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Cation-exchange resin and inhibition of intestinal absorption of thyroxine
1286
fortunate
ones did not need to see a physician again, but surely something would have seeped through? Populus vult decipi: decipiatur. But let us not deceive ourselves.
Charing Cross Hospital,
J. T. SCOTT
London W6 8RF, UK
Cation-exchange resin and inhibition of intestinal absorption of thyroxine SIR,-We report an interaction between thyroxine and the cation-exchange resin, sodium polystyrene sulphonate (SPS). The patient had been hypothyroid since 1975 after total thyroidectomy and z1 treatment for thyroid carcinoma. Thyroxine replacement 150 ug daily achieved satisfactory suppression of thyroidstimulating hormone (TSH). In 1984 she developed renal failure secondary to chronic interstitial nephritis, dialysis starting in 1987. In addition to thyroxine her medications were digoxin, clofibrate, nicotinic acid, calcium carbonate, ferrous sulphate, folic acid, and magnesium trisilicate. Representative thyroid function tests from this time showed TSH 0 67 mU/L (reference range 02-3-0), and free thyroxine index 48 (25-60). Despite haemodialysis and potassium restriction, she developed persistent hyperkalaemia which was treated daily with SPS (Resonium A, Winthrop) 15 g orally. No other changes were made to her therapy, and plasma potassium improved. 6 months later the patient reported lethargy, hoarse voice, facial fullness, and weight gain of 7 kg. Free thyroxine was 3-5 pmol/L (reference range 10-25) and TSH 139mU/L. She was compliant with treatment and we postulated that SPS was binding thyroxine in the gastrointestinal tract, preventing absorption. Thyroxine was increased to 200 ug daily and was taken 10 h after SPS (they had previously been taken simultaneously). After 6 weeks the clinical features of hypothyroidism had resolved and her weight returned to normal. Free thyroxine was 13 0 pmol/L and TSH 59 mU/L. Changes in thyroid function tests during SPS treatment are shown in the figure. In-vitro binding was investigated. Two 100 g thyroxine tablets were dispersed in 100 ml water and incubated in the presence or absence of 15 g SPS. The experiment was also repeated at pH 20 by the addition of hydrochloric acid. After incubation the mixture was centrifuged and thyroxine was measured in the supernatant by radioimmunoassay. The presence of SPS reduced the concentration of dissolved thyroxine by 93% at pH 2 and by 98% at pH 7, supporting the hypothesis that resin-binding caused the thyroxine malabsorption seen in our patient. SPS is
lies in its
absorbed from the intestinal tract and its clinical use ability to bind potassium ions in exchange for sodium.
not
However, the absorptive capacity of resin compounds is fairly
non-specific and other substances may be bound. Other resin-based drugs impede the intestinal absorption of thyroxine, notably cholestyramine and colestipol which are anion-exchange resins.l,2 In addition to their effects of the absorption of orally administered thyroid hormones, resins might also increase the clearance of endogenous thyroid hormones, some of which undergo enterohepatic. circulation after glucuronidation in the liver.3,4 Such an effect might precipitate hypothyroidism in an individual with impaired thyroid synthetic capacity. The recognised adverse effects of SPS treatment include sodium overload, constipation, and gastric irritation. Impairment of thyroid hormone absorption should now be added to this list. This effect can be at least partly overcome by separating the doses.
John Hunter Hospital, New Lambton, Newcastle, NSW 2310, Australia
MARK MCLEAN IAN KIRKWOOD MARTIN EPSTEIN
BERNARD JONES CHRIS HALL
JW, Stand EG Jr. The influence of cholestyramine thyroxine absorption. JAMA 1969; 208: 1857-61. 2. Cashin-Hemphill L, Spencer CA, Nicoloff JT, et al. Alteration in serum thyroid hormonal indices with colestipol-niacin therapy. Ann Intern Med 1987; 107: 1. Northcutt RC, Stiel JN, Bollifield on
324-29. 3. Witztum JL,
Jacobs LS, Schonfeld G. Thyroid hormone and thyrotropin levels in patients placed on colestipol hydrochloride. J Clin Endocrinol Metab 1978; 46:
838-40. 4. Curran PG, DeGroot LJ. The effect of hepatic enzyme-inducing drugs hormones and the thyroid gland. Endocrinol Rev 1991; 12: 135-50.
