Bruce J. Schlomer, MD
Laurence S. Baskin, MD, FACS, FAAP
BASICS
DESCRIPTION
• A micropenis refers to a stretched newborn penis that is <2.5 standard deviations below the normal mean in length (1)
• Full-term newborn micropenis would be <1.9 cm in length (1)
• Typical normal mean stretched penile length in a newborn is 3.5 cm
• The penis is normally formed but small, ie, no hypospadias (2)
• Scrotum usually normal but can be smaller
• Testicles usually descended but may not function normally
• A micropenis is generally not considered to be associated with ambiguous genitalia since the penis is normal in configuration, the scrotum is normal and the testes are usually descended.
• Micropenis is a finding with many causes
EPIDEMIOLOGY
Incidence
∼1.5/10,000
Prevalence
None
RISK FACTORS
• Maternal exposure to antiandrogen medications during pregnancy
• Advanced maternal age: Nondisjunction during meiosis can lead to Down syndrome, Klinefelter syndrome, and polysomy X syndromes
Genetics
• X-linked recessive, autosomal recessive, autosomal dominant have all been identified
• Idiopathic spontaneous mutations noted
• Specific known genetic conditions:
– Kallmann syndrome
– Prader–Willi syndrome
– Laurence–Moon–Biedl syndrome
– Polysomy X (Klinefelter)
– Translocation, deletion, trisomy of chromosome 8, 13, 18, and 21
– Partial androgen-insensitivity syndrome (PAIS)
– 5α-reductase deficiency
– Noonan syndrome
– Rud’s syndrome
PATHOPHYSIOLOGY
• Normal penile growth and development is both androgen dependent and independent.
• 1st trimester: Maternal hCG stimulates testicle Leydig cells to produce Testosterone (T). T is converted to dihydrotestosterone (DHT) by 5α-reductase in genital tubercle. Penis and urethra are completely formed by end of 1st trimester by influence of DHT.
• 2nd trimester: Fet al hypothalamus and pituitary drive T production by fet al testis which causes penile growth.
• Micropenis believed to be due to inadequate fet al T production or action after the 1st trimester (1).
ASSOCIATED CONDITIONS
• Hypogonadotropic hypogonadism:
– Most common cause of micropenis
– Kallmann syndrome: Anosmia, deficit in GnRH secretion, autosomal dominant
– Prader Willi syndrome: Short stature, hyperphagia, hypotonia, diabetes mellitus, behavior problems, hypogonadism
– Laurence–Moon–Biedl syndrome
– Rud’s syndrome
• Primary testicular failure:
– Gonadal dysgenesis
– Anorchia
– Klinefelter’s and polysomy X syndromes
– Luteinizing hormone (LH) receptor defects
– Defects in T steroidogenesis
– Noonan syndrome
– Robinow syndrome
– Laurence–Moon–Biedl syndrome
– Trisomy 8, 13, 18, and 21
• Defects in T action
– PAIS
– 5α-reductase deficiency
• Idiopathic form:
– Normal hypothalamic–pituitary–testicle axis
– Hypothesized to be due to delayed onset of fet al gonadotropin stimulation
GENERAL PREVENTION
Avoid maternal exposure to antiandrogens
DIAGNOSIS
HISTORY
• History of genetic syndrome (eg, Kallman)
• Maternal history: Medications during pregnancy, antenatal US, prior stillbirths, decreased fet al activity, or hypotonia at birth
• Family history: Genitourinary anomalies, hypospadias, cryptorchidism, infertility, major congenital anomalies
PHYSICAL EXAM
• Facies suggestive of midline cranial defect, mental retardation:
– Microcephaly, hypertelorism, low-set ears, small mouth, high-arched palate
• Weight and body habitus: Prader–Willi syndrome, growth hormone abnormality
• Skin: Nevi, ichthyosis
• Hearing: Deafness
• Smell: Anosmia suggests Kallmann syndrome
• Retinal pigment changes on funduscopic exam
• Penis:
– Always depress fat pad during exam
– Prepuce, meatus location, general appearance
– Stretched penile length (SPL): Measure from tip of glans to pubic symphysis
– Use physiologic age when comparing SPL with standard nomograms
– Penile girth usually normal and proportional to length
– Exclude other diagnoses such as hidden penis or buried penis (beware of a large suprapubic fat pad that may distort a normal penis)
• Scrotum: Size, symmetry, and appearance
• Gonads: Size, shape, and position
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Karyotype
• Genetic testing if history consistent with known syndromes such as Prader–Willi or Kallman
• Differentiate between hypogonadotropic hypogonadism and primary testicular failure
– Pituitary assessment: ACTH, GH, TSH, LH, FSH. Low levels suggest hypogonadotropic hypogonadism
– High prolactin suggests hypothalamus defect vs. low prolactin suggests pituitary defect
– Elevated levels of LH, FSH, and T are normal during 1st 6 mo of life. Low T during this time suggests testicular failure. Confirm with hCG stimulation test. LH, FSH should elevate but T will remain low in testicular failure
– hCG stimulation test: Assesses testicle for T biosynthesis: 1,000 U of hCG IV or IM for 3 days, measure serum T and DHT levels on days 0 and 4. If T at day 4 >100 ng/dL, response is normal. If no response, suggests primary testicular failure
– From 6 mo to puberty, levels of LH, FSH, and T are low. LH, FSH elevate with hCG stimulation test but serum T low in testicular failure
– For patients who have undergone or started puberty, LH and FSH are normally elevated as may be serum T. LH, FSH, and T are usually low in micropenis. Do hCG stimulation test and look for response; assess pubertal changes to be sure it is not constitutional pubertal delay
– Antimüllerian hormone is produced by functional sertoli cells and can be used to detect functional testis tissue
• Identifying defects in T action
– LH, FSH, T normal, or elevated with PAIS
– PAIS diagnosis often given after excluding other diagnoses
– Penis may grow with trial of T IM in PAIS
– Increased T/DHT ratio with hCG stimulation test or postpubertal suggests 5α-reductase deficiency
– AR gene mutation only found in 20% of PAIS
Imaging
• MRI of head: Assess hypothalamus, pituitary, brain, craniofacial anomalies, optic chiasm, 4th ventricle, corpus callosum
• Renal imaging: Assess kidneys and bladder; VCUG and MAG3 renal scan if US suggest renal or bladder anomaly or ectopia
Diagnostic Procedures/Surgery
• Laparoscopy to assess nonpalpable undescended testicles, look for müllerian duct structures, biopsy any dysgenetic tissue
• Genitogram indicated if dysgenetic gonads, ovotestis, müllerian duct structures are found or if androgen insensitivity is suspected
Pathologic Findings
• Newborn penis is proportional but <1.9 cm
• Kallmann syndrome: Anosmia, GnRH deficiency: 10% KAL1 gene defect on Xp22.3, 10% KAL2 on 8p12, 70% autosomal dominant with no identified gene defect
• Prader–Willi syndrome: Short stature, hyperphagia, mental retardation, diabetes, hypotonia, behavioral problems; lacking expression of gene SNRPN or necdin on 15q of paternal origin
• Laurence–Moon–Biedl syndrome: Obesity, retardation, pigmented retinopathy, polydactyly
DIFFERENTIAL DIAGNOSIS
• Concealed penis: Large suprapubic fat pad
• Webbed penis: Prominent penoscrotal web
• Postcircumcision cicatrix:
– Residual foreskin scarred above glans tip
• Hypospadias with and without chordee
• Chordee
• Disorders of sex differentiation:
– Female DSD: Congenital adrenal hyperplasia, gonads not palpable in labia/scrotum
– Male DSD
• Hypothalamic–pituitary axis dysfunction (50% of cases):
– Syndromes: Kallmann, Prader–Willi, Laurence–Moon–Biedl, Rud’s
• Isolated hormone deficiency:
– GnRH deficiency without Kallmann syndrome
– LH deficiency
– GH deficiency or growth hormone receptor defect (Laron dwarfism)
• Primary testicular failure:
– Hypergonadotropic hypogonadism (25% of cases)
– Testicular dysgenesis (Klinefelter syndrome, 47XXY)
– Laurence–Moon–Biedl syndrome
– Polysomy X syndromes
– Anorchia; intrauterine testicular torsion
• 5α-reductase deficiency: Rare
• PAIS (Partial androgen insensitivity syndrome)
• CNS abnormalities:
– Anencephaly, congenital pituitary aplasia, agenesis of corpus callosum, malformation of fourth ventricle
• Chromosome defects:
