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The growth data for individual patients are presented in the Appendix. Results for groups of patients are expressed in this chapter as mean values, with the ranges in brackets, unless otherwise stated. To assess the effect of both GH insufficiency and LCH on growth, the patients were divided into 2 groups based on GH status. Patients with GH insufficiency (GHI) were called Group 1(n = 13). Patients without GH insufficiency (non-GHI) were classified as Group 2 (n =27). Each group was further subdivided into

a: patients who have completed growth/attained final stature (la n=12, 2 a n = 13) b: patients who have not yet attained final stature (1b n=1, 2b n = 14)

Group 1. Patients with GH insufficiency

The growth data for the 13 patients with GHI, all but one (pt 27) of whom have completed their growth, are shown in Tables 3.5 and 3.6. The mean age at diagnosis of LCH was 4.35 years, median age was 2.9 yrs (0.1 to 16.9 years). The height SDS at diagnosis of LCH was -0 .8 7 (-2.7 to 2.2). The age at diagnosis of GHI was 9.7 years (4.7 to 18 years). The height SDS at diagnosis of GHI was -2 .2 (-4.5 to - 0.1). Following treatment with GH, all patients showed catch-up growth with increased height velocity and an improvement in height SDS.

Short and long term response to GH therapy: The mean growth velocity SDS increased from -2.1 (-5.5 to 1.2) to 3.9 (-3 to 8.6) after 1 year of therapy [p<0.001]. The mean final height SDS was -0 .8 5 (-2.4 to 1.4) which was significantly greater than pre-treatment height SDS [p = 0.012]. However, final stature remained significantly below the mid-parental target height; 163.3 cm (148.9 to 181.1) vs 169.2 cm (159 to 183.7) [p <0.05]. Target height SDS was -0 .1 4 (-1.2 to 0.89). The height SDS for patients in Group la at diagnosis of LCH, at diagnosis of GHI and at final height are compared to the target height SDS in Fig. 3.3. The comparison of final height to target height for individual patients in Group la is shown in Fig. 3.5.

Group 2a. Patients without GH insufficiency who have completed growth Thirteen patients who do not have GHI have reached their final height. Their growth data is shown in Table 3.7. The mean age at diagnosis of LCH was 3.31 years, median age 1.6 yrs (0.6 to 11.2 years). Height SDS at diagnosis of LCH was -1 .2 (-3.3 to 0.57). Mean final height SDS was -0.68 (-3.5 to 1.4). Final stature remained below mid-parental target height; 165.2 cm (140.6 to 183.3) vs 168.3cm (155.5 to 183.5). Target height SDS was -0 .2 8 (-1.38 to 1,46).

The comparison of height SDS at diagnosis of LCH and at final height with target height SDS is shown in Fig. 3.4. The comparison of final height versus target height for individual patients is shown in Fig. 3.6. There was no significant difference in final height between the GH insufficient and non- GH insufficient patients -163. 3 cm (148.9 to 181.1) vs 165.2 cm (140.6 to 183.3).

Group 2b. Patients without GH insufficiency who have not completed growth Fourteen patients who are GH sufficient have not yet reached final height. Their growth data are shown in Table 3.8. Mean age at diagnosis of LCH for this group was 1.6 yrs, median age 1.3 years (0.4 to 3.8 years). Mean height SDS at diagnosis of LCH was -0.61 (-2.08 to 1.13). Height SDS at the last visit was -0 .33 (-2.0 to 1.59). Target height SDS was -0.31 (-1.29 to 1.68). (Fig. 3.7)

Figure 3.3. Growth of patients with GH insufficiency (Group 1a)

Ht SDS at diag LCH

Final Ht SDS

Ht SDS at diag GHI

Target Ht SDS

This graph depicts the growth of patients (n=12) with growth hormone insufficiency (GHI) who have reached their final height. The box plot compares the height standard deviation score (SDS) at diagnosis of LCH, at diagnosis of GHI, and at final height in these patients with their target height SDS based on parental heights. The graph shows the median, the interquartile range, and outlier for height SDS. The mean final height SDS was significantly greater than pre-treatment height SDS [p = 0.012] but, final stature remained significantly below the mid- parental target [p <0.05].

Figure 3.4. Patients without GHI who have completed growth

(Group 2a)

H t SDS at diag LCH

Final Ht SDS

Target H t SDS

This graph depicts the growth of patients (n=13) without growth hormone insufficiency who have reached their final height. The box plot compares the height standard deviation score (SDS) at diagnosis of LCH and at final height in these patients with their target height SDS based on parental heights. The graph shows the median and the interquartile range for height SDS. There was no statistically significant difference between final height and target height.

Figure 3.5. Final height versus target height in patients with GHi

This scatter plot compares the final height of each patient with GH insufficiency (on the Y axis) with their target height (on the X axis). The line of equivalence is drawn, and shows that 10 of 12 patients in this group lie below the line i.e. have not attained the expected height.

200 190 180 170 •5? 150 IT 140 160 170 180 200 140 150 190 Target height in cms

Figure 3.6. Final height versus target height in patients without GHi

This scatter plot compares the final height of each patient without GH insufficiency (on the Y axis) with their target height (on the X axis). Compared to Fig. 3.5 there is more even scatter around the line of equivalence showing that although 6 of 12 patients have not attained the expected height, their final height is closer to the target height than the patients with GHI.

200 190 180 170 iZ 140 140 150 160 170 180 190 200

Figure 3.7. Patients without GHI who have not completed growth

(Group 2b)

Ht SDS at diag LCH

target Ht SDS

HT SDS at assessment

This graph depicts the growth of patients (n=14) without growth hormone insufficiency who have not yet reached their final height. The box plot compares the height standard deviation score (SDS) at diagnosis of LCH and at last assessment in these patients with their target height SDS based on parental heights. The graph shows the median and the interquartile range for height SDS. There was no statistically significant difference between height at assessment and target height.

o th er anterior pituitary deficiencies: Six patients have multiple anterior pituitary hormone deficiencies. Three (Pts. No 4, 29, 32) have panhypopituitarism and are on replacement therapy with thyroxine, hydrocortisone and the appropriate gonadal hormone. One patient (Pt. No. 21) has GHI and gonadotrophin deficiency, while two others (Pts. No 33, 40) also have secondary hypothyroidism. These results are included in Tabie 3.3.

Pubertal development: All patients with panhypopituitarism (n=3), or gonadotrophin deficiency in addition to GHI (n=2), required induction of puberty with the appropriate gonadal hormone and remain on replacement therapy. Patient no 29. developed LCH after the onset of normal puberty. He then demonstrated regression in pubertal development and required testosterone supplements. One boy with GH insufficiency (Pt No.27) had “constitutional delay” in the onset of puberty, which responded to a six-month course of testosterone supplements. Since stopping the testosterone injections he has continued to progress in puberty. Pt. No. 26, a male, had a relatively early onset of puberty (Tanner genitalia stage 3 at age 11 yrs). As this was associated with abnormal aggressive behaviour, requiring admission to a child psychiatry unit, he was treated with a gonadotrophin releasing hormone (GnRH) analogue (leuprorelin) for 20 months. The treatment resulted in regression of puberty and an improvement in behaviour. Following discontinuation of the GnRH analogue he continued to progress through puberty normally. All the other patients with GHI had normal pubertal development. Of the patients who do not have anterior pituitary dysfunction 8 were prepubertal at the time of assessment, 6 have had normal onset and progress of puberty, while 13 have completed pubertal development.