Short Stature, Growth Retardation
Short stature. Short stature is well described as the only symptom of CD in some older children and adolescents, and it is believed that as many as 9%–10% of those with “idiopathic” short stature have CD.20–22 In these patients, both the bone age and growth velocity are significantly impaired.20,22,23 Some patients have also demonstrated impaired growth hormone production after provocative stimulation testing.23 This value returns to normal after introduction of a GFD.24
Current Approaches to Diagnosis and Treatment of Celiac
Disease: An Evolving Spectrum
ALESSIO FASANO* and CARLO CATASSI‡
*Center for Celiac Research and Division of Pediatric Gastroenterology and Nutrition, University of Maryland, Hospital for Children, Baltimore,
Maryland; and ‡Department of Pediatrics, University of Ancona, Ancona, Italy
Another type of clinical presentation that should be considered atypical is short stature. In Europe, reports have been published which state that up to 20% of short stature is due to celiac disease. At the University of Maryland, we have a serum bank where 20 years of serum samples are stored. I took advantage of this serum bank and had my colleagues pull samples from all those children who were diagnosed with growth hormone deficiency and who were followed in the growth failure clinic. These serum samples were analyzed for IgG anti-gliadin antibody. Their medical records were examined to see what their growth pattern was. Two populations were seen: 'good growers' and 'poor growers.' The 'good growers' who responded well to growth hormone therapy, all had antibody levels within normal range. Among those who did not respond to growth hormone, a large proportion had high titers of anti-gliadin antibodies. Of those in the high antibody group who consented to undergo small intestinal biopsy, all were found to have celiac disease. Now, at the University of Maryland, children admitted for growth failure are routinely tested for anti-gliadin antibodies.
Short stature is defined as height below the 5th percentile for age. There is a standard growth curve showing a scale from 1 to 100 for each age in childhood (a simple explanation: e.g 25th percentile means that
this kid would be the the 25th in the line of 100 children starting from the shortest one). This curves provide the basis to determine whether a child is short or not. Of course there are much more parameters used
during an evaluation. A few example why a child can have short stature:
1) growth hormone deficiency
2) chronic organic disease (kidney, liver etc )
3) short only until the teenage age group when his/her height became normal
4) has familial short stature when one of the parents is short
5) has bone anomaly
6) Has celiac disease. It is known that up to10% of short children may have celiac disease.
If any child with known celiac disease does not grow and her/his
height is below the fifth percentile while is on a strict gluten-free diet
she/he should be referred to a pediatric endocrinologist for further
Karoly Horvath, M.D., Ph.D,
Center for Celiac Research
...And Let's Remember...
In the landmark prevalence study on celiac disease, investigators determined that 60% of children and 41% of
adults diagnosed during the study were asymptomatic (without any symptoms).
Only 35% of newly diagnosed patients had chronic diarrhea, dispelling the myth that diarrhea must be present to diagnose celiac disease.
Small Stature may be the ONLY symptom!
On Pub Med:
Short stature, celiac disease and growth hormone deficiency.
PMID: 20020588 Oct 2009
Short stature in children with coeliac disease.
PMID: 19550380 June 2009
Characteristic mucosal lesions on jejunal biopsy confirmed the diagnosis of celiac disease. Institution of a gluten-free diet resulted in rapid gain in weight and improvement in height velocity.
Celiac disease in a child with beta-thalassemia major: a need for improved screening and awareness.
PMID: 19131778 Dec 2008
CONCLUSION: We conclude that the prevalence of celiac disease is high in patients with ISS and it is important to test all children with ISS for celiac disease by measuring serologic markers and performing an intestinal biopsy.
PMID: 19109872 Dec 2008
...the findings emphasize the fact that CD must be considered in a child with short stature, especially if the height is more than 3 SD below the mean for sex and age, even in the absence of gastrointestinal symptoms. In conclusion, the measurement of anti-TTG antibody should be included in the diagnostic evaluation of children with short stature.
Celiac disease in children with short stature.
PMID: 18334792 Feb 2008
Conclusion: All short children should be screened for CD irrespective of gastrointestinal symptoms.
Does every short stature child need screening for celiac disease?
PMID: 18086116 Dec 2007
Celiac disease as a cause of growth retardation in childhood.
PMID: 15273508 Aug 2004
The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.
Prevalence of celiac disease in Brazilian children of short stature.
PMID: 14689044 Jan 2004
BACKGROUND: It is generally accepted that celiac disease (CD) must always be considered when dealing with growth failure in children. Therefore, it is important to develop screening tests for detecting patients that need an intestinal biopsy. CONCLUSIONS: These results indicate that zinc deficiency is an important problem in CD children with short stature; however, plasma zinc levels are not useful as a screening test for selecting patients for jejunal biopsy.
Can zinc deficiency be used as a marker for the diagnosis of celiac disease in Turkish children with short stature?
PMID: 11192528 Dec 2000
In 65 patients antiendomysium antibody and a small-intestinal biopsy were performed. Forty-three children had a normal mucosa and 22 a subtotal villous atrophy. Three coeliac children were negative for both antigliadin and antiendomysium antibodies; one further 11-year-old boy was negative only for antiendomysium antibodies. Sensitivity and specificity for antigliadin antibodies were 94.75% and 93%, respectively, and for antiendomysium antibodies 88.3% and 90.5%. Our results show that the use of antiendomysium antibodies as a confirmatory test to select patients for biopsy could result in coeliac disease going undiagnosed in adolescents.
Serological screening (antigliadin and antiendomysium antibodies) for non-overt coeliac disease in children of short stature.
PMID: 8783760 May 1996
Growth retardation may be the only clinical manifestation of undiagnosed chronic intestinal disease.
[Celiac disease as a cause of short stature in children]
PMID: 7758069 March 1995
It is generally accepted that celiac disease (CD) must always be taken into consideration when dealing with children manifesting growth failure.
Short stature as the primary manifestation of monosymptomatic celiac disease.
PMID: 1573504 Jan 1992
Eighty-seven children with short stature (height more than 2 SD below the mean for age and sex) were investigated by small intestinal biopsy. There was no obvious reason for their growth retardation found by routine examination and they had no gastrointestinal symptoms. Coeliac disease was found in two children and probable coeliac disease in two children. Although the prevalence of coeliac disease was comparatively low in this study of Swedish children with short stature, it emphasizes the fact that coeliac disease must be considered in a child with short stature even in the absence of gastrointestinal symptoms.
Coeliac disease in children of short stature without gastrointestinal symptoms.
PMID: 3769972 Aug 1986
Symptomless coeliac disease is therefore a commoner cause of short stature than is hypopituitarism;
Can antigliadin antibody detect symptomless coeliac disease in children with short stature?
PMID: 2861409 June 1985
The Authors analyze the prevalence (30,8%) of short stature in 39 coeliac patients at variable age. Height defect was especially remarkable in the subjects diagnosed after the fourth year of life. In 8 out of the studied coeliac patients, short stature was the only clinical sign at the time of diagnosis. Nevertheless, remote anamnesis revealed the existence of classical gastroenteric symptoms during the first 2 years of life. The Authors extensively report the clinical history of a coeliac girl who had been initially considered and treated as hypothyroid.
[Celiac disease and short stature]
PMID: 6531229 Jan 1984
To determine the incidence of celiac disease in a group of nonselected children with short stature, duodenal biopsy was performed in 60 unselected children with short stature (below third centile) and absence of gastrointestinal tract symptoms. Examination revealed probable celiac disease in five children (8.3%). Analysis of the results of other tests that might possibly be considered as alternatives to biopsy (e.g., xylose test, antireticulin antibodies, gastrointestinal tract symptoms in the first two years of life, bone age, serum iron, iron load, triglyceride load) led us to conclude that no test or clinical measurement could have allowed us 100% certainty in making the correct diagnosis. None of the children with celiac disease had growth hormone deficiency. We conclude that asymptomatic celiac disease represents a cause of short stature that cannot be ignored, and that only by intestinal biopsy can all such patients be identified.
