Puberty and Growth Flashcards

Question

Prader Willi syndrome gene

Answer 1

lack of expression of paternally inherited imprinted genes on chromosome 15q11-13

Answer 2

GV <2cm/y BA fused

Answer 3

intracranial hypertension slipped capital femoral epiphysis (SCFE) scoliosis progression Insulin resistance Theoretical increased risk of malignancy Gynecomastia (for boys) Local reaction at site of injection Increased growth of nevi (?) Hypertrophy of tonsils/adenoids (?)

Answer 4

= GH insensitivity Molecular mechanism: - Primary GH resistance - Receptor mutation (decreased or absent). Note: Decreased serum GHBP levels - GH insensitivity - Post-receptor defects. Note: Normal GHBP levels - Primary IGF-1 deficiency – synthesis or receptor Autosomal recessive GH elevated due to decreased or absent IGF-1 Does not respond to GH treatment... need recombinant IGF-1

Answer 5

- constitutional tall stature - genetic tall stature - syndromes of tall stature ---Kilnefelter ---Marfan ----Cerebral gigantism ---Homocystinura ---Beckwith-Wiedemann - XYY and XYYY syndromes

Answer 6

Pituitary gigantism Sexual precocity Thyrotoxicosis IDM

Answer 7

pituitary gigantism before epiphyseal fusion acromegaly after

Answer 8

Grow excessively rapidly, coarse features, large hands and feet with thick fingers and toes, and often frontal bossing and large jaws glucose intolerance or frank diabetes mellitus, hypogonadism, and thyromegaly

Answer 9

1. GH secreting pituitary adenoma or somatotrophs 2. constitutive activation of GH secretion as is sometimes found in the McCune-Albright syndrome 3. excess secretion of GHRH ectopic GH secretion (rare)

Answer 10

increased growth, advanced bone age, and, if occurring in early life, craniosynostosis

Answer 11

GH suppression test with OGTT 1.75g/kg oral glucose (max 75g) measure serum GH before and two hours after glucose administration GH should be <1 or 5 ng/L depending on resource

Answer 12

- GH axis: low IGF1, normal or high GH - insulin: low - cortisol: high - thyroid: sick euthyroid - hypogonadotropic hypogonadism - decreased leptin and oxytocin - increase ghrelin, peptide YY and adiponectin

Answer 13

- Breast development (mainly from E, but other factors too) - Areolae become more pigmented and erectile as development progresses - Enlargement of the labia minora and majora - Dulling of the vaginal mucosa from its prepubertal reddish hue to pink (due to cornification of the vaginal epithelium), - Production of a clear or slightly whitish vaginal secretion prior to menarche

Answer 14

Starts with testicular enlargement 2.5cm or 4ml Most of the increase in testicular size is due to seminiferous tubular development secondary to stimulation by follicle-stimulating hormone (FSH), with a smaller component due to Leydig cell stimulation by luteinizing hormone (LH)

Answer 15

Leydig cells are stimulated by LH (not FSH) so the testis does not grow as large as in normal puberty. (but they do enlarge)

Answer 16

local aromatase activity in adipose tissue

Answer 17

- indirectly stimulates IGF-I production by increasing the secretion of GH - directly stimulates IGF-I production in cartilage - stimulating maturation of the chondrocytes and osteoblasts, ultimately leading to epiphysial fusion

Answer 18

Girls reach peak mineralization between 14 and 16 years of age, whereas boys reach a later peak at 17.5 years

Answer 19

exercise-induced amenorrhea, premature osteoporosis, and disordered eating

Answer 20

Factors that increase Estrogen (& Tamoxifen) / Pregnancy Thyroid hormone administration & hyperthyroidism Phenytoin Cirrhosis HIV? Factors that decrease Hypothyroidism Nephrotic syndrome GH administration / Acromegaly Obesity & hyperinsulinemic states Exogenous androgens Glucocorticoids

Answer 21

Males: - LH stimulates the Leydig cells to secrete testosterone, and - FSH stimulates the Sertoli cells to produce inhibin. Inhibin feeds back on the hypothalamic-pituitary axis to inhibit FSH Females: - FSH stimulates the granulosa cells to produce estrogen and the follicles to secrete inhibin

Answer 22

Leptin is a necessary component of pubertal development in human beings but not a major stimulant to this development; leptin is necessary but not sufficient for pubertal development.

