CMN 572 - Exam #4

Normal puberty in BOYS

1st sign of puberty in males begins between 10-12yo with TESTICULAR GROWTH Growth spurts 2 years earlier in girls Gynecomastia common in younger boys and disappear within 2 years 1. growth testes, change in voice, penis length, pubic hair 2. growth spurt peak 3. change in body shape 4. facial and underarm hair

Steps to dx delayed puberty

1st: XRAY left hand and wrist to obtain bone age. Delayed bone age if <12yo. 2nd: check labs if bone age >12yo or with no physical signs of puberty (FSH, LH, testo, karyotype). Elevated gonadrotopins means primary hypogonadism OR testicular failure (most common cause of hypogonadism is Turner syndrome and Klinefelter). Constitutional growth delays or being a "late bloomer" is the MOST COMMON CAUSE OF DELAYED PUBERTY Primary hypogonadism in girls: need eval if no pubertal signs by 13yo or no menarche by 16yo. Can be primary or secondary amenorrhea. Most common cause is Turner Syndrome. Primary hypogonadism in boys: needs eval if no secondary characteristics by 14yo, most common cause is Klinefelter syndrome **Hypogonodal pts will be placed on estrogen or testo to help prevent osteoporosis**

Definition of CKD

3 or more months of either kidney damage or eGFR <60 kidney damage: albuminuria, kidney biopsy findings, abnormal imaging low eGFR increases risk of CVD, HTN, bone disorders, anemia, mortality and ESRD

Precocious puberty in girls occurs if secondary characteristics are noted before what age in whites and what age in blacks? What about boys?

8yo in whites and 7yo in blacks More common in girls than boy, occurs between 6-8yo often due to obesity In boys consider precocious if they appear before 9yo

Testicular cancer screening for adolescents

AAP supports testicular examination for hernia, varicocele or epididymitis USPSTF does not recommend self or MD testicular screening

Blood pressure screening for adolescents

AAP supports to check annually USPSTF does not support

Lipid levels in adolescents

AAP: 9-11yo universal screen with nonfasting 12-17yo: fasting profile if parent with dyslipidemia, or high risk 18-21yo: non fasting nonHDL cholesterol or fasting profile in all once USPTSF do not recommend screening

Anemia screening for teenages

AAP: assess annually for RFs (diet low in iron, hx of IDA, excess menstrual periods. Screen with Hgb/Hct at minimum. CDC recommends all nonpregnancy women every 5-10 years starting in adolescence.

Scoliosis screening for teenagers:

AAP: female starts at 10yo and 12yo Males ONCE at 13 and 14yo USPSTF does not support asymptomatic screening

Obesity screening for teenagers

AAP: screen BMI annually USPTSF: Screen children >6yo for obesity + refer for intervention (behavioral)

PREMENOPAUSAL ABNORMAL UTERINE BLEEDING general considerations

AUB with descriptive terms denoting pattern of bleeding (heavy, light and menstrual. intermenstrual) AND etiology (acronym PALM-COEIN - polyp, adenomyosis, leiomyoma, malignancy, hyperplasia, coagulopathy, ovalutary dysfunction, endometrial, iatrogenic, and not yet classified). Teenagers with AUB: usually from anovulation d/t immature HPA axis and represents normal physiology. Once regular menses occurs, ovulatory dysfunction accounts for most AUB Women 19-39yo causes: pregnancy, structural lesions, anovulatory cycles, hormone use, endometrial hyperplasia

Psychosocial development in teenagehood

Adolescence is a period of progressive individualization and separation from family. Early adolescence (10-13yo): rapid growth and secondary sex, body image, self concept, esteem, more comfortable with members of same sex, cannot conceptualize future, think concretely. Vague and unrealistic professional goals Middle adolescence *14-16yo: teens more comfortable with new bodies, intense emotions and wide mood swings, formal operations and abstract thinking, new sense of omnipotence and belief the world can be changed merely by thinking about it. Think they don't need sexual protection, self centered, narcisistic relationships, peers determine standards for identification Late adolescence >17yo: less self centered, more caring of others, social shifts to peer to individual, dating more intimate, abstract thinking, plans for future, idealism period, rigid concepts of right and wrong

Boy SMR for Penis/scrotum (stage 5) and pubic hair (stage 5)

Adult genitalia, adult scrotum, inverse triangle hair to medial thigh

What is the definition and prevalence of cryptochordism?

Aka undescended testes prevalent in 2-4% of full term male newborns and 30% in preemies, descends after 6 months - intervention considered after 6mo

Classifications of CKD

Albuminuria categories: A1: <30mg/g (normal to mild) A2: 30-299mg/g (moderate) A3: >300 (severe) eGFR: G1: normal or high =<90 G2: mild dec 60-89 G3a: mild to mod 45-59 G3b: mod to severe 30-44 G4: severe 15-29 G5: kidney failure <15

How to take menstrual hx for all patients and for patients reporting HMB (heavy menstrual bleeding)

All pts: menarche age, cycle length, duration of bleeding, quantity of bleeding, menstrual products, first day of LMP, dysmenorrhea Pts reporting HMB: soaking through pads/tampon in 1 hr for 2-3hrs in a row?, blood clots>1inc in diameter (quarter size), double protection with pads and tampons, flooding, gushing, accidents and leaking, dx with anemia?

