A d o l e s c e n t G ro w t h a n d Development Veenod L. Chulani,
MD, MSEd, FSAHM
a,b,
*, Lonna P. Gordon,
MD, PharmD
c
KEYWORDS Adolescence Puberty Precocious puberty Delayed puberty Psychosocial development KEY POINTS Adolescence is a developmental stage defined by physical and psychosocial maturation. Pubertal growth and development is mediated by dynamic, physiologic changes in the neuroendocrine system. Although variability in the timing of attainment of pubertal milestones is common and most adolescents who display patterns of development outside of defined norms have no underlying pathology, abnormal patterns of development may be owing to underlying pathology and requires evaluation. The dynamic psychosocial changes of adolescence incrementally prepare youth to assume adult status and fulfill adult societal roles and expectations.
INTRODUCTION
Adolescence is a developmental stage defined by physical and psychosocial maturation. This stage encompasses puberty, a complex series of events mediated by genetic, hormonal, and environmental factors culminating in somatic maturity and the achievement of reproductive capacity. It is also accompanied by expanding cognitive abilities, the development of identity, and dynamic social transitions through which youth achieve adult status. Providers caring for adolescents require a sound knowledge of the physical and psychosocial changes of adolescence. This article reviews the neuroendocrine basis of puberty, normal pubertal development, and the evaluation and management of adolescents with suspected pubertal abnormalities. An overview of adolescent psychosocial development and the developmental tasks of adolescence is included.
Funding Sources: None. Conflict of Interest: None. a Division of Adolescent Medicine, Arnold Palmer Hospital for Children, 86 West Underwood Street, Suite 202, Orlando, FL 32806, USA; b Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32304, USA; c Icahn School of Medicine, Mount Sinai Adolescent Health Center, 320 East 94th Street, New York, NY 10128, USA * Corresponding author. 86 West Underwood Street, Suite 202, Orlando, FL 32806. E-mail address: [email protected] Prim Care Clin Office Pract 41 (2014) 465–487 http://dx.doi.org/10.1016/j.pop.2014.05.002 primarycare.theclinics.com 0095-4543/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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PHYSICAL GROWTH AND DEVELOPMENT Neuroendocrine Basis of Puberty
The neuroendocrine basis of puberty has been the subject of extensive investigation and the identification of the exact trigger of puberty onset has drawn considerable attention. Mediated by a complex interplay of inhibiting and activating factors, pubertal growth and development can be viewed as the result of physiologic changes in the hypothalamic-pituitary-gonadal (HPG), adrenal, and growth hormone axes.1–4 The various axes are depicted in Fig. 1.
Fig. 1. Simplified diagram of the hypothalamic-pituitary-gonadal (HPG) axes, hypothalamicpituitary-adrenal (HPA) axes, and growth hormone (GH) axes. The hypothalamus releases gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), and growth hormone–releasing hormone (GHRH), which stimulate the anterior pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), and growth hormone (GH), respectively. GnRH, LH, GHRH, and GH are released in a pulsatile fashion that varies with pubertal stage. In the HPG axis, FSH stimulates the ovarian follicles to produce estrogen (from androgenic precursors produced from theca cells), inhibin, progesterone, and ova. Estrogen provides both a positive and negative feedback on GnRH. In females, a critical amount of estrogen is needed to produce a positive feedback to stimulate the LH surge that leads to ovulation. In males, FSH stimulates Sertoli cells and seminiferous tubules to produce estrogen, inhibin, and sperm. LH stimulates theca cells in females and Leydig cells in males to produce androgens. On the HPA axis, ACTH stimulates the zona reticularis of the adrenal gland to secrete dihydroepiandrosterone (DHEA). DHEA is then converted to dihydroepiandrosterone sulfate (DHEAS) via sulfotransferase (ST), and to androstenedione (A4) via 3 b-hydroxysteroid dehydrogenase (3b). A4 is then converted to testosterone via 17b-hydroxysteroid dehydrogenase (17b) and estradiol via aromatase (AT). In the GH axis, GH stimulates the liver and epiphyses of bone to produce insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2).