– Polysomy X syndromes
– Translocation, deletion, and trisomy of chromosomes 8, 13, 18, and 21
• Rare syndromes: Rud, Robinow, Martsolf, Fanconi anemia, Smith–Lemli–Opitz syndromes
• Idiopathic: Normal hypothalamic pituitary axis:
– Virilize normally at puberty
TREATMENT
GENERAL MEASURES
• Generally coordinated with an endocrinologist
• Correct any metabolic disturbances
• Specific treatment based upon cause
• Adrenal insufficiency: Treat with hydrocortisone supplementation and IV saline to correct hypovolemia
MEDICATION
First Line
• Testosterone therapy: Diagnostic and therapeutic: 25–50 mg testosterone enanthate IM Q monthly × 3 mo in infancy or prepubertal
• Long-term cortisol replacement, growth hormone, and thyroid hormone if pan-hypopituitarism present
• For gonadal deficiency: Induce puberty later in life with T IM injection or transdermal patch/gels
• For central deficiency: Administer hCG injection or GnRH therapy
Second Line
None
SURGERY/OTHER PROCEDURES
• Manage cryptorchidism with orchiopexy or orchiectomy (if dysgenetic) as needed
• Penile surgery for length or bulk has not been shown to be effective
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Familial genetic counseling and screening
• Prenatal care:
– Amniocentesis or chorionic villous sampling for chromosomal anomalies and sex determination
– Fet al US to look for genitourinary and central nervous anomalies
Complementary & Alternative Therapies
Gender reassignment: Generally not done any more for micropenis and is of only historical interest
ONGOING CARE
PROGNOSIS
• Overall good, but long-term effects depend on underlying cause
• Most have stable male gender identity
• Generally good response to 3-mo course of T IM with 100% increases in length seen (3)
• Final adult penis size with treatment usually 3)
COMPLICATIONS
• Relate to endocrine abnormalities if present
• Side effects of testosterone:
– Premature closure of epiphyseal plates; limits long-bone growth
– Behavioral changes: More aggressiveness
– Early stimulation of penile growth does not affect ultimate penile length
• Psychosocial issues:
– Most patients have a stable male gender identify but some dissatisfied with penis length
FOLLOW-UP
Patient Monitoring
• Psychological support and psychiatric therapy as needed:
– Reassure concerns about penile size, function, gender, potency
– Address behavioral and psychosocial problems
• Hormone biochemical monitoring:
– Follow pituitary and gonadal hormone therapy
– Assess growth, vital signs, electrolytes, serum glucose, renin, ACTH, GH, LH, FSH, and T.
• Physical monitoring: Serial penile measurements
Patient Resources
None
REFERENCES
1. Wiygul J, Palmer LS. Micropenis. ScientificWorldJournal. 2011;11:1462–1469.
2. Tsang S. When size matters: A clinical review of pathological micropenis. J Pediatr Health Care. 2010;4:231–240.
3. Bin-Abbas B, Conte FA, Grumbach MM, et al. Congenital hypogonadotropic hypogonadism and micropenis: Effect of testosterone treatment on adult penis size – why sex reversal is not indicated. J Pediatr. 1999;134:579–583.
ADDITIONAL READING
Baskin LS, Kogan BA. Handbook of Pediatric Urology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
See Also (Topic, Algorithm, Media)
• Androgen insensitivity syndrome (AIS; OR Androgen Resistance Syndrome), Complete (CAIS) and Partial (PAIS)
• Disorders of Sexual Development (DSD)
• Micropenis (Microphallus) Image 
• Penis, Buried (Concealed, Trapped, or Hidden)
• Penis, Length, Normal
• Penis, Webbed
CODES
ICD9
752.64 Micropenis
ICD10
Q55.62 Hypoplasia of penis
CLINICAL/SURGICAL PEARLS
• Micropenis is a condition with many causes, most of which are either a form of hypogonadotropic hypogonadism or primary testicular failure.
• Thought to be due to deficient T synthesis or action after the 1st trimester.
• Watch out for large suprapubic fat pad leading to incorrect diagnosis.
• Surgery generally not indicated except for associated cryptorchidism.