Reversible Resistance to the Renal Action of Parathyroid Hormone in Human Vitamin D Deficiency

1982 ◽  
Vol 62 (4) ◽  
pp. 381-387 ◽  
Author(s):  
I. G. Lewin ◽  
S. E. Papapoulos ◽  
G. N. Hendy ◽  
S. Tomlinson ◽  
J. L. H. O'riordan

1. The response to exogenous parathyroid hormone (PTH) was tested in normal subjects and patients with osteomalacia due to vitamin D deficiency; 200 MRC units of bovine PTH were administered intravenously. 2. The rise in plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) and the increase in urinary excretion of cyclic AMP were reduced in the patients with vitamin D deficiency. After treatment with vitamin D the responses returned to normal. 3. It is suggested that this reversible resistance is due to the secondary hyperparathyroidism associated with vitamin D deficiency.

2019 ◽  
Vol 160 (4) ◽  
pp. 612-615 ◽  
Author(s):  
Bradley R. Lawson ◽  
Andrew M. Hinson ◽  
Jacob C. Lucas ◽  
Donald L. Bodenner ◽  
Brendan C. Stack

Objective To quantify how frequently intraoperative parathyroid hormone levels increase during thyroid surgery and to explore a possible relationship between secondary hyperparathyroidism due to vitamin D deficiency and elevation in intraoperative parathyroid hormone. Study Design Case series with chart review. Setting Tertiary academic center. Subjects and Methods A total of 428 consecutive patients undergoing completion and total thyroidectomy by the senior author over a 7-year period were included for analysis. All patients had baseline and postexcision intraoperative parathyroid hormone levels as well as vitamin D levels from the same laboratory. Institute of Medicine criteria were employed for vitamin D stratification (>30, normal; 20-29.9, insufficient; <20, deficient) . Other data analyzed include sex, age, neck dissection status, and parathyroid autotransplantation. Results A total of 118 patients (27.6%) had an intraoperative parathyroid hormone elevation above baseline. Patients with vitamin D deficiency were significantly more likely to experience hormone elevation ( P = .04). When parathyroid hormone rose, it did so by a mean 32.1 pg/mL. Patients with vitamin D deficiency demonstrated significantly larger hormone increases ( P = .03). Conclusion Elevation in intraoperative parathyroid hormone levels above baseline after completion and total thyroidectomy occurs in over one-fourth of cases and is significantly associated with vitamin D deficiency. This study is the first to report this observation. We hypothesize that vitamin D deficiency in these patients may create a subclinical secondary hyperparathyroidism that leads to intraoperative parathyroid hormone elevation when the glands are manipulated. Additional studies will be needed to explore this physiologic mechanism and its clinical significance.


2008 ◽  
Vol 35 (11) ◽  
pp. 2201-2205 ◽  
Author(s):  
YOLANDA BRAUN-MOSCOVICI ◽  
DANIEL E. FURST ◽  
DORON MARKOVITS ◽  
ALEXANDER ROZIN ◽  
PHILIP J. CLEMENTS ◽  
...  

ObjectiveSclerodactyly with acroosteolysis (AO) and calcinosis are prominent features of systemic sclerosis (SSc), but the pathogenesis of these findings is poorly understood. Vitamin D and parathyroid hormone (PTH) have a crucial role in bone metabolism and resorption and may affect AO and calcinosis. We assessed vitamin D and PTH in patients with SSc.MethodsMedical records of 134 consecutive patients with SSc (American College of Rheumatology criteria) followed at the rheumatology department during the years 2003–2006 were reviewed for clinical assessment, laboratory evaluation [including 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, PTH, creatinine, and albumin]; imaging data confirming AO and/or calcinosis. Patients followed routinely at least once a year were included (81 patients). Of these, 60 patients’ medical records were found to have complete, relevant clinical, laboratory, and radiographic imaging.ResultsThirteen patients had diffuse disease and 47 limited disease — 51 women and 9 men, 44 Jews and 16 Arabs; mean age 55 ± 14 years; disease duration 8 ± 6 years. AO with or without calcinosis was observed in 42 patients (70%). Vitamin D deficiency was found in 46% of patients (16 out of 44 Jewish patients, 10 out of 16 Arab patients). PTH was elevated in 21.7% of patients. Significant correlations were observed between acroosteolysis and PTH (p = 0.015), calcinosis (p = 0.009), and disease duration (p = 0.008), and between PTH and vitamin D levels (p = 0.01). All patients had normal serum concentrations of calcium, phosphorus, magnesium, and albumin, and liver and kidney functions.ConclusionIn this group of Mediterranean patients with SSc, the incidence of vitamin D deficiency and secondary hyperparathyroidism was surprisingly high. This finding correlated with the occurrence of AO and calcinosis. Low levels of vitamin D may reflect silent malabsorption and might be a risk factor for secondary hyperparathyroidism and bone resorption. Traditional dress habits and low exposure to sun may contribute to vitamin D deficiency in an Arab population but do not explain all the findings. The pathogenesis of these findings needs to be corroborated in other SSc populations.


