A nearly 9-year-old girl is brought in for evaluation of a growth spurt. Parents say she's showing signs of puberty earlier than her siblings. She's at the 96th percentile for height and 98th percentile for weight. Physical exam: Tanner stage 1 pubic hair, Tanner stage 2 breast development. Sparse, soft axillary hair. The core driver is:
THE RULE
One Cutoff Decides Everything
Before you touch labs, imaging, or differentials, ask one question: how old is the kid? The age decides whether you have a problem or a normal child.
Boys: puberty before age 9 = precocious. Age 9 to 14 = normal.🔑8 for girls, 9 for boys. Girls start a year earlier, just like in real life.
"Average puberty in America is 10 for girls, 11 for boys. Standard deviation, 1 year. Two SDs early: 8 for girls, 9 for boys. Before 8, before 9, that's precocious. Know your cutoffs."
The chain: signs of puberty → check age → above cutoff = normal variation → reassure, no workup. Below cutoff = precocious → start the algorithm.
The girl in the opener is almost 9. She's inside the 8 to 12 window. Her sequence is normal (breast first, then hair). She's just earlier than her siblings. That's variation, not pathology.
THE STAGES
Tanner Staging
Match the description to the number. Not the age. The description.
"How would you describe Tanner 3? What does it LOOK like? I don't care about the age. Tanner is a physical exam scale, not a calendar."
Trap word: "coarse." Coarse hair is Tanner 4, not Tanner 3. Tanner 3 is darker and curling. Tanner 4 is full adult texture, just not yet on the thighs. Every time.
"Tanner 1: nothing. Tanner 2: sparse, one here, one here. Tanner 3: there's a PATCH. See a patch, that's a 3. Don't overthink it."
"Tanner 4 covers the base. Tanner 5 reaches the thigh or climbs onto the pelvis. That's the whole system. Description to number. Every time."
BOYS' GENITAL STAGING
Same five stages. Testes and penis instead of breasts. Volume by orchidometer is the key metric.
THE SEQUENCE
Normal Order of Puberty
Puberty plays in a fixed order. Out-of-order = pathology, even if the age is normal. Hair before breasts in a girl? That's not late thelarche. That's an androgen source (adrenal tumor, CAH) until proven otherwise.
"First sign in a girl: breast bud. First sign in a boy: balls get bigger. Not pubic hair. The boards will try to fool you with hair, every time. Don't fall for it. Hair is adrenal. The first real puberty sign is gonadal."
BARS SHOW TYPICAL AGE RANGE
WHEN IT'S TOO EARLY
Precocious Puberty
Puberty before 8 (girls) or 9 (boys). One question runs the whole workup: is the brain driving this, or is something else making hormones on its own?
The chain: too-early signs → LH/FSH → GnRH stim test. The stim test answers the central vs peripheral question with one injection.
"See precocious puberty, the next question is always the same: central or peripheral? Brain's switch flipped early, or is something out there making the hormone on its own? That fork drives the whole differential."
| Central (GnRH-Dependent) | Peripheral (GnRH-Independent) | |
|---|---|---|
| Where | HPG axis flipped on early. Brain is driving it. | Hormones come from outside the axis. Tumor, adrenal, exogenous. |
| LH/FSH | High (pituitary fully active) | Suppressed (axis shut down by hormone flood) |
| GnRH stim | LH surges | LH stays flat |
| Sequence | Normal order, just early | Off-sequence (isolated breast or isolated hair) |
| #1 cause | Idiopathic (girls). CNS lesion / hamartoma (boys, until proven otherwise). | CAH, McCune-Albright, granulosa cell tumor, exogenous estrogen/androgen. |
| Rx | Leuprolide. Continuous GnRH agonist desensitizes the pituitary. | Treat the source. Remove tumor, stop exposure, block enzyme. |
"One injection tells you everything. GnRH only talks to the pituitary. It can't reach a tumor in the ovary or the adrenal. So if the shot makes LH jump, the pituitary is awake and primed. Central. If the shot does nothing, the pituitary is asleep because something else is doing the work. Peripheral. Find the source."
