Q&A: Delayed Puberty in a Young Male

Delayed puberty is defined clinically as the absence of the first signs of pubertal development beyond the normal range for the population. Most often, children simply develop later than their peers but ultimately develop normally. Sometimes, delayed puberty is caused by chronic medical problems, hormonal disorders, radiation therapy or chemotherapy, disordered eating or excessive exercise, genetic disorders, tumors, and certain infections.

In this article:
Delayed puberty
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

Delayed puberty

Generally, delayed puberty means absence of breast development by age 12 years in girls, or absence of testicular enlargement by age 14 years in boys. However, there are clear racial and ethnic variations in the timing of puberty, such as earlier onset of puberty in African American girls compared with Caucasian counterparts. These racial, social, and ethnic differences should be incorporated into decisions regarding the evaluation and therapy of pubertal disorders.

The most common cause of delayed puberty is a functional defect in production of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This may be due to physiologic individual variation, known as constitutional delay of growth and puberty, or other functional defects, such as undernutrition or chronic illness. The GnRH deficiency leads to defective secretion of gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) from the anterior pituitary, which results in inadequate steroid secretion by the gonads. Other causes of delayed puberty include a variety of hypothalamic, pituitary, and gonadal disorders.

MCQ exam: clinical scenario

A 15 year old is concerned about the size of his penis. He says his penis is too short and is teased about this at the gym. On examination he is noted to have delayed sexual development. He is also found to have a lack of normal smell. Investigations reveal a gonadotropin deficiency, although the serum luteinizing hormone and testosterone levels are normal.

The most likely diagnosis is:

a) Testicular dysgenesis
b) Kallmann's syndrome
c) Congenital adrenal hyperplasia
d) Constitutional delay
e) Craniopharyngioma

MCQ exam: answer

The correct answer is B.
Kallmann syndrome is characterized by delayed or absent puberty and an impaired sense of smell.

MCQ exam: explanation

The basic defect leading to hypogonadism in Kallmann's syndrome is an abnormality of hypothalamic GnRH secretion secondary to failure of gonadotropin-releasing hormone(GnRH)-producing neurons to migrate from the olfactory placode to the brain, and to agenesis of the olfactory bulbs. There is therefore a hypothalamic lack of the releasing hormone for gonadotrophins (GnRH).

Patients with Kallmann's syndrome usually come to medical attention because of a delayed puberty or incomplete sexual development.

Anosmia or hyposmia is present in 80% of the patients and establishes the diagnosis of the syndrome in individuals with isolated gonadotropin deficiency. Prepuberal testes, micropenis and cryptorchidism are usually seen. In women pubic and axillary hair are less reliable compared with absence of appearance of breast buds since adrenarche can occur independently of gonodarche.

Other manifestations include: skeletal abnormalities (syndactily, short fourth metacarpals, craniofacial asymmetry), mid-line defects (cleft-lip or -palate, color blindness, renal agenesis, nerve deafness), malrotation of the gut, congenital heart disease and neurologic findings (synkinesia, impaired 'smooth pursuit' eye movements and cerebellar dysfunction). X-linked disorder can be associated with X-linked ichthyosis, mental retardation, chondrodysplasia punctata, and short stature.

Hypogonadotropic hypogonadism is established in adults by the finding of normal or low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the presence of low concentrations of testosterone in males and estradiol in females.

Reference(s)
UpToDate: Approach to the patient with delayed puberty. Available online: https://www.uptodate.com/contents/approach-to-the-patient-with-delayed-puberty