NazishA.Khan* , Stephen J.Walsh** , JohnV.Tighe***
CoeliacDisease is an autoimmune disease. It affects genetically pre-disposed individuals, leading tomalabsorption of nutrients and patients presenting with a multitude of symptoms, which can sometimes go undiagnosed. We present a case where coeliac disease was identified as the cause of a giant cell tumor of hyperparathyroidism in the mandible.
Hyperparathyroidism is an interesting disease. Not only is it a disease but sometimes it may be a symptom of a deeper underlying pathology. Hyperparathyroidismand its linkwith Coeliac disease has been reported in literature, but is not commonly seen as a manifestation of Coeliac disease, therefore it is not usual to screen patients presenting with symptoms of hyperparathyroidism for Coeliac disease. Most studies have indicated a prevalence of 3 in 1000 in the general population, although one study found that it may be as high as 21 in 1000 in women aged 55-75 years . Coeliac disease is an autoimmune disease, resulting in malabsorption of nutrients and electrolytes due to modification of the intestinal mucosa upon exposure to gluten. This persistent malabsorption can lead to an imbalance of many electrolytes including calcium, which may lead to secondary hyperparathyroidism. This hyperparathyroidism may manifest itself as a giant cell granuloma (Brown Tumour) in one of the jaws, which may prompt a patient to seek help from an oral and maxillofacial surgeon. The diagnosis is oftenmade on the basis of previous history and a more definitive histopathological examination of the specimen. Mostly, upon confirming the presence of hyperparathyroidismand removing the giant cell granuloma, the role of an oral and maxillofacial surgeon may be considered to suffice. However, if hyperparathyroidism was infact a symptom and not the exact cause, then the disease would remain in its place and the patient would be at further risk of more damage. Therefore the need for appropriate referrals and further investigations to probe the exact cause of the disease is vital. This paper describes a case of a patient who presented with a giant cell granuloma, which turned out to be due to secondary hyperparathyroidism. Upon further investigations and different referrals, which went on for 7 months, the patient was finally diagnosed to be suffering fromCoeliac disease.
A 45-year-old gentleman was referred to the Maxillofacial Dept at the Queen Victoria Hospital, East Grinstead, UK with a slow growing mass in the left parasymphysis of his mandible. It had been present for 4 months. His teeth had become slightly displaced and his lower lip was numb. On examination, a 6cm mass was present in the left para symphyseal region. A biopsy revealed a giant cell granuloma with features consistent with hyperparathyroidism.
Blood biochemistry revealed, Hb- 10.7g/dl, RBC- 4.29/mcl, serumcreatinine- 132 umol/ L, serumALP- 158 IU/ L, uric acid -479 u mol/ L, serum parathyroid hormone- 118 pg/ml and total protein- 58 g/L. ACT scan was performed of the head, neck and upper thorax, which confirmed the lesion in the mandible but no other abnormality was noted particularly.A parathyroid adenoma was not visualized. An MRI was arranged targeting the thyroid area; again this failed to demonstrate any mass lesion. The mass in the mandible was surgically removed and the histopathology report confirmed it to be a benign giant cell tumor (Brown’s Tumor) of themandible. He was further referred to an endocrinologist and the metabolic medicine team. Medical evaluation revealed low vitamin D, positive coeliac antibodies, extremely low urinary calcium, normal serum calcium and phosphate and high parathyroid hormone. He also had a family history of coeliac disease and noted that eating gluten gave him severe diarrhoea and an itchy rash on the back and lower legs, which was missed by his general practitioner on routine checkups. Further referral to a gastroenterologist led to him undergoing an endoscopy and 7 duodenal biopsies, which confirmed the diagnosis of coeliac disease. He also complained of muscle aches, waddly gate and hip weakness and pains, all typical of osteomalacia. A metabolic bone density scan suggested other lesions in the skeleton similar to his jaw but smaller in size. The patient was diagnosed with coeliac disease resulting in secondary hyperparathyroidism due to malabsorption, which led to development of the lesion in the mandible. He is currently on a gluten-restricted diet and is under followup by themetabolicmedicine team.
Gluten is a protein, which is mostly found in wheat, barley and rye.Wemay not appreciate its significance, but for someone who suffers from coeliac disease, it depreciates the quality of life significantly.
In coeliac disease, gluten exposure causesmodification of the intestinal mucosa, and the immune system’s crossreaction with the bowel tissue, causing an inflammatory reaction leading to flattening of the lining of the small intestine and interfering with absorption of nutrients, as a result ofwhich the following symptomsmay arise:
.Osteoporosis (Due toCalciumMalabsorption)
The symptoms of coeliac disease are non specific and as suchmay not be a cause of attention for themedical practitioner.
However, chronically low blood calcium levels may lead to activation of the parathyroid glands and this long term increase in the level of parathyroid hormone may give rise to secondary hyperparathyroidism and the patient may present with.
The treatment of any disease depends on the presentation and severity of clinical features. At times a combined approach would be needed to treat not only the disease but also itsmanifestations.
Regular monitoring and a life long gluten free diet is the mainstay for treatment of coeliac disease. Treatment options for hyperparathyroidism however,vary. In a symptom less patient, conservativemanagement may be adopted For patients presenting with giant cell granulomas treatment is aimed towards surgical removal of the parathyroid adenoma. Correction of the endocrine status of the patient leads to spontaneous resolution of the bone lesions.
Silverman et al supported that excision of the brown tumor was not necessary when hyperparathyroidism resolved.
Severe effects of hyperparathyroidism are controlled with hemodialysis or renal transplantation and significant bone disease may be reduced by medical treatment including Vitamin D and Calcium Carbonate.
Understanding and diagnosing a diseasewith non-specific symptoms can be a real challenge and the importance of appropriate referrals cannot be over emphasized especially in such cases. If a patient presents with symptoms of hyperparathyroidism, a thorough investigation must be done to determine the cause, as hyperparathyroidism may only be a manifestation of another condition.
Many diseases occur in the human body concurrently. Some may infact lead to other diseases. Coeliac Disease is one such condition, which by its auto immune nature, modifies the intestinal mucosa of a genetically pre disposed individual and leads to malabsorption. This persistent and long-standing mal absorption may, in addition to other deficiencies, lead to the development of secondary hyperparathyroidism. Recognizing this and treating this is imperative, if relief is to be provided to the patient. Both these diseases present with vague and non-specific symptoms, but a thorough screening of the patient and appropriate referrals may offer relief. Many of these symptoms due to their nonspecific nature may go unnoticed for long periods of time. A giant cell lesion of the jaws caused by secondary hyperparathyroidism may sometimes be the first sign that may alarm the patient. A life long gluten free diet is the only treatment for Coeliac disease and where possible, surgical removal of giant cell lesions caused by secondary hyperparathyroidism may be needed. Endocrinological referrals should be made if necessary to assist with investigations. An early diagnosis is beneficial for maintenance of optimal health and avoiding complications.
1- Maida MJ, Praveen E, Crimmins SR,Swift GL. Coeliac disease and Primary hyperparathyroidism:an
association. PostgradMed J. 2006 ; 82(974):833-835.
2- Prado FO, Rosales AC, Rodrigues CI, Coletta RD , Lopes MA Brown Tumor of the Mandible associated
with secondary Hyperparathyroidism: A Case Report and Review of the Literature’, Gen Dent 2006,
3- Sauders Pocket Essentials of Clinical Medicine 3rd Edition- Ballinger A.,. S 2003
4- TriantafillidouK.,ZouloumisL.,KarakinarisG., KalimerasE., IordanidisF.-‘BrownTumors of the jaws
a s s o c i a t e d wi t h p r ima ry o r s e c o n d a r y hyperparathyroidism. ‘A clinical study and review of the literature’. American Journal of Otolaryngology Head and Neck Medicine and Surgery 2006, 27: 281- 286
5- Marx RE, Stern D.Inflammatory Reactive and infectious Diseases, fibro-osseous diseases and
systemic diseases affecting bone. In. Marx RE, Stern D, (eds) Oral and Maxillofacial pathology.A rationale for diagnosis and treatment. Carol Stream, IL: Quintessence PublishingCo, 2003, PP17-89, 739-770.
6- Silverman Jr s, Ware WHi, Gilhooly Jr C- Dental aspects of Hyperparathyroidism. Oral Surg Oral Med,
Oral Path 1968:26: 184-189