1.
2 reasons why men are taller than women: 1. 7cm more on average during puberty, 2. begin to mature later so get more years to growth as a child (5cm more average).
2.
2 stages of McCune-Albright Syndrome: 1. Intermittent periods of breast development and vaginal bleeding (Gonadotrphin independent), 2. Central precocious puberty (gonadotrophin dependent). Give GnRH to stop pituitary.
3.
Adrenarche: Maturational increase in adrenal 17-ketosteroid production. Due to androgen secretion into plasma by adrenals mainly (in girls, later from ovaries, in boys from testes). Causes acne and pubarche (growth of pubic and axillary hair).
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Average age of onset of puberty: 11 in girls, 12 in boys
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Central precocious puberty: Usually idiopathy in girls, in boys 50%, otherwise secondary to CNS abnormalities-strong genetic background: congenital anomalies (hydrocephalus-if corrected can cause CPP later), tumors (brain tumors in girls), acquired (infections, surgery, irradiation)
6.
Classification of delayed sexual maturation: 1. Constitutional delay of growth and puberty (CDGP-most common),2. Secondary: chronic systemic illess (asthma, renal failure, CHD, CLD), steroid treatment, psychosocial growth disturbance, anorexia nervosa. 3,. Hypogonadotrophic hypogonadism (isolated gonadotrophin deficiency, multiple pituitary hormone deficiency, secondary to CNS tumors or cranial irradiation). 4. Hypergonadotrophic hypogonadism (Klinefleters nd Turner's Syndromes-testicular problems, small penis. Primary or secondary gonadal failure. Check phenotype). 5. Dysmorphic syndromes (Noonan's syndrome, Prader-Willi, etc)
7.
Classification of precocious sexual maturation: 1. Gonadotrophin-Dependent (True Precocious puberty, central precocious puberty-normal physiology occurs earlier than expected), 2. Gonadotrophin-Independent (Pseudoprecocious puberty-peripheral), 3. Variants of precocious sexual maturation (premature telarche, pubarche, adrenarche, etc).
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Clitoromegaly and Adrenarche: Increased adrenal production of sex hormones, gonadotrophin secretion is prepubertal. Clitoromegaly (virilization) in girls and phallic enlargenent in boys with excessive bone age maturation suggests excessive production of sex hormones due to CAH or adrenal tumor.
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Concerns in delayed puberty: Sinister underlying cause, fear that puberty won't occur, emotional and psychosocial upset of immaturity, esp with short stature (consider for induction of puberty), long term; reduced bone mineralization properly.
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Consonance of Puberty: Important clinical application. Close relatinoship between secondary sexual characteristics (pubertal signs) and pubertal growth spurt. If disconnected, should suspect abnormality.
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Delayed Puberty: Onset of puberty after 13yo in girls, 14yo in boys (some say 14/15).
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Diagnosis of gonadotrophin-dependent precocious puberty: MRI scan (not a CT, not an Xray, look at pituitary and hypothalamus area)
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Drug of choice for CPP: Gonadotrophin releasing hormone anaglogues
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Environmental signals to puberty: Nutrition, light, stressors, endocrine disruptors. Lead to hypothalamic signals
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First signs of pubertal maturation: Girls: breast budding (thelarche), boys: increase in testicular volume (gonadarche)
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Gonadotrophin independent precocious puberty: Adrenal disorders (tumors secreting sex steroids, congenital adrenal hyperplasia), gonadal disorders (ovarian cyst/tumors secreting sex steroids/estrogens, can mesure, Leydic cell tumors-testicular tumors), exogenous sex steroids (gels, black market pills, vaginal lubes), McCune-Albright Syndrome, Testotoxicosis
17.
Gonadotrophin-Dependent precocious puberty symptoms and signs: Pulsatile gonadotrophin secretion, especially overnight, LH:FSH>1, gonadal activation with sex steroid production, develop secondary sexual characteristics, normal consonance (link btwn hormone level and growth (accelerated in girls>boys), bone age acceleration (estrogens affect bone, activate bone plates), final height impairment. Always isosexual.
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Hypothalamic signals: Genes: familial, ethnic and gender, lead to neurotransmitter, neuropeptides, and receptor to signals. GnRH under strong influence from KISS1 neuron receptorss and GPR54 receptors. Starvation and reduced food stores cause inhibition of puberty.
