help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shaker, J. L.
Right arrow Articles by Whyte, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shaker, J. L.
Right arrow Articles by Whyte, M. P.
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 1 384-385
Copyright © 1999 by The Endocrine Society

Letters to the Editor

Hyperparathyroidism and Increased Serum IGF-Binding Protein-2 Levels in Hepatitis C-Associated Osteosclerosis

Joseph L. Shaker

St. Luke’s Medical Center Milwaukee, Wisconsin 53215

Brian P. Moore

Appleton Medical Center Appleton, Wisconsin 54911

Michael P. Whyte

Washington University School of Medicine at Barnes-Jewish Hospital St. Louis, Missouri 63110

Recently, we described a 69-yr-old woman with hepatitis C-associated osteosclerosis (HCAO), which developed 14 yr after she acquired HC virus infection (1). Her hip and spine density had increased to 3.4–3.7 SD above mean values for age-matched women. Serum PTH levels were elevated. The cause of her hyperparathyroidism (HPT) was uncertain, because serum calcium concentrations were normal. Here, we recount new information pertinent to our patient’s HPT and, perhaps, to the pathogenesis of HCAO.

Six months after initial evaluation, our patient died from pneumonia. Postmortem examination revealed three grossly normal parathyroid glands, although a fourth gland was not identified. Microscopic examination of one of the glands showed an 8-mm diameter parathyroid adenoma (PA) (Fig. 1Go). The other two glands were unremarkable. Histological study of decalcified bone specimens from several sites revealed no evidence of peritrabecular fibrosis or osteoclast proliferation.



View larger version (148K):
[in this window]
[in a new window]
  		Figure 1. The adenoma (A) contains hypercellular parathyroid tissue that is separated from the normal gland (P) by an intact capsule (arrows). Hematoxylin and eosin stain, x100.

 
Discovery of a PA in our patient is provocative. Elevations in serum PTH levels have been documented in several other cases of HCAO (1). Sustained stimulation of the parathyroid glands, perhaps from enhanced bone formation, could lead to clonal proliferation of chief cells in HCAO. This process is documented in renal failure (2). However, lack of parathyroid gland hyperplasia, at autopsy, argues against this mechanism in our patient. Reexamination of her biochemical studies, spanning 1986–1997, showed 30 serum calcium values where correction for aberration in serum albumin and/or protein concentrations, by three methods (3, 4, 5), revealed no consistent disturbance. Depending on the method of adjustment, there were three borderline-high calcium values (1993 and 1994) and two borderline-low calcium values (1997). The other 25 determinations were normal. Furthermore, a single measurement of ionized calcium concentration was normal in 1997, when her HCAO was discovered.

Because HC virus infection causing a PA seems unlikely, mild primary HPT (PHPT) seems most likely in our patient. Perhaps hypercalcemia was masked by her increased bone accretion. Osteosclerosis does occur in patients with secondary HPT caused by renal failure (6) but is rare in PHPT, where primarily trabecular bone is affected (7). Our patient’s radiographs showed generalized osteosclerosis and hyperostosis (trabecular and cortical bone thickening, respectively), and there was no histological evidence of osteitis fibrosa cystica. PHPT, however, does not seem to be the explanation for the serum PTH elevations in other HCAO patients who were generally younger (1).

Perhaps our patient’s parathyroid adenoma and late onset of HCAO are related. HCAO, presenting years after HC virus is acquired, has been noted in other individuals (1). HCAO may result from a triggering event in susceptible patients. It is possible that increased PTH levels stimulate or act synergistically with other factors to enhance osteoblast activity in HCAO. PTH has been shown to increase secretion of insulin-like growth factor (IGF)-1 and IGF-2 from osteoblasts (8). These growth factors exert anabolic effects on bone forming cells. Recently, a disturbance in the IGF system in HCAO patients was described (9). Using a preserved specimen, we found that our patient had an elevated serum level of IGF-binding protein-2 [546 ng/mL (28–444 normal)] characteristic of HCAO (9).

Further study of patients with HCAO will provide additional insight concerning the pathophysiology of this disorder. Understanding and control of the biochemical mechanism of HCAO could provide a means to increase bone mass (1, 9).

Footnotes

Received August 6, 1998. Address all correspondence to: Joseph L. Shaker, M.D., Department of Medicine, St. Luke’s Medical Center, 2901 West Kinnickinnic River Parkway, Suite 503, Milwaukee, Wisconsin 53215-3660.

References

  1. Shaker JL, Reinus WR, Whyte MP. 1998 Hepatitis C-associated osteosclerosis: late onset after blood transfusion in an elderly woman. J Clin Endocrinol Metab. 83:93–98.[Abstract/Free Full Text]
  2. Arnold A, Brown MF, Urena P, Gaz RD, Sarfati E, Drucke TB. 1995 Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia. J Clin Invest. 95:2047–2053.
  3. Shane E. 1996 Hypercalcemia: pathogenesis, clinical manifestations, differential diagnosis, and management. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 3rd ed. Philadelphia: Lippincott-Raven; 177–186.
  4. Parfitt AM. 1974 Correction of plasma calcium measurements. [Letter] Brit Med J. 1:520.
  5. Pottgen P, Davis ER. 1976 Why measure total serum calcium? [Letter] Clin Chem. 22:1752–1753.
  6. Whyte MP. 1997 Skeletal disorders characterized by osteosclerosis or hyperostosis. In: Avidi LV, Krane SM, eds. Metabolic bone disease. San Diego: Academic Press; 697–738.
  7. Genant HK, Baron JM, Straus FH, Paloyan E, Jowsey J. 1975 Osteosclerosis in primary hyperparathyroidism. Am J Med. 59:104–113.[Medline]
  8. Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R. 1993 Anabolic actions of parathyroid hormone on bone. Endocr Rev. 14:690–709.[CrossRef][Medline]
  9. Khosla S, Hassoun AAK, Baker BK, et al. 1998 Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis: a means to increase bone mass in adults? J Clin Invest. 101:2165–2173.[Medline]




This Article
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shaker, J. L.
Right arrow Articles by Whyte, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shaker, J. L.
Right arrow Articles by Whyte, M. P.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals