brand logo

Am Fam Physician. 2017;96(9):590-599

Patient information: See related handout on early and delayed puberty.

Author disclosure: No relevant financial affiliations.

Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine years of age in boys. Patients with early isolated pubertal changes, prepubertal linear growth, and no worrisome neurologic symptoms typically have a benign pattern of development and should be monitored in the appropriate clinical context. Among patients with true precocious puberty, or full activation of the hypothalamic-pituitary-gonadal axis, most girls have an idiopathic etiology, whereas it is commonly due to identifiable pathology on imaging in boys. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); thyroid function testing; and bone age radiography. Brain magnetic resonance imaging should be performed in girls younger than six years, all boys with precocious puberty, and children with neurologic symptoms. Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Constitutional delay of growth and puberty is a common cause of delayed puberty; however, functional or persistent hypogonadism should be excluded. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); and bone age radiography. Abnormal growth velocity necessitates assessment of serum thyroid function, prolactin, and insulinlike growth factor I. Boys 14 years and older and girls 13 years and older may benefit from sex steroid treatment to jump-start puberty. Referral to a pediatric endocrinologist may be warranted after the initial evaluation.

Puberty is a developmental stage characterized by physical and psychosocial maturation. Abnormal pubertal timing can adversely affect a child's physical and psychosocial well-being and may be caused by a range of generally benign or pathologic etiologies. Physicians must identify which findings are suitable for surveillance over time and which suggest treatable underlying pathology.

Clinical recommendationEvidence ratingReferences
Girls with signs of puberty before eight years of age and boys with signs of puberty before nine years of age should be evaluated for precocious puberty.C5, 6
Girls without breast development by 13 years of age should be evaluated for delayed puberty, and girls without menarche by 15 years of age should be evaluated for primary amenorrhea.C5, 7, 25
Boys who do not have testicular growth to at least 4 mL in volume or 2.5 cm in length by 14 years of age should be evaluated for delayed puberty.C5, 7, 25
In patients with precocious puberty, brain magnetic resonance imaging should be performed in girls younger than six years, all boys, and children with neurologic symptoms to evaluate for a central nervous system lesion.C5, 6, 9
Boys older than 14 years and girls older than 13 years with possible constitutional delay of growth and puberty may benefit from a short course of sex steroids to jump-start puberty.C7, 25

Hormonal and Physical Changes of Normal Development

The physical changes of puberty are a result of gonadal sex hormone production, the start of which (gonadarche) indicates pubertal onset. Gonadarche is triggered by the pulsatile release of gonadotropin-releasing hormone, which activates the hypothalamic-pituitary-gonadal (HPG) axis.13 Adrenarche (i.e., adrenal androgen production leading to pubic and axillary hair, body odor, and mild acne) is a separate but usually concurrent process and does not in itself indicate true pubertal onset in boys or girls.47

In girls, increased ovarian estradiol secretion causes breast development at a mean age of 10 years (range: eight to 12 years). Menarche typically follows 2.5 years after the onset of breast development, at an average age of 12.5 years (range: nine to 15 years).15 In boys, testicular enlargement to at least 4 mL in volume or 2.5 cm in length is the first sign of true puberty and occurs at an average age of 11.5 years (range: 9.5 to 14 years).14,813 Physical changes are described using sexual maturity ratings (Table 115,9,14 and Table 215,9,14 ), such as Tanner stages, and are affected by body habitus and demographic factors.15,12,14

RatingBreast developmentPubic hairPubertal event
1PrepubertalNoneNone
2Subareolar breast budsSparse, long, slightly pigmented, straight or slightly curled, along the medial labiaPeak height velocity
3Breasts and areolae are further enlarged with a continuous rounded contourDarker, coarser, more curled, spread sparsely over the mons pubisPeak height velocity
4Areola and nipple form a secondary mound above the contour of the breastAdult type, but the area covered is smaller and there is no extension to the medial thighsMenarche
5Mature adult stage, nipple projection without the secondary moundAdult type and quantity, sometimes extending to the medial thighsMenarche
RatingGenital developmentPubic hairPubertal event
1PrepubertalNoneNone
2Enlargement of the testes (more than 4 mL in volume and more than 2.5 cm in length) and scrotum, but not the penisSparse, long, slightly pigmented, straight or slightly curled, at the base of the penisNone
3Continued testicular and scrotal enlargement with penile growthDarker, coarser, more curled, spread sparsely over the pubisPeak height velocity, spermarche
4Continued testicular, scrotal, and penile growth with enlargement of the glansAdult type but the area covered is smaller and there is no extension to the medial thighs or linea albaPeak height velocity, spermarche, facial hair, voice change
5Mature male genitaliaAdult quality and distribution with spread to the medial thighsNone

