Pediatric Examination and Board Review (121 page)

FIGURE 73-1.
The classical phenotypic characterstics of women with Turner syndrome. (Reproduced, with permission, from Schorge JO, Schaffer JI, Halvorson LM, et al. Williams Gynecology. New York: McGraw-Hill; 2008: Fig. 16-4.)

7.
(C)
The complete androgen insensitivity syndrome is an X-linked recessive disorder in which 46,XY individuals appear phenotypically to be women. These patients have testosterone insensitivity because of a defect in androgen receptors and therefore do not develop testosterone-dependent male sexual characteristics. At puberty, breast development occurs, but pubic and axillary hair is sparse. Although they typically present with normallooking female external genitalia, testes may be palpable in the labia majora or inguinal area. There is regression of the müllerian structures leading to absence of the fallopian tubes, uterus, and upper third of the vagina. The diagnosis can be confirmed by the finding of elevated testosterone concentrations, XY karyotype, and pelvic ultrasonography results. Surgical excision of the testes is recommended given the increased risk of testicular cancer in this condition.

8.
(E)
The clinical history should include a detailed account of the onset and tempo of pubertal changes, including growth spurt, family history of pubertal delay, symptoms of virilization, galactorrhea, and medications. Headaches, visual field defects, polyuria, polydipsia, and fatigue should be investigated to exclude other hypothalamic-pituitary diseases. It is also essential to document recent stressors, changes in diet or exercise patterns, changes in body weight, and recent symptoms suggestive of severe or protracted illness.

9.
(E)
Adolescents with primary amenorrhea should have a complete physical examination, including current height and weight, calculated BMI, arm span, breast development, galactorrhea, and a search for signs of thyroid dysfunction. The skin should be examined for acne, hirsutism, striae, and hyperpigmentation. A growth chart review will be essential to assess progression of linear growth and its temporal relation with weight changes. A careful external genital examination is needed to evaluate pubertal development, clitoral size, and appearance of the hymen. The presence of a normal vagina, cervix, uterus, and ovaries can sometimes be determined by a gentle one-finger vaginal-abdominal or recto-abdominal examination but is more accurately defined by ultrasonography. Findings consistent with Turner syndrome and other genetic disorders should be documented. Hypertension, if present, may suggest coarctation of the aorta, one of Turner syndrome’s typical stigmata. High BP may also be a feature of 17α-hydroxylase deficiency, a rare disorder leading to decreased cortisol synthesis with increased production of adrenocorticotropic hormone (ACTH), mineralocorticoid excess, and lack of pubertal development. The presence of acne is associated with normal or increased production of adrenal and gonadal steroids.

10.
(D)
It is essential to confirm the presence or absence of a normal vagina, cervix, and uterus (either clinically or by ultrasound) as a first step in the workup of primary amenorrhea. If the uterus is absent, a karyotype and testosterone levels are obtained to distinguish between isolated, abnormal müllerian development with absent uterus, 46,XX karyotype that has normal testosterone levels, and androgen insensitivity syndrome. If the correct diagnosis is the last, the karyotype will be 46,XY and the testosterone levels will be elevated. If, however, the uterus is present and there are no outlet obstructions such as imperforate hymen or vaginal atresia, an endocrine evaluation should be performed.

11.
(E)
Pregnancy should always be excluded first by testing human chorionic gonadotropin (hCG) in serum or in urine. A CBC, complete metabolic panel, and ESR may help to exclude undiagnosed chronic illnesses leading to hypothalamic dysfunction. It is useful to obtain FSH levels, which, if elevated, will indicate primary ovarian failure and will lead to the investigation of the potential causes of hypergonadotropic hypogonadism such as Turner syndrome or mosaicism, Noonan syndrome, autoimmune oophoritis, or gonadal damage secondary to chemotherapy or radiation. Elevated FSH levels in the presence of hypertension suggest either Turner syndrome with coarctation of the aorta or 17α-hydroxylase deficiency. An elevated serum progesterone, low cortisol, low 17α-hydroxyprogesterone, and increased serum deoxycorticosterone can confirm this latter condition, a rare form of congenital adrenal hyperplasia.

Normal or low FSH levels suggest a hypothalamic dysfunction such as functional hypothalamic amenorrhea, usually secondary to weight loss, excessive exercise, stress, or severe or prolonged illness. Less common causes of hypothalamic dysfunction include inflammatory or infiltrative diseases, craniopharyngiomas and other brain tumors, cranial irradiation, or brain injury. Serum prolactin and TSH are necessary to exclude hyperprolactinemia and thyroid disorders. Testosterone and DHEA-S levels are part of the laboratory workup, particularly if there is clinical evidence of hyperandrogenism. A bone age determination will be helpful in adolescent girls with primary amenorrhea and other signs of pubertal delay to exclude constitutional delay of puberty (a condition occurring more frequently in boys than in girls) and hypothyroidism. A bone densitometry determination would be helpful in this case, given the history of primary amenorrhea, strenuous athletic training, and stress fractures.

