Kallmann Syndrome - Diagnosis

Diagnosis

The diagnosis is often one of exclusion found during the workup of delayed puberty.

A paper published in 2012 by Prof.Jacques Younghighlights a typical example of the diagnositic work up involved in a suspected case of KS/HH.

One of the biggest problems in the diagnosis of Kallmann syndrome and other forms of HH is the ability to distinguish between a case of constitutional delay of puberty from a real case of Kallmann syndrome (KS) or hypogonadotropic hypogonadism (HH).

The main biochemical parameters in men are low serum testosterone and low levels of the gonadotropins LH and FSH, and in women low serum oestrogen and low levels of LH and FSH.

For both males and females, constitutional delay of puberty endogenous puberty will eventually commence without treatment. However a delay in treatment in a case of KS/HH will delay the physical development of the patient and can cause severe psychological damage. The "wait and see" approach of being a "late bloomer" is probably counterproductive to the needs of the patient whereas a step by step approach with hormone replacement therapy can be used as a diagnostic tool.

In females diagnosis is sometimes further delayed as other causes of amenorrhea normally have to be investigated first before a case of KS/HH is considered.

In males, treatment with age appropriate levels of testosterone can be used to distinguish between a case of KS/HH from a case of delayed puberty. If just delayed the testosterone can "kick-start" endogenous puberty proved by testicular enlargement. In a case of KS/HH there will be no testicular enlargement while on testosterone therapy alone. In the case of constitutional delay early treatment with age appropriate levels of testosterone will stimulate endogenous puberty. If no puberty is apparent, especially no testicular development than a review by a reproductive endocrinologist might be appropriate. Dr Richard Quinton, a leading UK expert on KS/HH suggests that if no puberty is not apparent by the age of 16 then the patient should be referred for endocrinological review.

A full endocrine work up will be required to measure the levels of the other pituitary hormones, especially prolactin to check the pituitary gland is working correctly. There can be other general health issues such as being overweight or having an underlying chronic or acute illness which could cause a delay of puberty. This makes it essential for a patient to get a full endocrine review to distinguish between a case of KS/HH or another cause for the pubertal delay.

Chronological bone age can be assessed using hand and wrist x-rays. If the chronological age is significant lower than the actual age of the patient, this could suggest delayed puberty unless there is another underlying reason for the discrepancy.

A karyotype may be performed to rule out Klinefelter syndrome and Turner syndrome although the hormones levels would also rule out both these relatively common reasons for hypogonadism.

A MRI test, (magnetic resonance imaging), can be used to examine for the presence of the olfactory bulb and to check for any physical irregularities with the pituitary gland or hypothalamus.

A standard smell test can be used to check for anosmia, but it must be remembered that even in total anosmia certain very caustic substatances such as bleach can still be detected by direct stimulation of the trigeminal nerve.

Genetic screening can be carried out, especially for the KAL-1 mutation, but in light of the uncertain genetic origin of the majority of KS and HH cases a negative result will not rule out a possible diagnosis.