S/s of precocious puberty in boys

Appearance of pubic hair is the MOST COMMON sign Examination of testes is a critical component of the eval Central precocity: testes enlarge >2cm Gonadotropin-independent causes: testes the same size Tumor or testes: asymmetrical or unilateral testicular enlargement.

Disorders of sexual development

Arise from gonadal differentiation, steroidogenesis or androgen action. Many evidence in newborn period, some present during pubertal development. Gonadal differentiation: testes or ovaries do not develop and causes ambiguous genital or sex reversal Deficiency of 21-hydroxylase: (DHT): enzyme in cortisol and aldosterone: overproduction of adrenal androgens causing congenial adrenal hyperplasia Disorders of androgen action: androgen insesitivity syndrome cause by inactivating mutation in receptor gene- normal appearing female external genitalia with a short vagina, absent mullerian sctructures and absent wolffian structures: gonads intra abdominal or inguinal, tx surgery for inguinal hernia reveals testes in hernia sack

What are the four interventions to reduce CKD progression?

BP control <140/90, ACEi/ARBs for albuminuria and HTN, DM control, correction of metabolic acidosis

Lab studies for delayed puberty in boys

Bone age >12 years = get LH and FSH levels If increased gonadotropins for bone age: PRIMARY hypogonadism or testicular failure If decreased gonadotropins for bone age: Possible CENTRAL hypogonodism = requires further eval = assess pituitary hormone deficiency, chronic illness, undernutrition, hyperprolactinemi, CNS abnormalities

Girl SMR for breasts (stage 4) and pubic hair (stage 4)

Breasts enlarged and greater amount, nipple including the areola forms a SECONDARY MOUND on breasts Pubic hair: adult type now, but covers area smaller than adults, no pubic hair on inside of thighs

Girl SMR for breasts (stage 5) and pubic hair (stage 5)

Breasts fully developed, areola receded into general contour of breasts Pubic hair: inverted triangle pattern

Girl SMR for breasts (stage 3) and pubic hair (stage 3)

Breasts more distinct, no separation between contours of breasts Pubic hair: darker, coarser, curlier, sparsely spread

Diagnostic testing for precocity in boys

Central: cranial MRI should be obtained to eval for CNS abnormality Peripheral: lab studies no consistent with CAH: imaging useful to detect hepatic, adrenal and testicular tumors.

What are the differential dx of central and peripheral PP?

Central: often idiopathic, any cause of peripheral PP, tumor (CNS), post-CNS trauma or damage (surgery, chemo, radiation, malformations, infections) Peripheral: tumors (hcg secreting, gonodal, adrenal), sex steroids, congenital adrenal hyperplasia, severe acquired hypothyroidism, mccune-albright syndrome, refeeding after severe malnutrition during early development Other disorders: Premature thelarche, premature adrenarche, obesity With precocious puberty, family NP will begin basic work-up and refer to pediatric endocrinology!!!!!

Why should providers watch growth charts for unexpected changes?

Children precocious puberty may be tall for their age, but their adult height is often shorter than expected

STD screening in adolescence according to CDC

Chlamydia: screen annually if <25yo if sexually active, retest 3 mo after tx. Gonorrhea: same as chlamydia + screen 3-6 mo if increased risk Herpes simplex virus: HSV serology in men and women coming for STD eval especially with multiple partners HIV: Screen all teenagers who seek eval and tx for STD. Screen sexually active MSM annually if status unknown or multiple partners Syphillis: screen sexually active MSM at least annually and q 3-6mo if inc risk. According to USPTS: screen all active females for chlamydia and gonorrhea, do not screen for HSV, screen teenagers >15yo for HIV at least once, screen for syphillis if inc risk (MSM, HIV, etc) AAP recommends screening for HIV between 15-18yo once and preserve confidentially.

What do clinicians need to know about assessing AUB in women?

Clinician must carefully assess: symptomatology during the consult to enable accurate diagnosis and management of HMB. Must elicit need for current or future fertility in routine history-taking to facilitate informed decision making of the women seeking treatment. Must exclude anatomical disorders like PALM (polyps, adenomyosis, leiomyomas, malignancy) and non anatomical like COEIN ( coagulopathies, ovulatory dysfunction, endometrial, iatrogenic, not known). Treatment Options: can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Antifibrinolytics NSAIDs preparations oral contraceptive pills oral, injectable and intrauterine progestogen SERMs

Progesterone only pill for tx of AUB

Cons: associated with irregular and unpredictable blood loss so it is not recommended for tx of AUB/HMB, however if no options are acceptable or safe - trial of a POP may be appropriate

What are the two dominant RFs of CKD?

DM and HTN testing and tx differes related to eGFR and UACR

Tx of premenopausal pt with AUB

Depends on etiology Pts with AUB secondary to submucosal myomas, infection, early abortion, thrombophilias or pelvic neoplasms: may required definite tx

Behavioral screenings for teenagers

Depression: AAP (PHQ2 starting at >12yo), USP 12-18yo for MDD only if appropriate systems in place. Substance use: AAP screen youth >11yo with CRAFT tool, USP no screening. Tobacco use: screen >11yo. USP clinicians should provide intervention, education and counseling

Goals of guidelines of adolescence screening

Deter teenagers from participating in behaviors that jeopardize health Detect physical, emotional and behavioral issues and intervene Reinforce and encourage behaviors that promote healthful living and provide immunizations against IDs Teenagers between 11 and 21yo have ANNUAL routine health visits including: complete physical, VS (height and weight on growth chart), BP, acne, acanthosis, nevi, tattoos, piercings, signs of abuse/neglect, scoliosis, assess SMR, breast examination for disorders, visual inspection of genitalia, scrotum, etc

