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.

Inpatient & 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.

Transfer

Transfer may be indicated for specific diagnostic testing or surgery.

Deterrence/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.

Complications

Complications include the following:

Congenital heart disease: Various cardiac lesions have been reported in a small subset of patients with Kallmann syndrome, including the following: ASD, atrioventricular block, Ebstein anomaly, right aortic arch, right bundle-branch block and WPW syndrome, transposition of the great vessels, and VSD. Early diagnosis and management of these conditions is important in order to minimize patient mortality and morbidity.
Primary adrenocortical insufficiency: Male patients with X-linked idiopathic hypogonadotropic hypogonadism and AHC usually present in infancy or childhood with adrenal insufficiency. This is fatal unless diagnosed and treated appropriately.
Neurologic manifestations: Anosmia or hyposmia occurs in all Kallmann syndrome cases. Some patients with Kallmann syndrome or idiopathic hypogonadotropic hypogonadism exhibit a variable neurologic symptomatology, including the following: cerebellar ataxia, gaze abnormalities, impaired vision, mental retardation, seizures, sensorineural deafness, spastic paraplegia, and synkinesia (mirror movements).
Osteoporosis: Patients with hypogonadism, including all individuals with Kallmann syndrome and idiopathic hypogonadotropic hypogonadism, are at increased risk for osteoporosis. Osteoporosis may be prevented or treated by adequate gonadal steroid replacement. Additional therapies for osteoporosis, including diet and exercise, bisphosphonates, and calcitonin, may be needed.
Short metacarpals and pes cavus
Ichthyosis
Cleft lip or palate

Prognosis

Patients with Kallmann syndrome and those with idiopathic hypogonadotropic hypogonadism can survive for lengthy periods in the absence of associated life-threatening conditions.

Fertility can be restored in most patients with classic Kallmann syndrome and idiopathic hypogonadotropic hypogonadism.

Although Kallmann syndrome and idiopathic hypogonadotropic hypogonadism were previously thought to be lifelong disorders, cases of patients with Kallmann syndrome or idiopathic hypogonadotropic hypogonadism who experienced spontaneous complete recovery of gonadal function have been reported.^[36]

Women with hypothalamic amenorrhea may also experience complete recovery of gonadal function, particularly if precipitating factors are corrected.

Some patients with congenital heart disease or neurologic manifestations may experience a limited lifespan.

Adrenocortical insufficiency is fatal unless recognized and treated; however, patients who are treated adequately should have long-term survival.

Osteoporosis increases the risk of fracture, which may compromise patient survival and quality of life.

Patient Education

Patients should be made aware of the risks and benefits of gonadal steroid replacement therapy.

Patients should know that current therapies permit fertility in most patients with Kallmann syndrome or idiopathic hypogonadotropic hypogonadism.

Patients should know that, although Kallmann syndrome or idiopathic hypogonadotropic hypogonadism are usually life-long conditions, spontaneous recovery of gonadal function is possible in some individuals.

Patients with adrenocortical insufficiency should be familiar with sick day rules.

Activity restrictions should be discussed in patients with osteoporosis, congenital heart disease, or seizures.

For excellent patient education resources, visit eMedicineHealth's Men's Health Center and Women's Health Center. Also, see eMedicineHealth's patient education articles Impotence/Erectile Dysfunction and Amenorrhea.

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Media Gallery

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).
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.