Effect of Dietary Composition on Fasting-Induced Changes in Serum Thyroid Hormones and Thyrotropin Fereidoun Azizi To assess the effect of starvation and refeeding on serum thyroid hormones and thyrotropin (TSH) concentrations, 45 obese subjects were studied after 4 days of fasting and after refeeding with diets of varying composition. All subjects showed an increase in both serum total and free thyroxine (T,), and a decrease in serum total and free triiodothyronine (Ts) following fasting. These changes were more striking in men then in women. The serum Ts declined during fasting even when the subjects were given oral L-T,, but not when given oral L-T,. After fasting, the serum reverse Ts (rTs) rose, the serum TSH declined, and the TSH response to thyrotropin-releasing hormone (TRH) was blunted. Refeeding with either a mixed
diet (n = 22) or a carbohydrate diet (n = 8) caused the fasting-induced changes in serum Ts, T,, rTs, and TSH to return to control values. In contrast, refeeding with protein (n = 6) did not cause an increase in serum Ts or in serum TSH of fasted subjects, while it did cause a decline in serum rTs toward basal value. The present data suggest that: (1) dietary carbohydrate is an important factor in reversing the fall in serum T, caused by fasting; (2) production of rTs is not as dependent on carbohydrate as that of T,; (3) men show more significant changes in serum thyroid hormone concentrations during fasting than women do, and (4) absorption of T, is not altered during fasting.
F
ASTING is associated with a decrease in serum T, ‘-’ and an increase in in serum T, is due to a deserum rT,. 3.6,7At least part of the reduction crease in the peripheral conversion of T, to T,. 2-7 It has been shown that serum T3 and rT, return to prefasting values upon refeeding with a mixed diet.3.5.b However, the effect of dietary composition on serum T3 and rT, after fasting has not been reported. Furthermore, there are conflicting data on the effect of fasting on serum free T4,3.5s6serum TSH,2*5.6.s and TSH response to TRH.‘,236V8In addition, perhaps due to the relatively small number of subjects previously studied, differences between men and women in the response of serum thyroid hormones to fasting have not been reported. We studied the effect of fasting on serum T,, free T,, T,, free T,, rT,, and TSH in a large number of obese men and women. We also compared the effects of refeeding with mixed, carbohydrate, protein, and fat diets on these parameters. In addition, we studied the effect of fasting on TSH and T3 responses to TRH and on serum T4, T,, and rT, during treatment with oral T3 in a smaller number of obese patients. MATERIALS AND Twenty-seven were studied.
female Thirty-five
and
18 male
subjects
obese
were studied
euthyroid
METHODS patients
while taking
ranging
no medication,
in age from 6 (5 women
20 to 60 yr and
I man)
From the St. Elizabeth’s Hospital and the Department of Medicine, Tufts Medical School, Boston, Mass. Receivedforpublication November 15, I977. Supported bv National Insiitutes of Health General Research Support Grant JSOIRR 05587-07. Address reprint requests to Fereidoun Azizi, M.D., St. Elizabeth’s Hospital, 736 Cambridge Street, Boston, Mass. 02135. a 1978 by Grune & Stratton, Inc. 0026~049_F/78/‘2708~OOO8%OI,OO/O Metabolism,
Vol.