Tx plan for AUB

Determine hemodynamic status(pallor, tachy, murmur) and anemia degree Remember it takes 2 years for teenagers to regulate menses (82%) Perform pelvic exam Refer to GYN/hematology Hx: menstrual calendar, assess for anemia and clotting if severe bleeding (von will) Initial labs: UPT, CBC, PT/PTT, TSH, FIBRINOGEN, IRON General meds: iron, NSAIDs, OCPs, antiemetics d/t estrogen causing nausea If not bleeding: use OCP (depo-provera) or noethindrone If bleeding: monophasic OCP 30-50ug ethinyl estradiol/0.3mg norgestrel If estrogen contraindicated: norethindrone acetate 5-10mg Severe cases: hospitalized for Hg <7 and or orthostasis

Cervical biopsy and endometrial sampling for AUB

Determines if hyperplasia or carcinoma is present Endometrial biopsy/sampling: done in pts with AUB that are older than 45yo or in younger pts with unopposed estrogen exposure or failed mgmt Abnormal pap smear or gross cervical lesion visualized: colposcopy directed biopsy and endocervical curettage indicated

Treatment of delayed puberty

Estrogen alone at lowest dose available (oral or topical) Increase dose gradually every 6 months 18-24 months after initiation: add progesterone (cyclically or continuously) May change to estrogen-progestin combined pill if desired. Need progesterone therapy to counteract effects of estrogen on uterus (hyperplasia). Estrogen necessary to promote mineralization and prevent osteoporosis.

Combined oral contraceptive pill for tx of AUB

Estrogen and progesterone given for 3 weeks followed by pill free week - hormonal withdraw bleed. Can be tricycled without pill free week to reduce menses and volime of blood loss. Produces reduction in blood by 50%. Good for women experiencing frequent and irregular bleeding. Causes bloating, breast tenderness and mood changes. CI in BMI >35, smokers >35, women with HTN, vascular dx, migrain with aura, current or recent breast cancer hx, personal or family hx of PE/VTE, coagulation mutation Caution because estrogen causes clots, stroke, cv disase, breast cancer and in BF women, it decreases milk supply In absence of RF, women can used COCP until menopause if desired.

Girl SMR for breasts (stage 2) and pubic hair (stage 2)

First sign of development: breast budding, palpable, aerola a little bigger Pubic hair: small amount of LONG pubic hair along vaginal lips

How do we know puberty is occurring early in girls and boys?

Girls: breast development, rapid growth acceleration, early menses usually around 2 years after breasts Boys: penile and testicular enlargement, increase muscles and body hair, rapid growth acceleration and voice deepens.

Central and Peripheral precocious puberty in girls

GnRH HPA activation, increase in gonadotropin secretion, inc in sex steroids, idiopathic or secondary to CNS abnormality (abscess, chemo, radiation, surgical trauma, arachnoid cyst, hydrocephalus, hematoma, tumors). Peripheral: LH response to GnRH stimulation is suppressed by feeback of the HPA axis. Girls with ovarian cyst or tumor will have elevated levels of estradiol. If girl presents with pubic or axillary hair and no breast development: obtain androgen level and 17-hydroxyprogesterone. S/s: breast development into pubic growth and menarche, accelerated growth being tall for age, final adult stature might be compromised. Labs: draw estradiol to r/t ovarian tumor or cyst Advanced bone age: further lab tests required. Random FSH/LH may still be in prepubertal range - if so, document maturity of HPA axis depends on LH response to GnRH agonist Tx for CENTRAL: GnRH analogues that downregulates pituitary: LEUPROLIDE once a month IM or HISTRELIN subdermal implant annually. Final height increase as a result of slowing skeletal maturation. After stopping tx, pubertal progression resumes and ovulation and pregnancy is possible. Tx for PERIPHERAL: depend on cause, no intervention for ovarian cyst, but obtain serial US to document regression. Surgical resection and chemo for rare adrenal or ovarian tumor.

Puberty characteristics

HPA axis activation in late childhood Timing due to genetics and ethnicity(50%), nutrition, general health. Inhibition of GnRH removed - pulsatile LH and FSH = ONSET OF PUBERTY Pulse frequency and amplitude of LH and FSH increases causing to stimulate gonads to produce estrogen/testo Females: FSH causes ovarian maturation and estradiol secretion. LH causes ovulation, CL formation and progesterone secretion. Inc in estradiol causes maturation of genital tract and breasts. Males: LH causes testes to secrete testosterone and produce spermatocytes - inc >20fold in testo correlating with physical changes and skeletal maturation

Why treat central PP in children?

Halt progression of premature sexual development and slow linear growth and skeletal maturation to improve childs final adult height and promote psychosocial wellbeing

AUB dx depends on what?

