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Influence of diazepam on thyroid function tests in normal Nigerians
I~I. J. Nucl. Med. Biol. Vol. 11, No. 2, pp. 203-204, Pergamon Press Ltd 1984. Printed in Great Britain. 0047s0740/84 $3.00 + 0.00
levels. The drug was continued until after the measurement of the 48 h “‘I uptake. (III) After another period of about 3 weeks the tests were repeated. 13’1 (5 PCi) was administered orally on each occasion and uptake levels were measured at 4,24 and 48 h. T3 resin uptake and T4 levels were determined with the use of T3 uptake MAA and Armerlex T4 kits supplied by Amersham International Ltd, (Amersham, U.K.).
1984
Influence of Diazepam on Thyroid Function Tests in Normal Nigerians
Results Seventeen subjects were investigated 5 of whom were female. The average age of the group was 25. Table I presents a summary of the results. It was expected that stage II of each test period would show a significant depression. This is true in every case except in three subjects. The mean iodine uptake values of 17.7, 36.0 and 39.3% at 4-24 and 48 h respectively for stage I were similar to those obtained in this laboratory from a similar group of subjects 8 years ago.‘s’ A significant depression (P < 0.05) was obtained at stage II of each test period. As expected, the mean uptake values had begun to return to normal at stage III following the withdrawal of the drug. On the whole 76.6% of the subjects showed a depression at 4 h uptake while on diazepam, 70.6% at 24 h and 58.8% at 48 h. An average of 58.87: showed a depression at all three stages. The serum T4 levels showed a slight but insignificant rise at stage II while the resin uptake dropped slightly but also insignificantly during the same stage.
0. T. OGUNLEYE’ and A. B. EJIWUNM12 Departments of ‘Radiation Biology & Radiotherapy and ‘Anatomy, College of Medicine, University of Lagos, P.M.B. 12003, Lagos, Nigeria (Received 6 Nouernber 1983) It has often been reported that certain drugs, in particular benzodiazepines, significantly depress the results of thyroid function studies.““‘) In spite of the significance of this side effect very few systematic and conclusive studies have been reported in the literature. One of the benzodiazepine drugs, Diazepam, is the most commonly prescribed in our environment. A number of patients referred to our thyroid function laboratory are usually placed on this drug. In most cases a complete drug history is unobtainable. It was decided therefore to evaluate the effect of this drug on the thyroid function tests we most routinely carry out viz. T3 resin uptake T4 and “‘I uptake.
Discussion It is observed from this study that the previous anecdotal reports of a depressive effect of benzodiazepine d-5 of iodine uptake is a significant phenomenon. Thou the depression observed from the mean values is about 27%. the depression in individuals could be as high as 66% as wslg the case in one of our subjects. These findings therefore e the report of Harvey (*Iwho noticed that none of his aeven hyperthyroidic patients on similar medication had r&& iodine uptakes. At the dose given i;. .nis study-5 nq nocte, the depressive effect is such that all patients presentirrg for thyroid function tests ought to be thoroughly screened. How long they should be off the drug before a reliable test may be obtained is difficult to determine as up to 50% of our normal subjects still showed some slight degree of depression after 2-3 weeks at phase III relative to phase I. It has been suggested that the site of action of the benzodiazepine drug may be on the thyroid gland itself.“) The fact that neither T4 nor T3 values were affected in these normal subjects supports the idea that the drugs and their metabolites may be primary antithyroid drugs. It would be
Materials and Methods Adult volunteers were recruited from among the student population and staff members of the College of Medicine. Their free consent was obtained. Euthyroid status was established by physical examination and a careful history to eliminate recent ingestion of any drug of the benzodiazepine class, iodine-containing drugs or recent radiological examinations involving the use of iodine-containing contrast media. The studies were divided into three stages: (I) Initial determination of T3 resin uptake, T4 and “‘I uptake levels in the subjects which served as the control. (II) After a period of about 3 weeks (when the residual level of radioiodine in the thyroid should be insignificant i.e. about background level) the subject took a daily dose of diazepam (5 mg) at bed time for 7 days. On the morning following the fourth night they reported to our laboratory for the determination of T3 resin uptake, T4 and 13’1uptake
Table
1. “‘I uptake,
T’ resin uptake
and p
values
at various
stages
Stages Norma, __I_
Tests
____
_ ~~
values __~~_.._
.~_~ _~_~ ~~__~~ 11 ~~__
I
~~
III
~~_~~
%‘j’I
uptake 4h 24h 48 h % T3 RU T4 ~g/lOOml
20.3 36.0 37.7 28.5 8.5
+_4.3 f 7.9 k 8.1 f 2.1 + 3.8
18.5 37.2 42.0 29.1 9.5
* ‘i + f f
203
4.3 8.1 10.6 3.2 3.5
13.8 27.2 30.4 27.4 10.1
* f * f *
3.8 9.1 8.0 2.X 5.1
16.6 33.2 34.3 28.9 9.5
& 4.4 k 8.1 f 7.1 k 2.3 & 3.5
204
Case Report
interesting to see if hypertensive patients who are on long term adjuvant treatment with Diazepam have a tendency of becoming hyprothyroidic. In conclusion, we would like to suggest that in an environment such as this in which self-medication is quite common, thyroid function studies should be performed on patients who have been off benzodiazepine drugs for at least four weeks.
References
1. 2. 3. 4. 5.