on
thyroid
AIDS predictions SiR,—Your April 3 editorial perpetuates the myth that the unlinked anonymous serosurvey technique is weak because the data obtained are too crude. On the contrary, exposure risk data can be obtained, then unlinked and anonymised together with the associated clinical specimens, and deductive disclosure avoided.l Although in-depth interviews of HIV-infected individuals diagnosed through voluntary confidential HIV testing can reveal details of sexual behaviour,this surveillance approach is timeconsuming, expensive, and may give a biased picture. Suitably designed unlinked anonymous serosurveys can demonstrate the true extent of HIV transmission in sub-populations at risk through particular behaviours. For example, the prevalence of HIV infection in large numbers of individuals whose only exposure is likely to be vaginal sex can be monitored by the technique. In 1990 and 1991 a total of 48 (0-6%) HIV-1 infections were detected in the 7403 female heterosexuals who had never injected drugs and who attended two London genitourinary medicine clinics, whereas in four clinics outside London only 16 (0 17%) of 9604 such attenders were infected.3 Further insight into HIV transmission through heterosexual sex will be obtained when information on the country of birth of such clinic attenders is gathered within the expanded England and Wales, unlinked, anonymous, HIV-prevalence
monitoring programme. Erroneous assumptions about heterosexual spread were not the for the difference between the 1988 and 1990 forecasts of AIDS incidence for England and Wales, as Professor Stewart says (April 13, p 898). The critique of AIDS predictions Stewart presents does not include the official planning figure for 1991 or 1992, makes no allowance for reporting delay, and makes no use of the publicly available non-aggregate data file.4 The facts with respect to official predictions are as follows. In 1988 the Cox report, with various methods and data to the end of June, 1988, gave as a basis for planning an incidence of AIDS for England and Wales in 1992 of 4500 (including a 20% under-reporting allowance).5This report, however, also recognised that the abrupt flattening in the number of reports of AIDS cases in late 1987 and early 1988 could be explained by a sharp slowing down in the rate of transmission of HIV infection among homosexual men from about 1984, and recommended that AIDS forecasts should be regularly updated. Acccordingly, the Chief Medical Officer requested the Director of the Public Health Laboratory Service to convene another working reason
Weeks from commencement of SPS
TSH and free thyroxine
(T4).
Mane=in the morning, nocte= at night.
fortunate
ones did not need to see a physician again, but surely something would have seeped through? Populus vult decipi: decipiatur. But let us not deceive ourselves.
Charing Cross Hospital,
J. T. SCOTT
London W6 8RF, UK
Cation-exchange resin and inhibition of intestinal absorption of thyroxine SIR,-We report an interaction between thyroxine and the cation-exchange resin, sodium polystyrene sulphonate (SPS). The patient had been hypothyroid since 1975 after total thyroidectomy and z1 treatment for thyroid carcinoma. Thyroxine replacement 150 ug daily achieved satisfactory suppression of thyroidstimulating hormone (TSH). In 1984 she developed renal failure secondary to chronic interstitial nephritis, dialysis starting in 1987. In addition to thyroxine her medications were digoxin, clofibrate, nicotinic acid, calcium carbonate, ferrous sulphate, folic acid, and magnesium trisilicate. Representative thyroid function tests from this time showed TSH 0 67 mU/L (reference range 02-3-0), and free thyroxine index 48 (25-60). Despite haemodialysis and potassium restriction, she developed persistent hyperkalaemia which was treated daily with SPS (Resonium A, Winthrop) 15 g orally. No other changes were made to her therapy, and plasma potassium improved. 6 months later the patient reported lethargy, hoarse voice, facial fullness, and weight gain of 7 kg. Free thyroxine was 3-5 pmol/L (reference range 10-25) and TSH 139mU/L. She was compliant with treatment and we postulated that SPS was binding thyroxine in the gastrointestinal tract, preventing absorption. Thyroxine was increased to 200 ug daily and was taken 10 h after SPS (they had previously been taken simultaneously). After 6 weeks the clinical features of hypothyroidism had resolved and her weight returned to normal. Free thyroxine was 13 0 pmol/L and TSH 59 mU/L. Changes in thyroid function tests during SPS treatment are shown in the figure. In-vitro binding was investigated. Two 100 g thyroxine tablets were dispersed in 100 ml water and incubated in the presence or absence of 15 g SPS. The experiment was also repeated at pH 20 by the addition of hydrochloric acid. After incubation the mixture was centrifuged and thyroxine was measured in the supernatant by radioimmunoassay. The presence of SPS reduced the concentration of dissolved thyroxine by 93% at pH 2 and by 98% at pH 7, supporting the hypothesis that resin-binding caused the thyroxine malabsorption seen in our patient. SPS is
lies in its
absorbed from the intestinal tract and its clinical use ability to bind potassium ions in exchange for sodium.