Hx of the duration and amount of flow, associated pain, relationship to LMP, presence of blood clots and degree of inconvenience. Hx of pertinent illness (infections) and emotional stressors (thyroid) Hx of medications (coumadin, hormones) or herbal medicines (gingko, motherwort, ginseng) Hx of coagulation disorders (family or individual hx) Complete physical (eval excess weight and signs of PCOS, thyroid disease, insulin resistance, bleeding disorders) Pelvic exam (rule out vulvar/vaginal lesions, pregnancy, uterine myomas, adnexal masses, adenomyosis, or infection)

Initial work up for precocious puberty

Hx, growth chart, XRay of left hand/wrist to check bone age (assess how quickly puberty is progressing), LH, FSH, estradiol, testosterone labs. Elevated Estradiol points to ovarian cyst or tumor If blood tests shows central precocious puberty then ORDER MRI of brain to check for underlying abnormalities of pituitary gland

Injectable progesterone for AUB tx

IM q 12 weeks, depot medroxyprogesterone, alternative to PO or IUD. Induces amenorrhea in 50% of women. Excellent for women experiencing frequent and irregular HEAVY bleeding. SE: weight gain, greasy skin, acne, bloating. Causes loss in bone density with long term use.

GnRH tx for AUB

IM, subQ or intranasal - short term use only Synthetic peptides 5mg tab 3x/d from day 5-26 Causes medical menopause - amenorrhea in 90% of women Tx of uterine fibroids (leiomyomas) prior to surgical intervention SE: flushing, vaginal dryness, ha, dec libido

Levonorgestrel-releasing system for AUB (IUD)

IUD, adrogenic progestogen, acts on local endometrial to prevent proliferation and impact frequency of ovulation, dec blood loss by 96% after 1 year of use, stays in place for 5 years, excellent contraceptive when in situ and advantage of fit and forget method, no compliance needed, reduces dysmenorrhea. SE: bloating, breast tender, mood changes CI: pregnancy, unexplained vaginal bleeding and uterine sepsis Caution with SLE, severe liver dx, breast cancer, leiomyomas and fibroids Counsel women on complications: unscheduled bleeding in the first 3-6mo, daily spottings will settle, 1 in 5 women will have ongoing bleeding d/t long term progesterone and urine fragility, infection risk 3 weeks after insertion, do no use tampons, vaginal discharge (seek medical care), expulsion risk in the first 6 weeks higher in nulliparous women, check threads by self-exam on regular basis and have speculum 6 weeks after insertion. 1:1000 cases cause perforation, infection if <4weeks PP, seek care if cramps no eased with OTC analgesics. No visible threads: US and ABD xray to r/o perf

Teenagers transition into adult care

Incorporates education, guidance, stepwise planning, pts need to be actively involved in process AAP key components: provider readiness(assess pt for transition readiness), family readiness, patient readiness, adult care model implement (communication between pediatric and adult care providers)

What labs are necessary to eval for cryptochordism?

Infants between 2-6 months: measure LH, FSH, inhibin B and testosterone to determine if testes are present After that, get hCG stimulation test to confirm presence or absence of functional abdominal testes. Dx for cyrpto in normal appearing male ONLY CONSIDER AFTER POSSIBILITY CHILD IS FULLY VIRILIZED FEMALE WITH PONTENTIALLY FATAL SALT LOSING Cogenital Adrenal Hyperplasia HAS BEEN RULED OUT.

What are the major risks of untreated cryptochordism?

Infertility and testicular malignancy - 5-10x greater than normal cancer risk = changes occur after 6 months of undescended testes Unknown cause, but abnormalities in the HPA axis, intrinsic testicular development defects and androgen defects predisposes.

Anovulatory AUB/DUB characteristics

Irregular cycles, short cycles with scanty flow or perior of amenorrhea caused by alteration in HPA axis Corpus luteum not formed - no progesterone - inc estradiol - inc endometrial growth - inc necrosis and bleeding (heavy bleeding) Prevalence: 95% of DUB in teenagers due to anovulation

Diagnostic criteria for CKD

Kidney function abnormalities present for more than 3 months with health complications. eGFR<60, ACR>30 and markers like 1+ hematuria, kidney biopsy, polycystic kidney dx, imaging Remember that normal GFR varies with AGE, SEX, BODY SIZES and declines with age CKD epi creatinine equation is the most accurate and least biased method to estimate eGFR

Boy SMR for Penis/scrotum (stage 4) and pubic hair (stage 4)

Length and breadth of penis is bigger, well developed glans, scrotal skin darker adult hair but covers areas smaller than adults, not thigh spread

Central hypogonadism eval, labs and imaging

Low gonadotropin levels Determine if functional or permanent hypogonadism Labs: id chronic diseases and hyperprolactinemia Obtain cranial MRI

Motivation interviewing for teenagers

Majority of morbidity and mortality is preventable r/t unhealthy behaviors. Anticipatory guidance not helpful in this group. MI: effective for tobacco use, substance use, T1D, - counseling style that guide pts towards behavior change by helping solve ambivalence. MI promotes collaboration pt/provider with pt deciding goals to achieve. 1st step: assess readiness for change using 0-10 scale using change talk (hallmark of MI). Avoid: asking why is not important (elicits defensiveness). Roll with resistance and righting reflex - provider rolls with pts goals and reflect on challenges. Express empathy, meet the patient where they are in the process, listen reflectively, avoid confrontation, and roll with resistance. Stages of change: precontemplative, contemplative, prep, action. Medical instability: MI not appropriate.

