Very brief introduction into Kallmann syndrome & CHH - a cause of delayed puberty.

 

Kallmann syndrome is a congenital hormonal condition that results in the failure to start or the failure to complete puberty. Kallmann syndrome is a form of congenital hypogonadotropic hypogonadism (CHH) that is accompanied with a lack of sense of smell (anosmia).

The condition affects both men and women but is more often diagnosed in men. The actual incidence is unknown but is thought to be in the region of 1 in 50,000. The condition is congenital and shows all forms of inheritance, over 25 separate genes have been identified in causing cases of Kallmann syndrome and CHH but still approximately 50% of cases have an unknown genetic origin. 

The underlying cause of KS / CHH is a deficiency in the production of GnRH produced by the hypothalamus gland which affects the productions of the gonadotropins from the pituitary gland. 

 

GnRH = gonadotropin releasing hormone.

This is the hormone that should be produced by the hypothalamus, located inside the brain. It is the absence of this hormone that is the root cause of KS / CHH. GnRH can be used in fertility treatments and puberty induction but is not widely available and sometimes only available to women. It can be a very effective treatment however.

GnRH levels cannot be measured directly by a blood test as it is not normally present in the general circulation.


FSH = follicle stimulating hormone

LH = leutinising hormone. 

Together these two hormones are called the gonadotropins. These are normally produced by the pituitary gland, located next to the hypothalamus in response to GnRH. In KS / CHH patients there is no GnRH so no or insufficient levels of FSH and LH are produced.

In women FSH allows the egg to mature

In women LH is responsible for the production of oestrogen and progesterone from the ovaries

In men FSH allows sperm production

In men LH is responsible for the production of testosterone from the testes.

FSH and LH can be used in both fertility treatments and pubertal induction.

 

FSH can be manufactured in pure form (eg Gonal-F) or it can be produced from female urine in the form of hMG - human menotropin (eg Menopur or Repronex)

 

LH cannot be manufactured or extracted directly. 

Instead hCG is used = human chorionic gonadotropin. hCG has the same activity as LH. 

 

hCG can be manufactured in pure form (Pregnyl or Novarel) or it can be sometimes be extracted from placental tissue. Some men with KS / CHH can take Pregnyl or Novarel on their own, just for testosterone production. In order to achieve fertility men normally (but not always) have to take FSH or hMG as well in order to achieve sperm production.

For most (but not all) KS / CHH patients the use of hormone replacement therapies; oestrogen and progesterone in women and testosterone in men will not induce fertility.


KS = Kallmann syndrome.

CHH = congenital hypogonadotropic hypogonadism. The term IHH is sometimes used instead where the “I” stands for idiopathic, meaning having an unknown cause.

Kallmann is a form of CHH which is accompanied by a lack of sense of smell. About 50% of CHH cases have no sense of smell or reduced sense of smell and can be termed Kallmann syndrome. 

The condition can be called Aureliano Maestre de San Juan syndrome in some Spanish speaking countries after the person who first discovered it.