Immunoreactive Parathyroid Hormone Concentrations Research Articles

Rat Serum Osteocalcin Concentration Is Decreased by Restriction of Energy Intake

We studied the effects of energy restriction on serum osteocalcin concentration and bone formation rate in rats. The experiment was designed to achieve energy restriction by reducing the carbohydrate intake while providing identical quantities of protein, fat, vitamins and minerals. Energy intakes of three groups of post-weaning male rats were restricted by 20, 40 and 60% for 4 wk. Serum calclum, phosphorus, transthyretin, triiodothyronine (T3), thyroxine (T4), 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol and immunoreactive parathyroid hormone (iPTH) concentrations were determined. Energy restriction (20, 40 and 60%) produced a significant and gradual drop of serum osteocalcin concentrations, although the serum concentrations of its key regulators, i.e., 1,25-dihydroxycholecalciferol and iPTH, were not significantly affected. On the contrary, serum concentrations of calcium, phosphorus, transthyretin, T3 and T4 were significantly lower in the energy-restricted groups. However, our results do not support their implication in the regulation of serum osteocalcin synthesis by energy intake. Serum osteocalcin concentration was positively correlated with bone mineral apposition (r = 0.50, P < 0.05) and bone mineralization (r = 0.50, P < 0.05) rates suggesting that its decrease resulted from a reduction of bone formation, and not from abnormal mineralization, because osteoid seam thickness was not modified. Energy intake seems to be an important determinant of serum osteocalcin concentration and bone formation; however, the exact mechanism underlying this regulation remains to be determined.

Muscle strength, physical performance, and metabolic changes after subtotal parathyroidectomy for secondary hyperparathyroidism

BackgroundHyperparathyroidism in patients on chronic hemodialysis presents with bone pain, pruritus, and extra-skeletal calcifications. Little attention has been paid to low plasma protein concentrations and muscle weakness in these patients. The present study was undertaken to characterize the impact of subtotal parathyroidectomy for chronic hemodialysis on body composition, muscle strength, plasma proteins, quality of life, and long-term clinical course. MethodsWe performed a prospective observational before-after assessment study of consecutive chronic hemodialysis patients referred for parathyroidectomy. Patients were investigated at baseline before parathyroidectomy and then at 1 and 6 months after surgery, with the aim to assess changes in metabolic parameters, body composition by bioimpedance, muscle strength, and quality of life (36-items Short Form Health Survey questionnaire). Follow-up was terminated when patients reached 1 of the 3 pre-defined end points: recurrence of secondary hyperparathyroidism, transplantation, or death. ResultsA group of 23 patients on hemodialysis were included. Preoperative handgrip strength was diminished by 52.4 ± 17%. After parathyroidectomy, a drop of immunoreactive parathyroid hormone concentrations (1,153 vs 237 pg/mL; P < .001) was observed together with increases in plasma protein (total: 6.8 vs7.8 g/dL, s-albumin 3.7 vs 4.4 g/dL and prealbumin: 31.7 vs 35.2 mg/dL; P < .001), handgrip strength (18.3 vs 22.9 kg: P = .001) as well as an improvement in physical dimension (32.9 vs 35.6; P = .004) and vitality (32.3 vs 47.1; P = .002) domains of the 36-items Short Form Health Survey questionnaire. After10 years, one-third of the patients had died, one-third of the patients had a recurrence of secondary hyperparathyroidism, and one-third of patients had received a kidney transplant and maintained a normal parathyroid function. ConclusionSubtotal parathyroidectomy improves protein metabolic markers, muscle strength, and physical performance in chronic hemodialysis patients.

