New website

A clinical research team at CHUV, Switzerland is leading European wide consortium that aims to bring together all the research on Kallmann syndrome / CHH into one place. Part of the project is to host a website for clinicians, researchers and patients to use to obtain the latest information on the genetics, diagnosis & treatment of Kallmann syndrome and other GnRH deficient conditions that cause a disruption of puberty.

The website is live now with the start up information. Patient orientated information will be added in the next couple of months followed in time with clinical guidelines for the diagnosis & treatment of Kallmann syndrome.

http://www.gnrhnetwork.eu/

USA Patient Meeting - 26th October 2013

There will be a patient meeting for patients with Kallmann Syndrome or CHH in America on 26th October 2013.

It will be held at Saddleback Memorial Hospital, Laguna Hills, Orange County, California.

The meeting will be for patients and families of patients. The meeting will be a mixture of presentations by experts in KS / CHH, a chance to ask the experts questions and more importantly the chance to meet with fellow patients in a relaxed atmosphere.

It will be a relaxed, informal meeting with plenty of time to socialise & talk with other patients.

More details will be provided soon, or please contact:


kschh2013@hotmail.com

or

neilsmith38@hotmail.com

Programme on CBC in America on Kallmann Syndrome.

Hopefully attached are links to three videos on AOL from an episode of "Doctors" on CBC in America where a 27 year old gets his first diagnosis of Kallmann syndrome.

They explain the basics on Kallmann syndrome very well and Brandon does an excellent job of explaining his condition.


http://www.aol.com/video/brandons-delayed-puberty/517683899/?icid=maing-grid7%7Cmaing6%7Cdl4%7Csec3_lnk1%26pLid%3D275735

http://www.aol.com/video/mri-to-examine-pituitary-gland/517683902/

http://www.aol.com/video/delayed-puberty-explained/517683901/

Nebido Injection

Nebido is a long lasting testosterone injection that is effective for treating patients with Kallmann syndrome and CHH.

It was first developed and produced by the Bayer health group and is licenced and distributed under the trade name Reandron 1000 in Australia, Reandron in Spain and Nebid in Italy.

It is a 4ml injection of testosterone undecanoate that is given as a deep muscular injection.

Two loading injections are first taken 6 weeks apart then injections are normally given at 10 to 13 week intervals depending on the response. Some patients enjoy the convenience of only having to have an injection every 3 months; it is not unknown for some patients to go 6 months in-between injections and still achieve normal testosterone levels.

Most patients achieve steady normal physiological levels of testosterone while using Nebido, without the peaks and troughs seen with shorter lasting injections.

It is a large volume to inject and sometimes there can be some short lasting localised pain at the injection site but this can be avoided by warming the vial in hot water for 5 minutes before injecting to allow the solution to become more viscous.

The injection is widely available throughout the world apart from the USA where under the trade name Aveed but it has yet to be licenced.

http://www.nebido.com

British Medical Journal article. Patient Journey - Kallmann syndrome._


The British Medical Journal todays posted an article, wrtitten by me about my story of having Kallmann syndrome.

I was diagnosed with Kallmann syndrome at the age of 22 after spending my teenage years and early adulthood being labelled as a “late developer” or “late bloomer”.

Kallmann syndrome is a form of hypogonadotrophic hypogonadism with the associated symptom of anosmia. It affects both men and women but is at least five times more common in men. It is a congenital condition with currently nine known gene defects linked to its cause which combined still only account for less than 40% of cases. Patients are left with poorly developed or no secondary sexual characteristics, are infertile and at increased risk of osteoporosis.

 Childhood years:

My early childhood was fairly uneventful medically apart from 70% hearing loss in one ear and no sense of smell. I reached the normal pre-puberty Tanner stages and up to the age of twelve nothing seemed to be amiss. Going through the early teenage years it was a case of waking up each day and hoping something was going to start to develop. I knew I was getting late to start puberty but I assumed it would all start soon enough. Eventually I was the only one in my year group not to show any development and was certainly noticed by the rest of the year group.

A routine health inspection by the school nurse as part of the health screen for the permit to work on a newspaper delivery round led to a referring to a GP at the age of 15. At that stage the GP said I was just late starting and I should wait and see and was sent on my way.

