Vol. 29, No.6, June 1978 Printed in U.8A.

FERTILITY AND STERILITY Copyright

©

1978 The American Fertility Society

EVALUATION OF TESTICULAR FUNCTION IN PREPUBERTAL BOYS BY MEANS OF THE LUTEINIZING HORMONE-RELEASING HORMONE TEST*

ZVI DICKERMAN, M.D. JACOB LANDMAN, M.D. RUTH PRAGER-LEWIN, M.Sc. ZVI LARON, M.D.t Institute of Pediatric and Adolescent Endocrinology, Beilinson Medical Center, Petah Tivka, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Luteinizing hormone (LH)-releasing hormone (LH-RH) tests (50 Mlsq m intravenously) were performed in 112 prepubertal boys ages 1 3/ 12 to 11 years (mean ± standard deviation, 7 5/ 12 ± 1 6/ 12 years) suspected of having a testicular disorder because of improperly located testes (77 boys) or hypogonadism (35 boys). Four of the patients were retested within a period ranging from 6 to 16 months. Of the 112 boys tested, 17% were found to have high basal levels of follicle-stimulating hormone (FSH) and 23% were found to have an abnormally high release of FSH after LH-RH administration. Only three patients had abnormally high basal levels of LH andlor elevated LH responses to LH-RH. The basal plasma testosterone levels were found to be normal in all 112 boys. The fact that plasma FSH levels were elevated more often than LH levels suggests that the tubular elements are damaged more frequently than are the Leydig cells. The surprisingly high incidence ofan abnormal response of plasma FSH to LH-RH in boys with mobile testes calls for an increased awareness of the importance of regular examination of these patients until full puberty has been achieved. It is concluded that determination of basal plasma FSH levels and the response to LH-RH stimulation is a useful diagnostic tool for evaluating testicular function in prepubertal boys with suspected pathology of the testes.

The diagnosis of testicular dysfunction prior to puberty is difficult. Clinical examination, palpation, and estimation of testicular volume are usefup,2 but of limited value. The measurement of plasma or urinary testosterone concentrations before and after the administration of human chorionic gonadotropin, which has been given a trial by several groups of investigators, does not always expose prepubertal testicular disorders, since Leydig cell function may be preserved until adulthood even when there is tubular damage. 3-6 There have been some indications that the determination of basal plasma follicle-stimulating

hormone (FSH) levels and the response to luteinizing hormone (LH)-releasing hormone (LH-RH) might contribute to the diagnosis of such disorders. Lee et al. 7 reported elevated levels ofpasal plasma FSH due to primary hypogonadism in prepubertal boys. Studies carried out in our Institute on young children with Bloom's syndrome and hypogonadism also showed elevated basal levels of FSH as well as an abnormal response to LH-RH.8 A study was therefore carried out to obtain data on the levels of basal plasma LH and FSH and their response to LH-RH in prepubertal boys with improperly located testes and hypogonadism of various etiologies.

Received December 12, 1977; accepted January 4, 1978. *Supported in part by a grant from the Harry C. Bernard Fund (to R. P.-L.). tEstablished Investigator of the Chief Scientist's Bureau, Ministry of Health. To whom reprint requests should be addressed.

SUBJECTS AND METHODS

During the years 1974 to 1976 the LH-RH test was performed in 112 boys ages P/ 12 to 11 years

655

TABLE 1. Distribution of 112 Prepubertal Boys with Improper Location of the Testes or Hypogonadism in Whom an LH-RH Test Was Performed Group

Diagnosis

Age range

No.

Abnormal gonadotropin response to LH-RH

yr

1

2

Total

June 1978

DICKERMAN ET AL.

656

Undescended testes Bilateral Unilateral Mobile testes"

4-11 46 1t2-10

66 /12-10 1 /12

Hypogonadism 13/12-10 Idiopathic Bloom syndrome 28 /12-7 Klinfelter's syndrome 5-9 Anorchia 581t2

34 26 17

7 6

28 2 4 1

5

112

26

5

1 1 1

"Mobile testes (retractable testes): testes which at examination were palpated in the inguinal region but which could easily be pulled down into the scrotum.

