International Journal of Urology

(2002)

9,

604–606

Case Report

Blackwell Science, LtdOxford, UKIJU

International Journal of Urology0919-81722002 Blackwell Science Asia Pty Ltd

910October 2002522

Idiopathic hypogonadotropic hypogonadismT Kobayashi

et al.

10.1046/j.0919-8172.2002.00522.xCase Report604606BEES SGML

Correspondence: Osamu Ogawa, Professor and Chairman,Department of Urology, Graduate School of Medicine,Kyoto University, Shogoinkawahara-cho 54, Sakyo-ku,Kyoto 606-8507, Japan. Email: ogawao@kuhp.kyoto-u.ac.jp

Received 23 January 2002; accepted 8 April 2002.

Adult-onset idiopathic hypogonadotropic hypogonadism presented with erectile and ejaculatory disorder

TAKASHI KOBAYASHI,

1

HIROSHI OKUNO,

1

HIROYUKI NISHIYAMA,

1

EIJIRO NAKAMURA,

1

OSAMU OGAWA,

1

MASAHIRO KAWAHARA

2

AND AKIRA SHIMATSU

3

Departments of

1

Urology and

2

Medicine and Clinical Science, Graduate School of Medicine, Kyoto University and

3

Clinical Research Institute, Kyoto National Hospital, Kyoto, Japan

Abstract

A 37-year-old man who had fathered a child five years previously presented with erectile and ejac-ulatory disorder. Endocrinological examinations revealed isolated luteinizing hormone-releasinghormone (LHRH) deficiency of hypothalamus, resulting in hypogonadotropic hypogonadism, and nocausative abnormality was detected in imaging studies, including magnetic resonance imaging(MRI). Having a diagnosis of adult-onset hypogonadotropic hypogonadism, the patient receivedpulsatile subcutaneous administration of gonadotropin-releasing hormone (GnRH). Sperm analysisand serum level of testosterone improved to normal in a few months. His wife became pregnant usingartificial insemination with her husband’s semen 15 months after the beginning of the treatment.

Key words

adult-onset, erectile dysfunction, hypogonadotropic hypogonadism.

Introduction

We report a case of adult-onset idiopathic hypogonado-tropic hypogonadism (IHH) arising in a sexually matureman. Adult-onset IHH is a rare form of HH withunknown etiology that develops after puberty, whichusually presents with loss of libido or infertility at theonset.

1

The case we report here presented with erectileand ejaculatory dysfunction as chief complaints at theinitial presentation.

Case report

A 37-year-old man presented with erectile dysfunctionand dry ejaculation. He had fathered a child five yearspreviously but had been unable to father any childrensince. There was no history of mental, physical, or

pubertal development retardation and no episode ofanosmia, cryptorchidism, head injury, granulomatousdisease such as tuberculosis, excessive exercise, expo-sure to chemicals, or drug abuse. He had no family his-tory of male or female infertility.

Physical examination revealed bilateral hypotrophictestes (10 mL in volume each), loss of axillary hair, andnormal pubic hair. Blood tests revealed very low levelsof serum testosterone (less than 20 ng/dL), luteinizinghormone (LH, less than 0.5 mU/mL), and follicle-stimulating hormone (FSH, 1.5 mU/mL), and normallevels of the other pituitary hormones including prolac-tin, growth hormone (GH), adrenocorticotropic hor-mone (ACTH), thyroid-stimulating hormone, as well asferritin and iron. Head X-ray, computed tomography(CT), and magnetic resonance imaging (MRI) revealedno abnormalities including the sella turcica, hypophysisand hypothalamus.

Based on an initial diagnosis of adult-onset idio-pathic hypogonadotropic hypogonadism, the patientunderwent endocrinological loading tests. Multipleloading tests including growth hormone-releasinghormone, corticotropin-releasing hormone, andthyrotropin-releasing hormone revealed the promptreaction of pituitary hormones to the releasingfactors. Insulin-induced hypoglycemia showed normal

Idiopathic hypogonadotropic hypogonadism 605

responses of ACTH and GH. Gonadotropin-releasinghormone (GnRH) loading test showed decreasedresponses of LH and FSH. Repetitive GnRH loadingtest (400

m

g/day for 5 consecutive days) showedstronger and more stable responses in both LH andFSH.

Pulsatile subcutaneous administration of 10

m

g ofGnRH every 2 h with a portable intermittent injectionpump (NIPRO SP-3I; Osaka, Japan) was started, andthis resulted in the recurrence of erection and ejacula-tion in a few months. Semen analysis including semenvolume, sperm count, and sperm motility were normal-ized 6 months after the beginning of the treatment(Fig. 1). His wife became pregnant using artificialinsemination with her husband’s semen 15 months afterthe beginning of the treatment.