12.
(E)
A cranial MRI is indicated in girls with hypogonadotropic hypogonadism, particularly in the presence of headaches, visual field defects, an abnormal sella documented on a radiograph, or any other signs of hypothalamic-pituitary dysfunction. It would be the least helpful in the workup of amenorrhea secondary to hypergonadotropic hypogonadism because the elevation of gonadotropins in that case results from ovarian failure.

13.
(E)
Exercise is clearly beneficial for young women because it leads to improved cardiovascular fitness, weight control, lower BP, and improved lipid profile. In addition, it promotes socialization, a greater sense of well-being, and self-esteem. There are, however, some potential problems associated with strenuous athletic training, including delayed pubertal development and menarche, eating disorders such as anorexia nervosa, bulimia, purging, binging and fasting, and hypoestrogenic amenorrhea. Disordered eating has been reported in 15-62% of young female athletes. Strenuous exercise also increases the risk of osteoporosis and stress fractures.

14.
(E)
In female athletes, bone mineral density correlates with weight, weight/height, and estrogen and testosterone levels. Low bone density is associated with low estrogen levels, delayed puberty and menarche, low calcium and protein intake, low weight, low BMI, low androgen levels, disordered eating, and family history of osteoporosis. Use of oral contraceptives in the postmenarchal athletic female decreases the likelihood of osteoporosis. Delayed menarche associated with hypoestrogenemia can have a significant effect on bone mineralization in adolescent athletes, given the fact that 48% of skeletal mass in women is normally attained during puberty.

15.
(B)
An eating disorder should be considered in the differential diagnosis of this 16-year-old girl with a history of weight loss in the past, strenuous exercise, and amenorrhea. Postural dizziness, depressive symptoms, constipation, hair loss, cold intolerance, epigastric pain, nausea, vomiting, fatigue, cramps, and muscle weakness would be among the common presenting symptoms of anorexia nervosa.

16.
(E)
Eating disorders are among the causes of hypothalamic dysfunction leading to primary amenorrhea. Anorexia nervosa is 10 times more common in girls than in boys. The mean age of onset is 13.7 years, but it can start in children as young as 10 years. Amenorrhea is present in almost 100% of the cases, coinciding with weight loss in half of them, following it in 25%, and preceding it in 25% of anorectic girls.

17.
(C)
The most common signs of anorexia nervosa are decreased weight and cachexia, decreased temperature, bradycardia, hypotension, dry, hyperkeratotic skin, edema, acrocyanosis, nail pitting, and increased lanugo hair.

18.
(C)
Young women with eating disorders typically have a constellation of psychological features, including low self-esteem, perfectionism, depression, anxiety, obsessional thoughts, social anxiety, and overachievement. Disturbed body image, increased preoccupation with food, and decreased sexual interest are common features in this condition.

19.
(E)
In this 16-year-old with strenuous athletic training leading to primary amenorrhea, in whom other etiologies have been excluded, it would be reasonable to offer counseling about decreasing physical activity to a level adequate to maintain appropriate weight and bone mineral density while at the same time increasing calcium intake to avoid osteoporosis and stress fractures. If estrogenization is thought to be adequate, in the absence of menses, a progesterone challenge test may help bring about her periods. If the response to this test is positive, a repeat progesterone challenge may be offered every 2-3 months. Some authors advocate the cyclic use of estrogens and progestins to treat girls with hypothalamic amenorrhea once an acceptable height has been attained.

S
UGGESTED
R
EADING

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Pediatric and Adolescent Gynecology.
5th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005.

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CASE 74: A 17-YEAR-OLD GIRL WITH PAINFUL MENSES

A 17-year-old girl comes to the clinic complaining of painful periods. You have been her pediatrician for several years and know that she has been a healthy, welladjusted adolescent. She started her menses at age 14 years. Her periods have been regular for the most part, although she has occasionally complained about heavy but painless periods lasting up to 6 days. Over the past year, her periods have become painful to the point that she had to miss school an average of 2 days a month. She also reports associated nausea during menses. She has tried over-the-counter pain relievers without success. She has been dating for a year but denies sexual activity. She has heard that “the pill may help with cramps” and wants to know your opinion about that. Her past medical history is noncontributory. Her mother had a history of severe menstrual cramps during adolescence. The review of systems shows that she had vomiting on 2 occasions during menses during the past 3 months. She also mentions increased nervousness, headaches, and backaches, all of which have developed over the past year and usually present together with her episodes of pelvic pain.