27,
NO. 8 (August),
1978
935
FEREIDOUN
936
AZIZI
were studied after taking 100 pg of L-T3 daily for at least 4 wk, and 4 women were studied after taking 0.3 mg L-T4 daily for at least 4 wk. After obtaining baseline blood samples, each subject was fasted for 4 days with free water intake of at least 2000 ml. After the fast, each was refed with an 800 kcal diet. Twenty-eight subjects (6 while taking oral T3) were refed with a mixed diet containing 70 g carbohydrate, 50 g protein, and 35 g fat for 4 days; 8 subjects (4 while taking oral T4) received a liquid carbohydrate diet consisting of soft drinks and Hycale (BeechamMassengill Pharmaceuticals, Bristol, Term.) for 4 days; 6 subjects had a protein diet (2 patients received lean steaks and 4 received a protein mixture-EMFo, Control Drug, Port Reading, N.J.) for 4 days followed by a mixed diet as above for 4 days, and three subjects were refed with a fat diet consisting of lipomuI@ (Upjohn) for 4 days followed by a carbohydrate diet for 4 days. Blood samples were drawn in most patients after the 4 days of fasting or after the Cday periods on the refeeding diets. In subjects taking Ts or T4, blood samples were drawn 24 hr after the last dose of thyroid hormone. Blood samples were obtained daily from the 6 subjects who were refed with a protein diet followed by mixed diet. The serum TSH and T3 responses to thyrotropin releasing hormone (TRH) were determined in 8 subjects (4 women and 4 men) before and after the 4-day fasting period. Blood samples were obtained at - 10, 0, 10,20,30,45,60,90, and 120 min after i.v. injection of 100 rg TRH. All samples from each patient were analyzed concurrently and in duplicate. Serum total T4 and total Ts were measured by radioimmunoassay.‘*” The percent free T4 and percent free Ts were measured by equilibrium dialysis.“*12 Serum rTj was measured using a kit and pure L-rT3 (Serono Laboratories, Boston, Mass.); in 40 normal subjects the mean f SD was 20.4 f 5.1 ng/lOO ml, and cross-reaction with T4 in the assay for rTs was less than O.OS’A.TSH concentration in serum was also measured by RIA,t3 using materials supplied by the National Institutes of Health and human TSH standard 68/38. Statistical analyses were performed using the paired and unpaired t testI RESULTS
Eflect of Fasting on Serum Thyroid Hormone Concentrations
Serum T3 fell significantly after 4 days of fasting in both men and women (Table 1). The fall was significantly greater in men than in women (p < 0.001). Conversely, the serum T4 rose significantly after 4 days of fasting in both men and women (Table 1). Again, the increase was greater in men than in women (p < 0.02). In addition, the free T3 fell significantly in both men and women (men: 214 f 34 to 126 f 48 pg/lOO ml, p < 0.001; women: 190 f 38 to 144 f 44 pg/lOO ml, p < 0.001) and the free T4 rose in both men and women after fasting (men: 1.40 f 0.27 to 1.85 i 0.25 ng/lOO ml, p < 0.001; women: 1.41 k 0.17 to 1.69 f 0.18 ng/ 100 ml, p < 0.001). Again, the change was greater in men than in women ( p < 0.01 for free T3 and < 0.02 for free T4). Serum rT, increased after 4 days of fasting in both men and women (Table 1); there was no Table 1.
of Fasting and Refeeding on the Serum Concentmtions of
Ekt
1, , T3, rlj , and TSH in Obese, Euthyroid Subjects SeNm T4
SennnT3
(Ire/TM ml) Gmup
C
F
(w/la R
C
F
SerumTSH
SerumrT3 (w/l00 ml)
ml) R
C
F
(N/ml) R
C
F
R
WDmMl MwJn
8.1
SD(n)
1.1(18)
8.6’ 1.2(18)
8.0
144
l.,(M)
24(N)
109’
148
18.9
26.7.
20.1
2.0
1.*t
25(18)
23(18)
3.8(12)
4.1(12]
4.1(12)
1.4(15)
O.O(lS)
1.0 l.O(lS)
Men MelIn
7.0
9.1.
7.9
151
89’
SD(n)
1.4(17)
1.9(17)
1.3(17)
27(17)
32(17)
Abbmvfaffonr;C, control;F, 4 + *p < O.CQi. cornpad to conkd tp < o.D25. tp < 0.005.
153 28(V)
19.9
19.8’
21.2
3.0
2.1%
2.8
4.5(11)
4.8(Il)
4.2(11)
1.4(17)
1.2(17)
1.3(17)
after fasffng; R, 4 dq offer refeedingrifh 800 kcatm&addht; n, numberof wbiech. values by usingpoked t tssh.
tPaired
t test, compared
zk SD.
not significant.
