Pierre D’Amour

Normal Parathyroid Function with Decreased Bone Mineral Density in Treated Celiac Disease

Decreased bone mineral density (BMD) has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH) remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7+/-3.7 years (range 1.1 to 15.9). In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH) (3.77+/-0.88 pmol/L versus 2.28+/-0.63 pmol/L, P<0.001), which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score), patients had significantly lower BMDs of the hip (-0.60+/-0.96 SDs, P<0.05) and lumbar spine (-0.76+/-1.15 SDs, P<0.05). T scores were also decreased for the hip (-1.3+/-0.9 SDs, P<0.0001) and lumbar spine (-1.4+/-1.35 SDs, P<0.0001), with two to three patients being osteoporotic (T score less than -2.5 SDs) and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs) in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not, an important determinant of the actual bone mass of patients. Normal parathyroid function in treated patients suggests a lack of previous severe secondary hyperparathyroidism and/or complete adaptation to prior changes in parathyroid function.

Immunological evidences for post-translational control of the parathyroid function by ionized calcium in dogs.

To outline the role of post-translational events in the control of the parathyroid function in vivo, we have studied the parathyroid function of normal dogs receiving i.v. infusions of CaCl2 and Na2EDTA with intact (I), carboxylterminal (C) and midcarboxylterminal (M) iPTH assays and evaluated the influence of ionized calcium on circulating molecular forms of iPTH via alterations in C/I, M/I and M/C iPTH ratios. Furthermore, the use of the mathematical model fitting the sigmoidal relationship between ionized calcium and iPTH ratios was improved through the generation of more iPTH ratio points in the ascending part of the sigmoid function. Quantitatively, the response to hypocalcemia was highest with M (98.7 +/- 36.8 pmol/l; P < 0.0167 vs. L and P < 0.0001 vs. I) and higher with L (83.1 +/- 26.1 pmol/l; P < 0.0001 vs. I) than with I (12.1 +/- 3.2 pmol/l). Similar results were observed for the non-suppressible fraction of iPTH measured by the three iPTH assays in hypercalcemia. The slope of the sigmoid function was more acute for I than for C or M, while all three secretion set-points were similar at 1.30 mmol/l. Qualitatively, all iPTH ratios increased from hypo- to hypercalcemia, results being more pronounced for the M/I and C/I iPTH ratios (7.66 +/- 2.57 to 73.9 +/- 41.4 and 6.76 +/- 1.93 to 49.8 +/- 27.5) than for the M/C iPTH ratio (1.24 +/- 0.48 to 1.82 +/- 1.16). The slopes of the three ratios were similar as were the set-points, but in this last case, values were higher (1.40 mmol/l) than for secretion set-points. These results indicate that dog parathyroid function is similar to that of man. The lower set-points for secretion and higher ones for regulating M/I and C/I iPTH ratios favor an optimal amount of I in face of decreasing ionized calcium and permit to control the non-suppressible fraction of iPTH secretion via M and C fragments production in face of increasing ionized calcium. These events are important to understand the implication and signification of post-translational events in the parathyroid glands and in peripheral blood in the phenomenon of PTH immunoheterogeneity. They further outline that the tools used here will be useful to study similar phenomenons in individuals in face of diseased parathyroid glands.

Inhibition of l,25(OH)2D production by hypercalcemia in osteitis fibrosa cystica: influence on parathyroid hormone secretion and hungry bone disease

Primary hyperparathyroidism is usually associated with normal or elevated serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. We report a 63-year-old patient with extreme hypercalcemia (ionized serum calcium, 2.51 mmol/l; normal range, 1.19-1.36), very high serum concentrations of intact immunoreactive parathyroid hormone (iPTH) (145 pmol/l; normal range, 1-6.8), radiological lesions of osteitis fibrosa cystica, only mildly impaired renal function (creatinine clearance, 69 ml/min/m2) and very low serum levels of 1,25(OH)2D (28.8 pmol/l; normal range, 72-120). Presurgery normalization of the calcemia with normal saline, salmon calcitonin and pamidronate caused an increase in 1,25(OH)2D serum concentration to 228.3 pmol/l. A negative correlation could be established between ionized calcium and 1,25(OH)2D levels during that period (r2 = 0.80, P < 0.04). While serum calcium decreased with treatment, serum iPTH also decreased to 48.6 pmol/l, suggesting some 1,25(OH)2D inhibition of parathyroid adenoma function. Serum alkaline phosphatase also rose from 309 to 390 units/l (normal range, 25-97), suggesting the beginning of resolution of her osteitis fibrosa cystica prior to surgery. Surgical removal of a parathyroid adenoma was associated with a decrease in serum calcium and iPTH levels. To our surprise, the hypocalcemia could be managed easily with 1500 mg of oral calcium carbonate daily, even if the hungry bone disease became more active with an increase in alkaline phosphatase to 486 units/l. This was explained by the very high levels of serum 1,25(OH)2D (> 200 pmol/l) which prevailed in the postsurgery period and were probably related to decreased bone resorption and increased bone formation. This case illustrates that normalizing serum calcium prior to surgery in patients with primary hyperparathyroidism and osteitis fibrosa cystica can be highly beneficial.

Primary and Secondary Hyperparathyroidism Testing and Assays

Once considered rare disorders, primary (p) and secondary (s) hyperparathyroidism (HPT), are now frequently seen in all parts of the world in relation to the development of routine total calcium measurement and the availability of accurate parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D) assays. Both conditions can present with a very different biochemical profile, but normocalcemic primary HPT (pHPT) can also be very difficult to distinguish from mild sHPT. In the following chapter, we analyze which biochemical tests are best suited to investigate and diagnose these disorders.

Nontruncated amino-terminal parathyroid hormone overproduction in two patients with parathyroid carcinoma: a possible link to HRPT2 gene inactivation: Third/second-generation PTH ratio in parathyroid cancer

Objective  Some patients with parathyroid carcinoma present with an over‐production of nontruncated amino‐terminal (NT‐N) parathyroid hormone (PTH), a post‐transcriptionally modified form of PTH(1‐84). This is usually picked up on an elevated whole (W) PTH (third‐generation)/total (T) (second‐generation) PTH assay ratio (N > 0·8).