Linear growth velocity is about 5 cm per year from four years of age to puberty with a nadir before the pubertal growth spurt. Girls achieve peak height velocity during sexual maturity ratings 2 and 3 (mean: 8.3 cm per year, age 11 or 12 years) and boys during sexual maturity ratings 3 and 4 (mean: 9.5 cm per year, age 13 or 14 years). On average, girls complete linear growth at 15 years of age and boys at 17 years of age. After menarche, girls grow an average of 7 cm.14,1418

When to Suspect a Disorder of Puberty

PRECOCIOUS PUBERTY

Precocious puberty is diagnosed when secondary sexual characteristics are identified in girls younger than eight years and boys younger than nine years.5,6 Data suggest a trend toward early pubertal development. Approximately 20% of black girls and 5% to 10% of white girls seven to eight years of age in the United States have glandular breast development, particularly if obese.1923 Eight years of age can be considered a reasonable cutoff for evaluation in girls.5,6 Because of more frequent pathology in boys with precocious puberty than girls, all pubertal boys younger than nine years should be fully evaluated.5,6,24

DELAYED PUBERTY

Puberty is considered delayed when there are no signs of breast development by 13 years of age in girls or testicular enlargement by 14 years of age in boys.5,7,25 Clinicians should suspect pubertal delay if there is halting or regression of pubertal development. In girls with initial pubertal changes, absence of menarche by 15 years of age is also concerning.

Evaluation of a Suspected Disorder of Puberty

HISTORY

The clinician should inquire about the onset and progression of body odor, acne, breast or testicular development, and pubic and axillary hair. Current or previous therapies, including chemotherapy, radiation therapy, or exogenous sex steroids, may indicate the underlying etiology. Neurologic symptoms may reveal intracranial pathology. For delayed puberty, a history suggestive of underlying chronic disease (e.g., fatigue, pain, abnormal stools), nutrition and exercise patterns, poor psychosocial functioning, cryptorchidism, anosmia [i.e., in Kallmann syndrome]) is important.

Growth patterns, such as constitutional delay, may be familial. Thus, family history should include pubertal timing, especially the mother's age of menarche and father's age of reaching adult height.7,9

Table 316,9 and Table 415,7,8 summarize history and physical examination findings in the evaluation of early and delayed puberty.

FindingsPossible diagnoses
Abdominal painGonadal malignancy
Asymmetric testesGonadal tumor
Body mass index and weight (growth charts)High: may be associated with precocious puberty
Café au lait spotsMcCune-Albright syndrome, neurofibromatosis
Dull pink (vs. red) vaginal mucosaEstrogen exposure (unspecified)
Enlarged thyroidHyper- or hypothyroidism
Exposure to exogenous sex steroidsPeripheral precocious puberty
Family history of early pubertyFamilial pattern
Growth velocityPubertal growth spurt, pathologic growth due to an underlying condition
Head traumaCentral precocious puberty
Height (growth chart)Short stature: thyroid disease
Hirsutism, acne, body odorHyperandrogenism: premature adrenarche, peripheral precocious puberty
Neurologic assessment (abnormal examination findings, or symptoms such as headaches or vision changes)Intracranial pathology
Radiation treatment, brain tumorCentral precocious puberty
Sexual maturity ratingEarly pubertal development (unspecified)
Temperature intolerance, gastrointestinal symptoms, tremor, depression, palpitationsThyroid disease
Vaginal bleeding (isolated)Benign variant, genital trauma or abuse, foreign body, infection, McCune-Albright syndrome
Virilization in girlsAndrogen-secreting tumor, congenital adrenal hyperplasia
FindingsPossible diagnoses
Abdominal painGastrointestinal disease
AnosmiaKallmann syndrome
Asymmetric testesOophoritis or orchitis
Body mass index and weight (on growth charts)Low: eating disorder, caloric insufficiency, gastrointestinal or other systemic disease
Chemotherapy, radiation treatment, brain tumorHypogonadism
Cryptorchidism or orchidopexyHypogonadism
Dysmorphic features (webbed neck, short stature, low hairline)Turner syndrome
Enlarged thyroidHypothyroidism
Family history of late pubertyConstitutional delay of growth and puberty
GalactorrheaHyperprolactinemia
Growth velocityPeripubertal growth slowing, pathologic growth due to underlying condition
Height (growth chart)Short stature: Turner syndrome, constitutional delay of growth and puberty
Tall stature: Klinefelter syndrome
Joint painInflammatory disorder
Neurologic assessment (abnormal examination findings or symptoms such as headaches, vision changes)Intracranial pathology
Red (vs. dull pink) or thin vaginal mucosaLack of estrogen exposure (hypogonadism)
Sexual maturity ratingDelayed pubertal development (unspecified)
Small, firm testesKlinefelter syndrome
Temperature intolerance, gastrointestinal symptoms, tremor, depression, palpitationsThyroid disease
Trauma (head)Hypogonadism
Vasomotor symptoms in girlsOvarian insufficiency
Weight loss, stress, excessive exercise, inadequate nutrition, fatigueEating disorder, caloric insufficiency

