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PubMed2000

[Surgical therapy concept in primary hyperparathyroidism].

INTRODUCTION: Primary hyperparathyroidism is a relatively rare disease caused in 80-85% of cases by solitary adenoma of the parathyroid glands. The laboratory findings are hypersecretion of PTH and hypercalcaemia. We distinguish between asymptomatic and symptomatic primary hyperparathyroidism. 25 patients of our clinic who underwent surgery in 1996 and 1997 are presented to illustrate our surgical concept of therapy. METHODS: 7 patients were asymptomatic and 18 symptomatic with regard to primary hyperparathyroidism. Preoperative localisation was facilitated by ultrasonography of the neck, which was used in all cases. Bilateral exploration of the neck under general anaesthesia similarly to thyroidectomy was the gold standard. Monitoring the inferior laryngeal nerve helped to protect it. In 6 cases intraoperative parathyroid hormone monitoring (rapid PTH assay) was applied. RESULTS: More than a third of the symptomatic group of patients had neurological or psychiatric diseases, followed by symptoms of the musculoskeletal and urological systems. Possible reasons for surgical intervention were persistent hypercalcaemia, age over 50, radiological findings of kidney stones or decreased kidney function. In 17 patients the preoperative ultrasonographic localisation was consistent with the intraoperative clinical findings. The sensitivity of this method was 68%. Intraoperative pathology showed 17 patients with a solitary adenoma, 4 ectopic, 2 cases had double adenoma, and 2 others hyperplasia with enlargement of all glands. After resection of the pathological parathyroid glands there was a decrease of parathyroid hormone in intraoperative hormone monitoring of approximately 60%. The preoperative hypercalcaemia (mean 2.99 mmol/l) usually normalised 4 hours postoperatively. There was no severe intraoperative bleeding and the inferior laryngeal nerve was preserved in all cases. All patients were monitored at 3-month intervals for parathyroid hormone and serum calcium during the first year after operation. One patient had persistently elevated parathyroid hormone without clinical findings. DISCUSSION: Parathyroidectomy is an efficient and safe operation with excellent normalisation of serum calcium and parathyroid hormone and a high rate of patient satisfaction. In this study assessment of ultrasonography was the preferred method of locating enlarged parathyroid glands before operation. However, this method is not based on unilateral exploration of the glands. Therefore, we prefer to locate all four glands, an approach based on the literature [1, 2]. Intraoperative monitoring of parathyroid hormone facilitates assessment of the operative result [3]. Normalisation of calcium in serum and the effectiveness and safety of the surgical method are confirmed in other publications [4-8]. In 24 of our patients normocalcaemia resulted within 12 hours after operation and in one patient within 4 days. One year after operation and endocrinological checkup all 25 patients were asymptomatic and normocalcaemic, while one patient had persistently high parathyroid hormone of unknown origin.

Adenoma↗
PubMed2001

Minimally invasive, radioguided surgery for primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism affects 1 in 700 individuals in the United States. A single adenoma is responsible in over 85% of cases. Surgery remains the most effective treatment. This study was designed to assess the feasibility of minimally invasive radioguided parathyroidectomy (MIRP) with confirmation of excision by ex vivo radioactivity alone. METHODS: Seventy-five consecutive patients with primary hyperparathyroidism were prospectively studied. Following sestamibi scan, patients underwent unilateral neck exploration guided by a handheld gamma probe, which was also used to measure ex vivo radioactivity of excised tissue. RESULTS: The sestamibi scan was positive in 88% of the patients. A small incision (mean, 3.2+/-0.3 cm) was sufficient. Ectopic gland sites were localized in five patients with positive scans and single adenomas. Mean operative time was 48 minutes (range, 15-125 minutes), with shorter procedures after the initial 20 cases (mean, 24 vs. 72 minutes; P < .01). Radioguided parathyroidectomy was successful in 97%, with a mean follow-up of 11 months (range, 1-26 months). As noted previously, adenomatous parathyroid glands contained more than 20% of the background radioactivity. CONCLUSIONS: MIRP is a feasible alternative to bilateral dissection with the advantages of guided dissection and rapid confirmation, and may become the procedure of choice for primary hyperparathyroidism.

Adenoma↗
PubMed1992

[Hypercalciuria and primary hyperparathyroidism in patients with kidney calculi. II. Primary hyperparathyroidism].

Among 1819 patients with renal stone disease 44 cases with primary hyperparathyroidism (p.h.p.) were diagnosed. In all cases the diagnosis of php was confirmed by histomorphological examination. In 34 patients with php solitary adenoma was found, in 5 patients an adenoma with concomitant hyperplasia of the parathyroid glands, in 2 patients hyperplasia and in 3 patients carcinoma of the parathyroid glands. Hypercalcemia was found in 86% of patients, while elevated plasma levels of PTH in 90% of patients with php. Not in all patients PTH secretion was entirely autonomous. No significant correlation was found between plasma levels of PTH and kind of pathology of the parathyroid glands as well as clinical feature of php respectively.

Adult↗
PubMed2000

Two cases of primary hyperparathyroidism associated with primary cutaneous lymphoma.

Primary hyperparathyroidism has been described previously in association with malignancy, but to our knowledge has not been reported in association with primary cutaneous lymphoma. We report two cases of parathyroid adenoma with primary cutaneous lymphoma, the first in a 42-year-old woman with CD30-negative cutaneous large cell lymphoma, and the second in a 67-year-old man with mycosis fungoides and CD30-positive anaplastic large cell lymphoma.

Adult↗
PubMed2003

Bone strength in primary hyperparathyroidism.

In primary hyperparathyroidism, as is the case for any metabolic bone disease like osteoporosis, bone strength is a function of many variables. In addition to bone density, considerations of bone size, microarchitecture, and dynamic variables related to the evolution of the disease are all likely to influence bone strength. With greater tools to investigate these points and with newly identified cohorts of this disease, some of whom are presenting with the earliest manifestations of abnormal parathyroid function, it is expected that fresh insights will emerge. Greater knowledge of the disease should help in understanding anabolic aspects of PTH when it is used as a treatment for osteoporosis.

Bone Density↗
PubMed2005

Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) and vitamin D insufficiency are common conditions that can occur in combination. However, low plasma 25-hydroxyvitamin D (25OHD) may also enhance the risk of PHPT or modify disease severity. AIM: To compare the risk of vitamin D insufficiency and deficiency stratified by age, sex and season between PHPT patients and controls and to assess associations between plasma 25OHD and adenoma weight, biochemical variables, bone mineral density (BMD) and clinical complications. DESIGN: Cross-sectional study. MATERIAL: A total of 289 consecutive Caucasian patients with PHPT aged 65.9 (24-92) years, 289 sex-, age- and season-matched normocalcaemic controls and 187 healthy adult blood donors. PHPT diagnosis was confirmed in 214 by neck exploration. RESULTS: Vitamin D insufficiency (plasma 25OHD < 50 nmol/l) was observed in 81% of PHPT patients compared with 60% of sex- and age-matched controls (P < 0.001) and 35% of blood donors (P < 0.001). During summer, 77%vs. 53% (P < 0.001) and 4% (P < 0.001), respectively, had vitamin D insufficiency. Average plasma 25OHD was 41 (range 9-87) nmol/l among 27 PHPT patients compared with 87 (21-173) nmol/l (P < 0.001) among aged-matched blood donors. During winter, 86%vs. 66% (P < 0.001) and 71% (P < 0.05), respectively, had vitamin D insufficiency. Vitamin D deficiency (plasma 25OHD < 25 nmol/l) was observed in 33% of PHPT patients compared with 20% of age- and sex-matched controls (P < 0.001) and 13% of blood donors (P < 0.001). Both PHPT patients and controls showed seasonal variations in 25OHD related to the average number of sun hours, but values were lower in PHPT patients at all calendar months. In PHPT patients low plasma 25OHD was associated with higher plasma levels of calcium, PTH and alkaline phosphatase and with lower renal calcium excretion, femoral neck and forearm BMD. No association was found between plasma 25OHD and adenoma weight (total or divided into tertiles). There was a trend towards increased risk of osteoporotic fractures (P < 0.08) with low plasma 25OHD. CONCLUSION: Vitamin D insufficiency and deficiency are common findings in PHPT and occur more often than in a sex- and age-matched control group referred from general practice and in normal blood donors irrespective of season. Low plasma 25OHD levels are associated with an aggravated clinical presentation of PHPT but do not affect adenoma size.