Answer 23

kisspeptin (KISS1) GRP54 (kisspepin receptor, G protein–coupled receptor 54) MKRN3 (precocious puberty) DLK1 (precocious puberty) LEP LEPR TAC3 TAC3 receptor

Answer 24

The adrenal cortex normally secretes the weak androgens dehydroepiandrosterone (DHEA), its sulfate, dehydroepiandrosterone sulfate (DHEAS), and androstenedione in increasing amounts beginning at about 6 to 7 years of age in girls and 7 to 8 years of age in boys

Answer 25

boys: hematocrit rises high-density lipoprotein (HDL) concentrations fall both boys and girls alkaline phosphatase rises normally during the pubertal growth spurt Serum IGF-I concentrations rise with the pubertal growth spurt, but IGF-I is more closely correlated with sex steroid concentration than with growth rate

Answer 26

1 year after peak growth velocity is reached and remain elevated for 4 years thereafter, even though growth rate is decreasing

Answer 27

Constitutional delay in growth and adolescence Hypogonadotropic hypogonadism Hypergonadotropic hypogonadism

Answer 28

Constitutional delay in growth and adolescence Central nervous system disorders - Congenital disorders of the hypothalamus or pituitary - Tumors - Other acquired disorders - Infection - Trauma - Irradiation Defects of the hypothalamic-pituitary axis - Isolated gonadotropin deficiency ---Kallmann syndrome ---Gonadotropin deficiency with normal sense of smell (Idiopathic Hypogonadotropic Hypogonadism) - Multiple pituitary hormonal deficiencies - Miscellaneous disorders ---Syndromes ---Chronic disease ---Weight loss ---Anorexia nervosa ---Increased physical activity in female athletes ---Hypothyroidism Genetic syndromes - Prader-Willi syndrome - Bardet-Biedl syndrome

Answer 29

Male phenotype - Klinefelter syndrome (gonadal dysgenesis) - Other forms of primary testicular failure (including chemotherapy, autoimmune, radiation, trauma) - Enzymatic defects of androgen production - Anorchia or cryptorchism Female phenotype - Turner syndrome(gonadal dysgenesis) - Other forms of primary ovarian failure (including chemotherapy) Pseudo–Turner syndrome Noonan syndrome XX and XY gonadal dysgenesis

Answer 30

Hypergonadotropic Hypogonadism primary testicular failure – seminiferous tubule dysgenesis decreased upper segment-lower segment ratios small testes developmental delay personality disorder

Answer 31

Onset of puberty is not usually delayed, because Leydig cell function is characteristically less affected than seminiferous tubule function in this condition and testosterone is adequate to stimulate pubertal development. Serum gonadotropin levels rise to castrate concentrations after the onset of puberty; the testes become firm and are rarely larger than 3.5 cm in diameter After the onset of puberty, there are histologic changes of seminiferous tubule hyalinization and fibrosis, adenomatous changes of the Leydig cells, and impaired spermatogenesis

Answer 32

46,XY otherwise normal a late fetal loss of the testes normal infantile male genital development, including Wolffian duct formation and Müllerian duct regression. The testes were presumably present in these patients early in fetal life during sexual differentiation, but degenerated after the 13th week of gestation for unknown reasons

Answer 33

isosexual precocity: feminization in girls and virilization in boys contrasexual precocity: feminization in boys and virilization in girls

Answer 34

- Constitutional - Idiopathic - Central nervous system disorders (including congenital defects) ---Tumors (Hypothalamic hamartoma, astrocytoma, glioma) ---Infection ---Trauma ---Radiation ---CNS disorders (static encephalopathy, low dose cranial irradiation, hydrocephalus) ---Following androgen exposure -Profound hypothyroidism

Answer 35

Males Gonadotropin-secreting tumors Excessive androgen production Testicular or adrenal tumors Virilizing congenital adrenal hyperplasia Premature Leydig and germinal cell maturation hCG secreting tumours Females Ovarian follicular cysts Estrogen-secreting neoplasms Severe hypothyroidism Granulosa cell tumour Males and females McCune-Albright syndrome Exogenous exposure

Answer 36

Lifestyle – weight loss is 1st line therapy in overweight/obese subjects OCPs: Raise SHBG -> decrease testosterone effects; may decrease ovarian hyperandrogenism; induces regular menses Metformin: induces regular menses; short term improvement of metabolic derangements in obese subjects Anti-Androgen: spironolactone – as adjuvant with OCPs and metformin

Answer 37

○ height standard deviation score (SDS) ≤ –2.25 (PES) ○ unlikely to permit attainment of adult height in the expected range

Answer 38

GH deficiency Turner syndrome ISS SGA with no catch up growth by age 3 yo SHOX haploinsufficiency CKD Prader-Willi

Answer 39

● GH deficiency ● GH resistance ● Malnutrition ● Hepatic failure ● Age (low in newborns, increases throughout childhood, peaks during puberty) ● Pubertal status ● Chronic disease and infections ● Pregnancy ● Thyroid function

Answer 40

i) Leri-Weill dyschondrosteosis (heterozygous defect) ii) Langer mesomelic dysplasia (homozygous defect) iii) Turner Syndrome

Answer 41

i) Mesomelia - shorter forearms and lower legs (with reductions in arm span and leg length compared with trunk) ii) Madelung deformity of the forearm (focal dysplasia of the distal radial physis) iii) Short 4th or 5th metacarpal or metatarsal iv) cubitus valgus (increased carrying angle of the arm) v) high-arched palate vi) scoliosis vii) micrognathia viii) muscular hypertrophy (reflected as a short, stocky appearance)

Answer 42

1) Patients has all 3 of the following: auxological criteria, hypothalamic-pituitary defect, and deficiency of at least one additional pituitary hormone 2) Newborn with hypoglycemia who does not attain a serum GH concentration above 5 μg/L and has deficiency of at least one additional pituitary hormone and/ or the classical imaging triad (ectopic posterior pituitary and pituitary hypoplasia with abnormal stalk)

Answer 43

○ Starting dose should be 0.16-0.24 mg/kg/week

Answer 44

IGF-1 should be maintained in normal range throughout growth hormone therapy growth

Answer 45

- Height velocity below -2SD over 1 year - Height velocity more than 1.5SD below mean sustained over 2 years

Answer 46

● Hypotension ● Drowsiness ● Dizziness ● Dry eyes or mouth ● Blurry vision

Answer 47

● flushing ● nausea and vomiting ● hypoglycemia

Answer 48

For those with ISS they can expect a 5 cm height gain over 5 years of treatment

Answer 49

tyrosine kinase inhibitor needed for life in CML patients This can sometimes affect growth hormone tyrosine kinase receptor and IGF-1 signalling pathway as well as chondrocyte action at the growth plate. Due to this many patients have short stature, although most have catch up growth once they hit puberty.

Answer 50

Arginine inhibits somatostatin

Answer 51

Alpha adrenergic agonists (clonidine), dopamine (levodopa), and exercise cause release of GHRH

Answer 52

Russell Silver syndrome

Answer 53

Adrenal insufficiency Inhibition of 11β-hydroxysteroid dehydrogenase 1 - 11B HSD1 catalyzes cortisone → cortisol in adipose tissue and liver and 11B HSD2 cortisol → cortisone in kidney. Evidence that GH indirectly (through IGF-1) modulates cortisol metabolism by decreasing 11B HSD1 activity (ie you have less cortisone → cortisol conversion), which if there is some semblance of decreased cortisol production, can lead to AI once you give GH

Answer 54

Malnutrition usually causes a drop in IGF-1. This occurs by decreasing availability of the GH receptor on the liver. Therefore malnourished patients do not respond to GH.

Answer 55

no period by age 16 yo

Answer 56

no menses for more than 3 cycles or more in someone who previously had cyclic menses

Answer 57

tumour(cranio) 1. Pituitary adenoma 2. Kallmann syndrome 3. Malnutrition 4. Anorexia/extreme weight loss 5. Sheehan syndrome 6. Trauma 7. TB 8. Meningitis/Encephalitis 9. History of radiation 10. LCH 11. Sarcoidosis

Answer 58

● 17,20-lyase deficiency ● CYP17a deficiency ● StAR mutation

Answer 59

A transient increase in the estradiol to testosterone ratio

Answer 60

i) Tall stature (and/or developmental delay) ii) Stigmata of liver disease (spider angiomas, jaundice, scleral icterus, etc) iii) Abdominal mass iv) Testicular mass v) Gynecomastia greater than 4 cm in size vi) Undervirilized male genitalia vii) Small firm testes ■ Early accelerated linear growth (aromatase excess) ■ Signs of renal disease

Answer 61

i) Galactorrhea (more likely prolactinoma, etc) ii) Readily increasing gynecomastia iii) Lack of pubertal progression iv) Exogenous estrogen exposure v) History of testicular trauma/injury or pituitary trauma or injury vi) Symptoms of other pituitary deficiencies vii) History of cryptorchidism viii) Duration longer than 2 years ix) Breast cancer findings

Answer 62

Cushing syndrome, hyperthyroidism, growth hormone excess, hyperpararthyroidism

Answer 63

ovarian, Sertoli cell, adrenal tumours

Answer 64

some estrogen effects (breast devel) amenorrhea ○ Elevated FSH/LH ○ Low estradiol ○ Deletion of Xp only or iso-Xq (deletion of Xp causing fusion of 2 Xqs)

Answer 65

○ Pituitary tumor ○ Hyperprolactinemia ○ Surgery or radiation ○ Autoimmune ○ Infections ○ Hypotensive event (Sheehan syndrome)

Answer 66

○ Functional hypogonadotropic hypogonadism (low weight, low estradiol) ○ Turner syndrome (Webbed neck, high FSH) ○ Noonan’s (murmur, low LH on stim) ○ Prader Willi or Bardet Beidl (obesity, low LH on stim) ○ XX and XY gonadal dysgenesis (virilized genitalia, Y chromosome material on FISH) ○ Primary gonadal failure (post-radiation, etc) (normal external genitalia/vaginal atrophy/lack of pubertal development, high FSH) ○ CHH (incomplete or no breast development, LH low on stim) ○ Multiple pituitary hormone deficiencies (midline defect, low LH on stimulation testing) ○ Intact hymen (hematocolpos, normal estradiol) ○ Complete AIS (no virilizing features, Y chromosome on karyotype) ○ PCOS (androgenizing features, elevated testosterone) ○ NCCAH (androgenizing features, elevated 17-OHP)

Answer 67

aromatase inhibitor (anastrazole) selective estrogen receptor blocker (tamoxifen)

Answer 68

■ Drugs Marijuana use Spironolactone Estrogen ■ Hyperprolactinemia ■ Hypogonadism ■ Hyperthyroidism ■ AIS (partial) ■ Excessive aromatase activity ■ Liver disease ■ Uremia ■ Testicular germ cell or Leydig cell tumors ■ Feminizing adrenocortical adenoma or carcinoma ■ hCG-secreting nontrophoblastic neoplasm

Answer 69

○ Spironolactone ○ Cimetidine ○ Ketoconazole ○ Estrogens ○ Anti-androgens ○ Growth hormone ○ GnRH analogue ○ 5 alpha reductase inhibitors ○ Marijuana ○ TCA ○ Ethanol ○ Heroin ○ Amphetamines ○ Anabolic steroids

Answer 70

factors that increase SHBG -Drugs: tamoxifen/anti-epileptic drugs -Untreated hyperthyroidism -Estrogen -Pregnancy factors that decrease SHBG -Exogenous androgens -Glucocorticoid therapy -GH treatment -Untreated hypothyroidism -Obesity -Hyperinsulinemic states

Answer 71

1. T or DHT binds to androgen receptor 2. Androgen/androgen receptor complex dissociates from Heat Shock Proteins and chaperone proteins, leading to a conformational change 3. Conformational change leads to formation of a homodimer with another androgen/androgen receptor molecule 4. Homodimer translocated to nucleus via binding to transport proteins, importins 5. Now in the nucleus, androgen/androgen receptor molecule binds to androgen response elements in DNA and interacts with protein coactivators 6. Initiates transcriptional activity

Answer 72

■ Withdrawal bleed ■ Catch down growth (GV decreases within 5 months after the start of therapy)

Answer 73

■ Sterile abscesses ■ Decrease BMD

Answer 74

a) LH predominance -pubertal (central puberty) that you should treat b) FSH predominance -slow/intermittently progressing central precocious puberty

Answer 75

At medium dose cranial radiation there is a chance of developing precocious puberty (central), however at a high dose individuals can develop LH and FSH deficiencies

Answer 76

Ovarian failure due to follicle depletion

Answer 77

AMH is representative of ovarian reserve. However inhibin B is present during the follicular phase if there is a dominant follicle. Therefore AMH s reflective of future fertility, but inhibin B and FSH are representative of current fertility ability.