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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 12 3989-3992
Copyright © 1997 by The Endocrine Society

Original Studies

Effects of Luteinizing Hormone-Releasing Hormone Analog-Induced Pubertal Delay in Growth Hormone (GH)-Deficient Children Treated with GH: Preliminary Results1

Fernando Cassorla, Verónica Mericq, Martha Eggers, Alejandra Avila, Cristian García, Ariel Fuentes, Susan R. Rose and Gordon B. Cutler, Jr.

Institute of Maternal and Child Research, University of Chile (F.C., V.M., M.E., A.A., C.G., A.F.), Santiago, Chile; and the Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health (S.R.R., G.B.C.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Fernando Cassorla, Institute of Maternal and Child Research, University of Chile, Casilla 226–3, Santiago, Chile.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
To study the effect of delaying epiphyseal fusion on the growth of GH-deficient children, we studied 14 pubertal, treatment naive, GH-deficient patients (6 girls and 8 boys) in a prospective, randomized, placebo-controlled trial. Chronological age was 14.5 ± 0.5 yr, and bone age was 11.6 ± 0.3 yr (mean ± SEM) at the beginning of the study. Patients were assigned randomly to receive GH and LH-releasing hormone (LHRH) analog (n = 8) or GH and placebo (n = 6) during 3 yr, with planned continuation of GH treatment until epiphyseal fusion. Patients were measured with a stadiometer and had serum LHRH tests, serum testosterone (boys), serum estradiol (girls), and bone age performed every 6 months.

Patients treated with GH and LHRH analog showed a clear suppression of their pituitary-gonadal axis and a marked delay in bone age progression. We observed a greater gain in height prediction in these patients than in the patients treated with GH and placebo after 3 yr of treatment (mean ± SEM, 14.0 ± 1.6 vs. 8.0 ± 2.4 cm; P < 0.05). These preliminary findings suggest that delaying epiphyseal fusion with LHRH analog in pubertal GH-deficient children treated with GH increases height prediction and may increase final height compared to treatment with GH alone.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
PATIENTS with GH deficiency may attain an adult height that is at least 2 SD below the mean after long term treatment with GH (1). The onset of puberty represents a critical problem in such patients because puberty enhances epiphyseal maturation, and this process eventually terminates linear growth. In addition, GH-deficient children can experience an attenuated pubertal growth spurt during GH therapy (2, 3). This may be due to the accelerated rate of pubertal maturation that may occur during GH therapy and that may shorten the period of pubertal growth (4).

One of the strategies to optimize GH therapy during adolescence is to delay epiphyseal fusion with a LH-releasing hormone (LHRH) analog. Administration of such analogs to children with central precocious puberty has caused a regression of their clinical signs of puberty, a slowing of their rate of bone age maturation (5), and an increase in their final height (6, 7, 8, 9). Moreover, patients with GH deficiency associated with hypogonadotropic hypogonadism have a mean final height greater than that observed in patients with isolated GH deficiency (3, 10). This suggests that delaying sex steroid exposure in these patients may enhance final height.

In this study, we have treated early pubertal children with GH deficiency with both GH and a long acting analog of LHRH. We postulate that the delay of bone maturation induced by LHRH analog prolongs the duration of growth prior to epiphyseal fusion and, thus, enhances height prognosis and ultimate height. This study has tested this hypothesis through a prospective, randomized comparison of the effects of LHRH analog and placebo in children with isolated GH deficiency. GH therapy was initiated at the beginning of the study in all patients for their underlying GH deficiency. Simultaneously, either LHRH analog or placebo was administered for a period of 3 yr to delay epiphyseal fusion in half of the patients. In this report we present data obtained during the first 3 yr of the study.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Fourteen GH-deficient early pubertal children (six girls and eight boys) were enrolled in the study (Table 1Go). Their chronological age was 14.5 ± 0.5 yr, and their bone age was 11.6 ± 0.3 yr (mean ± SEM) at the beginning of the study. Their height was at least 2.4 SD score units below the mean for age, and their mean height velocity was under 5 cm/yr. All of the children had GH deficiency, as defined by a peak GH response below 7 µg/L to separate insulin and clonidine stimulation tests. The GH stimulation tests were performed during early puberty without sex steroid priming. In addition, most patients had a low serum concentration of insulin-like growth factor I for bone age. One patient had a GH gene splice mutation. Three patients had associated TSH deficiency, which was treated with replacement doses of T4. The diagnosis of GH deficiency was made after excluding other identifiable systemic, genetic, nutritional, or psychological causes of short stature (11). At the beginning of the study, all girls were premenarchal and had up to Tanner III breast development. Boys had a maximum testicular volume of 12 cc.