Adolescent Growth and Development
Hypothalamic Pituitary-Gonadal Axis
The HPG axis is functional by 10 weeks’ gestation and remains active until early infancy when it enters into a relatively quiescent phase.5 The onset of puberty is marked the by the reemergence of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Although the exact signals for the pulsatile release of GnRH remain undetermined, the role of hormones associated with nutritional status such as leptin, kisspeptin, and insulin-like growth factor-1 has been suggested.6–9 GnRH stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by gonadotrophs in the anterior pituitary that promote gonadal maturation and the production of sex steroids or gonadarche. In females, mature HPG axis activity is also characterized by the development of positive feedback loop where a critical level of estrogen triggers a large release in GnRH and the subsequent LH surge resulting in ovulation.10 Adrenal Gland Changes
The adrenal cortex is divided into 3 zones, with the zona reticularis predominantly responsible for the secretion of the adrenal androgens, dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione. The zona reticularis involutes shortly after birth and secretes only small amounts of DHEA and androstenedione.11–13 Activation of the zona reticularis with increased secretion of adrenal androgens or adrenarche occurs between 6 and 8 years of age.12,14 Adrenarche is independent from and precedes activation of the HPG axis by approximately 2 years.11 Growth Hormone Axes
During puberty, elevated sex steroid concentrations stimulate the activation of the GH axis characterized by an increase in the amplitude in the pulsatile release of GH. Circulating insulin-like growth factor-1 mediates the anabolic somatic effects of GH and increases correspondingly during puberty, with levels correlating with SMR stages and sex steroid levels.12,14 PHYSICAL CHANGES OF PUBERTY Development of Secondary Sexual Characteristics
The development of secondary sexual characteristics is a hallmark of puberty. Sexual maturity ratings (SMR) scales developed by Marshall and Tanner provide for the staging of genital development in males and breast and pubic hair development in females (Figs. 2 and 3).15–17 These scales allow monitoring of the development of secondary sexual characteristics. They also provide better correlation for the timing of pubertal events than does chronologic age owing to variability in the timing and tempo of pubertal development. Although variability in the timing and tempo is commonly observed, the sequence of pubertal events in males and females is highly predictable and is illustrated in Figs. 4 and 5. The estimated age range of normal variation of pubertal development in US adolescent females is controversial in light of evidence of racial and ethnic differences and decreasing age onset of pubertal changes overall.18–20 The normal age range of puberty is 7 to 13 years for white girls and 6 to 13 years in African-American girls.5,21 Current estimates on the timing of attainment of various SMR stages in females is presented in Table 1. Female puberty generally begins with thelarche (B2), which commonly precedes pubarche (PH2) by about 1 to 1.5 years, although the latter may occur first or simultaneously.22 Despite the earlier onset of breast and pubic hair development, the mean age at menarche of 12.9 (1.20) years in white girls and 12.1 (1.21) years in AfricanAmerican girls20,23 is not significantly younger than previously reported. Menarche most commonly occur during PH4 and usually occurs 2 to 2.5 years after thelarche.17,24
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Fig. 2. Sexual maturity rating (SMR) stages in males. Stage 1 is prepubertal, with no pubic hair and childlike phallus and a testicular volume of 1.6 mL. Stage 2 shows sparse, straight pubic hair along the base of the penis with testicular enlargement and reddening and thinning of the scrotum, and a testicular volume of 1.6 to 6 mL. In stage 3, the hair is darker, coarser, and curlier, extending over the mid-pubis. Further testicular and scrotal enlargement and increase in phallic length. Testicular volume is 6 to 12 mL. In stage 4, hair is adult-like in appearance but does not extend to inner thighs. Further testicular and scrotal enlargement and increased phallic length and circumference; testicular volume is 12 to 20 mL. In stage 5, hair is adult in appearance, extending to the inner thigh. There is an adult scrotum and phallus. Testicular volume is 20 mL. (From Roede MJ, van Wieringen JC. Growth diagrams 1980: Netherlands third nation-wide survey. Tijdschr Soc Gezondheids 1985;63:1–34.)
Adolescent Growth and Development
Fig. 3. (A) Sexual maturity rating (SMR) of breast development in girls. Stage 1 is prepubertal, with no palpable breast tissue. In stage 2, a breast bud develops, with elevation of the papilla and enlargement of the areolar diameter. In stage 3, the breast enlarges, without separation of areolar contour from the breast. In stage 4, the areola and papilla project above the breast, forming a secondary mound. In stage 5, the areola recesses to match the contour of the breast; the papilla projects beyond the contour of the areola and breast. (B) Sexual maturity rating (SMR) stages of pubic hair development in girls. Stage 1 is prepubertal, with no pubic hair. In stage 2, there is sparse, lightly pigmented straight hair along the medial border of the labia. In stage 3, there is a moderate amount of darker, coarser, and curlier and extends over the mid-pubis. Stage 4 hair resembles adult hair in coarseness and curliness, but does not extend to the inner thighs. Stage 5 hair is adult in appearance and extends to the inner thighs. (From Roede MJ, van Wieringen JC. Growth diagrams 1980: Netherlands third nation-wide survey. Tijdschr Soc Gezondheids 1985;63:1–34.)