Arterial Stiffness in Chronic Renal Failure and After Renal Transplantation

Arterial stiffness is an independent cardiovascular risk factor, along with aging, hypertension, and cardiovascular disease. The augmentation index (AIx) and pulse wave velocity (PWV) are early markers of atherosclerotic vascular changes. Arteriography was used to determine systolic and diastolic blood pressure, pulse pressure (PP), AIx, and PWV in 82 male and 64 female renal transplant recipients (mean [SD] age, 45.3 [11.2] years). Cardiovascular risk was assessed using echocardiography and ultrasonography of the carotid arteries. The left ventricular wall thickness, ejection fraction, and stenosis of the carotid arteries were also measured. Fasting serum creatinine, cystatin C, homocysteine, C-reactive protein, immunoreactive parathyroid hormone, lipid, and calcium-phosphorus concentrations were determined. The serum cystatin concentration was 2.1 (0.2) mg/L, and the homocysteine concentration, 15.2 (2.6) μmol/L. After transplantation, body mass index, fat mass, and visceral fat area increased significantly ( P < .01). The AIx was increased (AIx ≥10%) in 20% of men and 37% of women, PWV was increased (>10 m/s) in 43% of men and 34% of women, and PP was pathologically high (>12 m/s) in 10% of men and 12% of women. The PWV was significantly related to age ( r = 0.52) and ventricular wall thickness ( r = 0.46). Pulse pressure, BMI, and systolic and diastolic blood pressure correlated positively but modestly with PWV. There was a significant relationship between AIx80 and systolic ( r = 0.42) and diastolic ( r = 0.39) blood pressure and PP ( r = 0.33). The ejection fraction correlated negatively with PWV and AIx. There was a strong association between carotid artery stenosis, PWV, and AIx80. All patients with PWV greater than 10 m/s demonstrated carotid artery stenosis. In conclusion, arteriography is an objective, noninvasive, and convenient method for early diagnosis and follow-up of atherosclerosis.

CEREBRAL CALCINOSIS WITH LATE ONSET ENCEPHALOPATHY UNUSUAL TYPE OF PSEUDO-PSEUDOHYPOPARATHYREOIDISM

A family from Western Norway is described in which 5 out of 9 members in one generation developed a progressive encephalopathy in middle life. Massive, symmetrical calcifications located in basal ganglia, dentate nuclei and cerebral sulci of the brain were seen on roentgenograms of the skull. All affected members exhibited a clinical syndrome which included mental deterioration, extrapyramidal motor deficit, cerebellar ataxia and tremor. The biochemical investigation showed normal serum calcium and phosphorous and concentration of immunoreactive parathyroid hormone was normal. The Ellsworth-Howard test with exogenously administered parathyroid extract revealed a subnormal phosphorous diuresis while urinary excretion of cyclic AMP was normal. Thus, the defect appears to be an insufficient intracellular response to cyclic AMP. The late onset of symptoms is compatible with the slight disturbance in calcium-phosphorous metabolism we have demonstrated. The family probably represents an unusual type of pseudo-pseudohypoparathyroidism of which only one other family has been reported earlier. The investigations and pedigree analysis of the present kindred is suggestive of an autosomal recessive inheritance of the disorder.

Vitamin D deficiency in Iranian mothers and their neonates: a pilot study

We conducted a pilot study to assess the prevalence of hypovitaminosis D among Iranian women and their newborns. Blood samples were taken from 50 mothers (age 16–40 yr) and their neonates at term delivery in the largest Tehran hospital. The results showed that 80% of the women had 25-hydroxyvitamin D (25-OHD) concentrations of less than 25 nmol/l. Mean maternal plasma calcium and phosphatase alkaline concentrations were in the normal range. The mean maternal serum immunoreactive parathyroid hormone concentration of women with hypovitaminosis D (i.e., 25-OHD levels < 25 nmol/l) was above normal range and significantly different from that of women without hypovitaminosis D. Conclusion: The mean cord serum 25-OHD concentration was very low (4.94 ± 9.4 nmol/l) and that of infants of mother with hypovitaminosis D were almost undetectable (1.2 ± 1.2 nmol/l).

Vitamin D deficiency in Iranian mothers and their neonates: a pilot study

We conducted a pilot study to assess the prevalence of hypovitaminosis D among Iranian women and their newborns. Blood samples were taken from 50 mothers (age 16-40 yr) and their neonates at term delivery in the largest Tehran hospital. The results showed that 80% of the women had 25-hydroxyvitamin D (25-OHD) concentrations of less than 25 nmol/l. Mean maternal plasma calcium and phosphatase alkaline concentrations were in the normal range. The mean maternal serum immunoreactive parathyroid hormone concentration of women with hypovitaminosis D (i.e., 25-OHD levels <25 nmol/l) was above normal range and significantly different from that of women without hypovitaminosis D. The mean cord serum 25-OHD concentration was very low (4.94+/-9.4 nmol/l) and that of infants of mother with hypovitaminosis D were almost undetectable (1.2+/-1.2 nmol/l).

