Original Article Ann Clin Biochem 1995; 32: 385-391

Euthyroid sick syndrome in pulmonary

tuberculosis before and after treatment
C C Chow, T W L Mak l , C H S Chan and C S Cockram
From the Departments of Medicine and 'Cnemicat Pathology, Chinese University
of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong

SUMMARY. Alterations of circulating thyroid hormones are frequently present in

chronic nonthyroidal illnesses and may predict prognosis. Pulmonary tuberculosis,
a common treatable debilitating disease, may provide a useful model for detailed
evaluation of changes of thyroid hormones in relation to subsequent recovery or
mortality. Over a period of 12 months, we performed a prospective study of 40
consecutive Chinese patients aged over 50 years and admitted with newly diagnosed
pulmonary tuberculosis. Blood samples were drawn for serial thyroid function tests
[free thyroxine (T 4 ) , free triiodothyronine (T 3 ) and thyroid-stimulating hormone]
before treatment and at I, 2 and 4 months afterwards. Mortality was determined
up to 12 months of follow-up. The euthyroid sick syndrome occurred in 63% of
patients at presentation. Twelve of 25 euthyroid sick patients died as compared to
one of 15 patients with normal baseline thyroid function tests (P<0·02). Among
euthyroid sick patients, those who died had significantly lower free T 3 concentration
at presentation than those who survived (P<Oo05). An undetectable free T 3
concentration at presentation was associated with a subsequent mortality of 75% (9
of 12). Of the survivors, all patients demonstrated a significant rise in serum free
T 4 concentrations following treatment, which was apparent by 1 month. These data
suggest that an undetectable free T 3 concentration at presentation reflects severity
of illness and predicts a subsequent high mortality.
Additional key phrases: non-thyroidal illness; free thyroxine; free triiodothyronine;
thyrotropin

It is well recognized that alterations of circulating
thyroid hormone concentrations occur in a
variety of nonthyroidal illnesses. 1,2 The changes
are characterized by reduction in serum
total triiodothyronine (T 3 ) as well as free T 3
concentrations, Serum total thyroxine (T 4 )
concentrations may be reduced, elevated or
normal; free T 4 concentrations vary depending on
assay methodology and are difficult to interpret. 3
Despite these changes, most patients remain
clinically euthyroid and have a relatively normal
basal serum thyroid-stimulating hormone (TSH)
concentration with a normal or blunted response
to thyrotropin-releasing hormone (TRH); hence
the term euthyroid sick syndrome. 1,2
Pulmonary tuberculosis remains a significant
problem in many developing countries and an
Correspondence: Dr C C Chow.
upsurge of tuberculosis, partly related to acquired
immunodeficiency syndrome has recently been
observed in many industrial societies." Pulmonary
tuberculosis is a chronic debilitating disease, which,
although treatable, still carries a high mortality
particularly in the elderly.5,6 Thus, pulmonary
tuberculosis provides a potential model for the
study of changes of thyroid hormones associated
with euthyroid sick syndrome. We have followed
prospectively thyroid hormone concentrations,
before and after treatment, in 40 Chinese
patients with newly diagnosed active pulmonary
tuberculosis.
SUBJECTS AND METHODS
Subjects
Forty Chinese patients (30 men, 10 women) aged
over 50 years (mean age 73 years, range 51-86)

385
 386 Chow et al.
with newly diagnosed pulmonary tuberculosis
were studied. Thirty-three patients (830/0) had
parenchymal tuberculosis (26 smear positive and
all culture positive). Seven had tuberculosis
pleural effusions, in which caseating granulomata
identified in pleural biopsy or a positive culture
of tubercle bacilli on pleural aspirate were
considered diagnostic. Patients with known
neurological, hypothalamic-pituitary or thyroid
disease were excluded. None of the patients were
receiving medications known to interfere with
thyroid hormone metabolism (such as iodide,
lithium, corticosteroids, dopamine, dobutamine,
(3-blockers, and phenytoin).
All patients were treated with conventional
antituberculous chemotherapy including
streptomycin (or ethambutol), isoniazid,
rifampicin and pyrizinamide in accordance with
recommended guidelines. Initial treatment was
supervised and monitored in hospital. Patients
who were stable after initial treatment were either
transferred to a convalescent chest hospital or
discharged. Discharged patients were reassessed
monthly as outpatients up to the completion of
treatment at 6 months or more.
Blood samples were drawn, with informed
consent, for thyroid function tests before
treatment and at 1,2 and 4 months afterwards.
Euthyroid sick syndrome was diagnosed on
the basis of clinical euthyroidism, low free T 3
concentrations « 3 . 3 pmollL) with a lack of
significant elevation of TSH, and variable
changes in free T 4 • Mortality was determined up
to 12 months of follow-up (range 6-12 months).
Assays
The serum TSH concentration was measured by
an immunochemiluminometric assay (Ciba
T AHLE I. Clinical characteristics and baseline hormone concentrations of subjects with normal thyroid function
and subjects with euthyroid sick syndrome at presentation. Results are mean (SEM)
Duration of
Age illness
(years) Male (months)
Reference range
Normal baseline 65'6 (2'4) 8 3·7 (1'1)
thyroid function
(n= 15)
Euthyroid sick 71'2 (1'7) 22· 2,1(0,4)
syndrome
(n=25)
·P<0·05 compared with normal baseline thyroid function subjects (x 2 test).
Ip<O'OOI compared with normal baseline thyroid function subjects (Wilcoxon rank sum test).
lp<0'OO5 compared with normal baseline thyroid function subjects (Wilcoxon rank sum test).
TSH = Thyroid stimulating hormone.
Ann Clin Biochem 1995: 32
Corning Diagnostics, Norwood, MA, USA) with
a detection limit of 0·02 mUlL. Serum free T 3
and T 4 concentrations were determined by
commercial immunoassay kits (Amerlex-M,
Amersham Corporation, Arlington Heights, IL,
USA for T 3 and Gammacoat two step assay,
Baxter, Cambridge, MA, USA for T 4 ) . The
analytical coefficients of variations of the
methods were 6·4%, 4·8%, and 7· 5% for TSH,
free T 3 and free T 4' respectively. Reference
ranges are shown in Table I.
Statistical analysis
All data are presented as the mean and standard
error of the mean (SEM). Student's paired t-test
and two-tailed Wilcoxon rank sum tests were used
for comparison of groups where appropriate.
Statistical comparisons of ratios were performed
using the x2 test. P values of less than 0·05 were
considered to indicate statistical significance.
RESULTS
Baseline thyroid hormones studies
and clinical outcome
Table I summarizes the clinical characteristics and
baseline hormone concentrations of subjects with
normal thyroid function tests and subjects
with euthyroid sick syndrome at presentation.
Twenty-five subjects (63%) had euthyroid sick
syndrome. The age and duration of illness were
similar in both groups of subjects. However,
euthyroid sick syndrome subjects were pre-
dominantly male (22 of 25, P<0·05). Mean
serum concentrations of free T 3 , as expected,
were lower in the euthyroid sick syndrome
subjects (P<O·OOI), and TSH was higher
Free T J Free T. TSH
Mortality (pmoI/L) (pmol/L) (mUlL)
3,3-8,2 7·0-21,8 0·3-4,0
I (6'7070) 4·4 (0'2) 17·9 (0'7) 0·91 (0'1)
12 (48%)· 1·6 (0'2)1 17·8 (0'1) 1·59 (0'3)1
 Euthyroid sick syndrome 387

TABLE 2. Clinical characteristics and baseline hormone concentrations of the euthyroid sick syndrome subjects
who survived and who died in the study. Results are mean (SEM)
Duration of
Age illness Free T] Free T 4 TSH
(years) Male (months) (pmoIlL) (pmoIlL) (mUlL)
Reference range 3· 3-8' 2 7·0-21·8 0,3-4,0
Survivors 68·6 (2'9) 10 1·7 (3 '0) 2·0 (0'2) 19'6 (0'9) 1·49 (0'4)
(n = 13)
Died 73,9(1'5) 12 2· 5 (0'6) 1·2 (0'1)· 15·9 (1'6) 1·70 (0'4)
(n= 12)

·P<0·05 compared with survivors (Wilcoxon rank sum test).

TSH = Thyroid stimulating hormone.

