Kallmann Syndrome & Hypogonadism

2012-01-28T11:15:00.001-08:00

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.

2012-01-15T05:45:00.000-08:00

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

2011-08-09T05:40:00.000-07:00

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

2011-08-09T05:37:00.000-07:00

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

2011-05-10T11:36:00.000-07:00

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

2011-04-14T03:16:00.000-07:00

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.

2011-03-28T13:29:00.000-07:00

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.

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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.

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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.

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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.

2011-03-19T07:45:00.000-07:00

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.

2011-01-20T07:58:00.000-08:00

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.

2010-12-17T05:14:00.000-08:00

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.

2010-12-08T02:50:00.000-08:00

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.

2010-12-05T06:12:00.000-08:00

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.

2010-10-24T08:29:00.000-07:00

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.

2010-10-23T11:49:00.000-07:00

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.

2010-09-03T03:10:00.000-07:00

Treatment options available for Kallmann syndrome or HH.

Hormone replacement only:

Tablets - not normally effective as dose is far too low

Daily gel application - gives good levels but can cause skin irritation with some
Daily patch application

Fortnightly or monthly injection, normally with Sustanon.

Injection every 3 months, such as Nebido. Not available in every country but appears to be very effective for treating KS or HH with stable levels throughout the treatment cycle.

Implants every 6 months, convienient but can leave scarring at implant site.

Injection with hCG / Pregnyl, can be expensive but the best method to give a more natural testosterone level and does have the advantage of increased testicular size in some men.

hCG is also the pre-cursor for fertility treatments. If a good response is achieved with hCG then a FSH type injection such as Gonal-F or Perganol is used to start sperm production and hopefully achieve fertility.

2010-09-03T03:02:00.000-07:00

http://kallmanns.org/node/257

2007-02-08T13:12:00.000-08:00

Link to a recent paper mentioned in an earlier blog. This is the full paper.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?doi=10.1172/JCI29884

This paper represents recent work from researchers / doctors from the UK and USA about the inheritance of Kallmann syndrome and Hypogonadotrophic Hypogonadism.

In the past inheritance was thought due to be a defect in a single gene. This may now not be the case. It appears that the cause may be a combination of gene defects. To date there have been 7 different genes identified that lead to Kallmann syndrome or HH.

While this may not have an effect on the treatment of Kallmann syndrome at the moment but it might lead to a better chance of earlier diagnosis in the future.

2007-01-19T10:45:00.000-08:00

Current views on the genetics of Kallmann Syndrome and

Hypogonadotrophic Hypogonadism.

In the past Kallmann Syndrome (KS) and Hypogonadotrophic Hypogonadism (HH) were thought to be caused by single gene defects.

To date there have been 7 different genes on 7 different chromosomes that have been implicated in causing either or both KS or HH.

It has been recognised that different people with the same detectable gene defect for KS or HH show different symptoms. Even within family groups with the same inherited gene defect there is a variation in symptoms seen.

Recent evidence presented by researchers from Boston, USA (Dr Nelly Pitteloud)and Newcastle, UK (Dr Richard Quinton) has presented a new method to explain the inheritance of KS and HH.

It is proposed that some KS and HH cases are caused by a combination of gene defects on two different genes at the same time. This digenic inheritance of two separate gene defects would help to explain the range of symptoms seen in KS and HH cases. Mild or more severe symptoms would depend on what 2 genes are involved and the type of defect in each of the genes.

This has implications for the prediction of inheritance of KS and HH. On a single gene model it was fairly straight forward to give a 0%, 25%, 50% or 100% chance of passing on a gene defect. With 2 genes involved the situation becomes more complex and it becomes increasingly difficult to predict the chances of passing on KS or HH.

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The 7 genes currently thought to cause KS or HH:

FGFR-1 (8p 12) Fibronectin growth factor receptor.

NELF (9q 34.3) Nasal embryonic GnRH factor.

KAL-1 (Xp 22.32) Anosmin

PROK2 (3p 21.1) Prokineticin (G protein 73)

PROKR2 (20p 12.3) Prokineticin receptor

GNRHR (4q 21.2) GnRH receptor

GPR54 (19p 13.3) G-protein 54 receptor (also called KISS-2 receptor)

2007-01-19T10:03:00.000-08:00

Abstract from a paper due to be published in February's issue of The Journal of Clinical Investigation:

http://www.jci.org/

ENDOCRINOLOGY :

The more mutations the worse the disease in idiopathic hypogonadotropic hypogonadism:

Idiopathic hypogonadotropic hypogonadism (IHH) is an inherited genetic disorder that results in impaired sexual development due to a deficiency in a sex hormone known as GnRH. Although individuals are thought to inherit IHH by having just one gene defect (in any one of a number of genes), not all the evidence supports this hypothesis, for example, not all family members with a given gene defect have the same symptoms.

