scholarly journals Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats

2005 ◽  
Vol 153 (3) ◽  
pp. 429-434 ◽  
Author(s):  
P Cettour-Rose ◽  
T J Visser ◽  
A G Burger ◽  
F Rohner-Jeanrenaud
Keyword(s):  
Specific Inhibitor ◽  
Adult Rats ◽  
Reverse T3 ◽  
Brown Adipose ◽  
Tsh Secretion ◽  
Serum T3 ◽  
Serum T4 ◽  
Serum Tsh ◽  
Tsh Levels

Objectives: Intrapituitary triiodothyronine (T3) production plays a pivotal role in the control of TSH secretion. Its production is increased in the presence of decreased serum thyroxine (T4) concentrations and the enzyme responsible, deiodinase type 2 (D2), is highest in hypothyroidism. In order to document the role of this enzyme in adult rats we developed an experimental model that inhibited this enzyme using the specific inhibitor, reverse T3 (rT3). Methods: Hypothyroidism was induced with propylthiouracil (PTU; 0.025 g/l in drinking water) which in addition blocked deiodinase type 1 (D1) activity, responsible for the rapid clearance of rT3 in vivo. During the last 7 days of the experiment, the hypothyroid rats were injected (s.c.) for 4 days with 0.4 or 0.8 nmol T4 per 100 g body weight (bw) per day. For the last 3 days, the same amount of T4 was infused via s.c. minipumps. In additional groups, 25 nmol rT3/100 g bw per day were added to the 3-day infusion of T4. Results: Infusion of 0.4 nmol T4/100 g bw per day did not affect the high serum TSH levels, 0.8 nmol T4/100 g bw per day decreased them to 57% of the hypothyroid values. The infusions of rT3 inhibited D2 activity in all organs where it was measured: the pituitary, brain cortex and brown adipose tissue (BAT). In the pituitary, the activity was 27%, to less than 15% of the activity in hypothyroidism. Despite that, serum TSH levels did not increase, serum T4 concentrations did not change and the changes in serum T3 were minimal. Conclusions: We conclude that in partly hypothyroid rats, a 3-day inhibition of D2 activity, without concomitant change in serum T4 and minimal changes in serum T3 levels, is not able to upregulate TSH secretion and we postulate that this may be a reflection of absent or only minimal changes in circulating T3 concentrations.

Benefit of Combined Triiodothyronine (LT3) and Thyroxine (LT4) Treatment in Athyreotic Patients Unresponsive to LT4 Alone

2011 ◽  
Vol 120 (02) ◽  
pp. 121-123 ◽  
Author(s):  
D. Solter ◽  
M. Solter
Keyword(s):  
Thyroid Hormone ◽  
Combination Therapy ◽  
Genetic Basis ◽  
Normal Range ◽  
Serum T3 ◽  
Serum T4 ◽  
Serum Tsh ◽  
Tsh Levels

AbstractDespite some reports, the usefulness of levothyroxine ( LT4) and levotriiodothyronine (LT3) combination therapy in hypothyroidism remains controversial. The objective of this paper is to study a benefit of additional LT3 in athyreotic patients who failed to normalize TSH on LT4 alone even with hyperthyroid serum T4 values.In a survey of 200 athyreotic patients treated between 2006 and 2009, about 7% failed to normalize serum TSH levels following treatment with LT4, though serum T4 values in the hyperthyroid range were achieved. These patients (characterized by serum T4≥160 nmol/L and TSH≥5.0 mIU/L), were additionally treated with 10 μg b. i. d LT3. LT3 and LT4 combination therapy resulted in decreased serum TSH levels into the normal range (12.8 vs. 1.22 mIU/L; p<0.01) and reduced LT4 dose (153.3 vs. 117.5 μg; p<0.01) required for normalization of serum T4 values (170.6 vs. 123.3 nmol/L; p<0.01). Serum T3 values were higher (1.3 vs. 2.26 nmol/L; p<0.01) than those during monotherapy with LT4.Our results indicate a subpopulation of athyreotic patients that could significantly benefit from combined LT4 + LT3 therapy in restoring normal TSH and thyroid hormone patterns. Further research should be undertaken to provide a genetic basis for these findings.

scholarly journals Distinct Roles of Deiodinases on the Phenotype of Mct8 Defect: A Comparison of Eight Different Mouse Genotypes

