Adolescent Gyn Flashcards
the Van Wyk–Grumbach syndrome
hypothyroidism associated with precocious puberty is caused by primary thyroid insufficiency, usually Hashimoto thyroiditis. The pathophysiology of this syndrome is a result of the diminished negative feedback of thyroxine, resulting in an increased production of TSH, which may be accompanied by an increase in production of gonadotropins. Another possible mechanism is the stimulation of the FSH receptor by high levels of TSH.
the only cause of precocious puberty in which the bone age is retarded is…
hypothyroidism, This syndrome is usually observed in girls between the ages of 6 and 8 years.
The most common cause of pseudo or feminizing precocious puberty is
an estrogen-secreting ovarian cyst or large functioning follicle.
the most common type of solid ovarian tumor resulting in precocious puberty is
Granulosa cell tumors These tumors are usually larger than 8 cm in diameter when associated with precocious puberty; 80% can be palpated abdominally.
Other ovarian tumors that may be associated with precocious puberty include thecomas, luteomas, teratomas, Sertoli-Leydig tumors, choriocarcinomas, and benign follicular cysts.
rare condition caused by a mutation in the G3 protein leading to activation of adenylate cyclase
McCune-Albright syndrome (MAS)
Clinically there is a triad of café-au-lait spots, polyostotic fibrous dysplasia, and cysts of the skull and long bones
Approach to precocious puberty
meticulous history and physical examination. Must rule out life-threatening neoplasms of the ovary, adrenal gland, or CNS by a series of tests, including neurologic and ophthalmologic examinations, EEGs, and brain imaging. Then delineate the speed of the maturation process, Tanner stage, Ultrasound, CT, or MRI of the abdomen and pelvis should be performed to evaluate enlargement of the ovaries (ovarian volume), uterus, or adrenal glands.
Serum levels of FSH, LH, prolactin, TSH, E2, testosterone, DHEA-S, hCG, androstenedione, 17-hydroxyprogesterone, tri- iodothyronine (T3), and thyroxine (T4) may be of value in establishing the differential diagnosis.
A GnRH agonist stimulation test is diagnostic in differentiating incomplete from true precocious puberty.
Labial adhesions literally mean the labia minora have adhered or agglutinated together at the midline. Another term sometimes used to describe this condition is
adhesive vulvitis
Labial adhesion treatment
Topical estrogen twice per day Care should be taken to not prolong the topical use of estrogen for more than 6 to 8 weeks. Prolonged use of topical estrogen has been associated with breast budding and in some less common cases vaginal bleeding from the peripheral effects of the absorption of estrogen. Failure of separation within the normal time frame should trigger alternate treatment. When patients fail estrogen therapy, and symptoms persist, the use of topical corticosteroids twice a day for 6 to 8 weeks. Once the condition has been resolved, recurrence can often be prevented by applying a bland ointment (such as zinc oxide cream or petroleum jelly) to the raw epithelial edges for at least 1 month or even longer.
Labial adhesion ddx
the combination of labial adhesions and scarring of the posterior fourchette, especially in children with new-onset labial adhesions after age 6, should prompt the clinician to consider sexual abuse in the differential diagnosis.
Differential Diagnosis of Prepubertal Bleeding without Any Breast Development
Foreign object-Genital trauma-Sexual abuse - Lichen sclerosus - Infectious vaginitis (especially Shigella) - Urethral prolapse - Breakdown of labial adhesions - Friable genital warts or vulvar lesions - Vaginal tumor (sarcoma botryoides and endodermal sinus tumors of the vagina) - Rare presentation of McCune-Albright syndrome (typically have breast development) - Isolated menarche (controversial) - Dermatologic conditions with secondary excoriation - Nongenital bleeding; mistaken as genital: rectal and urinary
the definition of precocious development or puberty (PROS new guideline)
Was defined as early breast development, early pubic hair development, or both with menses before age 8 years. Because of earlier pubertal milestones among different ethnicities,some recommend to define it as
thelarche or adrenarche prior to age 6 in African-American girls or 7 in white girls. (Controversial)
McCune-Albright Syndrome affected gene
GNAS1, somatic mutation that occurs during embryogenesis in neural crest cells affects G protein receptors and has a variable expression
Classic triad of McCune-Albright Syndrome
café-au-lait spots, abnormal bone lesions, and endocrinopathy most commonly precocious puberty due to overfunction of the ovary (peripheral)
But The presence of higher levels of sex steroids in peripheral precocious puberty may cause the activation of the hypothalamic–pituitaryovarian axis and the patient may develop central precocious puberty.
clitorimegaly
In children more than 1 cm
In adult more than 2.5 cm
Triad of ambiguous genitalia
- clitorimegaly >1cm
- partial or complete fused labia majora
- urethral and vaginal deformity (UGS)
The most common cause of central precocious puberty is
idiopathic (in greater than 50% of girls with central precocious puberty)
however, central nervous system lesions must be excluded like CNS tumors or anomaly or infection, Head trauma, lschemia, Iatrogenic: radiation, chemotherapy, surgical
Leuprolide stimulation test may help differentiate premature thelarche from true central and peripheral precocious puberty.
How is it done ?
Leuprolide (Lupron), which is an initial GnRH agonist, is given as a single intravenous dose of 20 µg/kg and does not to exceed a total dose of 500 µg. FSH plus LH levels are measured at 1, 2, and 3 hours. An estradiol level is measured at 24 hours. Central precocious puberty is confirmed by a rise in serum LH levels following infusion of the GnRH agonist.
In contrast, high estradiol levels and low gonadotropin levels during the stimulation test suggest peripheral precocious puberty
isolated, premature adrenarche treatment
reassurance and monitoring at 3-to 6-month intervals for other signs of puberty.
Precocious puberty is classified as
- gonadotropin dependent (central or true)
- gonadotropin independent (peripheral or pseudo):The source of the sex steroids is either exogenous (accidental ingestion) or endogenous (McCune–Albright syndrome or sex steroidproducing tumor).
In cases of central precocious puberty, the goal is to suppress the excessive gonadotropin production. This can be achieved through the use of
GnRH analogs such as leuprolide acetate. Leuprolide will cause suppression of the gonadotropin production from the pituitary, which will in turn reduce sex steroid production from the ovaries.
treatment of sexual precocity in McCune–Albright syndrome
Aromatase inhibitors, These medications inhibit aromatase activity by competitively binding to the cytochrome P450 subunit of the aromatase enzyme, decreasing estrogen biosynthesis.
Like newer third-generation aromatase inhibitors, anastrozole and letrozole, have the advantage of once-daily dosing.
Or Testolactone aromatase inhibitor
congenital adrenal hyperplasia due to enzyme defects in
(21-hydroxylase deficiency, 11β-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency),
Evaluation for premature adrenarche includes
a history, physical examination, review of growth records, and laboratory testing for DHEAS, follicle-stimulating hormone, luteinizing hormone, testosterone, thyroid- stimulating hormone, and morning 17-hydroxyprogesterone levels. Typically, DHEAS levels are elevated compared with chronologic age but are normal for the pubertal stage. An ACTH stimulation test for CAH should be performed in cases with screening 17-hydroxyprogesterone levels greater than 200 ng/dL. In patients with hypertension, additional testing should include blood deoxycortisol, deoxycorticosterone levels to evaluate for 11β-hydroxylase deficiency, and 24-hour urinary free cortisol to evaluate for Cushing disease. Adrenal and ovarian tumors are rare and most often will be accompanied by signs of virilization. Pelvic ultrasonography is indicated in patients with testosterone levels greater than 200 ng/dL. Adrenal imaging may be necessary in patients with abnormal cortisol levels and in individuals with greatly elevated DHEAS levels (greater than 700 micrograms/dL). Height and bone age are advanced for chronologic age but normal for pubertal age, and predicted adult height is normal. In contrast to central precocious puberty, follicle-stimulating hormone and luteinizing hormone levels are consistent with age.
The virilizing forms of CAH are due to decreased activity of
21-hydroxylase (P450c21), 11β-hydroxylase (P450c11B1), or 3β-hydroxysteroid dehydrogenase type 2.
The most common form of CAH that accounts for approximately 90–95% of cases is
21-hydroxylase deficiency. The reported incidence of classic 21- hydroxylase deficiency ranges from 1 in 9,000 to 1 in 15,000
The most common tumor that causes central precocious puberty is
a hypothalamic hamartoma, in which astroglial cells within the tumor release transforming growth factor-beta protein to induce GnRH release from the hypothalamus.
Causes of Isosexual Female central Precocious Puberty
Idiopathic
International adoption
Hypothalamic hamartoma
Brain tumors
Hydrocephalus
Previous encephalitis, meningitis, head trauma, granulomatous disease
Subarachnoid cyst
Neurofibromatosis 1
Sturge–Weber syndrome
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Causes of Isosexual Female peripheral Precocious Puberty
Estrogen-producing ovarian tumor Simple ovarian cyst Hypothyroidism Estrogen-producing adrenal tumor McCune–Albright syndrome Exogenous estrogen Peutz–Jeghers syndrome Silver–Russell syndrome
The evaluation of isosexual precocious puberty includes
a history with close attention to possible estrogen exposure, review of growth records looking for an increase in height percentile, and a physical examination to determine Tanner stages and presence of skin lesions. Initial testing includes a bone age test and blood analysis for estradiol, FSH, LH, and TSH. Bone age is increased in all cases of precocious puberty except when caused by primary hypothyroidism. A high estradiol level with a low gonadotropin level suggests an ovarian tumor with the next test being pelvic ultrasonography. A high gonadotropin level for age is consistent with central precocious puberty and the next step is magnetic resonance imaging.
Treatment for McCune–Albright syndrome
requires the use of enzyme inhibitors given the autonomous action of the gonadotropin receptors independent of ligand. Options include the use of ketoconazole, which blocks production of sex steroids primarily through inhibition of 17α-hydroxylase activity; letrozole through inhibition of aromatase; and fulvestrant through antagonism of the estrogen receptor.
Ddx Disorders of sex development (DSD) or as Called previously ambiguous Genitalia along with Female Karyotype:
- CAH (1:1000), 21-Alpha hydroxylase def led high Androgen, no testis, + uterus.
- exposure in utero to exogenous or endogenous maternal androgens
- placental aromatase def
Ddx Disorders of sex development (DSD) or as Called previously ambiguous Genitalia along with male Karyotype:
- partial gonadal dysgensis
- complete androgen insensitivity (testicular feminization)
- partial androgen insensitivity
- 5-Alpha- reductase
the gold standard test to identify central precocious puberty (CPP)
Gonadotropin-releasing hormone (GnRH) stimulation test
(Luteinizing hormone (LH) increments of ≥4–5 IU/L at 30–60 minutes after GnRH administration are well-known criteria to diagnose CPP.1,7) Values >5 IU/L at both 40 and 45 minutes post-GnRH stimulation have shown 98% sensitivity and 100% specificity
precocious puberty, differentiation of causes into 3 main categories these are
gonadotropin-dependent precocious puberty, gonadotropin-independent precocious puberty, and pubertal variants in patients with isolated signs of puberty without underlying pathology.
Causes of Vaginal Bleeding in Children
Foreign body
Genital tumors
Urethral prolapse
Lichen sclerosus
Vulvovaginitis
Condyloma acuminata
Trauma
Precocious puberty
Exogenous hormone usage
Premature pubertal development may result from various causes. These have been categorized based on pathogenesis and include
central precocious puberty, peripheral precocious puberty, heterosexual precocious puberty, and temporal variation of normal puberty.
the most common cause of Peripheral Precocious Puberty (Gonadotropin Independent)
granulosa cell tumor, which accounts for more than 60 percent of cases
Most common cause central precautious puberty tumours are
Hamartomas
The evaluation of a girl with precocious puberty
identify underlying causes. After physical examination and Tanner staging, it is recommended to test the patient’s concentrations of LH, Follicle-stimulating hormone, estradiol, thyroidstimulating hormone, bone age, and GnRH stimulation as well as to perform central nervous system imaging with either computed tomography or magnetic resonance imaging. If peripheral causes are suspected, pelvic ultrasonography is indicated to rule out a tumor.
Adrenarche normally begins at ages
6–8 years
Pelvic radiotherapy greater than – Gy could destroy 50% of available primordial follicles, and radiotherapy greater than – Gy produces irreversible damage.
Pelvic radiotherapy greater than 2 Gy could destroy 50% of available primordial follicles, and radiotherapy greater than 8 Gy produces irreversible damage.Therefore, it is prudent to have a discussion with patients who are about to initiate cancer therapy should fertility preservation be a desired option.
the most common cause of delayed puberty
Constitutional delay of growth and puberty
Lichen sclerosus treatment
Clobetasol is applied twice daily for 2–12 weeks with frequent reassessment. The frequency of application is tapered after symptoms abate because rebound may occur with abrupt cessation of steroid use.