(mean ± standard deviation, 75 / 12 ± 16 / 12 years) who were suspected of having a testicular disorder because of uni- or bilateral hypogonadism (i.e., a testicular volume of 1 ml or less 2 ) or improperly located testes. These boys were separated into two diagnostic groups (Table 1). Group 1 comprised 77 patients with improperly located testes. Group 2 comprised 35 patients with hypogonadism of various etiologies, with or without chromosomal abnormalities. Four patients (patients 7,11,16, and 17; see Tables 2 and 3) were tested twice within a period ranging from 6 to 16 months. Testicular volume was estimated with an orchidometer, I, 2 by comparative palpation, and by measurement with a caliper (for scrotal testes). Bone age was assessed according to the atlas of Greulich and Pyle. 9 The LH-RH test (50 p,g/sq m, given intravenously in one bolus) was performed on an outpatient basis as previously described, 10 blood being sampled before and at 15, 30, 45, 60, and 90 minutes after the LH-RH administration. Plasma LH and FSH levels were determined by a doubleantibody radioimmunoassay (RIA) method according to the technique of Midgley. 11. 12 For the hLH RIA system, LER-960 was used for iodination; the anti-hLH serum was batch no. 1 NPA. For the hFSH RIA system, LER-1366 was used for iodination; the anti-hFSH serum was batch no. 3 NPA. Results are expressed in milli-international units ofLH or FSH per milliliter of plasma, LER-907 serving as the reference preparation. The biologic potency of 1 mg is 20 IU of FSH and 48 IU of LH.I~ The results in terms of mass of

LER-907 (nanograms per milliliter) can be expressed by multiplying the concentration of LH (milli-international units per milliliter) by 20.8 and that of FSH by 50. Plasma testosterone levels were measured by a modification of the RIA method described by Weinstein et al,14 (for details see reference 10). Statistical evaluations were made by using Student's t-test. In a previous study 15 the following values for plasma testosterone, LH, and FSH in healthy prepubertal boys, before and after LH-RH administration (mean ± standard deviation), were found: basal LH, 0.5 ± 0.1 mIU/ml; peak LH, 1.3 ± 0.2 mIUlml; basal FSH, 0.6 ± 0.2 mIU/ml; peak FSH, 1.5 ± 0.5 mIU/ml; basal testosterone, 12.3 ± 5.0 ng/dl; peak testosterone, 12.5 ± 5.0 ng/dl. RESULTS

When the basal plasma LH and FSH levels and the response to LH-RH in the 112 prepubertal boys with improperly located testes or hypogonadism were compared with those of healthy prepubertal children 15 it was found that 94 boys had basal LH and FSH levels within the normal range; the LH response to LH-RH in these boys was also within normal limits.' The mean FSH response to LH-RH was slightly higher (2.1 ± 0.5 mIU/ml) than that of the controls, but the difference was not statIstically significant. Eighteen boys (17%) had elevated basal plasma FSH levels; two of them also had elevated LH levels. In 26 boys (23% ) there was an abnormal gonadotropin response to LH-RH. These boys have been evaluated in detail. The pertinent clinical data and the basal and peak plasma gonadotropin levels are shown in Table 2 and Table 3. In five of six boys with unilateral undescended testis (patients 8, 9, 10, 12, and 13), compensatory hypertrophy of the contralateral testis was found. These testes were 1.5 to 2 times the mean normal size for age. 2

Basal Levels of Plasma Gonadotropins Bilateral Undescended Testes. Thirty-three of thirty-four boys had a normal mean level of basal plasma LH (0.62 ± 0.1 mIUlml) and of plasma testosterone (11.5 ± 5.5 ng/dl). Only one patient (patient 7) had a basal LH level higher than normal, in the second of two tests which he underwent. The mean basal FSH level of four patients (patients 2, 3, 5, and 6: 1.8 ± 0.3 mIU/ml) and that of patient 7 were significantly higher (P < 0.001) than normal.