Adenoma↗
PubMed2006

Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with heart disease. The aims of the present study were to evaluate how cardiac function and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlate in patients with mild PHPT, and how the plasma level of NT-proBNP is influenced by cure of the parathyroid disease. DESIGN AND PATIENTS: Forty-two patients with PHPT without symptoms of heart disease were examined before and 1 year after curative parathyroidectomy. MEASUREMENTS: Plasma or serum concentrations of NT-proBNP, calcium, PTH, creatinine, oestradiol, testosterone and SHBG were measured. Cardiac function was evaluated by equilibrium radionuclide angiography (ERNA). RESULTS: At baseline, NT-proBNP levels correlated negatively with systolic function [left ventricular ejection fraction (LVEF), P < 0.001]. Twelve per cent of the patients had NT-proBNP levels above normal reference values preoperatively. One year postoperatively, the corresponding proportion was 21%. The mean plasma concentration of NT-proBNP increased after parathyroidectomy (P < 0.01) in parallel with a dip in diastolic function (peak filling rate, P < 0.05) and a falling trend in systolic function (LVEF, P = 0.08). The postoperative percentage changes in circulating NT-proBNP and total oestradiol correlated positively (P < 0.05). CONCLUSIONS: Patients with mild PHPT and normal renal function may have high levels of circulating NT-proBNP despite the absence of symptomatic heart disease. Cure of the parathyroid disease is followed by a further increase in NT-proBNP secretion in parallel with ERNA measures, indicating subclinical changes in heart function. These results are in line with data indicating an association between PHPT and increased risk of premature death.

Aged↗
PubMed2007

Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism.

In primary hyperparathyroidism (PHPT), excess PTH secretion by adenomatous or hyperplastic parathyroid glands leads to elevated serum [Ca(2+)]. Patients present complex symptoms of muscular fatigue, various neuropsychiatric, neuromuscular, and cardiovascular manifestations, and, in advanced disease, kidney stones and metabolic bone disease. Our objective was to characterize changes in muscle and hematopoietic gene expression in patients with reversible mild PHPT after parathyroidectomy and possibly link molecular pathology to symptoms. Global mRNA profiling using Affymetrix gene chips was carried out in biopsies obtained before and 1 yr after parathyroidectomy in seven patients discovered by routine blood [Ca(2+)] screening. The tissue distribution of PTH receptor (PTHR1 and PTHR2) mRNAs were quantitated using real-time RT-PCR in unrelated persons to define PTH target tissues. Of about 10,000 expressed genes, 175 muscle, 169 hematological, and 99 bone-associated mRNAs were affected. Notably, the major part of muscle-related mRNAs was increased whereas hematological mRNAs were predominantly decreased during disease. Functional and molecular network analysis demonstrated major alterations of several tissue characteristic groups of mRNAs as well as those belonging to common cell signaling and major metabolic pathways. PTHR1 and PTHR2 mRNAs were more abundantly expressed in muscle and brain than in hematopoietic cells. We suggest that sustained stimulation of PTH receptors present in brain, muscle, and hematopoietic cells have to be considered as one independent, important cause of molecular disease in PHPT leading to profound alterations in gene expression that may help explain symptoms like muscle fatigue, cardiovascular pathology, and precipitation of psychiatric illness.

Aged↗
PubMed2006

R990G polymorphism of the calcium-sensing receptor and renal calcium excretion in patients with primary hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) shows a great variability in clinical course and severity. Data concerning the association between polymorphic variants of the gene encoding the calcium-sensing receptor (CaSR) and clinical characteristics of PHPT are not conclusive. OBJECTIVE: To evaluate the frequency of three polymorphisms; A986S, R990G, and Q1011E of CaSR in patients with PHPT and to correlate the genotypes with clinical and biochemical parameters. PATIENTS AND METHODS: The study included 94 consecutive unrelated patients referred to our Departments for PHPT diagnosis and management between 2000 and 2005 and 137 age and sex-matched healthy subjects. Patients and controls were genotyped according to standard procedures. Due to the rarity of 990G allele, homozygous and heterozygous subjects were grouped in R/G+G/G set. All PHPT patients were studied for calcium metabolism parameters and renal and bone complications. RESULTS: The proportion of CaSRvariants was similar in PHPT patients and controls. In PHPT patients, only R990G polymorphism was associated with disease parameters; in comparison with R/R, R/G+G/G patients showed lower mean serum parathyroid hormone (PTH) and phosphate levels (139.9 +/- 62.2 vs 199.9 +/- 136.3 pg/ml, P < 0.05 and 0.69 +/- 0.12 vs 0.81 +/- 0.18 mmol/l, P = 0.031 respectively), higher mean 24-h urine calcium concentration and calcium excretion (9.05 +/- 2.05 vs 6.77 +/- 4.31 mmol/24 h, P = 0.012 and 67 +/- 20 vs 51 +/- 26 mumol/l GF, P = 0.039), and increased prevalence of nephrolithiasis (90.0 vs 44.2%, P = 0.007). CONCLUSIONS: The study showed that patients with PHPT, bearing the 990G allele, had lower serum PTH levels and higher urinary calcium excretion in comparison with the other genotype, suggesting an increased sensitivityof the variant receptor to extracellular calcium. Since this variant was associated with increased occurrence of nephrolithiasis, analysis of this polymorphism might help to predict renal complication of the disease.

