Endocrine and Reproductive Disorders

A 3-year-old has tall stature (well above the 97th percentile), macrocephaly, and a broad forehead with hypertelorism, large ears, and a small chin. The fingers stay flexed at rest (camptodactyly). Bone age is advanced by several years. Development is mildly delayed.

A 6-year-old girl has precocious puberty with breast development and vaginal bleeding. She has large café-au-lait macules with irregular "coast of Maine" borders and fibrous dysplasia of the femur.

A child has asymmetric overgrowth affecting one leg with vascular malformations and epidermal nevi. Tissue biopsy reveals a somatic *PIK3CA* variant.

A macrosomic male newborn has coarse facial features, a large tongue, and supernumerary nipples. He has developmental delay and renal anomalies.

A 16-year-old with female external genitalia and primary amenorrhea is found to have a blind-ending vagina and absent uterus. Karyotype is 46,XY. Testes are identified in the inguinal canal.

A 46,XX newborn presents with ambiguous genitalia (virilized female). The mother experienced progressive virilization during pregnancy (deepening voice, acne, hirsutism). At puberty, the patient fails to develop breasts and has primary amenorrhea with hypergonadotropic hypogonadism and tall stature.

A newborn female has ambiguous genitalia with clitoromegaly and labial fusion. She develops a salt-wasting crisis at 2 weeks of age with hyponatremia and hyperkalemia.

A phenotypically male adult presents with infertility and small testes. Karyotype reveals 46,XX. FISH shows the _SRY_ gene translocated to one X chromosome. The patient has male external genitalia, no uterus, and azoospermia.

A male infant presents in the first weeks of life with vomiting, hyponatremia, hyperkalemia, and shock. Cortisol and aldosterone are low. ACTH is markedly elevated. Years later, he fails to enter puberty: gonadotropins are inappropriately low. A maternal uncle died of "adrenal crisis" in infancy.

A thin 18-year-old is diagnosed with diabetes without ketosis. He has negative islet autoantibodies. His mother and grandfather both developed diabetes before age 25.

A newborn with severe IUGR develops hyperglycemia in the first week of life requiring insulin. Diabetes resolves by 12 weeks but recurs in adolescence.

A teenager with type 1 diabetes is found to have progressive vision loss (optic atrophy). Audiometry reveals sensorineural hearing loss. Urological workup shows diabetes insipidus.

A 17-year-old male has not entered puberty. He has anosmia (cannot smell). MRI shows hypoplastic olfactory bulbs.

A 32-year-old man with primary infertility for 2 years has azoospermia on two semen analyses, normal LH/FSH/testosterone, and normal testicular volume. Karyotype is 46,XY. Y chromosome microdeletion testing reveals an AZFc deletion. Counseling covers the option of testicular sperm extraction with ICSI and the certainty that any resulting sons will inherit the same AZFc deletion and infertility.

A 5-year-old has severe growth failure, alopecia, and aged appearance with thin skin and prominent veins. Cardiac workup reveals severe atherosclerosis.

A child with severe proportionate short stature has a "bird-like" face with a prominent beaked nose and receding forehead. Microcephaly is severe with intellectual disability.

A patient at 10 weeks gestation has vaginal bleeding, a uterus larger than expected for dates, severe hyperemesis, and a markedly elevated β-hCG (>100,000 mIU/mL). Ultrasound shows a "snowstorm" intrauterine pattern with no embryo and bilateral theca lutein cysts. Suction D&C cytogenetics shows **46,XX of paternal-only origin**: a complete hydatidiform mole.