Medical Care
Evaluation and therapy can usually be implemented on an outpatient basis. Inpatient evaluation and treatment may be necessary for patients with congenital heart disease or acute adrenocortical insufficiency.
All postpubertal-age patients with Kallmann syndrome and idiopathic hypogonadotropic hypogonadism are candidates for gonadal steroid replacement therapy in the absence of specific contraindications. Additional therapies to restore fertility can be implemented on request.
Behavioral modification and psychological counseling may benefit individuals with hypothalamic amenorrhea. Such approaches should be offered before estrogen replacement therapy.
Medical therapies are used to treat associated conditions, including osteoporosis, adrenocortical insufficiency, congenital heart disease, and neurologic disorders.
Surgical Care
Assisted reproductive technologies, including in vitro fertilization (IVF), zygote intrafallopian transfer (ZIFT), and gamete intrafallopian transfer (GIFT), have been used successfully when male patients with Kallmann syndrome or idiopathic hypogonadotropic hypogonadism do not achieve adequate sperm counts on either GnRH or gonadotropin therapy.
Patients with Kallmann syndrome and congenital heart disease may need corrective surgery. A detailed description of the pertinent procedures is beyond the scope of this review.
Patients with cleft lip or palate also need surgical correction.
Consultations
Adult or pediatric specialists should be consulted, depending on the patient's age.
Consultations include the following:
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Endocrinologist and reproductive endocrinologist
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Cardiologist
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Cardiothoracic surgeon and pediatric surgeon
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Neurologist and psychiatrist
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Otolaryngologist
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Dermatologist
Diet and Activity
Diet
No dietary restrictions are required in the absence of congenital heart disease. Salt restriction (adult Na+ intake < 2 g/d) is advised for patients with congestive heart failure.
All patients must ensure an adequate calcium (1200-1500 mg/d) and vitamin D (800-1000 U/d) intake, especially if they are osteopenic. Dietary supplements may be necessary for patients to achieve these goals.
Activity
Routine activity restrictions are not necessary; however, patients with osteoporosis need to avoid high-impact sports and situations conducive to falls.
Activity restrictions are also appropriate in patients with certain forms of congenital heart disease or seizures.
Further Care
Further outpatient care
Medications include gonadal steroid replacement (testosterone in males and estrogen-progestin in females) in postpubertal-aged patients.
Male and female patients with Kallmann syndrome or idiopathic hypogonadotropic hypogonadism who desire fertility may choose between pulsatile gonadorelin (GnRH) infusion and gonadotropin therapy (the former is no longer available in the US). Clomiphene may be helpful in women with hypothalamic amenorrhea and should be tried first in this patient population after correction of the precipitating factors, if possible. Assisted reproductive technologies, including IVF, ZIFT, GIFT, and intracytoplasmic sperm injection (ICSI), have been used successfully when male patients do not achieve adequate sperm counts on GnRH or gonadotropin therapy.
Patients with primary adrenocortical insufficiency need glucocorticoid and mineralocorticoid replacement therapy.
Antiepileptic medications are needed in patients with seizures.
Patients with congenital heart disease may need pharmacologic therapy as well. Details of these therapies are beyond the scope of this review.
Patients with ichthyosis are treated with alpha-hydroxy acids, such as glycolic acid or lactic acid.
Further inpatient care
Admit patient for diagnostic testing and surgery as needed.
Transfer
Transfer may be indicated for specific diagnostic testing or surgery.
Inpatient and outpatient medications
Medications include gonadal steroid replacement (testosterone in males and estrogen-progestin in females) in postpubertal-aged patients.
Male and female patients with KS or IHH who desire fertility may choose between pulsatile gonadorelin (GnRH) infusion and gonadotropin therapy (the former is no longer available in the US). Clomiphene may be helpful in women with hypothalamic amenorrhea and should be tried first in this patient population after correction of the precipitating factors, if possible. Assisted reproductive technologies, including IVF, ZIFT, GIFT, and ICSI have been used successfully when male patients do not achieve adequate sperm counts on GnRH or gonadotropin therapy.
Patients with primary adrenocortical insufficiency need glucocorticoid and mineralocorticoid replacement therapy.
Antiepileptic medications are needed in patients with seizures.
Patients with congenital heart disease may need pharmacologic therapy as well. Details of these therapies are beyond the scope of this review.
Patients with ichthyosis are treated with alpha-hydroxy acids, such as glycolic acid or lactic acid.
Prevention
Patients at risk of osteoporosis should avoid high-impact sports and situations conducive to falls.
Patients with certain forms of congenital heart disease should avoid strenuous exercise.
Patients with recent seizures must refrain from certain activities and sports (such as diving) that would put them at risk if another seizure were to occur during participation.
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MRI of the brain in patients with Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH). Panel A is a coronal T1-weighted image of a male with KS showing (abnormal) medially oriented olfactory sulci (black arrows) and normal appearing olfactory bulbs (white arrows). Panel B is an axial T1-weighted image of the same male with KS showing the presence of olfactory sulci (white arrows). Panel C is a coronal T1-weighted image of a female with IHH showing normal olfactory bulbs (large arrows) and sulci (small arrows). Panel D is a coronal T1-weighted image of a female with KS showing lack of olfactory bulbs with shallow olfactory sulci (arrows). (Images reproduced from Quinton R, et al: The neuroradiology of Kallmann's syndrome: a genotypic and phenotypic analysis. J Clin Endocrinol Metab 1996; 81: 3010-3017, with permission from the Endocrine Society).
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This is a frequently sampled serum luteinizing hormone (LH) profile in a male patient with Kallmann syndrome (KS) in comparison with a healthy individual. It shows lack of LH pulsatility in the former.