eMedicine Specialties > Endocrinology > Pituitary Gland

Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism: Follow-up

Author: Nicholas A Tritos, MD, DSc, MMSc, FACE, FACP, Assistant Professor of Medicine, Tufts University School of Medicine; Senior Staff Physician, Department of Endocrinology, Lahey Clinic Medical Center
Contributor Information and Disclosures

Updated: Nov 26, 2008

Follow-up

Further Inpatient Care

  • Admit patient for diagnostic testing and surgery as needed.

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.

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

  • 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.23
  • 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 eMedicine's Men's Health Center and Women's Health Center. Also, see eMedicine's patient education articles Impotence/Erectile Dysfunction and Amenorrhea.

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize the presence of an underlying condition, such as hemochromatosis or a pituitary tumor, in patients presenting with hypogonadotropic hypogonadism
  • Failure to obtain semen analysis before recommending that a man with Kallmann syndrome or idiopathic hypogonadotropic hypogonadism does not need to take contraceptive precautions
  • Failure to recognize the presence of Kallmann syndrome-associated conditions, including osteoporosis, adrenocortical insufficiency, congenital heart disease, or neurologic manifestations
  • Failure to implement endocarditis prophylaxis in patients with certain forms of congenital heart disease

Special Concerns

  • Prenatal diagnosis of X-linked Kallmann syndrome and idiopathic hypogonadotropic hypogonadism is possible for family members with a known mutation of the KAL1 gene or DAX1 gene, respectively, by using molecular genetic and cytogenetic analysis (Southern blot or fluorescence in situ hybridization) of fetal DNA.
 


More on Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism

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Differential Diagnoses & Workup: Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism
Treatment & Medication: Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism
Follow-up: Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism
Multimedia: Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism
References
Further Reading
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References

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Keywords

Kallmann syndrome, KS, idiopathic hypogonadotropic hypogonadism, IHH, gonadotropin-releasing hormone, De Morsier syndrome, olfactogenital dysplasia, acquired idiopathic hypogonadotropic hypogonadism, gonadotropin-releasing hormone deficiency, hypothalamic amenorrhea, GnRH deficiency, DAX1, fertile eunuch syndrome, classic KS, classic IHH, congenital KS, congenital IHH, adult-onset IHH, acquired IHH, X-linked KS, gonadal steroid replacement therapy, anosmia, hyposmia

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Contributor Information and Disclosures

Author

Nicholas A Tritos, MD, DSc, MMSc, FACE, FACP, Assistant Professor of Medicine, Tufts University School of Medicine; Senior Staff Physician, Department of Endocrinology, Lahey Clinic Medical Center
Nicholas A Tritos, MD, DSc, MMSc, FACE, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Medical Association, Endocrine Society, Massachusetts Medical Society, and Pituitary Society
Disclosure: Nothing to disclose.

Medical Editor

Ghassem Pourmotabbed, MD†, Former Associate Professor, Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Tennessee School of Medicine and Health Science Center
Ghassem Pourmotabbed, MD† is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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