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Hyponatraemia and mesothelioma
Br.
J. Dis.
Chest
(1979)
73, 89
Short Communication HYPONATRAEMIA
AND MESOTHELIOMA
W. H. PERKS, R. STANHOPE AND M. GREEN
Brompton Hospital, London Summary Hyponatraemia was found in 18 (62%) of 29 patients with histologically proven mesothelioma. The mechanism for the development of the hyponatraemia is discussed. It is suggested that patients with mesothelioma should be monitored for electrolyte abnormalities. If hyponatraemia is found the syndrome hormone should be suspected as treatment with the quality of life in an otherwise fatal illness.
of inappropriate secretion demethylchlortetracycline
of antidiuretic may improve
A patient with the syndrome of inappropriate secretion of antiduretic hormone (ADH) associated with a pleural mesothelioma has recently been described (Perks et al. 1978). It was postulated that the ADH hypersecretion was mediated through a vagal reflex, either from involvement of the pulmonary baroreceptors or by direct stimulation of vagal afferents by tumour. For this hypothesis to be correct the inappropriate ADH syndrome should be common in patients with pleural mesothelioma. Careful review of the mesothelioma literature, however, revealed no other reports of this association. To ascertain the frequency of hyponatraemia in patients with mesothelioma we performed a retrospective analysis of the records of patients admitted to Brompton Hospital.
Patients, Materials
and Methods
The records of 37 patients with histologically proven mesothelioma admitted to Brompton Hospital were examined. The age at diagnosis, sex and the serum electrolytes (sodium potassium Table
I. Serum
electrolytes
of patients with mesothelioma, Mesothelioma
Number Lowest mean Number than Number than Serum Serum mean
29
serum sodium
(mmol/litre
;
13 3 .8 + 5 .4
Controls 29 139.4f1.6
controls
and normal
Normal values 135-145
values Significance -
P
*SD)
with lowest sodium less 135 mmol/litre (% total) with lowest sodium less 130 mmol/litre (% total) urea (mmol/litre; mean) potassium (mmol/litre ; &SD)
* Mann-Whitney U-test. t Fisher’s exact probability
test.
P
i,
-
(2:)
ii
-
4.5 4.2kO.4
4.1
5.0 f0.4
2.5-5.8 3.8-4.8
P
90
W. H. Perks, R. Stanhope and M. Green
and urea) were recorded. Electrolyte measurements made during treatment with diuretics, corticosteroids or drugs known to produce hyponatremia were excluded. Similarly measurements within 14 days after surgical operation or within 28 days of death were excluded. This left 29 patients with mesothelioma and estimates of plasma electrolyte levels who fulfilled the criteria for analysis. In each patient the electrolyte studies with the lowest serum sodium were analysed. Control subjects with chronic bronchitis, asthma or bronchiectasis matched for age and sex were taken randomly from the in-patient medical records. The electrolytes with the lowest serum sodium were obtained as with the mesothelioma patients. The mean age of both groups was 53 years (standard deviation + 10) and the male/female ratio was 6.4 : 1. As the distribution of the data was not Gaussian, non-parametric statistical analysis was used. Hyponatraemia was significantly more common in the mesothelioma patients. There was no significant difference in serum levels of urea and potassium between the two groups (Table I).