Teenage years:

Up to the age of 14 I was a normal enough school boy I think, I was in the Scouts and was involved in my local cricket club. I gradually got left out of social events as I lacked the confidence to go and had no sexual drive at all. I knew the basics from a purely physical point of view but had no libido or interest in any sort of teenage activities. I made up excuses not to go to social events and eventually I stopped being invited.

By the age of 17 it was clear nothing was starting so I was referred to a general medical consultant and then an urologist at Derifford hospital in Plymouth. I was put on low dose Sustanon monthly but with no follow up assessment, it was just assumed it would all start naturally.

By the time I went to University it was obvious something was wrong but I did not have the drive to do anything about it. I even stopped taking the Sustanon for a time at University as it seemed to having no effect on me at all. Looking back now there were opportunities for me at University but without the drive and the knowledge of the condition I did not have the interest or confidence to notice them, let alone follow up on them.

Diagnosis:

The first time I actually saw an endocrinologist was when I started my first job as a Biomedical Scientist at the Royal Free Hospital in North London. I had studied endocrinology and haematology as part of my biomedical science degree and had a bit of an understanding on how puberty was supposed to work. When I started work at the Royal Free I was determined to talk to and endocrinologist even though my GP still had not referred me. Under my own volition I contacted Dr Richard Quinton, at the time a specialist registrar in endocrinology under Prof. Pierre-Marc Bouloux. One of the first questions he asked was “did I have a sense of smell”. It was the first time any doctor had asked me that question.

From there the correct diagnosis came soon after and I was put on a suitable dose of testosterone, first in the form of Testogel and then later Nebido. The delay from the age of 16 to 22 meant I went six years with a very low testosterone level with the subsequent delay in secondary sexual development and bone strength.

Blood tests then confirmed the low levels of FSH and LH which, combined with the anosmia confirmed the diagnosis. A subsequent MRI showed the absence of the olfactory bulbs. A DEXA scan showed osteopenia and I was prescribed Fosamax at the time, which has now been replaced with high dose Vitamin D therapy. At the time of diagnosis I probably looked 10 years younger than I was and never shaved.

Delay of Diagnosis.

On a physical level the late diagnosis has left me with osteopenia which is still present but at least not deteriorating. The lack of gonadotrophins and hence androgens in my teenage years also resulted in a delay in the development of secondary sexual characteristics. The lack of testicular development will always be present in Kallmann syndrome but the lack of penile growth will always leave the question of what would have happened if testosterone treatment had been started earlier and at the correct dose.

It is on the psychological level that the late diagnosis has the biggest impact in my view. Judging by my own experiences and those of fellow patients I meet and talk to now this is an area which is very frequently overlooked.

With puberty and adolescence being so closely linked if a patient does not enter puberty at almost the same stage as his peer group he risks being left behind socially and emotionally as well as physically. I feel that this emotional development of social interaction is difficult to catch up on and is often a result of feeling socially isolated when puberty fails to start.

In my experience with fellow patients it is those who are diagnosed early and treated early who cope with the condition better. For a lot of people I talk to the very fact they can put a name to the condition and realise that they are not the only person in the world not going through puberty is a big step in being able to cope with the condition.

Treatments available:

Referral to a reproductive endocrinologist allows for the possibility for fertility treatments. Even though there is a reported good success rate with gonadotrophin therapy for both men and women with KS there is not universal availability of treatments across the country probably due to the high cost FSH treatments.

I feel there is a good argument for FSH treatment to be available to younger men with KS even if fertility is not the ultimate goal. The testicular development achieved while on FSH can help with self confidence and emotional development.

Pregnyl / hCG can be used in isolation just for testosterone production and is useful indicator for the effectiveness of FSH treatment.

The type of hormonal replacement therapy used is also important for both men and women. The Nebido injection for men may be more suitable than the Sustanon injection due its length of action, while for some the gel, capsules or deep muscular implants may be more beneficial.

The most important treatment is possibly the diagnosis itself. Being labelled as a “late starter” or “late bloomer” when in your early twenties can be very self destructive. The ability to put a label on the condition and the knowledge that it is a recognised condition is the first step in coming to terms with a condition that is difficult to describe to others. The use of patient support groups on Yahoo and Facebook also play a big part in people being able to talk about the condition but this can only be achieved once they have got the correct diagnosis.

What are hormones?

