UK Patient meetings 2014.

There are patient meetings planned for January 2014.

18th Jan. Royal Victoria Infirmary, Newcastle-upon-Tyne.

25th Jan. Royal Free Hospital, London.


The meetings will be a combination of a chance to ask KS experts questions and the chance to meet and talk to fellow patients.

Further details to follow or e-mail neilsmith38@hotmail.com for more information.

US Kallmann syndrome meeting 2013. Notes taken. Part 3.

USA Patient Meeting 2013. Notes taken. Part 3.

Obtaining medications with health insurance.

There are companies that can provide basic testosterone medication free of charge without insurance in the USA as long as you have a valid prescription. There is a post in the Facebook groups listing these companies.

Gaining hCG and hMG medications on health insurance is possible but it is a time consuming and lengthy process. One key point is emphasise the point that the hCG / hMG medications are required for testosterone production only and not for fertility. Insurance companies are very unlikely to approve medication for fertility use. However in patients with KS / CHH the primary reason is testosterone production and osteoporosis prevention. If you leave a message in the Facebook groups somebody who has had a lot of experience in dealing with insurance companies will be able to help and advice you.

 

Genetics.

The understanding of the genetics of KS / CHH is changing all the time and it is difficult to give many clear cut answers.

So far over 20 different genes have been implicated in causing cases of KS / CHH.

With puberty being such a defining point in human development it is not surprising there are many different genes involved in its control. No one single gene is responsible for the initiation of puberty so a defect in one gene does not always mean puberty is delayed or is absent.

KS / CHH is primarily a two or more gene defect condition, which accounts for its rarity. One gene defect on its own might cause visible symptoms such as hearing loss, dental problems, cleft lip, and delayed puberty. However it is only when this gene defect is combined with another that you get a case of KS / CHH with the full range of symptoms. It is clear by looking at families with KS / CHH that the range and severity of symptoms is not consistent, even within siblings. This makes the prediction of inheritance and the genetic screening for KS / CHH very problematic.

Over 50% of KS / CHH cases still show an unknown genetic origin. You can screen blood for the currently known genes but any negative result just means it is negative for the genes discovered so far. Research centres in Boston & Augusta in the USA or in Switzerland will test blood samples for current gene defects and then store the samples for re-testing once new gene defects are discovered.

The only exception to this is the KAL-1 mutation on the x-chromosome. KAL-1 is termed a high penetrance gene. A mutation in the KAL-1 gene can cause a case of KS on its own with no other gene defect present. Any small defect in the KAL-1 gene gives rise to a high probability of having Kallmann syndrome. The KAL-1 mutation is the one associated with the additional symptoms of anosmia, mirror movements of the hands, absence of one kidney and hearing loss.

KAL-1 causes x-linked KS, so is only found in males (there is a theoretical chance of a female having x-linked KS but has never been proved yet). X-linked KS accounts for less than 10% of all KS / CHH cases but is the one that is most easily tested for.

US Kallmann syndrome meeting 2013. Notes taken. Part 2.

USA Patient Meeting 2013. Notes taken. Part 2.

 

Growth spurt.

The growth spurt seen in late puberty in both males and females is controlled primarily by testosterone and oestrogen levels under the influence of growth hormone. Normally height will increase until the pre-determined height is reached and then the end plates of the long bones fuse & harden preventing any further growth.

In KS / CHH where there is a lack of testosterone & oestrogen no growth spurt occurs but instead there is a linear height increase under the influence of growth hormone. This can lead to patients with KS / CHH being of above average height unless they start hormone treatment at the appropriate time.

The lack of oestrogen or oestrogen in KS / CHH patients can lead to early onset osteoporosis which should be checked for by the use of DEXA / bone density scan.

No puberty v partial puberty.

In patients with KS / CHH it is estimated that 60% of cases will show no pubertal development at all while the remaining 40% will show partial pubertal development.

Use of hCG in males.

hCG is human chorionic gonadotropin, it is normally derived from human placentas and has the same activity as luteinising hormone (LH). In males hCG can be given instead of testosterone preparations in order for the testes to produce their own testosterone. Pregnyl is a common trade name for hCG.

hCG acts on the Leydig cells in the testes in the same way as LH, with the production of testosterone. Normal levels of testosterone can be achieved within two months of starting treatment. Injections are given sub-cutaneously and the dose and frequency given is dependent on the testosterone levels achieved.

There is normally no increase in size in the testes when on hCG injections.

There was a bit of debate at the meeting about the possibility of achieving sperm production while on hCG alone. It is certainly possible for some patients with KS / CHH to achieve a low level of sperm production while on hCG injections alone but normally this tends to be the patients who have had some form of gonadotropin treatment in the past or who have partial testicular development already.

Patients with KS / CHH can sometimes achieving fertility with sperm counts a lot lower than those seen in other men. The theory is that fertility is based on the quality of sperm produced and not just the number produced.

There is no evidence of any long term adverse risk in males using hCG injections.

Use of FSH injections in fertility treatments in males.

Follicle stimulation hormone (FSH) acts on the Sertoli cells in the testes in order to induce sperm production. It is the increase in the Sertoli cells that gives the testes their size. Normally testes need to be 4ml or bigger in order to produce enough sperm for natural conception.

In most males, but not all, with KS / CHH FSH type medication is required to induce fertility. It is thought that giving FSH on its own for a few months before the addition of hCG increases the chances of sperm production and can speed up production.

In the past hCG has been given on its own first but new evidence suggests that pre-treatment with FSH can be more effective.

FSH can be given in its pure form or combined with LH in the form of human menopausal gonadotropin (hMG or menotropin).

