Hypercalcemia in pulmonary TB


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Hypercalcemia in pulmonary TB

  1. 1. Hypercalcemia in Pulmonary TB Chou Chien-Wen M.D. Endocrine and Metabolism Section Chi-Mei Medical Center 8 Aug 2003
  2. 2. Case Report <ul><li>Name: 王 x 賜 </li></ul><ul><li>Sex: Male </li></ul><ul><li>Age: 87y/o </li></ul><ul><li>Admission Date: 92/6/20-92/7/3 </li></ul><ul><li>PI: intermittent conscious disturbance with irrelevant speech, poor appetite, general malaise and weakness for 1-2 days </li></ul><ul><li>PH: COPD BPH with TURP in 90-8 </li></ul>
  3. 3. Laboratory Datas (1) <ul><li>WBC 11700, HB 14.2, Pl 27 x 10^3 </li></ul><ul><li>U/A: WBC 8-10/HPF </li></ul><ul><li>BUN 38.6, Cr 3.01, Glu 91.5, </li></ul><ul><li>Na 138, K 3.78, Ca 12.88, P 3.1, </li></ul><ul><li>Alb 3.2, Alk.p 225, CRP 141 </li></ul><ul><li>24 hours urine Ca 425 mg, P 622 mg </li></ul>
  4. 4. Laboratory Datas (2) <ul><li>CXR: bronchiectasis superimposed infection over both lungs, emphysematous change of both lungs </li></ul><ul><li>Sputum culture: K-P. </li></ul><ul><li>B/C: no growth </li></ul><ul><li>U/C: Pseudomonas Aeruginosa >10000 </li></ul><ul><li>T4 6.52, TSH 2.03, CEA 6.2, PSA 4.57, i-PTH 6.8 pg/ml (normal 10-65) </li></ul><ul><li>Skull X ray: small geographic lucencies at right frontal region </li></ul><ul><li>Bence-Jones protein: negative </li></ul>
  5. 6. Laboratory Datas (3) <ul><li>Sputum cytology: negative </li></ul><ul><li>92/6/22 Sputum smear: Acid-fast stain ++ </li></ul><ul><li>92/6/25 Vit D1,25-OH 136 pg/ml (normal 15.9-55.6) </li></ul><ul><li>92/6/26 Serum Ca 11.3 </li></ul><ul><li>92/6/30 Serum Ca 9.4, BUN 20.8, Cr 1.97 </li></ul><ul><li>92/6/30 Sputum smear: Acid-fast stain negative </li></ul>
  6. 7. Treatment <ul><li>Normal saline iv 80 cc/h </li></ul><ul><li>Bonefos 300 mg in 500 cc N/S iv 6 h for 2 days </li></ul><ul><li>Haldol 1 amp stat </li></ul><ul><li>92/6/20 Cefazolin 1 gm iv q8h, GM 80 mg iv qd </li></ul><ul><li>92/6/23 Rifater 5# qd, EMB 2# qd, vit B6 1# qd till discharge </li></ul>
  7. 8. Hypercalcaemia and hypokalaemia in tuberculosis <ul><ul><li>In two patients with extensive pulmonary tuberculosis who developed hypercalcaemia and hypokalaemia </li></ul></ul><ul><ul><li>the hypercalcaemia appeared related to the use of small doses of vitamin D , which suggested patients with tuberculosis were hypersensitive to vitamin D. </li></ul></ul><ul><ul><li>The hypercalcaemia was quickly suppressed with steroids. </li></ul></ul><ul><ul><li>The hypokalaemia was associated with increased renal excretion of potassium , and was probably due to distal tubular damage from hypercalcaemia. </li></ul></ul>Bradley GW. Thorax. 33(4):464-7, 1978 Aug .