1977 ◽  
Vol 53 (5) ◽  
pp. 431-438
Author(s):  
D. A. Walker ◽  
S. Joyce Davies ◽  
K. Siddle ◽  
J. S. Woodhead

1. The maximum tubular reabsorption capacity for phosphate relative to glomerular filtration rate (Tm,P/GFR) was found to range from 0·8 to 1·5 mmol/l in 32 normal fasting subjects. In 14 patients with primary hyperparathyroidism and five patients with hyperparathyroidism secondary to vitamin D deficiency or malabsorption values ranged from 0·2 to 0·8 mmol/l. 2. Plasma parathyroid hormone concentrations measured by an immunoradiometric technique ranged from <0·15 to 0·9 ng/ml in the normal subjects and from 0·5 to 10 ng/ml in the patients with hyperparathyroidism. There was no correlation, however, between plasma parathyroid hormone and Tm,P/GFR in either normal or abnormal groups. 3. Plasma parathyroid hormone was lower in 11 out of 13 patients with primary hyperparathyroidism 3 or 4 weeks after tumour removal than immediately before the operation. In all cases there was a rise in Tm,P/GFR, though not all values were normalized. 4. Changes in plasma parathyroid hormone, Tm,P/GFR and plasma and urinary cyclic AMP concentrations were measured during infusion of bovine parathyroid hormone into normal fasting subjects. Phosphate reabsorption fell markedly in response to low doses of parathyroid hormone (0·5 i.u. h−1 kg−1), higher doses (4 i.u. h−1 kg−1) producing little additional change in Tm,P/GFR despite large changes in cyclic AMP excretion. At the highest doses used (8 i.u. h−1 kg−1) apparent saturation of the renal adenylate cyclase occurred. During an infusion of hormone, 0·25 i.u. h−1 kg−1 over 3 h, a fall in Tm,P/GFR was recorded at concentrations of immunoreactive parathyroid hormone within the normal range for endogeneous hormone. At such concentrations it was not possible to detect significant changes in either plasma or urine cyclic AMP. 5. It is concluded that parathyroid hormone is an important regulator of renal phosphate handling under normal physiological conditions. Such a regulatory process has been implicated in the control of vitamin D metabolism.


2011 ◽  
Vol 1 (2) ◽  
pp. 25-31
Author(s):  
Bassem S. El Deek

Objectives (background): Both sickle cell disease and vitamin D deficiency are common among Saudi population. The present work asses Parathyroid hormone/Vitamin D axis as well as bone dynamics in young Saudi adults with sickle cell disease. Methods: A case-control study includes forty patients known to have sickle cell disease from the outpatient clinics of North Western Armed Forces Hospital, Tabuk were randomly selected for the study. Another 120 healthy individuals were involved as control. Cases and control were subjected to full history taking, clinical examination, and radiologic and laboratory investigations. Results: Bone image revealed diffuse osteopenia in 16 (40%) of the cases, avascular necrosis of the femoral head in 6 (15%), code fish vertebral bodies in 6 (15%) and coarse trabecular pattern in 6 (15%). Laboratory investigations for patients revealed hypocalcemia in 18 (45%), secondary hyperparathyroidism in 24 (60%), non-detectable vitamin D in 30 (75%) and detectable but subnormal vitamin D in 10 (25%). The mean level for serum calcium in cases was significantly less than that for the control (p < 0.001). The mean level for serum intact parathyroid hormone was significantly higher in the patients than the control (p < 0.001). The mean serum level for the Serum 25-hydroxyvitamin was significantly lower in the studied cases than the control. For the serum bone, specific alkaline phosphatase the mean level was significantly higher in case than control (p < 0.001). Conclusion: Vitamin D deficiency through a common finding it is more severe in patients with sickle cell disease with subsequent secondary hyperparathyroidism and frequent hypocalcemia.


1979 ◽  
Vol 57 (5) ◽  
pp. 435-443 ◽  
Author(s):  
M. A. Dambacher ◽  
J. A. Fischer ◽  
W. H. Hunziker ◽  
W. Born ◽  
J. Moran ◽  
...  

1. The distribution of intact parathyroid hormone-(1–84) [PTH-(1–84)] and of its COOH-terminal fragments was determined in human serum by column chromatography. In addition to PTH-(1–84) (peak I), COOH-terminal fragments having molecular weights of approximately 4000–7000 (peak II) and immunoreactive components co-eluting with human PTH-(1–12) (peak III) were observed. 2. Mean concentrations of intact PTH-(1–84) and of its COOH-terminal fragments were significantly raised in chronic renal failure as compared with those of normal subjects. Mean amounts of peak II were higher in patients with chronic renal insufficiency than in nutritional vitamin D deficiency, in pseudohypoparathyroidism and in primary hyperparathyroidism, despite comparable amounts of PTH-(1–84). 3. In chronic renal failure as well as in a group of patients with vitamin D deficiency, pseudohypoparathyroidism and primary hyperparathyroidism and in controls, significant linear relations were found between the serum concentrations of calcium and log (peak II/peak I). Our findings suggest that the conversion of intact PTH-(1–84) into COOH-terminal fragments by the parathyroid glands (resulting in a raised secretion of fragments) and/or in peripheral organs may be directly related to the serum concentration of calcium. However, the degradation of the fragments may also be suppressed in a calcium-dependent manner.