The mean age of onset of male pubertal development is 11 years, with a normal range of variation of 9 to 14 years.25 Estimates on the timing of attainment of various SMR stages in males are presented in Table 2. Male pubertal development typically begins with testicular enlargement (G2). Pubertal testicular enlargement is characterized by a longitudinal testicular measurement of >2.5 cm or testicular volume of >4 mL.16,26,27 Pubarche (PH2) generally follows closely and correlates with penile growth under the common influence of androgens. Additional pubertal events include spermarche between G3 and G4 and the appearance of facial hair and voice change in SMR stage G4.28 Height Growth
Height growth averages approximately 5 to 6 cm per year throughout childhood,6,29 with a slight deceleration in height growth immediately preceding puberty. During puberty, height velocity increases sharply and peaks during the adolescent growth spurt to ultimately account for about 20% of final adult height. In females, height velocity
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Fig. 4. Sequence of pubertal events in males. PHV, peak height velocity. (From Root AW. Endocrinology of puberty. J Pediatr 1973;83(1):1–19.)
accelerates at a mean age of 9 years and peak height velocity of approximately 8.3 cm per year is attained at a mean age of 11.5 years between SMR stages 2 and 3.30 Height growth rates generally decelerate significantly and there is limited growth potential after menarche. In males, height growth accelerates at a mean age of 11 years and reaches a peak height velocity of approximately 9.5 cm per year at the mean age of 13.5 years during SMR stages 3 to 4.30 Height growth rate decreases thereafter and is generally complete by SMR 5. The 12- to 13-cm male height advantage over females is best explained by the 2 additional years of prepubertal growth and greater peak height velocity rate.29 Prediction of adult height is useful in the monitoring of pubertal development. A commonly used method is based on the calculation of mid-parental height. Most individuals have an adult height that is within 10 cm or 4 inches (2 SD) of the midparental height as calculated below31: For girls 5
ðfathers height 13 cm or 5 inchesÞ 1 mothers height 2
For boys 5
ðfathers height 1 13 cm or 5 inchesÞ 1 mothers height 2
Additional methods of height prediction are often employed in the specialty referral setting, including the Bayley Pinneau method,32 which uses a combination of chronologic age, height, and skeletal age matched to standards.
Adolescent Growth and Development
Fig. 5. Sequence of pubertal events in females. PHV, peak height velocity. (From Root AW. Endocrinology of puberty. J Pediatr 1973;83(1):1–19.)
Differential linear growth in upper and lower extremities results in changes to the upper/lower (U/L) segment ratio during puberty. With greater linear growth in the lower extremities, the U/L segment ratio decreases from about 1.4 in the prepubertal period to a mean of 0.92 in white and 0.85 in African-American adults.33 Body Composition
Despite an overall increase in lean body mass, the percentage of lean body mass in females decreases from about 80% of body weight in early puberty to about 75% at maturity owing to a greater rate of increase in adipose mass.34 The percentage of body fat increases in females during puberty and is related to menstrual function, with 17% required for the initiation and 22% for maintenance of menstruation.35 In males, lean body mass increases from 80% to 85% in early puberty to about 90% at maturity, reflecting increasing muscle mass and decreasing adiposity.34 Approach to Normal Pubertal Variations and Abnormal Pubertal Growth and Development
Clinicians caring for adolescents are tasked with monitoring the timing and progression of puberty and identifying abnormal patterns of growth and development. It should be noted that the majority of adolescents who display patterns of development outside of statistical norms have no pathology and simply lie within the extremes of normal variation. Definitions between normal and abnormal are purely arbitrary and are based on the assumption that pubertal events assume a normal distribution in the population, with a range of 2 standard deviations (SD) above and below the
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Chulani & Gordon Table 1 Descriptive statistics for the timing of sexual maturity stages in females Onset of Stage Stage
Mean Age for Stage
Mean
SD
Mean
SD
11.2
0.7
11.3
1.1
12.5
1.5
Breast stages Stage 2 Roche et al (Ohio) Herman-Giddens et al (USA) African American
8.9
1.9
White
10.0
1.8
12.0
1.0
Stage 3 Roche et al (Ohio) Herman-Giddens et al (USA) African American
10.2
1.4
White
11.3
1.4
12.4
0.9
11.0
0.5