LH stays flat after GnRH → pituitary is suppressed → Peripheral PP → DHEAS, 17-OHP, hCG, ovarian/adrenal imaging. Treat the source.
Boy with central PP: assume CNS lesion (hypothalamic hamartoma is classic) until MRI proves otherwise. Boys with early puberty get their brain imaged.
1. ALL boys with central precocious puberty.
2. Girls younger than 6 with precocious puberty.
3. Any child with neurologic symptoms (headache, vision change, vomiting).🔑Boys always get MRI. Girls only if <6 or neuro symptoms. Girls 6 to 8 with idiopathic CPP usually skip MRI.
INTERACTIVE
GnRH Stimulation Test Simulator
Same shot, two patients. Watch what the LH curve tells you.
CHALLENGE
Sort: Central or Peripheral?
Tap a card, then tap the bin where it belongs.
THE LINEUP
Puberty Disorders
Tap to expand.
- Clue: Girl <8 or boy <9 with normal sequence (just early).
- Mechanism: Brain flipped the switch ahead of schedule. Hypothalamus → GnRH → LH/FSH → gonads.
- Labs: LH and FSH pubertal. LH surges after GnRH stim.
- #1 cause: Girls = idiopathic. Boys = CNS lesion (hypothalamic hamartoma) until MRI says otherwise.
- Rx: Leuprolide. Continuous GnRH agonist desensitizes the pituitary → LH/FSH drop → puberty pauses until age-appropriate.
- Clue: Off-sequence puberty (isolated breast or isolated hair, virilization in a girl, etc.).
- Mechanism: Sex hormones from outside the HPG axis → flood → pituitary shuts off in negative feedback.
- Labs: LH/FSH suppressed. Flat LH after GnRH stim.
- Top sources: CAH (21-OH def), McCune-Albright, granulosa cell tumor (girls), Leydig cell tumor (boys), exogenous estrogen/androgen, hCG-secreting tumor.
- Rx: Treat the source. Leuprolide does nothing here, the axis isn't the problem.
- Triad: Precocious puberty + polyostotic fibrous dysplasia + cafe au lait spots with jagged "coast of Maine" borders.
- Mechanism: Somatic GNAS mutation locks Gs-alpha ON → constitutive cAMP → multiple endocrine glands fire without upstream signal.
- Labs: Peripheral PP pattern. LH/FSH suppressed, estradiol high.
- Bonus: May also see hyperthyroidism, Cushing's, GH excess, hyperphosphatemia. Any Gs-driven gland is fair game.
- Board pearl: Fracture + early puberty + jagged cafe au lait = McCune-Albright.
- Clue: No signs by 13 (girls) or 14 (boys), short for age, plus a parent who was a "late bloomer."
- Mechanism: Normal variant. HPG axis is fine, just clocking late.
- Bone age: Delayed. Matches the kid's developmental stage, not the birthday.
- Labs: LH, FSH, testosterone all low, but appropriate for the bone age.
- Discriminator: Smell is normal. That rules out Kallmann.
- Rx: Reassure. Short course of testosterone or estrogen if psychosocial distress.
- Clue: Teen with no puberty AND anosmia (can't smell coffee, gasoline, mint).
- Mechanism: GnRH neurons share an embryonic origin with olfactory neurons. They fail to migrate from the nose to the hypothalamus together → no GnRH AND no smell.
- Labs: Low LH, low FSH, low sex steroids (hypogonadotropic hypogonadism).
- MRI: Hypoplastic or absent olfactory bulbs.
- Board pearl: Always ask about smell in delayed puberty. Anosmia + no puberty = Kallmann. Every time.
- Karyotype: 45,XO (one X missing).
- Body: Short, webbed neck, shield chest with wide-spaced nipples, cubitus valgus, lymphedema of hands and feet at birth.
- Gonads: Streak ovaries → primary amenorrhea → no estrogen → no puberty.
- Cardiac: Bicuspid aortic valve, coarctation of the aorta.