“Mean
NS,
value.
17.5 f 3.6
pvolue Serum rT~(ng/lOO ml)
to control
8.1 f 1.0
pvaluet SerumT,(pg/1OOml)
D value
153 +17*
SerumT~(ng/lOO ml)
Control
12i-*13
diet (n = 22) or a carbohydrate diet (n = 8) caused the fasting-induced changes in serum Ts, T,, rTs, and TSH to return to control values. In contrast, refeeding with protein (n = 6) did not cause an increase in serum Ts or in serum TSH of fasted subjects, while it did cause a decline in serum rTs toward basal value. The present data suggest that: (1) dietary carbohydrate is an important factor in reversing the fall in serum T, caused by fasting; (2) production of rTs is not as dependent on carbohydrate as that of T,; (3) men show more significant changes in serum thyroid hormone concentrations during fasting than women do, and (4) absorption of T, is not altered during fasting.
F
ASTING is associated with a decrease in serum T, ‘-’ and an increase in in serum T, is due to a deserum rT,. 3.6,7At least part of the reduction crease in the peripheral conversion of T, to T,. 2-7 It has been shown that serum T3 and rT, return to prefasting values upon refeeding with a mixed diet.3.5.b However, the effect of dietary composition on serum T3 and rT, after fasting has not been reported. Furthermore, there are conflicting data on the effect of fasting on serum free T4,3.5s6serum TSH,2*5.6.s and TSH response to TRH.‘,236V8In addition, perhaps due to the relatively small number of subjects previously studied, differences between men and women in the response of serum thyroid hormones to fasting have not been reported. We studied the effect of fasting on serum T,, free T,, T,, free T,, rT,, and TSH in a large number of obese men and women. We also compared the effects of refeeding with mixed, carbohydrate, protein, and fat diets on these parameters. In addition, we studied the effect of fasting on TSH and T3 responses to TRH and on serum T4, T,, and rT, during treatment with oral T3 in a smaller number of obese patients. MATERIALS AND Twenty-seven were studied.
female Thirty-five
and
18 male
subjects
obese
were studied
euthyroid
METHODS patients
while taking
ranging
no medication,
in age from 6 (5 women
20 to 60 yr and
I man)
From the St. Elizabeth’s Hospital and the Department of Medicine, Tufts Medical School, Boston, Mass. Receivedforpublication November 15, I977. Supported bv National Insiitutes of Health General Research Support Grant JSOIRR 05587-07. Address reprint requests to Fereidoun Azizi, M.D., St. Elizabeth’s Hospital, 736 Cambridge Street, Boston, Mass. 02135. a 1978 by Grune & Stratton, Inc. 0026~049_F/78/‘2708~OOO8%OI,OO/O Metabolism,
Vol.
