A boy with tall stature and delayed puberty Professor of Pediatric Endocrinology Isfahan University Of Medical Sciences M. Hashemipour

Case: An 18 year old boy was referred because of delayed puberty . Reduced facial and body hair .

What do you ask him?

Social and family history Student Non-smoker His older brother had spontaneous puberty at the age of 13 years His mother’s menarche occurred at the age of 15 years He was born after an uncomplicated delivery He has always been healthy At present , he is in his last year of high school

Sense of smell Unremarkable past medical history

What's important in Physical examination?

. His target height (TH) is 178cm He has not experienced a pubertal growth spurt His height velocity has continued in a prepubertal pattern

Arm span - Height =7cm

Physical examination physical examination reveals No pubertal genital development Testicular volume is 2ml on each side Moderately pubichair &axillary hair

Physical Examination What physical features suggest a pubertal disorder ?

Eunuchoid Long legs Lack of pubertal development Gynecomastia

Investigations What additional growth related information would you need before making a diagnosis?

Bone age Serum testosterone level Upper to lower segment

Upper to lower segment =0.8 BA=15 Y Tes= 0.6ng/ml Upper to lower segment =0.8

Problem Definition How would you diagnose his pubertal complaint?

He is normal and will develop normally He has constitutional delay of growth and puberty He has delayed puberty He has hypogonadotropin hypogonatism

Pituitary failure

Medical history What further information from his medical history would be relevant in dealing with his complaint?

surgery or medical treatment for undescended testes Member of his family has experienced fertility problems Normal sense of smell Headaches visual disturbances psychosocial situation

His mother recalls that at birth His testes were undescended Medical history His mother recalls that at birth His testes were undescended . After 2years, his testes had not descended spontaneously, and needed orchiopexy

bear child Investigation His family history revealed that one of his maternal aunts was not able to bear child

What's your plan?

cdpuberty kallman kallmann Pituitary failure

Measure Gonadotropin

Investigation To exclude : Hypergonadotropic hypogonadism Why would you collect basal levels of LH and FSH? To exclude : Hypergonadotropic hypogonadism Hypogonadotropic hypogonadism To make a distinction between HH & CDGP

levels of LH and FSH are low

Advanced Investigations It is sometimes difficult to make a distinction between delayed puberty and hypogonadotropic hypogonadism. GnRH test may be helpful

Investigation GnRH tests are performed: 60min 30min 0min 0.1 Testosterone (nmol.L) 1.6 1.8 <1 LH(U/L 1.2 1.9 1 FSH(U/L) How would you interpret these results?

The rise in Gonadotropin in response to GnRH is minimal Investigation In hypothalamic dysfunction The rise in Gonadotropin in response to GnRH is minimal

Differential Diagnoses He likely has HH BA=14.5 years: indicates that he has a pubertal disorder.

What differential diagnoses would you make ?

Impaired GnRH secretion (kallmann syndrome ) Constitutional delay of G&P Isolated gonadotropin deficiency Chronic disease

Investigations What additional test would be useful in making a diagnosis?

An olfactometric (smell) test An MRI or CT of hypothalamic/ pituitary region family history

What is your opinion about induction of his puberty?

For psychosocial reasons , induction of puberty is indicated Further delay of pubertal development would compromise normal development of bone mass.

Therapy He asks you what his options are with respect to pubertal induction and fertility

Therapy Long –term treatment for fertility If he has intact LH&FSH producing pituitary cells Long –term treatment for fertility HCG and HMG Biosynthetic LH /FSH preparation pulsatile GnRH Could be used to induce gonadal development and spermatogenesis .

Therapy He was treated with testosterone He was pleased with his pubertal development. He reached a final height of 199 cm at the age of 21 years