What is the appropriate workup and management for a 14-year-old boy with delayed puberty and short stature?

Workup for 14-Year-Old Boy with Delayed Puberty and Short Stature

Begin with serum prolactin measurement, bone age radiograph, complete blood count, comprehensive metabolic panel, thyroid function tests, and assessment of FSH, LH, and testosterone to differentiate constitutional delay from pathologic causes requiring intervention. 1, 2, 3

Initial Clinical Assessment

Critical Historical Elements

• Document birth parameters (weight, length, head circumference) to identify intrauterine growth restriction, which suggests different etiologies than postnatal-onset short stature 2, 4
• Obtain parental heights to calculate midparental height and assess genetic potential for growth 2, 3, 4
• Review parental pubertal timing, as constitutional delay is often inherited and fathers frequently experienced late puberty 4, 5
• Assess growth velocity over the past 6-12 months, as crossing several centile lines indicates pathologic short stature requiring urgent evaluation 1, 3

Essential Physical Examination Findings

• Measure testicular volume using orchidometer; volume <4 mL at age 14 confirms delayed puberty 6, 5, 7
• Evaluate body proportions (sitting height to standing height ratio) to distinguish proportionate from disproportionate short stature 2, 4
• Document dysmorphic features including facial characteristics, limb abnormalities, and any major or minor malformations that suggest chromosomal abnormalities or genetic syndromes 1, 2, 4
• Assess for signs of hypogonadism including gynaecomastia, which may indicate hyperprolactinaemia 1

Laboratory Workup

First-Line Testing

• Serum prolactin (single measurement at any time of day) to exclude prolactinoma, which commonly presents with delayed puberty and growth failure 1
• FSH, LH, and testosterone to differentiate hypogonadotropic hypogonadism (low FSH/LH) from hypergonadotropic hypogonadism (elevated FSH/LH) 1, 3, 7
• Thyroid function tests (TSH, free T4) to exclude hypothyroidism as a reversible cause 2, 3, 7
• Complete blood count and comprehensive metabolic panel to rule out chronic disease and assess renal/hepatic function 3, 7
• IGF-1 level (age-specific and sex-specific reference ranges) to screen for growth hormone deficiency 1

Radiologic Assessment

• Bone age radiograph (left wrist and hand) to determine growth potential and differentiate constitutional delay (delayed bone age) from familial short stature (normal bone age) 2, 3, 4
• Repeat bone age every 6 months if treatment is initiated to monitor epiphyseal maturation 8

Differential Diagnosis Framework

Constitutional Delay of Growth and Puberty (Most Common)

• Characteristics: Normal growth velocity (4-7 cm/year), delayed bone age by 2+ years, family history of late puberty, eventual normal adult height 2, 3, 4
• This is a diagnosis of exclusion requiring ruling out pathologic causes 5, 7

Pathologic Hypogonadotropic Hypogonadism

• Low FSH, LH, and testosterone with delayed puberty indicates central deficiency 3, 7
• Consider prolactinoma if prolactin >4,000 mU/L (188 μg/L), though lower levels occur with microprolactinomas 1
• Obtain brain MRI if neurologic symptoms, visual field defects, headaches, or confirmed hyperprolactinaemia are present 1, 7

Pathologic Hypergonadotropic Hypogonadism

• Elevated FSH and LH with low testosterone indicates primary gonadal failure 7
• Karyotype analysis is mandatory to exclude Klinefelter syndrome 7

Genetic/Syndromic Causes

• Turner syndrome variants can present in phenotypic males; chromosome analysis should be performed if dysmorphic features or disproportionate short stature are present 1, 2, 3
• SHOX gene testing if clinical or radiographic findings suggest dyschondrosteosis 2, 3
• Skeletal survey if disproportionate short stature suggests skeletal dysplasia 2, 3

Management Algorithm

If Constitutional Delay is Confirmed

• Reassurance and observation are often sufficient if the patient is not experiencing significant psychosocial distress 6, 5
• Short-term testosterone therapy (testosterone enanthate 50-100 mg IM monthly for 3-6 months) can be offered to boys experiencing psychosocial stress 8, 6, 5, 7
• Monitor for spontaneous resumption of pubertal progression after treatment cessation 6, 5

If Hypogonadotropic Hypogonadism is Confirmed

• Long-term testosterone replacement is required, starting with low doses and escalating to mimic normal puberty 8, 6, 5
• Testosterone enanthate is FDA-approved for hypogonadotropic hypogonadism and delayed puberty in carefully selected males 8
• Continue treatment until completion of pubertal development and growth, discontinuing when height velocity drops below 2 cm/year and epiphyseal plates close 3, 8

If Hypergonadotropic Hypogonadism is Confirmed

• Lifelong testosterone replacement is necessary as spontaneous recovery will not occur 6

If Prolactinoma is Diagnosed

• Dopamine agonist therapy is first-line treatment 1
• Genetic testing should be considered for MEN1, MEN1-like, or familial isolated pituitary adenoma syndromes 1

Critical Pitfalls to Avoid

• Missing Turner syndrome or its variants by failing to obtain karyotype in boys with unexplained short stature and dysmorphic features 2, 3
• Overlooking prolactinoma by not measuring prolactin in all cases of delayed puberty with growth failure 1
• Initiating testosterone therapy without bone age assessment, which risks premature epiphyseal closure and compromised final adult height 8
• Assuming constitutional delay at age 14 without excluding pathologic causes, as true constitutional delay should show some pubertal signs by this age 9, 7
• Failing to monitor bone age every 6 months during androgen treatment, as accelerated bone maturation without compensatory linear growth compromises final height 8

When to Refer to Pediatric Endocrinology

• Severe growth velocity deceleration (crossing multiple centile lines) 2
• Confirmed hypogonadotropic or hypergonadotropic hypogonadism requiring hormone replacement 6, 7
• Elevated prolactin levels requiring further evaluation and management 1
• Dysmorphic features or disproportionate short stature suggesting genetic syndromes 2, 3
• Age 16 or older without pubertal onset, as constitutional delay becomes less likely and pathologic causes more probable 9, 7