Unusual endocrine and somatic phenotypic abnormalities in a 14-year-old boy with classic Klinefelter syndrome (47,XXY)

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    Dear Editor,Klinefelter syndrome (KS) is the most common chromo-somal disorder. This condition affects 1 in 500-1000males who carry an additional X chromosome, but itsprevalence is surely underestimated and diagnosis is gen-erally delayed because of variable clinical presentationsand insufficient professional awareness of the syndromeitself (1, 2). The original description of the syndrome in-cluded 9 men with gynecomastia, small testes, azoosper-mia, and elevated gonadotropin levels (3).We have observed unusual clinical features in a 14-yr-oldboy with classic chromosomal aberration, who was re-ferred to our outpatient clinic for disharmonic tall statureand eunuchoidal body status. On physical examination,auxological data were: height 182.5 cm (3.2 SD), de-creased sitting height/total height ratio (SH/H=0.488,2.3 SD), weight 58.5 kg (90 C), body mass index 17.6kg/m2. Parents target was 167.9 cm (height for target4.2 SD). Bone evaluation was 15.8 yr (Tanner-Whitehouse2) with predicted final height higher than target height(187.6 cm). Pubertal development, which started whenthe boy was 11 yr old, was normal (G4-Ph3), volume ofboth testes was 6 cc and gynecomastia was absent. Manyphenotypic abnormalities were evident: depressed nasalbridge, prognathism, pigeon and narrow chest, long sec-ond toe with large first interdigit, poor muscle develop-ment (Fig. 1). Psychological evaluation showed behav-ioral inadequacy and poor socialization.Endocrine evaluation revealed normal baseline FSH (6.3IU/l), LH (4.4 IU/l), and 17-estradiol (20.0 pg/ml) levels,whereas total and free testosterone values were low (2.1ng/ml and 6.7 pg/ml, respectively). Serum PRL concentra-tion and thyroid function were normal. LHRH-stimulated(100 g, iv) FSH peak (10.1 IU/l) was normal, whereas LH-peak (43.0 IU/l) was elevated. Seminal cytoanalysis showedazoospermia, and peripheral lymphocyte karyotyping re-vealed a 47,XXY genotype, confirming our diagnostic sus-picion. Ultrasonographic evaluation showed a slightly de-creased testicular volume (right testis: 271316 mm; lefttestis: 291617 mm). No cardiac abnormality was ap-parent on clinical examination and echocardiographicstudy. The patient was started on testosterone enanthatereplacement therapy 100 mg im every 28 days for the first2 months and the dose schedule was gradually increasedup to 250 mg every 3 weeks.KS is the most common genetic cause of human maleinfertility. This condition is characterized by tall stature,

    narrow shoulders, broad hips, decreased upper/lowerbody segment ratio, sparse or absent body hair, de-creased muscle mass, with a feminine distribution of adi-pose tissue, including gynecomastia, mild mental retar-dation and/or behavioral problems. The testes are usu-ally small, but with androgen production from Leydigcells often in the low-normal range, whereas spermato-genesis is defective, resulting in azoospermia and infer-tility. Gonadotropin levels increase due to lack of feed-back inhibition of the pituitary gland (4). Karyotype47,XXY is the most prevalent type but, on occasion,there are other chromosomal and mosaic patterns thatrepresent variants of KS.In our case, gonadotropin and 17-estradiol levels werenormal while total and free testosterone values were

    Accepted April 9, 2009.

    First published online June 18, 2009.

    Unusual endocrine and somatic phenotypic abnormalities in a14-year-old boy with classic Klinefelter syndrome (47,XXY)

    J. Endocrinol. Invest. 32: 865-866, 2009DOI: 10.3275/6376

    2009, Editrice Kurtis


    Fig. 1 - Phenotypic features of our patient with classic Klinefel-ter syndrome.

  • Unusual abnormalities in Klinefelter syndrome


    low. Moreover, the clinical features of the patient wereunusual despite the presence of just 1 extra X chromo-some.Poor knowledge of this syndrome reflects insufficient da-ta in literature. However, an early diagnosis is important,in order to start testosterone replacement therapy, aimedat correcting the androgen deficiency, and to permit anappropriate virilization. In fact, this treatment amelioratesphysical, psychological, and social development and hasa protective effect against osteoporosis, even if an opti-mal dosage of testosterone for patients with KS remainsto be established (5).This case demonstrates that, in patients with KS, unusu-al somatic abnormalities may be associated with an in-appropriate normagonadotropic hypogonadism, and itunderlines the need to perform, in these cases, a carefulmedical and endocrinological examination, as it is veryimportant to initiate early testosterone replacement ther-apy, in order to minimize the effects of androgen defi-ciency. For this reason, primary care physicians shouldfamiliarize themselves with this condition.

    REFERENCES1. Smyth CM, Bremner WJ. Klinefelter syndrome. Arch Intern Med

    1998, 158: 1309-14.2. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelters

    syndrome. Lancet 2004, 364: 273-83.3. Klinefelter HF Jr, Reifenstein EC Jr, Albright F Jr. Syndrome char-

    acterized by gynecomastia, aspermatogenesis without a-leydigismand increased secretion of follicle-stimulating hormone. J ClinEndocrinol Metab 1942, 2: 615-27.

    4. Capell PT, Paulsen CA, Derleth D, Skoglund R, Plymate S. The ef-fect of short-term testosterone administration on serum FSH, LHand testosterone levels: evidence for selective abnormality in LHcontrol in patients with Klinefelters syndrome. J Clin EndocrinolMetab 1973, 37: 752-9.

    5. Bojesen A, Gravholt CH. Klinefelter syndrome in clinical practice.Nat Clin Pract Urol 2007, 4: 192-204.

    L. Curt1, M.F. Messina2,F. Trimarchi1, and S. Cannav1

    1Department of Medicine and Pharmacology,Unit of Endocrinology; 2Department of Pediatrics,

    University of Messina, Messina, Italy

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