(P< 0,005). No difference between both groups
of subjects was found in the mean serum free T 4
concentration. Mortality in the euthyroid sick
syndrome subjects (12 of 25) was higher
(P< 0,05) than in subjects with normal baseline
thyroid function (I of 15).
Since the euthyroid sick syndrome was
associated with a much higher mortality, we
further analysed this group of subjects by
subdividing them into two categories: those
who died and those who survived (Table 2).
No differences were found between the
subjects who died and those who survived
for the mean serum concentrations of TSH
and free T 4' However, mean (SEM) serum
free T) concentration remained significantly
lower (P< O' 05) in the deceased euthyroid sick
syndrome subjects [1' 2 (0'1) pmol/L] than that
of the surviving euthyroid sick syndrome subjects
[2'0 (0'2) pmol/L].
Nine of 13 subjects who died during the study
period had a pretreatment free T) concentration
below the detection limit (Table 3), whereas
only three of 13 euthyroid sick syndrome who
survived had undetectable free T) (data not
shown). Thus, an undetectable serum free T] at
presentation is associated with high mortality (9
of 12). Serum free T 4 concentrations were
variable although most were within the reference
range (Table 3). All but one patient (patient 26)
had a normal TSH. The median survival of 13
patients (12 euthyroid sick syndrome, one normal
baseline thyroid function) who died during
treatment for pulmonary tuberculosis was 14 days
(range 3-82) from the commencement of anti-
tuberculous drugs.
Longitudinal thyroid hormone profdes in survivors
Both normal baseline thyroid function and
euthyroid sick syndrome subjects who survived

TABLE 3. Baseline thyroid hormone concentrations of 13 subjects who died during treatment for pulmonary
tuberculosis. All were men
Subject Age Free T] Free T 4 TSH Survival after
No. ( years) (pmoIlL) (pmoIlL) (mUlL) treatment (days)
2 66 1·1 13·6 3·36 82
6 77 < 1·0 20·3 1·05 14
7 85 <1·0 18·9 1·85 12
14 77 <1·0 9·8 0·43 48
15 75 <1·0 21·6 0·82 34
19 70 2·2 19·2 1·01 12
20 75 3·9 22·8 0·71 58
25 68 <1·0 12·2 1·90 3
26 72 < 1·0 4·4 5·14 4
36 76 1·7 23·9 1·99 78
37 74 1·7 13·4 1·52 7
39 70 <1·0 15·2 0·48 5
40 77 <1·0 17·8 0·87 30

Reference range 3,3-8,2 7,0-21,8 0,3-4,0

TSH = Thyroid stimulating hormone.

Ann Clin Biochem 1995: 32

388 Chow et al.

showed a rise in serum concentrations of free T) P<O·OOI and P<0·05, respectively); 19·9
and TSH, with a gradual fall in free T 4 on (l'O)pmol/L to 13·7(l·I)pmol/L at month 4
recovery with antituberculosis treatment (Fig. I). in the surviving euthyroid sick syndrome subjects
Mean (SEM) serum concentrations of free T) (P<0·05)]. Serum TSH concentrations increased
rose significantly in both groups of subjects in the normal baseline thyroid funtion subjects
during follow-up [4· 5 (0' 2) pmol/L to 5·5 [0'9 (0'1) mUlL to 1·1 (0'2) mUlL at month 1
(0'4)pmol/L at month 2 and 5·5 (0'4)pmol/L and 1·3 (0'2) mUlL at month 4; both P<0·05)],
at month 4 in the normal baseline thyroid but not significantly in the surviving euthyroid
function subjects (P<O'OOI and P<O'01, sick syndrome subjects. Two survivors had
respectively); 1· 9 (0' 2) pmol/L to 4· 2 (0' 3) pmol/L transient mild elevation of serum TSH on
at month 1, 4· 2 (0' 4) pmol/L at month 2 recovery (peak 4· 52 and 6·81 mUlL, respectively),
and 4· 9 (0' 3) pmol/L at month 4 in the and two had marginally low serum TSH at
surviving euthyroid sick syndrome subjects (all presentation (both 0·26 mUlL).
P<O·OOI)]. Simultaneously, serum con-
centrations of free T 4 fell significantly in both
groups [17' 0 (0' 6) pmol/L to 14· 0 (0' 8) pmol/L
DIISCUSSION
at month 1, 13· 5 (0' 7) pmol/L at month 2 and
15· 3 (0' 7) pmol/L at month 4 in the normal In this study, we have shown that euthyroid
baseline thyroid functions subjects (P<0·05, sick syndrome is frequently present (63070) in
hospitalized pulmonary tuberculosis patients aged
over 50 years. As in previous reports.t-" a high
mortality (33070) was observed despite carefully
supervised antituberculosis treatment. The
occurrence of euthyroid sick syndrome at
presentation indicates more severe illness within
8 (a) this group of patients and equates with clinical
....--' *.. outcome. Patients with euthyroid sick syndrome
0 6
E were predominantly male and almost half (48070)
2-
4 died. More than 90070 of deaths were associated
'"
l-
LL with euthyroid sick syndrome at presentation.
E 2
2 An undetectable serum free T) concentration
'"
If)
0 before treatment predicted a subsequent mortality
:J
.... 20 of 75070 among our patients. Serum free T 4 ,
0
16 however, did not differentiate between survivors
~ 12 and non-survivors.
'<t
l-
LL 8 Previous studies measuring total thyroid
E hormone have indicated that the combination of
2 4
'"
If)
0
reduced serum total T) and T 4 concentrations
:J (e) (low T) and low T 4 syndrome) occurs in patients
....
:::J 3 with more severe illness and indicates a poor
E prognosis.>" However, most of these studies
:I:
2
If) investigated change of thyroid function in hetero-
l-
E geneous groups of patients with a variety of
2 illnesses. When free T 4 values are measured,
'"
If) 0
012 normal, elevated or reduced levels are found and
DlJ'ation of treatment (months) are difficult to interpret. 2,) Recent studies
involving relatively homogeneous patient groups
FIGURE I. Mean serum free T3 (a), free T. (b) and show that total or free T) concentrations are
thyroid stimulating hormone (TSH) (c) concentrations more closely related to severity and clinical
at different duration of antituberculosis treatment outcome. Simons et al. reported that euthyroid
in 14 subjects with normal baseline thyroid function sick syndrome is very common among hospitalized
before treatment (D) and 13 euthyroid sick syndrome elderly patients, and a low serum T) concentration
subjects who survived ( ~ ). Bars indicate standard error
of mean. correlates with severity of illness and mortality
*P<O'05, **P<O'Ol, ***P<O·OOl compared with in hospital. 10 Hamilton et al. in a study of 84
baseline (Student's t test), hospitalized patients with chronic advanced heart