Development of a Scintillation Proximity Assay for High-Throughput Measurement of Intact Parathyroid Hormone

A simple, high-throughput scintillation proximity assay (SPA) for parathyroid hormone (1-84) (PTH) has been developed. Fifteen commercially available N-terminal and six C-terminal anti-PTH antibodies were evaluated for detection of human PTH(1-84). Two C-terminal antibodies (CR1073M and 10-P55) gave the most consistent results. Using one of these antibodies (10-P55), an assay was developed with a sensitivity of 4 pg/ml for human and rat PTH(1-84). Porcine PTH(1-84) was not detectable. The intra-assay and inter-assay coefficients of variation for a 467 pg/ml sample were 6.1 and 6.5%, respectively, and for a 21 pg/ml sample, 6.2 and 4.4%. Human PTH(1-34), while not detected in the assay, interfered with the detection of PTH(1-84). Smaller fragments [for example, human PTH(3-34)] and a C-terminal PTH fragment [PTH(53-84)] did not interfere in the assay. The procedure gave 106–110% recovery of human PTH(1-84) spiked into samples. Immunoreactive PTH concentrations in serum of rats administered EGTA were determined by SPA and by a commercially available PTH immunoassay. There was a good correlation between the two assays with significant increases in serum immunoreactive PTH concentrations at 15 and 30 min after EGTA injection and a rapid decrease to baseline values by 60 min. The SPA gives a high-throughput method for simply and accurately determining PTH(1-84) concentrations in serum.

Pathogenesis of secondary hyperparathyroidism.

Hyperplasia of the parathyroid glands and increased concentrations of immunoreactive parathyroid hormone are among the earlier alterations of mineral metabolism in patients with chronic renal failure. In the past five years several investigators have demonstrated that phosphorus retention plays a key role in the development of secondary hyperparathyroidism and chief cell hyperplasia of the parathyroid glands. Since phosphorus regulates the production of 1,25D3 by altering the enzyme 1-alpha-hydroxylase it is possible that the effect of phosphorus retention is mediated by a decrease in the synthesis of 1,25D3. This has been shown in patients with early renal insufficiency. However, in patients with advanced renal failure the reduced renal mass may limit the production of 1,25D3. It is clear now that phosphorus per se independent of the levels of ionized calcium and 1,25D3 can increase the synthesis and secretion of PTH in vivo and in vitro. The abnormalities in vitamin D metabolism are not only characterized by low levels 1,25D3 but by low number of vitamin D receptors. Thus, the parathyroid glands are resistant to the action of 1,25D3 and high pharmacological concentrations of 1,25D3 in blood are necessary to suppress the levels of parathyroid hormone in advanced renal failure. The development of monoclonal changes in glands obtained from patients with secondary hyperparathyroidism further complicates the treatment of secondary hyperparathyroidism in patients maintained on haemodialysis. Thus, correction of serum phosphorus is imperative for the success of 1,25D3 to control the levels of parathyroid hormone. Currently several laboratories are studying at the molecular level the mechanisms by which dietary phosphorus induces chief cell hyperplasia.

Severe hypocalcemia in a patient with protein-losing enteropathy

We report a 53-year-old woman with hypocalcemia associated with protein-losing enteropathy. She had had lymphedema of the left lower extremity since 20 years of age and had loose bowels and hypoproteinemia. Her daily fecal excretion of α1-antitrypsin was extremely high, suggesting massive intestinal protein loss. This was demonstrated by scintigraphy using 99 mTc-labeled human serum albumin, in which significant amounts of radioactivity were first accumulated in the lower part of the small intestine and then went down along the colon. She not only had hypocalcemia, but also an increased serum concentration of immunoreactive parathyroid hormone (PTH) and 1,25 (OH)2D, and increased percent tubular reabsorption of phosphate. In addition, she had low serum levels of fat-soluble vitamins including 25 (OH) D. In the Ellsworth-Howard test, urinary excretion of cyclic AMP and phosphate in response to exogenous PTH was rather exaggerated. These results suggest that hypocalcemia in this case was due mainly to malabsorption of calcium and vitamin D secondary to protein-losing enteropathy.