In a study that appears online on January 18 in advance of publication in the February print issue of the Journal of Clinical Investigation, Nelly Pitteloud and colleagues from Massachusetts General Hospital in Boston show that in two separate families with distinct forms of IHH (Kallmann syndrome and normosmic IHH, respectively) different combinations of several gene defects result in different disease symptoms. In the first family, the individual with the most severe phenotype had mutations in two different genes (FGFR1 and NELF). By contrast, his parents and siblings with only one or other of the mutations exhibited less severe disease. Similarly, in the second family, the most severely affected individual had 2 mutations in her GNRHR genes and 1 mutation in her FGFR1 gene, whereas the less severely affected family members did not have all 3 genetic mutations.

This study indicates that IHH is not caused by a defect in a single gene, something that has implications for the genetic counseling of IHH.

TITLE: Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism

AUTHOR CONTACT:

Nelly Pitteloud
Massachusetts General Hospital, Boston, Massachusetts, USA.
Phone: (617) 724-1830; Fax: (617) 726-5357; E-mail: .

2006-04-15T10:05:00.000-07:00

A personal story from a Kallmann syndrome patient in the UK:

I was born on the 18th January 1978, along with my sister, one of twins 11 weeks early. We were kept on the special care baby ward for three months until we were big enough to be allowed home. However I still needed to gain some weight, as I needed surgery to correct my harelip. I gained the weight quite quickly thanks to my uncles who insisted on feeding me more than required. I had the corrective surgery and was allowed home.

About a year later I was diagnosed as having epilepsy and deafness I have around 75% hearing in my right ear and around 10-15% in my left. At 2 years old I had a fit that was severe enough to stop both my heart and my lungs completely. Luckily I survived anyway the severity of the fit was enough that I was put onto phenobarbital and phenytoin.

I stayed on these drugs until my early teens when the doctors thought it best to wean me off them. The side effects were pretty drastic, some days I would forget who I was and where I lived and on occasion would have the whole street out looking for me. There even a few incidents of violent outbursts on my behalf, which anyone who knows me would agree that, that is about as far away from me as you can get. Anyway this landed me in the offices of a child psychologist, who as I was only 10 years old, did not give me enough credit to think I didn't know I was being observed through that big two way mirror. They could not find anything psychologically wrong with me nor could they explain my outbursts of violent behaviour. I would say it was probably due to the large dosage of barbiturates being thrown down my neck, but what would I know.

Anyway as I started approaching my teens I was noticing that I wasn't changing like the rest of my friends my age this puzzled me and I remember being taken to the doctors by my mum who was told "oh he's just a late developer". Secondary school was a nightmare as I was constantly bullied because the other lads my age knew I was different. I used to forget my PE kit on purpose in an attempt to not have to change or shower with the rest of the lads. However there would be the odd time where a spare kit my size would be found and I would be forced to participate. Detentions were common for me as forgetting your kit was a punishable offence

I didn't really mind as it meant less bullying in one respect but my schoolwork did suffer. Meanwhile the doctors were just fobbing mum off with the same excuse. So I left school and went to the local agricultural college where I did my animal care and veterinary nursing diploma. I went on to do a further two animal care related courses. All this time and still puberty was determined not to show. I put this to the back of my mind and just carried on with life I became quite depressed.

As time went on I turned to drink and one night during a heart to heart with a close friend's mum I told her. The very next day she marched me off to the doctors determined to sort it out. My GP, admittedly out of his depth referred me to the endocrinologist at our local hospital he put me onto the testosterone injections. He did not tell me why or even perform any other tests apart from x-raying my wrists. I figured best not to question his ways of doing things he must know what he's doing. It was only when my twin sister saw the same doctor and he told he that she could not have kids and that she was too young to be trying anyway that alarm bells started ringing (we were twenty at that point) so a friend of mine started doing a bit of research.

We came across the HYPOHH site online so I rang Mark Saunders spoke to him, wow what an awesome relief. He advised me to get a second opinion ASAP so when I went to the HYPOHH conference in Birmingham of that year I did just that. I went up at the Bristol Royal Infirmary. They explained everything and they were great. I had several MRI scans and ultrasound scans. It was discovered that I had un-descended testes so an operation was arranged to have them removed. I had a prosthesis put in place I figured life would now take on some form of normality.

My care was handed over to my GP. However the prosthesis did not fall into its correct place and caused me a great deal of pain for two years. I tried all sorts of drugs and even acupuncture. In the end I decided the best thing to do was to have them removed. It was around this time that I discovered the Yahoo group and I discovered that in fact everything was not as it should be, again I had been grossly mistreated.

So I eventually plucked up the courage to change my GP and demanded a referral back to an endocrinologist (a different one this time). I saw him last month and the appointment went better than I ever could have imagined. I finally found a doctor that listens to me and takes my point of view. I never thought I would find one. Everything is now under control and for the first time in my life. I am looking forward to the future and it's all thanks to this group, the HYPOHH site and a few good friends.

I wanted to write this for two reasons

1) To thank everyone for there help and support and prompting

2) To make anyone stuck in a similar predicament see there is a light at the end of the tunnel.

Help is available all you need do is ask

Many thanks Paul C.

2006-03-15T05:19:00.000-08:00

Kallmann Syndrome is a rare enough condition without having trouble finding information on the internet because of spelling...

The German / American scientist who published the landmark paper on this syndrome in 1944 was Franz Kallmann.

