Pharmacology + Puberty Flashcards

Question

Ovarian cycle

Answer 1

Follicular + luteal phases Follicular: development of mature graafian follicle and secondary oocyte estrogen gradually increases, causing + feedback and LH/FSH peak, while progesterone remains low throughout --> ovulation, formation of corpus luteum (CL) Luteal: CL = residucal theca and granulosa cells of follicle; synthesise and secrete estrogen and progesterone t maintain the feralised oocyte If fertalisation doesnt occur (ie no HCG produced), the CL regresses and forms corpus albicans (non functional scar like structure)--> occurs 10-12 days after ovulation in absence of HCG

Answer 2

< 8 years in girls, <9 years in boys central: gonadotropin dependant peripheral: gonadotropin independant --> incomplete, atypically sequenced or rapid pubertal progression

Answer 3

iii. Caused by excess secretions of 1. Sex hormones (estrogens or androgens) from the gonads 2. Exogenous sources of sex steroids 3. Ectopic production of gonadotropin from a germ cell tumour (eg. hCG) iv. Not true puberty as hypothalamic-pituitary-gonadal axis is not activated Examples: CAH, androgen secreting tumor, McCune Albright syndrome, severe hypothyroidism (ovarian stimulation secondary to high TSH which mimics FSH)

Answer 4

Central: increased pulsatile GNRH--> increased LH and FSH --> increased estradiol and testosterone increased LH and FSH with GNRH stimulation test Peripheral: no GNRH pulse --> low LH and FSH, elevated estradiol and testosterone - HCG in boys to exclude hcg secreting germ tumor TFTs Cholesterol DHEAS, 17OH (CAH) Abdo/pelvis USS Xray for bone age

Answer 5

Lucrin (GNRH agonist if central tanner stage 2-3 breast development may regress, if >3, tends to remain Menses ceases pubic hair stays the same aim to slow prior to epiphyseal fusion, as risk short stature with premature growth spurt peripheral- treat cause ca consider lucrin to prevent secondary central precocious puberty

Answer 6

GnRH dependent KEY = due to early activation of the hypothalamic-pituitary-gonadal axis More common in girls Idiopathic in 80-90% of girls and only 25-60% of boys 75% of boys have CNS abnormality a. Idiopathic (80%) i. Almost all idiopathic cases are girls b. Organic brain lesions c. Hypothalamic hamartoma (Most common CNS cause of precocious puberty) d. Brain tumours (glioma, intracranial germ cell tumor (usually pineal)) hydrocephalus, severe head trauma e. Hypothyroidism prolonged and untreated f. Acquired CNS insults i. CNS irradiation – commonly associated with GH deficiency ii. Hydrocephalus, subarachnoid cysts, CP, tuberous sclerosis g. NF type --> optic glioma interrupt HPG axis h. Previous excess sex steroid exposure eg. CAH

Answer 7

a. All components of puberty normal but early b. Girls = early development of breasts, early menstrual cycles c. Boys = early development of testes, early spermatogenesis d. Both i. Height, weight and osseous maturation are advanced  early closure of epiphyses 1. Without treatment 1/3 girls and most boys = <5th centile height as adults

Answer 8

a. Key = elevated basal LH and/or stimulated LH concentration post GnRH b. Sex hormone concentrations – usually appropriate for the stage of puberty c. GnRH stimulation test (GnRH administered) or GnRH agonist (leuprolide) – helpful diagnostic test d. Pelvis USS = may show enlarged ovaries, enlarged fundus and the whole uterus e. X-ray bone age = advanced bone age f. MRI = CNS pathology, may show physiological enlargement of pituitary (normal in puberty)

Answer 9

a. Caused by excess secretion of sex hormones (estrogens and/or androgens) derived from i. Gonads ii. Adrenal glands iii. Exogenous sources b. Low or suppressed gonadotropin concentrations with elevated sex hormone levels ie no activation of HPA axis c. Pubertal status needs to be monitored for 6/12 after treatment as treatment of peripheral precocity can trigger central precious puberty Girls: ovarian cysts (may be secondary to McCune Albright Syndrome), ovarian tumors Boys: Leydig cell tumors, hcg secreting tumors (eg hepatoblastoma0 Both: exogenous hormones, adrenal tumors, CAH, hypothyroidism pituitary gonatrotrophin secreting tumors, McCune Albright syndrome

Answer 10

1. Peripheral precocious puberty 2. Irregular café-au-lait skin pigmentation 3. Fibrous dysplasia of bone Hyperthyroidism GH excess--> gigantism/acromegaly Cushings syndrome Renal phosphate wasting --> hypophosphatemic rickets

