Endocrine Flashcards
What percentage of kids experience pubic hair growth as first sign of puberty?
20%
When do GnRH neurons migrate to hypothalamus
6-9 wga
When does FSH/LH secretion start in the fetus
12 weeks
When do fetal levels of FSH/LH peak
20-24 weeks
What happens to FSH/LH after delivery
GnRH pulsatility starts with FSH/LH rising with FSH > in females (peaks 12-18 months)
LH > males (peaks 3-6 months)
**Then there is change in central inhibition of pulsatile GnRH and high sensitivity to low levels of gonadal steroid feedback –> diphasic pattern of secretion
How does adrenarche start and when?
Age 6
Increased in responsiveness of adrenal glands to ACTH causing shift in sex steroid production
Decreased 3B HSD activity + increased activity in P450 Cyp 17
Shunts towards DHEA/DHEAS
Genes associated with early puberty
LIN28B, FTO, NEGR1
Shift in body composition associated with puberty
% body fat
16-23%
Leptin and puberty
Made by adipocytes and acts on CNS to regulate eating/energy balance
Leptin knockout mice have normal sexual development but are anovulatory
What is precocious puberty
Pubertal development occurring more than 2.5 SD earlier than the norm
Types of precocious puberty
GnRH Dependent: early activity of HPG axis
-constitutional (RUNS IN FAMILY) /idiopathic (does NOT RUN in family & onset is usually younger)
-CNS pathology
-Hypothyroidism
GnRH Independent:
-Sex steroid production independent of HPG axis
-Ovarian tumors
-McCune Albright
-Adrenal disease
-Exposure to estrogens
Hypothalamic hamartoma
Heterotopic neuronal masses of GnRH neurons that function as ectopic GnRH pulse generator
PP in first few years of life
Craniopharyngioma
Neuroepithelial CNS tumor
Disrupts normal pre-pubertal HP axis inhibition
Hypothyroidism and GnRH dependent PP
Delayed bone age (Thyroid hormones have permissive activity directly on bone and GH)
High TSH stimulates FSH-R and causes high prolactin and galactorrhea
Gonadoblastoma
complex tumor with a mix of gonadal elements
90% associated with abnormal karyotype, gonadal dysgenesis, or Y chromosome
Premature adrenarche
pubic hair < 8 yo
consider checking bone age to make sure there isn’t precocious puberty too (~20% have both)
Most significant outcome of precocious puberty
short stature because of premature epiphyseal closure
GnRH stimulation test
Check basal LH
leuprolide 20 ug/kg subcu
if LH > 5 IU/L suggests HPG axis activation
if LH is normal/low eg < 5 then likely to be GnRH independent
When to treat precocious puberty
-Sexual maturity advances to next stage in 3-6 months
-growth velocity > 6 cm/year
-bone age is advanced by > 1 year
-predicted adult height is < target range or decreased on serial measurements
Treatment for GnRH dependent precocious puberty
lupron
monitor symptoms and E2 (<10 pg/mL) at 3-6 month intervals
Delayed puberty
Absent or incomplete sexual maturation by age at which 95% of kids of same sex started pubertal development
Short stature
height 2 or more standard deviations below mean height for children of same sex/age
-Dx: familial/constitutional, chromosomal (downs/turners), idiopathic
Treatment of short stature
consider GH if height > 2.25 SD below mean
Treatment of tall stature
start treatment before menarche
ethinyl estradiol 15-30 ug (low dose OCP)
continue until epiphysis close
Metformin
Biguanide antihyperglycemic approved for T2DM not adequately managed by diet and exercise.
Does not cause hypoglycemia
Decrease hepatic glucose production, thus reducing the need for insulin secretion
Decreases intestinal absorption of glucose.
Lowers free fatty acid concentrations, thus reducing gluconeogenesis
Where is DHEA made?
Adrenal 50%
Ovary 20%
DHEAS conversion 30%
Where is androstenedione made?
Adrenal 50%
Ovary 505
Where is testosterone made?
