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      Inhibition of Growth Hormone Secretion in Mild Primary Hyperparathyroidism

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          Abstract

          Introduction: Impairment in growth hormone (GH) secretion has been reported to occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml) plasma PTH and free Ca levels. Patients with these characteristics are relatively few, whereas the great majority of patients with biochemically diagnosed PHP are asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels. We wondered whether also patients in these latter conditions show a defective GH secretory pattern. Methods: In order to answer this question, 8 female subjects (mean age ± SE: 44 ± 1.3 years) were selected at the time of a checkup examination from a larger population of persons in fairly good clinical condition. Inclusion criteria were plasma PTH values slightly above the normal range (up to 50% higher than the maximum limit) with free Ca levels in the upper normal range or slightly higher (experimental group). Normal values in our laboratory are ionized calcium: 1.22–1.42 mmol/ml and plasma PTH: 12–72 pg/ml. A group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle normal range and significantly lower than values found in the experimental group was also selected and used as control. Experimental and control groups were tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30 min and arginine plus GH-releasing hormone (GHRH; 1 µg/kg BW in an intravenous bolus injection). The GH responses to these challenging stimulations were compared between groups. Results: Basal serum GH values were similar in all subjects. Both arginine and arginine plus GHRH induced a significant GH rise in both groups; however, the GH responses were significantly lower in the experimental than in the control group. Mean GH peak was 27.7 and 14.6 times higher than baseline after arginine and 57.5 and 26.6 times higher than baseline after arginine plus GHRH in the control and experimental group, respectively. No significant correlation was observed between PTH or Ca levels and the GH responses to challenging stimuli in any group. Conclusion: These data show that impairment in GH secretion is associated with slightly elevated levels of PTH in the presence of serum Ca values in the upper normal range. GH responses to stimulations were reduced by about 50% in our hyperparathyroid subjects. A long-time duration of this relatively small decline of GH secretory activity may be supposed to contribute to age-related catabolic processes in a large number of patients with mild primary hyperparathyroidism.

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          Most cited references 5

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          A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery.

          In the United States, most patients with primary hyperparathyroidism have few or no symptoms. The need for parathyroidectomy to treat all patients with this disorder has therefore been questioned. We studied the clinical course and development of complications for periods of up to 10 years in 121 patients with primary hyperparathyroidism, 101 (83 percent) of whom were asymptomatic. There were 30 men and 91 women (age range, 20 to 79 years). During the study, 61 patients (50 percent) underwent parathyroidectomy, and 60 patients were followed without surgery. Parathyroidectomy in patients with or without symptoms led to normalization of serum calcium concentrations and a mean (+/-SE) increase in lumbar-spine bone mineral density of 8+/-2 percent after 1 year (P=0.005) and 12+/-3 percent after 10 years (P=0.03). Bone mineral density of the femoral neck increased 6+/-1 percent after 1 year (P=0.002) and 14+/-4 percent after 10 years (P=0.002). Bone mineral density of the radius did not change significantly. The 52 asymptomatic patients who did not undergo surgery had no change in serum calcium concentration, urinary calcium excretion, or bone mineral density. However, 14 of these 52 patients (27 percent) had progression of disease, defined as the development of at least one new indication for parathyroidectomy. All 20 patients with symptoms had kidney stones. None of the 12 who underwent parathyroidectomy had recurrent kidney stones, whereas 6 of the 8 patients who did not undergo surgery did have a recurrence. In patients with primary hyperparathyroidism, parathyroidectomy results in the normalization of biochemical values and increased bone mineral density. Most asymptomatic patients who did not undergo surgery did not have progression of disease, but approximately one quarter of them did have some progression.
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            Primary hyperparathyroidism detected in a health screening

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              Parathyroid tissue in normocalcemic and hypercalcemic primary hyperparathyroidism recruited by health screening.

              Parathyroid tissue from 57 women (mean age 65.5 years) with sporadic primary hyperparathyroidism (HPT) was analyzed mainly to clarify its characteristics versus tissue from those with normocalcemia. Patients were recruited by population-based health screening of menopausal women. Analysis of three or four total serum calcium values showed normocalcemia in 16 patients (mean 2.53 mmol/L); 20 and 21 of the women were consistently (mean 2.82 mmol/L) or intermittently (mean 2.59 mmol/L) hypercalcemic, respectively. Parathyroid operation demonstrated a single adenoma in 81% of the individuals, and these lesions were most prevalent and commonly dominated by oxyphil parathyroid cells in the persistently hypercalcemic patients. Chief cell hyperplasia (two or three abnormal glands) of the nodular type was found more often in the normocalcemic patients. Total glandular weight was the smallest (mean 270 mg) among the normocalcemic women and contributed to delicate decisions with regard to the extent of resection. Immunostaining of cryosections with a monoclonal antibody recognizing a putative Ca2+ sensor demonstrated variably heterogeneous down-regulation of the recognized glycoprotein in the pathologic parathyroid glands from all the individuals. Dose-response relations for PTH release and the cytoplasmic Ca2+ concentration ([Ca2+]i) were determined in Ca2+ 0.5-3.0 mmol/L by examining dispersed cells with radioimmunoassay and microfluorometry after fura-2 loading, respectively. ED50 for PTH release and [Ca2+]i and the [Ca2+]i concentrations at Ca2+ 3.0 mmol/L were the least deranged in cells from pathologic glands of the normocalcemic patients. The findings substantiate that the abnormal parathyroid tissue of normocalcemic HPT principally is characterized by the same, albeit less extensive, morphologic and functional derangements, which consistently have been demonstrated in patients with HPT accompanied by hypercalcemia and detected clinically.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2004
                September 2004
                13 September 2004
                : 62
                : 2
                : 88-91
                Affiliations
                aDepartment of Internal Medicine and Biomedical Sciences and bDepartment of Public Health, University of Parma, School of Medicine, Parma, Italy
                Article
                79613 Horm Res 2004;62:88–91
                10.1159/000079613
                15249740
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 1, References: 14, Pages: 4
                Categories
                Original Paper

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