FSH and hMG injections are expensive and not always easy to get hold of but can provide an effective form of fertility treatment for me along with the psychological benefit of testicular development.

 

 

 

 

 

US Kallmann syndrome meeting 2013. Notes taken. Part 1.

USA Patient Meeting 2013. Notes taken. Part 1.

Gender difference between males & females.

It used to be thought that there were about five times more cases of KS / CHH in males than in females. This has never been fully explained by genetics.

One school of thought is that there is actually no gender imbalance in reality. The disproportion in diagnosed cases might well be due to the lack of correct diagnosis of KS / CHH in females. It is not easy to correctly diagnose KS in females, especially if the oral contraceptive pill is used in treatment.

Un-published work done in Boston took the numbers of 600 patients in known KS / CHH families and came out with a ratio of 1 : 1.3 male to female cases.

Definition of a “rare disease”.

A rare disease is defined as one that is found in 1 in 2,000 of the general population. With KS / CHH being at around the 1 in 20,000 mark roughly it falls neatly in this category. About 8% of the general population of the USA could be classified as having a rare disease.

Start of puberty.

The age of onset of puberty has a range of 10 to 15 years in females with a mean of 12 years old. In males the range is 12 to 16 with a mean of 13 years old. Typically puberty takes 5 years to fully complete.

The age puberty starts in males is not easy to distinguish in boys whereas in girls it is marked by the first menstrual bleed.

2% of the population will show a constitutional delay of puberty. This group will start puberty naturally at some stage but early hormonal treatment might be given in appropriate cases.

Any delay of puberty by the age of 15 in females and 16 in males should be investigated by a reproductive endocrinologist or a paediatric endocrinologist.

Un-descended testes at birth.

Occurs in 2% of the male population but in up to 40% of boys with Kallmann syndrome.

GnRH and sexual differentiation.

Sexual differentiation into the male and female physical forms occurs in the first few weeks of life and is controlled by the hCG derived from the placenta. This is normally unaffected in people with KS / CHH so they are born physically male or female.

Normally there is a GnRH surge from the hypothalamus in the developing baby in the final trimester and into the first 6 months of life. This is a “mini-puberty” and can give rise to detectable levels of LH / FSH / testosterone or oestrogen. This mini-puberty is missing in patients with KS / CHH. This can be used as a diagnostic tool for babies where there is a likelihood of KS / CHH being passed on. This test is more sensitive in male infants than female infants.

The presence of micro-penis and un-descended testes at birth seen in some boys with KS / CHH is related to the lack of testosterone in boys in this mini-puberty.

Kallmann Syndrome Information page on Facebook.

I am in the process of creating a new information page on Facebook for Kallmann Syndrome and Hypogonadotropic Hypogonadism.

It is work in process at the moment but I hope to be able to post information that might be helpful to fellow patients and news of any upcoming meetings or recent medical papers.

Facebook Information page for Kallmann Syndrome.

Kallmann syndrome & anosmia.

Anosmia or the lack of sense of smell is an important symptom in Kallmann syndrome as it is the one symptom that can be noticed well before the age puberty is due.

Anosmia accompanied by pubertal delay should alert doctors to the potential of a case of Kallmann syndrome.

Anosmia is only found in patients with Kallmann syndrome.

An absence of puberty and no sense of smell might not seem related at first. They are linked because the part of the brain that controls smell (olfactory bulb) and the part of the brain that controls the initiation of puberty (hypothalamus) are located very close together. During the very early development of the foetal brain any problem in the development of the structure of the olfactory bulb can prevent a the part of the hypothalamus that controls puberty from working correctly later in life.

Around 50% of cases of congenital hypogonadotropic hypogonadism (CHH) occur with a normal sense of smell. The other 50% of cases have anosmia or hyposmia (reduced sense of smell), it is these cases that can also be termed Kallmann syndrome.

Since patients with Kallmann syndrome have had no sense of smell all their lives some patients do not realise how important the sense of smell can be.

There are issues such as fire & gas safety, food wastage, personal hygiene & body odour that can be easily overlooked, especially if a person lives by themselves.

There is an excellent support group for people with all forms of anosmia, called Fifth Sense. Here is a link to their website:

Fifth Sense Website.

USA Patient Meeting. 26th October 2013.

There will be a patient meeting for patients with Kallmann syndrome / CHH .

It will be held at the Saddleback Memorial Hospital,  Laguna Hills, California, USA on 26th October 2013

Attending the meeting will be top KS experts Professor. Nelly Pitteloud and Andrew Dwyer.

The meeting will be a mixture of medical information and a social event. It will be a good chance for patients and their families to meet other patients.

More information can be obtained by e-mailing:

kschh2013@hotmail.com

Early blood test for KS / CHH - from birth to 6 months of age.

In both males and females there is a "miny puberty" which lasts from birth until 6 months of age. It is more apparent in males than females. In males it sets the body up ready for normal puberty to start at around 11 or 12 years of age.

In this short period of time from birth to six months of age there would be detectable levels of FSH and LH in the blood and detectable testosterone levels in males.

In males and females with Kallmann syndrome or CHH this miny puberty does not occur.
It works better in boys than girls but if there is a delectable level of FSH, LH, testosterone / oestrogen it would strongly suggest that it is not a case of KS / CHH.

The lack of detectable levels would not confirm a KS / CHH diagnosis but would be a big clue towards the correct diagnosis. Conversely if you do find the hormones present at that age it can be very reassuring that CHH / KS is not present.

If a blood test reveals no detectable levels of testosterone at 6 months of age and there has been either micro-penis or undescended testicles it would give doctors a very good indication that KS / CHH is a distinct possibility.

I have added here a one page link to a web site which also confirms the possibility of testing up to the age of 6 months.

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=174590

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