144
LITHIUM, HYPERCALCÆMIA, AND HYPERPARATHYROIDISM
SIR,-Garfinkel et al.’ outlined a case in which hypercalcaemia and primary hyperparathyroidism (P.H.P.T.) may have been associated with lithium-carbonate medication. I have studied six patients, all females aged 32-45, who had been on lithium because of manic excitement for 2-4 years. All of them were under psychiatric observation, and their mental illness was well managed by lithium. All these patients developed hypercalca:mia after an average of one year, without any other manifestations characteristic of hypercalca:mia or P.H.P.T., such as nephrolithiasis, findings of subperiosteal resorption on skeletal X-ray, raised parathyroid hormone concentration, and low serum-phosphate. There was no evidence of increased urinary excretion of calcium. All six females were studied while in the Serafimerlasarettet, Stockholm. A standardised daily dietary intake (calcium 800 mg, phosphorus 800 mg, and magnesium 300 mg) was used but no other cause of the repeatedly raised serum-calcium was found apart from possible P.H.P.T. Regular check-ups and previous records confirmed that none of the patients had had a serumcalcium above the upper limit until about a year after the start of therapy with lithium. After that values were consistently between 2.75 and 2.80 mmol/1 (upper normal limit 2-64). Causes of hypercalcaemia other than P.H.P.T. were excluded as far as possible. After discharge the six patients were checked every third month, and the hypercalca:mia persisted. After consultation with the psychiatrist, lithium was discontinued in four patients; after 3 weeks all these women had normal serum-calcium levels. The four women were readmitted and studied under dietary restrictions. No laboratory abnormalities were revealed and urinary calcium excretion was normal. Lithium was re-introduced after 3-4 months, and 3-4 weeks later the serum-calcium was again high. After another week in hospital and further studies under standardised dietary intake all the patients underwent surgery, which revealed single parathyroid adenomas, dominated by chief cells, in each case. Apart from the raised serum-calcium there were no other laboratory abnormalities. The hypercalceemia disappeared postoperatively and lithium treatment was re-introduced. No rise of the serumcalcium level has been noted after this and check-ups have been performed every third month (up to 18 months). Depression, loss of initiative, and fatigue are among the characteristic psychic changes of P.H.P.T.2 Manic excitement is not usually a feature, though the occasional patient may be aggressive or irritable. Lithium treatment was supervised by a psychiatrist, with monitoring of serum concentration. Renal filtration (creatinine clearance) was intact in all cases. The association between lithium and the development of hypercalcxmia and P.H.P.T. might be fortuitous rather than causal. However, the hypercalcaemia did disappear after discontinuation of lithium and it reappeared when lithium was re-introduced. Some people may have a tendency to reversible hypercalcaemia, or it may be provoked by thiazides, for example,3 or, as here possibly, by lithium. Normocalcwmic P.H.P.T. has been described,4 and the six patients may have had normocalcsemic P.H.P.T. and been provoked into raised serum- calcium. The effect of lithium on electrolyte metabolism is controversial ; Aronoff et a1. found no effect on serum-calcium. The mechanism behind the apparent association between lithium therapy and hypercalcsemia and P.H.P.T. calls for further investigation. I suggest that the serum-calcium be checked routinely in patients on lithium.
This study has been supported by grants from Clas Groschinsky’s Fund, Stockholm, the research funds of the Svenska Läkaresällskapet (Stockholm) and of Svenska Sallskapet f6r medicinsk forskning
(Stockholm). Department of Medicine, Serafimerlasarettet, S-112 83 Stockholm, Sweden
TONY A. T. CHRISTENSSON
NUTRITIONAL STATUS AND THYROID HORMONES
SIR,-We found the report by Professor Bray and his col-
leagues (June 5, to
p.
