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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 2  |  Issue : 3  |  Page : 251-256

Prevalence of short stature in juvenile hypothyroidism and the impact of treatment on various skeletal manifestation and growth velocity in a teritary care center


1 Department of Endocrinology, LLRM Medical College, Meerut, Uttar Pradesh, India
2 Department of Radiodiagnosis, SGPGI, Lucknow, Uttar Pradesh, India
3 Consultant Physican, RBI ,Kanpur, India
4 Department of Medicine, KGMU, Lucknow, India

Date of Web Publication12-Jun-2015

Correspondence Address:
Manish Gutch
D-15, LLRM Medical College, Meerut - 250 004, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2348-3334.158704

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  Abstract 

Background: Juvenile hypothyroidism is a very common problem in developing parts of world, and produces various skeletal manifestations. One of them is short stature and it is the most common reason for referral to endocrinologist. Aim and Objectives: To study the prevalence of short stature in juvenile hypothyroidism, to study the various radiological manifestations of juvenile hypothyroidism and to study the impact of treatment on growth velocity and various skeletal manifestations. Materials and Methods: Out of total nine hundred hypothyroid patients, eighty seven patients found to be of juvenile hypothyroidism were enrolled in the study those were 6-18 years of age with newly diagnosed or on follow in the endocrine clinic over a period of 1 ½ years were evaluated clinically and by laboratory tests. Serial assays of TSH, T4, and skeletal X-rays and anthropometry were done at regular interval and clinical and radiological outcome of patients were analyzed. Statistical Analysis: Data were analyzed by SPSS version 17, the P < 0.05 was considered significant. Result: The mean age of diagnosis of juvenile hypothyroidism was 11.2 years, and the females had twice the incidence than that of males, the mean TSH value was 118 ± 24.3 μIU/ml. Prevalence of short stature was found to be 45% while delayed bone age was found to be 72% in juvenile hypothyroid populations. Height SDS increased from -2.9 ± 0.9 at the start of thyroxine therapy to -1.8 ± 0.8 after 12 months (P < 0.001). Bone age SDS increased from 8.9 ± 2.5 at the start of thyroxine therapy to 10.8 ± 2.7 after 12 months. Height of velocity increased from 4.9 ± 0.8 cm/year in the year before treatment to 8.7 ± 1.3 during treatment (P < 0.001). Conclusion: The presentations of juvenile hypothyroidism may be varied; prompt recognition of the findings can lead to early and effective treatment, and improving the skeletal defects.

Keywords: Juvenile hypothyroidism, short stature, skeletal manifestations


How to cite this article:
Gutch M, Kumar S, Razi SM, Gupta A, Kumar S, Gupta KK, Singh MM. Prevalence of short stature in juvenile hypothyroidism and the impact of treatment on various skeletal manifestation and growth velocity in a teritary care center. CHRISMED J Health Res 2015;2:251-6

How to cite this URL:
Gutch M, Kumar S, Razi SM, Gupta A, Kumar S, Gupta KK, Singh MM. Prevalence of short stature in juvenile hypothyroidism and the impact of treatment on various skeletal manifestation and growth velocity in a teritary care center. CHRISMED J Health Res [serial online] 2015 [cited 2020 Aug 15];2:251-6. Available from: http://www.cjhr.org/text.asp?2015/2/3/251/158704


  Introduction Top


Short stature is a term used to describe a condition in which a child or a teen's height is well below the 3 rd percentile or 2 SD below the mean height for age and gender and when the patient's linear growth velocity diminishes to less than 4 cm/yr (child's growth shifts to a lower channel). Health related causes of impaired linear growth include diverse systemic diseases, nutritional and emotional deprivation, endocrine diseases and a wide range of dysmorphic syndromes, inborn errors of metabolism, and chromosomal abnormalities. [1],[2]

Thyroid hormone mediates growth and development of skeleton through its direct effects, as well as through permissive effects on growth hormone. [3] Thyroid hormone is of relatively little importance in the growth of the fetus, but it has significant effects on postnatal growth and bone maturation. Patients with hypothyroidism have decreased spontaneous GH secretion and blunted responses to GH provocative tests.

The classic findings of hypothyroidism in bone are all described in association with congenital hypothyroidism, where the thyroid hormone is inadequate before the formation of epiphysis. [4] There are various studies which showed the effect of congenital hypothyroidism on growing skeletal and the positive effect of thyroxine replacement on growth velocity and height. [5] But, the effects of low thyroid hormone levels on a growing skeleton, after formation of epiphysis are less well defined, and the data on these findings are scarce. [6]

Juvenile hypothyroidism constitutes one of the major treatable causes of short stature, which is frequently unrecognized and under treated in developing part of world. Hypothyroidism constitutes about 8-10% cases of short stature in the developed nations, [3] while it is a major problem in developing part of world where it constitutes 25-30% cases of short stature. [7] The exact incidence of short stature due to juvenile hypothyroidism was not well established in western U.P, and the effects of thyroxine replacement on short stature and skeletal manifestations are not reported so far in any part of world. And it is first original piece of work from western U.P. which shows the prevalence of short stature due to juvenile hypothyroidism and the impact of thyroxine replacement on short stature and various skeletal manifestations.


  Aims and Objectives Top


  1. To study the prevalence of short stature in juvenile hypothyroidism
  2. To study the various skeletal manifestations of juvenile hypothyroidism
  3. To study the impact of treatment on growth velocity and various skeletal manifestations.



  Materials and Methods Top


Children between the age groups of 6-18 years (juvenile) who were diagnosed to have hypothyroidism were studied. Only patients with antithyroid antibody positive status or fine needle aspiration cytology (FNAC) thyroid suggestive of auto immune thyroid disease were included in the study. Patients who are negative for Anti TPO are subjected to FNAC (after consent). Patients with mental retardation, congenital hypothyroid, sub acute thyroiditis, central hypothyroidism or anti thyroid peroxidase (TPO) negative patients were not included. A total of 87 patients were studied, height, weight, anthropometry, goitre (asses clinically) and the skeletal X-rays, X-ray skull lateral- view (sella), X-ray hand PA view, X-ray spine AP and lateral views, X-ray pelvis AP view and X-ray left knee AP view were taken for all the patients to study for the effects of thyroid hormone deficiency on growing skeleton. Follow up done after ensuring compliance and a normal thyroid stimulating hormone (TSH) the same X-rays were repeated at 3 month, 6 month and at 1 year, and it was determined whether the previous X-ray findings were still present or not. The X-ray was reported first by experience endocrinologist and then by radiologists, and if both agreed on a finding, it was accepted. Bone age was assessed using the Tanner Whitehouse 2 system. Delayed bone age was defined as difference of at least 24 months between chronological age and bone age. Ethical clearance for the study was taken from the institution.

Statistical Analysis

All categorical variables were expressed as percentages and all continuous variables were expressed as mean ± standard deviation. Categorical variables were compared using Fischer-Exact test and Chi square test, whichever is applicable. Continuous variables were compared using t-test and ANOVA as applicable. All P-values < 0.05 were taken as significant. Bivariate correlations were calculated using Pearson's correlation coefficient. Statistical analysis was performed by using software SPSS version 17.


  Results Top


A total of 900 hypothyroid patients were screened in the study during the study period of 1 ΍ years, 87 patients were found to have juvenile hypothyroidism based on inclusion and exclusion criteria.

[Table 1] Shows the baseline parameters of juvenile hypothyroidism patients, the mean age of diagnosis of juvenile hypothyroid patients was 11.2 ± 2.3 years, the male female ratio was found to be 1:2.22 (27 males and 60 females), the mean TSH was 118 ± 24.3 μIU/ml (range 21.6-321.8 μIU/ml) in juvenile hypothyroid patients and mean T3 and T4 were very low, anti TPO antibody positivity was found in 86.2% of study population, while FNAC positivity was found in 75.0% (12/16) of study population. The prevalence of goitre (asses clinically) in the study population was found to be 24.13% (21/87). Skeletal manifestations were found in 82.7% of study population. Bone age, height SDS, and growth velocity were found to be 8.9 ± 2.5, 2.9 ± 0.9, and 4.9 ± 0.8.
Table 1: Baseline parameters


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[Table 2] Shows the prevalence of short stature, delayed bone age and various skeletal manifestations in juvenile hypothyroid patients; prevalence of short stature was found to be 45% while delayed bone age was found to be 72% in our juvenile hypothyroid population, skeletal manifestations of hypothyroidism were predominantly found in hand and knee X-rays. The most common finding in hand was delayed bone age and dwarfism, in knee it was thickened band at metaphysis, increased intervertebral distance in vertebra, enlarged sella and wormian bones in skull.
Table 2: Skeletal manifestations of juvenile hypothyroidism


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[Table 3] shows the growth parameters and clinical characteristics of the 87 juvenile hypothyroid patients (27 boys and 60 girls) enrolled in the study. Height SDS increased from -2.9 ± 0.9 at the start of thyroxine therapy to -1.8 ± 0.8 after 12 months of therapy (P < 0.001). Bone age SDS increased from 8.9 ± 2.5 at the start of thyroxine therapy to 10.8 ± 2.7 after 12 months. Height velocity increased from 4.9 ± 0.8 cm/year in the year before treatment to 8.7 ± 1.3 during treatment (P < 0.001). Serum TSH decreased and serum T4 levels increased after treatment (P < 0.001). There were no serious adverse effects during treatment. Linear regression analysis showed that height SDS after 1 year of thyroxine treatment was negatively correlated with the bone age measured at the start of treatment (r2 = 0.934, P < 0.001).
Table 3: Evaluation of height SDS, growth velocity, and serum TSH and T4 during thyroxine replacement therapy


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[Table 4] Shows the impact of thyroxine replacement on various skeletal manifestations, post treatment, skeletal findings like delayed bone age, dwarfism, improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends.
Table 4: Impact of treatment, comparing pre - and post-treatment findings


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Goitre regressed in all patients after the follow up period of 6 months; anti TPO was not included in follow up due to financial issues.


  Discussion Top


This study is a prospective, observational study of the growth-promoting efficacy of thyroxine replacement in children with juvenile hypothyroidism. There was an obvious height gain compared with the national standards. Short stature is a general characteristic of children with juvenile hypothyroidism because thyroid hormone mediates growth and development of skeleton through its direct effects, as well as through permissive effects on growth hormone. [3] Patients with hypothyroidism have decreased spontaneous GH secretion and blunted responses to GH provocative tests. [3] This common entity-juvenile hypothyroidism is often overlooked, here, thyroid hormone becomes inadequate in childhood or adolescence, after the brain development is complete, and it is being increasingly recognized off late. Early autoimmune destruction of the thyroid gland is the commonest cause, [8] and it usually presents as delayed puberty, short stature, goitre and menses irregularity, due to the popularity of congenital hypothyroidism screening programs, the untreated congenital hypothyroid patient is now a rarity. But the entity of juvenile hypothyroidism is still prevalent in developing parts of the world. [9] Due to paucity of data the exact prevalence of juvenile hypothyroidism is not very well known. The mean age of diagnosis of juvenile hypothyroid patient was 11.2 ± 2.3 years, the male female ratio was found to be 1:2.22, the mean TSH was 118 ± 24.3 μIU/ml (range 21.6-321.8 μIU/ml) in juvenile hypothyroid patients, anti TPO antibody positivity was found in 86.2%, while FNAC positivity was found in 75.0% (12/16) of study population. The prevalence of goitre (asses clinically) and skeletal manifestations were found in 24.13% (21/87) and 82.7% in study population. Bone age, height SDS, and growth velocity were found to be 8.9 ± 2.5, 2.9 ± 0.9, and 4.9 ± 0.8.

Hypothyroidism was found to be a common form of thyroid dysfunction affecting 10.9% of the general population in India. [10] In our study the prevalence of juvenile hypothyroidism was found to be 9.3%, in total screened hypothyroid population, if we look into the study done by Unnikrishnan et al. [10] which gives the prevalence of hypothyroidism in general population, in our study the overall prevalence of juvenile hypothyroidism was found to be 1/10 of total hypothyroid population.

Several studies have reported final height data after thyroxine replacement in children with congenital hypothyroidism. [4],[5],[11] However, these studies were done on congenital hypothyroid patients; the effects of juvenile hypothyroidism on growth and effect on thyroxine replacement are very rare and mainly limited to case reports. [6],[12],[13]

Hypothyroidism is a major cause of short stature in developing part of world, where health resources are limited. In one study done by Chowdhury et al. 'Short stature in children: Experience from a tertiary care hospital in Kolkata, India'-the authors found that the incidence of hypothyroidism in short stature was 19% in male and 28% in female, while in our study the prevalence of short stature was found to be 45% in overall juvenile hypothyroid patients, and it is around 14% in males and around 31% in females. [7]

In the present study the height SDS increased from -2.9 ± 0.9 at the start of thyroxine therapy to -1.8 ± 0.8 after 12 months of therapy (P < 0.001). Bone age SDS increased from 8.9 ± 2.5 at the start of thyroxine therapy to 10.8 ± 2.7 after 12 months. Height velocity increased from 4.9 ± 0.8 cm/year in the year before treatment to 8.7 ± 1.3 during treatment (P < 0.001). Serum TSH decreased and serum T4 levels increased after treatment (P < 0.001). There were no serious adverse effects during treatment. Linear regression analysis showed that height SDS after 1 year of thyroxine treatment was negatively correlated with the bone age measured at the start of treatment (r2 = 0.934, P < 0.001). Presently, there is no large study which shows the effect of thyroxine replacement on short stature juvenile hypothyroid patients.

The importance of recognizing the various skeletal manifestations and the prevalence of short stature in juvenile hypothyroidism and impact of treatment outcome in this condition can profoundly improve the growth velocity.

When hypothyroidism is acquired during the growing age, as in juvenile hypothyroidism, the manifestations are different than congenital hypothyroidism. Skeletal maturation, defined as the appearance of secondary centers of ossification, is predominantly affected, with delayed fusion of epiphysis, and delayed bone age. The epiphyseal centers are heterogeneous with irregular ossification. But the classical stippled epiphyseal dysgenesis, described with congenital hypothyroidism, does not occur.

The prevalence, the X-ray findings of juvenile hypothyroidism and impact of thyroxin replacement on skeleton are less well defined, and the data are confined mostly to case reports. Skeletal manifestations of hypothyroidism were predominately found in hand and knee X-rays. The most common finding in hand was delayed bone age and dwarfism, in knee it was thickened band at metaphysis, increased intervertebral distance in vertebra, enlarged sella and wormian bones in skull. The various skeletal manifestations of juvenile hypothyroidism as given by Patidar [14] are summarized in [Table 2]. [14]

Post treatment, skeletal findings like delayed bone age, dwarfism, improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. The most significant impact was on advancement of bone age.