Ann Clin Biochem 1995: 32


failure, demonstrated that a low freelreverse
T] ratio is associated with poor clinical outcome
while the free T 4 index is normal in all patients. I I
LoPresti and Nicoloff reported that, in human
immunodeficiency virus infected patients with
life-threatening Pneumocystis carinii pneumonia,
a fatal outcome is associated with persistent
undetectable serum T] values. Thus, an extremely
low serum total or free T] value reflects the
severity of illness in a variety of chronic
debilitating illness, while the serum free T 4 value
is of little predictive value.
In contrast to two previous reports.Pv'"
biochemical secondary hypothyroidism, as
defined by both subnormal T 4 and TSH values
was rarely encountered in our euthyroid sick
syndrome patents. We observed borderline
subnormal TSH concentrations in only three
of 25 euthyroid sick syndrome patients and
all had a normal free T 4' Only one patient
(No. 26) had a low free T 4 concentration
(4' 4 pmollL) associated with a mildly elevated
TSH (5 ·14 mUlL). Our findings are in agree-
ment with recent studies by Faber et al. and
Romijn et al. when confounding variables
such as dopamine and exogenous steroids
were excluded from the study populaticn.P'I?
Thus, unrecognized central nervous system
tuberculosis involvement as an explanation of
the observed thyroid dysfunction in our patients
is unlikely.
The mechanism by which euthyroid sick
syndrome develops in non-thyroidal illness is
not known. In this study, free T] concentrations
were lower, and TSH values higher, in patients
with euthyroid sick syndrome. Mean free T 4
levels were within the high normal range in both
groups of patients and were elevated in six
patients at presentation. These observations
support the view that euthyroid sick syndrome
develops as a consequence of altered thyroid
hormone metabolism in non-thyroidal illness.
First, a decrease in peripheral conversion of T 4
to T], as indicated by previous studies, would
account for the reduction in circulating free
T] together with a normal or elevated free T 4
concentration.!'!" It has been suggested that a
thyroid-binding inhibitor may alter the availability
of T 4 for metabolism and inhibit iodothyronine
5/ -monodeiodinase (type I), mainly in liver and
kidney. IS Profound suppression of enzyme
activity with more severe illness would produce
very low circulating free T] concentrations.
Secondly, the lower than expected rise in TSH in
response to reduced circulating free T] in
Euthyroid sick syndrome 389
euthyroid sick syndrome patients could be
explained by stable or even increased intrapituitary
5/ -monodeiodinase (type II) activity. 19,20 An
intrapituitary euthyroid state could then be
maintained by increased conversion of circulating
T 4 to T]. Alternatively, increased concentrations
of circulating agents such as glucocorticoids and
catecholamine may act at a suprapituitary level
to inhibit TSH secretion in non-thyroidal
illness. 2 1, 22
Recently described evidence of humoral links
between the immune and endocrine systems 2] ,24
may help to explain the genesis of the observed
hormonal changes in inflammatory conditions
such as pulmonary tuberculosis. Interleukin-l
(IL-I), secreted by activated lymphocytes, induces
hypothalamic corticotropin-releasing hormone
release with consequent pituitary-adrenal
stimulation. IL-l also releases vasopressin,
which may further stimulate adrenocorticotropic
hormone release. Additionally, IL-I triggers a