Stage 4 Roche et al (Ohio) Tanner pubic hair Tanner Stage 2 Roche et al (Ohio) Herman-Giddens et al (USA) African American
8.8
2.0
White
10.5
1.7
11.8
1.0
Tanner Stage 3 Roche et al (Ohio) Herman-Giddens et al (USA) African-American
10.4
1.6
White
11.5
1.2
12.4
0.8
Tanner Stage 4 Roche et al (Ohio) Menarche Herman-Giddes et al (USA) African American
12.2
1.2
White
12.9
1.2
Percent menstruating
At Age 11
At Age 12
African American
27.9%a
62.1%
White
13.4%a
35.2%
Onset of axillary hair (stage 2) African American
10.1 2.0
White
11.8 1.9
Mean age for stage 2, 11.3 1.1; mean age for stage 3, 12.5 1.5. a African-American girls enter puberty approximately 1 to 11/2 years earlier than white girls and begin menses 81/2 months earlier. Data from Roche AF, Weilens R, Attie KM, et al. The timing of sexual maturation in a group of U.S. white youths. J Pediatr Endocrinol 1995;8:11–8; Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 1997;99:505–12; and From Melmed S, Polonsky K, Larsen PR, et al. Williams textbook of endocrinology. 12th edition. Philadelphia: Saunders; 2011. p. 1061. Table 25-2.
Adolescent Growth and Development
Table 2 Descriptive statistics for the timing of sexual maturity stages in males Time Between Stages (y) Percentile Stage
Mean Age of Onset ±2 SD (y)
Stage
Mean
5th
G2
11.6 2.1
G2–3
1.1
0.4
95th 2.2
G3
12.9 2.1
PH2–3
0.5
0.1
1.0
PH2
13.4 2.2a
G3–4
0.8
0.2
1.6
G4
13.8 2.0
PH3–4
0.4
0.3
0.5
PH3
13.9 2.1
G4–5
1.0
0.4
1.9
PH4
14.4 2.2
PH4–5
0.7
0.2
1.5
G5
14.9 2.2
G2–5
3.0
1.9
4.7
PH5
15.2 2.1
PH2–5
1.6
0.8
2.7
a
Mean is probably too high owing to experimental method. From Barnes HV. Physical growth and development during puberty. Med Clin North Am 1975;59:1305.
mean used to define the limits of normal variability.1,2,36 A proportion of adolescents, however, display abnormal patterns of development owing to underlying pathology, which makes the clinical evaluation of development outside statistical norms necessary. An approach in the evaluation of adolescents with abnormal development is presented. History A comprehensive history pertaining to general health and growth, including a review of growth charts and the calculation of growth velocity.37–40 Timing of observed pubertal changes, including whether pubertal changes are completely absent or if earlier pubertal noted changes have failed to progress.23,40 General health conditions in the family, heights and growth patterns of parents and siblings, and their timing of attainment of pubertal milestones.41–44 Nutritional history and review of eating habits.39,40,45 Review of systems to rule out chronic illnesses, including a thorough review of the gastrointestinal, endocrine, and central nervous (CNS) systems.39 Physical Examination Determination of height and calculation of height velocity in the prior 6 to 12 months. A 6- to 12-month period is recommended to minimize the effect of observed seasonal variation in height growth.41,42,46,47 Determination of weight and body mass index. HPG axis suppression with delay or disruption of puberty is observed at 50% being peripheral cases, such as neoplasm.39,48 A thorough history and physical examination is necessary in the evaluation of the child with precocious puberty. Determination of bone age and levels of serum estradiol and testosterone are key to the initial evaluation. Significant advancement of bone age beyond chronologic age and pubertal levels of sex hormones confirm precocious puberty and necessitate referral to a pediatric endocrinologist.50 Algorithms for the further evaluation of sexual precocity in males and females are presented in Figs. 7 and 8. Determination of basal LH levels and LH response to GnRH stimulation provide useful diagnostic information. LH levels demonstrate increase in pubertal pattern after GnRH stimulation in CPP and remain prepubertal or suppressed in peripheral precocious puberty. Males with CPP require MRI of the brain to exclude CNS pathology. It is also required in females who have CPP and are
MD, MSEd, FSAHM
a,b,
*, Lonna P. Gordon,
MD, PharmD
c
KEYWORDS Adolescence Puberty Precocious puberty Delayed puberty Psychosocial development KEY POINTS Adolescence is a developmental stage defined by physical and psychosocial maturation. Pubertal growth and development is mediated by dynamic, physiologic changes in the neuroendocrine system. Although variability in the timing of attainment of pubertal milestones is common and most adolescents who display patterns of development outside of defined norms have no underlying pathology, abnormal patterns of development may be owing to underlying pathology and requires evaluation. The dynamic psychosocial changes of adolescence incrementally prepare youth to assume adult status and fulfill adult societal roles and expectations.