Baron J. M. Br. Med. J. 1, 699 (1967). Harvey R. F. Br. Med. J. 2, 52 (I 967). Turner P. and Sneddon J. M. Er. Med. J. 2, 52 (1967). Hamilton D. R. J. Nucl. Med. 14, 472 (1973). Fregene A. 0. and Daramola G. F. Niger. Med. J. 4, 1.52(1974).
levels. The drug was continued until after the measurement of the 48 h “‘I uptake. (III) After another period of about 3 weeks the tests were repeated. 13’1 (5 PCi) was administered orally on each occasion and uptake levels were measured at 4,24 and 48 h. T3 resin uptake and T4 levels were determined with the use of T3 uptake MAA and Armerlex T4 kits supplied by Amersham International Ltd, (Amersham, U.K.).
1984
Influence of Diazepam on Thyroid Function Tests in Normal Nigerians
Results Seventeen subjects were investigated 5 of whom were female. The average age of the group was 25. Table I presents a summary of the results. It was expected that stage II of each test period would show a significant depression. This is true in every case except in three subjects. The mean iodine uptake values of 17.7, 36.0 and 39.3% at 4-24 and 48 h respectively for stage I were similar to those obtained in this laboratory from a similar group of subjects 8 years ago.‘s’ A significant depression (P < 0.05) was obtained at stage II of each test period. As expected, the mean uptake values had begun to return to normal at stage III following the withdrawal of the drug. On the whole 76.6% of the subjects showed a depression at 4 h uptake while on diazepam, 70.6% at 24 h and 58.8% at 48 h. An average of 58.87: showed a depression at all three stages. The serum T4 levels showed a slight but insignificant rise at stage II while the resin uptake dropped slightly but also insignificantly during the same stage.
0. T. OGUNLEYE’ and A. B. EJIWUNM12 Departments of ‘Radiation Biology & Radiotherapy and ‘Anatomy, College of Medicine, University of Lagos, P.M.B. 12003, Lagos, Nigeria (Received 6 Nouernber 1983) It has often been reported that certain drugs, in particular benzodiazepines, significantly depress the results of thyroid function studies.““‘) In spite of the significance of this side effect very few systematic and conclusive studies have been reported in the literature. One of the benzodiazepine drugs, Diazepam, is the most commonly prescribed in our environment. A number of patients referred to our thyroid function laboratory are usually placed on this drug. In most cases a complete drug history is unobtainable. It was decided therefore to evaluate the effect of this drug on the thyroid function tests we most routinely carry out viz. T3 resin uptake T4 and “‘I uptake.
Discussion It is observed from this study that the previous anecdotal reports of a depressive effect of benzodiazepine d-5 of iodine uptake is a significant phenomenon. Thou the depression observed from the mean values is about 27%. the depression in individuals could be as high as 66% as wslg the case in one of our subjects. These findings therefore e the report of Harvey (*Iwho noticed that none of his aeven hyperthyroidic patients on similar medication had r&& iodine uptakes. At the dose given i;. .nis study-5 nq nocte, the depressive effect is such that all patients presentirrg for thyroid function tests ought to be thoroughly screened. How long they should be off the drug before a reliable test may be obtained is difficult to determine as up to 50% of our normal subjects still showed some slight degree of depression after 2-3 weeks at phase III relative to phase I. It has been suggested that the site of action of the benzodiazepine drug may be on the thyroid gland itself.“) The fact that neither T4 nor T3 values were affected in these normal subjects supports the idea that the drugs and their metabolites may be primary antithyroid drugs. It would be
Materials and Methods Adult volunteers were recruited from among the student population and staff members of the College of Medicine. Their free consent was obtained. Euthyroid status was established by physical examination and a careful history to eliminate recent ingestion of any drug of the benzodiazepine class, iodine-containing drugs or recent radiological examinations involving the use of iodine-containing contrast media. The studies were divided into three stages: (I) Initial determination of T3 resin uptake, T4 and “‘I uptake levels in the subjects which served as the control. (II) After a period of about 3 weeks (when the residual level of radioiodine in the thyroid should be insignificant i.e. about background level) the subject took a daily dose of diazepam (5 mg) at bed time for 7 days. On the morning following the fourth night they reported to our laboratory for the determination of T3 resin uptake, T4 and 13’1uptake
Table
1. “‘I uptake,
T’ resin uptake
and p
values
at various
stages
Stages Norma, __I_
Tests
____
_ ~~
values __~~_.._
.~_~ _~_~ ~~__~~ 11 ~~__
I
~~
III
~~_~~
%‘j’I
uptake 4h 24h 48 h % T3 RU T4 ~g/lOOml
20.3 36.0 37.7 28.5 8.5
+_4.3 f 7.9 k 8.1 f 2.1 + 3.8
18.5 37.2 42.0 29.1 9.5
* ‘i + f f
203
4.3 8.1 10.6 3.2 3.5
13.8 27.2 30.4 27.4 10.1
* f * f *
3.8 9.1 8.0 2.X 5.1
16.6 33.2 34.3 28.9 9.5
& 4.4 k 8.1 f 7.1 k 2.3 & 3.5
204
Case Report
interesting to see if hypertensive patients who are on long term adjuvant treatment with Diazepam have a tendency of becoming hyprothyroidic. In conclusion, we would like to suggest that in an environment such as this in which self-medication is quite common, thyroid function studies should be performed on patients who have been off benzodiazepine drugs for at least four weeks.
References
1. 2. 3. 4. 5.
Baron J. M. Br. Med. J. 1, 699 (1967). Harvey R. F. Br. Med. J. 2, 52 (I 967). Turner P. and Sneddon J. M. Er. Med. J. 2, 52 (1967). Hamilton D. R. J. Nucl. Med. 14, 472 (1973). Fregene A. 0. and Daramola G. F. Niger. Med. J. 4, 1.52(1974).