In a general sense hormones are the body’s messenger service. There are over 40 known hormones that act within the body. They are each released by a specific endocrine gland (such as the pituitary gland, adrenal glands, pancreas or testes / ovaries) in response to a specific stimulus, possibly another hormone. A hormone is released to generate a specific result. In normal circumstances the hormonal system works on a negative feedback mechanism.

A stimulus causes the endocrine gland to release a hormone -> The hormone causes the stimulus to be stopped or reduced -> The endocrine gland stops producing the hormone

The classic example is the role of insulin in the role of maintaining the blood sugar levels. Insulin is only released in response to an increase in sugar levels, as soon as blood sugar levels falls; the production of insulin is stopped. The breakdown in this regulation causes the most common hormonal diseases – diabetes mellitus.

In normal puberty the pathway is:

Hypothalamus gland produces GnRH (gonadotrophin releasing hormone)

Which causes the

Pituitary gland to produce LH & FSH (luteinsing hormone / follicle stimulating hormone)

Which cause the

Testes to produce testosterone & sperm

Or

Ovaries to produce progesterone and oestrogen & allow ovulation to occur

The sex hormones also have other effects around the body, not just linked to puberty and fertility.

In KS or HH either the pituitary gland does not receive the GnRH, or it is unable to respond to the GnRH. Without the first signal the pituitary will not produce its hormones (LH and FSH) that in turn will prevent the testes or ovaries producing their own hormones at the required time to cause puberty. For some people with KS / HH there is no physical problem with the testes or ovaries, they just have not had correct signal from the pituitary gland in order to function correctly.

The treatments people get with KS / HH will be replacing one of the hormones missing in the chain. Normally this is either testosterone or oestrogen / progesterone. However it is also possible to be given FSH / LH or GnRH in certain circumstances, especially if fertility is desired.

Can a person with KS or HH become fertile?

Yes, possibly, but only with specialist treatment and if other circumstances are favourable. There have been many cases of people with KS / HH having children, sometimes through a form of IVF or other assisted fertilisation programmes. As with any type of fertility treatment there are many other factors to consider and it can take many months of treatment and there is no guarantee as with any form of fertility treatment. It has been noted that fertility can be achieved with Kallmann’s women more quickly than with other patients.

Is there any effect on expected lifespan?

There is no reliable evidence that KS or HH has any effect on the life span on an individual. It is worth point bearing in mind though that there are some rare symptoms that can occur with KS and HH that may have an effect on life span. These other symptoms may be connected to KS or HH or may have arisen regardless.

Are there any risks if KS or HH is left untreated?

Yes there can be. The major problem with a person with untreated KS or HH is the increased risk of osteoporosis or ‘brittle bone disease’. The greatly reduced levels of sex hormones seen with KS and HH have a detrimental effect on the strength of the bones. This can be easily treated with the appropriate drugs that will reduce the risk of osteoporosis to that seen in the rest of the population. It is advised that a person with KS or HH should have a bone scan (DEXA) at least every 5 years to assess their bone age and to assess the risk of osteoporosis. There is increasing evidence that Vitamin D levels play a vital role general health, not just bone strength. It is not unknown for people with KS / HH to have their Vitamin D levels monitored and prescribed tablets if the level is too low.

A patient’s perspective:

 “Long term psychological effects of delayed diagnosis of Hypogonadotrophic Hypogonadism in patients with delayed puberty”.

"Puberty is considered to be clinically delayed if sexual maturation has not become apparent by the age of 14 years in boys or age 13 years in girls."

"Using these criteria, approximately 2.5% of healthy adolescents will be identified as having pubertal delay"

Delayed Puberty. Rosen, DS, Foster C. Pediatrics in Review 2001;22;309

While the majority of these individuals will go on to experience normal puberty, albeit a couple of years later than their peer group; there is a perhaps a need to evaluate all patients who appear to be delayed to eliminate other causes for their pubertal failure.

One possible cause of a delay or absence of puberty is Kallmann syndrome (KS) and other forms of hypogonadotrophic hypogonadism (HH). Most cases are not detected as adolescents, even if they display the anosmia seen in KS. Both KS and HH show variable physical symptoms even within family members, which in addition to the absence of a clear cut genetic test make diagnosis of KS and HH problematic at times.

Combined KS and HH have a probable incidence of approximately 1 in 4,000 males and 1 in 25,000 females. Without treatment patients will remain infertile with no or poorly defined secondary sexual characteristics and be at increased risk of developing osteoporosis.

From a patient’s point of view I feel there is a need to ensure that any adolescent with pubertal delay should be referred on for an endocrinology review. The benefits of early diagnosis and treatment of KS / HH both on a physical level and on a psychological level cannot be overestimated. An early endocrine review will be able separate a case of normal constitutional delay of puberty from a case which will require extra investigation.

From my own personal experience and from conversations with others in patient support groups the label of “late bloomer” or “late developer” can lead onto deeper psychological issues later in life as patients get left behind both physically and emotionally from their own peer group.

The social isolation some patients feel can be avoided by early diagnosis and treatment. It is clear from conversations within our support groups the earlier a diagnosis is made and the correct treatment started the more beneficial it is to the patient in later life. The ability to put a name to the condition would at least allow the patient to know there is a reason for the absence of puberty and they are not alone with the condition.

Neil Smith.

neilsmith38@hotmail.com
www.kallmanns.org

A meeting for patients with Kallmann syndrome or HH is planned for

Saturday 12th November at the the Royal Free Hospital in London.

Guest speakers will be Prof. Pierre Bouloux from London and Prof. Nelly Pitteloud from Switzerland.

It will be a fairly informal meeting with a few medical presentations, question & answer sessions and plenty of time to talk to fellow patients.

More details to follow, but to register your interest please e-mail:

neilsmith38@hotmail.com

Being able to talk to other people with Kallmann syndrome and hypogonadotrophic hypogonadism makes a lot of difference to how a person copes with having the condition.

Since the condition is so rare and it involves an area which is difficult to talk about people with KS can feel very isolated and feel like they are the only person with the condition.

The ability to contact, talk to and meet other people with the condition is almost always a very worthwhile exercise.

There are 2 groups on Facebook where you can contact other people.

One is called "Kallmann's syndromers". It is an open group where you can post comments and ask questions. There is also a chat option to talk to other members. Other people on your Facebook profile will see you are a member of this group.

http://www.facebook.com/#!/groups/114162694465

If you wish to remain totally anonymous there is an also a private, "secret" KS group on Facebook which is only visible to members and people can post and chat in the knowledge that only people in the group can see the posts in the groups. Nobody on your profile will see that you are a member of the group. You can gain entry to the group by asking one of the current members to let you in, or send me an e-mail.

There is also a contact group on Yahoo containing some members very knowledgeable on KS.

http://health.groups.yahoo.com/group/kallmanns-syndrome

I am always happy to hear from new people and will try to pass on contact details if other people want to get in touch.

neilsmith38@hotmail.com

Kallmann syndrome and other forms of hypogonadotrophic hypogonadism are rare conditions. It is some times very difficult to find primary physicians or GP's who have even heard of the condition.

Sometimes even when we are treated by consultants in hospitals we might be the only patient with KS or HH that they are seeing at that time.

It is sometimes difficult to find reliable information on the condition. Partly this is due to the fact that there is so much still to learn about the genetic causes of KS / HH. However there is information to be gained on the current diagnosis and treatments available for KS / HH.

One area is the number of different forms of testosterone treatments available now. A lot of people I speak to seem to be unaware of the different forms of treatments that are available. Some will work better than others and will suit different people.

There are a number of good websites about where you get information and some forum groups where you can talk to other people with Kallmann syndrome. I have left some links to some below. A lot of people with KS or HH find it very helpful to be able to talk to fellow patients. The majority of people with the condition will have never met anybody else with the condition and there can be a big advantage in meeting with and talking to other people who have gone through similar situations and know how you feel.

I talk to a lot of people with Kallmann syndrome through MSN messenger or Facebook and am always happy to talk to new people or try to introduce them to other people they may wish to talk to.

My e-mail address: neilsmith38@hotmail.com

e-medicine web page on Kallmann syndrome:

http://emedicine.medscape.com/article/122824-overview

Kallmanns.org web page:

http://www.kallmanns.org

Facebook group on Kallmann syndrome:

http://www.facebook.com/topic.php?topic=22250&post=361565&uid=77192005117#!/group.php?gid=77192005117

Yahoo Forum group on Kallmann syndrome:

http://health.groups.yahoo.com/group/kallmanns-syndrome

A review article on Kallmann syndrome.

