celiac disease

Short Stature and Failure to Thrive— Is It Celiac Disease?

Mayo Clinic

Dr Absah is a pediatric gastroenterology and hepatology fellow in the division of pediatric gastroenterology and hepatology at Mayo Clinic College of Medicine in Rochester, Minn. Financial disclosure: None.

A 4 ½-year-old white girl with short stature, a long history of failure to thrive, and suspected refractory celiac disease presented for a presurgical evaluation before placement of a gastrostomy tube.

History. The child was born at full term with a birth weight of 3.2 kg. At age 2 months, her length and weight were at the 25th percentile and head circumference was at the 97th percentile. Her weight and length decelerated and were below the 3rd percentile at age 9 months (Figure 1). However, no workup was done.

chart - deceleration of growth

At age 2 years, she was hospitalized because of rotavirus infection. Significant growth retardation was noted. An extensive evaluation at that time included the following studies: complete blood cell (CBC) count, electrolyte levels (including calcium and phosphorus), thyroid-stimulating hormone (TSH), free thyroxine (FT4), parathyroid hormone; 25-hydroxy vitamin D, bone age, karyotype, and liver function tests. Results were normal except for alkaline phosphatase (ALP), which was 1407 U/L (range, 134 to 346 U/L). Her random growth hormone (GH) level was also normal; however, insulin-like growth factor 1 (IGF-1) was 25 ng/mL (range, 34 to 238 ng/mL). Celiac disease serology of anti-tissue transglutaminase (anti-TG2) IgA was 149 units (normal, < 20 units) with normal serum IgA at 68 mg/dL. The patient’s poor growth and low IGF-1 level were attributed to celiac disease, and a gluten-free diet was initiated.

After 2 years, the child’s height and weight remained below the 3rd percentile, with head circumference at the 75th percentile (Figure 2). Refractory celiac disease was considered, and corticosteroid treatment with gastrostomy tube placement was recommended. The parents requested a second opinion before the surgery.

Workup. Repeated serologies showed a normal serum IgA of 88 mg/dL and an anti-TG2 of less than 1.2 (normal, < 4); celiac HLA gene testing was positive for HLA DQ2. CBC count and TSH, FT4, electrolyte, AST, and ALT levels were normal. ALP was 61 U/L. Random serum GH was 0.12 ng/mL (range, 0.01 to 3.61 ng/mL) and IGF-1 was less than 25 ng/mL.

The majority of patients with celiac disease (92% to 96%) carry the HLA DQ2 gene, and most of the rest (6% to 8%) carry HLA DQ8, which gives the test very high negative predictive value. The results can be useful in excluding celiac disease in cases in which histology is not pathognomonic, or the diagnosis is in doubt. On the other hand, 30% to 40% of white patients carry either HLA DQ2 or HLA DQ8, but celiac disease will develop in only 1%. Although having the right gene makes the patient susceptible, it is not enough to cause celiac disease.

This patient had negative celiac serological titers and persistent failure to thrive despite adhering to a strict gluten-free diet. This suggested that an endocrine etiology rather than celiac disease was the true cause of her persistent failure to thrive. MRI of the brain showed an area of T1 hyperintensity in the upper pituitary stalk and hypoplastic pituitary stalk and gland, with absence of the posterior pituitary bright spot (Figure 3). Findings were consistent with posterior pituitary gland ectopia.

Results of a GH stimulation test confirmed the deficiency, and replacement therapy was started.

chart - head circumference and weight

Figure 2 – The patient’s head circumference, measured at age 4 months, 9 months, 12 months, 17 months, and 24 months, remained in the 75th percentile.


There have been many reports of GH deficiency in association with posterior pituitary gland ectopia. There is no clear etiology for the condition; data suggest a pathogenesis similar to that of septo-optic dysplasia.1,2 Possible theories are defective neuronal migration during embryogenesis and transection of the pituitary stalk followed by hypertrophy of the proximal axons with subsequent reorganization. Whatever the origin,
releasing factors of the hypothalamus only reach the anterior pituitary lobe via general circulation. This results in frequent GH deficiency and, in some instances, panhypopituitarism.3

Diagnosis is usually made by brain MRI that shows high T1 signal at the median eminence (floor of the third ventricle) and absent normal posterior pituitary bright spot.4

No treatment is required for the ectopic pituitary per se, but the frequently associated GH deficiency, or less frequently panhypopituitarism, is managed with replacement therapy.

MRI pituitary gland


A child with celiac disease or other form of malnutrition typically has a drop-off in weight first followed by a drop-off in height later. This child seemed to have a length drop-off first, and the weight for height looked relatively normal. In addition, the child’s parents were not short (mother’s height was 158 cm and father’s height was 176 cm). Thus, the child’s growth curve suggested short stature due to an endocrine problem rather than a malnutrition problem, and referral to a pediatric endocrinologist was warranted at 9 months.

If the patient’s parents were of short stature, familial short stature would be another consideration. However, in this case, MRI revealed posterior pituitary ectopia, which led to the correct diagnosis of GH deficiency.