Safety in patients with CKD

Medication dose adjustments necessary based on eGFR If lactic acidosis, d/c or briefly hold: RAAS blocks, nsaids, diuretics, metformin NSAIDs cause AKI, long term NSAIDs inc rate of CKD Inquire about OTC meds and educate about NSAID harm (can cause interstitial nephritis, htn, edema,hyperkalemia) - avoid if eGFR<30 Caution with CKD and RAAS blocking agent and/or diuretics Discontinue metformin if GFR <30 and caution for pts eGFR 30-45. Not recommended for creatinine >1.5 in men and >1.4 in women = risk of lactic acidosis Minimize contrast used. IVF 1ml/kg/hr 1 hr to procedure and continue for 3-6hrs post, measure kidneys 48-96 hours after procedure

Mild AUB treatment

Mild: duration of heavy bleeding <3mo with normal Hgb Observe, keep menstrual calendar, antiprostaglandin meds to decrease menorrhagia

Tx of moderate AUB

Moderate: menses heavy/frequent q 1-3 weeks + mild anemia If NOT bleeding: cyclic OCP like medroxyprogesterone or norethidrone acetate If BLEEDING: use taper method of monophase OCP to stop bleeding (30mg ethinyl estradiol/0.3mg norgestrel): 1 pill q 6 hr for 2 days then 1 pill q 8hrs for 2 days then 1 pill q 12 hrs for 2 days then 1 pill daily for 3 days - then open new 21-day pack and take 1 per day Give nausea medicine with this medicine to decrease nausea (phenergan) OCP for 3-6mo If estrogen is contraindicated, use norethindrone acetate 5-10mg daily

Girl SMR for breasts (stage 1) and pubic hair (stage 1)

No breasts, no pubic hair

Delayed puberty in girls prevalence and diagnosis

No puberty signs by age 13 or menarche by 16yo Primary amenorrhea: absence of menarche Secondary amenorrhea: 6 mo or more without a period after already established. Most common cause: constitutional growth delay. Other causes: hypogonadism or anatomic. Growth pattern: short stature, normal growth velocity, delay skeletal maturation Timing of puberty: commensurate to bone age, not chronological age Other causes: hypothyroidism Primary hypogonadism: primary abnormality of ovaries; Turner syndrome most common, lacks secondary X chromosome; adrenarche signs present Central hypogonadism: HPA deficiency (GnRH, FSH or LH): can be reversible, caused by stress, undernutrition, prolactinemia, excess exercise, chronic illness, signs of adrenarche usually present

Normal menstrual cycles in girls

Normal menarche between 11-14yo, average 12.5yo Can start as early as 10year and as late as 16yos Cycle length normal 21-45days and lasting as much as 7 days 1. breast budding 2. pubic hair 3. growth spurt peak 4. first period 5. underarm hair 6. body shape change 7. adult breast size

Oral progesterone for tx of AUB

Oral pill (norethisterone: most commonly used) 5mg tab 3x/d from day 5 to 26, reduces blood loss in 80% of women Only prescribed as short term measure (for a holiday or important event)

What is the definite tx for cryptochordism?

Orchidopexy performed by 6-12 months of age - decreases infertility and cancer risk

Hormonal tx for AUB

Ovarian hormones act on endometrial function Progesterone act on secretory phase of MC No pregnancy: corpus luteum regresses, progesterone declines rapidly, influx of inflammatory mediators = menstruation. Maintenance of progesterone limits endometrial inflammation and prevents menstruation, therefore, the most effective medication for AUB is hormones (limits fertility during tx)

Boy SMR for Penis/scrotum (stage 3) and pubic hair (stage 3)

Penis increases in length, small increase in breadth. Scrotum bigger. Hair spreads over pubic symphysis, darker and coarser, more curly

Boy SMR for Penis/scrotum (stage 1) and pubic hair (stage 1)

Penis/scrotum: genitalia increase slightly, but not change in appearance Pubic hair: none or just fine velus

Clinical evaluation of delayed puberty in girls

Pertinent hx (start of puberty, exercise level, nutrition, stressors, sense of smell, chronic illness, family hx) Assess appropriateness of height and weight on chart Physical exam for body proportions, breasts and genitalia Pelvic exam or US for primary amenorrhea Obtain BONE AGE X-ray: obtain this 1st!! Bone age attained <12yo with pubertal onset focus on finding cause of bone age delay. If short and normal growth velocity: constitutional growth delay likely Abnormal growth rate: eval for causes of growth delay (FSH and LH not helpful) Bone age attained >12yo + minimal or no signs of puberty on physical exam: OBTAIN FSH AND LH LEVELS Increase FSH/LH with primary ovarian failure Decreased FSH/LH with central hypogonadism Elevated gonadotropins: karyotype to eval for Turner syndrome

Premenopausal Abnormal Uterine Bleeding

Pregnancy should always be ruled out Eval depends on age and RFs Normal bleeding average of 5 days (2-7days) ~40mL loss per cycle Menorrhagia: >80mL and anemia Metrorrhagia: bleeding between periods Polymenorrhea: bleeding more often than 21 days Oligomenorrhea: bleeding less frequent than 35 days

What labs are needed for AUB?

Pregnancy, CBC, thyroid Coagulation studies for teenagers with heavy bleeding or adults with a positive screening hx (18% of women with severe merrhagia have coag dx) Vaginal or urine samples: PCR and culture to r/t chlamydia - cervical cytology should be obtained for chlamydia

benign variants of precocious puberty

Premature adrenarche (benign): early development of pubic hair, axillary hair, acne, body odor with normal linear growth and no or minimal bone advancement: labs to differentiate benign premature from late onset CAH and adrenal tumors Premature thelarche, occurs most commonly in girls younger than 2 years, isolated breast development without other signs of puberty, present since birth, waxes and wanes in size, uni or bilateral, tx with parental reassurance regarding self-limited nature of condition, observation of child q few months indicated: ONSET OF THELARCHE AFTER AGE 36MO or with other associated signs: REQUIRES REFERRAL.

