Differentials

Premature thelarche

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Isolated, often fluctuating, unilateral or bilateral breast development.

Unaccompanied by other signs of puberty.

Growth velocity is normal and bone age is not advanced.

Presents typically between 6 months and 3 years of age in girls.

Benign and self-limiting.

INVESTIGATIONS

Clinical diagnosis.

Typically associated with only a minimal degree or no increase of follicle-stimulating hormone secretion; LH is prepubertal.

Pelvic ultrasound may demonstrate small follicular development. Single cyst can be demonstrated when breast size is fluctuating.

Premature adrenarche

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Early or exaggerated adrenarche.

Pubic hair development. No breast development and only a minimal increase in growth velocity.

Typically presents between 6 and 9 years, particularly in girls, and those in the black population.

Congenital adrenal hyperplasia and virilising adrenal tumours need to be excluded when there is rapid progression of signs and accelerated growth.

INVESTIGATIONS

Clinical diagnosis.

Mild increase in serum androgens: testosterone and dehydroepiandrostenedione sulfate.

Gonadotrophin-releasing hormone (GnRH) test is normal with prepubertal concentrations of follicle-stimulating hormone and LH.

Congenital adrenal hyperplasia (CAH)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

The classic form, 21-hydroxylase, presents as ambiguous genitalia in girls and precocious puberty in boys. In addition, the salt wasting form may present with an adrenal crisis but mainly in the newborn period.

An increased height velocity, advanced bone age, and genital maturation in the absence of testicular enlargement in boys or breast development in girls (i.e., disconsonant puberty) suggests CAH.

INVESTIGATIONS

Serum 17-hydroxyprogesterone (17-OHP) is elevated in 21-hydroxylase classic CAH.

Other adrenal hormone precursors are elevated in other forms of CAH.

A standard adrenocorticotropic hormone stimulation test is often necessary to stimulate these adrenal hormone precursors.

Adrenal tumours

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

A short history of virilisation, accelerated growth rate, and advanced bone age is present. Cushing's syndrome may be present if there is hypersecretion of cortisol.

INVESTIGATIONS

Urinary steroid profile analysis reveals an abnormal pattern of adrenal hormone secretion.

Imaging of the adrenal glands identifies the tumour.

Cushing's syndrome

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Due to adrenal disease.

Presents with virilisation, without testicular enlargement in boys or breast development in girls, in addition to typical Cushingoid features such as central obesity with thin extremities, nuchal fat pad, moon facies, purple striae, bruisability.

INVESTIGATIONS

Twenty-four-hour urinary free cortisol is elevated.

8 a.m. serum cortisol is elevated with loss of circadian rhythm.

Adrenocorticotropic hormone is undetectable.

Low and high dexamethasone suppression tests show failure of cortisol suppression.

Polycystic ovary syndrome

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Females present with obesity, hirsutism, acne, oily skin, and weight gain.

Virilisation (pubic and axillary hair) may be present without breast development.

On examination the patient is usually obese and may have acanthosis nigricans.

INVESTIGATIONS

Pelvic ultrasound may show polycystic ovaries with a peripheral pattern of follicular distribution, and variable endometrial thickness.

Serum testosterone, androstenedione, dehydroepiandrostenedione sulfate, and basal LH are elevated.

Fasting insulin is elevated, with concomitant lowering of sex hormone binding globulin, indicating insulin resistance.

Primary hypothyroidism

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Long-standing hypothyroidism can result in high thyroid-stimulating hormone (TSH) with elevated follicle-stimulating hormone (FSH), leading to isolated breast development or testicular enlargement without other secondary sexual characteristics.

There is no pubertal progression in the majority of cases; bone age is delayed and growth velocity is poor.

TSH directly activates the FSH receptor, as the two hormones have structural similarity.

INVESTIGATIONS

Low free thyroxine; elevated TSH.

Use of this content is subject to our disclaimer