Presentation on theme: "RECOGNIZING AND MANAGING DISORDERS OF PRECOCIOUS PUBERTY"— Presentation transcript:
1 RECOGNIZING AND MANAGING DISORDERS OF PRECOCIOUS PUBERTY Mike T. Swinyard, MD, FAAPBoard Certified Pediatric Endocrinology/DiabetesMountain Vista Medicine, PCSouth Jordan, Utah(801)
2 AT THE CONCLUSION OF THIS PRESENTATION, PARTICIPANTS WILL BE ABLE TO: Be able to explain puberty to families, so they can understand the basis for any necessary laboratory testing to evaluate abnormal early pubertyCompare and contrast premature adrenarche with normal pubertyCompare and contrast premature thelarche with normal pubertyI have worked in both a general pediatric setting and an pediatric endocrine setting. I would like to present information that I wish I knew before.
3 GROWTH AND PUBERTY ASSESSMENT Detailed Medical HistoryDetailed Physical ExamBone Age Assessment (the single most important test to order)Focused and Precise Laboratory TestingAn appropriate growth assessment will include: Let’s discuss each one in detail.
4 MEDICAL HISTORY Onset and progression of signs of puberty Patient’s stage of puberty, as estimated by familyMother’s height and age of menarcheFather’s height and age of pubertal growth spurtFamily’s concerns (assess their anxiety & agenda, as preparation for your opportunity to teach them)Current and previous illnesses/trauma/surgeryExposure to cosmetics/topical hormonesAdd more to chronic disease? Add more to meds
5 PHYSICAL EXAMAn accurate determination of height is crucial, using a reliable stadiometer in those age two years and overFor those patients under two years old, care should be taken to measure an accurate length—Infantometer more reliable than making two marks on exam table paperTechnique is important.Using centimeters has less potential for error in rounding, etc.
6 PHYSICAL EXAM Accurately recording height is crucial Plot both parents’ heights on growth chartDetermine if projected adult height is consistent with parental heightsHow to determine mid-parental target height needed
8 PHYSICAL EXAMIn assessing growth, the pattern of growth over time is more useful than a single measurement of heightDetermine interval growth and annual growth velocity from previous height measurementsPlot growth velocity on growth velocity chart
9 CALCULATING GROWTH VELOCITY Example:10/02/07 HT: cm04/12/08 HT: cmInterval growth in 6 months:= 2.4Annual growth rate determined by projecting interval growth for 12 months:A x 12/B = growth velocity(A=Interval Growth, B=Months between measurements)2.4 x 12/6 = 4.8 cm/yearGrowth velocity chart with info on how to determine growth velocity.
10 PHYSICAL EXAM Females—Staging breast development (contour, not size) Males—Staging of testicular size (length)Skin exam (café-au-lait spots)Enlarged, rubbery thyroid suggestive of Hashimoto’s thyroiditis.
11 TANNER STAGES FOR GIRLS (BREAST DEVELOPMENT) Tanner Stage 1 No breast tissue. Beware of lipomastia as an imitator. (“Donut sign”)Tanner Stage 2 Areolar enlargement with breast budTanner Stage 3 Enlargement of breast and areola as single moundTanner Stage 4 Projection of areola above breast as double moundTanner Stage 5 Adult. Papilla (nipple) projects out of areola. Stage 4 and Stage 5 may be difficult todistinguish.
12 TANNER STAGES FOR BOYS (TESTICULAR LENGTH) Tanner Stage Prepubertal. Length is less than 2.5 cm (less than one inch). Gently stretch scrotum over testis.Tanner Stage Testicular length is 2.5 cm (one inch)Tanner Stage Testicular length is 3 cmTanner Stage Testicular length is 3.5 cmTanner Stage Testicular length is 4 cm or greater
13 TANNER STAGES FOR PUBIC HAIR Tanner Stage 1 Velus hair similar to abdominal wall or no hair at allTanner Stage 2 Dark, sparse hair at base of penis or along inner labia majoraTanner Stage 3 Dark, curled hair spreading over junction of pubesTanner Stage 4 Adult type of hair, but no spread to medial thighTanner Stage 5 Spread to medial thigh and growth of escutcheon
14 AVERAGE TIMING OF PUBERTAL EVENTS IN GIRLS Onset of Breast Development Age 10Tanner Stage 2 to Menarche Years(growth rate tapers after menarche)Age At Menarche YearsStart to Finish (End of Growth) YearsExplain how Bone Age and IGF-I help in determining cause of short stature.
