Minimally symptomatic hypocalcaemia unmasking celiac disease

Introduction

We report a case of celiac disease in an adult with hypocalcaemia as the primary manifestation without any gastrointestinal symptoms.

Case presentation

A 55-year-old Caucasian male presented in the emergency department of our hospital complaining of numbness and tingling of upper extremities starting earlier that day. He also mentioned involuntary movements of his thumbs. Laboratory tests performed on an outpatient basis revealed marked hypocalcaemia, and the patient was referred to our hospital. On admission, he reported no other symptoms, including gastrointestinal complaints and weight loss.

Reviewing his medical history, anaemia, osteoporosis and hypocalcaemia were diagnosed two years ago. As a result, daily treatment with oral calcium, vitamin D and ferrum supplements was initiated along with a subcutaneous injection of denosumab, administered every six months. The patient exhibited poor compliance to the prescribed medication due to gastrointestinal side effects. Due to anaemia, lower endoscopy was performed, which revealed a tubulovillous adenoma with moderate grade dysplasia. The adenoma was resected and an endoscopy performed 15 months ago demonstrated no abnormalities.

A thorough physical examination revealed no signs of malabsorption or other remarkable findings. Body mass index was 22.5 kg/m². Signs of tetany were absent. Routine haematological and biochemical examinations demonstrated anaemia (Hb = 12.2 g/dl) normochromic, normocytic, hypoferritinaemia (8.4 ng/ml, reference values for men 22–322 ng/ml), folic acid deficiency (1.10 ng/ml, reference rate 3–20 ng/ml), hypocalcaemia (6.6 mg/dl), hypoalbuminaemia (3.2 mg/dl) and hypophosphataemia (2.0 mg/dl). Very low levels of total cholesterol (76 mg/dl), high-density (22 mg/dl) and low-density lipoprotein (44 mg/dl) were also detected. No electrocardiogram abnormalities were present, and kidney function was normal (eGFR = 105 ml/min/1.73 m²).

Further diagnostic work-up yielded increased levels of parathyroid hormone (716 pg/ml, reference rate 7–53 pg/ml) which substantiated the case of secondary hyperparathyroidism, at the same time excluding the diagnosis of hypoparathyroidism. Moreover, low levels of Vitamin D (5.1 ng/ml, reference rate 5–20 ng/ml) were detected.

According to the laboratory results, the differential diagnosis included syndromes of malabsorption. Towards that direction, celiac disease antibodies were ordered, and upper gastrointestinal endoscopy was performed. Endoscopy findings revealed gastritis and duodenitis followed by a mucosal biopsy specimen’s acquisition. The histological result revealed malabsorption syndrome stage IIIB. Anti-tissue transglutaminase IgA antibodies (anti-TGA) were found positive (174.05 U/ml, upper normal limit 10 U/ml) as well as anti-endomysial and anti-reticulin antibodies, all suggesting celiac disease. Following diagnosis, the patient received calcium gluconate infusions and then oral Vitamin D and calcium supplements. Upon discharge, the patient was put on a gluten free diet along with oral calcium, Vitamin D, folic acid and ferrum supplementation. During follow-up, calcium (9.0 mg/dl) and anaemia (Hb = 13.5 g/dl) were restored to normal levels.

Discussion

We report a case of celiac disease presenting with numbness and tingling of the upper extremities attributed to hypocalcaemia. Reviewing the literature, adult cases of hypocalcaemia-induced tetany without an alarming clinical picture (carpopedal spasm, seizures, laryngospasm) leading to the diagnosis of celiac disease are scarce.^1–3 Moreover, hypocalcaemia as the first presenting finding unmasking celiac disease is rare.^4–6

Celiac disease is an autoimmune disease characterised by small intestinal damage typically associated with loss of absorptive villi and hyperplasia of the crypts, leading to malabsorption. ⁷ Emphasis must be given on the clinical manifestations of the disease in adults ranging from common gastrointestinal symptoms like diarrhoea, abdominal pain and weight loss to completely atypical presentations including anaemia, hypocalcaemia and osteoporosis.^4,8–10 Hypocalcaemia, which was the most prominent finding in our patient, is attributed to calcium malabsorption. Normally, calcium is actively absorbed in the small intestine, primarily in the duodenum. The process is highly stimulated by the action of Vitamin D which is also not absorbed by the inflamed epithelium of patients with celiac disease.

Our patient’s history included hypocalcaemia, osteoporosis and anaemia treated with oral medical supplementation. The above findings in combination with the complementary laboratory tests indicated the diagnosis of malabsorption. The pathology results along with the serological antibody tests confirmed the diagnosis of celiac disease. The patient followed a gluten-free diet, and supplements of vitamin D, calcium, folic acid and iron were prescribed. At follow-up, our patient presented with normal lab results and most importantly complete remission of his symptoms.

In conclusion, hypocalcaemia due to malabsorption may be the sole manifestation of celiac disease. An ever-growing number of adult patients with celiac disease can present with only minor and subclinical manifestations of the disease. A high index of suspicion is needed in order to diagnose early and treat properly the atypical and asymptomatic cases.