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  		Table 1. Clinical characteristics of patients at study entry

 
The study was approved by the institutional review boards of the NICHHD and the University of Chile. Informed consent was obtained from at least one parent of each patient. All patients were naive to GH therapy before their participation in this study. They were started on GH therapy (Nutropin, generously donated by Genentech, South San Francisco, CA) at a dose of 0.1 U/kg·day, sc (0.27 mg/kg·week), at the beginning of this protocol, with planned continuation of treatment until epiphyseal fusion. At the same time, the patients were assigned randomly to receive either placebo or LHRH analog (Depot Lupron, generously donated by TAP Pharmaceuticals, Deerfield, IL) for 3 yr administered by a single im injection every 28 days at a dose of 300 µg/kg (12).

Patients were evaluated before entering the study and every 3 months during treatment. Every 6 months, height was measured 10 times by the same observer (A.A.) with a Harpenden stadiometer. Bone age was determined according to the method of Greulich and Pyle (13) by a single observer (C.G.), who was not aware of the patient’s treatment status, and adult height was predicted according to the Bayley-Pinneau method (13). Pubertal staging was performed by the method of Tanner (14, 15). Testicular volume was measured with a Prader orchidometer (16). One serum sample for determination of sex steroid levels was obtained at baseline (0800 h). In addition, serum was obtained for gonadotropin measurements (LH and FSH) before and 15, 30, 45, and 60 min after the iv administration of 100 µg native LHRH before starting LHRH analog therapy and every 6 months during the study. The interval between the LHRH bolus test and the previous dose of Lupron was approximately 25 days. Screening blood tests to assess metabolic, hepatic, renal, hematological, and thyroid functions were also performed at each evaluation.

Serum LH and FSH were measured in duplicate by RIA (17). Serum estradiol and testosterone were measured in duplicate by RIA as previously reported (18). Serum GH was measured in duplicate by a double antibody RIA (Diagnostic Products Corp., Los Angeles, CA). Serum insulin-like growth factor I was measured in duplicate by RIA after acid-ethanol extraction (19). Statistical analysis of the data was performed by ANOVA. Data are expressed as the mean ± SEM.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Mean chronological age, mean bone age, and mean height SD score at the beginning of the study were similar in the two groups of patients (Table 1Go). Treatment with GH and LHRH analog suppressed basal and LHRH-stimulated plasma LH and FSH levels at all times of observation compared to pretreatment levels and to the levels observed in the GH- plus placebo-treated patients (Fig. 1Go; P < 0.01). Testosterone levels in the boys were significantly lower during GH and LHRH analog treatment compared to pretreatment levels and to the levels observed in the GH- plus placebo-treated patients (Fig. 2Go; P < 0.01). We did not perform a similar statistical analysis for serum estradiol due to the small number of girls who participated in our study.



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  		Figure 1. Peak LHRH-stimulated gonadotropin serum levels before and during the study. *, P < 0.01 compared to GH plus placebo treatment.

 


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  		Figure 2. Serum testosterone levels before and during the study. *, P < 0.01 compared to GH plus placebo treatment. The multiplication factor 0.288 to convert nanomoles per L to nanograms per mL.

 
The mean breast and pubic hair stages remained relatively stable during the 3 yr of treatment with GH and LHRH analog. In the GH- plus placebo-treated subjects, breast and pubic hair stages progressed at a normal rate of approximately one Tanner stage per yr. Mean testicular volume at the beginning of the study was 8.3 ± 1.8 cc in the GH- plus LHRH analog-treated group and 10.0 ± 1.4 cc in the GH- plus placebo-treated group. Testis volume remained relatively stable throughout the 3 yr of the study in the GH- plus LHRH analog-treated patients (4.5 ± 0.6 cc at 1 yr, 5.0 ± 1.3 cc at 2 yr, and 4.3 ± 1.3 cc at 3 yr) and was significantly lower at each year of treatment compared to that in the GH plus placebo group (15.8 ± 3.4 cc at 1 yr, 20.8 ± 1.5 cc at 2 yr, and 21.8 ± 1.4 cc at 3 yr; P < 0.05).

