syndrome or leprechaunism
IUGR, fasting hypoglycemia and post prandial hyperglycemia with profound insulin resistance
mutation or deletion of both insulin receptor gene
most die before 1 year of age
172
What are the criteria for metabolic syndrome
3 of the following
1. evidence of hypertension
2. Elevated triglycerides
3. Low HDL
4. glucose intolerance
5. central obesity with waist circumference and weight > 85% for age
173
What critical labs need to be obtained in patients who present with hypoglycemia
```
glucose
insulin
GH
cortisol
lactate
ketones
alanine
```
174
What is the treatment for hypoglycemia
15 g or carbohydrate
wait 15 min and recheck glucose
repeat
or give IV glucose or glucagon in those who are unconcsious