Answer 11

Letrezole = aromatase inhibitor Tamoxifn- anti estrogen CAH- glucocorticoids

Answer 12

Letrzole Tamoxien anti androgens- spirnolactone, flutamide CAH- glucocorticoids

Answer 13

SUPPRESSED FSH and LH elevated oestrogen/testosterone No response to GNRH stimulation

Answer 14

Elevated FSH AND LH Response to GNRH >6

Answer 15

Usually occurs

Answer 16

Driven by adrenal androgens Normal growth velocity No enlargement of testes/penis or breasts/ovaries/clitoris Normal or slightly advanced bone age Diagnosis requires biochemical demonstration of serum steroid pattern DHEAS >40 More common in girls than boys Girls will have slightly increased risk of developing PCOS and metabolic syndrome Tend to have linear growth rate and bone age that are above average, but still within normal range Ix: 17 hydrohyprogesterone: normal excludes non classical CAH Mod elevattion suggests CAH, need to confirm with ACTH Very elevated- diagnostic of non classical CAH Serum DHEAS Bone age - Increased. 30% hav bone age more than 2 years above chronological age a. Slowly progressive condition that requires no therapy b. Monitor to assess height velocity and watch for signs of rapid progression or breast development indicating central precocious puberty

Answer 17

Premature pubarche but no biochemical evidence of adrenarche Bone age + DEHAS and androgens = normal

Answer 18

· Isolated vaginal bleeding in a girl with no other puberty, with normal growth, normal bone age, and no evidence of infection or foreign body · MUCH less frequent than premature thelarche or premature adrenarche · Diagnosis of exclusion – need to exclude vulvovaginitis, FB, sexual abuse, urethral prolapse, sarcoma botryoides · Majority of girls with idiopathic premature menarche only have 1-3 episodes of bleeding · Puberty usually occurs at normal time, menstrual cycles are normal · Investigations o Gonadotropins – low o Estradiol – occasionally elevated due to ovarian estrogen secretion associated with ovarian follicular cysts \ USS pelvis: prepubertal uterus and ovaries

Answer 19

Girls: Absence of breast development by 13 years Boys: Failure of testicular enlargement to 4ml by 14 years · Constitutional · Functional hypogonadism (eg. Chronic disease, nutritional inadequacy, excessive exercise) · Primary hypogonadism – testicular or ovarian pathology Secondary hypogonadism – hypothalamic pituitary disturbance/GnRH deficiency

Answer 20

Primary hypogonadism = ↑ FSH and LH i. Congenital 1. Chromosomal abnormalities = Turner (females), Klinefelter (males) 2. Disorders of sex development 3. Gonadal dysgenesis ii. Acquired 1. Autoimmune 2. Post-infectious (mumps, orchitis, coxachie virus – in males) 3. Following trauma or surgery 4. Following chemotherapy or radiotherapy

Answer 21

(hyogonadotropic hypogonadism) = ↓/normal FSH and LH Congenital: Isolated GnRH deficiency = idiopathic hypogonadotropic hypogonadism a. Without anosmia or With anosmia (Kallman syndrome) b. Caused by a variety of genetic mutations c. Associated with adrenal hypoplasia, midline defects (cleft lip/palate), hearing loss, renal agenesis, skeletal anomalies 2. GnRH deficiency associated with mental retardation/obesity a. Prader-Willi syndrome 3. Combined pituitary hormone deficiency 4. Congenital brain malformation causing GnRH or gonadotropin deficiencies (often associated with craniofacial abnormalities) ii. Acquired 1. Tumours = benign, craniopharyngioma, any other CNS tumour 2. ‘Functional’ gonadotropin deficiency a. Constitutional delay of growth and puberty b. Chronic systemic illness eg. celiac disease c. Acute illness d. Malnutrition e. Hypothyroidism, hyperprolactinaemia, diabetes mellitus, Cushing’s disease f. Anorexia nervosa

Answer 22

iv. Is pubertal development totally absent, or did it start then stall? Any early signs of puberty that then regressed? v. Is there a normal sense of smell b. Examination i. Growth, height, weight, HC, height velocity, arm span>height (Kallaman syndrome- arm span often >5cm greater than height) ii. Dysmorphism/midline defects iii. Olfaction (Kallman’s syndrome) iv. Neurological v. Signs of chronic disease/endocrinopathy vi. Tanner staging – puberty vii. Bilateral cryptorchidism, micropenis, anosmia, synkinesia- Kallman syndrome viii. Delayed cognitive development, obesity +/- dysmorphic features – genetic syndromes eg Prader Willis

