Hypercalcemia in Pulmonary TB

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Hypercalcemia in Pulmonary TB

• Chou Chien-Wen M.D.
• Endocrine and Metabolism Section
• Chi-Mei Medical Center
• 8 Aug 2003

2
Case Report

• Name ?x?
• Sex Male
• Age 87y/o
• Admission Date 92/6/20-92/7/3
• PI intermittent conscious disturbance
  with irrelevant speech, poor appetite,
  general malaise and weakness for 1-2 days
  
• PH COPD BPH with TURP in 90-8

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Laboratory Datas (1)

• WBC 11700, HB 14.2, Pl 27 x 103
• U/A WBC 8-10/HPF
• BUN 38.6, Cr 3.01, Glu 91.5,
• Na 138, K 3.78, Ca 12.88, P 3.1,
• Alb 3.2, Alk.p 225, CRP 141
• 24 hours urine Ca 425 mg, P 622 mg

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Laboratory Datas (2)

• CXR bronchiectasis superimposed
  infection over both lungs,
  emphysematous change of both lungs
• Sputum culture K-P.
• B/C no growth
• U/C Pseudomonas Aeruginosa gt10000
• T4 6.52, TSH 2.03, CEA 6.2, PSA 4.57, i-PTH 6.8
  pg/ml (normal 10-65)
• Skull X ray small geographic lucencies at right
  frontal region
• Bence-Jones protein negative

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Laboratory Datas (3)

• Sputum cytology negative
• 92/6/22 Sputum smear Acid-fast stain
• 92/6/25 Vit D1,25-OH 136 pg/ml
  (normal 15.9-55.6)
• 92/6/26 Serum Ca 11.3
• 92/6/30 Serum Ca 9.4, BUN 20.8, Cr 1.97
• 92/6/30 Sputum smear Acid-fast stain negative

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Treatment

• Normal saline iv 80 cc/h
• Bonefos 300 mg in 500 cc N/S iv 6 h for 2 days
• Haldol 1 amp stat
• 92/6/20 Cefazolin 1 gm iv q8h, GM 80 mg iv qd
• 92/6/23 Rifater 5 qd, EMB 2 qd, vit B6 1 qd
  till discharge

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Hypercalcaemia and hypokalaemia in tuberculosis

• In two patients with extensive pulmonary
  tuberculosis who developed hypercalcaemia and
  hypokalaemia
• the hypercalcaemia appeared related to the use of
  small doses of vitamin D, which suggested
  patients with tuberculosis were hypersensitive to
  vitamin D.
• The hypercalcaemia was quickly suppressed with
  steroids.
• The hypokalaemia was associated with increased
  renal excretion of potassium, and was probably
  due to distal tubular damage from hypercalcaemia.

Bradley GW. Thorax. 33(4)464-7, 1978 Aug.
9
Hypercalcemia in active pulmonary tuberculosis

• 79 consecutive patients with active pulmonary
  tuberculosis and a control group of 79 patients
  with COPD
• 22 patients developed hypercalcemia (serum
  calcium gt 10.5 mg/dl) within 4 to 16 weeks after
  initiation of chemotherapy for tuberculosis.
• The duration of hypercalcemia ranged from 1 to 7
  months, and remission occurred spontaneously in
  all patients.
• The mean daily vitamin D supplement was greater
  in hypercalcemic patients than in the
  normocalcemic group.
• There was a positive correlation between daily
  vitamin D supplement and degree and duration of
  hypercalcemia.
• 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.
• Hypercalcemia appears to be related to the
  activity of pulmonary tuberculosis and the intake
  of vitamin D the exact mechanism, however,
  remains unknown.

Abbasi AA. Annals of Internal Medicine.
90(3)324-8, 1979 Mar.
10
Evidence for abnormal regulation of circulating 1
alpha, 25-dihydroxyvitamin D in patients with
pulmonary tuberculosis and normal calcium
metabolism

• 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
• 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.
• Serum calcium was normal and remained within the
  normal range in all subjects and patients.
• significant abnormality in the regulation of
  circulating 1 alpha, 25(OH)2D in normocalcemic
  patients with pulmonary tuberculosis.

Epstein S. Calcified Tissue International.
36(5)541-4, 1984 Sep
11
Hypercalcemia associated with increased
circulating 1,25 dihydroxyvitamin D in a patient
with pulmonary tuberculosis.

• 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.
• Serum 25-hydroxyvitamin D (25OHD) was suppressed
  during the abnormal elevation of serum
  1,25(OH)2D.
• It is concluded that tuberculosis is a chronic
  granulomatous disease in which hypercalcemia may
  result from abnormal metabolism of vitamin D.

Bell NH. Calcified Tissue International.
37(6)588-91, 1985 Dec.
12
Are tuberculous patients at a great risk from
hypercalcemia?.

• The risk of tuberculous was investigated in 33
  patients aged 19 to 80.
• 22 of the 33 received no vitamin D supplements.
• 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.
• 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.
• When chemotherapy was added to 25(OH)D, the five
  patients showed high normal 1,25(OH)2D levels.
• The last six patients received 25(OH)D together
  with or after starting chemotherapy.
• None of the 33 patients developed hypercalcemia,
  even when supplemented with 25(OH)D for two
  months.
• It appears that hypercalcemia is uncommon in
  tuberculosis.

Fuss M. Quarterly Journal of Medicine.
69(259)869-78, 1988 Nov.
13
Hypercalcemia in pulmonary tuberculosis

• 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 /-
  0.16 (SD) vs 2.43 /- 0.07 mmol/l p less than
  0.001) and 25 of the patients had hypercalcemia.
  
• After one year of successful tuberculostatic
  treatment the serum calcium values had normalized

Lind L. Upsala Journal of Medical Sciences.
95(2)157-60, 1990
14
Hypercalcemia in active pulmonary tuberculosis
and its occurrence in relation to the
radiographic extent of disease

• 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.
• Only one (1.6) patient had a corrected plasma
  calcium level above the reference range for our
  laboratory.
• There was a positive relationship between the
  corrected plasma calcium levels and the
  radiographic extent of disease (r 0.37), p lt
  0.01).
• a low prevalence of "absolute" hypercalcemia in
  Hong Kong could be related to the low dietary
  calcium intake in these subjects.

Chan TY Southeast Asian Journal of Tropical
Medicine Public Health. 23(4)702-4, 1992 Dec.
15
Ketoconazole decreases the serum ionized calcium
and 1,25-dihydroxyvitamin D levels in
tuberculosis-associated hypercalcemia

• Two boys (aged 10.5 years and 14.7 years) with
  active tuberculosis and hypercalcemia.
• 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).
• 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).
• 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

Saggese G. American Journal of Diseases of
Children. 147(3)270-3, 1993 Mar
16
The prevalence of hypercalcaemia in pulmonary and
miliary tuberculosis--a longitudinal study.

• We studied the prevalence of hypercalcaemia in 34
  Chinese patients with pulmonary (n 32) or
  miliary (n 2) tuberculosis.
• None of these subjects were given vitamin D or
  calcium supplements. .
• 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.
• 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.
• 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.

Chan TY. Singapore Medical Journal. 35(6)613-5,
1994 Dec
17
Hypercalcemic crisis in a patient with pulmonary
tuberculosis

• Hypercalcemia occurs in 16 to 28 of patients
  with pulmonary tuberculosis.
• Rarely, however, does the calcium rise to a level
  that requires emergency management.
• In this report, a 49-year-old woman undergoing
  treatment for pulmonary tuberculosis presented
  with vomiting and weakness secondary to severe
  hypercalcemia. .
• Physicians must maintain a high index of
  suspicion since prompt recognition and therapy
  will ensure a successful outcome.

Pruitt B. Journal - Oklahoma State Medical
Association. 88(12)518-20, 1995 Dec
18
Hypercalcemia and pulmonary tuberculosis in east
Tennessee

• In a study of 83 patients with active pulmonary
  tuberculosis who were treated in East Tennessee,
  only three developed hypercalcemia.
• The incidence of hypercalcemia in East Tennessee
  is markedly lower than that quoted in earlier
  studies performed in the United States.
• 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.

Hourany J. Tennessee Medicine. 90(12)493-5, 1997
Dec
19
Hypercalcemia, inappropriate calcitriol levels,
and tuberculosis on hemodialysis.

• a female patient undergoing hemodialysis who
  developed tuberculosis, hypercalcemia, and
  inappropriately elevated calcitriol levels.
• These findings suggest ectopic production of
  calcitriol by tuberculous granulomas.
• Successful treatment of tuberculosis led to a
  substantial decrease in the levels of calcium and
  calcitriol

Peces R. Scandinavian Journal of Urology
Nephrology. 34(4)287-8, 2000 Aug
20
Hypercalcaemia in Greek patients with
tuberculosis before the initiation of
anti-tuberculosis treatment

• We prospectively evaluated all patients with
  newly-diagnosed TB presenting, either as
  inpatients or as outpatients, to our hospital,
  during a 3-year period.
• 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).
• 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.

Roussos A. Respiratory Medicine. 95(3)187-90,
2001 Mar
21
Hypercalcaemia in Greek patients with
tuberculosis before the initiation of
anti-tuberculosis treatment

• 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), Plt0.05).
• In the TB group no correlation between type of
  disease and albumin-adjusted or ionized calcium
  concentration was seen.
• Hypercalcaemia was detected in 22 patients with
  TB (25) but only three showed symptoms
  associated with it.
• We conclude that, although hypercalcaemia is a
  common laboratory finding among Greek patients
  with TB before anti-TB chemotherapy, it is
  usually asymtomatic.

Roussos A. Respiratory Medicine. 95(3)187-90,
2001 Mar
22
Sarcoidosis and other granulomatous diseases

• Unregulated synthesis of 1,25(OH)2D3, found even
  in an anephric patient
• Isolated sarcoid macrophages express the gene
  encoding the identical 25(OH)d 1 alfa-hydroxylase
• Unusual sensitivity to b\vitamin D and become
  hypercalcemic in response to ultraviolet
  radiation or oral vitamin D intake
• Also associated with other granulomatous
  diseases, such as tuberculosis, fungal
  infections. and berylliosis, Wegeners
  granulomatosis, AIDS-related Pneumocystitis
  carinii and extensive granulomatous foreign body
  reactios

Williams Textbook of Endocrinology, Tenth Edition