The Final Height of Turner’s Patients in Algeria   

Ali El Mahdi Haddam1 , Djamila Meskine1 , Farida Chentli2 , Nora Soumeya Fedala2
1. Department of endocrinology bologhine hospital 16000
2. Department of endocrinology Bab el oued hospital
Author    Correspondence author
International Journal of Clinical Case Reports, 2015, Vol. 5, No. 20   doi: 10.5376/ijccr.2015.05.0020
Received: 18 Mar., 2015    Accepted: 03 May, 2015    Published: 22 May, 2015
© 2015 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:

Haddam et al., 2015, The Final Height of Turner’s Patients in Algeria, International Journal of Clinical Case Reports, Vol.5, No.20 1-4 (doi: 10.5376/ijccr.2015.05.0020)

Abstract

Summary Turner syndrome is the most common chromosomal abnormality in women. It is linked to the absence or abnormality of one of the two X chromosomes and characterized by short stature, gonadal dysgenesis, and a variety of dysmorphic traits and associated anomalies. . We report the results on final height in 30 patients who have reached adulthood and who have been since their diagnosis. All patients received treatment with biosynthetic growth hormone. Mean ± SD (range) age at diagnosis was 9 ± 0.19(4- 17) years. Height at diagnosis was -4.0 ± 0,1 SD below the population mean (M) and -3DS below the parental Target Height (TH). Final height was -3, 5 ± SD and -2.5 SD below M and TH respectively.

Keywords
Growth failure; Short stature; Turner syndrome; Growth hormone; Karyotype

Turner syndrome is the most common chromosomal abnormality in women. It is linked to the absence or abnormality of one of the two X chromosomes (Dyshriver, 2013). Its prevalence is 1/2 500 female births (Baena et al., 2004).

The absence of all or part of a chromosome X leads to short stature and gonadal dysgenesis, variable phenotype, and a range of associated disorders – especially cardiovascular - which may reduce the life expectancy of patients (Tauber and al 1998). The almost invariable growth failurein Turner syndrome is responsible for a reduction in adult height (Sempe et al., 1996).
Treatment with recombinant growth hormone (GHr) has shown a significant improvement in the velocity of growth and final height with varying responses according to studies and countries (Soriano-Guillen, 2005).
The objective of our study was to report the results on growth and adult height of 30 patients with Turner’s syndrome who have become adults and who have been followed at our department of endocrinology since their diagnosis.
Population, Methodology
All patients were under treatment with biosynthetic GHr (average dose 0.040mg / kg / day). The induction of puberty was done very gradually at an average age of 13. State the oestrogen induction regime used with 17β estradiol at a daily dose of about 0,2 mg orally for about 2 years;
Estrogens are then gradually increased (0.4 mg orally r 3thYea and 1 mg orally 4th year) to reach the adult replacement therapy and addition of progestogen.
For girls in puberty age at diagnosis (n: 18), the oestrogenisation was undertaken after a year and a THIRTY CHILDREN WITH TURNER SYNDROME WAS TREATED BY GHR AND FOLLOWED BETWEEN January 2OO3 and February 2015.
The mean ± (SD) (range) age at diagnosis was 9 ± 0.3 (4- 17) years, 45% of the patients being over 10 years old. 41.6% of patients had a monosomy, 50% have a mosaique. In the other cases, there were structural abnormalities of the X chromosome. A genotype phenotype correlation is observed in all cases
Bone age at diagnosis was similar to chronological age at 9 ± 0.1 years old [n=?] give number of available bone ages – or were they done in all 30 patients? (n: 22) in the other cases bone age was delayed 7 ±0’4 years old.
Hheight at diagnosis was -4 ± 0,1 SD / M and -3DS / TC. The age at initiation of treatment was 10 ± 0.1 years. Average treatment duration was 5 ± 0.1 years. The final height was -3, 5 ± SD / M and -2.5 DS / TC with a mean (range) average of 138 ± 0.2 (give range here) cm (136-144).
Eighteen girls were 13,5 years chronological average age (12.5 -18) state what this was) at the time of diagnosis. These girls received oestrogen treatment after a year and a half on average of treatment with GHr and at an average age of 15 ± 0.1 years old. What regime did the girls receive? According to a very progressive introduction of estrogen therapy (see methyodologynearly half of the patients received GHRr treatment irregulary and for an insufficient period of time (Table 1) due to financial difficulties and availability of treatment between 2003 and 2009.