1206)
on
the relation of
thyroid hormones
body-weight stimulating. We have investigated the
effects of dietary, geographical, and environmental factors on thyroid hormones amongst Nigerian students. Three groups of apparently healthy subjects were investigated-15 male Nigerian medical students in Ibadan, Nigeria, 15 male Nigerian students living in bedsitters in Manchester, and 4 male Nigerian students, normally resident in Manchester, but who had gone home on holidays. Blood was collected from this last group when the students were in Manchester and again after they had stayed in Nigeria for at least 4 weeks. In all students the serum triiodothyronine (T 3) and thyroxine (T4) were measured by radioimmunoassay using kits obtained from the Radiochemical Centre, Amersham. Serum retinol-binding protein (R.B.P.) and transferrin were estimated by the single radial immunodiffusion technique of Mancini et al.’ using monospecific antisera obtained from Hoechst, U.K. Ltd. The results obtained are summarised in the table. Students in Ibadan had significantly higher serum T 3’ R.B.P., and transferrin than Nigerian students living in bedsitters in Manchester. There was, however, no statistically significant difference in serum-T4 concentrations between the two groups. It was also observed that the serum-T rose significantly in those students who went home on holidays-whereas there was no significant change in serum-T4. MEAN AND STANDARD DEVIATIONS OF SERUM
T3, T4’ R.B.P.,
AND
TRANSFERRIN IN DIFFERENT GROUPS
T, undergoes removal of a single iodine atom from phenolic ring (5’-monodeiodination) to yield 3,5,3’-triiodothyronine (T3), a product which is metabolically more active than the parent T 4’ This conversion is affected by many factors including starvation and diet. For example, Vagenakis et al.3 showed that, in man, the serum-T, fell during periods of caloric deprivation and that this was rapidly reversed by refeeding. It is, therefore, likely that the observed low serum- T levels in Nigerian students living in bedsitters in
its
In man,2 outer,
Manchester was a reflection of their inadequate nutritional status. This view is strengthened by the observations that the serum concentrations of R.B.P. and transferrin which are said
be sensitive indices of nutritional status4-6 were significantly lower in this group of students. Their inadequate nutrito
1. Mancini, G.,
Carbonara, A. O., Heremans, J. F. Immunochemistry, 1965,
2, 235. 1. Garfinkel, P. E., Ezrin, C., Stancer, H. C. Lancet, 1973, ii, 331. 2. Petersen, P. Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie, heft. 120. Berlin, 1967. 3. Middler, S., Pak, C. Y. C , Murad, F., Bartter, F. C. Metabolism, 1973, 22, 139. 4. Grimelius, L., Johansson, H., Lindquist, B., Thorén, L., Werner, I. Acta chtr. scand. 1973, 139, 42. 5. Aronoff, M. S., Evens, R. G., Durell, J. J. psychiat. Res. 1971, 8, 139.
2. Braverman, L. E., Ingar, S. H., Sterling, K. 3. Vagenakis, A. G., Burger, A., Portnay, G. I.
J. J.
clin. Invest 1970, 49, 855 clin. Endocr. Metab. 1975,
41, 191. 4. Smith, F. R., Suskind, K., Thanangkul, O., Leitzmann, C., Goodman, D. S, Olson, R. E. Am. J. clin. Nutr. 1975, 28, 732. 5. Antia, A. U., McFarlane, H., Soothill, J. F. Archs Dis Childh. 1968, 43, 459. 6. Olusi, S. O., McFarlane, H., Osunkoya, B. O., Adesina, H. Clin. Chim. Acta, 1975, 62, 107.
145 tional status could be attributed to the fact that Nigerian students are not used to cooking for themselves and consequently they tend to eat less when they have to live on their own. However, the effects of geographical and economic factors cannot be ruled out. Investigations on a large number of samples are now being carried out by us. Department of Medical Biochemistry, Medical School, University of Manchester, Manchester M13 9PT
S. O. OLUSI H. MCFARLANE
Department of Chemical Pathology, Bolton Royal Infirmary, Bolton
D. ORRELL
Lancs
Department of Physiology, University of Ibadan,
R. A. ELEGBE
Nigeria
THYROID STORM AND IODINE-131 TREATMENT
the usual form of therapy in with diffuse goitre.1 A thyroid storm was seen in some cases just after ’3’I application2 and explained by a release of preformed thyroid hormones by the damaged follicles.3 Shafer and Nuttal4 reported an abrupt raise in serum-triiodothyronine (T3) and thyroxine (T 4) one day after application of 13’1. On the other hand, Wise et al.s could not find acute changes of T3 after 13 ’1 application. We will report briefly our results in a greater-number of patients. Forty-six patients with diffuse toxic goitre, well established by clinical and laboratory findings, were investigated. By diagnostic uptake measurements of 131I up to 48 h a dose of 1311 was estimated giving a radiation exposure of 7000 rad to the gland. Patients were resting in bed for 2 days before and 7 days after iodine application. Blood was collected every day; hormone concentrations were measured with commercial kits (’Tetralute’ and ’Seralute’). All samples from an individual patient were estimated in one batch. The intra-assay variance was calculated with less than 5% for T4 and T3’ Statistical