A new enzyme immunoassay for intact human calcitonin in serum

A simple, high-throughput scintillation proximity assay (SPA) for parathyroid hormone (1-84) (PTH) has been developed. Fifteen commercially available N-terminal and six C-terminal anti-PTH antibodies were evaluated for detection of human PTH(1-84). Two C-terminal antibodies (CR1073M and 10-P55) gave the most consistent results. Using one of these antibodies (10-P55), an assay was developed with a sensitivity of 4 pg/ml for human and rat PTH(1-84). Porcine PTH(1-84) was not detectable. The intra-assay and inter-assay coefficients of variation for a 467 pg/ml sample were 6.1 and 6.5%, respectively, and for a 21 pg/ml sample, 6.2 and 4.4%. Human PTH(1-34), while not detected in the assay, interfered with the detection of PTH(1-84). Smaller fragments [for example, human PTH(3-34)] and a C-terminal PTH fragment [PTH(53-84)] did not interfere in the assay. The procedure gave 106–110% recovery of human PTH(1-84) spiked into samples. Immunoreactive PTH concentrations in serum of rats administered EGTA were determined by SPA and by a commercially available PTH immunoassay. There was a good correlation between the two assays with significant increases in serum immunoreactive PTH concentrations at 15 and 30 min after EGTA injection and a rapid decrease to baseline values by 60 min. The SPA gives a high-throughput method for simply and accurately determining PTH(1-84) concentrations in serum.

Prevention of Enhanced Parathyroid Hormone Secretion, Synthesis and Hyperplasia by Mild Dietary Phosphorus Restriction in Early Chronic Renal Failure in Rats: Possible Direct Role of Phosphorus

In order to evaluate the effect of dietary phosphorus (P) restriction on the pathogenesis of secondary hyperparathyroidism (2 degrees HPT) in chronic renal failure (CRF), we studied parathyroid function and parathyroid cell proliferation in 5/6 nephrectomized rats (CRF rats) fed with three different dietary P contents (0.6, 0.3 and 0.1%). Four weeks after 5/6 nephrectomy, serum immunoreactive parathyroid hormone (PTH) concentration, PTH mRNA level in parathyroid glands and the size of parathyroid glands were increased in CRF rats compared to those of sham-operated rats when both groups of rats were fed with normal P (0.6%) diet. These changes were not accompanied by any detectable changes of serum concentrations of calcium (Ca), inorganic phosphate (Pi) or calcitriol. In contrast, such evidence of 2 degrees HPT was obliterated in CRF rats fed with 0.3 or 0.1% P diet. In rats fed with 0.3% P diet, serum concentrations of Ca, Pi, and calcitriol were not different from those of sham-operated rats or from CRF rats fed with normal P diet. In contrast, serum Ca and calcitriol concentrations increased and serum Pi decreased in CRF rats fed with 0.1% P diet. These data suggest that 2 degrees HPT can be completely prevented at the levels of PTH secretion, synthesis and parathyroid cell proliferation by mild dietary P restriction (0.3%) alone, and that such effects may not depend upon the changes in serum concentrations of Ca, Pi or calcitriol, but may depend on reduced dietary P content per se. Thus, mild dietary P restriction from the early stage of CRF may be clinically effective for the prevention of 2 degrees HPT.

Effect of citrate on serum aluminum concentrations in hemodialysis patients: a prospective study.

Twenty hemodialysis patients were prospectively evaluated to determine if concomitant citrate and aluminum administration enhances the absorption of aluminum, thereby increasing the possibility of toxicity. The four-phase study consisted of phase I, a washout phase; phase II, an aluminum treatment phase; phase III, a treatment phase combining aluminum and soluble calcium citrate; and phase IV, a treatment phase with the patient's original prestudy phosphate binder. Results disclosed a progressive rise in serum aluminum levels (microgram/L) from 47 +/- 8 (phase I) to 62 +/- 12 (phase II) to 74 +/- 13 (phase III) and a drop to 58 +/- 12 (phase IV). The difference in levels between phases I and III was significant. Additionally, and despite the fact that serum calcium concentrations did not change, serum phosphate and immunoreactive parathyroid hormone concentrations were significantly lower when aluminum and citrate were used together. This suggests that citrate enhances the absorption of aluminum and therefore increases the possibility of toxicity in the patient with end-stage renal disease.

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 [l,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/m 2) and very low serum levels of l,25(OH) 2D (28.8 pmol/1; normal range, 72–120). Presurgery normalization of the calcemia with normal saline, salmon calcitonin and Pamidronate caused an increase in l,25(OH) 2D serum concentration to 228.3 pmol/1. A negative correlation could be established between ionized calcium and l,25(OH) 2D levels during that period ( r 2 = 0.80, P < 0.04). While serum calcium decreased with treatment, serum iPTH also decreased to 48.6 pmol/l, suggesting some l,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/I. This was explained by the very high levels of serum l,25(OH) 2D (>200 pmol/1) 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.