Table 1 Distribution of patients according to the duration of GHr treatment


We noted some side effects: epiphysiolysis of the femoral head in two cases, a worsening of the scoliosis in one case and an advance in bone age in 7 cases. These were the younger patients and those who received the most regular treatment.
State how many patients were treated for <1 year and < 2 years stating reasons (poor compliance, financial difficulties is applicable). State if there were any adverse events.
Discussion
Short stature with growth failure is the main reason for consultation in Turner syndrome. The growth impairment is observed very early in intrauterine life and is characterized by intrauterine growth failure affecting height more than weight (Rosenberg and Tell, 1972). The postnatal deceleration in growth rate is gradual at first, with more progressive stature from the age of two years (Toublanc, 1973). The absence of puberty and thus peak pubertal growth linked to ovarian failure increases the stature deficit and spontaneous final height is an average of 136 ± 5 cm (Suwa, 1993). As for the general population, the height in girls with Turner’s syndrome is dependent on genetic factors. Depending on the country concerned, final height in Turner’s syndrome varies between 146.8 ± 5 cm in Denmark to 139.5 ± 3.5 cm in Japan (Naeraa and Nielsen, 1990). Whatever the population studied, the average final height is about 20 cm below that of the reference population (Bondy, 2007).
Treatment with growth hormone has significantly improved adult height (Stephure, 2005) (reference the Canadian study of Stephure DK; Canadian Growth Hormone Advisory Committee. Impact of growth hormone supplementation on adult height in turner syndrome: results of the Canadian randomized controlled trial, J. Clin. Endocrinol. Metab. 2005, 90: 3360-3366.
In fact, many observational studies for more than two decades have demonstrated the effectiveness of treatment with GHr on the growth rate. Therapeutic responses on growth, however, are highly variable between studies and countries (Soriano-Guillen et al., 2005) (Guyda, 1999). Several factors influence the height gain in growth hormone. Among these factors, the age of initiation of treatment, duration of treatment, the dose of GH and parental target height are the most important factors (Davenport, 2007). The age at starting GH treatment is dependent on the age of diagnosis, which remains late in our country - on average around the age of 9 to 10 years. This is explained by ignorance concerning growth problems by some practitioners and also by the lack of systematic practice of performing karyotype for any delay stature in girl due to the unavailability of this exploration at hospital and its high cost in outpatient settings.
The age at start, and the duration of treatment are important factors in optimizing adult height. If GH treatment is started before the age of 4 years old the early slow down in stature is prevented, with a significant difference from untreated children (Sas, 1999). Unavailability of regular treatment and non-payment of growth hormone until in recent years in our country are other factors that have adversely affected final height outcome. Thus, the average adult height of our patients is similar to those who had a spontaneous growth (Tauber, 1998). This is also similar to early data from Scotland but with improved outcome subsequently (Chu et al., 1997; Gault et al., 2003).
Birth size and parental target height also exert a positive influence on the final height. Indeed, a birth length and/or birth weight of +1 SD increases final adult height by 0.1 SD for the general population and 0.2 for the parental target height. The same is true for height at the start of treatment. A height SD of +1 increases the final height by 0.7 SD (Soriano-Guillen, 2005) (Rosenberg and Tell, 1972). Bone age delay alsoincreases the positive effect on the height gain but if marked may be due to autoimmune hypothyroidism which will adversely affect height outcome (El-Mansoury et al., 2005). The dosage and duration of growth hormone treatment will also after final height outcome. The use of higher doses (0.045 -0.05 mg / kg / m2) than those used in early studies has improved adult height (van Pareren, 2003). Beyond these doses, there is a plateau effect and circulating concentrations of insulin-like growth factor 1 (IGF-1) above + 2 DS (Soriano-Guillen L, 2005) (van Pareren YK, 2003) which may be undesirable (Carel, 2012) (reference Carel’s work). Furthermore many authors emphasize the treatment period before the introduction of estrogen (give references) (Ross et al., 1986; Davenport, 2007).
Randomized studies which have evaluated the influence of estrogen introduction according to age have claimed a negative impact of too early an introduction (Chernausek, 2000). In contrast, when estrogens have been introduced very slowly, with initial doses corresponding to about 10% of adult replacement doses increased very gradually, no difference was observed in terms of height gain between induction after 14-15 years old or between 12 and 13 years old (Reiter, 2001; van Pareren et al., 2003; Rosenfield, 2005; Gault et al., 2011). See work of Van Pareren and also Gault et al. 2011 (BMJ). More physiological methods of estrogen delivery such as transdermal rather than oral administration may be preferable; height gain was slightly higher (+ 0.4 SD) due to a lower dose (transdermal versus oral) in one study (Rao, 1997).
The use of oxandrolone in Turner syndrome is discussed. Indeed, the production of adrenal androgens is normal in this syndrome and, moreover, androgens must be aromatized to estrogens to act on the growth plate. High doses were used initially inducing virilisations in some cases, transient delay of breast development and bone maturation (Rosenfeld, 1992; Joss et al., 1997).
The lowest doses lower than 62.5 mg / kg / day are not associated with this type of side effect.
There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age of starting this treatment, or the optimal dose. However, in girls with TS who are severely short for age, in whom very short adult stature is anticipated, or in whom the growth rate is modest despite good compliance with GH, adjunctive treatment with Ox at a dosage of 0.03-0.05 mg/kg/day starting from the age of 8-10 years onwards can be considered (Sas et al., 2014). Although the final height patients with Turner syndrome have improved considerably with rGH, it cannot completely restore normal adult height to the uuderlying bone dysplasia of the condition, which reduces the therapeutic effects of treatment (Rappold, 2007). Growth in Turner syndrome is largely influenced by the haploidentical insufficient growth SHOX locates in Xpter-Xp22.3, pseudoautosomal common area to the X and Y chromosomes (PAR1) (Rappold, 2007). In case of deletion or mutation of this gene, the stature deficit is about 12 to 14 cm. If dyschondrosteosis frank, the prognosis is more severe with a deficit stature from 17 to 20cm (Bondy, 2007; Rappold, 2007; King, 2007)
Conclusion
Adverse outcomes in our patients are explained by the delay of diagnosis. The treatment can be effective if undertaken precociously and regularly. Systematic search of a Turner syndrome in case of girl with short stature is required. The oestrogenisation should be undertaken very gradually at adequate pubertal age.
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