Peds Endo # 1

Precocious puberty:
is defined as the appearance of breast development prior to age 6 to 7 years in Caucasian girls and prior to 5 to 6 years in African-American girls, as is sexual development before 9 years in boys.Delayed Puberty:If there is no evidence of Sexual Maturity Rating stage 1 genital development by 13 years in girls and 14 years in boys.

1. PCO: Polycystic ovarian syndrome
q 73/08 describes a typical example: A 16-year-old p/w irregular menstrual periods. She had menarche at 11 years of age and experiences menstrual periods every 2 weeks to 3 months. She has noticed increased acne, facial hair growth, and a 20-lb weight gain over the past year .

= This is PCO.
a] Abnormalities observed in patients who have PCOS occur in four key areas: 1) increase in LH secretion, 2) increase in adrenal androgen production, 3) increase in body mass, and 4) onset of adult patterns of insulin resistance.
b] Other criteria often used to support a diagnosis include insulin resistance, perimenarcheal onset, elevated LH-to-FSH ratio, and US abnormalities.
c] Patients are at increased risk for DM, obesity, insulin resistance, infertility, and impaired quality of life.

2. Q 133/06
You see a 6-year-old girl whose mother tells you the child has had adult body odor since the age of 5 years. On physical examination, you note that she has pubic hair with a sexual maturity rating of 3. What kind of personality will you see in this isolated early adrenarche:

Ans: an obese African-American and has a growth rate of 2 inches in the past year

Theory:
i) Breast bud development (Thelarche) is the first sign of puberty in 90% of Caucasian girls, with pubarche (appearance of pubic hair) occurring within 6 months of thelarche. Pubarche may be the first sign of puberty in 10% of these girls and in a larger proportion of African-American and Hispanic girls. Progression through puberty takes 3 to 5 years. The pubertal growth spurt occurs in the earliest phases of female puberty (stage 2 to 3 thelarche); menarche usually occurs later in puberty at about stage 4 thelarche.

ii) Now, African-American girls, particularly those overweight, often have early isolated adrenal puberty (adrenarche) at a relatively early age. The appearance of pubic hair at age 6 years, if associated with a normal growth rate, is considered within the range of normal in this population.
A rapid growth rate or other signs of androgen effect (clitoromegaly) deserve more thorough evaluation for the source and nature of the androgen.

NB: Adrenarche is less common as the first sign of puberty in Caucasian girls, although it may occur.

Progression of full puberty (thelarche) in any girl who also has adrenarche at 6 years of age requires a more substantial evaluation, including bone age radiography.

3. Q 10/2008: During the health supervision visit of a 5-year-old girl, you notice pubic hair (SMR 3). Her height is at the 75th percentile and weight is at the 95th percentile. She has no acne or clitoromegaly. Her mother tells you the girl developed an adult body odor around 8 months ago, and the mother noticed the pubic hair about 6 months ago. She adds that the pubic hair is a little more noticeable now than when she first saw it.
Of the following, the MOST important initial screening study is:
Ans: Bone age radiographs.

This is Adrenarche. Early adrenal puberty (adrenarche) is the usual reason for slow development of pubic and axillary hair without evidence of rapid masculinization (increased growth rate, clitoral enlargement, acne) in children older than 4 years of age. The growth rate is stable in such children, and the only signs of masculinization are usually adult body odor followed by increased pubic and axillary hair, as described for the girl in the vignette. The first step in evaluation of such children is to determine their bone age. The bone age rarely is more than 1 year advanced beyond chronologic age, and if bone radiographs document that fact, usually only clinical follow-up is necessary.
ii) If the bone age radiograph is advanced more than 1 year beyond chronologic age, there is a possibility that the patient may have late-onset congenital adrenal hyperplasia (CAH). This condition is caused most commonly by mild 21-hydroxylase deficiency and is associated with an elevated 17-hydroxyprogesterone value either at baseline or following adrenocorticotropic hormone (ACTH) stimulation.

4. A 8 yrs gilr has developed breast buds (Thelarche). How soon she will achieve menarche? q 149/06

Ans: within 2- 3 yrs of initiation of thelarche.

i) Although the age of normal initial development of breast tissue (thelarche) is a bit earlier than previously assumed, the pace of female puberty has not changed in the past 30 years.

