The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Sherrel L. Hammar. This current third edition chapter is a revision and update of the original author’s work.
A 15-year-old male is seen by his primary care physician for short stature and delayed sexual development. His past medical history is unremarkable except for asthma during early childhood, which has been well controlled. He is currently on no medications. He is an average student currently in the 9th grade and is the smallest in his class. He has been harassed by older classmates because of his size. His parents are concerned because they feel he is becoming withdrawn.
PMH: Pregnancy and delivery were uncomplicated. Birth weight and length were 3.86 kg (8.5 pounds) and 51 cm (20"), respectively. His HC was 35 cm. His immunizations are current.
Family History: His mother is 48 years old and in good health. Her height is 167 cm (50%tile). Her menarche began at age 13.0 years. His father is 51 years old, also in good health. His height is 184.0 cm (75%tile). His father's onset of puberty is not known but he was shaving regularly by age 15. There is one older male sibling, age 18, who is in good health. His puberty began at age 11 years. There is no history of smoking, alcoholism, mental illness, drug abuse or learning problems in the family.
Exam: VS T 37.1, P 110, R 32, BP 100/60. Ht 158 cm (3%ile), Wt 42.0 kg. (10%ile). He is pale and anxious but cooperative. His HEENT exam is normal. His chest is clear. Heart regular, no murmurs. His pulses are symmetrical and equal. There are no masses or areas of tenderness in his abdomen. Genitalia: Normal circumcised phallus, SMR (sexual maturity rating or Tanner stage) pubic hair stage 1, genital stage 2. His testes are firm, 2.5 cm in length and 4 ml in volume. His scrotum is darker and stippled. The remainder of his physical exam is unremarkable.
Lab: CBC: Hgb 13, WBC 9.5, normal differential, platelets 350,000. UA is normal. Bone Age: (left hand and wrist) 12.0 years. LH and FSH are decreased but normal for SMR stage 1-2.
Impression: Constitutional Short Stature, Delayed Puberty
Clinical Course: Over the next 6 months, pubic hair growth is noted. His testes enlarge to 3-4 cm in length and his height increases by 5 cm.
Puberty refers to the biological changes that lead to reproductive capability and is characterized by various hormonal changes with resulting sexual development (1). The sequence of events that occur during puberty are generally fairly predictable while the age at which these events occur may be variable as influenced by genetics, overall health status, psychosocial factors, and environmental exposures (1). Overall, the ages of onset of puberty and menarche appear to be declining over the last century (1).
Sexual Maturity Rating (SMR) scale, also known as Tanner stages, are widely used to assess the progression of pubertal development in males and females and range from stage 1 (preadolescence) to stage 5 (sexual maturity) (1). These stages utilize pubic hair development and breast development for females and pubic hair development and genital development for males (1).
The first clinical sign of puberty in females is thelarche (the appearance of breast buds) between ages 7 and 12 years (1), followed by pubarche (the appearance of pubic hair) usually 6 to 12 months later (2). These changes identify a Tanner stage II (see Table 1). In a minority of females, pubarche precedes thelarche. Between Tanner stages II and III, females also experience a very rapid increase in their height. The peak rate of their height growth (peak height velocity, PHV) occurs at an average age of 11 to 12 years (2) at a rate of 8 to 9 cm per year (1). Females who reach their peak height velocity at an earlier age will attain their final height earlier. Menarche (the onset of menstrual activity) always follows the peak height velocity by approximately 6 months (1) and is typically between ages 9 to 15 years with the mean age being 12.8 years (2). The age at menarche is usually within 3 years of thelarche (2). Early cycles of menstruation (first year following menarche) are often anovulatory and irregular, but typically occur every 21 to 45 days (1).
Table 1. SMR Stages of Breast and Pubic Hair Development in Females (1)
| SMR Stages | Breast Development | Pubic Hair Development |
|---|---|---|
| I. Prepuberty | None | None |
| II. Typically age 7 to 12 years | Breast bud forms as small mound, areola diameter increases | Sparse, lightly pigmented, straight, medial border of labia |
| Peak height velocity (PHV) typically between age 11 and 12 years | ||
| III. | Breast and areola enlarge but without separation in contour | Increased, darker, beginning to curl |
| IV. | Breast enlarges and secondary mound forms | Coarse, curly, abundant but confined to suprapubic area |
| V. Adult Maturity | Adult breast contour, nipple projects, areola flattens | Adult feminine triangle, across pubis and on medial thighs |
Puberty in males also follows a regular sequence of events but lacks the clear-cut landmarks such as breast development and menarche. The onset of pubertal changes begins with enlargement of the testes as early as age 9.5 years (1) and indicates the transition from stage I to stage II. This is followed by pubarche and penile growth (see Table 2). The appearance of axillary and chest hair and deepening of the voice occurs about 2 years later, during stage III (3). Nocturnal emissions (wet dreams) may also first appear during stage III (1). In males, the pubertal growth spurt is a late event starting about two years later than in females (2). Peak height velocity of 9 to 10 cm per year (1) typically occurs during genital stage IV to V (between ages 13 and 14 years) (2). Growth may continue beyond age 18 years (2).