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Increased growth hormone with precocious puberty: Normal growth appearance but end up short. Spontaneous.
20.
Isolated Premature Thelarche: Isolated cyclic breast inlargement, usually <2yo. Absence of other pubertal signs (pubarche, menarche usually) or behaviour problems. Normal growth and bone maturation, predominant FSH pulsality (GnRH predominant), development of follicular ovarian cysts.
21.
Kallmann's syndrome: Congenital hypogonadotrophic hypogonadism, anosmia (no smell), check but not with irritnt, synkinesis (mirrored movement), low gonadotropin, low olfactory bulb. Can become fertile later.
22.
Length of puberty in females: 4 years on average, 1.5-8years range. End: attenuating end of growth (<1cm/yr) and attaining remaining events.
23.
LH, FSH, and E2/T in pubertal stages: LH increases more than FSH but both increase. Ratio one of signs of puberty. Plasma estradiol/testosterone increases with stages.
24.
McCune-Albright Syndrome signs/symptoms: Fibrous dysplasia of skull and long bone, cafe-au-lait patches (not nice and round like neurofibromatosis, "coast of maine") with serrated edges, autonomous endocrine activity varied (precosciuous puberty, hyerthyroidism, hypercortisolism/Cushing, pituitary adenomas secreting GH/PRL, hyperparathyroidism.
25.
Menarche: Physiologic leukorrhea (white vaginal secretion, normal estrogen effect) precedes menarche by 3-6mos. Occurs about 2 years post telarche, usually in Tanner stage 4 at avg age of 13 (closer to bone age) with ethnic variability. Regular ovulatory menstrual cycles (ability to conceive) don't develop until 1-2y post menarche.
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Neurobiology in puberty: LH/GnRH active during beginning of gestation until gonadotropin active, both inactive after birth (residual effects might lead to neonatal erections) and then testosterone or estrogen active upon puberty.
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Obesity and early puberty: Increased Tanner score with increasing BMI
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Ovarian regulation axis: Hypothalamus-GnRH release-->pituitary gland-FSH and LH release-->ovaries0inhibin and estrogen release.
29.
Pathophysiology of McCune-Albright Syndrome: Gene mutatino for the alpha subunit of the G protein, stimulating cAMP formation, doesn't need ligand anymore, g protein activated by g-hormone to receptor, phosphorylation activates the enzyme. Activatino of receptors that operate with a cAMP dependent mechanism. Somatic mutatino occurs early in embriogenesis in various tissues.
30.
Peripheral signals that lead to puberty: Leptin, Ghrelin, IGF-1insulin, sex steroids. Lead to hypothalamic signals. Ex: one time injection of sex steroids "prime" monkeys to begin puberty. Obesity leads to earlier puberty. Decreased laptin-->no puberty.
31.
Precocious Puberty vs Early Puberty: Precocious: onset before 8 in girls, 9 in boys. Early: onset between 8-9 in girls and 9-10 in boys.
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Premature pubarche: 6-8yo, early pubarche with or without axillary hair, puberty occurs at normal time, slight groth spurt and advance in bone maturation, final height prognosis not compromised.
33.
Primary hypothyroidism: Gonadotrophin dependent, look at thyroid axes.
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Pubarche: Usually occurs about 6 months after telarche but precedes telarche in some.
35.
Puberty vs Adolescence: Adolescence is physical, psychological and social transition. Puberty is the attainment of final height and fertility.
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Pulsatile GnRH secretion: Beginning in neonate, no change in daytime levels until puberty when increase of estrogen comes in, increase of LH secretion at night-cyclical in women. Infants have a similar pattern due to forming ovaries may cause "minipuberty". Not an explanation for puberty because still present in Turner's syndrome.
37.
Sexual Dimorphism: Usually idiopathic in girls, about 50% due to secondary lesions in CNS, look for organic causes, increase in LH:FSH.
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Signs/Symptoms of Delayed Puberty: Absence of a clear pattern of pulsatile gonadotrophin secretion (70% no response to stimulation), prepubertal LH and FSH levels, development of secondary sexual characteristics, normal consonance, bone age delay, final height is not impared except if severe degree of delay.
39.
