Disorders of Sexual Development (DSD) β Clinical Scenarios with Lab Data
You will be presented with 12 clinical scenarios of children with suspected disorders of sexual development.
For each, interpret the lab data and provide the most likely diagnosis, genetic basis, and next step.
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Case 1
A newborn with ambiguous genitalia (clitoromegaly, labial fusion), vomiting, and poor feeding. He is dehydrated and has a palpable mass in both inguinal regions.
Karyotype
46,XX
17-Hydroxyprogesterone (17-OHP)
12,000 ng/dL (elevated)
Serum Sodium
125 mEq/L (low)
Serum Potassium
6.8 mEq/L (elevated)
Blood Pressure
65/40 mm Hg
β Model Answer:
β’ Diagnosis: 46,XX DSD due to salt-wasting 21-hydroxylase deficiency (CAH).
β’ Evidence: 46,XX with virilization (clitoromegaly), elevated 17-OHP, hyponatremia, hyperkalemia, shock β adrenal crisis.
β’ Next step: IV hydrocortisone, normal saline bolus, IV dextrose. Start hydrocortisone + fludrocortisone. Genetic testing (CYP21A2).
Case 2
A newborn with ambiguous genitalia and hypertension.
Karyotype
46,XX
17-Hydroxyprogesterone (17-OHP)
800 ng/dL (mildly elevated)
11-Deoxycortisol
Elevated
Deoxycorticosterone (DOC)
Elevated
Serum Potassium
3.2 mEq/L (low)
Serum Sodium
145 mEq/L (normal)
Blood Pressure
85/55 mm Hg (hypertensive for newborn)
β Model Answer:
β’ Diagnosis: 46,XX DSD due to 11Ξ²-hydroxylase deficiency (CAH).
β’ Evidence: Virilization, hypertension, hypokalemia, elevated 11-deoxycortisol and DOC (mineralocorticoid excess).
β’ Next step: Start hydrocortisone (suppresses ACTH, reducing DOC). Genetic testing (CYP11B1). Monitor blood pressure.
Case 3
A 15-year-old girl with primary amenorrhea, no breast development, and a blind vaginal pouch.
Testosterone
600 ng/dL (normal range)
LH
15 mIU/mL (elevated)
FSH
8 mIU/mL (normal)
Estradiol
50 pg/mL (elevated β from peripheral aromatization)
Pelvic Ultrasound
Absent uterus, no ovaries, inguinal testes
Blood Pressure
118/72 mm Hg
β Model Answer:
β’ Diagnosis: Complete androgen insensitivity syndrome (CAIS) β 46,XY DSD.
β’ Evidence: 46,XY, female phenotype, blind vaginal pouch, absent uterus, inguinal testes, high testosterone with elevated LH (androgen resistance).
β’ Next step: Gonadectomy after puberty (age 16-18) to prevent malignancy, then estrogen replacement.
Case 4
A newborn with female external genitalia, no palpable gonads.
FSH
45 mIU/mL (elevated)
LH
30 mIU/mL (elevated)
Testosterone
20 ng/dL (low)
AMH
Undetectable
Pelvic Ultrasound
No uterus, no gonads visualized
Blood Pressure
70/45 mm Hg
β Model Answer:
β’ Diagnosis: Swyer syndrome (46,XY gonadal dysgenesis).
β’ Evidence: 46,XY female phenotype, streak gonads (no AMH), high gonadotropins (primary gonadal failure).
β’ Next step: Gonadectomy (high risk of gonadoblastoma), then estrogen replacement at puberty. Genetic testing (SRY, NR5A1).
Case 5
A 14-year-old boy with delayed puberty, micropenis, and bilateral cryptorchidism.
Karyotype
46,XY
LH
0.5 mIU/mL (low)
FSH
0.8 mIU/mL (low)
Testosterone
40 ng/dL (low)
Prolactin
Normal
MRI Pituitary
Normal
Blood Pressure
110/70 mm Hg
β Model Answer:
β’ Diagnosis: Hypogonadotropic hypogonadism (normosmic).
β’ Evidence: Low LH/FSH, low testosterone, normal sense of smell, normal MRI. Micropenis and cryptorchidism suggest congenital GnRH deficiency.
β’ Next step: Start testosterone replacement. Genetic testing (GNRHR, KISS1R, TAC3). Fertility: GnRH pump or gonadotropins.
Case 6
A newborn with ambiguous genitalia, palpable gonads bilaterally.
β Model Answer:
β’ Diagnosis: 5Ξ±-reductase type 2 deficiency (46,XY DSD).
β’ Evidence: 46,XY ambiguous genitalia, normal testosterone rise on hCG, low DHT, elevated T/DHT ratio (>15).
β’ Next step: Genetic testing (SRD5A2). Sex of rearing: often male (virilization at puberty). Testosterone therapy if needed.
Case 7
A 16-year-old boy with tall stature, small firm testes (3 mL), gynecomastia, and learning difficulties. He is otherwise healthy.