INTRODUCTION
Adolescence is a developmental stage defined by physical and psychosocial maturation. This stage encompasses puberty, a complex series of events mediated by genetic, hormonal, and environmental factors culminating in somatic maturity and the achievement of reproductive capacity. It is also accompanied by expanding cognitive abilities, the development of identity, and dynamic social transitions through which youth achieve adult status. Providers caring for adolescents require a sound knowledge of the physical and psychosocial changes of adolescence. This article reviews the neuroendocrine basis of puberty, normal pubertal development, and the evaluation and management of adolescents with suspected pubertal abnormalities. An overview of adolescent psychosocial development and the developmental tasks of adolescence is included.
Funding Sources: None. Conflict of Interest: None. a Division of Adolescent Medicine, Arnold Palmer Hospital for Children, 86 West Underwood Street, Suite 202, Orlando, FL 32806, USA; b Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32304, USA; c Icahn School of Medicine, Mount Sinai Adolescent Health Center, 320 East 94th Street, New York, NY 10128, USA * Corresponding author. 86 West Underwood Street, Suite 202, Orlando, FL 32806. E-mail address: [email protected] Prim Care Clin Office Pract 41 (2014) 465–487 http://dx.doi.org/10.1016/j.pop.2014.05.002 primarycare.theclinics.com 0095-4543/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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PHYSICAL GROWTH AND DEVELOPMENT Neuroendocrine Basis of Puberty
The neuroendocrine basis of puberty has been the subject of extensive investigation and the identification of the exact trigger of puberty onset has drawn considerable attention. Mediated by a complex interplay of inhibiting and activating factors, pubertal growth and development can be viewed as the result of physiologic changes in the hypothalamic-pituitary-gonadal (HPG), adrenal, and growth hormone axes.1–4 The various axes are depicted in Fig. 1.
Fig. 1. Simplified diagram of the hypothalamic-pituitary-gonadal (HPG) axes, hypothalamicpituitary-adrenal (HPA) axes, and growth hormone (GH) axes. The hypothalamus releases gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), and growth hormone–releasing hormone (GHRH), which stimulate the anterior pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), and growth hormone (GH), respectively. GnRH, LH, GHRH, and GH are released in a pulsatile fashion that varies with pubertal stage. In the HPG axis, FSH stimulates the ovarian follicles to produce estrogen (from androgenic precursors produced from theca cells), inhibin, progesterone, and ova. Estrogen provides both a positive and negative feedback on GnRH. In females, a critical amount of estrogen is needed to produce a positive feedback to stimulate the LH surge that leads to ovulation. In males, FSH stimulates Sertoli cells and seminiferous tubules to produce estrogen, inhibin, and sperm. LH stimulates theca cells in females and Leydig cells in males to produce androgens. On the HPA axis, ACTH stimulates the zona reticularis of the adrenal gland to secrete dihydroepiandrosterone (DHEA). DHEA is then converted to dihydroepiandrosterone sulfate (DHEAS) via sulfotransferase (ST), and to androstenedione (A4) via 3 b-hydroxysteroid dehydrogenase (3b). A4 is then converted to testosterone via 17b-hydroxysteroid dehydrogenase (17b) and estradiol via aromatase (AT). In the GH axis, GH stimulates the liver and epiphyses of bone to produce insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2).