Acute changes in calcium homeostasis during treatment of primary hyperparathyroidism with risedronate.

We administered risedronate, a potent oral bisphosphonate, to patients with mild primary hyperparathyroidism in order to 1) determine if we could normalize the serum calcium concentration in the short term, and 2) analyze changes in the homeostatic mechanisms responsible for maintaining hypercalcemia in this patient population. When administered for 7 days, risedronate reduced fasting serum calcium concentrations without significant toxicity in patients with primary hyperparathyroidism. The decrease in serum calcium was accompanied by evidence of inhibition of bone resorption, as assessed by measurement of urinary hydroxyproline, increased serum immunoreactive PTH concentrations, enhanced renal tubular reabsorption of calcium, and a progressive decrease in serum alkaline phosphatase. Serum PTH was partially suppressed by an oral calcium load in untreated patients as well as in patients treated with risedronate. Although patients treated with risedronate had normal fasting serum calcium levels, serum calcium values in these normocalcemic patients were labile after oral ingestion of calcium. After daily calcium intake of 2 g, serum calcium levels in risedronate-treated patients were similar to those in untreated patients with primary hyperparathyroidism, suggesting that there are likely to be fluctuations in serum calcium in risedronate-treated patients with normal fasting serum calcium during postprandial periods. These studies show that risedronate lowers fasting serum calcium during short term treatment. However, further studies are required to determine whether the lability in serum calcium in these patients after an oral calcium load has clinical significance, and whether longer term treatment would maintain serum calcium in the normal range.

A comparative study of atherosclerosis and osteopenia in elderly and young hemodialysis patients

The effects of aging on atherosclerosis and osteopenia in hemodialysis patients were investigated. Eighty patients on maintenance hemodialysis were subdivided according to age into old (greater than or equal to 65 years old, N = 40) and young (less than 65 years old, N = 40). Biochemical, radiologic, and biophysical studies were performed in each patient to assess the degree of atherosclerosis and osteopenia. Compared to age-matched controls, patients in the old group exhibited a significantly higher aortic pulse wave velocity (PWV), and old female patients had a significantly lower bone mineral content/bone width (BMC/W). Elderly patients also had a significantly higher aortic PWV and higher grade of aortic calcification as assessed radiologically; in contrast, the BMC/W was lower. Concerning sex differences, elderly male patients had the highest average grade of aortic calcification, the lowest serum Pi, [Ca] x [Pi], and immunoreactive parathyroid hormone concentrations, while elderly female patients had the lowest BMC/W and highest incidence of osteopenia. These observations suggest that elderly male hemodialysis patients are more prone to develop atherosclerosis and elderly female hemodialysis patients to develop advanced osteopenia.

A new syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features.

Twelve infants (six boys, six girls) with severe hypocalcaemic tetany or convulsions were seen over a three year period. Nine patients were symptomatic in the newborn period. Their hypocalcaemia was associated with hyperphosphataemia and very low concentrations of immunoreactive parathyroid hormone. None of the babies suffered from congenital cardiac disease. Cell mediated immunity, measured in five patients, was normal. There were no chromosomal abnormalities but all patients shared several dysmorphic features including deep set eyes, microcephaly, thin lips, beaked nose tip, external ear anomalies, micrognathia, and depressed nasal bridge. Mental retardation of varying degree was found in all patients. All had severe intrauterine and postnatal growth retardation. Four patients have died. The remaining eight patients are on treatments with vitamin D and calcium supplements with no change in their growth pattern. We believe that this association of congenital hypoparathyroidism with severe growth failure and dysmorphism represents a new syndrome.

Parathyroid Glands in Chronic Aluminum Intoxication

In chronic renal failure, aluminum overload may influence parathyroid function. In a study of possible aluminum-induced parathyroid abnormalities, parathyroid glands from nine parathyroidectomized patients on hemodialysis were examined by light and electron microscopy and by X-ray microanalysis. Aluminum overload was assessed by the presence of stainable aluminum (aluminum surface, 23.3% +/- 11% of total surface) in bone biopsy specimens. The mean plasma aluminum concentration was 7.7 +/- 1.9 mumol/L. All patients but one had elevated plasma concentrations of immunoreactive parathyroid hormone as well as osteitis fibrosa. The aluminum concentrations in bone and parathyroid gland from these patients were significantly higher than those in tissue from patients on hemodialysis without stainable bone aluminum. Abundant aluminum deposits were present in parathyroid chief cell cytoplasm in lipoid bodies, lipofuscin granules, and mitochondria. These cells exhibited features of active hormonal synthesis and contained numerous secretory granules. The data show that in the parathyroid glands of these aluminum-intoxicated patients the presence of aluminum deposits neither induced cellular damage or chief cell necrosis nor interfered with the production of parathyroid hormone.