cascade of other cytokines, principally IL-2, IL-6
and tumour necrosis factor which also activate
the hypothalamic-pituitary-adrenal axis. TSH
release is also suppressed directly by IL-I and
tumour necrosis factor, or indirectly by stimulation
of somatostatin secretion, 25
Longitudinal follow-up of survivors shows that
a rise in TSH was apparent after I month of
treatment and was accompanied by a rise in free
T] and gradual fall in free T 4 concentrations in
both normal baseline thyroid function and
euthyroid sick syndrome patients, although a
more marked change was seen in the latter. Two
patients (Nos 9 and 28) showed transient mild
elevation of TSH during recovery, as previously
described.P The correction of hormonal
disturbances within 1-2 months of anti-
tuberculosis treatment coincides with the
normalization of an initial highly-elevated soluble
IL-2 receptor concentration."
In our study, all patients received rifampicin
as a component of their antituberculosis
treatment. Ohnhaus et al. have shown that
rifampicin, a potent inducer of liver microsomal
enzyme activity, lowers total T 4 , free T 4 and
reverse T] concentrations.P-" It may also increase
T] at higher dosage, as a result of enhanced
peripheral conversion of T 4 and T]. Theoretically,
this may hasten the recovery from euthyroid
sick syndrome after antituberculosis treatment.
However, it is doubtful whether any significant
effect on thyroid hormone metabolism would
be observed at the dosages used (450-600 mg/
day).
Ann Clin Biochem 1995: 32
390 Chow et al.
CONCLUSION
This study shows that euthyroid sick syndrome
occurs commonly in pulmonary tuberculosis
patients aged over 50. An undetectable serum
free T 3 concentration reflects severity and
subsequent mortality. On recovery with
treatment, free T 3 rises in parallel with TSH,
but free T 4 falls.
Acknowledgements
The authors are grateful to Rebecca Wong RN
and Eva Kan RN at Prince of Wales Hospital,
Shatin, NT, Hong Kong for their assistance with
this study.
REFERENCES
Wartofsky L, Burman KD. Alterations in thyroid
function in patients with systemic illness: the
'euthyroid sick syndrome'. Endocr Rev 1982; 3:
164-217
2 Chopra IJ, Hershman 1M, Pardridge WM, Nicoloff
IT. Thyroid function in nonthyroidal illness. Ann
Intern Med 1983; 98: 947-57
3 Sheppard MC, Ramsden DB. Abnormalities of
thyroid function tests in hospital in-patients.
Postgrad Med J 1985; 61: 983-7
4 Block AB, Rieder HL, Kelly GD, Cauthen GM,
Hayden CH, Snider DE. The epidemiology of
tuberculosis in the United States. Semin Respir Infect
1989; 4: 157-70
5 Allan WG, Snell Nl, Hill LE, Fayers PM, Scadding
lG, Fow W. A survey of deaths in Hong Kong
attributed to tuberculosis. Tubercle 1981; 62:
I-II
6 Humphries Ml, Byfield SP, Darbyshire JH, Davies
PDO, Nunn AJ, Citron KM, et al. Deaths occurring
in newly notified patients with pulmonary
tuberculosis in England and Wales. Br J Dis Chest
1984; 78: 149-58
7 Slag MF, Morley JE, Elson MK, Crowson TW,
Nuttall FQ, Shafer RB. Hypothyroxinemia in
critically ill patients as a predictor of high mortality.
JAMA 1981; 245: 43-5
8 Kaptein EM, Grieb DN, Spencer CA, Wheeler WS,
Nicoloff JT. Thyroxine metabolism in the low
thyroxine state of critical nonthyroidal illness. J C/in
Endocrinol Metab 1981; 53: 746-71
9 Kaptein EM, Weiner JM, Robinson WJ, Wheeler
WS, Nicoloff JT. Relationship of altered thyroid
hormone indices to survival in nonthyroidal illness.
Clin Endocrinol 1982; 16: 565-74
10 Simons RJ, Simon 1M, Demers LM, Santen RJ.
