Upsala J Med Sci 95: 157-160, 1990 

Hypercalcemia in Pulmonary Tuberculosis 
L. Lind, S. Ljunghall 

Department of Internal Medicine, University Hospital, Uppsala, Sweden 

ABSTRACT 
Tuberculosis can affect calcium metabolism, mainly through an enhanced 

production of active vitamin D. The incidence of hypercalcemia among unselected 
patients with active pulmonary tuberculosis was investigated, retrospectively, during a 
ten-year period. Among 67 patients, the mean serum calcium concentration on 
admission was significantly raised compared to healthy controls (2.51 f 0.16 (SD) vs 
2.43 f 0.07 mmol/l; p<O.OOl) and 25 % of the patients had hypercalcemia. After one 
year of successful tuberculostatic treatment the serum calcium values had normalized. 

INTRODUCTION 
Active pulmonary tuberculosis can be accompanied by disturbances of calcium 

metabolism (1, 3, 4, 6, 9, 10). Sevral mechanisms could be involved, e.g. increased 
production of bone-resorbing factors (8), a reduced degradation of prostaglandins (l), 
but an enhanced synthesis of active vitamin D is generally considered to be most 
important (3, 5, 6, 7, 9), as also established in sarcoidosis (2, 5, 11). 

In clinical practice hypercalcemia is not recognized as a common complication 
of tuberculosis but there is little information about its incidence among unselected 
patients. 

MATERIAL AND METHODS 
Hospital records from patients being treated for pulmonary tuberculosis at the 

Departments of Lung Diseases at Gavle County Hospital, Sweden, during the years 
1976 through 1985, were investigated in retrospect. All of the following criteria were 
fulfilled by each patient: 
1. Pulmonary tuberculosis visible at chest X-ray and verified by positive direct 

sputum examination or positive Loewenstein culture. 
2. Uninterrupted and uncomplicated treatment for one year with isoniazid and 

rifampicin, supplemented with myambutol for the first three months. 
3. Healing of the disease after one year as could be judged from chest X-ray, 

laboratory and clinical findings. 

157 



4. 

5. 

Pretreatment and post-treatment (at 1 1-1 2 months) values of serum calcium and 
albumin measured in the same autoanalyzer. 
The patient should not have received vitamin D or calcium supplementation 
either before or during chemotherapy. 
Sixty-seven patients (mean age 60 k 1 4  years, 39 men and 28 women) fulfilled 

the criteria. For comparison of serum calcium values a control group, recruited from a 
health survey, was investigated. Serum calcium and albumin were measured in the 
autoanalyzer (SMAC, Technicon, USA) used in hospital practice. The values of serum 
calcium, with a reference range of 2.20-2.60 rnmol/l, are all adjusted for albumin. The 
coefficient of variation for serum calcium is 1-2 %. 

Treatment effects as well as the comparison between patients and the controls 
were statistically analysed by Student's t-test. Comparisons of the proportions of 
hypercalcemia in patients and controls were made by the chi-square test. 

S e r u m  c a l c i u m  ( m m o l / l )  

0 

000 
0 
0 

0 
00 000 

000000 
0000000 

0000 
oooo 
OOOO 
ow 

OCCCCXX 
COCO 
COO 
0 
oooo 
3 
0 
0 

0 
0 

B A Controls 

158 



R E S U L T S  
Among the 67 patients with pulmonary tuberculosis 25 Yo were hypercalcemic 

(more than 2.60 mmolll) before initiation of chemotherapy. Only two persons (3 Yo) 
showed hypercalcemia in the control group (pcO.001). 

The mean value for serum calcium in the patients before treatment was 2.51 k 
0.16 (SD) mmol/l which was significantly higher than the mean level found in the 
control population (2.43 f 0.07, peO.001). 

After one month of treatment serum calcium levels had decreased to 2.45 f 0.1 1 
(p<0.05) and a further reduction to 2.39 f 0.10 mmol/l was seen at the end of 
chemotherapy (pe0.01, see figure). At this time only one patient had a serum calcium 
value above the reference range. All together 52 of the 67 patients (78 %) displayed a 
reduction of the serum calcium values during treatment. 