Table 2. SMR Stages of Pubic Hair, Penis, and Testes Development in Males (1)
| SMR Stages | Pubic Hair Development | Penis Development | Testes Development |
|---|---|---|---|
| I. Prepuberty | None | Preadolescent | Preadolescent |
| II. As early as age 9.5 years | Sparse, lightly pigmented, long | Minimal changes of appearance or size | Scrotum enlarges, pinkens, alterations in texture |
| III. | Small amount, darker, beginning to curl | Begins to lengthen | Larger |
| IV. | Increased amount, coarse, curly | Lengthens, glans and breadth enlarge | Larger, scrotum darkens |
| Peak height velocity (PHV) typically between age 13 and 14 years | |||
| V. Adult Maturity | Adult distribution, spread to medial thighs | Adult size | Adult size |
Precocious puberty is typically defined as pubertal development prior to age 8 years in females and prior to age 9 years in males (4). However, consideration should be made as the age of onset of puberty may vary widely, particularly in children of different ethnicities (4). Therefore, pubertal development that starts early may often be normal and not due to an identifiable pathology, though a full evaluation of the child is still indicated. Table 3 lists common causes of precocious puberty, classified as central precocious puberty (due to early hypothalamic-pituitary-gonadal activation; also known as true precocious puberty) or peripheral precocious puberty (due to increased peripheral synthesis of sex hormones and without hypothalamic-pituitary-gonadal activation; also known as precocious pseudopuberty) (4).
Table 3. Example Causes of Precocious Puberty
I. Central (GnRH-dependent)
A. Idiopathic (most common)
B. CNS tumors (e.g., craniopharyngioma)
C. CNS malformations (e.g., hypothalamic hamartoma)
D. CNS infection
E. Head trauma
F. Iatrogenic (e.g., radiation, surgical)
II. Peripheral (GnRH-independent)
A. McCune-Albright syndrome (most common)
B. Estrogen/testosterone-producing tumors (e.g., Sertoli-Leydig cell tumor)
C. Gonadotropin/hCG-producing tumors (e.g. choriocarcinoma)
D. Congenital adrenal hyperplasia
E. Aromatase excess syndrome
F. Ovarian follicular cysts
G. Primary hypothyroidism
H. Glucocorticoid resistance
I. Exogenous androgen/estrogen exposure
The absence of any secondary sexual characteristics by age 13 years in females or age 14 years in males is considered a delay in puberty (4). Table 4 lists the causes of delayed puberty.
Constitutional delay in growth and puberty (CDGP) is the most common cause of delayed puberty and is thought to be due to an idiopathic delay in activation of GnRH (gonadotropin-releasing hormone) pulses (5). It is a normal variant of the timing of puberty though normal growth velocity is consistently maintained (6). Most cases have a family history of late bloomers with delayed puberty or growth (5). Patients still maintain good linear growth potential and their predicted final height is appropriate for the family (5). CDGP is a diagnosis of exclusion as delayed puberty may be the first sign of many underlying conditions (5). Nevertheless, a child with a near-normal height velocity who is otherwise healthy and has a similar family history makes the diagnosis of CDGP likely. Additionally a bone age may help support this diagnosis if it is delayed compared to their actual age (7).
The patient described in the case above is not only short statured but is delayed in his pubertal development. Based on the physical exam and reassuring lab findings described, he would fit a presumptive diagnosis of constitutional delay of growth and maturation. Males with a constitutional delay of growth and maturation usually have a normal birth weight and length, and progress along their normal growth percentile for the first several years of life. However, the patient’s growth gradually deviates and when their peers begin having growth spurts in early adolescence, the patient’s height is usually at or below the 3rd percentile (4).
In most adolescents with constitutional delay, a watch and wait approach is indicated for 6 to 12 months. The patient presented in the case could have been prescribed a short-term course of testosterone in order to stimulate sexual maturation and growth hormone production (5). In general, such treatment has been reserved for teenagers experiencing significant psychosocial (self-image) distress due to their delayed puberty (6).