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1180-1191 ◽  
Author(s):  
Xiao-Hui Liao ◽  
Caterina Di Cosmo ◽  
Alexandra M. Dumitrescu ◽  
Arturo Hernandez ◽  
Jacqueline Van Sande ◽  
...  
Keyword(s):  
Growth Response ◽  
Pituitary Thyroid Axis ◽  
Severe Impairment ◽  
Serum T3 ◽  
Serum T4 ◽  
Thyroid Axis ◽  
Mct8 Deficiency ◽  
The Brain ◽  
Insight Into ◽  
Serum Tsh

Mice deficient in the thyroid hormone (TH) transporter Mct8 (Mct8KO) have increased 5′-deiodination and impaired TH secretion and excretion. These and other unknown mechanisms result in the low-serum T4, high T3, and low rT3 levels characteristic of Mct8 defects. We investigated to what extent each of the 5′-deiodinases (D1, D2) contributes to the serum TH abnormalities of the Mct8KO by generating mice with all combinations of Mct8 and D1 and/or D2 deficiencies and comparing the resulting eight genotypes. Adding D1 deficiency to that of Mct8 corrected the serum TH abnormalities of Mct8KO mice, normalized brain T3 content, and reduced the impaired expression of TH-responsive genes. In contrast, Mct8D2KO mice maintained the serum TH abnormalities of Mct8KO mice. However, the serum TSH level increased 27-fold, suggesting a severely impaired hypothalamo-pituitary-thyroid axis. The brain of Mct8D2KO manifested a pattern of more severe impairment of TH action than Mct8KO alone. In triple Mct8D1D2KO mice, the markedly increased serum TH levels produced milder brain defect than that of Mct8D2KO at the expense of more severe liver thyrotoxicosis. Additionally, we observed that mice deficient in D2 had an unexplained marked reduction in the thyroid growth response to TSH. Our studies on these eight genotypes provide a unique insight into the complex interplay of the deiodinases in the Mct8 defect and suggest that D1 contributes to the increased serum T3 in Mct8 deficiency, whereas D2 mainly functions locally, converting T4 to T3 to compensate for distinct cellular TH depletion in Mct8KO mice.

Human cold air habituation is independent of thyroxine and thyrotropin

1992 ◽  
Vol 72 (6) ◽  
pp. 2134-2139 ◽  
Author(s):  
R. L. Hesslink ◽  
M. M. D'Alesandro ◽  
D. W. Armstrong ◽  
H. L. Reed
Keyword(s):  
Single Daily Dose ◽  
Plasma Norepinephrine ◽  
Free T4 ◽  
Cold Air ◽  
Brown Adipose ◽  
Daily Dose ◽  
Before And After ◽  
Serum T4 ◽  
The Relationship ◽  
Serum Tsh

Thyroxine (T4) is required in species possessing brown adipose tissue (BAT) for the maintenance of cold tolerance and adaptation. In humans, who possess negligible quantities of BAT, the importance of T4 has not been demonstrated. We studied the effects of decreased serum T4 and thyrotropin (TSH) on human cold habituation after repeated cold air exposures. Eight men (T3+) received a single daily dose of triiodothyronine (T3; 30 micrograms/day), and another eight men (T3-) received a placebo. All 16 normal thyroid men underwent a standardized cold air test (SCAT) under basal conditions in January and again in March after eighty 30-min 4.4 degrees C air exposures (10/wk). Measurements of basal metabolic rate (BMR), O2 consumption (VO2), mean arterial pressure (MAP), plasma norepinephrine (NE), serum TSH, free and total T4, and free and total T3 were repeated before and after 8 wk of exposure. TSH, free T4, and total T4 were 50% lower for T3+ than for T3- subjects. Total and free T3 were not different between groups. BMR was unchanged after habituation, whereas the cold-stimulated VO2, MAP, and NE were significantly reduced for all subjects in March. The relationship between VO2 and NE (r2 = 0.44, P less than 0.001) during the initial SCAT was unchanged with habituation. We suggest that human cold habituation is independent of major changes in circulating T4 and TSH.

Is There Compensated Hypothyroidism in Infancy?