Adolescent Growth and Development
Hypothalamic Pituitary-Gonadal Axis
The HPG axis is functional by 10 weeks’ gestation and remains active until early infancy when it enters into a relatively quiescent phase.5 The onset of puberty is marked the by the reemergence of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Although the exact signals for the pulsatile release of GnRH remain undetermined, the role of hormones associated with nutritional status such as leptin, kisspeptin, and insulin-like growth factor-1 has been suggested.6–9 GnRH stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by gonadotrophs in the anterior pituitary that promote gonadal maturation and the production of sex steroids or gonadarche. In females, mature HPG axis activity is also characterized by the development of positive feedback loop where a critical level of estrogen triggers a large release in GnRH and the subsequent LH surge resulting in ovulation.10 Adrenal Gland Changes
The adrenal cortex is divided into 3 zones, with the zona reticularis predominantly responsible for the secretion of the adrenal androgens, dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione. The zona reticularis involutes shortly after birth and secretes only small amounts of DHEA and androstenedione.11–13 Activation of the zona reticularis with increased secretion of adrenal androgens or adrenarche occurs between 6 and 8 years of age.12,14 Adrenarche is independent from and precedes activation of the HPG axis by approximately 2 years.11 Growth Hormone Axes
During puberty, elevated sex steroid concentrations stimulate the activation of the GH axis characterized by an increase in the amplitude in the pulsatile release of GH. Circulating insulin-like growth factor-1 mediates the anabolic somatic effects of GH and increases correspondingly during puberty, with levels correlating with SMR stages and sex steroid levels.12,14 PHYSICAL CHANGES OF PUBERTY Development of Secondary Sexual Characteristics
The development of secondary sexual characteristics is a hallmark of puberty. Sexual maturity ratings (SMR) scales developed by Marshall and Tanner provide for the staging of genital development in males and breast and pubic hair development in females (Figs. 2 and 3).15–17 These scales allow monitoring of the development of secondary sexual characteristics. They also provide better correlation for the timing of pubertal events than does chronologic age owing to variability in the timing and tempo of pubertal development. Although variability in the timing and tempo is commonly observed, the sequence of pubertal events in males and females is highly predictable and is illustrated in Figs. 4 and 5. The estimated age range of normal variation of pubertal development in US adolescent females is controversial in light of evidence of racial and ethnic differences and decreasing age onset of pubertal changes overall.18–20 The normal age range of puberty is 7 to 13 years for white girls and 6 to 13 years in African-American girls.5,21 Current estimates on the timing of attainment of various SMR stages in females is presented in Table 1. Female puberty generally begins with thelarche (B2), which commonly precedes pubarche (PH2) by about 1 to 1.5 years, although the latter may occur first or simultaneously.22 Despite the earlier onset of breast and pubic hair development, the mean age at menarche of 12.9 (1.20) years in white girls and 12.1 (1.21) years in AfricanAmerican girls20,23 is not significantly younger than previously reported. Menarche most commonly occur during PH4 and usually occurs 2 to 2.5 years after thelarche.17,24
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Fig. 2. Sexual maturity rating (SMR) stages in males. Stage 1 is prepubertal, with no pubic hair and childlike phallus and a testicular volume of 1.6 mL. Stage 2 shows sparse, straight pubic hair along the base of the penis with testicular enlargement and reddening and thinning of the scrotum, and a testicular volume of 1.6 to 6 mL. In stage 3, the hair is darker, coarser, and curlier, extending over the mid-pubis. Further testicular and scrotal enlargement and increase in phallic length. Testicular volume is 6 to 12 mL. In stage 4, hair is adult-like in appearance but does not extend to inner thighs. Further testicular and scrotal enlargement and increased phallic length and circumference; testicular volume is 12 to 20 mL. In stage 5, hair is adult in appearance, extending to the inner thigh. There is an adult scrotum and phallus. Testicular volume is 20 mL. (From Roede MJ, van Wieringen JC. Growth diagrams 1980: Netherlands third nation-wide survey. Tijdschr Soc Gezondheids 1985;63:1–34.)
Adolescent Growth and Development
Fig. 3. (A) Sexual maturity rating (SMR) of breast development in girls. Stage 1 is prepubertal, with no palpable breast tissue. In stage 2, a breast bud develops, with elevation of the papilla and enlargement of the areolar diameter. In stage 3, the breast enlarges, without separation of areolar contour from the breast. In stage 4, the areola and papilla project above the breast, forming a secondary mound. In stage 5, the areola recesses to match the contour of the breast; the papilla projects beyond the contour of the areola and breast. (B) Sexual maturity rating (SMR) stages of pubic hair development in girls. Stage 1 is prepubertal, with no pubic hair. In stage 2, there is sparse, lightly pigmented straight hair along the medial border of the labia. In stage 3, there is a moderate amount of darker, coarser, and curlier and extends over the mid-pubis. Stage 4 hair resembles adult hair in coarseness and curliness, but does not extend to the inner thighs. Stage 5 hair is adult in appearance and extends to the inner thighs. (From Roede MJ, van Wieringen JC. Growth diagrams 1980: Netherlands third nation-wide survey. Tijdschr Soc Gezondheids 1985;63:1–34.)
