PEDIATRIC GYNECOLOGY AND GYNECOLOGICAL DISORDERS IN CHILDREN AND ADOLESCENTS

1. PEDIATRIC GYNECOLOGYAND GYNECOLOGICAL DISORDERS IN CHILDRENAND ADOLESCENTS Rukset Attar, MD, PhD Obstetrics and Gynecology Department

2. Pediatric & AdolescentGynecology • Gynecologic care begins in the delivery room, with inspection of the external genitalia during routine newborn examination. • Evaluation of the external genitalia continues through routine well-child examinations, permitting early detection of infections, labial adhesions, congenital anomalies, and even genital tumors. • A complete gynecologic examination is indicated when a child has symptoms or signs of a genital disorder

3. CommonGynecologicDisorders • Newborn Infants • During the first few weeks of life, residual maternal sex hormones may produce physiologic effects on the newborn • Breast budding occurs in nearly all female infants born at term. In some cases, breast enlargement is marked, and there may be fluid discharge from the nipples - No treatment is indicated. • The labia majora are bulbous, and the labia minora are thick and protruding • Vaginal bleeding may occur • Vaginal discharge is common, composed mainly of cervical mucus and exfoliated vaginal cells.

4. CommonGynecologicDisorders • Congenital Anomalies of the Female Genital Tract • Anomalies of the Vulva & Labia • Anomalies of Clitoris • Anomalies of the Hymen

5. CommonGynecologicDisorders • LabialAdhesions • %1.4 • estrogendeficiencyandinflammation • applyingestrogencreamtothefinethinraphetwice a dayfor 2 weeksfollowedbyoncedailyapplicationfor 2 weeks. • parentsareaskedtorepeatthecourse of treatment in 6-month to 1-year intervalsifrecurrenceoccurs.

6. CommonGynecologicDisorders • estrogen cream can be systemically absorbed, parents may notice transient breast development • Forceful manual separation is not advised • as this is often painful and traumatic to the child • recurrence is much more common. • Surgical separation is rarely justified and only applicable if urinary problems result and estrogen therapy has failed.

7. CommonGynecologicDisorders • Imperforate Hymen • A mucocolpos or hematocolpos can develop • is apparent as a bulging thin membrane at the introitus with the Valsalva maneuver or crying • Surgical incision

8. CommonGynecologicDisorders • Vulvitis • vulvar discomfort or itching • The first step is to take a careful history in regards to any possible irritants • the level of hygiene, • urinary incontinence, • frequency of diaper changes, and • bathing habits. • Diaper dermatitis

9. CommonGynecologicDisorders • Common organisms causing prepubertal vulvitis are • Candida • usu. under the age of 2 • may follow a course of antibiotics in the infant • underlying factors such as juvenile onset diabetes or immunosuppression • antifungal creams such as clotrimazole, miconazole, or butaconazole applied twice a day to the affected area for 10 to 14 days or until rash is cleared

10. CommonGynecologicDisorders • Pinworms (Enterobius vermicularis) • Diagnosis is made by • inspecting at night with a flashlight to observe worms exiting the anus • a morning inspection with "Scotch tape" to the anal region can identify the eggs. • Treatment consists of mebendazole (Vermox) 100 mg orally once and repeated in 1 week. • It is advised to treat the entire family to prevent reinfection • Group A β-hemolytic streptococcus • appropriate antibiotic for 2 weeks and occasionally for longer periods of time (up to 4 weeks)

11. CommonGynecologicDisorders • Contact or allergic vulvitis • Treatment may consist of removing the irritant • if itching is severe • providing an oral medication, such as hydroxyzine hydrochloride (Atarax), 2 mg/kg/d divided into four doses, • application of topical hydrocortisone cream 2.5% twice a day for a week and then discontinuing.

12. CommonGynecologicDisorders • Lichen Sclerosus • itching, irritation, soreness, bleeding, and dysuria. • The vulva is characteristically white, atrophic, with parchmentlike skin and occasionally evidence of subepithelial hemorrhages, excoriations, fissures, and inflammation • Treatment consists of clobetasol (Temovate) cream 0.05% applied nightly to the affected area for 6 weeks. • Follow-up should be scheduled at that time and if there is significant improvement the dose is tapered progressively until it is being used only one time weekly at bedtime.

13. CommonGynecologicDisorders • Nonspecific Vulvovaginitis • is the most common gynecological disorder of prepubertal girls (accounts for over 50% of visits) • Poor hygiene practices at home or daycare program • Inadequate front-to-back wiping • Smaller labia minora, which are less protective of the vestibule, with a short distance from the anus to vagina • Vulvovaginal epithelium that is not well estrogenized and thus thinner and more prone to irritation • Foreign body such as toilet paper, small toys, or pieces of cloth, which may be inadvertently inserted in the vagina by the child • Chemical irritants such as bubble baths, shampoos, or bath oils, and certain deodorant soaps • Dermatologic conditions such as eczema and seborrhea • Chronic disease and altered immune status • Sexual abuse

14. CommonGynecologicDisorders • The pathogenesis of vulvovaginitis is not well defined • may be associated with an alteration of the vaginal flora with an overgrowth of fecal aerobes or an overabundance of anaerobes contributing to the symptoms of odor and discharge. • Cultures performed indicate a variety of organisms considered normal vaginal flora such as diphtheroids, enterococci, coliforms, and lactobacillus. • Escherichia coli is often found on vaginal culture, suggesting poor hygiene; contamination with bowel flora may contribute to the problem.

15. CommonGynecologicDisorders • Infectious Vulvovaginitis • Hemophilus influenzae, Staphylococcus aureus, group A β-hemolytic streptococci, and Streptococcus pneumoniae causing a yellowish to greenish purulent vaginal discharge (S. pneumoniae infection and group (amoxicillin 40 mg/kg divided three times a day for 10 days) • Shigella flexneri, an enteric pathogen, can cause a mucopurulent, sometimes bloody discharge following an episode of diarrhea in some young girls(trimethoprim (TMP)-sulfamethoxazole (Bactrim) 6 to 10 mg/kg/d TMP by mouth, divided every 12 hours. Treatment may require more than 10 to 14 days of medication.)

16. CommonGynecologicDisorders • Physiologic Discharge • resulting from maternal estrogen exposure in utero • may appear as clear mucous, whitish in color or clear • On occasion, a bloody discharge is noted and results from exposure to maternal estrogens in utero, causing transient endometrial shedding. • This will most often resolve within a few hours to days.

17. CommonGynecologicDisorders • Condyloma Acuminata • in children less than 2 years of age, the mode of transmission is vertical from mother to child during childbirth. • After age 2, sexual abuse is a primary concern in children presenting with condylomatous lesions (in approximately one third of cases)

18. CommonGynecologicDisorders • treatment • trichloroacetic acid • podophyllin • cryotherapy • CO2 laser vaporization therapy • more recently the advent of imiquimod cream (Aldara), an immune response modifier supplied in a cream base, has eased and revolutionized therapy for external genital warts (A thin layer of cream is applied to the wart(s) at bedtime and left on for 6 to 10 hours, after which it is washed off. Therapy is for 3 days a week (i.e., Monday, Wednesday, and Friday) and continued until the warts are completely gone, or up to 16 week )

19. CommonGynecologicDisorders • Urethral Prolapse • usually presents with unexplained bleeding, often thought to be coming from the vagina. • The child experiences no pain and has no recent history of vulvar trauma. • On physical examination a bright red, friable annular mass is noted just above the hymen surrounding the urethral opening • Treatment consists of estrogen cream to the area nightly for 1 to 2 weeks.

20. CommonGynecologicDisorders • Foreign Bodies • The vaginal discharge is often dark brownish in color • occurs daily, requiring the use of a panty liner by the child. • The discharge is often malodorous

21. CommonGynecologicDisorders • Sexual Abuse • Genital infection with Neisseria gonorrhoeae is associated with a purulent thick yellow discharge along with vulvar erythema and edema. • Chlamydia trachomatis may present with vulvovaginitis, pruritis, and discharge. Infants born to mothers with chlamydia may carry the organism for up to 18 months

22. Collection of Specimens • Vaginal cultures are easily collected by a technique described by Pokorny using a catheter within a catheter. A 4-inch segment of the tip of a no. 12 red rubber catheter is placed over the hub end of a butterfly catheter attached to a 1-mL tuberculin syringe . Sterile normal saline (0.05 to 1 mL) is instilled slowly and aspirated back to acquire fluid • Collection of material to evaluate for gonorrhea may be collected by swabbing visible discharge on the perineum or in a similar manner as with chlamydia. • Cultures for chlamydia must include material taken directly from the mucosal surface using a saline-moistened calcium alginate swab (male urethral swab). The swab is inserted into the vagina as the child coughs, which makes the hymen gape open and serves as a distraction.

23. Radiological tests may be performed in those children who are unable to cooperate or have specific problems, such as suspicion of an abdominal mass, abdominal pain, or precocious puberty. • Pelvic ultrasound • computed tomography • magnetic resonance imaging (MRI) scan

24. Puberty • Puberty is the general termforthetransitionfromsexualimmaturitytosexualmaturity. • It is theperiodthatfertility is acquired. • Therearetwo main physiologicalevents in puberty: • Gonadarche is theactivation of thegonadsbythepituitaryhormonesfollicle-stimulatinghormone (FSH) andluteinizinghormone (LH). • Adrenarche is theactivation of production of androgensbythe adrenal cortex.

25. Puberty Themeanageforthefirstsigns of puberty is about 10.5 years of age in girls, with a rangefromabout 8 to 12 years. Inboys, themeanage of pubertalonset is about 11.5 years, with a rangefromabout 9 to 13 years, withsomeracialvariation Typicalagethresholdsforevaluatingchildrenforprecociouspubertyaresigns of breastdevelopmentbeforeeightyears in girlsandtesticularenlargementbefore nine years in boys- Inclinicalpractice, theneedforclinicalevaluation of girlswhodevelopsigns of pubertybetweensixandeightyears of agedepends on thedegreeand rate of maturation

26. Puberty Inmostgirls, theearliestsecondarysexualcharacteristic is breast/areolardevelopment (thelarche), althoughabout 15 percenthavepubichair as theinitialmanifestation. Menarcheoccurs, on average, 2.6 yearsaftertheonset of pubertyand 0.5 yearsafterpeakheightvelocity

27. Puberty • The most visible changes during puberty are • growth in stature and • development of secondary sexual characteristics • changes in body composition; • the achievement of fertility; • and changes in most body systems, such as the neuroendocrine axis, bone size, and mineralization; and the cardiovascular system (normal cardiovascular changes, including greater aerobic power reserve, electrocardiographic changes, and blood pressure changes, occur during puberty).

28. Puberty • Thelarche is theappearance of breasttissue, which is primarilyduetotheaction of estradiolfromtheovaries. • Menarche is the time of firstmenstrualbleed • is often not associatedwithovulation • typicallyis causedsolelybytheeffects of estradiol on theendometriallining. • Menstrualbleeding in regularmenstrualcyclesaftermaturity is causedbytheinterplay of estradiolandprogesteroneproducedbytheovaries.

29. Puberty Spermarche is the time of thefirst sperm production (heraldedbynocturnal sperm emissionsandappearance of sperm in theurine), which is duetotheeffects of FSH and LH, viatestosterone Pubarche is theappearance of pubichair, which is primarilyduetotheeffects of androgensfromthe adrenal gland. Theterm is alsoappliedtofirstappearance of axillaryhair, apocrine body odor, andacne.

30. AbnormalPuberty • Abnormal female development • Precocious puberty • Delayed puberty • Growth problems in normal adolescents • Short stature • Tall stature

31. Precocious Puberty Pubertal development beginat an earlier age than is expected based upon established normal standards ( beforeage 8 )-is defined as pubertalonset at an age 2 to 3 standarddeviations (SD) belowthemeanage of onset of puberty The cause of precocious puberty may range from a variant of normal development (eg, premature adrenarche) to pathologic conditions with significant risk of morbidity and even death (eg, malignant germ-cell tumor and astrocytoma). Usuallythefirstsign is an increase in height Sometimesmenarche is thefirstsign

32. Precocious Puberty • Types of Precocious Puberty • Isosexual ( early pubertal growth) • Idiopathic %80 • Ovarian or adrenal estrogen secreting tumors • CNS disease • Gonadotropin releasing tumors • Hypothyroidism • Iatrogenic • Heterosexual ( with virilisation, acne, hirsutismus) • Ovarian ( cystortumor) • Adrenal tumors • McCune-AlbrightSyndrome • Congenital Adrenal Hyperplasia • Ectopicgonadotropinproduction • Cushing syndrome

33. Precocious Puberty • Precociouspuberty can be classifiedbasedupontheunderlyingpathologicprocess • Central precociouspuberty • Peripheralprecocity • Benignornon-progressivepubertalvariants

34. Precocious Puberty • Centralprecociouspuberty( CPP, gonadotropin-dependentprecociouspubertyortrueprecociouspuberty) • is causedbyearlymaturation of thehypothalamic-pituitary-gonadalaxis • is characterizedbysequentialmaturation of breastsandpubichair in girls / testicularandpenileenlargementandpubichair in boys • Thesexualcharacteristicsareappropriateforthechild'sgender (isosexual) • is pathologic in upto 40 to 75 percent of cases in boyscomparedwith 10 to 20 percent in girls

35. Precocious Puberty Causes of Central precocious puberty Idiopathic— 80 to 90 percent of cases of girls, but in only 25 to 60 percent of boys CNS lesions — Contrast-enhanced magnetic resonance imaging (MRI) is therefore recommended, even in the absence of clinically evident neurologic abnormalities Any type of intracranial disturbance can cause precocious puberty

36. Precocious Puberty • Causes of Central precocious puberty • CNS lesions • Hamartomas – Hamartomas of the tuber cinereum are benign tumors that are the most frequent type of CNS tumor to cause precocious puberty in very young children, although in most cases, the mechanism by which these tumors lead to CPP is unknown. • Other CNS tumors –astrocytomas, ependymomas, pinealomas, and optic and hypothalamic gliomas

