Differentials
Premature ovarian failure
SIGNS / SYMPTOMS
Females may have had normal pubertal development or pubertal arrest.
Present with primary or secondary amenorrhea.
INVESTIGATIONS
High serum follicle-stimulating hormone with low estradiol, inhibin B, and anti-Mullerian hormone.
Karyotype is indicated, microarray and genetic sequencing may be indicated (requires discussion with clinical genetics).
Ovarian antibodies may be positive.
Premature testicular failure
SIGNS / SYMPTOMS
Males may have had normal pubertal development or present with pubertal arrest.
Present with decreased libido, features of testosterone deficiency, and/or infertility.
INVESTIGATIONS
High serum follicle-stimulating hormone with low testosterone, inhibin B, and anti-Mullerian hormone.
Karyotype is indicated, microarray and genetic sequencing may be indicated (requires discussion with clinical genetics).
Hypogonadotropic Hypogonadism
SIGNS / SYMPTOMS
May present with features of androgen deficiency and a lack, delay or stop of pubertal sexual maturation.
INVESTIGATIONS
Blood testosterone and pituitary hormone levels are low.
Hypothyroidism
SIGNS / SYMPTOMS
Pathophysiology of delayed puberty not known.
Up to half of patients have no or nonspecific symptoms.
Common symptoms include weakness, lethargy, slow speech, cold sensation, forgetfulness, constipation, and weight gain.
On exam, patients have coarse, dry skin and bradycardia.
Unless symptoms are long-standing, patients generally have some pubertal development; females report menstrual irregularities.
INVESTIGATIONS
Thyroid-stimulating hormone levels are elevated in primary hypothyroidism; free thyroxine levels are decreased.
Polycystic ovary syndrome
SIGNS / SYMPTOMS
Females may present with obesity, hirsutism, primary amenorrhea, or oligomenorrhea.
May have normal pubertal development but anovulatory cycles may lead to primary amenorrhea.
On exam, there may be acanthosis nigricans, hirsutism, and obesity.
INVESTIGATIONS
Pelvic ultrasound may reveal polycystic ovaries with variable endometrial thickness (however, the presence of polycystic ovaries are not essential for the diagnosis of polycystic ovary syndrome).
Measurement of serum androgens reveals elevated dehydroepiandrosterone sulfate (DHEAS) and testosterone.
Fasting glucose and insulin are elevated due to insulin resistance.
Outflow tract obstruction, including imperforate hymen or transverse vaginal septum
SIGNS / SYMPTOMS
Normal pubertal development but cyclic pelvic pain and lack of menarche.
On exam, girls have either a perirectal mass or a bulging hymen with hematocolpos.
INVESTIGATIONS
Pelvic ultrasound reveals variable abnormalities such as imperforate hymen, blood within the vagina, or thickened tissue within the vagina. The uterus and ovaries are normal.
MRI pelvis may be required.
Mayer-Rokitansky-Kuster-Hauser syndrome
SIGNS / SYMPTOMS
Mullerian agenesis syndrome.
Normal-onset pubertal development except menarche.
Phenotypically female external genitalia with blind vaginal pouch.
INVESTIGATIONS
Pelvic ultrasound reveals variable absence of Mullerian structures.
MRI pelvis may be required.
Complete androgen insensitivity
SIGNS / SYMPTOMS
Phenotypically female with normal timing of breast development, minimal to no pubic hair growth, and no menarche.
On exam, females have an absent or blind vaginal pouch and a palpable inguinal mass (testes).
INVESTIGATIONS
Chromosomal analysis reveals a 46XY male in a phenotypic female.
Pelvic ultrasound reveals the presence of testes with no ovaries or uterus.
5-Alpha-reductase deficiency
SIGNS / SYMPTOMS
Boys present with poor virilization at puberty, although vast majority have genital ambiguity on exam.
INVESTIGATIONS
Testosterone: dihydrotestosterone ratio is markedly elevated.
Cushing syndrome
SIGNS / SYMPTOMS
May present with oligomenorrhea in females; pubertal development is normal.
Additionally, patients have central obesity with thin extremities, nuchal fat pad, moon facies, purple striae, bruisability, and hirsutism in females.
INVESTIGATIONS
24-hour urinary free cortisol and morning (0800 hours) serum cortisol are elevated on dexamethasone suppression test.
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