True hypogonadism in boys can be either primary and central. What are the differences between primary and central hypogonadism in boys?

Primary due to testicular malfunction such as anorchia, klinefelter, enzymatic defect, inflammation or destruction of testes after infection, autoimmune, radiation or tumor. Central due to pituitary of HPA axis insuffiency. Multiple hormones or isolated hypogonadotropic such as Kallmann syndrome without abnormalities in smell. Other causes: hyperprolactinemia, LH or FSH deficiency, anterior pit lesions, infection, prader willi, laurence moon syndrome.

Delayed puberty with adequate breast development + amenorrhea evaluation:

Progesterone challenge to determine if sufficient estrogen is being produced and eval anatomical defects. Adequate estrogen: pt will withdrawal bleed 5-10days after progesterone Estrogen deficient or anatomical defect: pt have little to no bleeding; eval similar to those with delayed puberty MOST COMMON CAUSE OF AMENORRHEA WITH SUFFICIENT ESTROGEN: PCOS

Clinical eval of delayed puberty in boys

Pt hx: onset of puberty, testicular descent abnormalities, chronic illness, nutrition, sense of smell, family hx of delayed puberty Physical Exam for body proportions (hypogonadism will see decrease upper proportion), height, weight, pubertal stage, testicular location and consistency (testes <2cm in length or <4cm using prader beads = pre-pubertal), testes symmetry (>2.5 cm or >4mL = puberty onset) Xray of left hand and wrist to assess bone age = FIRST STEP IN EVALUATING A BOY WITH DELAYED PUBERTY (bone age delayed related to chronological age and growth velocity normal = constitutional delay dx)

Dx and prevalence of PRECOCIOUS PUBERTY in girls

Puberty development younger than age limit set for normal puberty. Onset of sex characteristics before age 8yo in whites and 7yo in blacks/hispanics. More common in girls than boy, advanced with obesity

Non-hormonal tx of AUB

Regular exercise and healthy BMI should be recommended (high BMI causes anovulations and anemia) Women with HMB have shown to have over activation of fibrinolytic system during menses - inc bleeding Antifibrinolytics (Tranexamic Acid): 1g 3-4x/day (short half-life) during menses. SE: minimal, GI. Ok for women trying to conceive or those with extreme SE from hormonal tx. CI: used in caution in women with PERSONAL hx of thromboembolism. Causes 50% reduction in menses. NSAIDs: reduces proinflammatory cytokine TNF-alpha which by turn decreases bleeding in women with HMB. Mefenamic Acid: reduces blood loss by 25-50%. SE: GI, not good for women who had/have PUD or for women with coagulation disorders. Not very effective. CI: NSAIDs and antifibrinolytic meds can be used together but should be stopped after 3 mo if no improvement. If benefial, continue it indefinitely as adjuvant therapy.

Sexual maturation in Adolescence

SMR useful to categorize genital development. Chronological age is a bad predictor of physiologic and psychosocial development. Skeletal maturation correlates WELL with growth and pubertal development. Menarche: average age 12.5 yo, average height 158cm, avg weight 48 kg, may be delayed as late as 16yo or as ealy as 10yo 1st measurable sign of puberty in girls: DEVELOPMENT OF BREAST BUDS BETWEEN 8-11yo. Growth spurt starts at age 9, peaks at 11yo - usually SMR 3-4 for breast, and SMR of 3 for pubic hair. Spurt ends at 14yo. Height correlates with breast development 1st measurable sign of puberty in BOYS: scrotal and testicular growth (10-12yo), pubic hair appears early (10-15yo), penis grows a year or so after testes and pubic hair. First ejaculation: 1 year after growth of testes. Gyneconomastia in majority of boys and peaks at 14-15yo and disappear after 6mo-2years. Height spurt at age 11, peaks at 13.5, pubertal growth not completed until 18. Axillary hair, voice changes, chest hair: mid puberty 2 years after pubic hair: facial hair around 16-17yo

Diabetes screening for teenagers

Screen if child >10yo and 2 or more RF (screen q 2 y) RFs: BMI>85, t2d family hx, hispanic/black, acanthosis, dyslipidemia, htn, pcos.

Boy SMR for Penis/scrotum (stage 2) and pubic hair (stage 2)

Scrotum enlargement starts, reddening and texture change in scrotal skin Sparse growth of lightly pigmented hair, straight, either side of base of penis

Precocious puberty in BOYS dx and prevalence

Secondary sexual characteristics appearing before age 9yo. Central PP frequency much lower in boys than girls; boys more likely to have CNS abnormality and require medical evaluation.

Gynecomastia prevalence, pathology and treatment

Self-limited, common and occurs in 75% of pubertal boys and more common in obese boys. May occur in male hypogonadism or SE of meds. Typically resolves within 2 years, but if >2cm it might not resolve. Tx: antiestrogens and/or aromatase inhibitors beneficial if initiated early. Consider surgery promptly if prolonged or severe cases.

Tx for severe AUB

Severe: prolonged, heavy flow + anemia Hgb<9 If Hgb<7 and orthostatic: hospital for clotting studies and thyroid If Hgb 8-10: tx at home with tapering OCPs (30mg EE/0.3 norgestrel): use every 4 hrs until bleeding stops: then 1 pill q 6 hrs for 2 days, then q 8 hrs for 2 days, then q 12 for 21 days - then cyclic OCP use Need IRON SUPPLEMENTATION AND NAUSA MEDICINE If can't take medicine, use IV premarin q 4hrs until stop bleeding then PO If estrogen CI: noerhindrone 5-10mg q 4 hrs with similar taper as above

What is the treatment for delayed puberty in boys?

Simple constitutional delay + troubled by stature and/or prepubertal appearance: low dose testosterone for 4 to 6 months (50-100mg/mo) to provide viralization and jump start development Teenager boys + permanent hypogonadism: tx with DEPOT testosterone initiated with 50-100mg IM each month then increase gradually over 3 to 4 years to adult dose of 200mg every 2-4 weeks. Alternative is testosterone gel single dose or pump set applied DAILY.

CKD detection

Targeted testing for CKD among high risk pts with DM and HTN Detection occurs during routine care with serum creatinine in BMP and CMP Early detection allows for management before symptoms occur and slows loss of kidney function Avoid use of NSAIDs, rx for ACEi/ARBs when indicated, and nephro care Kidney function = estimated glomerular filtration rate - eGFR - most accurate assessment of kidney function; inaccurate in AKI Urine studies = evals for albuminuria or proteinuria - albuminuria is critical to eval prognosis spot UACR: more sensitive and specific marker of CKD than spot urine protein/creatinine ratio

Teenager physical growth

Teen weight doubles in adolescence. Height increases by 15-20%. Major organs double in size except lymphoid which decreases in mass. Muscle mass increases. Boys attain strength and mass in late puberty, motor coordination lags behind growth in stature. Pubertal growth spurt begins 2 years earlier in girls than in boys and lasts for about 2 to 4 years but it continues LONGER IN BOYS. Peak height for girls: 11.5 to 12yo. Peak height for boys: 13.5-14yo, muscle mass doubles between 10-17yo. nearly 90% of boys/girls attain ultimate height at 12y(boy) and 11yo(girl) Sexual orientation: emerges before or early in adolescence. Gender identity is knowledge of one's self as being male of female. Awareness of gender identity happens by age 3yo, by age 4yo gender is stable.

CKD patient referral to nephrologist

Timely referral = improves preparation for kidney replacement therapy, lower use of hemodialysis / emergent dialysis, and increase use of kidney transplants / self-care dialysis. PCPs care with nephrologist to provide complementary services. Refer if: GFR <30, >25% drop in eGFR, sustained progression of CKD >5yrs, consistent significant albuminuria, persistent unexplained hematuria, CKD and HTN refractory to 4 or more BP meds, abn potassium, hereditary KD, secondary hyperpara, persistent anion gap acidosis, non IDA. Severe albuminuria + DM does not require referral Stage G4/5 CKD with limited life expectancy, adv dementia: conservatively, suggest hospice If patient is >65yo with eGFR 45-60 and NO albuminuria or abnormal UA - manage conservatively by avoiding RAAS blockers, NSAIDs and contrast If elderly and G3a CKD: monitor for AKI after surgeries (heart cath)

CKD and safety concerns

Toxicity, improper dosing, inadequate monitoring, hyperkalemia, magnesemia, phosphatemia, hypoglycemia, drug resistant, arm preservation, contrast dye, gadolinium dye, nephrogenic systemic fibrosis, sodium phosphate bowel prep, missed CV dx, improper mgmt, hypotension, aki, CHF Avoid NSAIDs, avoid dual RAAS blockage, avoid any med >30% renal clearance, no biphosphonates for GFR <30, avoid gadonolinium based contrast for GFR <30

What medicine is used for heavy menses in women who may not desire to have their fertility affected and may wish to conceive?

Tranexamic acid (antifibronolytic)

What are the diagnostic imaging for AUB?

Transvaginal US (dx intrauterine/ectopic preg, masses and thickness of endometrium) Sonohysterography or hysteroscopy: dx endometrial polyps or myomas MRI: not first choice but can more definitely dx submucous myomas and adenomyosis

Turner syndrome and klinefelter syndrome

Turner: missing X chromosome (XO). Short, infertile, no ovarian function, webbed neck, puffy face, swelling hands and feet, skeletal abnormalities, heart defects, kidney problems. brown spots, elbow deformed, low hairline, shielded thorax Klinefelter: extra X chromosome (XXY). Tall, narrow chest, wider hips, female type pubic area, frontal baldness, impaired IQ, OP, testicular atrophy

CKD progression and complications

Tx aims to delay progression of kidney damage and prevent/mng complications 1. Manage HTN and target BP <130/80, sodium <2,000 2. Use ACEi or ARB for albuminuria and HTN: use in CKD with or w/o DM and A2 and 3 albuminuria; monitor for hyperkalemia, restrict dietary K, monitor several weeks after initiation. If hyperkalemia develops: no diet K, id metabolic acidosis, consider thiazide/loop diuretic/resin. RAAS blocker only considered when interventions fail. When eGFR decreases over 25% within 3 mo of RAAS med initiation: investigate overdiuresis causes or renal stenosis. Never use combo ARB ACEi in HTN and CKD. THIAZIDE Diuretics used for stages G1-3b CKD (1st line), loop diuretics (second line for stage G4 CKD -- PO BID.) 3. Statins reduce vascular events in CKD 4. Control DM and target A1C<7%, higher for limited life expectancy or risk of hypoglycemia 5. CKD anemia - get Hgb at least annually - started at G3a CKD 6. CKD bone disorders: secondary hyperparathy, hypocalcemia, hyperphosphatemia, dec vitD, vascular calcification - begins in state G3b and measure at least once to document baseline of Ca, Ph, PTH, and vitamin D 7. Correct metabolic acidosis: oral alkali to achieve normal serum bicarb and decrease kidney dx progression. If bicarb <22 = rx for sodium bicarb (650mg TID) - alternative: sodium citrate 30ml/d - refer to nephro if all these fail