Menarche usually occurs within 2 to 3 years after the onset of thelarche.
Girls typically reach menarche when they have reached sexual maturity rating stage 3 to 4 thelarche (Item C149A), but menarche is a marker of uterine estrogen effect and does not correlate precisely with pubertal staging.

In Caucasian girls, the earliest normal onset of pubertal change now is considered 7 years; for African-American girls, the age is 6 years. Many girls who develop breast tissue early have a slower progression to menarche. The average age at menarche has changed little in the past 30 years (about 12 years for African-American girls and 12.5 years for non-Hispanic Caucasian girls). The earliest normal age for menarche is 9 years. The growth spurt in girls usually occurs at the very beginning of puberty and is influenced by stimulatory low levels of estrogen. By sexual maturity rating stage 3 puberty, the growth rate begins to slow.

5. Question 10/07
A 15-year-old boy comes to your office: expresses concern that he is only 5 ft, 2 in tall and is not competitive in track. P/E: he appears healthy, has a height of 62 in, and weighs 96 lb. His testes are 8 mL in volume bilaterally, there is slight pubertal phallic enlargement, and he has Sexual Maturity Rating 3 pubic hair. He has a small amount of subareolar breast tissue. His last health supervision visit was 2 years ago. He did not have pubic hair at the last visit, and his testes were described as "prepubertal" in size.

= constitutional delayed puberty
It is not exercise-induced growth delay or undernutrition.

Puberty is considered delayed in boys: if there is no testicular enlargement by age 14 years. Unless other features are present on physical examination or history, it is very difficult to to separate boys who have delayed puberty clinically from those who have true hypogonadotropic hypogonadism until failure of pubertal progression persists for several years. After puberty commences, adult testicular size usually is achieved by 3.2±1.8 years. The boy described in the vignette is of normal height for age and is progressing into puberty, based on review of his previous visit and his present appearance. Most likely, he has only mild constitutional delayed puberty. Most boys who have constitutional delayed puberty are underweight and do not have other signs of chronic illness. Exercise and weight loss rarely induce the type of marked growth delay in boys that is seen in girls who are competitive gymnasts or active in ballet. Although Klinefelter syndrome may lead to failure to progress through puberty, the increasing testicular size of the boy in the vignette makes this diagnosis unlikely. Prolactinomas can inhibit pubertal growth, but are not common. Underweight caused by undernutrition must be severe before it inhibits growth and puberty. Only close follow-up is required for a boy who seems to be progressing into puberty. However, if there is evidence of failure to progress into puberty, a full evaluation to determine if the boy has an underlying chronic illness such as celiac disease or inflammatory bowel disease, hypergonadotropic hypogonadism as seen in Klinefelter syndrome, or other endocrine disorder such as a prolactinoma, is indicated.

6. Q 26/ 07A 16-year-old boy is brought to your office by his parents because he wants medicine to help him grow and develop muscles. He has been working out for 1 year without much effect. On physical examination, his height is 63 in (adjusted mid-parental height, 73 in), he weighs 106 lb, and he has testes that are 8 mL in volume. He appears healthy but very young. His father says that he was very small as a boy but was given three injections of growth hormone when he was 16 and grew to his present height of 71 in during late high school and college.
Laboratory test results for the boy are normal, including a complete blood count, erythrocyte sedimentation rate, electrolytes, blood urea nitrogen, creatinine, prolactin, insulin-like growth factor-1, tissue transglutaminase antibody, quantitative immunoglobulin A, free thyroxine, and thyroid-stimulating hormone.
A bone age radiograph is reported to resemble that of a 13-year-old.Of the following, your BEST approach is to:
= Counsel that this is delayed puberty and that he will grow over the next few years.

NB: A normal insulin-like growth factor-1 concentration does not entirely rule out GH deficiency, but the boy's regular growth rate, reasonable height, strong family history for pubertal delay, and signs of puberty make growth hormone deficiency very unlikely.

7. Q 42.07 presents a 16 yrs old f with arrest of puberty and bitemporal visual field defects and asks you what to measure[choose one]: IGF or prolactin or LH or TSH

Answer is: Prolactin

i) The 16-year-old girl described in the vignette has had arrest of pubertal development with failure of menarche for at least 2 years. The bitemporal visual field deficits imply the presence of a large suprasellar mass.

The two most common causes for such a mass lesion are :
pituitary macroadenomas and craniopharyngiomas.