PEDIATRICS ◽  
1992 ◽  
Vol 90 (2) ◽  
pp. 207-211
Author(s):  
Ramin Alemzadeh ◽  
Silvia Friedman ◽  
Pavel Fort ◽  
Bridget Recker ◽  
Fima Lifshitz
Keyword(s):  
Screening Program ◽  
Thyroid Stimulating Hormone ◽  
Normal Serum ◽  
Close Monitoring ◽  
Normal Range ◽  
Thyroid Screening ◽  
Serum T4 ◽  
Hypometabolic State ◽  
Serum Tsh ◽  
Tsh Levels

The state-mandated newborn thyroid screening program may uncover infants who exhibit normal thyoxine (T4) levels with various degrees of hyperthyrotropinemia. To elucidate further the thyroid status, the basal metabolic rate (BMR) of 10 infants (7 boys, 3 girls; aged 9 to 63 days) was studied by indirect calorimetry. They were clinically euthyroid and healthy with no evidence of overt biochemical hypothyroidism (low T4, high thyroid-stimulating hormone [TSH]). Confirmatory testing indicated that all infants had normal serum T4 levels for age (mean ± SD: 10.3 ± 3.2 µg/dL). However, serum TSH levels varied from 2.3 to 99.2 µU/mL In 4 infants (2 boys, 2 girls) the BMR was low (38.1 ± 4.1 kcal/kg per day), while the other 6 patients (5 boys, 1 girl) demonstrated BMRs within the normal range (49.6 ± 1.9 kcal/kg per day, P &lt; .001). The serum TSH levels were above 7.0 µU/mL among those infants with a low BMR, whereas the serum TSH levels were always below 6.0 µU/mL among the normometabolic infants. All infants who had a low BMR received thyroid therapy and promptly became normometabolic (BMR: 48.7 ± 1.0 kcal/kg per day) with suppression of TSH levels (3.2 ± 1.3 µU/mL) within 3 weeks of therapy, while their serum T4 levels remained within the normal range. The observed normalization of BMR In parallel to reduction of TSH levels following thyroid replacement therapy strongly suggests that these patients demonstrated a hypometabolic state, despite normal serum T4 levels. Therefore, the assessment of BMR may help define subclinical hypothyroidism in infancy in conjunction with a close monitoring of TSH concentration.

Rapid adaptations of serum thyrotrophin, triiodothyronine and reverse triiodothyronine levels to short-term starvation and refeeding

1984 ◽  
Vol 105 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Jean-Noel Hugues ◽  
Albert G. Burger ◽  
A. Eugene Pekary ◽  
Jerome M. Hershman
Keyword(s):  
Serum Cortisol ◽  
Starvation Period ◽  
Short Term ◽  
Mean Values ◽  
Fed State ◽  
Tsh Secretion ◽  
The Mean ◽  
Serum Tsh ◽  
Tsh Levels

Abstract. Nutrition influences thyroid function at the level of TSH secretion, at the level of monodeiodination, and possibly elsewhere. In order to study the effect of starvation on TSH secretion, 8 healthy male volunteers fasted for 30 h and were then refed with 800 kcal. Refeeding was performed at 19.00 h and blood was sampled at 20 min intervals until midnight. Control experiments were performed in the same subjects both when they were normally fed and when the starvation period was prolonged a further 5 h until midnight. Starvation decreased serum TSH levels to below 1 mU/l, and without refeeding the nocturnal peak of the TSH nycthemeral rhythm was abolished. With refeeding serum TSH tended to increase towards midnight and was significantly higher than during starvation. However, the serum TSH levels remained significantly below those at the same time of the day in the absence of a preceding starvation period. Serum T3 levels were significantly lower than in the fed state. The mean values were 1.84 ± 0.03 vs 2.30 ± 0.06 nmol/l (120 ±2 vs 150 ± 4 ng/100 ml, mean ± sem P < 0.01). Refeeding did not result in a measurable change in serum T3 concentration (1.80 ± 0.05 nmol/l; 120 ± 3 ng/100 ml, mean ± sem, n.s.). The contrary was true for rT3 levels which increased in starvation and tended to fall with refeeding, but this decrease was not significant. As glucocorticoids have been implicated in the control of monodeiodination and TSH secretion, serum cortisol levels were also measured. They did not differ during the 3 experimental periods. The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion. The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion.