27,
NO. 8 (August),
1978
935
FEREIDOUN
936
AZIZI
were studied after taking 100 pg of L-T3 daily for at least 4 wk, and 4 women were studied after taking 0.3 mg L-T4 daily for at least 4 wk. After obtaining baseline blood samples, each subject was fasted for 4 days with free water intake of at least 2000 ml. After the fast, each was refed with an 800 kcal diet. Twenty-eight subjects (6 while taking oral T3) were refed with a mixed diet containing 70 g carbohydrate, 50 g protein, and 35 g fat for 4 days; 8 subjects (4 while taking oral T4) received a liquid carbohydrate diet consisting of soft drinks and Hycale (BeechamMassengill Pharmaceuticals, Bristol, Term.) for 4 days; 6 subjects had a protein diet (2 patients received lean steaks and 4 received a protein mixture-EMFo, Control Drug, Port Reading, N.J.) for 4 days followed by a mixed diet as above for 4 days, and three subjects were refed with a fat diet consisting of lipomuI@ (Upjohn) for 4 days followed by a carbohydrate diet for 4 days. Blood samples were drawn in most patients after the 4 days of fasting or after the Cday periods on the refeeding diets. In subjects taking Ts or T4, blood samples were drawn 24 hr after the last dose of thyroid hormone. Blood samples were obtained daily from the 6 subjects who were refed with a protein diet followed by mixed diet. The serum TSH and T3 responses to thyrotropin releasing hormone (TRH) were determined in 8 subjects (4 women and 4 men) before and after the 4-day fasting period. Blood samples were obtained at - 10, 0, 10,20,30,45,60,90, and 120 min after i.v. injection of 100 rg TRH. All samples from each patient were analyzed concurrently and in duplicate. Serum total T4 and total Ts were measured by radioimmunoassay.‘*” The percent free T4 and percent free Ts were measured by equilibrium dialysis.“*12 Serum rTj was measured using a kit and pure L-rT3 (Serono Laboratories, Boston, Mass.); in 40 normal subjects the mean f SD was 20.4 f 5.1 ng/lOO ml, and cross-reaction with T4 in the assay for rTs was less than O.OS’A.TSH concentration in serum was also measured by RIA,t3 using materials supplied by the National Institutes of Health and human TSH standard 68/38. Statistical analyses were performed using the paired and unpaired t testI RESULTS
Eflect of Fasting on Serum Thyroid Hormone Concentrations
Serum T3 fell significantly after 4 days of fasting in both men and women (Table 1). The fall was significantly greater in men than in women (p < 0.001). Conversely, the serum T4 rose significantly after 4 days of fasting in both men and women (Table 1). Again, the increase was greater in men than in women (p < 0.02). In addition, the free T3 fell significantly in both men and women (men: 214 f 34 to 126 f 48 pg/lOO ml, p < 0.001; women: 190 f 38 to 144 f 44 pg/lOO ml, p < 0.001) and the free T4 rose in both men and women after fasting (men: 1.40 f 0.27 to 1.85 i 0.25 ng/lOO ml, p < 0.001; women: 1.41 k 0.17 to 1.69 f 0.18 ng/ 100 ml, p < 0.001). Again, the change was greater in men than in women ( p < 0.01 for free T3 and < 0.02 for free T4). Serum rT, increased after 4 days of fasting in both men and women (Table 1); there was no Table 1.
of Fasting and Refeeding on the Serum Concentmtions of
Ekt
1, , T3, rlj , and TSH in Obese, Euthyroid Subjects SeNm T4
SennnT3
(Ire/TM ml) Gmup
C
F
(w/la R
C
F
SerumTSH
SerumrT3 (w/l00 ml)
ml) R
C
F
(N/ml) R
C
F
R
WDmMl MwJn
8.1
SD(n)
1.1(18)
8.6’ 1.2(18)
8.0
144
l.,(M)
24(N)
109’
148
18.9
26.7.
20.1
2.0
1.*t
25(18)
23(18)
3.8(12)
4.1(12]
4.1(12)
1.4(15)
O.O(lS)
1.0 l.O(lS)
Men MelIn
7.0
9.1.
7.9
151
89’
SD(n)
1.4(17)
1.9(17)
1.3(17)
27(17)
32(17)
Abbmvfaffonr;C, control;F, 4 + *p < O.CQi. cornpad to conkd tp < o.D25. tp < 0.005.
153 28(V)
19.9
19.8’
21.2
3.0
2.1%
2.8
4.5(11)
4.8(Il)
4.2(11)
1.4(17)
1.2(17)
1.3(17)
after fasffng; R, 4 dq offer refeedingrifh 800 kcatm&addht; n, numberof wbiech. values by usingpoked t tssh.
tPaired
t test, compared
zk SD.
not significant.
“Mean
NS,
value.
17.5 f 3.6
pvolue Serum rT~(ng/lOO ml)
to control
8.1 f 1.0
pvaluet SerumT,(pg/1OOml)
D value
153 +17*
SerumT~(ng/lOO ml)
Control
12i-*13