1979 ◽  
Vol 57 (2) ◽  
pp. 167-171 ◽  
Author(s):  
R. Bouillon ◽  
P. Geusens ◽  
J. Dequeker ◽  
P. De Moor

1. Parathyroid hormone and 25-hydroxy-vitamin D concentrations were measured in patients with severe primary osteoporosis and the results were compared with those found in normal subjects and in patients with primary hyperparathyroidism of vitamin D deficiency. 2. The parathyroid hormone concentrations in 19 patients with primary osteoporosis were within the normal range, both in the basal state (215 ± 85 ng/l, mean ± sd) and during a maximal stimulation (460 ±154 ng/l) induced by the infusion of disodium EDTA (70 mg/kg body weight). Increased serum concentrations of parathyroid hormone were found in patients with primary hyperparathyroidism (821 ± 323 ng/l, n = 33) and nutritional vitamin D deficiency (565 ± 144 ng/l, n = 11). 3. Serum 25-hydroxy-vitamin D concentrations (16·8 ± 7·7 μg/l) were found to be normal in patients with primary osteoporosis. Slightly (9·1 ± 2·1 μg/l) or markedly lower (2·2 ± 1·1 μg/l) 25-hydroxy-vitamin D concentrations were found respectively in patients with primary hyperparathyroidism and secondary hyperparathyroidism due to vitamin D deficiency. The serum concentration of the vitamin D-binding protein was normal in all groups. 4. A clearcut separation was therefore obtained between osteoporotic subjects (normal parathyroid hormone and normal 25-hydroxy-vitamin D concentrations) and patients with either primary hyperparathyroidism (increased parathyroid hormone and normal 25-hydroxy-vitamin D) or vitamin D deficiency (high parathyroid hormone and very low 25-hydroxy-vitamin D).


2011 ◽  
Vol 1 (2) ◽  
pp. 25-31
Author(s):  
Bassem S. El Deek

Objectives (background): Both sickle cell disease and vitamin D deficiency are common among Saudi population. The present work asses Parathyroid hormone/Vitamin D axis as well as bone dynamics in young Saudi adults with sickle cell disease. Methods: A case-control study includes forty patients known to have sickle cell disease from the outpatient clinics of North Western Armed Forces Hospital, Tabuk were randomly selected for the study. Another 120 healthy individuals were involved as control. Cases and control were subjected to full history taking, clinical examination, and radiologic and laboratory investigations. Results: Bone image revealed diffuse osteopenia in 16 (40%) of the cases, avascular necrosis of the femoral head in 6 (15%), code fish vertebral bodies in 6 (15%) and coarse trabecular pattern in 6 (15%). Laboratory investigations for patients revealed hypocalcemia in 18 (45%), secondary hyperparathyroidism in 24 (60%), non-detectable vitamin D in 30 (75%) and detectable but subnormal vitamin D in 10 (25%). The mean level for serum calcium in cases was significantly less than that for the control (p < 0.001). The mean level for serum intact parathyroid hormone was significantly higher in the patients than the control (p < 0.001). The mean serum level for the Serum 25-hydroxyvitamin was significantly lower in the studied cases than the control. For the serum bone, specific alkaline phosphatase the mean level was significantly higher in case than control (p < 0.001). Conclusion: Vitamin D deficiency through a common finding it is more severe in patients with sickle cell disease with subsequent secondary hyperparathyroidism and frequent hypocalcemia.


1974 ◽  
Vol 47 (5) ◽  
pp. 481-492 ◽  
Author(s):  
S. Tomlinson ◽  
P. M. Barling ◽  
J. D. M. Albano ◽  
B. L. Brown ◽  
J. L. H. O'Riordan

1. Administration of highly purified bovine parathyroid hormone (BPTH) (200 MRC units) increased the concentration of adenosine 3′,5′-cyclic monophosphate (cyclic AMP) in the peripheral plasma of normal subjects within minutes, whether the hormone was given as a bolus injection or an infusion. 2. The subsequent disappearance of cyclic AMP from the circulation was also rapid (t1/2 = 14 min) and was associated with a prompt decline (t1/2 = 4.6 min) in the concentration of the ammo-terminal part of BPTH, as measured in a region-specific immunoradiometric assay. 3. The concentration of cyclic AMP in plasma from a renal vein was found to increase more rapidly and to reach a greater peak than plasma from a peripheral vein. 4. The administration of BPTH to anephric subjects caused no increase in cyclic AMP. 5. These investigations indicate that parathyroid hormone can act extremely rapidly, with a short half-life, and that the kidney makes a major contribution to the changes in plasma cyclic AMP induced by the hormone. In addition, they form the basis for the development of a simplified Ellsworth—Howard test, using changes in circulating cyclic AMP after BPTH administration as an index of responsiveness to the hormone.


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