PHYSICAL EXAMINATION

Height, weight, and body mass index should be plotted on growth curves, and the height velocity should be calculated.3,23 Target height (midparental height) can be determined using the following equation: [mother's height + father's height + 13 cm in boys or − 13 cm in girls] ÷ 2.18,26 A target height differing from the projected height, as established by extending the growth curve to adulthood or bone age radiography, by approximately more than 10 cm may suggest a pathologic condition.26 Because of the effects of sex steroids on epiphyseal maturation, patients with precocious puberty may present with relatively tall stature (leading to shorter adult height), and those with delayed puberty may present with short stature.26

The patient's sexual maturity rating should be noted, as well as the amounts of acne and axillary and facial hair. In boys, determining the location, consistency, and size of the testes can evaluate for cryptorchidism, malignancy, or Klinefelter syndrome (firm testes), and help determine pubertal staging. In girls, dull pink vaginal mucosa suggests estrogen exposure; virilization (e.g., clitoromegaly) should be excluded.47,9,27

The thyroid, abdomen, and neurologic system should be examined for evidence of thyroid or gastrointestinal disease or intracranial pathology. Any dysmorphic features or café au lait spots may suggest Turner or McCune-Albright syndrome.47,9,27

Early Pubertal Development

eTable A includes the differential diagnosis of isolated pubertal changes and true precocious puberty.

Diagnosis*CharacteristicsTreatment
Generally benign variants
LipomastiaFat tissue but no glandular breast tissue on palpation; associated with obesitySurveillance
Nonprogressive precocious pubertyEarly but normal sequence of pubertal events that does not progress prematurelySurveillance every 3 to 6 months to evaluate for progression of pubertal development
Premature adrenarchePubic and axillary hair growth, body odor, sweating, and/or mild acne; may have mildly elevated dehydroepiandrosterone sulfate, but normal levels of FSH, LH, 17-hydroxyprogesterone, estradiol, and testosterone; no change in linear growth velocity or enlargement of the testes, penis, breasts, ovaries, or clitorisSurveillance every 3 to 6 months to evaluate for progression of pubertal development; linear growth velocity should be normal (i.e., consistent with bone age)
Premature thelarcheGlandular breast tissue on palpation (as opposed to lipomastia) without other secondary sexual characteristicsSurveillance every 3 to 6 months to evaluate for progression of pubertal development
Prepubertal vaginal bleedingAbsence of secondary sexual characteristics, genital trauma or abuse, foreign body, infection, evidence of McCune-Albright syndrome; possible ovarian enlargement on ultrasonographySurveillance for heavy or recurrent bleeding
Central (LH‐ or FSH ‐mediated) precocious puberty
Central nervous system lesion (e.g., hypothalamic hamartoma), radiation, traumaEarly but normal sequence of pubertal events; possible magnetic resonance imaging abnormalitiesTreatment of underlying cause, which may involve GnRH analogue
IdiopathicEarly but normal sequence of pubertal events; possible reproductive organ enlargement on ultrasonography (unlike premature thelarche)GnRH analogue in selected cases
Prior sex steroid exposure (e.g., peripheral precocious puberty)Early but normal sequence of pubertal events with suggestive historyGnRH analogue in selected cases
Peripheral (LH‐ or FSH‐independent) precocious puberty
Adrenal tumorPubic or axillary hair growth, possibly acne and clitoromegaly; prepubertal testes; elevated adrenal hormone (e.g., dehydro-epiandrosterone sulfate); adrenal imaging abnormalitiesTreatment of the tumor
Congenital adrenal hyperplasiaPubic or axillary hair growth, possibly acne and clitoromegaly; prepubertal testes; elevated adrenal hormone (e.g., 17-hydroxy-progesterone)Referral to a pediatric endocrinologist for multisystem treatment and surveillance
Exogenous sex steroidsExposure to contraceptives, testosterone preparations, phthalates, or lavender tree oilEliminate exposure
HypothyroidismElevated thyroid-stimulating hormone, breast or testicular developmentTreatment of thyroid disease
McCune-Albright syndromeMultiple café au lait spots and fibrous dysplasia of bones, ovarian enlargement or testicular abnormalities on ultrasonography; may have menstrual bleeding before other developmentReferral to a pediatric endocrinologist for multisystem treatment and surveillance
Ovarian or testicular tumorMay be apparent on physical examination or imaging and accompanied by elevated serum testosterone or estradiol; human chorionic gonadotropin–secreting germ cell tumors activate testes in boys; may occur outside of the gonadsTreatment of the tumor; ovarian tumor should be differentiated from a benign ovarian cyst

ISOLATED PUBERTAL CHANGES

Premature thelarche, defined by isolated glandular breast tissue on palpation, should be differentiated from lipomastia (isolated fatty breast tissue), which is common in obese children.21 To differentiate these conditions, clinicians may examine the patient in the supine position, thereby making the breasts less prominent, to determine presence or absence of glandular tissue under the areolae. Isolated prepubertal vaginal bleeding not caused by trauma, abuse, a foreign body, infection, or an exceedingly rare tumor is usually benign.6,28

Premature adrenarche, driven by adrenal androgens rather than activation of the HPG axis, leads to slowly progressive appearance of pubic and axillary hair, body odor, sweating, and/or mild acne without change in linear growth velocity or enlargement of the testes, penis, breasts, ovaries, or clitoris. Dehydroepiandrosterone sulfate may be at a pubertal level (i.e., slightly elevated for the patient's chronologic age), whereas estradiol, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) remain at prepubertal levels.5,6,9 Less than 5% of patients have an elevated 17-hydroxyprogesterone level, suggesting mild nonclassic congenital adrenal hyperplasia, which does not usually require treatment. Thus, laboratory evaluation for such isolated findings may be delayed.6 Deferring laboratory tests also applies in cases of fine, sparse pubic hair growth that sometimes occurs in infancy.6

Patients with early isolated pubertal changes, prepubertal linear growth, and no worrisome neurologic symptoms typically have a benign pattern of development, necessitating only surveillance over three to six months to evaluate for progression.36,9,29 Laboratory or bone age assessment may be deferred initially. Notably, bone age advancement by two standard deviations has low predictive value in differentiating benign pubertal variants from concerning causes of precocious puberty.6,30

Gynecomastia, or estrogen-mediated glandular breast tissue, is common in pubertal boys. Evaluation for chronic disease; hyperprolactinemia; testicular or adrenal neoplasm; use of prescription, recreational, or performance-enhancing drugs; or hypogonadism (e.g., Klinefelter syndrome) should be initiated if symptoms persist for 18 to 24 months or the patient has no pubertal changes.31

CENTRAL AND PERIPHERAL PRECOCIOUS PUBERTY

Precocious puberty can be characterized by the pathologic location. In central precocious puberty, the HPG axis is activated, resulting in early but normal development, symmetric progression of secondary sexual characteristics, and increasing growth velocity.6,9,32 Central precocious puberty is approximately 10-fold more common in girls than in boys.33 Although usually idiopathic in girls, it can be incited by head trauma, neoplasm, radiation, or genetic conditions.5,6,9 Pathologic causes of central precocious puberty are more common in boys.5,6,9

