Kallmann syndrome is a rare genetic disorder that causes low levels of gonadotropin-releasing hormone (GnRH). This also leads to inadequate production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
These hormone changes can cause delayed or absent puberty, reduced or absent sense of smell, infertility, and cleft palate. Symptoms can vary from person to person.
Treatment for Kallmann syndrome is managed by a doctor and may include hormone therapy with testosterone or estradiol, treatments to support fertility, therapy sessions, and, in some cases, surgery.
Main symptoms
The main symptoms and characteristics of Kallmann syndrome are:
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Delayed or absent puberty
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Lack of pubic hair and underdeveloped breasts in women
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Absence of facial hair and a deep voice in men
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Infertility
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Small testicles, micropenis, or undescended testicles in men
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Primary amenorrhea in girls
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Abnormal hearing or hearing loss
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Color blindness
People with this condition may also have a reduced or absent sense of smell, kidney abnormalities, a cleft lip or palate, neurological or musculoskeletal issues, dental problems, and unusually short fingers.
People with Kallmann syndrome also have a higher risk of developing osteoporosis later in life due to chronically low sex hormone levels.
Confirming a diagnosis
Diagnosis is usually made by a pediatrician or endocrinologist during adolescence, when signs of delayed puberty become apparent. However, it may be identified earlier if there are warning signs such as congenital abnormalities or a family history of delayed puberty.
To confirm the diagnosis, the doctor may order blood tests to check levels of luteinizing hormone (LH), testosterone, estradiol, prolactin, TSH, inhibin, and cortisol, for example.
In addition, the doctor may order genetic testing, smell tests, or stimulation tests with GnRH, hCG, or kisspeptin. Bone densitometry and MRI may also be requested.
Possible causes
Kallmann syndrome is caused by abnormal brain development during the embryonic stage, which leads to low levels of gonadotropin-releasing hormone (GnRH) and an impaired or absent sense of smell.
Congenital GnRH deficiency prevents proper production of LH and FSH, which are essential for sexual development and fertility, delaying puberty.
Treatment options
Recommended treatments may include:
1. Hormone replacement
For boys, doctors may recommend testosterone replacement therapy, usually starting around age 12. This may be given as injections or applied as a gel.
For girls, estradiol may be prescribed, typically as a transdermal patch, starting around age 12 or later in adolescence or adulthood.
2. Fertility treatment
Fertility treatment may involve pulsatile GnRH given under the skin or gonadotropin injections, such as FSH and hCG.
For women, these treatments can help induce ovulation. For men, they can help stimulate sperm production.
According to an Endocrine Society review, fertility can usually be induced in people with congenital hypogonadotropic hypogonadism using pulsatile GnRH therapy or gonadotropin regimens.
These options may allow people with Kallmann syndrome to have children.
3. Supplements and medications
Calcium and vitamin D are often recommended because people with Kallmann syndrome have a higher risk of developing osteoporosis.
In addition, bisphosphonate medications such as alendronate, ibandronate, and risedronate may also be prescribed.
4. Surgery
Surgery may be recommended to correct undescended testicles (cryptorchidism) in males.
A doctor may also suggest surgery to treat other conditions, such as cleft palate or cleft lip.
5. Therapy
Because delayed or absent puberty can have negative emotional, psychological, psychosexual, and social effects, therapy sessions may also be recommended.