The mean age of onset of male pubertal development is 11 years, with a normal range of variation of 9 to 14 years.25 Estimates on the timing of attainment of various SMR stages in males are presented in Table 2. Male pubertal development typically begins with testicular enlargement (G2). Pubertal testicular enlargement is characterized by a longitudinal testicular measurement of >2.5 cm or testicular volume of >4 mL.16,26,27 Pubarche (PH2) generally follows closely and correlates with penile growth under the common influence of androgens. Additional pubertal events include spermarche between G3 and G4 and the appearance of facial hair and voice change in SMR stage G4.28 Height Growth
Height growth averages approximately 5 to 6 cm per year throughout childhood,6,29 with a slight deceleration in height growth immediately preceding puberty. During puberty, height velocity increases sharply and peaks during the adolescent growth spurt to ultimately account for about 20% of final adult height. In females, height velocity
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Fig. 4. Sequence of pubertal events in males. PHV, peak height velocity. (From Root AW. Endocrinology of puberty. J Pediatr 1973;83(1):1–19.)
accelerates at a mean age of 9 years and peak height velocity of approximately 8.3 cm per year is attained at a mean age of 11.5 years between SMR stages 2 and 3.30 Height growth rates generally decelerate significantly and there is limited growth potential after menarche. In males, height growth accelerates at a mean age of 11 years and reaches a peak height velocity of approximately 9.5 cm per year at the mean age of 13.5 years during SMR stages 3 to 4.30 Height growth rate decreases thereafter and is generally complete by SMR 5. The 12- to 13-cm male height advantage over females is best explained by the 2 additional years of prepubertal growth and greater peak height velocity rate.29 Prediction of adult height is useful in the monitoring of pubertal development. A commonly used method is based on the calculation of mid-parental height. Most individuals have an adult height that is within 10 cm or 4 inches (2 SD) of the midparental height as calculated below31: For girls 5
ðfathers height 13 cm or 5 inchesÞ 1 mothers height 2
For boys 5
ðfathers height 1 13 cm or 5 inchesÞ 1 mothers height 2
Additional methods of height prediction are often employed in the specialty referral setting, including the Bayley Pinneau method,32 which uses a combination of chronologic age, height, and skeletal age matched to standards.
Adolescent Growth and Development
Fig. 5. Sequence of pubertal events in females. PHV, peak height velocity. (From Root AW. Endocrinology of puberty. J Pediatr 1973;83(1):1–19.)
Differential linear growth in upper and lower extremities results in changes to the upper/lower (U/L) segment ratio during puberty. With greater linear growth in the lower extremities, the U/L segment ratio decreases from about 1.4 in the prepubertal period to a mean of 0.92 in white and 0.85 in African-American adults.33 Body Composition
Despite an overall increase in lean body mass, the percentage of lean body mass in females decreases from about 80% of body weight in early puberty to about 75% at maturity owing to a greater rate of increase in adipose mass.34 The percentage of body fat increases in females during puberty and is related to menstrual function, with 17% required for the initiation and 22% for maintenance of menstruation.35 In males, lean body mass increases from 80% to 85% in early puberty to about 90% at maturity, reflecting increasing muscle mass and decreasing adiposity.34 Approach to Normal Pubertal Variations and Abnormal Pubertal Growth and Development
Clinicians caring for adolescents are tasked with monitoring the timing and progression of puberty and identifying abnormal patterns of growth and development. It should be noted that the majority of adolescents who display patterns of development outside of statistical norms have no pathology and simply lie within the extremes of normal variation. Definitions between normal and abnormal are purely arbitrary and are based on the assumption that pubertal events assume a normal distribution in the population, with a range of 2 standard deviations (SD) above and below the