SIR,-lodine-131
the
treatment is
elderly thyrotoxic patient
CHANGES OF
*Significantly (r
LITHIUM, HYPERCALCÆMIA, AND HYPERPARATHYROIDISM
SIR,-Garfinkel et al.’ outlined a case in which hypercalcaemia and primary hyperparathyroidism (P.H.P.T.) may have been associated with lithium-carbonate medication. I have studied six patients, all females aged 32-45, who had been on lithium because of manic excitement for 2-4 years. All of them were under psychiatric observation, and their mental illness was well managed by lithium. All these patients developed hypercalca:mia after an average of one year, without any other manifestations characteristic of hypercalca:mia or P.H.P.T., such as nephrolithiasis, findings of subperiosteal resorption on skeletal X-ray, raised parathyroid hormone concentration, and low serum-phosphate. There was no evidence of increased urinary excretion of calcium. All six females were studied while in the Serafimerlasarettet, Stockholm. A standardised daily dietary intake (calcium 800 mg, phosphorus 800 mg, and magnesium 300 mg) was used but no other cause of the repeatedly raised serum-calcium was found apart from possible P.H.P.T. Regular check-ups and previous records confirmed that none of the patients had had a serumcalcium above the upper limit until about a year after the start of therapy with lithium. After that values were consistently between 2.75 and 2.80 mmol/1 (upper normal limit 2-64). Causes of hypercalcaemia other than P.H.P.T. were excluded as far as possible. After discharge the six patients were checked every third month, and the hypercalca:mia persisted. After consultation with the psychiatrist, lithium was discontinued in four patients; after 3 weeks all these women had normal serum-calcium levels. The four women were readmitted and studied under dietary restrictions. No laboratory abnormalities were revealed and urinary calcium excretion was normal. Lithium was re-introduced after 3-4 months, and 3-4 weeks later the serum-calcium was again high. After another week in hospital and further studies under standardised dietary intake all the patients underwent surgery, which revealed single parathyroid adenomas, dominated by chief cells, in each case. Apart from the raised serum-calcium there were no other laboratory abnormalities. The hypercalceemia disappeared postoperatively and lithium treatment was re-introduced. No rise of the serumcalcium level has been noted after this and check-ups have been performed every third month (up to 18 months). Depression, loss of initiative, and fatigue are among the characteristic psychic changes of P.H.P.T.2 Manic excitement is not usually a feature, though the occasional patient may be aggressive or irritable. Lithium treatment was supervised by a psychiatrist, with monitoring of serum concentration. Renal filtration (creatinine clearance) was intact in all cases. The association between lithium and the development of hypercalcxmia and P.H.P.T. might be fortuitous rather than causal. However, the hypercalcaemia did disappear after discontinuation of lithium and it reappeared when lithium was re-introduced. Some people may have a tendency to reversible hypercalcaemia, or it may be provoked by thiazides, for example,3 or, as here possibly, by lithium. Normocalcwmic P.H.P.T. has been described,4 and the six patients may have had normocalcsemic P.H.P.T. and been provoked into raised serum- calcium. The effect of lithium on electrolyte metabolism is controversial ; Aronoff et a1. found no effect on serum-calcium. The mechanism behind the apparent association between lithium therapy and hypercalcsemia and P.H.P.T. calls for further investigation. I suggest that the serum-calcium be checked routinely in patients on lithium.
This study has been supported by grants from Clas Groschinsky’s Fund, Stockholm, the research funds of the Svenska Läkaresällskapet (Stockholm) and of Svenska Sallskapet f6r medicinsk forskning
(Stockholm). Department of Medicine, Serafimerlasarettet, S-112 83 Stockholm, Sweden
TONY A. T. CHRISTENSSON
NUTRITIONAL STATUS AND THYROID HORMONES
SIR,-We found the report by Professor Bray and his col-
leagues (June 5, to
p.