Signs/Symptoms of Gonadotrophin independent precocious puberty: Sex steroid production from gonads/adrenal gland/exogenous source, GnRH/gonad levels low-Suppressed LH and FSH levels, secondary sex characteristics of virilization, growth acceleration, bone age acceleration with final height impairment. Isosexual or contrasexual/virilized depending on hormone secreted by ovarian tumor.
40.
Size of testes: Stage 1: 2mL or smaller, stage 2: 4-6mL, stage 3: 8-10mL, stage 4: 12-15, stage 5: >15mL. Measured with orchinometer. Left testicle usually larger.
41.
Stage of pubertal growth spurt: Girls: B2-3, Boys: G3-4, 10mL testicular volume.
42.
Tanner stage 2 by age and race: African americans higher than whites at all ages, levels off by age 12. By age 7, 27.2% have had telarche or pubarche.
43.
Tanner's stage 1 of girls' puberty: Prepubertal, no breast tissue, no pubic hair.
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Tanner's Stage 2 in boys' puberty: Enlargement of testes to 4mL, redness of scrotum, a few darker hairs at the penile base.
45.
Tanner's stage 2 in girls' puberty: Areolar enlargement with breast bud, a few darker hairs along labia. Height spurt begins.
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Tanner's stage 3 in girls' puberty: Enlargement of breast and areola as single mound. Curly pigmented hairs across pubic area increased. Peak of height spurt.
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Tanner's stage 3 of boys' puberty: Lengthening and thickening of penis, further enlargement of testes to 6-10mL. Curly pigmented hairs across pubic area.
48.
Tanner's stage 4 in girls' puberty: Projection of areola above breast as double mound. Skipped in many girls. Small adult configuration, contour same as adult but distributed less.
49.
Tanner's stage 4 of boys' puberty: Broadening of penis glans, growth of testes to 10-15mL. Small adult configuration of pubic hair. Growth stimulated by testosterone. Peak of height spurt.
50.
Tanner's stage 5 of girls' puberty: Mature adult breast with single contour. Adult pubic hair distribution. Menarche occurs, growth velocity decline.
51.
Tanner's Stage 5 of puberty: Adult size and function of genitals, adult configuration of pubic hair. Apex of strength spurt.
52.
Tanner's Stage I in boys' puberty: Prepubescent, Genitals 2mL volume, no pubic hair.
53.
Telarche: Growth of breasts. First pubertal sign in most but not all girls. Asymmetric as a rule.
54.
Testicular regulation Axis: Hypothalamus-GnRH release-->pituitary gland-FSH and LH-->testes-inhibin (Sertoli cells) and testosterone (Leydig cells)
55.
Testotoxicosis: Occurs only in boys, autosomal dominant. Gain of function of LH receptor. Normal consonance. Extreme degree of virilization compared to testicular enlargement. Prepubertal (suppressed) values of FSH and LH, failure to respond to GnRH analogue treatment because not central, st needed later, due to a mutation in LH receptor with constant activation of G protein even ithout a ligand. More testosterone produced, final height compromised behavior "disturbing".
56.
Treatment of gonadotrophin-dependent precocious puberty: Consider therapy (depends on age of child, speed of process, expected final impairment, psychological consequences), DepoGnRH analogue-accelerate if sudden (so menses may appear on first dose) but if constant, suppresses pituitary secretion. Inject every 28d, never late.
57.
Types of Early Pubertal Development: Unsustained Central Precocuious Puberty (CPP-telarche comes and goes), Classical CPP (fully functional reproductive adult at age 5-6), slowly progressive CPP (growth and other indicators at normal time)
58.
Types of Late or Absent Puberty: IHH (idiopathic hypogonadotropic hypogonadism normally attains normal height but may be susceptible to future osteoporosis but no further sequelae)-classical (flatline), constitutional delay, adult-onset IHH
59.
Variants of precocious sexual maturation: Isolated premature thelarche (Usually in small girls, transient, may find follicle in ovary but etiology unknown, won't progress to full puberty), Isolated menarche(rare, r/o child abuse, UTI, FB, sarcoma), premature adrenarche (look for clinical signs, higher risk for PCOS), unclassified forms
60.
What are the possible triggers for puberty: 1. Decreased sensitivity of HPG axis to sex steroids (less sensitized negative feedback)
2. Decreased inhibition of HPG axis by higher cortical centers.