15 AVERAGE TIMING OF PUBERTAL EVENTS IN BOYS Onset of Testicular Enlargement ½ YearsTime from onset of puberty to Tanner YearsStage 4 (beginning of growth spurt)Start to Finish (End of Growth) Years
16 REMEMBER In both girls and boys… the peak growth rate occurs in the secondhalf of puberty…Tanner Stage 3 and later
17 DEFINITION OF PRECOCIOUS PUBERTY Secondary sexual characteristics evident before age 8 years in girlsSecondary sexual characteristics evident before age 9 years in boys
18 CLASSIFICATION OF PRECOCIOUS PUBERTY Gonadotropin-dependent (central or true precocious puberty). Characteristics match gender of patient (isosexual)Gonadotropin-independent (peripheral precocious puberty). Characteristics may be isosexual or contrasexual, (inappropriate for child’s gender), including virilization (masculinization) of girls or feminization of boys.Incomplete precocious puberty (“normal variants”), including premature thelarche and premature adrenarche
19 GONADOTROPIN-DEPENDENT PRECOCIOUS PUBERTY Early maturation of the hypothalamic-pituitary-gonadal axisIdiopathic in more than 80%Almost all idiopathic cases are in girls)
20 CAUSES OF GONADOTROPIN-INDEPENDENT PRECOCIOUS PUBERTY Excess (“independent” or unregulated) secretion of sex hormones (androgens or estrogens) from the gonads or adrenalsExposure to exogenous sources of sex steroids (estrogen-containing creams, testosterone gel used to treat adult hypogonadism in men)Ectopic production of hCG from a germ cell tumorVery rare disorders (McCune-Albright syndrome)May be helpful to mark chart and closely monitor growth of child during WCC.
21 PREMATURE THELARCHEIsolated and non-progressive breast development in an infant/toddler girlNo acceleration of height growthNo acceleration of bone development(Less than 2 SDs above the mean for chronological age)
22 PREMATURE ADRENARCHEEarly appearance of adrenal androgen-mediated skin changes in any combination of pubic hair, axillary hair, body odor, oily skin, oily hair, and mild acne…in either boys or girls.No clitoromegaly in girls (no larger than a pencil eraser or less than 5 mm in diameter)No acceleration in height growth or advanced bone development (Less than 2 SDs above the mean for chronological age)
23 BONE AGE ASSESSMENTDetermined by a radiograph of the left hand and wrist compared with the standards in the Greulich and Pyle Atlas for males and femalesThe delay (or advancement) of the bone age is expressed in standard deviations (SDs) below or above the patient’s chronological ageAn advanced bone age is 2 or more SDs above the mean for chronological ageObese children or children with tall stature and tall parents may have a bone age which is 2-3 SDs above the mean for chronological age
24 EVALUATION OF PRECOCIOUS PUBERTY IN THE PRIMARY CARE SETTING The most helpful screening test in the work-up of the patient with precocious puberty is the bone age.It is non-invasive and provides valuable information, as to whether further testing may even be needed.Few other tests used in medicine can make that claim.Decreased growth rate—Isaac Ipson
25 LH AND FSH TESTING PROCEED WITH CAUTION Although readily available at hospital and reference laboratories, measurement of LH and FSH in children is fraught with problems, including…Need for relatively higher sample volumes in childrenVery poor sensitivity at the levels seen in the earliest stages of puberty
26 LH AND FSH TESTINGIf incomplete forms of early puberty (premature thelarche or premature adrenarche) are not a possibility, then measure LH, FSH and estradiol (in girls) and LH, FSH and total testosterone (in boys) with isosexual precocious pubertySend out these labs to Esoterix or Quest Diagnostics for high-sensitive assays to save your patients a redraw
27 REVIEWMeasurement of LH and FSH will guide the evaluation of precocious puberty, if development is isosexual. Also measure total testosterone in boys and estradiol in girls.Measurement of LH and FSH will not help the evaluation of contrasexual development, since it is “contrary to” the patient’s gender and not consistent with activation of the hypothalamic-pituitary-gonadal axis
28 REVIEWCentral precocious puberty is gonadotropin-dependent, so LH and FSH levels are detectablePeripheral precocious puberty is gonadotropin-independent, so LH and FSH levels are very low or undetectable
29 ADDITIONAL STUDIESIsosexual central precocious puberty in girls with pubic hair and breast growth, or any girl with menstrual periodsPelvic ultrasound to assess uterus/ovariesPituitary MRI and/or leuprolide stimulation testing after consultation with a pediatric endocrinologist