not
However, the absorptive capacity of resin compounds is fairly
non-specific and other substances may be bound. Other resin-based drugs impede the intestinal absorption of thyroxine, notably cholestyramine and colestipol which are anion-exchange resins.l,2 In addition to their effects of the absorption of orally administered thyroid hormones, resins might also increase the clearance of endogenous thyroid hormones, some of which undergo enterohepatic. circulation after glucuronidation in the liver.3,4 Such an effect might precipitate hypothyroidism in an individual with impaired thyroid synthetic capacity. The recognised adverse effects of SPS treatment include sodium overload, constipation, and gastric irritation. Impairment of thyroid hormone absorption should now be added to this list. This effect can be at least partly overcome by separating the doses.
John Hunter Hospital, New Lambton, Newcastle, NSW 2310, Australia
MARK MCLEAN IAN KIRKWOOD MARTIN EPSTEIN
BERNARD JONES CHRIS HALL
JW, Stand EG Jr. The influence of cholestyramine thyroxine absorption. JAMA 1969; 208: 1857-61. 2. Cashin-Hemphill L, Spencer CA, Nicoloff JT, et al. Alteration in serum thyroid hormonal indices with colestipol-niacin therapy. Ann Intern Med 1987; 107: 1. Northcutt RC, Stiel JN, Bollifield on
324-29. 3. Witztum JL,
Jacobs LS, Schonfeld G. Thyroid hormone and thyrotropin levels in patients placed on colestipol hydrochloride. J Clin Endocrinol Metab 1978; 46:
838-40. 4. Curran PG, DeGroot LJ. The effect of hepatic enzyme-inducing drugs hormones and the thyroid gland. Endocrinol Rev 1991; 12: 135-50.
on
thyroid
AIDS predictions SiR,—Your April 3 editorial perpetuates the myth that the unlinked anonymous serosurvey technique is weak because the data obtained are too crude. On the contrary, exposure risk data can be obtained, then unlinked and anonymised together with the associated clinical specimens, and deductive disclosure avoided.l Although in-depth interviews of HIV-infected individuals diagnosed through voluntary confidential HIV testing can reveal details of sexual behaviour,this surveillance approach is timeconsuming, expensive, and may give a biased picture. Suitably designed unlinked anonymous serosurveys can demonstrate the true extent of HIV transmission in sub-populations at risk through particular behaviours. For example, the prevalence of HIV infection in large numbers of individuals whose only exposure is likely to be vaginal sex can be monitored by the technique. In 1990 and 1991 a total of 48 (0-6%) HIV-1 infections were detected in the 7403 female heterosexuals who had never injected drugs and who attended two London genitourinary medicine clinics, whereas in four clinics outside London only 16 (0 17%) of 9604 such attenders were infected.3 Further insight into HIV transmission through heterosexual sex will be obtained when information on the country of birth of such clinic attenders is gathered within the expanded England and Wales, unlinked, anonymous, HIV-prevalence
monitoring programme. Erroneous assumptions about heterosexual spread were not the for the difference between the 1988 and 1990 forecasts of AIDS incidence for England and Wales, as Professor Stewart says (April 13, p 898). The critique of AIDS predictions Stewart presents does not include the official planning figure for 1991 or 1992, makes no allowance for reporting delay, and makes no use of the publicly available non-aggregate data file.4 The facts with respect to official predictions are as follows. In 1988 the Cox report, with various methods and data to the end of June, 1988, gave as a basis for planning an incidence of AIDS for England and Wales in 1992 of 4500 (including a 20% under-reporting allowance).5This report, however, also recognised that the abrupt flattening in the number of reports of AIDS cases in late 1987 and early 1988 could be explained by a sharp slowing down in the rate of transmission of HIV infection among homosexual men from about 1984, and recommended that AIDS forecasts should be regularly updated. Acccordingly, the Chief Medical Officer requested the Director of the Public Health Laboratory Service to convene another working reason
Weeks from commencement of SPS
TSH and free thyroxine
(T4).
Mane=in the morning, nocte= at night.