Peripheral precocious puberty occurs when hormonal influences originating outside of the HPG axis produce incomplete, atypically sequenced or rapid pubertal progression.5,6,9 Quickly progressing or significant hyperandrogenic findings may warrant workup for congenital adrenal hyperplasia or an androgen-secreting tumor. Elevated estradiol levels in the setting of low LH may suggest an estrogen-secreting tumor.6 Hypothyroidism and exogenous steroid use should be excluded. Multiple café au lait spots and fibrous dysplasia of bones are concerning for McCune-Albright syndrome or neurofibromatosis.5,6,9

The initial workup should include measurement of serum FSH, LH, and testosterone in boys or estradiol in girls; thyroid function testing; and bone age radiography (eTable B, Figure 15,6,9). In cases of hyperandrogenic findings, measuring serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone is indicated. An LH level of more than 0.3 mIU per mL (0.3 IU per L) is the most reliable laboratory finding for central precocious puberty; however, in patients with lower values and high clinical suspicion, a gonadotropin-releasing hormone analogue stimulation test may be warranted.6,34 In cases of diagnostic uncertainty, pelvic ultrasonography can evaluate for increased uterine and ovarian volume expected for age, which may indicate central precocious puberty or a tumor.6

TestCondition-specific findings
Precocious pubertyDelayed puberty
Laboratory testing (refer to local reference values)
First-line
Serum estradiolElevated (girls): estrogen exposure; if markedly elevated (> 100 pg per mL [367 pmol per L]), evaluate for ovarian tumor, especially if luteinizing hormone is suppressedLow (girls): prepubertal, may suggest poor ovarian function in response to gonadotropins
Serum testosteroneElevated: testicular (boys), adrenal, or exogenous sourceLow (boys): prepubertal, poor response of testes to gonadotropin stimulation
Serum LH and follicle-stimulating hormonePrepubertal levels: benign variant or peripheral precocious pubertyHigh: gonadal insufficiency, Turner syndrome, Klinefelter syndrome
Postpubertal levels > 0.3 mIU per mL (0.3 IU per L): central precocious pubertyLow: hypogonadotropic hypogonadism, constitutional delay of growth and puberty
If indicated
Directed testing (e.g., for celiac disease; diabetes mellitus; or hepatic, renal, or inflammatory conditions)Functional hypogonadotropic hypogonadism, seek underlying cause
Gonadotropin-releasing hormone analogue stimulation testElevated LH: central precocious puberty (vs. benign variant) in complex clinical scenariosUsed in complex clinical scenarios
Suppressed LH but elevated sex steroids: peripheral precocious puberty
KaryotypingTurner syndrome, Klinefelter syndrome
Serum 17-hydroxyprogesteroneElevated: nonclassic (late onset) congenital adrenal hyperplasia
Serum dehydroepiandrosterone sulfateElevated: adrenal source, premature adrenarche (mild elevation) vs. peripheral precocious pubertyNormal for age: may suggest persistent hypogonadotropic hypogonadism rather than constitutional delay of growth and puberty
Serum human chorionic gonadotropin (boys)Elevated: human chorionic gonadotropin–secreting germ cell tumor
Serum insulinlike growth factor ILow: growth hormone deficiency (if low for both bone and chronologic age)
Serum prolactinHigh: prolactin-secreting tumor, hypothyroidism, other neoplasm
Serum thyroid-stimulating hormone and free thyroxineThyroid diseaseThyroid disease
Imaging
First-line
Bone age radiographyAdvanced (> 2 standard deviations): more likely to be central or peripheral precocious puberty, less likely to be benign pubertal variantDelayed: constitutional delay of growth and puberty, underlying chronic disease
If indicated
Adrenal imagingAdrenal tumor
Magnetic resonance imaging (brain and pituitary)Central nervous system lesionCentral nervous system lesion
Pelvic or testicular ultrasonographyOvarian or testicular tumor; greater ovarian volume may indicate central precocious puberty (vs. benign variant)Absence of the uterus (e.g., androgen insensitivity, Müllerian system abnormalities)

The appropriate timing for neuroimaging to identify central nervous system lesions (e.g., hypothalamic hamartoma, malignancy) in children with precocious puberty is controversial. Girls younger than six years, all boys with precocious puberty, and children with neurologic symptoms such as headache, vision changes, or seizures should be screened with magnetic resonance imaging.5,6,9 Some experts discourage routine neuro-imaging for asymptomatic girls six to eight years of age because pathology requiring treatment is exceedingly rare. With shared decision making, parents can weigh the risks of sedation, intravenous contrast media, and follow-up imaging (leading to anxiety and high cost) against the low likelihood that imaging will show a new central nervous system malignancy (at most 1%).5,6,35

If started early in the course of central precocious puberty, gonadotropin-releasing hormone analogues (e.g., leuprolide [Lupron]) appear to safely prevent premature fusion of growth plates, thereby preserving height potential.36 Because of high annual costs, treatment may be most appropriate if bone age suggests impending short stature or if the patient exhibits aggression (boys) or profound emotionality in response to menses (girls).10,37

Delayed Puberty

Delayed puberty is the absence of breast development by 13 years of age in girls or the absence of testicular growth to at least 4 mL in volume or 2.5 cm in length by 14 years of age in boys.79,25,38 Constitutional delay of growth and puberty is the most common cause of delayed puberty in boys (60%) and girls (30%).39,40 It represents an extreme of the normal spectrum of pubertal timing and is a diagnosis of exclusion.39,40 For more than 75% of patients with constitutional delay of growth and puberty, family history may reveal parental pubertal delay.41,42

Other etiologies of delayed puberty are categorized based on gonadotropin levels. In hypergonadotropic hypogonadism, gonadal insufficiency delays puberty and results in elevated levels of FSH and LH. Conditions causing hypergonadotropic hypogonadism can be congenital or acquired and are collectively more common in girls (26%) than in boys (7%) with delayed puberty.7,39

Hypogonadotropic hypogonadism is characterized by low levels of FSH and LH and further classified by the pathology. Functional hypogonadotropic hypogonadism is caused by chronic disease, stress, or inadequate nutrition, and the condition may be transient or reversed. Persistent hypogonadotropic hypogonadism is caused by a congenital abnormality in the HPG axis or an acquired etiology such as a central nervous system tumor, trauma, surgery, or radiation.7,43 Patients with persistent hypogonadotropic hypogonadism require treatment to induce puberty, maintain normal adult levels of sex steroids, and optimize fertility.44 eTable C includes the differential diagnosis of delayed or absent puberty.

DiagnosisCharacteristicsTreatment
Generally benign variant
Constitutional delay of growth and pubertyNormal growth velocity, history of delayed puberty in parents, delayed bone ageSurveillance every 6 months to evaluate for progression of pubertal development
Functional hypogonadotropic hypogonadism*
Celiac diseaseAbdominal pain, malabsorption, anemia, poor weight gain; short stature may be the only symptom; positive serology results, confirmed with endoscopic biopsyGluten-free diet, surveillance
Diabetes mellitusPolyuria, polydipsia, polyphagia, weight loss, or known but poorly controlled disease; confirmed by serologyTreat underlying disease
HyperthyroidismWeight loss, heat intolerance, insomnia, tachycardia, hypertension; confirmed with serologyTreat underlying disease
HypothyroidismWeight gain, cold intolerance, fatigue, bradycardia; confirmed with serologyTreat underlying disease
Inadequate nutrition for metabolic needs (e.g., eating disorder)Weight loss or poor weight gain, excessive exercise, food restriction, purgingWeight restoration, treatment of underlying disorder
Inflammatory bowel diseaseAbdominal pain, constipation, diarrhea, hematochezia, poor weight gain, elevated serum erythrocyte sedimentation rate and C-reactive protein; confirmed with endoscopic biopsyTreat underlying disease
Persistent hypogonadotropic hypogonadism
Genetic
Congenital hypogonadotropic hypogonadismGonadotropin-releasing hormone deficiency, bilateral cryptorchidism, micropenis, unilateral renal agenesis, synkinesis (mirror movements), cleft lip or palate, hearing loss, dental agenesis, skeletal malformationsReferral to a pediatric endocrinologist for hormone therapy
Kallmann syndromeAnosmia in addition to congenital hypogonadotropic hypogonadism presentationReferral to a pediatric endocrinologist for hormone therapy
Acquired
CNS trauma, surgery, or radiationHistory of trauma, surgery, or CNS radiation for prior malignancy; may present similarly to CNS tumor if acuteReferral to a pediatric endocrinologist for hormone therapy; other referrals as necessary for treatment of underlying disease
CNS tumorsHeadaches, vision changes, seizures, suggestive magnetic resonance imaging findings of the brain and pituitaryReferral for diagnosis and treatment of underlying disease (e.g., neurosurgeon, endocrinologist)
Hypergonadotropic hypogonadism§
Chemotherapy, radiation, or trauma to gonadsHistoryReferral to a pediatric endocrinologist for hormone therapy
Klinefelter syndrome (boys)Tall stature, learning disabilities, relatively small testes (3 to 6 mL) for degree of androgenization; 47,XXY karyotypeReferral to a pediatric endocrinologist for hormone therapy
Oophoritis or orchitisHistory of mumps infection in boysReferral to a pediatric endocrinologist for hormone therapy
Turner syndrome (girls)Short stature, facial dysmorphism, webbed neck, brachydactyly, heart defects; in cases of mosaicism, short stature may be the only sign; 45,X or related karyotypeReferral to a pediatric endocrinologist for hormone therapy and other comprehensive care

Initial workup should include measurements of serum FSH, LH, testosterone in boys or estradiol in girls, and bone age radiography (eTable B, Figure 27,8,25,44,45). If abnormal growth velocity is a concern, serum thyroid function, prolactin, and insulinlike growth factor I should be assessed.7 Constitutional delay of growth and puberty can be difficult to distinguish from persistent hypogonadotropic hypogonadism; the latter may be diagnosed at 18 years of age if there is inadequate response to jump-start therapy (which is defined later in this section), and sex steroid replacement is still required.7,45

Bone age indicates the degree of sex steroid effect on bone maturation and future growth potential.7,9 For example, patients with constitutional delay of growth and puberty generally have a delay of more than two years, but this finding is nonspecific.8

Delayed puberty can cause significant psychological distress and low self-esteem.46,47 Girls older than 13 years and boys older than 14 years with possible constitutional delay of growth and puberty or gonadotropin-releasing hormone deficiency may be offered jump-start therapy to induce puberty.5,7,8,25,45 For example, treating boys with testosterone cypionate or enanthate (e.g., 50 to 100 mg intramuscularly per month) and girls with overnight transdermal estradiol (e.g., 6.2 mcg, one-fourth of the 25-mcg 24-hour patch) for three to six months may accelerate attainment of final adult height and generally does not lead to premature epiphysis closure.7,25 If pubertal progression does not occur within four to six months after completing therapy, further evaluation for persistent hypogonadotropic hypogonadism and long-term hormone therapy should be initiated.5,7 Indications for referral to a pediatric endocrinologist are listed in eTable D.

Concern for early puberty*
Any pubertal changes before 6 years of age in girls and 9 years of age in boys
Pubertal changes with associated headaches, vision changes, new-onset seizures
Rapid pubertal progression
Confirmed central or peripheral precocious puberty (not a generally benign variant)
Known predisposing conditions (e.g., neurofibromatosis, previous irradiation, known neoplasm)
Concern for delayed puberty
Boys without testicular growth to at least 4 mL in volume or 2.5 cm in length by 14 years of age
Girls without breast development by 13 years of age

This article updates a previous article on this topic by Blondell, et al.48

Data Sources: A PubMed search was completed using the MeSH function with the key term puberty and at least one of the following qualifiers: early, precocious, delayed, absent, or disorder. The search included meta-analyses, randomized controlled trials, observational studies, and reviews. Nonhuman studies and studies older than 10 years were excluded. The reference lists of included reviews were searched for additional studies of interest. Other searches included Essential Evidence Plus, the Cochrane Database of Systematic Reviews, and the U.S. Preventive Services Task Force website. Search dates: October 1, 2016, to May 21, 2017.

The views expressed in this publication are those of the authors and do not reflect the official policy or position of the Departments of the Army, Navy, or Air Force; the Department of Defense; or the U.S. government.

Continue Reading


More in AFP

Copyright © 2017 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See https://www.aafp.org/about/this-site/permissions.html for copyright questions and/or permission requests.