DISCUSSION
The inappropriate ADH syndrome can be diagnosed when there is hyponatraemia, a low serum osmolality and simultaneously a less than maximally dilute urine (De Troyer & Demanet 1976). Although hyponatraemia occurred in 62% of our patients with mesothelioma they had not been fully investigated with matched osmolalities because the inappropriate ADH syndrome was not suspected. However, the most likely cause of the hyponatraemia is inappropriate secretion of ADH since other causes were excluded by our selection of patients and the absence of abnormalities in serum levels of urea and potassium. Ectopic production of hormones has not been described with mesothelioma and is rare in other tumours of mesenchymal origin. Hypoglycaemia and hypophosphataemic osteomalacia are occasionally found with mesenchymal tumours, although there is uncertainty whether there is an ectopic humoral syndrome in the latter case (Rees 1975). It seems unlikely therefore that the hyponatraemia in our patients was caused by the ectopic production of ADH by the tumour. Perks et al. (1978) have recently proposed secretion of ADH as a reflex via the vagus nerve to be the mechanism for the hyponatraemia associated with mesothelioma. The pulmonary baroreceptors acting via the vagus are important in controlling the release of ADH from the posterior pituitary; for example loss of intravascular volume or positive pressure ventilation leads to secretion of ADH (Kleeman 1970). Compression of the pulmonary baroreceptors or infiltration of the vagus nerve by mesothelial tumour could therefore lead to reflex secretion of ADH. Against this hypothesis is the absence of previous reports of the association of hyponatraemia with mesothelioma. The finding of hyponatraemia commonly in patients with mesothelioma is further evidence for a reflex mechanism for the secretion of ADH with mesothelioma. Finally, all patients with mesothelial tumours should be investigated for the inappropriate ADH syndrome since treatment with demethylchlortetracycline may improve the quality of life in an otherwise fatal condition (Perks et al. 1976).
ACKNOWLEDGEMENTS
We thank Mrs Ellen Dyche for secretarial help and Mr D. Brown for statistical advice.
Hyponatraemia
and Mesothelioma
91
REFERENCES DE TROYER, A. & DEMANET, J. C. (1976) Clinical, biological and pathogenic features of the syndrome of inappropriate secretion of antidiuretic hormone. Q. Jl Med. 180, 521. KLEEMAN, C. R. (1970) Hypo-osmolar syndromes secondary to impaired water excretion. A. Rev.
Med. 21, 259. PERILS, W. H., CROW, J. C. & GREEN, M. (1978) Mesothelioma associcated with the syndrome of inappropriate secretion of antidiuretic hormone. Am. Rev. resp. Dis. 117, 789. PERKS, W. H., MOHR, P. & LIVERSEDGE, L. A. (1976) Demeclocycline in inappropriate ADH syndrome. Lancet 2, 1414. &ES, L. H. (1975) The biosynthesis of hormones by non-endorcrine turnours: A review. J.
Endow.
67, 143.
J. Dis.
Chest
(1979)
73, 89
Short Communication HYPONATRAEMIA
AND MESOTHELIOMA
W. H. PERKS, R. STANHOPE AND M. GREEN
Brompton Hospital, London Summary Hyponatraemia was found in 18 (62%) of 29 patients with histologically proven mesothelioma. The mechanism for the development of the hyponatraemia is discussed. It is suggested that patients with mesothelioma should be monitored for electrolyte abnormalities. If hyponatraemia is found the syndrome hormone should be suspected as treatment with the quality of life in an otherwise fatal illness.
of inappropriate secretion demethylchlortetracycline
of antidiuretic may improve
A patient with the syndrome of inappropriate secretion of antiduretic hormone (ADH) associated with a pleural mesothelioma has recently been described (Perks et al. 1978). It was postulated that the ADH hypersecretion was mediated through a vagal reflex, either from involvement of the pulmonary baroreceptors or by direct stimulation of vagal afferents by tumour. For this hypothesis to be correct the inappropriate ADH syndrome should be common in patients with pleural mesothelioma. Careful review of the mesothelioma literature, however, revealed no other reports of this association. To ascertain the frequency of hyponatraemia in patients with mesothelioma we performed a retrospective analysis of the records of patients admitted to Brompton Hospital.
Patients, Materials
and Methods
The records of 37 patients with histologically proven mesothelioma admitted to Brompton Hospital were examined. The age at diagnosis, sex and the serum electrolytes (sodium potassium Table
I. Serum
electrolytes
of patients with mesothelioma, Mesothelioma
Number Lowest mean Number than Number than Serum Serum mean
29
serum sodium
(mmol/litre
;
13 3 .8 + 5 .4
Controls 29 139.4f1.6
controls
and normal
Normal values 135-145
values Significance -
P
*SD)
with lowest sodium less 135 mmol/litre (% total) with lowest sodium less 130 mmol/litre (% total) urea (mmol/litre; mean) potassium (mmol/litre ; &SD)
* Mann-Whitney U-test. t Fisher’s exact probability
test.