37. Precocious Puberty • Causes of Central precocious puberty • CNS irradiation –is commonly associated with growth hormone (GH) deficiency • Other CNS lesions –hydrocephalus, cysts, trauma, CNS inflammatory disease, and congenital midline defects, such as optic nerve hypoplasia

38. Precocious Puberty • Causes of Central precocious puberty • Genetics — Specific genetic mutations have been associated with CPP, although each appears to be rare: • Gain-of-function mutations in the Kisspeptin 1 gene (KISS1) [27] and its G protein-coupled receptor KISS1R (formerly known as GPR54) • CPP also can be caused by loss-of-function mutations in MKRN3 (makorin ring finger protein 3), an imprinted gene in the Prader-Willi syndrome critical region

39. Precocious Puberty Causes of Central precocious puberty Previous excess sex steroid exposure— Children who have been exposed to high serum levels of sex steroid (eg, those with poorly controlled congenital adrenal hyperplasia and McCune Albright Syndrome) may sometimes develop superimposed CPP, either from the priming effect of the peripheral precocity-derived sex steroid on the hypothalamus, or from sudden lowering of the sex steroid levels following improved control of the sexual precocity

40. Precocious Puberty Causes of Central precocious puberty Pituitary gonadotropin-secreting tumors — These tumors are extremely rare in children and are associated with elevated levels of LH and/or follicle-stimulating hormone (FSH)

41. Precocious Puberty • Peripheral precocity (peripheral precocious puberty or gonadotropin-independent precocious puberty) • is caused by excess secretion of sex hormones (estrogens and/or androgens) derived either from the gonads or adrenal glands, or from exogenous sources • isosexual or contrasexual ( heterosexual)

42. Precocious Puberty • Causes of Peripheral precocity • Ovarian cysts — A large functioning follicular cyst of the ovaries is the most common cause of peripheral precocity in girls- often present with breast development, followed by an episode of vaginal bleeding-due to estrogen withdrawal once the cyst has regressed. These cysts may appear and regress spontaneously, so conservative management is usually appropriate. Large cysts may predispose to ovarian torsion.

43. Precocious Puberty • Causes of Peripheral precocity • Ovarian tumors • Granulosa cell tumors, the most common type, typically present as isosexual precocity • Sertoli/Leydig cell tumors (arrhenoblastoma), pure Leydig cell tumors, and gonadoblastoma may make androgens and cause contrasexual precocity

44. Precocious Puberty • Causes of Peripheral precocity • Primary hypothyroidism  • Exogenous sex steroids  • Adrenal pathology • McCune-Albright syndrome 

45. Precocious Puberty BENIGN OR NON-PROGRESSIVE PUBERTAL VARIANTS Premature thelarche Premature thelarche occurs in two peaks: one during the first two years of life and the other at six to eight years of age Most cases of premature thelarche are idiopathic and present around two years of age (but may start at birth). Many cases will remit spontaneously, and most others do not progress.

46. Precocious Puberty • Premature thelarche • Key features of premature thelarche are: • Isolated breast development, either unilateral or bilateral – typically not beyond Tanner stage 3 • Absence of other secondary sexual characteristics • Normal linear growth velocity for age (not accelerated) • Normal or near-normal bone age

47. Precocious Puberty • Premature adrenarche • is characterized by the appearance of pubic and/or axillary hair (pubarche) prior to the age of eight years in girls and nine years in boys, in conjunction with a mild elevation in serum dehydroepiandrosterone sulfate (DHEAS) for age. • It is more common in girls, African-American and Hispanic females, and individuals with obesity and insulin resistance. • Premature adrenarche is considered a variant of normal development

48. Precocious Puberty Initial evaluation Medical history  Physical examination  Pubertal staging  Bone age  Initial laboratory evaluation ( Basal serum LH, Basal serum FSH, Serum estradiol , Serum testosterone , Serum LH concentrations after GnRH agonist stimulation ), Serum adrenal steroids, TSH Imaging-MRI, pelvic USG, X-ray may be done of the left hand and wrist

49. Delayed puberty • Pubertal development beginat a later age than is expected based upon established normal standards ( after 13 years ofagefor girls, 14 years of age for boys ) • Types of Delayed Puberty • Constitutional • Delayed Puberty with sexual infantism • Hypogonadotropic hypogonadism ( CNS diseases, Kallman Syndrome, multiplhypophisialhormon deficiency, functional hypophisialhormon deficiency-chronic systemic diseases, malnutrition, hypothroidism, Cushing, DM, Hyperprolactinemia, anorexia nervosa, etc) • Hypergonadotropic hypogonadism ( Klinifelter S, Turner S, etc)