- Renal: Horseshoe kidney.
- Labs: High FSH/LH (hypergonadotropic). Pituitary screaming at gonads that never answer.
- Rx: GH for height. Estrogen + progesterone for puberty.
- Karyotype: 47,XXY (one extra X).
- Body: Tall, long limbs, gynecomastia, sparse facial/body hair, small FIRM testes.
- Mechanism: Extra X scars the seminiferous tubules → tubules fibrose → testes feel firm AND can't make sperm. Leydig cells fail too → low testosterone.
- Labs: Low testosterone, high FSH/LH (hypergonadotropic), azoospermia.
- Board pearl: Tall teen with gynecomastia and small firm testes → karyotype. Don't biopsy first.
- Rx: Testosterone replacement. Fertility is very limited.
- Clue: Girl <8 with isolated breast development. Tanner 1 hair. Normal growth velocity.
- Mechanism: Brief, low-grade estrogen pulse. Often bilateral, sometimes asymmetric. Benign variant.
- Bone age: Normal (this is the test that rules in benign).
- Rx: Reassure. Re-check every 6 months. If hair, growth spurt, or rapid progression appear → restart the precocious puberty workup.
- Pearl: One sign = benign. Two signs = investigate.
- Clue: Pubic or axillary hair, body odor, mild acne before 8 (girls) or 9 (boys). No breast, no testicular growth.
- Mechanism: Adrenal zona reticularis turns on early → DHEAS rises → hair follicles activate. Gonadal axis stays quiet.
- Bone age: Normal or just slightly advanced.
- Rule out: Non-classic CAH. Check 17-OHP.
- Rx: Reassure once CAH is excluded. Benign, but flag obesity and insulin resistance risk later.
- Karyotype: 46,XY. Phenotypically female.
- Mechanism: Androgen receptor is broken. Testes make testosterone, but the body can't hear it. Testosterone aromatizes to estrogen → breast development. No androgen action → scant pubic/axillary hair.
- Anatomy: Testes present (inguinal or intra-abdominal). No uterus (AMH destroyed Mullerian ducts). Blind-ending vaginal pouch.
- Presentation: Primary amenorrhea in a girl with breasts but no body hair. Inguinal masses on exam.
- Rx: Let endogenous estrogen finish puberty. Gonadectomy AFTER puberty (2 to 3% gonadoblastoma risk). Lifelong estrogen replacement.
- Karyotype: 46,XY. Undervirilized external genitalia at birth (often raised female).
- Mechanism: Cannot convert testosterone to DHT. DHT drives external male genitalia in utero. At puberty, rising testosterone (which doesn't need 5-AR for muscle, voice, phallus growth) causes virilization.
- Clue: "Girl" who virilizes at puberty. Phallic enlargement, voice deepening, muscle growth. Testes descend.
- Internal structures: Normal. AMH is intact, so Mullerian ducts regressed. Wolffian ducts developed (testosterone works for those).
- Board pearl: Phenotypic female at birth who masculinizes at puberty = 5-AR deficiency until proven otherwise.
- Karyotype: 46,XX. Normal ovaries. Normal secondary sexual characteristics.
- Problem: Mullerian ducts failed to develop → absent uterus, absent upper vagina. Ovaries are NOT Mullerian, so they work fine.
- Presentation: Primary amenorrhea in an otherwise normal girl with breasts AND normal pubic hair.
- Discriminator: Normal pubic hair separates MRKH from AIS. AIS has scant hair (broken androgen receptor). MRKH has normal hair (working androgens, just no uterus).
- Associations: Renal anomalies (unilateral agenesis), skeletal anomalies.
- Clue: Adolescent girl with normal puberty, cyclic pelvic pain, no visible menses. Bulging bluish membrane at introitus.
- Mechanism: Menstrual blood accumulates behind the imperforate membrane → hematocolpos (blood filling the vagina), then hematometra (filling the uterus).
- Imaging: Pelvic US shows fluid-filled vagina and uterus.
- Rx: Surgical incision of the hymen. Curative.