In most cases, the evaluation of a patient suspected of delayed sexual maturity can be conservative. A thorough medical and family history, physical examination, and assessment of sexual maturity stage will often show signs of early pubertal changes (4). Gonadotropins such as LH (luteinizing hormone) and FSH (follicle stimulating hormone), serum estradiol, and serum testosterone usually reflect the sexual maturity status of the patient (4). A chromosomal karyotype is indicated for all short statured females who are delayed (for possible Turner's syndrome) and for males who are tall with small soft testes with or without delayed sexual maturity (Klinefelter's syndrome) (4).
Table 4. Causes of Delayed Puberty (4)
I. Constitutional Delay in Growth and Maturation
II. Hypogonadotropic hypogonadism (defect of hypothalamus and/or pituitary gland resulting in low gonadotropin levels)
A. Central nervous system disorders
1. Tumors
a. Craniopharyngiomas
b. Gliomas
c. Germinomas
2. Radiation Therapy
3. Congenital Malformations
4. Infections
B. Isolated gonadotropin hormone deficiency
1. Kallmann Syndrome
2. Congenital adrenal hypoplasia
3. Isolated LH or FSH deficiency
Miscellaneous Disorders
1. Prader-Willi Syndrome
2. Hypothyroidism
3. Malnutrition
4. Exercise amenorrhea
5. Cushing disease
6. Diabetes mellitus
III. Hypergonadotropic hypogonadism (high gonadotropin levels but low/absent gonadal response)
A. Turner Syndrome
B. Klinefelter Syndrome
C. Other XX and XY gonadal dysgenesis
D. Noonan Syndrome
E. Radiation or chemotherapy
Questions
1. What is the first visible sign of puberty in males and females?
2. What is the order in which physical signs of puberty occur in females and males?
3. What is the difference in age between when peak height velocity occurs in females vs males?
4. What are the considered ages for precocious puberty? Delayed puberty?
5. What is the most common cause of delayed puberty?
References
1. Holland-Hall CM. Chapter 132. Adolescent Physical and Social Development. In: Kliegman RM, St. Geme JW, Blum NJ, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020, Elsevier, Philadelphia, PA. pp:1014-1020.
2. Garibaldi LR, Chemaitilly W. Chapter 577. Physiology of Puberty. In: Kliegman RM, St. Geme JW, Blum NJ, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020, Elsevier, Philadelphia, PA. pp:2898-2899.
3. Sass AE, Richards MJ. Chapter 4. Adolescence. In: Bunik M, Hay WW, Levin MJ, Abzug MJ (eds). Current Diagnosis & Treatment: Pediatrics, 26th edition. 2022, McGraw Hill, New York, NY. pp:92-129.
4. Garibaldi LR, Chemaitilly W. Chapter 578. Disorders of Pubertal Development. In: Kliegman RM, St. Geme JW, Blum NJ, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020, Elsevier, Philadelphia, PA. pp:2899-2912.
5. Escobar O, Gurtunca N, Viswanathan P, Witchel SF. Chapter 9. Pediatric Endocrinology. In: Zitelli BJ, Nowalk AJ, McIntire SC, Garrison J (eds). Zitelli and Davis’ Atlas of Pediatric Physical Diagnosis, 8th edition. 2023, Elsevier, Philadelphia, PA. pp:342-381.
6. Styne D. Chapter 15. Puberty. In: Gardner DG, Shoback D (eds.) Greenspan’s Basic & Clinical Endocrinology, 10th edition. 2017, McGraw Hill, New York, NY. pp:547-573.
7. Bakhtiani P, Geffner M. Delayed Puberty. Pediatr Rev. 2022;43(8):426-435. doi.org/10.1542/pir.2020-005291
Answers to questions
1. The first visible sign of puberty and the hallmark of SMR 2 in males is testicular enlargement typically between 10 and 12 years of age. In females, it is typically thelarche (the appearance of breast buds) between 7 and 12 years old.
2. Females: thelarche, then pubarche, then menarche. Males: enlargement of the testes, then pubarche and penile growth.
3. There is typically a 2-year difference in the age at which peak height velocity occurs in females vs males (ages 11-12 vs 13-14, respectively).
4. Puberty is considered precocious when there is secondary sexual development occurring before age 8 years in females and 9 years in males, though consideration of what is normal is race/ethnicity dependent. Delayed puberty is when there is no sign of pubertal development by age 13 years in females and 14 years in males.
5. The most common cause of delayed puberty is a constitutional delay in growth and maturation.