30 ADDITIONAL STUDIESIsosexual central precocious puberty (penile and testicular enlargement) in boysPituitary MRI and/or leuprolide stimulation testing after consultation with a pediatric endocrinologistSS >3SD not growing according to FH background—find a chart
31 ADDITIONAL STUDIESContrasexual peripheral precocious puberty in virilized girls (clitoromegaly) with or without pubic hairTotal testosterone as an overall indicator of androgen exposureDHEA-Sulfate as a screen for virilizing adrenal tumor17-hydroxyprogesterone and androstenedione as a screen for congenital adrenal hyperplasiaACTH stimulation testing or adrenal imaging next with guidance from pediatric endocrinologist
32 ADDITIONAL STUDIESIsosexual peripheral precocious puberty in boys with or without pubic hairhCG measurement for testicular tumorDHEA-Sulfate as a screen for virilizing adrenal tumor17-hydroxyprogesterone and androstenedione as a screen for congenital adrenal hyperplasiaACTH stimulation testing, adrenal, or testicular imaging next with guidance from pediatric endocrinologist
33 TREATMENTIncomplete Precocious Puberty (premature thelarche and premature adrenarche)…REASSURANCE AND FOLLOW-UPCentral Precocious Puberty (treatment is GnRH agonists, e.g. LupronPeripheral Precocious Puberty (eliminate exposure to exogeneous source of sex steroids; surgery to remove testicular, ovarian or adrenal tumor or ovarian follicular cyst)Sometime growth in straightforward, other times it is Inconclusive
34 TREATMENT (2) Peripheral Precocious Puberty (rare forms)… Congenital Adrenal Hyperplasia is treated with glucocorticoidsMcCune-Albright Syndrome and Familial Male-Limited Precocious Puberty are treated with aromatase inhibitors and antiandrogens
35 REFERENCESCarel JC, Leger J. Clinical practice: Precocious puberty. N Engl J Med 2008; 358:2366.Muir A. Precocious puberty. Pediatr Rev 2006; 27:373.
36 CASE STUDY #18 year old boy with several dark pubic hairs at the base of the penis for the past several months. No genital enlargement. He has always been tall, as per parents. They describe him as moody and quick to cry. They have noticed strong body odor and oily hair.PMH unremarkable. Father 6’ 2’’. Mother 5’10’’.Height and weight are at the 97th percentileTanner stage 3 pubic hair with testicle <2.5 cm
37 CASE STUDY #1Bone Age is 9 ½ years which is 18 months (2 SDs) above the mean for chronological ageDIAGNOSIS?TREATMENT?
38 CASE STUDY #27 ½ year old African American girl who experienced a menstrual period a few months before. She has pubic hair, body odor, oily skin and mild acne.Mother is 5’6’’with menarche at age 12. Father’s height and onset of puberty are not available.Child is at the 90th percentile for both height and weight with no recent acceleration in either parameter.Child is Tanner Stage 4 for both pubic hair and breast development. No café-au-lait spots.FTT
39 CASE STUDY #2Bone Age is 11 years at a chronological age of 7 7/12 years. This is 3.4 SDs above the mean for chronological age.LH was 18 (nl for prepubertal girls is <0.03). FSH was 8.5 (nl is <4.2) and estradiol was 39 (nl <15). These results were during leuprolide stimulation testing.
40 CASE STUDY #2Pelvic ultrasound was read as abnormal because of a prominent endometrial stripe on the lateral views, which is typically seen in pubertal girls. Ovaries were unremarkable.Pituitary MRI indicated some slight prominence of the gland, given her age, but no overt pathology.
41 CASE STUDY #2Treatment with Lupron has stabilized bone development and she has had no further menstrual periods.She continues to be at Tanner Stage 4 for pubertal development
42 CASE STUDY #3A six year old girl developed a bump in the left breast over the preceding several months. This had progressed to both sides, but most recently the right side regressed, so only left-sided breast growth remains. She has had no vaginal discharge, neither bloody or mucous in nature. No pubic hair growth, body odor or skin changes. No acceleration in height growth.
43 CASE STUDY #3Mother is 5’7’’ with onset of menarche at age 12 years. Father is 5’11’’ with normal onset of puberty.Height and weight are at the 50th percentileTanner Stage 2 on the left. Tanner 1 on rightTanner Stage 1 pubic hair.
44 CASE STUDY #3Bone Age is 1 SD above the meanWhat Next?
45 CASE STUDY #3 LH was 0.021 (nl is <0.03) FSH was (nl is <4.2)Estradiol was 2.0 (nl is <15)Diagnosis?What Next?
46 THANK YOUWhat do we want with that vast worthless area, that region of savages and wild beasts, of deserts, of shifting sands and whirlwinds of dust, of cactus and prairie dogs?To what use could we ever hope to put those great deserts, those endless mountain ranges, impenetrable and covered to their bases with eternal snow?Daniel Webster1844