Clinical_Rounds_in_Endocrinology_Volume_II_-_Pediatric_Endocrinology

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92. A 25-year-old male presented with primary infertility. On evaluation, he had
    eunuchoidal habitus, sparse facial hair with Tanner staging A+, P 2 and bilat-
    eral 4 ml, firm testes and stretched penile length of 8 cm. Hormonal profile
    showed serum LH 15.2 mIU/ml, FSH 40.2 mIU/ml, and testosterone 15 nmol/L.
    What to do next?
    The differential diagnoses in this young man, who presented with primary
    infertility and small testes and had normal testosterone with high gonadotro-
    pins, include androgen insensitivity syndrome, Sertoli-cell-only syndrome,
    and Klinefelter’s syndrome. The possibility of androgen insensitivity syn-
    drome (AIS) is considered in view of poor virilization and inappropriately
    elevated gonadotropin in relation to testosterone. However, the presence of
    eunuchoidal habitus, very small testes, and rise in FSH greater than LH
    excludes the diagnosis of AIS. In patients with AIS, very high LH and normal
    to high FSH with elevated testosterone are characteristic biochemical abnor-
    malities. High LH is due to loss of negative feedback as a consequence of
    impaired testosterone action; whereas, FSH is primarily regulated by inhibin
    B which is normally produced by Sertoli cells in these patients. The possibility
    of Sertoli-cell-only syndrome is also unlikely because of eunuchoidal propor-
    tions, poor virilization, and very small testes. However, the biochemical pro-
    file in patients with Sertoli-cell-only syndrome may be similar as shown in the
    index patient. The possibility of Klinefelter’s syndrome is high in the index
    patient, as he had eunuchoidal proportions, small-sized firm testes, and ele-
    vated gonadotropin with FSH greater than LH. The normal levels (low-normal
    to mid-normal) of serum testosterone in patients with Klinefelter syndrome
    are observed in 50 % of the patients as seen in the index case. It occurs as a
    result of preserved Leydig cell function during early pubertal period and
    higher SHBG levels due to relatively increased estradiol. His karyotype was
    47,XXY, thus confirming the diagnosis of Klinefelter’s syndrome.

Further Readings

1. Bhasin S, Cunningham G, Hayes F, Matsumoto A, Snyder P, Swerdloff R, et al. Testosterone
   therapy in adult men with androgen deficiency syndromes: an Endocrine Society Clinical
   Practice Guideline. J Clin Endocrinol Metab. 2006;91:1995–2010.


2. Braunstein G. Gynecomastia N Engl J Med. 2007;357:1229–37.


3. DeGroot L, Jameson J. Endocrinology. Philadelphia: Saunders/Elsevier; 2010.


4. Dunkel L, Quinton R. Transition in endocrinology: induction of puberty. Eur J Endocrinol.
   2014;170:R229–39.


5. Groth K, Skakkebek A, Host C, Gravholt C, Bojesen A. Klinefelter syndrome—a clinical
   update. J Clin Endocrinol Metab. 2013;98:20–30.


6. Harrington J, Palmert M. Distinguishing constitutional delay of growth and puberty from iso-
   lated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests. J Clin
   Endocrinol Metab. 2012;97:3056–67.


7. Melmed S, Williams R. Williams textbook of endocrinology. Philadelphia: Elsevier/Saunders;
   2011.


8. Menon PSN, Khatwa UA. The child with micropenis. Indian J Pediatr. 2000;67:455–60.

7 Delayed Puberty