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Chulani & Gordon Table 1 Descriptive statistics for the timing of sexual maturity stages in females Onset of Stage Stage
Mean Age for Stage
Mean
SD
Mean
SD
11.2
0.7
11.3
1.1
12.5
1.5
Breast stages Stage 2 Roche et al (Ohio) Herman-Giddens et al (USA) African American
8.9
1.9
White
10.0
1.8
12.0
1.0
Stage 3 Roche et al (Ohio) Herman-Giddens et al (USA) African American
10.2
1.4
White
11.3
1.4
12.4
0.9
11.0
0.5
Stage 4 Roche et al (Ohio) Tanner pubic hair Tanner Stage 2 Roche et al (Ohio) Herman-Giddens et al (USA) African American
8.8
2.0
White
10.5
1.7
11.8
1.0
Tanner Stage 3 Roche et al (Ohio) Herman-Giddens et al (USA) African-American
10.4
1.6
White
11.5
1.2
12.4
0.8
Tanner Stage 4 Roche et al (Ohio) Menarche Herman-Giddes et al (USA) African American
12.2
1.2
White
12.9
1.2
Percent menstruating
At Age 11
At Age 12
African American
27.9%a
62.1%
White
13.4%a
35.2%
Onset of axillary hair (stage 2) African American
10.1 2.0
White
11.8 1.9
Mean age for stage 2, 11.3 1.1; mean age for stage 3, 12.5 1.5. a African-American girls enter puberty approximately 1 to 11/2 years earlier than white girls and begin menses 81/2 months earlier. Data from Roche AF, Weilens R, Attie KM, et al. The timing of sexual maturation in a group of U.S. white youths. J Pediatr Endocrinol 1995;8:11–8; Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 1997;99:505–12; and From Melmed S, Polonsky K, Larsen PR, et al. Williams textbook of endocrinology. 12th edition. Philadelphia: Saunders; 2011. p. 1061. Table 25-2.
Adolescent Growth and Development
Table 2 Descriptive statistics for the timing of sexual maturity stages in males Time Between Stages (y) Percentile Stage
Mean Age of Onset ±2 SD (y)
Stage
Mean
5th
G2
11.6 2.1
G2–3
1.1
0.4
95th 2.2
G3
12.9 2.1
PH2–3
0.5
0.1
1.0
PH2
13.4 2.2a
G3–4
0.8
0.2
1.6
G4
13.8 2.0
PH3–4
0.4
0.3
0.5
PH3
13.9 2.1
G4–5
1.0
0.4
1.9
PH4
14.4 2.2
PH4–5
0.7
0.2
1.5
G5
14.9 2.2
G2–5
3.0
1.9
4.7
PH5
15.2 2.1
PH2–5
1.6
0.8
2.7
a
Mean is probably too high owing to experimental method. From Barnes HV. Physical growth and development during puberty. Med Clin North Am 1975;59:1305.
mean used to define the limits of normal variability.1,2,36 A proportion of adolescents, however, display abnormal patterns of development owing to underlying pathology, which makes the clinical evaluation of development outside statistical norms necessary. An approach in the evaluation of adolescents with abnormal development is presented. History A comprehensive history pertaining to general health and growth, including a review of growth charts and the calculation of growth velocity.37–40 Timing of observed pubertal changes, including whether pubertal changes are completely absent or if earlier pubertal noted changes have failed to progress.23,40 General health conditions in the family, heights and growth patterns of parents and siblings, and their timing of attainment of pubertal milestones.41–44 Nutritional history and review of eating habits.39,40,45 Review of systems to rule out chronic illnesses, including a thorough review of the gastrointestinal, endocrine, and central nervous (CNS) systems.39 Physical Examination Determination of height and calculation of height velocity in the prior 6 to 12 months. A 6- to 12-month period is recommended to minimize the effect of observed seasonal variation in height growth.41,42,46,47 Determination of weight and body mass index. HPG axis suppression with delay or disruption of puberty is observed at 50% being peripheral cases, such as neoplasm.39,48 A thorough history and physical examination is necessary in the evaluation of the child with precocious puberty. Determination of bone age and levels of serum estradiol and testosterone are key to the initial evaluation. Significant advancement of bone age beyond chronologic age and pubertal levels of sex hormones confirm precocious puberty and necessitate referral to a pediatric endocrinologist.50 Algorithms for the further evaluation of sexual precocity in males and females are presented in Figs. 7 and 8. Determination of basal LH levels and LH response to GnRH stimulation provide useful diagnostic information. LH levels demonstrate increase in pubertal pattern after GnRH stimulation in CPP and remain prepubertal or suppressed in peripheral precocious puberty. Males with CPP require MRI of the brain to exclude CNS pathology. It is also required in females who have CPP and are
