Clin Pediatr Endocrinol 1993; (Suppl 3):15-33 Copyright (C)1993 by The Japanese Society for Pediatric Endocrinology Assessment of Skeletal and Sexual Maturity: Theoretical and Practical Aspects Milo Zachmann Department of Pediatrics, University of Zurich, Kinderspital, Ziirich, Switzerland Abstract. Physical changes of sexual maturation and their clinical relevance are discussed in the first part, and the timetable of development in Swiss girls and boys as established from the Zurich longitudinal study is presented. The second part deals with changes in body size and shape and aspects of skeletal maturation. Prepubertal height is nearly identical in both sexes. During puberty important sex differences become evident and maturation is faster in girls by about 2 years. Puberty bigins at the same stage of skeletal maturation (sesamoid bone) in both sexes, and milestones (e.g. peak height velocity) are reached at the same degree of maturation. For bone age estimation, the Greulich and Pyle method is frequently used, but depending on the situation, that of Tanner et al. may be more useful. For height prediction, the methods of Bayley and Pinneau, Roche et al. and Tanner et al. are most widely used. None of them is always the most accurate one, but depending on the condition and relation between bone and chronologic age, the criteria for selection are discussed. Sex hormones modulate body proportions but have no influence on adult height. Adult height and velocity of maturation are independent multifactorial variables. The sex difference in adult height (12.5cm in Switzerland) is due to several components. Puberty is also characterized by changes in body composition. Lean body mass increases early in boys and girls. In girls, it peaks at menarche and then diminishes. The amount and distribution of water increases in boys and decreases in girls secondary to the greater accumulation of fat in girls. Hormonal changes during puberty are discussed in the last part. Basal gonadotropin levels increase, FSH more in girls than in boys, LH about equally in both sexes. More important is the advent of rhythmic, pulsatile gonadotropin secretion. The most obvious changes are the increas- ing secretion rates of sex steroids. To avoid extreme variation of normal values, estradiol and testoserone should be related to bone age and/or pubertal stages rather than to chronologic age. The role of DHEA in puberty is unclear. It increases before puberty at adrenarche. Also growth hormone, its binding protein, and IGF I and its binding protein 3 increase. Finally, synergistic metabolic effects between GH and sex hormones with examples using the stable isotope 15N are discussed. Key words: puberty, growth, bone age, height prediction Puberty is, apart from the fetal period, the time during human life where the most Correspondence: Milo Zachmann, M.D. Professor of Pediatric Endocrinology Department of Pediatrics University of Zurich Kinderspital Steinwiesstr. 75 CH-8032 Ztirich Switzerland 15 16 ZACHMANN dramatic somatic changes take place. If one only occurs before menarche. It can now be looks at the simplest thing, the weight of easily studied by echography. different organs, it can be seen how tremen- One of the first signs of puberty in girls is dous these changes are. Compared with the the onset of breast development. The physical age of 10 years, the body weight, the anterior characteristics of the stages of breast develop- pituitary and the pancreatic islets about dou- ment have been outlined by Tanner and his ble during this period, the thyroid triples, the group [5,6]. Many clinicians combine breast ovaries increase five-, and the testes even and pubic hair standards into one staging; about 20-fold. however, it seems to be important to stage In the following, first a short account will breast and pubic hair development separately be given of the physical changes of sexual to be able to determine if there is a discrep- maturation and their clinical relevancel. [1]. ancy between the two stages, as can be the In the second part, a short review of aspects of case e.g. in excessive adrenal androgen secre- growth and skeletal maturation will be given tion such as in late-onset congenital adrenal and finally, hormonal changes that take place hyperplasia. Breast development is mainly during pubery will be briefly discussed. regulated by ovarian estrogen secretion, but pubic hair development is stimulated by adrenal androgen secretion. The stages of Female secondary sex characteristics breast development are individually variable: In girls, secondary sexual development some adult women never progress beyond includes the enlargement of the ovaries, stage IV, and some girls progress directly from uterus, vagina, labia, and breasts and the stage III to stage V. Unilateral breast develp- growth of pubic hair [2,3]. The vagina begins ment is normal in early puberty and may to increase in length before the appearance of persist for several months before the other secondary sex characteristics and continues to breast bud appears. Marked or prolonged enlarge until menarche. The cytologic developmental asymmetry, however, may changes of the vagina occur as a result of reflect estrogen insensitivity of the breast tis- estrogen stimulation. The vaginal epithelium sue, prior trauma, or underdevelpment of the undergoes a transformation from parabasal to underlying pectoral muscle. Adolescent girls about 50% intermediate cells. At approximate- are often concerned about breast size, think- ly one year before menarche, the vaginal pH ing their breasts might be either too small or converts from neutral to an acidic environ- too large, but there are no normal standards ment secondary to the presence of lactobacilli. for size. Height, weight, level of estrogen and With puberty the size of the mons pubis progesterone once in the normal adult range, increases by fat accumulation and the labia or breast size of other women in the family majora become larger. The surfaces of the does not have a high correlation with amount labia develop fine wrinkles. With great indi- of breast tissue, but overall non-gladular vidual variation, the clitoris also increases in breast size is somewhat influenced by weight. size [4]. Concerning the uterus, it has no flex- Experience with tall girls treated with ion during childhood. In the prepubertal high doses of estrogens to reduce final adult period, the corpus increases only slightly, height also shows that breast size is not direct- accounting for about one third of the com- ly related to the quantity of circulating bined weight of cervix and corpus. The estrogens, because in these girls breast size is growth of the uterus during early puberty is not larger than in normal untreated girls [7]. primarily caused by the enlargement of the The age at which each stage of breast myometrium. The endometrium does not development occurs has been determined in begin to develop until after the onset of secon- longitudinal studies in American, British and dary sexual characteristics, and rapid increase Swiss girls [3,6,8]. The complete process of 17 Skeletal and Sexual Maturation breast development, from the appearance of cycles in 12- to 14- year-old girls are anovular, stage II to the attainment of stage V, takes an whereas at the age of 21 years, 60% to 80% of average of 4 years, with a range of 1.5 to 9.0 the cycles are ovular. years. As far as pubic hair is concerned, the Some voice change occurs in pubertal sequence in girls generally begins with the girls, but unlike in boys, may consist more of appearance of breast buds and linear growth an alteration in quality than in pitch [9]. A acceleration but a number of normal girls time plan in girls has been established from develop pubic hair before breast enlargement the Swiss study by Largo and Prader [8]. has occurred. The age at which each stage of pubic hair development occurs has also been determined in longituidinal studies. Marshall Male secondary sex characteristics and Tanner [6] used photographs to study Secondary sexual development in boys pubic hair growth so the ages at which sub- includes genital development, testicular vol- jects were said to reach stage II are somewhat ume, pubic and axillary hair growth and later than in other studies. The mean duration change of voice. The sequence of pubertal of time to progress from stage II to stage V development of the external genitalia in most pubic hair is 2.5 years, with a range of 1.4 to 3. normal boys begins with testicular enlarge- 1 years. There is a high correlation between ment. The changes at puberty in boys are breast and pubic hair stages for black and primarily the result of androgen secretion by white American girls [3]. Black girls are more the testes. Adrenal androgens account, if at advanced than whites for each chronologic all, for a small part of very early pubic hair age and girls in Western regions of the United only. Again, it is better to describe the genital States lagged slightly behind girls from other stage separately from the pubic hair stage. regions in pubertal development. Cross-sectional data of testicular volume Axillary hair occurs at a mean age of 13.1 are not very valuable, because they show a years in American girls, 12.5 years in British very wide distribition. A testicular volume of girls, and somewhere in beween in Swiss girls. about 8ml may still be normal. In this context, Axillary hair takes approximately 15 months it has to be said that the inexperienced exam- from first appearance to adult distribution. iner using Prader's orchiometer generally The apocrine glands of the axilla and vulva obtains too high volumes. Although measure- start to function at about the same time as ment of tesicular volume with this instrument hair appears in these regions.