The correct notation is now Kallmann Syndrome, rather than Kallmann's Syndrome. It was recently agreed that all the personal notation associated with disease names would be dropped, so for instance Down's syndrome is now Down syndrome and Klinefelter's is now Klinefelter syndrome.

2006-02-15T05:12:00.000-08:00

The first medical paper to use the name Kallmann syndrome was published in 1944 in the unfortunately titled magazine "American Journal of Mental Deficiency".

It was first thought that Kallmann Syndrome was linked to a marked level of mental incompetence. This is NOT the case.

The fact that the few people in the first paper had Kallmann syndrome and mental problems was a coincidence and not a direct result of having Kallmann syndrome.

There is no link between intelligence, mental awareness and having Kallmann syndrome.

2006-01-15T05:21:00.000-08:00

Kallmann Syndrome and the closely related hypogonadotrophic hypogonadism are genetic conditions.

However unlike a lot of other genetic conditions its route cause is still not fully understood.

At present there are 4 different genes that are known to cause this condition, and there may well be more out there. It has been estimated that these 4 genes only account for about 30% of all cases.

The lack of complete understanding of the genetic cause of Kallmann Syndrome prevents an effective, reliable screening test from being developed.

If any person with Kallmann Syndrome is going through fertility treatment they should be aware that there is a chance of passing the condition on but it is impossible to give an assessment of the risk.

2005-10-14T15:57:00.000-07:00

Kallmann's Syndrome is not a very well known condition, even in the medical community.

The actual incidence is difficult to know for certain but estimates are in the range of 1 in 10,000 for men and 1 in 50,000 for women.

On one hand it is a very mild condition to have, there is no change in life expectancy and no pain associated with having the condition. The only big thing to watch out for is the increased risk of developing osteoporosis, or "brittle bones" due to the low levels of circulating sex hormones. The lack of sense of smell may get noticed from time to time and may cause a few embarrassing or awkward situations during life.

However the psychological damage of not going through puberty at the same time as you peer group, or even not all, can be immense. Just how damaging will depend from individual to individual and will be affected by age of diagnosis / treatment, knowledge of the condition and family & friends.

There are two aspects of not going through puberty that have to be considered. One is the feeling of being physically different from the people around you and the other is the fact that you will be infertile without treatment. Each of these may be more important than the other depending if you are male or female or at what stage of life you are at.

2005-09-27T11:37:00.000-07:00

Since this is a new blog, I thought I would post a little more information on myself in the vain hope that somebody will read this blog one day.

I was born in Swindon, but grew up in Plymouth, Devon here in the UK. After a fairly uneventful time at school I went to University in Plymouth, Bradford and Portsmouth.

I work as biomedical scientist, usually in a blood transfusion lab somewhere in the country. After my training at the Royal Free in London, I have worked in hospitals in Harefield, Harlow, Watford, Gillingham, Birmingham, Oxford & Glasgow. I am just about to start another placement in Burnley.

I like traveling, but I only started going abroad since starting my first real job. My first ever trip abroad was to Pakistan, I have since been to Sweden, Belgium, America and Australia. There are two places that a person must visit if they get chance in the life: The Grand Canyon and the Great Barrier Reef.

I work in professional sport during the summer as a cricket scorer and statistician. What started out as a hobby is now a full time job during the summer months when I work for Worcestershire County Cricket Club. During the winter months I go back to work as a biomedical scientist.

That should be enough boring information for now.....if anything exciting happens, I may just post again...

2005-09-27T08:03:00.000-07:00

Kallmann's syndrome is a form of hypogonadotrophic hypogonadism (HH). This is a very long winded way of saying that there is a breakdown in the communication between he brain and the gonads, either the testes or ovaries.

In Kallmann's or HH there is a failure to start or to fully complete puberty. A person will Kallmann's will also have an absent or very reduced sense of smell. Without the correct treatment a person with Kallmann's or HH will not go through puberty, most probably be infertile and have a increased risk of developing osteoporosis.

People with Kallmann's have to take a form of hormone replacement therapy to replace the hormones that are normally produced by the testes or ovaries.

It is a rare genetic, hormonal disorder. The exact genetic cause is unknown, though are a few genes under investigation. It is a lot rarer then the better known Kleinfelter's and Turner's syndromes which have a known genetic cause. It can be inherited if a person undergoes fertility treatment.

It is not a very well known condition, even in the medical community. A lot of ideas have changed about delayed and absent puberty in the last 10 years so a lot of medical text book are out of date.

There are at least 2 patient groups, one on Yahoo and one on MSN where people can get more information.

There are also 2 web sites where information can also be obtained.

www.hypohh.net

www.kallmanns.org

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That is enough about Kallmann's for the moment. I am sure I will mention it again.....

New blog !!

2005-09-27T06:52:00.000-07:00

Hello everybody,

I thought it was about time I started a web blog as well.

I have attached it to a web site I run about a medical condition I have. It is called Kallmann's syndrome. It is a rare hormonal condition that means I have no sense of smell and did not go through normal puberty when I was younger.

I may come up with more interesting things to write about, about my work, sports & travels in the next few weeks.