1206)
on
the relation of
thyroid hormones
body-weight stimulating. We have investigated the
effects of dietary, geographical, and environmental factors on thyroid hormones amongst Nigerian students. Three groups of apparently healthy subjects were investigated-15 male Nigerian medical students in Ibadan, Nigeria, 15 male Nigerian students living in bedsitters in Manchester, and 4 male Nigerian students, normally resident in Manchester, but who had gone home on holidays. Blood was collected from this last group when the students were in Manchester and again after they had stayed in Nigeria for at least 4 weeks. In all students the serum triiodothyronine (T 3) and thyroxine (T4) were measured by radioimmunoassay using kits obtained from the Radiochemical Centre, Amersham. Serum retinol-binding protein (R.B.P.) and transferrin were estimated by the single radial immunodiffusion technique of Mancini et al.’ using monospecific antisera obtained from Hoechst, U.K. Ltd. The results obtained are summarised in the table. Students in Ibadan had significantly higher serum T 3’ R.B.P., and transferrin than Nigerian students living in bedsitters in Manchester. There was, however, no statistically significant difference in serum-T4 concentrations between the two groups. It was also observed that the serum-T rose significantly in those students who went home on holidays-whereas there was no significant change in serum-T4. MEAN AND STANDARD DEVIATIONS OF SERUM
T3, T4’ R.B.P.,
AND
TRANSFERRIN IN DIFFERENT GROUPS
T, undergoes removal of a single iodine atom from phenolic ring (5’-monodeiodination) to yield 3,5,3’-triiodothyronine (T3), a product which is metabolically more active than the parent T 4’ This conversion is affected by many factors including starvation and diet. For example, Vagenakis et al.3 showed that, in man, the serum-T, fell during periods of caloric deprivation and that this was rapidly reversed by refeeding. It is, therefore, likely that the observed low serum- T levels in Nigerian students living in bedsitters in
its
In man,2 outer,
Manchester was a reflection of their inadequate nutritional status. This view is strengthened by the observations that the serum concentrations of R.B.P. and transferrin which are said
be sensitive indices of nutritional status4-6 were significantly lower in this group of students. Their inadequate nutrito
1. Mancini, G.,
Carbonara, A. O., Heremans, J. F. Immunochemistry, 1965,
2, 235. 1. Garfinkel, P. E., Ezrin, C., Stancer, H. C. Lancet, 1973, ii, 331. 2. Petersen, P. Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie, heft. 120. Berlin, 1967. 3. Middler, S., Pak, C. Y. C , Murad, F., Bartter, F. C. Metabolism, 1973, 22, 139. 4. Grimelius, L., Johansson, H., Lindquist, B., Thorén, L., Werner, I. Acta chtr. scand. 1973, 139, 42. 5. Aronoff, M. S., Evens, R. G., Durell, J. J. psychiat. Res. 1971, 8, 139.
2. Braverman, L. E., Ingar, S. H., Sterling, K. 3. Vagenakis, A. G., Burger, A., Portnay, G. I.
J. J.
clin. Invest 1970, 49, 855 clin. Endocr. Metab. 1975,
41, 191. 4. Smith, F. R., Suskind, K., Thanangkul, O., Leitzmann, C., Goodman, D. S, Olson, R. E. Am. J. clin. Nutr. 1975, 28, 732. 5. Antia, A. U., McFarlane, H., Soothill, J. F. Archs Dis Childh. 1968, 43, 459. 6. Olusi, S. O., McFarlane, H., Osunkoya, B. O., Adesina, H. Clin. Chim. Acta, 1975, 62, 107.
145 tional status could be attributed to the fact that Nigerian students are not used to cooking for themselves and consequently they tend to eat less when they have to live on their own. However, the effects of geographical and economic factors cannot be ruled out. Investigations on a large number of samples are now being carried out by us. Department of Medical Biochemistry, Medical School, University of Manchester, Manchester M13 9PT
S. O. OLUSI H. MCFARLANE
Department of Chemical Pathology, Bolton Royal Infirmary, Bolton
D. ORRELL
Lancs
Department of Physiology, University of Ibadan,
R. A. ELEGBE
Nigeria
THYROID STORM AND IODINE-131 TREATMENT
the usual form of therapy in with diffuse goitre.1 A thyroid storm was seen in some cases just after ’3’I application2 and explained by a release of preformed thyroid hormones by the damaged follicles.3 Shafer and Nuttal4 reported an abrupt raise in serum-triiodothyronine (T3) and thyroxine (T 4) one day after application of 13’1. On the other hand, Wise et al.s could not find acute changes of T3 after 13 ’1 application. We will report briefly our results in a greater-number of patients. Forty-six patients with diffuse toxic goitre, well established by clinical and laboratory findings, were investigated. By diagnostic uptake measurements of 131I up to 48 h a dose of 1311 was estimated giving a radiation exposure of 7000 rad to the gland. Patients were resting in bed for 2 days before and 7 days after iodine application. Blood was collected every day; hormone concentrations were measured with commercial kits (’Tetralute’ and ’Seralute’). All samples from an individual patient were estimated in one batch. The intra-assay variance was calculated with less than 5% for T4 and T3’ Statistical
SIR,-lodine-131
the
treatment is
elderly thyrotoxic patient
CHANGES OF
*Significantly (r