P
i,
-
(2:)
ii
-
4.5 4.2kO.4
4.1
5.0 f0.4
2.5-5.8 3.8-4.8
P
90
W. H. Perks, R. Stanhope and M. Green
and urea) were recorded. Electrolyte measurements made during treatment with diuretics, corticosteroids or drugs known to produce hyponatremia were excluded. Similarly measurements within 14 days after surgical operation or within 28 days of death were excluded. This left 29 patients with mesothelioma and estimates of plasma electrolyte levels who fulfilled the criteria for analysis. In each patient the electrolyte studies with the lowest serum sodium were analysed. Control subjects with chronic bronchitis, asthma or bronchiectasis matched for age and sex were taken randomly from the in-patient medical records. The electrolytes with the lowest serum sodium were obtained as with the mesothelioma patients. The mean age of both groups was 53 years (standard deviation + 10) and the male/female ratio was 6.4 : 1. As the distribution of the data was not Gaussian, non-parametric statistical analysis was used. Hyponatraemia was significantly more common in the mesothelioma patients. There was no significant difference in serum levels of urea and potassium between the two groups (Table I).
DISCUSSION
The inappropriate ADH syndrome can be diagnosed when there is hyponatraemia, a low serum osmolality and simultaneously a less than maximally dilute urine (De Troyer & Demanet 1976). Although hyponatraemia occurred in 62% of our patients with mesothelioma they had not been fully investigated with matched osmolalities because the inappropriate ADH syndrome was not suspected. However, the most likely cause of the hyponatraemia is inappropriate secretion of ADH since other causes were excluded by our selection of patients and the absence of abnormalities in serum levels of urea and potassium. Ectopic production of hormones has not been described with mesothelioma and is rare in other tumours of mesenchymal origin. Hypoglycaemia and hypophosphataemic osteomalacia are occasionally found with mesenchymal tumours, although there is uncertainty whether there is an ectopic humoral syndrome in the latter case (Rees 1975). It seems unlikely therefore that the hyponatraemia in our patients was caused by the ectopic production of ADH by the tumour. Perks et al. (1978) have recently proposed secretion of ADH as a reflex via the vagus nerve to be the mechanism for the hyponatraemia associated with mesothelioma. The pulmonary baroreceptors acting via the vagus are important in controlling the release of ADH from the posterior pituitary; for example loss of intravascular volume or positive pressure ventilation leads to secretion of ADH (Kleeman 1970). Compression of the pulmonary baroreceptors or infiltration of the vagus nerve by mesothelial tumour could therefore lead to reflex secretion of ADH. Against this hypothesis is the absence of previous reports of the association of hyponatraemia with mesothelioma. The finding of hyponatraemia commonly in patients with mesothelioma is further evidence for a reflex mechanism for the secretion of ADH with mesothelioma. Finally, all patients with mesothelial tumours should be investigated for the inappropriate ADH syndrome since treatment with demethylchlortetracycline may improve the quality of life in an otherwise fatal condition (Perks et al. 1976).
ACKNOWLEDGEMENTS
We thank Mrs Ellen Dyche for secretarial help and Mr D. Brown for statistical advice.
Hyponatraemia
and Mesothelioma
91
REFERENCES DE TROYER, A. & DEMANET, J. C. (1976) Clinical, biological and pathogenic features of the syndrome of inappropriate secretion of antidiuretic hormone. Q. Jl Med. 180, 521. KLEEMAN, C. R. (1970) Hypo-osmolar syndromes secondary to impaired water excretion. A. Rev.
Med. 21, 259. PERILS, W. H., CROW, J. C. & GREEN, M. (1978) Mesothelioma associcated with the syndrome of inappropriate secretion of antidiuretic hormone. Am. Rev. resp. Dis. 117, 789. PERKS, W. H., MOHR, P. & LIVERSEDGE, L. A. (1976) Demeclocycline in inappropriate ADH syndrome. Lancet 2, 1414. &ES, L. H. (1975) The biosynthesis of hormones by non-endorcrine turnours: A review. J.
Endow.
67, 143.