Short-term effects of parathyroidectomy on plasma biochemistry in chronic uremia

Parathyroidectomy (PTx) is indicated in hemodialysis (HD) patients who have severe osteitis fibrosa unresponsive to vitamin D therapy or in whom the latter treatment is contraindicated. Immediately after PTx, plasma immunoreactive parathyroid hormone, calcium and phosphorus concentrations decline abruptly. However, little is known in such patients about the short-term effects of PTx on plasma alkaline phosphatase (AP) activity and plasma aluminum (Al) levels. The present, preliminary study was performed to determine such parameters in 37 HD patients, and to correlate them with data of bone histology. Mean plasma AP activity started to increase after PTx from day 4 onwards. Thus, AP values significantly higher than pre-PTx values were observed at day 7 and 14 (415 +/- 54 vs. 619 +/- 77 and 749 +/- 83 IU/liter, means +/- SEM; N = 37; P less than 0.05 and 0.001, respectively). This increase, in the absence of changes in liver function, was mainly due to the bone-specific iso-AP. Moreover, the degree of increase in plasma AP activity was higher in the subgroup with negative (group I, 21 patients) than in that with positive bone Al staining (group II, 16 patients). However, plasma osteocalcin (BGP) did not change after PTx (N = 8). Basal plasma Al levels were significantly higher in group II both before and two weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Ectopic Production of Parathyroid Hormone by Small Cell Lung Cancer in a Patient with Hypercalcemia*

Severe hypercalcemia (serum calcium, 4.37-4.84 nmol/L) was found in a 70-yr-old man who had a small cell carcinoma of the lung with multiple metastases. The plasma immunoreactive PTH concentration was markedly elevated, as measured in three different PTH assays [N-terminal PTH, 4,650 ng/L (normal, 230-630); midregion PTH, 13,850 ng/L (normal, 180-560); C-terminal PTH, 9,900 ng/L (normal, less than 1,300)], but at autopsy the parathyroid glands were histologically normal. The PTH concentration of a liver metastasis was 503.5 ng/g wet wt (normal liver, less than 4.2-5.9), and the PTH in the tumor extract eluted at nearly the same position as synthetic human PTH-(1-84) on gel filtration chromatography. Northern blot analysis revealed PTH mRNA in the tumor as a single band of 0.9 kilobase. These results indicate that the ectopic PTH production by the lung cancer was the cause of hypercalcemia in this patient.

Hyperparathyroidism and portacaval shunt: A syndrome or a coincidence?

This is a report of six patients with cirrhosis of the liver in whom primary hyperparathyroidism occurred due to a solitary parathyroid adenoma 3 months to 9 years after undergoing emergency portacaval shunt for hemorrhage from esophageal varices. The presenting symptoms in all six patients were weakness and bone pain. Three patients had a bone fracture after insignificant trauma, one and probably two passed kidney stones, and a duodenal ulcer developed in two. Bone x-ray films showed generalized osteoporosis in all patients. Renal function and arterial blood pH were within normal limits in every patient. The diagnosis of primary hyperparathyroidism in each patient was based on repeated demonstrations of hypercalcemia, hypophosphatemia, and markedly elevated serum immunoreactive parathyroid hormone concentrations. In all six patients, removal of the parathyroid adenoma resulted in disappearance of symptoms; normalization of serum calcium, phosphorus, and immunoreactive parathyroid hormone levels; and, in four of the six, improvement in radiographic evidence of osteoporosis during follow-up of from 1 to 6 years. The association of cirrhosis, portacaval shunt, and primary hyperparathyroidism has not been documented previously. Our six patients with primary hyperparathyroidism constitute 3.4 percent of 174 survivors of emergency portacaval shunt in a series of 264 unselected, consecutive patients with cirrhosis and bleeding esophageal varices. Hepatic osteodystrophy is known to have occurred in only 11 of these 174 survivors. Primary hyperparathyroidism may be a more common cause of hepatic osteodystrophy than has been previously recognized, and should be considered in patients with cirrhosis in whom weakness, bone pain, and bone demineralization develop, particularly if they have a portacaval anastomosis.