(Chest. 2000;117:1195-1196.)
© 2000
American College of Chest Physicians
Hypercalcemia Due to Talc Granulomatosis*
Alexander Woywodt, MD;
Wolfgang Schneider, MD;
Ursula Goebel, MD and
Friedrich C. Luft, MD
*
From the Franz Volhard Clinic, Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany.
Correspondence to: Friedrich C. Luft, MD, Franz-Volhard-Clinic, Wiltbergstrasse 50, 13125 Berlin, Germany; e-mail: luft{at}fvk-berlin.de
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Abstract
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Pulmonary disease due to talc, a group of hydrous magnesium
silicates, is almost exclusively encountered after occupational
exposure. One form of this rare disorder is talc granulomatosis. In
varying degrees, hypercalcemia is typical of granulomatous disease but
has not yet been reported in talcosis. We report the case of a former
mold maker who presented with hypercalcemia. Laboratory findings
indicated extra-renal 1-
-hydroxylation of 25-hydroxyvitamin D.
Pulmonary infiltrates prompted a lung biopsy that disclosed talc
granulomatosis. We suggest that talc granulomatosis should be added to
the list of granulomatous disorders capable of causing hypercalcemia
due to increased extra-renal 1--hydroxylation of 25-hydroxyvitamin
D.
Key Words: granulomatous inflammation • hypercalcemia • talc • vitamin D
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Introduction
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Talc,
a heterogeneous group of hydrous magnesium silicates, is widely used
as a glidant and lubricant for a broad variety of industrial purposes.
Manufacturing of ceramic, plastic, rubber and cosmetics accounts for
the majority of talc consumption worldwide, but even the paint and
confectionery industries use talc. Talc granulomatosis is one form of
pulmonary disease due to inhalation of pure talc. We report the first
case of hypercalcemia, a salient feature of many granulomatous
disorders, in a 68-year-old former mold maker with talc granulomatosis.
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Case Report
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A 68-year-old man was found to have a serum calcium
concentration of 3.36 mmol/L and an increased serum creatinine of 281
µmol/L at a routine follow-up examination for aortic and mitral valve
replacement that had been performed in 1997. At that time, both calcium
and creatinine concentrations had been within the normal range.
However, a chest roentgenogram had shown reticulonodular infiltrations
of both lung fields that had been interpreted as sequelae to congestive
heart failure. The patient had occasionally observed a dry cough,
without shortness of breath or fatigue for years. He was a nonsmoker
and had already presented with hypercalcemia 6 months earlier when he
had eventually undergone neck exploration elsewhere for suspected
hyperparathyroidism based on elevated parathyroid hormone values. To
the consternation of his physicians, all four parathyroid glands had
been normal. Thereafter, his serum calcium concentrations had decreased
to within the normal range. The patient was a retired gardener but had
worked at various professions. He denied weight loss, immobilization,
excessive intake of milk, thiazide diuretics, vitamins or
over-the-counter medications. On admission, he appeared chronically
ill. His cardiac examination revealed no evidence of aortic or mitral
prosthesis malfunction. He had harsh, end-inspiratory crackles over
both lung fields. There was no evidence of congestive heart failure.
Pulmonary function tests revealed almost normal lung volumes with a
mild decrease in diffusing capacity. A chest roentgenogram showed
extensive nodular infiltrations of both lung fields (Fig 1
). A CT scan confirmed multiple ill-defined coalescing nodular
structures. Lymph nodes of up to 1 cm in diameter were observed in the
mediastinum. The alkaline phosphatase concentration was 11 U/L
(normal), parathyroid hormone concentration < 10 ng/L (low),
25-hydroxyvitamin D 60 nmol/L (normal), and 1,25-dihydroxyvitamin D 201
pmol/L (elevated). Angiotensin-converting enzyme levels were normal. An
open lung biopsy was performed, revealing fibrous reactions with
granuloma formation. The granulomas were atypical for sarcoidosis.
Microscopy with polarized light demonstrated the presence of talc (Fig 2
). Inquiries into the occupational history revealed that he had
manufactured molds for porcelain insulators during the 1960s. Talc was
used to permit the separation of the insulators from the molds. A
diagnosis of talc pneumoconiosis was made, and the patient responded
well to steroids; serum calcium and serum creatinine reverted to
normal.
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Figure 2. Specimen obtained during open lung biopsy.
Left: foreign body giant cells with inclusions and mild
fibrosis (hematoxylin/eosin stain, original x250).
Right: microscopy with polarized light reveals strongly
birefringent particles typical of talc deposition.
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Comment
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Talc1
is defined as hydrous magnesium silicate with
the approximate formula
Mg3(Si2O5)2(OH)2.
A crystalline structure of magnesium ions sandwiched in between sheets
of silica accounts for the smoothness commonly associated with talcum
powder. Five to six million tons of talc are mined yearly throughout
the world. Consumer applications of talc include pharmaceutical tablet
production, confectionery manufacturing, and cosmetic applications such
as antiperspirant sticks or body powder. In contrast, impure talc, used
as a gliding, lubricating, or dusting agent for industrial purposes,
contains free silica, sulfides, asbestos, and iron. Since Thorel’s
original description in 1896, talc pneumoconiosis2
has
been attributed to various contaminants such as silica, rather than
talc itself, and the term mixed pneumoconiosis has been coined. Mixed
pneumoconiosis in mold makers, our patient’s earlier profession, has
been reported previously.3
Our patient presented with severe hypercalcemia, and laboratory
findings indicated increased 1,25-dihydroxyvitamin D production. We
felt that sarcoidosis, a disorder not infrequently complicated or even
heralded by hypercalcemia, was the most likely diagnosis and concluded
that the elevated parathyroid hormone value leading to neck surgery was
probably erroneous. However, hypercalcemia from granulomatous disease
can occasionally be associated with elevated instead of low parathyroid
hormone values. Young et al4
recently described a patient
with sarcoidosis who had a parathyroid hormone concentration above
normal. In that patient, parathyroidectomy was also performed,
revealing normal glands. The combination of sarcoidosis and
hyperparathyroidism is quite uncommon, but has been
reported.5
Interestingly, sarcoid granulomas may also
produce parathyroid hormone-related peptide.6
Extra-renal
1--hydroxylation of 25-hydroxyvitamin D by activated macrophages in
granulomatous lesions is believed to be primarily responsible for
hypercalcemia.4
7
Considerable overlap has been reported
between talc pneumoconiosis and sarcoidosis, both in terms of clinical
presentation and laboratory findings.8
The list of granulomatous disorders that are capable of endogenous
1,25-dihydroxyvitamin D production is a lengthy one and includes
diverse conditions such as tuberculosis, leprosy, and Crohn’s disease.
Recently, cat- scratch disease was added.9
Reporting the
first case of hypercalcemia in this disorder, we believe that talc
pneumoconiosis should be added to the list. We conclude that
granulomatous disorders in general are capable of causing hypercalcemia
by increased 1--hydroxylation of 25-hydroxyvitamin D in activated
macrophages.4
7
Received for publication July 9, 1999.
Accepted for publication September 7, 1999.
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References
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Zazenski, R, Ashton, WH, Briggs, D, et al (1995) Talc: occurrence, characterization, and consumer applications. Regul Toxicol Pharmacol 21,218-229[Medline]
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Gibbs, AE, Pooley, FD, Griffiths, DM, et al (1992) Talc pneumoconiosis: a pathologic and mineralogic study. Hum Pathol 23,1344-1354[CrossRef][Medline]
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Mark, GJ, Monroe, CB, Kazemi, H (1979) Mixed pneumoconiosis: silicosis, asbestosis, talcosis, and berylliosis. Chest 75,726-728[Abstract/Free Full Text]
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Young, C, Burrows, R, Katz, J, et al (1999) Hypercalcemia in sarcoidosis. Lancet 353,374[CrossRef][ISI][Medline]
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Tomita, A (1995) Primary hyperparathyroidism associated with sarcoidosis. Nippon Rinsho 53,949-952
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Zeimer, HJ, Greenaway, TM, Slavin, J, et al (1998) Parathyroid-hormone-related protein in sarcoidosis. Am J Pathol 152,17-21[Abstract]
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Sharma, OP (1996) Vitamin D, calcium, and sarcoidosis. Chest 109,535-539[Abstract/Free Full Text]
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Tukianinen, P, Nickels, J, Taskinen, E, et al (1984) Pulmonary granulomatous reaction: talc pneumoconiosis or chronic sarcoidosis? Br J Ind Med 41,84-87[Medline]
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Bosch, X (1998) Hypercalcemia due to endogenous overproduction of active vitamin D in identical twins with cat-scratch disease. JAMA 279,532-534[Abstract/Free Full Text]
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Abstract
Introduction