This may be only of interest to those people with KS or HH but this article from Clinical Endocrinology 2010; 72(6) gives a very good overview of the diagnosis & treatment of the condition.

It is authored by Prof. Pierre Bouloux at the Royal Free hospital in London, who is my specialist and one of the first doctors to diagnose me when I worked there back in the 1990's.

By the time I left university I still was not diagnosed correctly, still labelled a "late developer" which at 21 seemed more than a bit annoying. It was only by chance that my first job after university was in the blood transfusion lab at the Royal Free Hospital in London. Prof. Bouloux and his senior registrar at the time, Dr Richard Quinton (now consultant in Newcastle) were both working at the Royal Free and specialised in treating people with KS / HH.

The fact I managed to start work at the very hospital that contained the two specialists who could diagnose me correctly was certainly a strange coincidence. The first question Dr Quinton asked me was "can I smell ". Such a simple question at the time, but none of my previous specialists or GP's had ever asked it before.

It was the first time a name was put to the condition, and a couple of months later I met somebody else with the condition for the very first time. It is difficult to put into words to people who don't have the condition the sense of relief knowing that it is a recoginsed condition, it has a name you can put to it and there are other people out there with the same condition.

The following quote was posted as a Facebook status by a colleague of mine with type I diabetes:-

“Dear diabetes, since entering my life in a rather forcible manner fifteen years ago, you have since been a most unwelcome guest who out stayed their welcome the minute they arrive. Now kindly do the decent thing and fuck off out of my life. I don't want to be defined by you anymore.”

This quote struck a chord with me. I don’t have diabetes, I have another endocrine condition called Kallmann syndrome. The above quote could quite as easily be attributed to Kallmann syndrome as it can diabetes type I.

Kallmann syndrome is a rare hormonal condition in which the major symptom is the failure for the patient to enter puberty or to fully complete puberty. Untreated patients would have very poorly developed secondary sexual characteristics and will almost invariably be infertile. It is also associated with a lack of sense of smell. The root cause is the failure of the release of the gonadotrophin hormones (LH and FSH) by the pituitary gland.

======================================================
Diabetes is fairly straightforward to diagnose, even if doctors sometimes get Type I and Type II mixed up.

KS is harder to diagnose as it is normally a case of eliminating all other possibilities first. The biggest hurdle is getting a diagnosis when as a teenager you are constantly being dismissed as a “late developer”. There is no simple blood test for KS. It is not a widely known condition and diagnosis is often delayed well into late teens & early 20’s by which time the benefits of early treatment and diagnosis are lost.

Diabetes is far more intensive to treat, can be a major struggle getting blood sugar levels correct and can have serious complications, both short term and long term if you do not get the treatment right.

KS is fairly straightforward to treat in comparison; a lot of people with KS get a testosterone injection every three months and this is all they need. It gets a little more complicated if fertility is required, but compared to diabetes the treatment of KS is very simple. Testosterone, while an important hormone to have is not in the same league as insulin when it comes to its importance for day to day life.

========================================================
In both conditions you are treating the symptoms rather than the root cause. You never cure either condition; you can only hope to control its effects.

In both conditions you are often left feeling tired & lethargic, either due to fluctuating blood sugar levels or very low testosterone levels.

In both conditions you sometimes have to deal with some medical professionals who have little idea or understanding of the condition. Knowing that Type I diabetics are not the same as Type II’s and have different needs & requirements would be a good start. It is the same for people with KS as most of us are seen by doctors who have not even heard of the condition and don’t know the full range of available treatments that are available.

In both conditions you are stuck with a condition you have little control over. You can’t really escape either condition and it is only really a fellow patient who can totally understand the problems you go through.

=========================================================

Just how much each condition defines our life is a debatable point; I think it varies from person to person. I think it is impossible to live with a condition such as KS or diabetes type I and not let it affect your life. However by talking to patients with other endocrine conditions sometimes you can get a better perspective on your own condition.

In my conversations with my colleague I think we can both safely say neither of us would want to swap conditions.

The genetics of Kallmann syndrome and other forms of HH is a long way from being fully understood.