  8. 9. Hypercalcemia in active pulmonary tuberculosis <ul><ul><li>79 consecutive patients with active pulmonary tuberculosis and a control group of 79 patients with COPD </li></ul></ul><ul><ul><li>22 patients developed hypercalcemia (serum calcium > 10.5 mg/dl) within 4 to 16 weeks after initiation of chemotherapy for tuberculosis. </li></ul></ul><ul><ul><li>The duration of hypercalcemia ranged from 1 to 7 months , and remission occurred spontaneously in all patients. </li></ul></ul><ul><ul><li>The mean daily vitamin D supplement was greater in hypercalcemic patients than in the normocalcemic group. </li></ul></ul><ul><ul><li>There was a positive correlation between daily vitamin D supplement and degree and duration of hypercalcemia . </li></ul></ul><ul><ul><li>Mean serum calcium in patients with tuberculosis was higher than in patients with chronic obstructive pulmonary disease supplemented with the same dose of vitamin D . </li></ul></ul><ul><ul><li>Hypercalcemia appears to be related to the activity of pulmonary tuberculosis and the intake of vitamin D ; the exact mechanism, however, remains unknown. </li></ul></ul>Abbasi AA. A nnals of Internal Medicine. 90(3):324-8, 1979 Mar.
  9. 10. Evidence for abnormal regulation of circulating 1 alpha, 25-dihydroxyvitamin D in patients with pulmonary tuberculosis and normal calcium metabolism <ul><ul><li>vitamin D, 100,000 units a day for 4 days , were compared in 25 normal subjects and 11 patients with active pulmonary tuberculosis who were normocalcemic </li></ul></ul><ul><ul><li>Whereas vitamin D increased mean serum 25-OHD from 20 +/- 2 (+/- SE) to 40 +/- 5 ng/ml (P less than 0.001) and did not change mean serum 1 alpha, 25(OH)2D in the normals (33 +/- 2 vs. 31 +/- 2 pg/ml), it increased mean serum 25-OHD from 21 +/- 4 to 55 +/- 13 ng/ml (P less than 0.05) and mean serum 1 alpha, 25(OH)2D from 28 +/- 2 to 35 +/- 3 pg/ml (P less than 0.05) in the patients . </li></ul></ul><ul><ul><li>Serum calcium was normal and remained within the normal range in all subjects and patients. </li></ul></ul><ul><ul><li>significant abnormality in the regulation of circulating 1 alpha, 25(OH)2D in normocalcemic patients with pulmonary tuberculosis. </li></ul></ul>Epstein S. Calcified Tissue International. 36(5):541-4, 1984 Sep
  10. 11. Hypercalcemia associated with increased circulating 1,25 dihydroxyvitamin D in a patient with pulmonary tuberculosis. <ul><ul><li>a 53-year-old man with far-advanced pulmonary tuberculosis who developed transient increases in circulating 1,25 dihydroxyvitamin D (1,25(OH)2D) and hypercalcemia while on antituberculous treatment . </li></ul></ul><ul><ul><li>Serum 25-hydroxyvitamin D (25OHD) was suppressed during the abnormal elevation of serum 1,25(OH)2D. </li></ul></ul><ul><ul><li>It is concluded that tuberculosis is a chronic granulomatous disease in which hypercalcemia may result from abnormal metabolism of vitamin D. </li></ul></ul>Bell NH. Calcified Tissue International. 37(6):588-91, 1985 Dec.
  11. 12. Are tuberculous patients at a great risk from hypercalcemia?. <ul><ul><li>The risk of tuberculous was investigated in 33 patients aged 19 to 80. </li></ul></ul><ul><ul><li>22 of the 33 received no vitamin D supplements . </li></ul></ul><ul><ul><li>After 17 to 34 days of chemotherapy serum calcium corrected for albumin and 1,25(OH)2D levels were lower without change in serum D-binding protein. </li></ul></ul><ul><ul><li>In 11 patients 25(OH)D, 50 micrograms/day, was given orally for two months . 25(OH)D given three days before chemotherapy in five patients induced an increase of levels of 1,25(OH)2D which was greater than in 10 control patients with similar serum levels of 25(OH)D. </li></ul></ul><ul><ul><li>When chemotherapy was added to 25(OH)D, the five patients showed high normal 1,25(OH)2D levels. </li></ul></ul><ul><ul><li>The last six patients received 25(OH)D together with or after starting chemotherapy. </li></ul></ul><ul><ul><li>None of the 33 patients developed hypercalcemia, even when supplemented with 25(OH)D for two months . </li></ul></ul><ul><ul><li>It appears that hypercalcemia is uncommon in tuberculosis. </li></ul></ul>Fuss M. Quarterly Journal of Medicine. 69(259):869-78, 1988 Nov.
