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  Kallman's syndrome
 
Authors: Shehzad Basaria, MD, Adrian Dobs Last modified: January 3, 2002
DIAGNOSTIC CRITERIA

  EPIDEMIOLOGY

  • Hypogonadotropic hypogonadism originally described by Kallman
  • This syndrome is a result of deficient secretion of GnRH from the hypothalamus.
  • Most cases are sporadic, however, familial occurrence has been reported.
  • Although X-linked inheritence is the predominant mode, autosomal dominant or recessive transmission has been reported.

  RISK FACTORS

  • Deletion in a gene on the short arm of the X chromosome (Xp22.3) resulting in deficiency of a molecule called KALIG-1.
  • Lack of this protein leads to the inability of GnRH neurons to reside in the hypothalamic arcuate nucleus or the olfactory bulb.
  • These abnormalities result in hypogonadotropic hypogonadism and anosmia.

  SIGNS AND SYMPTOMS

  • Anosmia - either complete or partial loss of smell
  • Hypogonadism - delayed puberty, sexual dysfunction, female estchetueon, tall stature, osteopenia, osteoporosis.
  • Other non-endocrine abnormalities include midline defects such as cleft palate and urogenital abnormalities, neurosensory deafness and red-green color blindness.

  DIFFERENTIAL DIAGNOSIS

  • Hypothalamic or pituitary tumor - can be excluded by MRI
  • Craniopharygioma - common tumor of childhood, generally calcified on imaging
  • Klinefelters syndrome - usually with firmer testes, elevated gonadotropins key indicator of primary gonadal failure
  • Isolated idiopathic hypogonadotropic hypogonadism.
  • Infiltrative hypothalamic or pituitary disease like sarcoidosis or histiocytosis.

  LABORATORY FINDINGS

  • Serum total and free testoterone - very low <50 ng/dl
  • LH and FSH very low 1-2 Iu/ml
  • MRI - negative for any hypothalamic/pituitary mass
 
TREATMENT
TESETOSTERONE REPLACEMENT THERAPY
  • Patches - Androderm 5-10 mg qhs, Testoderm 5-10 gm QAM
  • Gel therappy - Androgel 5-10 gm daily to skin
  • Injectable - Testosterone enanthate 200 mg i.m. q 2 weeks
TREATMENT FOR OSTEOPOROSIS
  • Calcium 1500 mg daily, vitamin 400 units, alendronate 70 mg p.o. weekly, risedronate 30 mg p.o. weekly
TREATMENT FOR INFERTILITY
  • HCG 2000 units i.m. three times a week. After 3-4 months of therapy add FSH 75 units s.q. three times a week
 
IMPORTANT POINTS/RECOMMENDATIONS
  • Testosterone replacement is the least expensive and most direct method of treatment for hypogonadal symptoms.
  • Infertility treatment should be reserved for those situations in which fertility is desired within two years.
 
REFERENCES
  1. Lieblich JM, Rogol AD, White BJ. ;  Syndrome of anosmia and hypogonadotropic hypogonadism (Kallmann syndrome). Clinical and laboratory studies in 23 cases. ;  Am J Med 1982, 73: 506.

  2. Bick D, Franco B, Sherins RJ. ;  Intragenic deletion of the Kalig-1 gene in Kallmann's syndrome. ;  New Engl J Med 1992; 326:1752.

  3. Hardelin JP, Levilliers J, Young J. ;  Xp22.3 deletions in isolated familial Kallmann's syndrome. ;  J Clin Endocrinol Metab 1993; 76: 827.

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