Thyroid dysfunction in elderly hospitalised patients.
Arch Intern Med 1990; 150: 1249-53
II Hamilton MA, Stevenson LW, Luu M, Walden JA.
Altered thyroid hormone metabolism in advanced
heart failure. J Am Coli Cardiol 1990; 16:
91-5
Ann Clin Biochem 1995: 32
12 Lopresti JS, Nicoloff JT. Changes in thyroid
hormone indices as a predictor of clinical outcome
in human immunodeficiency virus (HIV) infections.
10th International Thyroid Conference: Abstract
Book. The Hague, 1991: 313
13 Vierhapper H, Laggner A, Waldhausl W, Grubeck-
Loebenstein B, Kleinberger G. Impaired secretion
of TSH in critically ill patients with "10w-T4
syndrome". Acta Endocrinol 1982; 101: 542-49
14 Wehmann RE, Gregerrnan RI, Burns WH, Saral R,
Santos GW. Suppression of thyrotropin in the
low-thyroxine state of severe nonthyroidal illness.
N Engl J Med 1985; 312: 546-52
15 Faber J, Kirkegaard C, Rasmussen B, Westh H,
Busch-Sorensen M, Jensen IW. Pituitary-thyroid
axis in critical illness. J C/in Endocrinol Metab 1987;
65: 315-20
16 Romijn JA, Wiersinga WM. Decreased nocturnal
surge of thyrotropin in nonthyroidal illness. J Clin
Endocrinol Metab 1990; 70: 35-42
17 Kaptein EM, Robinson WJ, Grieb DA, Nicoloff JT.
Peripheral serum thyroxine, triiodothyronine and
reverse triiodothyronine kinetics in the low thyroxine
state of acute nonthyroidal illnesses. A non-
compartmental analysis. J C/in Invest 1982; 69:
526-35
18 Kaplan MM, Utiger RD. Iodothyronine metabolism
in rat liver hornogenates. J Clin Invest 1978; 61:
459-71
19 Larsen PR, Silva JE, Kaplan MM. Relationships
between circulating and intracellular thyroid
hormones: physiological and clinical implications.
Endocr Rev 1981; 2: 87-102
20 St Germaine DL, Galton VA. Comparative study
of pituitary thyroid hormone economy in fasting
and hypothyroid rats. J Clin Invest 1985; 75:
679-88
21 Delitala G. Dopamine and TSH secretion in man.
Lancet 1977; ii: 760-1
22 Brabant G, Brabant A, Ranft U, Ocran K,
Kohrle J, Hesch RD, et al. Circadian and pulsatile
TSH secretion in euthyroid man under the
influence of thyroid hormone and glucocorticoid
administration. J Clin Endocrinol Metab 1987; 65:
83-8
23 Besedovsky H, Del Rey A, Sorkin E, Dinarello CA.
Immunoregulatory feedback between interleukin-I
and glucocorticoid hormones. Science 1986; 233:
652-4
24 Sapolsky R, Rivier C, Yamamoto G, Plotsky P,
Vale W. Interleukin-I stimulates the secretion of
hypothalamic corticotropin-releasing factor. Science
1987; 238: 522-4
25 McCann SM, Rettori V, Milenkovic L, Jurcovicova J,
Gonzalez MC. Role of monokines in control of
anterior pituitary hormone release. Adv Exp Med
Bioi 1990; 274: 315-29
26 Hamblin PS, Dyer SA, Mohr VS, Le Grand BA,
Lim CF, Tuxen DV, et al. Relationship between
thyrotropin and thyroxine changes during recovery
from severe hypothyroxinemia of critical illness.
J C/in Endocrinol Metab 1986; 62: 717-22
27 Chan CHS, Lai CKW, Leung JCK, Lai KN.
Soluble interleukin-2 receptor levels in patients

with active pulmonary tuberculosis: effect of
chemotherapy. Am Rev Respir Dis 1991; 143
(suppl): A287
28 Ohnhaus EE, Studer H. The effect of different doses
of rifampicin on thyroid hormone metabolism. Br
J Clin Pharmacal 1980; 9: 285-6
Euthyroid sick syndrome 391
29 Ohnhaus EE, Burgi H, Burger A, Studer H. The
effect of antipyrine, phenobarbital and rifampicin
on thyroid hormone metabolism in man. Eur J Clin
Pharmacal 1981; 11: 381-7
Accepted for publication 21 December 1994
Ann Clin Biochem 1995: 32