- Board pearl: Primary amenorrhea + uterus present + cyclic pain = outflow obstruction. Don't overthink it.
- Clue: Severe longstanding hypothyroidism + signs of precocious puberty. Usually girls: vaginal bleeding, breast development, ovarian cysts.
- Mechanism: Massive TSH elevation cross-reacts with the FSH receptor (structural homology between TSH and FSH). Ovaries respond as if FSH is elevated.
- Unique board pearl: Bone age is DELAYED, not advanced. Every other cause of precocious puberty advances bone age. Van Wyk-Grumbach is the exception.
- Labs: Sky-high TSH, low T4, elevated FSH, ovarian cysts on ultrasound.
- Rx: Thyroid hormone replacement. Pseudopuberty reverses completely.
- When: Tanner genital stages 3 to 4. Up to 65% of boys get transient breast tissue during normal puberty.
- Mechanism: Transient estrogen/androgen imbalance as the HPG axis ramps up. Testosterone aromatizes to estrogen before full androgen levels stabilize.
- Resolves: Usually within 6 to 18 months. Self-limited.
- Red flags: Persists >24 months, progressive, painful, or occurs WITHOUT other pubertal progression. Evaluate: Klinefelter, prolactinoma, estrogen-secreting tumor, drug effect (spironolactone, marijuana).
- Board pearl: Bilateral, non-tender, Tanner 3 to 4 = reassure. Unilateral, firm, fixed = image it.
- Clue: Post-pubertal male with intellectual disability + large testes (macroorchidism) + long face + prominent ears.
- Mechanism: FMR1 gene CGG repeat expansion on the X chromosome. Silences FMRP protein needed for synaptic development.
- Testes: Enlarged AFTER puberty (>30 mL), unlike Klinefelter which has SMALL testes. That's the discriminator.
- Carrier effect: Female premutation carriers are at risk for primary ovarian insufficiency (premature menopause <40).
- Board pearl: Big testes + intellectual disability = Fragile X. Small firm testes + tall + gynecomastia = Klinefelter. Size and texture of the testes split them.
ALGORITHM
Decision Tree: Evaluating Early Puberty
Tap through the steps.
GROWTH MECHANICS
Hormones, Bone Age & Growth Plates
"Two engines, two tracks. The brain-gonad axis makes thelarche, menarche, testes. The adrenal axis makes hair, odor, acne. They normally run together, but they can run apart. Isolated hair? Think adrenal. Isolated breast? Think gonadal or estrogen exposure. Know which engine you're looking at."
| Group | Peak velocity | Tanner | Age |
|---|---|---|---|
| Girls | 8 to 9 cm/yr | Tanner 2 to 3 | 11 to 12 |
| Boys | 9 to 10 cm/yr | Tanner 3 to 4 | 13 to 14 |
Why men end up taller: the spurt is only slightly bigger, but it starts ~2 years later. Those 2 extra years of pre-spurt growth before the plates close are the entire difference.
Long bones grow at the epiphyseal plate (cartilage disc between metaphysis and epiphysis). Sex hormones close that plate by killing the chondrocytes and replacing cartilage with bone.
Estrogen closes plates. In BOTH sexes. Testosterone matters mostly because aromatase converts it to estrogen at the plate. Aromatase-deficient men keep growing into their 20s → tall stature, eunuchoid proportions. That's the proof.
- Most long-bone plates close: girls 15 to 16, boys 17 to 18.
- Hand & wrist (read for bone age): fused by 16 (girls) / 18 (boys).
- Clavicle, iliac crest: last to fuse (mid-20s).
Boards trap: precocious puberty kid looks tall today. Without leuprolide, plates close early → short adult. Treating them protects adult height.
Bone age = left-hand-and-wrist X-ray, compared to the Greulich-Pyle atlas. It tells you how mature the skeleton is, not how many birthdays the kid has had.
Why it matters: bone age tracks hormone exposure. Hormone signal advances the skeleton. So bone age vs chronological age is a direct readout of "how much sex steroid has this kid been seeing?"