Short stature and celiac disease: a relationship to consider even in patients with no gastrointestinal tract symptoms.
PMID: 6631596 Nov 1983
A case of coeliac disease associated with growth retardation and pubertal failure in a 19 year old female is reported. Diagnosis was delayed by use of the term 'undiagnosed short stature'. Investigations confirmed severe malabsorption, osteoporosis and marked delay in bone growth associated with small bowel mucosal atrophy. HLA screening of the patient's family led to the identification of coeliac disease in her brother aged 12 years and her asymptomatic mother both of whom were short in stature. The institution of a gluten free diet, appropriate vitamin and mineral supplements has restored growth and sexual development to normal in the affected children. These cases emphasize the variable nature of coeliac disease, its familial occurrence and the need to exclude the disorder in cases of undiagnosed (familial) short stature.
Familial short stature and coeliac disease: a family case report.
PMID: 6575296 Jul 1983
In this study 9 children ranging from 8 to 15 years of age affected by "short stature" not due to endocrine diseases underwent intestinal biopsy. In 5 of then a subtotal villous athrophy (STVA) has been shown and coeliac disease then diagnosed. The AA. underline the fact that in children with short stature, anamnestic and laboratoristic criteria are unreliable in suspecting the disease and stress the importance of jejunal biopsy as part of the diagnostic work-up in all cases of short stature which find any other clearcut explanations. The possibility monosymptomatic coeliac disease in the late childhood is in fact by now supported by documentary evidence.
[Detection of coeliac disease in the late childhood. Discussion on clinical presentation and diagnostic criteria.
PMID: 7343912 March 1981
Thirty-four patients with short stature of undetermined cause and no gastrointestinal symptoms underwent jejunal biopsy for exclusion of coeliac disease. Eight had subtotal or severe partial villous atrophy and seven showed a significant acceleration in height and weight velocity after the introduction of a gluten-free diet. Short stature by itself, in the complete absence of gastrointestinal symptoms, is an indication for jejunal biopsy, particularly if bone age is delayed by more than 4 years and/or there are associated haematological abnormalities.
Short stature as the primary manifestation of coeliac disease.
PMID: 6107721 Nov 1980
In 14 children and adolescents, abnormally short stature was shown to be due to celiac disease (CD) though the patients had no current gastrointestinal symptoms. Growth failure had appeared in the first years of life, and was associated with a marked lag in bone age. Subnormal growth hormone (GH) responses were demonstrated in 4 patients, and subnormal ACTH responses in 2. In 1 patient permanent isolated GH deficiency coincided with CD. A jejunal biopsy should form part of the routine diagnostic evaluation for abnormally short stature, except in patients who have had normal growth during the first year of life.
Growth failure from symptomless celiac disease. A study of 14 patients.
PMID: 216652 Dec 1978
Growth data, clinical symptoms and bone mineral parameters were analyzed in 20 children with coeliac disease in whom the diagnosis was established by biopsy at age 3-13 years. Small stature and bone age retardation (greater than 2 SD) were present in 65% and 60%, respectively. Typical clinical symptoms of coeliac disease as found in the younger child were present in many cases, but 3 were completely asymptomatic except for severe growth retardation. Metacarpal diameters and cortical thickness were significantly decreased for chronological age but in most cases normal for bone age. Quantitative bone mineral analysis of the radius by computed tomography revealed normal values for height and weight in the 4 cases investigated. It is concluded that coeliac disease should always be considered in the differential diagnosis of retarded growth and bone age. "Osteoporosis" may occur in coeliac disease, but does not necessarily accompany growth failure. The analysis of metacarpal diameters and cortical thickness in the search of "osteoporosis" may result in false interpretation if not correlated to height and weight.
Growth retardation and bone mineral status in children with coeliac disease recognized after the age of 3 years.
PMID: 216653 Dec 1978
The growth and bone maturation of 43 celiac patients were analyzed. A significant correlation between gluten intake and growth rate was found. The authors suggest this is a good parameter to advise the best moment to make the control biopsie and the provocation test.
[Growth rate and bone maturation in celiac disease
PMID: 697209 May 1978