Q11. What is the link between anosmia and failed puberty ?

At first glance there would appear to be no obvious link between a lack of sense of smell and puberty.  However in Kallmann syndrome they have a unique relationship due primarily to how the brain develops in the foetus in the first 15 weeks of development. 


A normal sense of smell and GnRH-secreting cells:


The hypothalamus normally contains a number of specialised nerve cells called GnRH releasing neurones. These cells act on impulses from other areas of the brain and release GnRH in a specific manner in order to stimulate the pituitary to release LH and FSH, which in turn allows puberty to occur and allow normal sexual function as an adult.

These GnRH releasing cells do not originate in the hypothalamus however. During the development of the foetal brain they are located in the area of the brain known as the olfactory placode. During early development, around 6 to 8 weeks old, they migrate into their final position linking into the the hypothalamus. The GnRH cells migrate through an area of the brain which will eventually become the olfactory bulbs and tract, an essential part of the olfactory system. The movement of the GnRH releasing cells is dependant on the olfactory tract being present to allow passage through to the hypothalamus.

Migration of GnRH producing cells.

Migration of GnRH producing cells.

In other words, GnRH-secreting cells (GnRH being the vital ingredient for normal puberty) can only migrate to the hypothalamus if the olfactory bulbs and tracts develop normally during the embryonic phase of development.


Anosmia and the failed migration of GnRH-secreting cells:

In Kallmann syndrome, the olfactory system does not develop normally during the first few weeks of an embryo's life and the GnRH-secreting cells have no means of migrating from the nose to the hypothalamus. Without olfactory bulbs and tracts, there is no sense of smell and with no GnRH-secreting cells in the hypothalamus, normal development during puberty is not possible.

One of the tests performed in diagnosing Kallmann syndrome is an MRI of the head. This is done to check the structure and location of the hypothalamus and pituitary glands to check there is no physical reason for the failure of the pituitary to function correctly, such as a tumour or empty sella syndrome. The second reason is to check for the presence of the the olfactory bulbs.

The absence of the olfactory bulbs on a MRI scan will not positively diagnose Kallmann syndrome, due to the nature of the scan sometimes the structures are difficult to see, but it is another clue that will lead an endocrinologist to reach the diagnosis of Kallmann syndrome.

Research has shown that GnRH releasing cells do have the potential of migrating during adult life and it is theorised that if migration can occur later and the cells reach the hypothalamus then the normal function of the reproductive system can start. There have been reported cases where Kallmann syndrome has "reversed" and normal function (apart from the sense of smell) has begun with normal sex hormone production and fertility in both men and women. The exact mechanism for this reversal is still unknown but is an area of current research.