Parathyroid adenoma with coeliac disease: primary or quaternary hyperparathyroidism?

Coeliac disease is a gluten-sensitive enteropathy of varying severity. Osteomalacia and hypocalcaemia can result from malabsorption of vitamin D and calcium, which, in turn, can lead to secondary hyperparathyroidism. If coeliac disease remains untreated for long, tertiary hyperparathyroidism can also develop through autonomy of the parathyroid glands via chronic stimulation. Primary hyperparathyroidism also has been reported in some cases of coeliac disease. We report the case of an adolescent with coeliac disease presenting with severe hypercalcaemia from a parathyroid adenoma. A 14 year-old girl was admitted to our department for delayed puberty and growth retardation. Laboratory examination revealed iron deficiency anaemia, low 25OH vitamin D level (7 ng/ml), high parathyroid hormone level (PTH) (955 pg/ml), and hypercalcaemia (13.4 mg/dl). Endoscopic biopsy was compatible with gluten enteropathy. Endomysium antibody was positive. A gluten-free diet was started. Her calcium returned to normal after excision of the parathyroid adenoma. After four months of the gluten-free diet, she began to mature, and puberty began with development of breasts and axillary-pubic hair growth. It has been suggested that autonomous four-gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation, and that this should be termed "quaternary hyperparathyroidism". More studies are required to explain the relationship between coeliac disease and hyperparathyroidism.

[Clinical and biological forms of secondary hyperparathyroidism in dialysis patients]. / Les formes cliniques et biologiques de l'hyperparathyroïdie secondaire en dialyse.

The diagnosis and treatment of hyperparathyroidism (HPT) are not yet well standardized in chronic renal failure patients. The aim of this study was to identify the main types of HPT on the basis of clinical and biological findings in a haemodialysis population. Between 2004 and 2010, all patients undergoing haemodialysis were observed and treated using the same strategy: conventional therapy with vitamin D supplements, phosphate binders, dialysate calcium adjusted to serum parathyroid hormone (PTH) level and calcitriol analogues (CA), along with regular bone marker analysis. Wherever required, cinacalcet (CC) was administered and parathyroidectomy (PTX) was performed. Of the 520 patients, 158 were classified as having HPT (30%) with a serum PTH level greater than 300 pg/mL. From this population, we identified five main types of HPT: (1) HPT with 'no bone impact' had normal or low bone marker levels (n=28, 17.7%); (2) 'secondary' HPT had elevated bone marker levels, but showed favorable response to CT (n=59, 37.7%); (3) 'tertiary' HPT was accompanied with hypercalcemia and required CC or PTX in case of CT failure (n=11, 6.9%); (4) 'mixed' HPT could not be completely treated with CT and required CC or PTX (n=57, 36%); (5) 'resistant' HPT did not show hypercalcemia, but required PTX after CT and CC failure (n=3, 1.8%). CC was prescribed in 51% cases, CA in 76%, and PTX in 7% of cases. We typified HPT on the basis of physiopathology and stages of HPT progression. Further studies on HPT that focus on bone marker levels are required to establish well-defined treatment strategies. In our study, HPT cases did not show uniform findings in Hémodialyse (HD) patients because of the variation in the stages of the disease at the time of diagnosis.

Hypothesis: the case for quaternary hyperparathyroidism.

We report the case of a young woman with hyperparathyroidism due to a large parathyroid adenoma associated with severe vitamin D deficiency. The case is noteworthy for the size of the parathyroid adenoma and for the young age at presentation, and is more typical of the presentation of hyperparathyroidism seen in developing countries where the prevalence of vitamin D deficiency is high. Vitamin D is known to have a suppressive effect on parathyroid cell proliferation and parathyroid hormone synthesis. Vitamin D deficiency may result in a compensatory increase in the secretion of parathyroid hormone (secondary hyperparathyroidism) which involves hyperplasia of all four parathyroid glands. Secondary hyperparathyroidism can become autonomous and this has been termed tertiary hyperparathyroidism, the underlying pathology of which has been variably described in the literature as adenoma formation or four gland hyperplasia. The pathogenesis of parathyroid adenoma formation in vitamin D deficiency remains unclear. It is possible that a proportion of cases represent the coincidence of primary hyperparathyroidism in patients with vitamin D deficiency. Alternatively, we hypothesise that autonomous four gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation and that this should be termed 'quaternary hyperparathyroidism'.

Reoperations for persistent and recurrent secondary hyperparathyroidism.

Forty-nine reoperations for persistent or recurrent secondary hyperparathyroidism (HPT) in 30 patients are reported. The patients are part of a total of 184 patients operated on for secondary HPT; 28 reoperations in 18 patients were performed in the neck or in the upper mediastinum for remaining glands. Eleven reoperations at the forearm autograft revealed hyperplasia of the grafted tissue as the reason for recurrent disease in seven patients; they were treated by excision of all grossly enlarged particles. Ten patients received autologous cryopreserved tissue because of permanent postoperative hypoparathyroidism. The rate of graft-dependent recurrent HPT was 7%, and inadequate graft function was found in 6% of the patients.