Both Male and Female

Delayed Puberty

What is delayed puberty?
Timing of onset of pubertal development has a wide range in both boys and girls. In girls, puberty is considered delayed if there is no breast development by age 13 years. In boys, puberty is considered delayed if testicular enlargement has not occurred by age 14 years. In addition to the above signs, children with delayed puberty also may have short stature. Although both boys and girls may have delayed puberty, boys tend to seek evaluation more commonly than girls.

What causes delayed puberty?
In most cases, children with delayed puberty may be just “late bloomers” and this condition is referred to as “constitutional delay or growth and puberty”. Often, one of the parents and/or other family members may also give a history of delayed puberty. Other less common causes of delayed puberty are:

• Certain genetic conditions that impair either the origination of the puberty signal in the brain (see Kallmann Syndrome/congenital idiopathic hypogonadotropic hypogonadism) or genetic conditions that prevent the testes or ovary from responding to puberty signals (e.g. Klinefelter syndrome in boys; Turner syndrome in girls)
• Some medical conditions that affect other organ systems in the body may also secondarily delay pubertal development (e.g. celiac disease)

How is delayed puberty diagnosed?
• Detailed medical history including family history
• General physical exam and specific exam to assess degree of pubertal development.
• In some cases, blood tests for hormonal measurements (e.g. testosterone, estrogen, pituitary hormones etc) may be performed. In addition, bone age examination using a simple X-ray of the hand will also be performed.
• A brain MRI exam or genetic blood tests may also be performed.

How is delayed puberty treated?
If no underlying medical condition is identified, no treatment may be required and your child may start puberty on their own and will only require serial monitoring and observation. Sometimes, your doctor may recommend taking hormones to help your body start puberty. These may include estrogen pills/patches in girls or testosterone injections/gels in boys.

Additional information available here

Normosmic Idiopathic Hypogonadotropic Hypogonadism (IHH)/Kallmann Syndrome (KS)

What is IHH/KS?
IHH/KS is a rare genetic disorder that results in delay/absence of signs of puberty due to lack of the hormonal signals from the brain that are required for sexual maturation. When it is associated with absent or reduced sense of smell, the condition is referred to as Kallmann Syndrome (KS) and when the sense of smell is normal, it is referred as normosmic idiopathic hypogonadotropic hypogonadism (IHH). Although IHH/KS may affect both sexes, for reasons that are not clearly understood, males are almost 5 times more likely to be diagnosed with this condition

What are the signs and symptoms of IHH/KS?
In addition to lack of puberty, patients with IHH/KS may also have additional physical symptoms and signs such as:
• Small penis and/or undescended testes at birth
• facial defects such as cleft lip and/ or palate
• renal agenesis (one kidney does not develop)
• short fingers, especially the 4th finger
• Deafness
• Eye movement abnormalities
• Bent spine
Typically, patient with IHH/KS are also infertile and require additional treatment for attaining fertility.

What causes IHH/KS?
HH/KS is caused by a variety of genetic defects that result in failure of secretion or action of a master reproductive hormone called gonadotropin-releasing hormone (GnRH). In many cases, this condition is familial and other family members may also be affected with IHH/KS or with just delayed puberty or inability to smell.

How is IHH/KS diagnosed?
• Detailed medical history including family history.
• The doctor will also assess for any nutritional problems, stress and also check for use of medications since these conditions can also result in delayed puberty and mimic IHH/KS. In such cases, treatment of the underlying problem or withdrawal of offending medications may often suffice for initiating puberty.
• General physical exam and specific exam to assess degree of pubertal development.
• Blood tests to check for hormonal levels (e.g. testosterone, estrogen, pituitary hormones, prolactin, thyroid hormones etc)
• A scratch and sniff smell test to ascertain sense of smell
• A brain MRI exam to exclude any pituitary/brain disorders that may mimic IHH/KS
• Bone density exam to look for evidence of sex hormone deficiency related decrease in bone density
• Genetic blood tests looking for specific genetic mutations may also be performed to confirm the diagnosis.

How is IHH/KS treated?
Your doctor will typically recommend treatment to improve the symptoms of IHH/KS. These may include:
• Hormone replacement therapy to induce puberty: Hormone replacement therapy may be prescribed in the form of estrogen /progesterone pills (in women) or testosterone injections/gels (in men)
• Since patients with IHH/KS may be at risk for bone loss, vitamin D and calcium supplements may also be prescribed.

Can patients with IHH/KS have successful fertility?

Both males and females with KS/IHH can receive treatment for fertility induction
For males, your doctor will prescribe hormonal therapy in the form of two gonadotropin injections to stimulate testicular growth and maturation. One of the two gonadotropin hormones used is called hCG (human chorionic gonadotropin) and is the mainstay for fertility induction; it can be used either alone or in combination with a second hormone called FSH (follicle stimulating hormone]. Some patients may require FSH therapy prior to hCG while others may require it later on; your doctor will explain to you which sequential therapy is most appropriate for your condition. You will require frequent clinic visits to monitor testicular growth as well as serial blood tests and seminal fluid analyses. Typically, sperm tend not to be seen in the ejaculate until testicular volume reaches at least 8 mL and this may take several months to achieve. In most IHH/KS individuals sperm function is expected to be normal and conception may occur even with relatively low sperm counts.

What additional information is available for IHH/KS patients?
The MGH Reproductive Endocrine Unit houses the Harvard Reproductive Endocrine Sciences Center which runs a world renowned research program involving patients with IHH/KS. Please ask your doctor if you may be eligible to participate in this research program. Additional information on this research program is available here