"Bone age two standard deviations above chronologic age. What does that tell you? Those bones are being driven. He's too young to have that much hormone on board. Something is making sex steroids that shouldn't be there yet. The X-ray caught it."
- Bone age > chronological age: too much hormone, too early. Precocious puberty, CAH, McCune-Albright, exogenous exposure.
- Bone age < chronological age: not enough hormone. Constitutional delay, hypogonadism, GH deficiency, chronic disease, malnutrition.
- Bone age = chronological age: on schedule. Isolated premature thelarche / adrenarche live here.
VISUAL REFERENCE
Clinical Images & Cafe Au Lait Discriminator
McCune-Albright: irregular cafe au lait ("coast of Maine")
Turner syndrome: webbed neck (pterygium colli)
Coarctation of aorta: Turner cardiac association
Gynecomastia: classic Klinefelter finding
Polyostotic fibrous dysplasia: McCune-Albright bone lesion
DISCRIMINATOR
Coast of Maine vs Coast of California
Same color spot. Border shape splits two completely different diseases.
"Big hyperpigmented patches with jagged borders, plus fractures, plus early puberty? McCune-Albright. Six or more smooth-bordered spots, plus axillary freckling, plus a Lisch nodule on slit lamp? That's NF1. Same color, different border, different disease. Know your clues."
WHEN IT'S TOO LATE
Delayed Puberty
The mirror image of precocious puberty. The HPG axis should have fired by now. It hasn't. One question runs the whole workup: is the clock just running slow, or is something actually broken?
Boys: no testicular enlargement (≥4 mL) by age 14 = delayed.
Girls: no menarche by 15, or >3 years after thelarche = evaluate.🔑Precocious: 8 girls, 9 boys. Delayed: 13 girls, 14 boys. Both sets are one year apart.
"Precocious puberty: before 8, before 9. Delayed puberty: no breast by 13, no testes by 14. Two sets of numbers. Know them cold. The most common cause of delayed puberty? Constitutional delay. More common in boys. Dad was a late bloomer. That's your #1 answer."
| Constitutional Delay | Hypogonadotropic | Hypergonadotropic | |
|---|---|---|---|
| Where | Normal variant. Clock is slow, all parts work. | Brain/pituitary not sending the signal. | Gonads not responding to the signal. |
| LH/FSH | Low, but appropriate for bone age. | Low (brain is quiet). | High (pituitary screaming at dead gonads). |
| Bone age | Delayed (matches developmental stage). | Delayed or normal. | Normal or delayed. |
| Smell | Normal. | Absent in Kallmann. | Normal. |
| Examples | Late-bloomer dad. Short today, normal adult height. | Kallmann, pituitary tumor, anorexia, chronic illness, exercise. | Turner (45,X), Klinefelter (47,XXY), chemo/radiation gonadal injury. |
| Rx | Reassure. Short testosterone/estrogen course if psych distress. | Treat cause. Replace sex steroids. | Replace sex steroids. GH for Turner. |
"Think of FSH and LH as the pituitary yelling at the gonads. If the gonads are dead (Turner, Klinefelter), the pituitary yells LOUDER. FSH and LH go sky-high. If the brain never sent the signal (Kallmann, constitutional), the pituitary is quiet. FSH and LH stay low. Direction of the gonadotropins. Every time."
THE WORKUP
Primary Amenorrhea
No period by 15. Or no period >3 years after thelarche. Or no pubertal development by 13.
Step zero: pregnancy test. Always. Then the algorithm branches on one question: are secondary sexual characteristics present?
"Primary amenorrhea algorithm: breasts or no breasts. No breasts? High FSH means dead ovaries, low FSH means the brain never asked. Breasts present? Check for a uterus. No uterus plus no hair equals AIS. No uterus plus hair equals Mullerian agenesis. Uterus plus pain equals outflow obstruction. Three branches. That's the whole tree."
BOARD PREP
Board-Style Walkthrough
34 original clinical vignettes. One at a time. Tap each teaching beat to reveal the chain.