Statistics from Altmetric.com
A 46 year old man was referred to hospital by his general practitioner with abnormal bone biochemistry. He had presented with poor appetite, fatigue, myalgia, and backache. Serum calcium, corrected for albumin, was 2.63 mmol/litre (reference range, 2.12–2.62), serum phosphate was 0.85 mmol/litre (normal range, 0.7–1.4), and alkaline phosphatase was 367 IU/litre (normal range, 80–280). There was no history of previous fractures or of renal calculi. The parathormone concentration was raised at 19 pmol/litre (normal range, 1.3–7.5) and the urinary calcium to creatinine ratio was 0.375 (normal range, 0.085–0.65). Bone densitometry provided evidence of osteoporosis (T score, −3.05). Ultrasound of his neck revealed a solid lesion of low echodensity at the lower pole of the right lobe of the thyroid gland, typical of a parathyroid adenoma. At surgery the lower right parathyroid gland was excised, and confirmed by histology to be an adenoma.
At outpatients one week before elective parathyroidectomy, the patient reported that he had passed a stone from a salivary gland. He had attended hospital as an emergency two months previously and had been diagnosed as having sialadenitis of the left submandibular gland with a small calculus present in the duct. Subsequently, he became exasperated with the pain and manually forced the calculus out of the duct. There was no history of chronic infection or of other pathology to explain the presence of the calculus. The calculus weighed 2 mg and consisted of calcium phosphate (59%) and calcium oxalate (41%).
Sialolithiasis has been reported in hyperparathyroidism secondary to chronic renal failure,1 but not previously in primary hyperparathyroidism. Salivary stone formation may be promoted by the combined effects of hypercalcaemia and secretory stimulation2; the mechanism involves excessive calcium release into the acinar lumina resulting in calcium phosphate aggregates. Such calcium phosphate intermediates may transform into more stable hard deposits. Their saturation in solution varies widely, partly because of the variation in pH that occurs in saliva. As a result, some of these calcium phosphate aggregates may precipitate.
Why do salivary stones occur so much less frequently than urinary stones in hyperparathyroidism? Some ions in saliva and urine, such as citrate, inhibit the growth of precipitated crystals, whereas others, like calcium and phosphate, accelerate growth. The balance of these and other molecules might favour stone formation in urine but not in saliva. Certainly, mechanisms invoked to explain urolithiasis in hyperparathyroidism include hypercalciuria, hyperphosphaturia, and hypocitraturia. However, salivary concentrations of calcium and phosphate are also raised in primary hyperparathyroidism3; the comparative rarity of salivary stones in hyperparathyroidism probably owes more to specific salivary proteins that control mineralisation, such as statherin and proline rich protein.4 It is possible that when salivary stones develop in hyperparathyroidism, they arise via the mechanism outlined above, with alterations in the concentrations of calcium and phosphate playing a primary pathogenetic role. Such a putative similarity in the pathogenesis of sialolithiasis and nephrolithiasis would be consistent with the observed association between the two conditions. In one large series, six of 56 patients with sialolithiasis were reported to suffer from nephrolithiasis as well.5
It is impossible to estimate accurately the true extent of any putative link between hyperparathyroidism and sialolithiasis, precisely because such a link has not been widely recognised. Certainly, most patients with salivary stones are not investigated for abnormal bone biochemistry. The time honoured mnemonic has it that hyperparathyroidism and other hypercalcaemic states were classically associated with “bones, stones, abdominal moans, and psychic groans”. Although this full blown clinical presentation is rarely seen today, we suggest that it may include salivary as well as urinary stones.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.