Adrenal 25%
Ovary 25%
Androstenedione conversion 50%
Insulin and PCOS
decreases SHBG
increases activity of LH on ovary
increase in IGF-1 potentiates response of ovary to LH
Hair stages
Anagen- growth
Catagen- involution phase
Telegen- quiescent phase
Clitoral index
> 35 mm (LxW)
Signs of virilization
deepening of voice
hirsutism
clitoromegaly
breast atrophy
muscle mass distribution
Spironolactone
aldosterone antagonist
50-100 mg BID
SE: dyspepsia, nausea, fatigue, HA
Feminization of male fetus
Eflornithine
Ornithine decarboxylase inhibitor
inhibition of cell division and synthetic function
13.9% application
SE: acne, folliculitis, pain/rash
Finasteride
5a reductase inhibitor
inhibits type II mostly
5mg QD
flutamide
androgen receptor blocker
500 mg daily
SE: green urine, hepatotoxicity
SRY gene
Gene encoding DNA-binding protein
Located next to pseudo-autosomal region on short arm of Y
Presence causes gonadal differentiation to testes
No SRY - ovaries
Normal fasting insulin
25 mIU/L
Normal triglyceride
< 150 mg/dL
normal total cholesterol
200 mg/dL
HAIR-AN
Hyperandrogenic insulin-resistant acanthosis nigricans
Differential diagnosis for low E2 level in pregnancy?
placental sulfatase deficiency
placental aromatase deficiency
impending fetal demise
fetal demise
adrenal hypofunction
drugs
Infant presentation with placental sulfatase deficiency
ichthyosis
hyperkeratosis develops because of alteration in cholesterol: cholesteryl ester ratio from accumulation of cholesterol sulfate
corneal opacities
pyloric stenosis
cryptorchidism
Amniotic fluid with placental sulfatase deficiency
Amniotic fluid has high levels of DHEAS, normal DHEA, and androstenedione
normal free T4
0.8-1.8 ng/dL
Premature ovarian insufficiency
<40
Elevated FSH and amenorrhea
1% of women and 90% idiopathic
5-10% may experience spontaneous ovulation
Ovulatory dysfunction for PCOS in adolescence
- Lack of menarche by 15 yo or 3 yr s/p thelarche
- Menarchal intervals < 21 or > 45 days (1-3 years post menarchal)
- Persistent menstrual intervals < 21 or > 35 days or < 8 cycles/year > 3 years post menarche to menopause
What hormones do ovaries lack?
21 hydroxylase
11 beta hydroxylase
**Favors androgen production
StAR
carrier protein aiding in cholesterol transport across the membrane
functions in adrenals and gonads but NOT the placenta
Congenital lipoid adrenal hyperplasia is caused by AR mutation in STAR causing males to have female external genitalia and adrenal glads to be filled with lipoid globules
Sequence of FSH/LH on receptors
FSH/LH bind to GPCR which stimulates adenylate cyclase and leads to release of cAMP and cholesterol transfer via StAR and nuclear steroidogenesis
What increases SHBG?
Hyperthyroidism
Pregnancy
Exogenous estrogen
What decreases SHBG?
Insulin
IGF-1
Corticoids
Androgens
Progestins
GH
Prolactin
What proportion of hormones are bound to carrier proteins?
SHBG: 69%
Albumin: 30%
Free: 1%
how many carbons does cholesterol have
27
Function of FSH at granulosa cells
induce more FSH R
induce transcription of aromatase leading to E2 production
As follicle grows FSH induces LH R appearance on granulosa cells –> progesterone production (LH mediated)
Prolactin levels caused by meds?
25-100
What med can increase prolactin to 300?
Risperidone
What meds can cause hyperprolactinemia?
risperidone, olanzapine, haloperidol, bupropion, TCA, SSRI, reglan, cimetidine, prochlorperizine, verapamil, methyldopa, opiates, OCPs, transgender meds, medicinal herbs
How do dopamine agonists suppress prolactin?
DA bind to D2 receptors on lactotrophs and decrease intracellular cAMP and lower prolactin secretion