The changes of serum calcium were also evident when the values were 
adjusted for the small rise (2 g/1) in serum albumin which occurred during therapy. 

D I S C U S S I O N  
Our study demonstrates that mild hypercalcemia is a common finding in 

unselected patients with pulmonary tuberculosis. While other reports found 
hypercalcemia generally associated with vitamin D supplementation and sunlight 
exposure, all our patients with high serum calcium levels were hypercalcemic without 
supplementation. The uniform distribution of calcium levels before treatment suggests 
that the alterations of calcium metabolism are not restricted to a few hypercalcemic 
subjects but is a general phenomenon which accompanies pulmonary tuberculosis. 
Serum calcium also decreased uniformly in most patients after prolonged 
chemotherapy . 

ACKNOWLEDGEMENTS 

County Hospital, who have given us advice for this study. 
We are grateful to the colleagues at the Department of Lung Diseases, Gavle 

REFERENCES 

1. 

2. 

3. 

4. 

5. 

Abbasi, A.A., Chemplavil, J.K., Farah, S., Muller, B.F. & Arnstein, A.R.: 
Hypercalcemia in active pulmonary tuberculosis. Ann Int Med 90: 324-328, 1979. 
Alberts, C. & van den Berg, H.: Calcium metabolism in sarcoidosis. A follow-up 
study with respect to parathyroid hormone and vitamin D metabolites. Eur J 
Respir Dis 68: 186-194, 1986. 
Cadranel, J., Milleron, B., Garabedian, M. & Aroun, G.: Serum concentration of 
vitamin D metabolites in untreated tuberculosis. Thorax 40: 639-640, 1985. 
Davies, P.D.O., Church, H.A., Brown, R.C. & Woodhead, J.S.: Raised serum 
calcium in tuberculosis patients in Africa. Eur J Respir Dis 71: 341-344, 1987. 
Epstein, S., Stern, P.H., Bell, N.H., Dowdeswell, I. & Turner, R.T.: Evidence for 
abnormal regulation of circulating 1,25-dihydroxyvitamin D in patients with 

159 



pulmonary tuberculosis and normal calcium metabolism. Calcif Tissue Int 36: 

Fuss, M., Karmali, R., Bergman, P., Gillet, C., Prigogine, T., Schmerber, J., ' 
Brauman, H. & Corvilain, J.: Hypercalcemia and elevated 1,25-dihydroxyvitamin 
D levels in a patients with end-stage renal disease and active pulmonary 
tuberculosis. New Engl J Med 312: 1520, 1985. 
Gkonos, P.J., London, R. & Hendler, E.D.: Hypercalcemia and elevated 1,25- 
dihydroxyvitamin D levels in a patient with end-stage renal disease and active 
tuberculosis. N Engl J Med 31 1 : 1683-1 685, 1984. 

8. Horton, J.E., Raisz, L.G., Simmons, H.A., Oppenheim, J.j. & Mergenhagen, S.E.: 
Bone resorbing activity in supernatant fluid from cultured human peripheral blood 
leukocytes. Science 177: 793-795, 1972. 

9. Narang, N.K., Gupta, R.C. & Jain, M.K.: Role of vitamin D in pulmonary 
tuberculosis, JAPl 32: 185-1 88, 1983. 

10. Need, A.G., Philips, P.J., Chiu, F.T.S. & Prisk, H.M.: Hypercalcemia associated 
with tuberculosis. Br Med J 1 : 831, 1980. 

11. Sandler, L.M., Winerals, C.G., Fraher, L.J., Clemens, T.L., Smith, R. & ORiordan, 
J.L.H.: Studies of the hypercalcemia of sarcoidosis: Effect of steroids and 
exogenous vitamin D3 on the circulating concentrations of 1,25-dihydroxyvitamin 
D3. Quart J Med 21 0: 165-1 80, 1984. 

541 -544, 1984. 
6. 

7. 

Correspondence to: Professor Sverker Ljunghall 
Department of Internal Medicine 
University Hospital 
S-751 85 UPPSALA, Sweden 

160