Aged↗
PubMed1976

Primary hyperparathyroidism in the primary care setting.

A series of 36 patients with surgically proved primary hyperparathyroidism is reported. From this group a clinical profile consisting of obesity, anxiety, and/or depression in a mildly hypertensive, middleaged female was derived. Women constituted 92 percent of the patients. The serum calcium was confirmed again as the single most valuable test in the evaluation of this disorder.

Depression↗
PubMed1995

Neuromuscular recovery after parathyroidectomy in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism today is diagnosed in the asymptomatic phase because of the inclusion of serum calcium in sequential multichannel analysis. The purpose of present study was to test for neuromuscular abnormalities in asymptomatic patients and to test the improvement of neuromuscular performance after parathyroidectomy. METHODS: Nine patients with primary hyperparathyroidism and nine patients with nodular goiter were enrolled in this study. Neuromuscular recovery including muscle power, sensation, and fine motor movement was studied before operation and 1 week and 4 weeks after operation. The muscle power was measured as grip power, palm pinch, lateral pinch, and three-chuck pinch. The sensation was measured as touch sensation and two-point discrimination. The fine motor movement was measured with the Purdue Pegboard Test and the Minnesota Manual Dexterity Test. RESULTS: Four weeks after the operation the patients with hyperparathyroidism had increased their muscle strength and had improved fine motor movement but no change was noted in two-point and touch sensation. When the postoperative muscle recovery was compared, there was a reversible correlation (r = -0.62; p < 0.05) with the preoperative muscle strength and no correlation with the preoperative serum calcium, phosphate, alkaline phosphatase, and intact parathyroid hormone levels. No such improvement was detectable among the control subjects. CONCLUSIONS: Surgery can improve muscle strength and fine motor movement but does not affect sensation in asymptomatic patients.

Adult↗
PubMed2001

Non-surgical therapy of primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is a commonly encountered illness that can usually be treated successfully with surgery. However, non-surgical ablation by either infusion of contrast media via angiography or percutaneous injection of ethanol has been reported from a few medical centers. METHODS: All patients undergoing non-surgical treatment of primary hyperthyroidism at the University of Oklahoma Health Sciences Center were identified and their records reviewed. RESULTS: We have used non-surgical techniques to treat three patients with primary hyperparathyroidism. The patients were considered poor surgical candidates or had persistent hypercalcemia after neck exploration. Hypercalcemia was improved or cured in each of the patients without recurrence. CONCLUSIONS: Our application of these techniques indicates that centers without extensive experience can successfully employ angiographic or ethanol ablation of parathyroid adenomas.

Adenoma↗
PubMed1991

[Mechanism of parathyroid cell proliferation in primary hyperparathyroidism].

In primary hyperparathyroidism molecular biology techniques applied to the pathological parathyroid tissue have shown that cell proliferation is monoclonal in many sporadic adenomas and in the largest parathyroid glands of multiple endocrine neoplasia type 1 (MEN-1). On the other hand, monoclonality has not been found in sporadic hyperplasia and in the smaller parathyroid glands of MEN-1. In addition, abnormalities have been observed in chromosome 11 which contains the parathyroid hormone (PTH) gene and the MEN-1 associated gene. The PTH gene was rearranged in sporadic adenomas, and there was a varying degree of chromosome 11 allele delection in sporadic adenomas and in MEN-1. The relationship between these abnormalities and parathyroid cell proliferation is controverted, and further studies are required to determine their exact role in the development of primary hyperparathyroidism.

Cell Division↗
PubMed1980

Primary hyperparathyroidism: possible cause of primary hyperaldosteronism in a 60-year-old woman.

Hypertension and hypokalemia were found in a 60-yr-old woman suffering from primary hyperparathyroidism. Laboratory investigations in this patient disclosed 1) elevated levels of plasma aldosterone (PA) which could not be suppressed by a high sodium diet alone or in combination with fludrocortisone (Florinef); 2) a decline of the elevated PA levels after 4 h of ambulation; and 3) low PRA which was unresponsive to stimulation by a low sodium diet coupled with diuretic-induced volume depletion and 4 h of ambulation. These findings were consistent with the diagnosis of primary hyperaldosteronism. Extirpation of a parathyroid adenoma reduced the patient's serum calcium level to normal, and subsequently, a normalization of her blood pressure, serum electrolytes, PA, and PRA were observed. On the basis of these data is is suggested that in this case hyperaldosteronism may have been caused directly or indirectly by primary hyperparathyroidism.

Adenoma↗