~

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~

TABLE 2. Group 1: Pertinent Clinical Data on Prepubertal Boys with Improper Location of Testes and Their Plasma Gonadotropin Responses to LH-RH Administration (50 pg/sq m Intravenously) Age at orchidopexy"

Patient

Age at LH·RH test"

Left

CA

yr

1 2 3 4 5 6

NO 4 NO NO NO 5

LH-RH test"

PlasmaFSH

Plasma LH

Basal Plasma

BA

Right

4 66/12 6 6 7 6

NP Fragment lng, 2 NP lng, 2 2

NP NP lng, 2 NP lng, 2 2

0.7 0.4 0.7 0.3 0.5 0.6 0.5 ± 0.2 2.1

1.3 1.1 6.9 1.3 1.2 1.1 ± 2.3

8.2 6.2 0.5 1.6 3.7 7.5 1.7 11.9 11.5 1.0 4.4 5.0 2.2 5.9 15.3 1.8 2.7 6.4 1.5 ± 0.6 6.1 ± 3.4 10.6 ± 5.0

1.5 1.5 4 3 3 1.5 2 3 NP

1.5 1.5 NP NP Ing

11.5 0.8 1.9 >25 0.5 1.4 1.4 0.4 0.5 2.0 2.4 0.5 2.4 0.5 0.3 1.3 0.9 3.6 0.5 ± 0.2 2.0 ± 0.8

6.8 >40 17.0 35.6 >40 15.5 4.4 7.0 0.5 1.2 5.9 7.2 6.0 0.5 3.9 4.1 10.2 1.5 0.5 3.9 11.5 4.8 8.4 1.8 2.1 5.2 17.0 1.1 ± 0.6 4.6 ± 0.7 10.0 ± 4.0

1.4 0.7 0.8 0.9 0.6 0.9 0.6 0.8 ± 0.3 2.3

1.5 1.8 0.5 1.1 0.5 0.7 1.7 1.1 ± 0.5 4.7

ml

yr

NO 6 NO NO NO 56/12

421t2 661t2 7 71°1t2 8 87/12

Left

Basal

Peak

Basal

Peak mIUlml

mIUlml

ngldl

Mean ± SD" Unilateral undescended testes

7a 7b 8 9 10 11a 11b 12 13

641t2

64/12

Scrotal Scrotal Scrotal Scrotal

NO 56 /12 NO NO

Scrotal 8

NO Scrotal

106/12 11 5 6 63/12 661t2 7 691t2 961t2

106/12 12 46/12 46/12 631t2 5 6 9112 661t2

NP NP NP 3

Mean ± SD Mobile testes 14 15 16a 16b 17a 17b 18 Mean ± SD

NO NO NO NO NO NO NO

0)

testosterone

Right

Bilateral undescended testes

Testicular volume at

~

NO NO NO NO NO NO NO

78 /12 83/12 851t2 991t2 89/12 10 98 /12

3 7 8 5 661t2 6

1.5 1.5 2 2 1.5 1.5 1.5

1.5 1.5 2 2 1.5 1.5 1.5

3.3 1.7 1.8 1.6 1.8 2.5 3.6 ± 0.8

5.6 8.0 4.4 8.7 14.0 3.4 3.9 6.0 3.5 10.0 14.0 6.1 5.8 6.0 ± 1.1 10.0 ± 3.5

aNO, Not operated. bCA, Chronologie age; BA, bone age. cNP, Not palpable; lng, inguinal. dData for patient 7, a and b, are not included in the calculation of the means ± standard deviation because of his very high gonadotropin levels, which were distinctly different from those of the rest of the group.

t.".l

Evaluation of testicular function in prepubertal boys by means of the luteinizing hormone-releasing hormone test.

Vol. 29, No.6, June 1978 Printed in U.8A. FERTILITY AND STERILITY Copyright © 1978 The American Fertility Society EVALUATION OF TESTICULAR FUNCTIO...
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