Discussion

Adult-onset idiopathic hypogonadotropic hypogo-nadism (IHH) was first categorized in 1997 byNaghtigall

et al

.

1

and described in 10 patients. Its diag-nosis is established by endocrinological examinationsdemonstrating castrated level of testosterone with sup-pression of gonadotropin release in response to GnRHadministration, as well as by detailed history and imag-ing studies to rule out causative factors for defects in

GnRH release. In the present case, endocrinologicalexaminations and clinical history revealed IHH withnormal pubertal development and fertility, indicatingadult-onset IHH.

Adult-onset IHH is an extremely rare endocrinolog-ical disorder, and, to our knowledge, there has beenno report of adult-onset IHH since Naghtigall

et al

.

1

classified this form of IHH. Although its epidemiologyand etiology is still unclear due to the limited numberof reports, all cases including ours presented goodresponse to GnRH administration, indicating thatadult-onset IHH is a hypothalamic disorder. In women,secondary hypothalamic amenorrhea is common, andit is often associated with drug abuse and alcoholabuse, excessive exercise, malnutrition and psychogenicstress. In this regard, none of these factors were identi-fied in the present case, suggesting that the etiology ofmale adult-onset IHH and female secondary hypothal-amic amenorrhea may be different.

In female secondary hypothalamic amenorrhea,despite obvious subjective abnormalities such as amen-orrhea, it is disappointingly infrequent for patients toseek medical advice.

2

In male adult-onset IHH, on theother hand, the lack of obvious and critical symptomsmakes their medical contact more infrequent thanfemales, which might strongly bias the low prevalenceof male adult-onset IHH. In this regard, the increasingincidence of erectile dysfunction in outpatient clinics

3

Fig. 1

Serum level of luteinizinghormone (LH), follicle-stimulatinghormone (FSH), and testosteronewere traced. The parameters wereimproved with pulsatile GnRHadministration. Erectile and ejacula-tory function recurred at 1 month,and the patient’s wife becamepregnant at 15 months after thebeginning of the treatment. (

�

)Testosterone; (

�

) FSH; (

�

) LH.*Aspermia; **Azoospermia. Pre-treatment 1 month 4 months 6 months 12 months

Testicular vol. rt.(mL) lt.Erection Ejaculation Sperm countMobility

1010--

AS*AS

1010++

AZ**AZ

1012++

23 ¥ 106

43%

1212++

29 ¥ 106

70%

40 400

0 0

1212++

68 ¥ 106

64%

30

20

10

300

200

100

Testosterone

FSH

LH

LH

-FSH

(m

U/m

L)

Tes

tost

eron

e (n

g/m

L)

606 T Kobayashi

et al

.

will make the clinical recognition of adult-onset IHHmore important.

The diagnosis of adult-onset IHH, like IHH, is veryimportant, because both are treatable with administra-tion of GnRH or human chorionic gonadotropin.

1,4,5

Todate, pulsatile GnRH injection with a portable pumpseems feasible, because it has less side-effects and ismore effective than gonadotropin therapy.

6

On the otherhand, the pulsatile GnRH injection needs technicalunderstanding of its management. In the present case,GnRH administration was selected, because the patienthad good compliance for the management of the pulsa-tile infusion therapy.

In conclusion, endocrinological examinations shouldbe performed in patients who present with erectile dys-function to rule out this treatable form of IHH, even ifnormal pubertal development and no causes of second-ary IHH are documented.

References

1 Naghtigall LB, Boepple PA, Pralong FP

et al.

Adult-onset idiopathic hypogonadotropic hypogonadism: Atreatable form of male infertility.

N. Engl. J. Med.

1997;

336

: 410–5.2 Munster K, Helm P, Schmidt L. Secondary amenorrhea:

prevalence and medical contact—a cross-sectional studyfrom a Danish country.

Br. J. Obstet. Gynaecol.

1992;

99

: 430–3.4 Sadovsky R. Integrating erectile dysfunction treatment

into primary care practice.

Am. J. Med.

2000;

109

(Suppl. 9A): 22S–30S.5 Finkel DM, Phillips JL, Snyder PJ. Stimulation of sper-

matogenesis by gonadotropins in men with hypogona-dotropic hypogonadism.

N. Engl. J. Med.

1985;

313

: 651.6 Schopohl J, Eversmann T, Mehltretter G

et al.

Compar-ison of gonadotropin-releasing hormone and gona-dotropin therapy in male patients with idiopathichypothalamic hypogonadism.

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56

:1143–50.