In a paper published in by the Proceedings of the National Academy of Sciences of the United States of America (PNAS) in 2010 a review listed 12 different genes that have been known, either in isolation or together that have been implicated in causing cases of KS or HH. Even with this number of genes involved over 60% of cases of KS and HH have an unknown genetic cause.

This means that there is no clear genetic test for KS or HH. Even if the you test for the two or three most common gene defects a negative result would not rule out a possible case of KS or HH.

PNAS 2010 Aug 107(34) 15140-4, Fig. 1

While Kallmann syndrome and HH cause a failure to enter puberty the root cause is located deep within the brain, specifically the communication between the pituitary and hypothalamus glands. It is a failure of the communication between these two glands that prevent the correct hormones being released by the pituitary gland which normally allow the development and correct function of the secondary sexual organs (testes / ovaries).

All the genes implicated so far in cases of KS / HH have some sort of role in the development of the communication pathways between the pituitary and hypothalamus. The pituitary and hypothalamus glands control many functions around the body. KS and HH are very specific conditions where only the sex hormone production side of their function is normally affected, leaving all the other functions intact. This is partly the reason why it is very a very difficult condition to detect early.

Apart from the lack of sense of smell, which is not unique, there is normally nothing to suggest a person has the condition until puberty fails to start. This makes diagnosis quite difficult sometimes, especially if doctors are not familiar with the condition. It is not unknown for some people with KS or HH to "know" they have a problem when young, but find it impossible to prove it or to persuade doctors to take them seriously.

Without a reliable genetic test too many people with KS or HH will be told they are "late bloomers" or "late starters" well into their late teens and are prevented from getting an early diagnosis or treatment.

Kallmann Syndrome, Self Image and Sex.

This is going to be a very personal blog entry and by its very nature it will be explicit in content in places.

I have spoken to a lot of people and met a lot of people with Kallmann syndrome (KS) and Hypogonadotrophic Hypogonadism and over time I have had some rather frank discussions.

To start with a little about me; as a 41 year old I am very sexually inexperienced, my total sexual experience amount to one failed sexual experience at the age of 37 and an occasional but not very fulfilling gay encounter (not full sex). Most people I talk to with KS are more sexually experienced than me but at the moment I can only speak from my own experience.

Looking back at certain situations certainly at University there were times when sex could have been available, but not being on treatment at the time I neither had the knowledge or the drive to take up the opportunity. I had no sex drive while as a teenage and had little interest or drive, I was just waiting for things to develop. I was 18 the first time I saw porn and had little knowledge of the small pieces of conversation I heard other boys having.

As with a lot (but not all) men with Kallmann syndrome I have underdeveloped genitals. With an erect length of a little over 4 inches it puts me in lower end of the range for “normal” men. As with some men with KS it is the lack of testicle size that is more of an issue for me than penis size. Not all men with KS are at the lower end size wise, some will consider themselves well in the “normal” range. I can just about live with being small; it is the lack of testicle size that is more annoying most of the time. Even though they play no part in penetrative sex, it does a lot to a man’s self image not to have a proper set of testicles.

Starting treatment early, preferably before the age of 17, appears to have a big impact on the final penis size. The earlier treatment is started the more likely it is for the penis to grow to whatever length it is pre-determined to get to.
I think in general men with KS have less sexual partners than other men and taking the first step is often taken with more trepidation than it is with every other man at some stage in their life. Most of the men I have spoken too were extremely nervous on the first attempt, but once sex drive overtakes inhibitions the outcome is well worth it.

Most men with KS will have normal sexual function with erections & ejaculation, but for some men the volume of ejaculate will be lower than some due to the underdevelopment of the testes and prostate gland. There will be a small percentage of men with KS with very under-developed penises (erect length of less than 1 inch) for whom penetrative sex would be very difficult.

In my many conversations with men with KS it is fair to say no one person is the same. I think all men with KS do have an issue with their self image and their sex lives at some stage. Most overcome it and end up in stable relationships with their partners. Finding the right partner is the key. Being in a stable relationship with an active sex life makes coping with Kallmann syndrome far easier for a lot of people I talk to.

Kallmann syndrome (and other forms of hypogonadotrophic hypogonadism) are not easy conditions to diagnose for a number of reasons.