  12. 13. Hypercalcemia in pulmonary tuberculosis <ul><li>The incidence of hypercalcemia among unselected patients with active pulmonary tuberculosis was investigated, retrospectively, during a ten-year period . </li></ul><ul><li>Among 67 patients , the mean serum calcium concentration on admission was significantly raised compared to healthy controls (2.51 +/- 0.16 (SD) vs 2.43 +/- 0.07 mmol/l; p less than 0.001) and 25% of the patients had hypercalcemia. </li></ul><ul><li>After one year of successful tuberculostatic treatment the serum calcium values had normalized </li></ul>Lind L. Upsala Journal of Medical Sciences. 95(2):157-60, 1990
  13. 14. Hypercalcemia in active pulmonary tuberculosis and its occurrence in relation to the radiographic extent of disease <ul><ul><li>The prevalence of hypercalcemia in tuberculosis in Hong Kong and its occurrence in relation to the radiographic extent of disease were studied in 57 patients with sputum smear (n = 44) and/or culture positive (n = 13) pulmonary tuberculosis and in five patients with military tuberculosis prior to treatment. </li></ul></ul><ul><ul><li>Only one (1.6%) patient had a corrected plasma calcium level above the reference range for our laboratory. </li></ul></ul><ul><ul><li>There was a positive relationship between the corrected plasma calcium levels and the radiographic extent of disease (r = 0.37 ), p < 0.01). </li></ul></ul><ul><ul><li>a low prevalence of &quot;absolute&quot; hypercalcemia in Hong Kong could be related to the low dietary calcium intake in these subjects. </li></ul></ul>Chan TY Southeast Asian Journal of Tropical Medicine & Public Health. 23(4):702-4, 1992 Dec.
  14. 15. Ketoconazole decreases the serum ionized calcium and 1,25-dihydroxyvitamin D levels in tuberculosis-associated hypercalcemia <ul><li>Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia. </li></ul><ul><li>At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L 72.4% in one boy and from 321.6 to 115.2 pmol/L 64.2% in the other). </li></ul><ul><li>coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L 13.0% in one boy and from 1.55 to 1.26 mmol/L 17.0% in the other). </li></ul><ul><li>CONCLUSIONS-- Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis </li></ul>Saggese G. American Journal of Diseases of Children. 147(3):270-3, 1993 Mar
  15. 16. The prevalence of hypercalcaemia in pulmonary and miliary tuberculosis--a longitudinal study. <ul><li>We studied the prevalence of hypercalcaemia in 34 Chinese patients with pulmonary (n = 32) or miliary (n = 2) tuberculosis . </li></ul><ul><li>None of these subjects were given vitamin D or calcium supplements. . </li></ul><ul><li>During the 6-month study period, two patients (6%) developed hypercalcaemia (plasma calcium greater than 2.51 mmol/l), as compared to figures of 16% to 28% in the United States and India. </li></ul><ul><li>By correcting the plasma calcium to a normal albumin, five ( 15%) of our patients were hypercalcaemic, as compared to a figure of 48% in Greece . </li></ul><ul><li>Apart from variations in methodology, discrepancies in the reported prevalence of hypercalcaemia in tuberculosis may be due to differences in sun exposure, and vitamin D and calcium intake. </li></ul>Chan TY. Singapore Medical Journal. 35(6):613-5, 1994 Dec
  16. 17. Hypercalcemic crisis in a patient with pulmonary tuberculosis <ul><li>Hypercalcemia occurs in 16% to 28% of patients with pulmonary tuberculosis. </li></ul><ul><li>Rarely, however, does the calcium rise to a level that requires emergency management . </li></ul><ul><li>In this report, a 49-year-old woman undergoing treatment for pulmonary tuberculosis presented with vomiting and weakness secondary to severe hypercalcemia . . </li></ul><ul><li>Physicians must maintain a high index of suspicion since prompt recognition and therapy will ensure a successful outcome. </li></ul>Pruitt B. Journal - Oklahoma State Medical Association. 88(12):518-20, 1995 Dec
  17. 18. Hypercalcemia and pulmonary tuberculosis in east Tennessee <ul><li>In a study of 83 patients with active pulmonary tuberculosis who were treated in East Tennessee, only three developed hypercalcemia. </li></ul><ul><li>The incidence of hypercalcemia in East Tennessee is markedly lower than that quoted in earlier studies performed in the United States. </li></ul><ul><li>The explanation for the infrequent occurrence of elevated serum calcium in our population is probably multifactorial, but does not appear to be related to the selection of antituberculous agents . </li></ul>Hourany J. Tennessee Medicine. 90(12):493-5, 1997 Dec
  18. 19. Hypercalcemia, inappropriate calcitriol levels, and tuberculosis on hemodialysis. <ul><li>a female patient undergoing hemodialysis who developed tuberculosis, hypercalcemia, and inappropriately elevated calcitriol levels. </li></ul><ul><li>These findings suggest ectopic production of calcitriol by tuberculous granulomas . </li></ul><ul><li>Successful treatment of tuberculosis led to a substantial decrease in the levels of calcium and calcitriol </li></ul>Peces R. Scandinavian Journal of Urology & Nephrology. 34(4):287-8, 2000 Aug
  19. 20. Hypercalcaemia in Greek patients with tuberculosis before the initiation of anti-tuberculosis treatment <ul><ul><li>We prospectively evaluated all patients with newly-diagnosed TB presenting, either as inpatients or as outpatients, to our hospital, during a 3-year period . </li></ul></ul><ul><ul><li>We evaluated 88 patients with TB (50 males and 38 females), aged between 23 and 89 years (mean age+/-SD: 46.4+/-19 years), and 65 age- and sex-matched controls with chronic obstructive pulmonary disease (36 males and 29 females), aged between 28 and 88 years (mean age+/-SD: 47.2+/-18 years). </li></ul></ul><ul><ul><li>Among TB patients, 56 had pulmonary TB, 20 had pleural TB without evidence of pulmonary parenchyma involvement, eight had pulmonary and pleural TB, and four had disseminated disease. </li></ul></ul>Roussos A. Respiratory Medicine. 95(3):187-90, 2001 Mar
  20. 21. Hypercalcaemia in Greek patients with tuberculosis before the initiation of anti-tuberculosis treatment <ul><ul><li>The mean (+/-SD) albumin-adjusted serum calcium concentration and the mean ionized calcium concentration were significantly higher in the TB group (2.49+/-0.21 mmol l(-1) and 1.27+/-0.02 mmol l(-1) respectively) than in the control group (2.36+/-0.11 mmol l(-1) and 1.19+/-0.02 mmol l(-1), P<0.05). </li></ul></ul><ul><ul><li>In the TB group no correlation between type of disease and albumin-adjusted or ionized calcium concentration was seen. </li></ul></ul><ul><ul><li>Hypercalcaemia was detected in 22 patients with TB (25%) but only three showed symptoms associated with it. </li></ul></ul><ul><ul><li>We conclude that, although hypercalcaemia is a common laboratory finding among Greek patients with TB before anti-TB chemotherapy, it is usually asymtomatic. </li></ul></ul>Roussos A. Respiratory Medicine. 95(3):187-90, 2001 Mar
  21. 22. Sarcoidosis and other granulomatous diseases <ul><li>Unregulated synthesis of 1,25(OH)2D3, found even in an anephric patient </li></ul><ul><li>Isolated sarcoid macrophages express the gene encoding the identical 25(OH)d 1 alfa-hydroxylase </li></ul><ul><li>Unusual sensitivity to bvitamin D and become hypercalcemic in response to ultraviolet radiation or oral vitamin D intake </li></ul><ul><li>Also associated with other granulomatous diseases, such as tuberculosis, fungal infections . and berylliosis , Wegener’s granulomatosis, AIDS-related Pneumocystitis carinii and extensive granulomatous foreign body reactios </li></ul>Williams Textbook of Endocrinology, Tenth Edition