Growth velocity increased in the GH- plus LHRH analog-treated patients from 4.7 ± 0.5 cm/yr before treatment to 8.4 ± 0.6 cm/yr at 1 yr, 5.7 ± 0.4 cm/yr at 2 yr, and 4.8 ± 0.7 cm/yr at 3 yr (P < 0.05 at 1 yr compared to pretreatment). Growth velocity increased in the GH- plus placebo-treated patients from 4.6 ± 0.2 cm/yr before treatment to 11.0 ± 1.0 cm/yr at 1 yr, 7.9 ± 1.3 cm/yr at 2 yr, and 4.0 ± 0.9 cm/yr at 3 yr (P < 0.01 at 1 yr and P < 0.05 at 2 yr compared to pretreatment). Height velocities were lower in the GH- plus LHRH analog-treated patients compared to those in the GH- plus placebo-treated patients during the first year of the study (P < 0.05). This difference may have been caused by the low sex steroid levels observed in the GH- plus LHRH analog-treated group, which probably reduced their synergistic effects with GH. In addition, height velocities were somewhat low during the third year of therapy, particularly in the GH- plus placebo-treated group, probably due to the fact that the bone ages had advanced in these patients and were approaching epiphyseal fusion.

The change in bone age relative to the change in chronological age decreased progressively in the GH- plus LHRH analog-treated patients. Thus, mean bone age progression in the GH- plus LHRH analog-treated patients was only 1.3 ± 0.3 yr during the 3 yr of GH plus LHRH analog treatment, whereas the mean bone maturation in the GH- plus placebo-treated patients was 3.5 ± 0.5 yr during the 3-yr period (P < 0.01).

Predicted adult height increased progressively in both the GH- plus placebo-treated and the GH- plus LHRH analog-treated patients during the study (Table 2Go). The increase in height prognosis was statistically different between the groups at 3 yr of treatment, when predicted adult height increased by 14.0 ± 1.6 cm in the GH- plus LHRH analog-treated group compared to 8.0 ± 2.4 cm in the GH- plus placebo-treated group (P < 0.05).


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  		Table 2. Change in predicted height (centimeters) during the study

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In view of the unsatisfactory final height exhibited by some GH children treated with classical GH therapeutic regimens (3, 20, 21, 22), different strategies have been considered to optimize growth during childhood and adolescence. A rational approach to this problem might include starting GH therapy as early as possible to optimize growth. This approach has been supported by Blethen et al., who found an inverse relationship between the age when GH is started and final height (23).

Another potential strategy to optimize growth would be to increase the dose of GH administered per kg BW to the pubertal GH-deficient patient in an attempt to mimic the physiological increment in GH concentrations that occurs during adolescence (24). A correlation between the dose of GH administered and pubertal growth velocity has been found by some investigators who have explored this strategy (2). Stanhope et al. treated 52 pubertal GH-deficient patients with either conventional GH therapy (15 U/m2·week) or an enhanced GH dose regimen (30 U/m2·week) during 4 yr (25). A faster rate of development of pubertal events was observed in the patients who received GH at twice the usual dose. This report suggests that caution should be exercised when increasing the dose of GH administered per kg BW during puberty because it may have a negative effect on final height.

Because some GH-deficient children treated with classical GH replacement regimens may exhibit a reduction in the duration of puberty (4), some investigators have attempted to prolong pubertal growth by using a LHRH analog. Both Toublanc et al. and Saggese et al. observed a small increase in predicted height after administration of LHRH analog to patients with isolated GH deficiency treated with GH (26, 27). These studies lack a placebo control group, however, and LHRH analog was employed for only 1 or 2 yr, so it is difficult to conclude whether this strategy can enhance final height.

Our study has investigated this hypothesis through a prospective, randomized, clinical trial comparing the effect of a 3-yr period of LHRH analog vs. placebo treatment on the height prognosis of pubertal GH-deficient children treated with GH. The preliminary results in the 14 patients who have completed the 3-yr treatment phase show that LHRH analog treatment decreases growth velocity in response to GH therapy, particularly during the first year of therapy. However, because this combined therapy also retards bone age advancement, it significantly increases predicted adult height by 14.0 ± 1.6 cm compared to 8.0 ± 2.4 cm (P < 0.05) after 3 yr.

Our findings are consistent with those of Burns et al. (3), Hibi et al. (10), and Frisch et al. (20), who compared the final height of GH-deficient patients who underwent spontaneous puberty with that of patients who had combined gonadotropin and GH deficiencies and, therefore, underwent a delayed, medically induced puberty. The patients with combined deficiency and delayed puberty were significantly taller (by ~8–12 cm) than patients with isolated GH deficiency who underwent an earlier, spontaneous puberty. Caution should be exercised with delaying sex steroid replacement therapy for too long, however, because it may produce deleterious clinical effects, such as psychosocial dysfunction, bone demineralization, and eunuchoid body proportions.

The increase in predicted adult height in our pubertal patients with GH deficiency treated with GH and LHRH analog is similar to the gain in predicted height after LHRH analog treatment in children with central precocious puberty (5) and in children with short stature and normally timed puberty (28). Similar results have been observed in children with central precocious puberty and GH deficiency (29) and in patients with GH deficiency and early puberty who have been treated with combined GH and LHRH analog therapy (30). However, in children with precocious puberty, approximately one third of the increase in predicted height may be lost between the conclusion of LHRH analog treatment and the attainment of final adult height (6). Thus, we suggest caution when extrapolating potential gains in predicted height to actual improvements in final height, because gains of the magnitude expected by height prediction may not be achieved.

In summary, the preliminary results of this study indicate that delay of epiphyseal fusion induced by 3 yr of LHRH analog treatment significantly increases predicted adult height in adolescents with GH deficiency treated with GH. Whether LHRH analog treatment increases final height, however, will not be known until these patients have achieved their adult height. Until such time, we recommend that LHRH analog therapy in pubertal patients with GH deficiency treated with GH be limited to an investigational setting.


   Acknowledgments
 
We are very grateful for the support of Kenneth Attie, M.D., and Neil Gesundheit, M.D., from Genentech, and of C. B. Clarke, R.N., M.A., and John Page, M.D., from TAP Pharmaceuticals, and for the expert secretarial assistance of Mrs. Nancy Zúñiga.


   Footnotes
 
1 Presented in part at the 10th International Congress of Endocrinology, San Francisco, CA, June 1996, and at the 5th Joint Meeting of the European Society for Paediatric Endocrinology, and the Lawson Wilkins Pediatric Endocrine Society, Stockholm, Sweden, June 1997. This work was supported in part by Fondecyt Grant 1940543, the NICHHD, Genentech, and TAP Pharmaceuticals. Back

Received June 12, 1997.

Revised August 12, 1997.