[Figure 1] and [Figure 2] hand X-rays show the advancement of bone age-mean increase in bone age was 15 months on replacement with thyroxin therapy for 6 months.
Figure 1: X-ray left wrist before thyroxine replacement, bone age 11.2 years

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Figure 2: X-ray left wrist after thyroxine replacement, bone age 12.5 years

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[Figure 3] sella X-ray shows the enlarged sella.
Figure 3: X-ray sella region showing AP diameter of 18 mm (normal 5-16 mm), vertical dimension 14 mm (normal 4-12 mm)

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[Figure 4] and [Figure 5] show X-ray left knee before and after thyroxine replacement therapy.
Figure 4: X-ray knee showing heterogeneous epiphysis with irregular ossification of growth plate (before thyroxine replacement therapy)

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Figure 5: X-ray knee (after replacement of thyroxine for 6 months) showing smooth epiphysis with regular ossification of growth plate

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  Conclusion Top


Juvenile hypothyroidism is about one-tenth as common as adult hypothyroidism, and it is one of the treatable causes of short stature. The presentations may be varied including short stature, spondylolisthesis, delayed bone age and irregular ossification of epiphysis. Prompt recognition of the findings can lead to early and effective treatment, improving the short stature and skeletal manifestations.

 
  References Top

1.
Lam WF, Hau WL, Lam TS. Evaluation of referrals for genetic investigation of short stature in Hong Kong. Chin Med J (Engl) 2002;115:607-11.  Back to cited text no. 1
    
2.
Rogol AD. Causes of short stature. In: Rose BD, editor. Up-to-date 15.1 [CD Rom]. Waltham MA: Up-to-date; 2007.  Back to cited text no. 2
    
3.
Ranke MB, Schwarze CP, Mohnike K, von Mühlendahl KE, Keller E, Willgerodt H, et al. Catch-up growth after childhood-onset substitution in primary hypothyroidism: Is it a guide towards optimal growth hormone treatment in idiopathic growth hormone deficiency? Horm Res 1998;50:264-70.  Back to cited text no. 3
    
4.
Bucher H, Prader A, Illig R. Head circumference, height, bone age and weight in 103 children with congenital hypothyroidism before and during thyroid hormone replacement. Helv Paediatr Acta 1985;40:305-16.  Back to cited text no. 4
    
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Salerno M, Micilli M, Di Maio S, Capalbo D, Ferri P, Lettiero T, et al. Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening. Eur J Endocrinol 2001;145:303-6.  Back to cited text no. 5
    
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Rivkees SA, Bode HH, Crawford JD. Long-term growth in juvenile acquired hypothyroidism: The failure to achieve normal adult stature. N Engl J Med 1988;318:599-602.  Back to cited text no. 6
    
7.
Chowdhury SP, Sarkar TK, Haldar D, Taraphdar P, Naskar TK, Sarkar GN. Short stature in children: Experience from a tertiary care hospital in Kolkata, India. The Health 2011;2:139-42.  Back to cited text no. 7
    
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Cappa M, Bizzarri C, Crea F. Autoimmune thyroid diseases in children. J Thyroid Res 2010;2011:675703.  Back to cited text no. 8
    
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Moreno-Reyes R, Boelaert M, El Badawi S, Eltom M, Vanderpas JB. Endemic juvenile hypothyroidism in a severe endemic goitre area in Sudan. Clin Endocrinol (Oxf) 1993;38:19-24.  Back to cited text no. 9
    
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Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M, Tewari N. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab 2013;17:647-52.  Back to cited text no. 10
    
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Grant DB. Growth in early treated congenital hypothyroidism. Arch Dis Child 1994;70:464-8.  Back to cited text no. 11
    
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Quintos JB, Salas M. Use of growth hormone and gonadotropin 109 releasing hormone agonist in addition to L-thyroxine to attain normal adult height in two patients with severe Hashimoto's thyroiditis. J Pediatr Endocrinol Metab 2005;18:515-21.  Back to cited text no. 12
    
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Minamitani K, Murata A, Ohnishi H, Wataki K, Yasuda T, Niimi H. Attainment of normal height in severe juvenile Hypothyroidism. Arch Dis Child 1994;70:429-31.  Back to cited text no. 13
    
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Patidar PP, Philip R, Toms A, Gupta K. Radiological manifestations of juvenile hypothyroidism. Thyroid Res Pract 2012;9:102-4.  Back to cited text no. 14
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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