LH
25 mIU/mL (elevated)
FSH
30 mIU/mL (elevated)
Testosterone
180 ng/dL (low for age)
Estradiol
40 pg/mL (elevated)
Testicular Ultrasound
Small hyperechoic testes
Blood Pressure
125/80 mm Hg
β Model Answer:
β’ Diagnosis: Klinefelter syndrome (47,XXY).
β’ Evidence: Tall stature, small firm testes, gynecomastia, hypergonadotropic hypogonadism (elevated LH/FSH, low testosterone).
β’ Next step: Testosterone replacement therapy. Fertility: testicular sperm extraction (TESE) + ICSI. Monitor for metabolic syndrome, breast cancer risk.
Case 8
A 14-year-old girl with primary amenorrhea, short stature (142 cm), webbed neck, and low posterior hairline. She has no breast development.
FSH
85 mIU/mL (elevated)
LH
40 mIU/mL (elevated)
Estradiol
15 pg/mL (low)
Pelvic Ultrasound
Streak ovaries, small uterus
Blood Pressure
118/72 mm Hg
β Model Answer:
β’ Diagnosis: Turner syndrome (45,X).
β’ Evidence: Short stature, webbed neck, primary amenorrhea, hypergonadotropic hypogonadism (streak ovaries).
β’ Next step: GH therapy for height, estrogen replacement at age 11-12 years, then progesterone. Screen for coarctation, renal anomalies, thyroiditis, celiac.
Case 9
A 14-year-old boy with delayed puberty and anosmia.
Karyotype
46,XY
LH
0.3 mIU/mL (low)
FSH
0.5 mIU/mL (low)
Testosterone
30 ng/dL (low)
Renal Ultrasound
Renal agenesis (right kidney absent)
Blood Pressure
115/72 mm Hg
β Model Answer:
β’ Diagnosis: Kallmann syndrome (hypogonadotropic hypogonadism + anosmia).
β’ Evidence: Low LH/FSH, anosmia, absent olfactory bulbs, renal agenesis β classic X-linked KAL1 (ANOS1) or FGFR1 mutation.
β’ Next step: Genetic testing (KAL1, FGFR1). Start testosterone replacement. For fertility, GnRH pump or gonadotropins.
Case 10
A newborn with ambiguous genitalia, no palpable gonads, and salt-wasting.
AMH
Undetectable
hCG Stimulation (Testosterone)
No response (baseline 15 ng/dL, post: 18 ng/dL)
17-OHP
Normal
Serum Sodium
122 mEq/L (low)
Serum Potassium
7.2 mEq/L (elevated)
Blood Pressure
60/38 mm Hg
β Model Answer:
β’ Diagnosis: Lipoid CAH (StAR deficiency) β 46,XY DSD.
β’ Evidence: 46,XY female phenotype, no AMH (no testicular tissue), no testosterone response to hCG, severe salt-wasting (all steroids deficient).
β’ Next step: IV hydrocortisone, fludrocortisone, normal saline. Genetic testing (StAR). Raise as female, estrogen at puberty.
Case 11
A 15-year-old with primary amenorrhea, normal breast development, and a blind vaginal pouch. Testes are palpable in inguinal canals.
Testosterone
550 ng/dL (normal male range)
LH
18 mIU/mL (elevated)
FSH
10 mIU/mL (normal)
Estradiol
60 pg/mL (elevated β peripheral aromatization)
Pelvic Ultrasound
Absent uterus, inguinal testes
Androgen Receptor Gene (AR)
Mutation present
Blood Pressure
120/75 mm Hg
β Model Answer:
β’ Diagnosis: Complete androgen insensitivity syndrome (CAIS) β confirmed by AR mutation.
β’ Evidence: 46,XY female phenotype, blind vaginal pouch, inguinal testes, elevated testosterone with LH elevation (androgen resistance).
β’ Next step: Gonadectomy after puberty (to prevent malignancy), then estrogen replacement. Genetic counseling for family.
Case 12
A newborn with ambiguous genitalia, a single perineal opening, and a palpable gonad on the right side. Karyotype is 45,X/46,XY.
Karyotype
45,X/46,XY mosaic
Pelvic Ultrasound
Right testis (inguinal), left streak gonad, small uterus
AMH
Low (from testicular tissue)
Testosterone
100 ng/dL
Serum Electrolytes
Normal
Blood Pressure
72/45 mm Hg
β Model Answer:
β’ Diagnosis: Mixed gonadal dysgenesis (45,X/46,XY mosaic).
β’ Evidence: Ambiguous genitalia, unilateral testis, contralateral streak gonad, MΓΌllerian remnants (uterus).
β’ Next step: Gonadectomy of streak gonad (high risk of gonadoblastoma). Sex of rearing based on phallic development. Testosterone if male sex of rearing.
β‘ Quick FCPSβstyle MCQ
A newborn with ambiguous genitalia, elevated 17-OHP, and salt-wasting. The most likely diagnosis and treatment are: