The diagnosis of Kallmann syndrome, or idiopathic hypogonadotropic hypogonadism with anosmia, is made on the basis of clinical findings that suggest reduced or incomplete sexual maturation associated with hypogonadism, with reduced or absent sense of smell.
The absence of pubertal changes that is evident during the physical examination is important in the diagnosis of the condition. In addition other diagnostic tests are performed to identify a reduced sense of smell, genetic mutations, or structural abnormalities of the endocrine glands that may cause similar symptoms.
The most distinctive sign that usually prompts patients to seek medical advice is the partial or complete absence of puberty.
Men may report symptoms such as decreased libido, erectile dysfunction, reduced muscle mass and reduced aggressiveness. Women with the syndrome may have amenorrhea, the absence of menstrual periods for at least six consecutive months.
A low body ratio (the ratio of the upper body segment (crown-pubis) to the lower body segment (pubis-heels) of less than 1:1 is evident in patients affected by Kallmann syndrome. Additionally, patients often have an arm span at least 5 cm greater than their height.
Men may have an absence of or reduced amount of facial, pubic and body hair growth, a high pitched voice, reduced muscle mass and strength, redistribution of fat to hips and chest and a small penis less than 8 cm in length. Women may experience a lack of breast development and have a deep red color in the vaginal mucosa.
There are various stages of puberty, which are defined as follows:
- Stage I: No pubic hair, no evidence of pubertal changes
- Stage II: Sparse pubic hair, slight pubertal changes evident
- Stage III: Public hair, more pubertal changes
- Stage IV: Pubic hair to cover pubis, more advanced pubertal changes
- Stage V: Normal pubic hair, mature adult genitalia
The degree of sexual maturation is variable among individuals. However, these stages may be useful in the diagnostic process.
Sense of Smell Testing
Another characteristic symptom of Kallmann syndrome is a reduced or absent sense of smell. This can be measured using a test such as the University of Pennsylvania smell identification test (UPSIT). This involves identifying the smell of 40 microencapsulated odorants, which can easily be conducted in a general practice setting. The sense of smell will be described as anosmia or hyposmia in patients with Kallmann syndrome.
Molecular genetic testing can help to identify the specific genes that are responsible for causing the condition. To date, mutations in the following genes may be used to confirm the diagnosis of Kallmann syndrome: KAL1, GNRHR, KISS1R, FGFR1, PROKR2, PROK2, CHD7, FGF8, GNRH1 and TACR3.
Other Diagnostic Tests
Biochemical testing is also used in the diagnostic process for Kallmann syndrome. As the level of GnRH cannot be measured directly, the serum concentration of gonadotropins such as luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormones are measured. Affected patients will have low or normal levels of LH and FSH, alongside low levels of testosterone and estradiol in males and females respectively.
Additionally, imaging techniques to examine the structure of the involved endocrine glands may be required. Magnetic resonance imaging (MRI) is often used to investigate for structural abnormalities that may cause the symptoms and require management.