Accepted August 26, 1997.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Libber SM, Plotnick LP, Johanson AJ, Blizzard RM, Kwiterovich PO, Migeon CJ. 1990 Long-term follow-up of hypopituitary patients treated with human growth hormone. Medicine. 69:46–55.[Medline]
  2. Price D. 1991 Puberty in children with idiopathic growth hormone deficiency on growth hormone treatment: preliminary analysis of the data from the Kabi Pharmacia International Growth Study. Acta Pediatr Scand. 379(Suppl):117–124.
  3. Burns EC, Tanner JM, Preece MA, Cameron N. 1981 Final height and pubertal development in 55 children with idiopathic growth hormone deficiency treated for between 2 and 15 years with human growth hormone. Eur J Pediatr. 137:155–164.[Medline]
  4. Darendeliler F, Hindmarsh PC, Preece MA, Cox L, Brook CGD. 1990 Growth hormone increases rate of pubertal maturation. Acta Endocrinol (Copenh). 122:414–416.[Abstract/Free Full Text]
  5. Manasco PK, Pescovitz OH, Hill SC, et al. 1989 Six-year results of luteinizing hormone releasing hormone (LHRH) agonist treatment in children with LHRH-dependent precocious puberty. J Pediatr. 155:105–108.
  6. Oerter KE, Manasco P, Barnes KM, Jones J, Hill S, Cutler Jr GB. 1991 Adult height in precocious puberty after long-term treatment with deslorelin. J Clin Endocrinol Metab. 73:1235–1240.[Abstract]
  7. Kauli R, Kornreich L, Laron Z. 1990 Pubertal development, growth and final height in girls with sexual precocity after therapy with the GnRH analogue D-Trp 6-LHRH. Horm Res. 33:11–17.[CrossRef][Medline]
  8. Brauner R, Adan L, Malandry F, Zantleifer D. 1994 Adult height in girls with idiopathic true precocious puberty. J Clin Endocrinol Metab. 79:415–420.[Abstract]
  9. Oostdijk W, Rikken B, Schreuder S., et al. 1996 Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Arch Dis Child. 75:292–297.[Abstract]
  10. Hibi I, Tanaka T, Tanae A, et al. 1989 The influence of gonadal function and the effect of gonadal suppression treatment on final height in growth hormone (GH)-treated GH-deficient children. J Clin Endocrinol Metab. 69:221–226.[Abstract]
  11. Rose SR, Ross JL, Uriarte M, Barnes KM, Cassorla FG, Cutler Jr GB. 1988 The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency. N Engl J Med. 319:201–207.[Abstract]
  12. Parker KL, Baens-Bailon RG, Lee PA. 1991 Depot leuprolide acetate dosage for sexual precocity. J Clin Endocrinol Metab. 73:50–52.[Abstract]
  13. Greulich WW, Pyle SI. 1959 Radiographic atlas of skeletal development of the hand and wrist, 2nd ed. Stanford: Stanford University Press.
  14. Marshall WA, Tanner JM. 1969 Variations in pattern of pubertal changes in girls. Arch Dis Child. 44:291–303.
  15. Marshall WA, Tanner JM. 1970 Variations in pattern of pubertal changes in boys. Arch Dis Child. 45:13–23.
  16. Zachmann M, Prader A, Kind HP, Hafliger H, Budliger H. 1974 Testicular volume during adolescence: cross-sectional and longitudinal studies. Helv Paediatr Acta. 29:61–72.[Medline]
  17. Sir T, Devoto L. 1989 Effect of clomiphene citrate on pulsatile luteinizing hormone profile in normal women and polycystic ovary syndrome. Horm Metab Res. 21:3703–3706.
  18. Devoto L, Soto E, Magofke AM, Sierralta M. 1980 Unconjugated steroids in the fallopian tube and peripheral blood during the normal menstrual cycle. Fertil Steril. 33:613–617.[Medline]
  19. García H, Henríquez, Ugarte F, et al. 1996 GH-IGF axis during catch-up growth in small for gestational age (SGA) infants. J Pediatr Endocrinol. 9:561–567.
  20. Frisch H, Birnbacher R. 1995 Final height and pubertal developmental in children with growth hormone deficiency after long-term treatment. Horm Res. 43:132–134.[Medline]
  21. Rikken B, Massa GG, Wit JM, Dutch Growth Hormone Working Group. 1995 Final height in a large cohort of Dutch patients with growth hormone deficiency treated with growth hormone. Horm Res. 43:135–137.[Medline]
  22. Severi F. 1995 Final height in children with growth hormone deficiency. Horm Res. 43:138–140.[Medline]
  23. Blethen SL, Baptista J, Kuntze J, Foley T, LaFranchi S, Johanson A. 1997 Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. J Clin Endocrinol Metab. 82:418–420.[Abstract/Free Full Text]
  24. Rose SR, Municchi G, Barnes KM, et al. 1991 Spontaneous growth hormone secretion increases during puberty in normal girls and boys. J Clin Endocrinol Metab. 73:428–435.[Abstract]
  25. Stanhope R, Albanese A, Hindmarsh P, Brook CGD. 1992 The effects of growth hormone therapy on spontaneous sexual development. Horm Res. 38(Suppl 1):9–13.
  26. Toublanc JE, Couprie C, Garnier P, Job JC. 1989 The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency. Acta Endocrinol (Copenh). 120:795–799.[Abstract/Free Full Text]
  27. Saggese G, Cesaretto G, Andreani G, Carlotti C. 1992 Combined treatment with growth hormone and gonadotropin-releasing hormone analogue in children with isolated growth hormone deficiency. Acta Endocrinol (Copenh). 127:307–312.[Medline]
  28. Municchi G, Rose SR, Pescovitz OH, Barnes JM, Cassorla FG, Cutler Jr GB. 1993 Effect of deslorelin-induced pubertal delay on the growth of adolescents with short stature and normally timed puberty: preliminary results. J Clin Endocrinol Metab. 77:1334–1339.[Abstract]
  29. Cara JF, Kreiter ML, Rosenfield RL. 1992 Height prognosis of children with true precocious puberty and growth hormone deficiency: effect of combination therapy with gonadotropin releasing hormone agonist and growth hormone. J Pediatr. 120:709–715.[CrossRef][Medline]
  30. Adan L, Souberbielle JC, Zucker JM, Pierre-Kahn A, Kalifa C, Brauner R. 1997 Adult height in 24 patients treated for growth hormone deficiency and early puberty. J Clin Endocrinol Metab. 82:229–233.[Abstract/Free Full Text]



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