Answer 23

a. Bone age b. Basic bloods – FBE, UEC, ESR,CRP, LFT c. Endocrine tests i. LH, FSH, estradiol and testosterone 1. Random (unstimulated) measurements of LH and FSH together with estradiol (girls) or early morning testosterone (boys) – distinguishes between primary and secondary hypogonadism 2. ↑ LH + FSH indicates primary hypogonadism 3. ↓or normal serum LH/FSH with low levels of testoerone or estradiol indicates constitutional delay or isolated GnRH deficiency ii. GnRH stimulation test – not recommended d. Prolactin – detect hyperprolactinaemia e. IGF-1 – excludes growth hormone deficiency as cause of delayed puberty f. TFTs – excludes hypothyroidism as cause of delayed puberty g. Coeliac bloods- functional delayed puberty h. Ultrasound – to detect underlying structural abnormality i. Additional tests i. Primary hypogonadism 1. Karyotype to establish diagnosis of Klinefelter/Turners 2. Girls have Turners until proven otherwise- always do karyotype ii. Secondary hypogonadism 1. Head MRI – assess for hypothalamic or pituitary disease 2. Anosmia – olfactory function test 3. If GnRH deficiency strongly suspected – genetic testing 4. Serum inhibin B (boys)- marker of Sertoli cell function

Answer 24

produced by the sertoli cells of prepubertal testes can be used as marker sertoli cell function Inhibin is secreted also by granulosa cells and has a role in regulating the pituitary secretion of FSH. Therefore, inhibin is a potential marker for ovarian function and follicular content.

Answer 25

Human chorionic gonadotropin (HCG) stimulation test is a reliable dynamic test for the evaluation of testicular function during childhood. A single dose of HCG injection at dose of 100 iu/kg is able to produce a progressive but modest rise in testosterone level for 72 to 120 hours in presence of a viable testicular Leydig cells.

Answer 26

Boys >14 yrs and girls >12 yrs who show few or no signs of puberty i. Females = estradiol ii. Males= testosterone iii. Cryptorchidism- surgical mx

Answer 27

delayed bone age

Answer 28

a. Spontaneous pubertal onset 30-40% i. Those with inhibin B are most likely to have spontaneous puberty ii. Continuing ovarian function most likely with AMH hormone levels b. Spontaneous menses 4% Fertile spontaneously 1%

Answer 29

a. Sex hormones i. Should NOT wait - start treatment with HRT around the age of 12 years ii. General management when complete pubertal progress is needed 1. Use estradiol (non ethinyl radical estradiol) – slowly increase dose over 2-3 years 2. Add progesterone at the end of this time iii. ALWAYS use continuous estrogen to prevent bone loss iv. Avoid use of contraceptive pill (as this induces hypertension – high lifetime risk in Turner syndrome) b. Growth hormone i. Growth hormone + estrogen gives best height outcome

Answer 30

Mini puberty (8-12 weeks of age) as relatively high LH FSH oestrogen/testosterone Later in childhood the hpa axis is suppressed so may not show a response to stimulation Pointless to test hormone levels in childhood as they will be very low in everyone

Answer 31

Somatic That’s why mutations may not be picked up on blood tests (may only be in certain organs) Wide range of phenotype

Answer 32

All sex hormones low and no rise in LH/FSH with stimulation test eg craniopharyngioma, pituitary adenoma, prolactinoma, septooptic dysplasia

Answer 33

low dose- precocious puberty high dose- delayed puberty GH most impacted ACTH second most impacted

Answer 34

High LH, FSH Low testosterone/oestradiol despite stimulation of gonads by pituitary eg Kleinfelters, Turners, trauma, chemotherapy (eg cyclophosphamide)radiation to gonads, cryptorchidism

Answer 35

40% of all pituitary tumors Delayed puberty hypogonadism ammenorrhoea infertility galactorrhoea bone loss *macroadenomas more common in kids **hyperprolactinemia interrupts pulsatile secretion of GnRH, inhibits release of LH and FSH and directly impairs gonadal steroidogenesis

Answer 36

IBD Hashimotos Graves Coeliac Hypothyroidism delayed puberty (only 30% will have spontaneous puberty, only 2-5% spontaneous menses, thus most have secondary ovarian failure soon after starting puberty) premature ovarian failure/ovarian dysgenesis infertility Short stature --> need GH Osteoporosis due to gonadal failure Rx: GH Ostrogen at 11-12 years (transdermal) and progesterone after 2 years of oestrogen treatment up to 90% have progressive SN hearing loss

Answer 37

Micropenis Hypospadias Cryptorchidism However most will have no features in the post natal period

Answer 38

Elevated FSH Low LH

Answer 39

60% will enter puberty spontaneously Consider testosterone treat cryptorchidism Vit D, calcium - for bone health Avoid high LH levels as this can reduce bone strength

Answer 40

Hypothyroidism metabolic syndrome diabetes obesity Breast cancer Osteoporosis , fractures Epilepsy Depression/anxiety

Pharmacology + Puberty Flashcards

(65 cards)