1. It is not widely known about in the medical profession, especially by primary care physicians and GP's. This leads to people with KS or HH being dismissed as "late developers" at the age of 16 if puberty has not started by then. The constant dismissal of people with this tag "late developer" gets to be very annoying after a while and being told to wait and see well into their late teens.

2. While KS / HH are genetic disorders there is no one genetic test that can detect them. While some gene defects are known to caused KS and some of these can be tested for the majority of KS cases still have an unknown genetic cause.

3. Diagnosis normally only occurs by eliminating other more common conditions.

4. It is difficult, but not impossible, to diagnose KS or HH before the age puberty is due. Still the majority of people are not diagnosed until their late teens or early 20's when puberty still has not started.

Not everybody will start puberty at the same age, in any peer group there will always be people who start earlier than others.

However there does come a stage when you end up being the last one to start. By the age of 15 most people, over 95% of them, should have at least started puberty.

By the age of 16 virtually everybody should have started.

Kallmann syndrome is not an easy condition to diagnose mainly because it is so poorly understood, especially by GP's or primary physicians. A lot of people in my position at the age of 15, 16, or 17 are told that they are just a late starter, late bloomer or told they should just go away and wait a few more months.

For some people this may well be true, but for those of us with Kallmann syndrome puberty will never start and you go into your late teens and early 20's thinking there is something very wrong, you are the only person in the world that missed out on puberty and getting a strong mistrust of the medical profession.

At the age of 16 if somebody has not started puberty they should be referred to an endocrinologist for specialist review. They then can determine whether it is a case of "delayed" puberty or a possible case of Kallmann Syndrome or HH.

Some doctors are reluctant to send teenagers for review and tell them all will be OK soon enough. This can be potentially very emotionally damaging to the person involved. Puberty is a very important step both physically and psychologically in any person's development and to fell left behind when the rest of the peer group is advancing can produce effects which last long into the person's life.

In all my conversations and meetings I have with people with Kallmann syndrome one point is made very clear, the people who cope better with this condition are those who are diagnosed and treated early in life, ideally between the ages of 15-17.

Kallmann Syndrome is not an easy condition for people to understand. Families, partners and friends of people with KS or HH will hopefully help to be understanding, but it is almost impossible for them to know what it is like to have a condition which prevents you from not going through a fundamental stage of development.

One of the big hurdles is the initial diagnosis with most cases of absent / delayed puberty not being taken seriously by primary clinicians. Far too often I hear stories about people who are 16 or older being told to "wait and see", or that they are a "late bloomer". Over 99% of people should have at least started puberty by the time they are 16. Anybody who is 16 with no obvious puberty signs should be referred for an endocrinologist review to determine if they could have KS / HH.

Once diagnosed treatment is fairly straight forward. The 3 monthly injection now available can be stretched to 6 months for some people. Fertility treatments are available and are successful in a lot of cases, both for the men and women.

While on the physical side Kallmann syndrome is a fairly benign condition. It has no shortened life expectancy associated with it and no physical pain. If left untreated the major problem would be the greatly increased risk of osteoporosis or brittle bones due to the low levels of testosterone or oestrogen.

It is the psychological side of Kallmann syndrome that is so poorly understood. I think a lot of it arises from the poor self image a lot of people with KS / HH have. Missing out on such a key developmental step, both physically and emotionally means some people with KS / HH take a long time to catch up with their peer group, if they ever do.

While most people with KS / HH can have normal sex lives, for a lot of people there is a major obstacle of poor self image that they have to overcome. In my own non-professional opinion, but through talking to a lot of guys with KS or HH it is those who have been diagnosed & treated at a later age that have the most trouble forming and keeping relationships.

Kallmann syndrome is a form of hypogonadotrophic hypogonadism (HH).

Kallmann syndrome can be described as HH with an associated lack of sense of smell.

As far as diagnosis & treatment is concerned there is no difference between Kallmann syndrome and HH.

Hypogonadism is the condition where the gonads (testes in men, ovaries in women) stop functioning correctly and do not produce the hormones they normally do. This is a fairly common occurrence in older age, especially in men when testosterone levels can fall from middle age onwards.

Hypogonadotrophic hypogonadism (HH) is not the same condition and is a lot rarer than normal hypogonadism. Normally the testes & ovaries are controlled by hormones produced by a structure within the brain called the pituitary gland. These hormones are called gonadotrophins.