The most common macroadenoma is a prolactinoma.
Elevations of prolactin values could be due to increased prolactin secretion from a prolactinoma or to compression of the pituitary stalk by another pituitary tumor, a craniopharyngioma, or other space-occupying lesion.

Because stalk compression interferes with the dopaminergic inhibitory influences on pituitary release of prolactin, prolactin concentrations of up to 200 mcg/L may be due solely to stalk compression. Prolactin concentrations in that range interfere with normal menstrual cycling and suppress normal puberty.
A large tumor also might interfere with pubertal and other pituitary hormones because of its mass. Accordingly, measuring prolactin will be most helpful in determining whether the girl has a prolactinoma.

ii) Rx of Prolactinomas: usually respond to treatment with medication such as cabergoline; surgery rarely is required.

8. Q 58/07A normal-appearing 9-month-old boy is discovered on routine herniorrhaphy to have bilateral Fallopian tubes and a rudimentary uterus. Biopsy of the gonads performed during this procedure revealed normal testicular tissue. On examination today, his phallus is normal in size and appearance, and his descended testes are both 2 mL in volume.The MOST likely sex chromosome complement for this child is: XY

Note that he will be XY because he has everything needed to be a boy!! That is easy! But there is one additional probelm: why he has fallopian tubes and rudimentary uterus!

Because he has the persistent müllerian duct syndrome.

A peptide hormone (müllerian inhibiting substance [MIS] or anti-müllerian hormone [AMH]) produced by the testis induces regression of the müllerian ducts during fetal development.

These ducts become the fallopian tubes and uterus as well as the upper part of the vagina if there is no regression.

This is an autosomal recessive disorder and is associated with an XY chromosomal pattern.

9. Question 74/07a 1-day-old infant has mild clitoromegaly (Item Q74A) and palpable masses in the labial folds bilaterally. Chromosome studies reveal : the infant has an XY karyotype.Of the following, additional history is MOST likely to reveal that the infant's:

Maternal aunts are infertile.

Now,
i) The baby described in the vignette, who has mild masculinization and palpable gonadal masses with an XY karyotype, is an undervirilized XY infant = male pseudohermaphroditism. Obviously!
No problem so far.

ii) Because gonads are present below the inguinal ligament, there is testicular tissue.
Even with careful evaluation, an underlying cause cannot presently be determined in up to 40% of undervirilized XY infants.

However, one of the most common findings is androgen insensitivity (AIS), which may be complete (CAIS) or partial (PAIS). The finding usually represents a defect in the androgen receptor and is inherited in an X-linked pattern. Therefore, some maternal aunts are likely to have the same disorder, have an XY chromosomal pattern, and be infertile.

10. Question 90/08

A newborn: her genitalia appear abnormal. There is an enlarged clitoris (1.5 cm in length) (Item Q90A) and a small amount of posterior labial fusion. Amniocentesis was performed during pregnancy, and the karyotype was 46,XX.Of the following, the maternal history is MOST likely to reveal exposure to:

Danazol/ ethinyl estradiol/ progesterone in oil/ organo P pesticides

Answer: Danazol

Note that it is a girl with male features. Thus a male harmone is the culprit and among choices, danazol fits the scheme.

i) Danazol, used to treat endometriosis, is a modified progestogen that has an androgenic effect. It has produced virilization in female fetuses.

Exposure after the first trimester can lead to clitoromegaly without midline fusion. Earlier exposure for more than 8 weeks after fertilization may cause labial fusion of varying degrees associated with clitoromegaly, as described for the newborn in the vignette.ii) Ethinyl estradiol is an estrogen commonly found in oral contraceptive agents. It has not been associated with masculinization of female fetuses.

iii) Progesterone in oil is the natural progesterone and has not been associated with masculinization; only substituted synthetic progestins have this effect.

11. Read q 186/07

12. q 202/07 shows a 14 yrs/m who is not getting taller and PREP will lead u to suspect GH def. But be carreful, here the boy is losing wt around the time he is attenuating.

T = Measure tissue transglutaminase antibody

However, severe attenuation of weight gain preceding attenuation of linear growth almost always is a sign of a severe underlying disorder.
NB: Celiac disease is a common cause of short stature associated with underweight. If Ig A levels are normal, measurement of TTG antibody is the best screening study for celiac disease.

NB: Measures of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 are good screening studies for growth hormone deficiency, although hepatic IGF-1 production also is stimulated by insulin and may be low in underweight children.

12. q 218/07 is interesting and confusing.