Tx of AUB (premenopausal + ovulatory dysfunction = AUB-O)

Tx: Progestins - limits and stabilizes endometrial growth Irregular or light bleeding: medroxyprogesterone acetate 10mg/d OR norethindrone acetate 5mg/d - both for 10 days - if successful, tx can be rpt'ed for several cycles, starting med on day 15 of subsequent cycle - can be restarted if amenorrhea or aub recurs Menorrhagia: NSAIDs (naproxen or mefenamic acid) - reduces blood loss (even for copper IUD) Heavier bleeding: taper any combo OCP with 30-35mcg of estrogen estradiol to control bleeding - 4x/daily for 1-2 days then 2pills/d until day 5 and 1pill/d until day 20 - pills taken on usual dosage for 3 cycles if withdraw bleeding occurs Intractable heavy bleeding: GnRH agonist (depot leuprolide 3.75mg IM/mo for 6 mos)- creates temporary cessation of menses by ovarian suppression - takes 2-4 weeks to work and stop bleeding Heavy bleeding requiring hospitalization: IV conjugated estrogen 25mg q 4 hrs followed by oral 2.5 mg daily for 3 weeks Abnormal bleeding uncontrolled with hormones: hysteroscopy with tissue sampling or saline infusion sonohysterography to eval lesions or neoplasms Bleeding unresponsive to medical therapy (after everything ruled out): endometrial ablation (oupt), levonorgestrel releasing IUD, hysterectomy(last resort) REFER WHEN BLEEDING NOT CONTROLLED WITH 1ST LINE THERAPY or lack of expertise Admit to hospital with uncontrollable bleeding with 1st line therapy or not hemo stable

Albumin-creatinine Ratio in urine

UACR: divide albumin [ ] by creatinine [ ] Assists with adjusting levels of urine concentration and more accurate than albumin alone Spot UACR quatifies proteinuria (normal, mild, moderate, severe) 1st void in the morning preferred - 24hr testing rarely necessary

What imaging is used for cryptochordism?

US, CT and MRI may detect testes in inguinal region - not completely reliable Differential dx: during PE cremasteric reflex may cause testes to go up into abd or inguinal canal. To prevent retraction put finger across abd ring and upper portion of canal and examine in squatting position - warm bath helpful - no tx for retractile testes necessary

Cervical cancer screening for adolescents

USPSTF: start cytology screening at 21yo, screen q 3 years if normal CDC: 21-29yo q 3 years with cytology (with HIV should be screened 1 year of sexual activity or initial HIV dx using liquid base cytology and then 6 months after

Novel Treatments for HMB - SPRMs

Ulipristal Acetate (UPA) the only SPRM restricted to 3 mo pretreatment of fibroids prior to surgery. For fibroid that are going under the knife that are 3cm-10cm. OK for pregnancy. Minor SE: HA, breast complaints No studies on women that do not have fibroids or have adenomyosis or other things related to HMB

Management of central and peripheral pp

XRAY left hand and risk to determine bone age If central PP = order MRI of brain to r/o lesion Girls with central PP: tx with GnRH analogues such as LEUPROLIDE and HISTRELIN Boys with central PP: treat with GnRH or tx cause Girls with peripheral PP: depends on cause In girls, if labs indicate PP, you may need to obtain ovarian and adrenal gland US

Gonad development

Y chromosome express SRY gene and direct testes formation. External male genitalia formation depends on adequate testosterone and DHT. Sexual differentiation completed by 2 weeks of gestation.

central PP vs Peripheral PP?

central- more common; identical to normal puberty, just earlier onset peripheral- triggered by independent release of endogenous estrogen or androgens from adrenal glands, gonads or exogenous exposure to steroids

What are the indications for CKD referral?

eGFR <30 (G4-50), persistent albuminuria >300, atypical progression of CKD such as over 25% drop in kidney function or sustained decline more than 5ml/min/year Refer AKI, red casts in urine, urine RBC>20 (sustained and not readily explained), HTN refractory to tx with >4 bp meds, persistent abnm K, recurrent nephrolithiasis, hereditary kidney disease CKD pts are at high risk for drug related adverse effects. 50% of FDA drugs are cleared by kidneys, consider kidney function and GFR when prescribing drugs

Early recognition of CKD allows for

enhanving kidney care by improving modifiable RFs, improves prediction of CV and events, encourages timely referral to nephro and limits patient pt safety risks with CKD. Improved CKD dx: inc urinary albumin testing, appropriate use of ACEi/ARB, avoid NSAIDs with low eGFR and appropriate nephro referral Modifiable risk: DM, HTN, NSAIDs, hx of AKI Non-modifiable risk: Fam hx, >60yo, AA, hispanic, asian/pi, indian eGFR provides insight in overall kidney function UACR provides insight regarding extent of kidney damage