In HH the levels of gonadotrophins are so low as to prevent the testes & ovaries from functioning correctly.

In normal hypogonadism the testes & ovaries did function correctly at one stage.

In HH the testes & ovaries never had the chance to function correctly as they never had the correct gonadotrophin levels produced by the pituitary in order to perform correctly.


Gonadotrophins = hormones that act on the gonads (ovaries / testes)

Hypogonadism = under performance by the testes / ovaries

Hypogonadotrophic hypogonadism = under performance by the testes / ovaries due to low levels of gonadotrophins.

In Kallmann syndrome / HH the failure to enter puberty is due to the lack of gonadotrophin release by the pituitary gland which prevents the development of the testes / ovaries normally seen at puberty.

Questions to ask the GP if you are worried about delayed puberty:

Puberty in boys should start between the ages of 12 – 14 and in girls between the ages of 11 – 13.

Some boys will always be later than other boys and there is a fundamental difference between a “constitutional delay of puberty” and a case of Kallmann syndrome.

Kallmann syndrome is a very rare condition and will not be the first condition that a GP would normally suspect when presented with a case of absent puberty.

It has been common for GP’s to have a “wait and see” approach to cases of delayed puberty, assuming that puberty will start eventually. For a lot of boys this indeed would be the case. However in a case of Kallmann syndrome puberty will not commence without treatment. It is not uncommon for people with Kallmann syndrome to be dismissed by their doctors so often as late developers they loose faith in going forward with such an embarrassing condition. It is not that uncommon for men to get into their 20’s or 30’s before a correct diagnosis is reached.

Experts in Kallmann syndrome now suggest that any boy who has not started puberty by 15 or a woman not started having periods by 14 should be referred to an endocrinologist for specialist review. An endocrinologist can then differentiate between a case of delayed puberty and a potential case of Kallmann syndrome.

If a boy has not started puberty by 14 or a girl who has not started periods by 13 and the levels of the pituitary hormones LH and FSH are low there should be no reason for a delay for a referral to an endocrinologist. The presence of other signs such as lack of sense of smell, family history of “late developing” or infertility, un-descended testes at birth should make an early referral even more important. This is particularly important with women as there can be a wide range of conditions that could prevent periods from commencing and it is important to get the correct diagnosis quickly.

What is the best age for treatment to start:
The age treatment starts will depend on a number of factors which the endocrinologist has to take into account. In younger patients there is a balance to be made between the time treatment starts and the dosage used. Before the age of 16 some doctors are reluctant to give the full adult dose of testosterone (around 200 – 400 mg per month) until it is sure that normal adult height is obtained. If full dose treatment starts too early it can risk fusing the growth plates of the long bones too early and full height is not obtained.

Once full adult dose treatment starts changes should normally start occurring within 6 months. One important point to bear in mind is that the levels of testosterone should be monitored during treatment so that the levels are of adequate adult dose throughout the treatment cycle.

For the younger patients, for ages from 13 – 16, doctors often use a step by step approach starting in small doses of testosterone, such as 50 or 100 mg per month. This is normally reviewed at 3 month or 6 month stages to see if there are any signs of pubertal development. If there is any increase in testicular size it could suggest that it is a case of delay of puberty rather than Kallmann syndrome. The doctor will then re-check the levels of the pituitary hormones LH and FSH to confirm the diagnosis. If LH & FSH remain low the doctor may step up the dose up to adult levels, the rate this occurs will vary from patient to patient but in general by the age of 16 the full adult dose is normally given. The treatment is normally in the form of injectable testosterone (Sustanon or Nebido) as this gives the best effectiveness. Oral testosterone is unlikely to be suitable to patients with Kallmann syndrome.

What changes will occur:
This will depend on the age treatment starts. A person with Kallmann syndrome will never go through a totally normal puberty while on hormone replacement therapy as the testes will not grow and the ovaries will not function. However all the other secondary sexual characteristics should occur including body & pubic hair growth, muscle development, voice breaking and a more adult like appearance.

Penile size is an issue for all men and not just those with Kallmann syndrome. As a general rule the earlier treatment starts, ideally before the age of 16, the more chance there is of a normal penile length. The later the treatment starts the less chance there is of the treatment of having any effect on penile size.

Changes should start occurring within six months of treatment and may take up to two years to complete as in any person going through puberty.