Serum thyroid hormones and tissue 5'-monodeiodinase activity in acutely thyroidectomized newborn lambs

1986 ◽  
Vol 251 (2) ◽  
pp. E151-E155 ◽  
Author(s):  
D. H. Polk ◽  
S. Y. Wu ◽  
D. A. Fisher
Keyword(s):  
Sham Operation ◽  
Fetal Sheep ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Brown Adipose ◽  
Serum T3 ◽  
Serum T4 ◽  
Serum Thyroid Hormones ◽  
Metabolic Significance

After either total thyroidectomy or sham operation in full-term fetal sheep, fetuses were delivered and serial blood samples were obtained for measurements of thyroxine (T4), triiodothyronine (T3), and catecholamines. Despite comparable serum T4 values (T4 means +/- SE, sham 7.1 +/- 0.6 micrograms/dl, thyroidectomized 6.8 +/- 0.7 micrograms/dl at 60 min after birth), serum T3 values were lower in the thyroidectomized animals (T3 means +/- SE, thyroidectomized 39 +/- 4.8 ng/dl, sham 153 +/- 20.1 ng/dl at 60 min after birth). Four hours after birth, the animals were killed with an intravenous overdose of barbiturate. Brain, thyroid, liver, kidney, and brown adipose tissues were dissected and analyzed for thyroxine 5'-monodeiodinase (5'-MDI) activity in vitro. 5'-MDI activity was comparable in all tissues from sham-operated and thyroidectomized lambs. Plasma epinephrine and norepinephrine concentrations, mean arterial pressure, mean pulse, rectal temperature, and arterial blood gas values were similar in the two groups of animals. These data support the hypothesis that the thyroid gland is the major source of T3 for the T3 surge in the immediate newborn period. They also indicate that the neonatal T3 surge has limited immediate metabolic significance in euthyroid newborns.

Cold-induced increase in brown fat thyroxine 5'-monodeiodinase is attenuated in Zucker obese rat

1987 ◽  
Vol 252 (1) ◽  
pp. E63-E67 ◽  
Author(s):  
S. Y. Wu ◽  
J. S. Stern ◽  
D. A. Fisher ◽  
Z. Glick
Keyword(s):  
Cafeteria Diet ◽  
Treatment Groups ◽  
Brown Adipose ◽  
Obese Rats ◽  
Serum T3 ◽  
Serum T4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

In this study we examined the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for enzymic conversion of thyroxine (T4) to triiodothyronine (T3) in BAT. A total of 34 lean and obese rats, approximately 4 mo old were divided into three treatment groups: group 1 (5 lean and 6 obese) was fed Purina rat chow for 21 days, and group 2 (5 lean and 6 obese) was fed a cafeteria diet for 21 days, and group 3 (6 lean and 6 obese) was fed Purina rat chow and maintained in the cold (8 +/- 1 degrees C) for 7 days. The lean and obese rats in all three groups of animals were matched closely for age and respective body weight. Activity of T4 5'-deiodinase was determined as the rate of T3 production from added T4 under controlled in vitro conditions. Serum T4 and T3 were determined by radioimmunoassay. The rate of T4-to-T3 conversion in BAT was similar in the lean and obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet (approximately 40-50 pmol T3/scapular BAT depot per h). However, expressed per scapular BAT depot, lean rats exposed to cold displayed about a fivefold increase in BAT T3 production (P less than 0.0001), whereas only a small increase was observed in the cold-exposed obese rats. Serum T3 levels tended to be reduced in the Zucker obese rats. Our data indicate a reduced capacity for T3 production in Zucker rat BAT exposed to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

Deficient pulsatile thyrotropin secretion in the low-thyroid-hormone state of severe non-thyroidal illness

1994 ◽  
Vol 130 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Nicola Custro ◽  
Vincenza Scafidi ◽  
Salvatore Gallo ◽  
Alberto Notarbartolo
Keyword(s):  
Thyroid Hormone ◽  
Healthy Subjects ◽  
Normal Subjects ◽  
Healthy Individuals ◽  
Circadian Variations ◽  
Tsh Secretion ◽  
Thyroid Hormone Levels ◽  
Rhythmic Change ◽  
Serum Tsh ◽  
Tsh Levels

Custro N, Scafidi V, Gallo S, Notarbartolo A. Deficient pulsatile thyrotropin secretion in the low-thyroid-hormone state of severe non-thyroidal illness. Eur J Endocrinol 1994;130:132–6. ISSN 0804–4643. Twenty-four-hour thyrotropin (TSH) profiles in eight severely ill patients were compared with those of six healthy subjects. The profiles were assessed using the cosinor method to evaluate circadian variations and using the Pulsar algorithm to analyze episodic secretion. In the normal subjects, the typical periodicity of TSH secretion showed a mean level in the rhythm (mesor) of 2.03 mU/l, The amplitude (half the extent of rhythmic change in the cycle) was 0.58 mU/l; the acrophase (the delay from midnight (0 degrees) of the highest level in the rhythm) was −9.9 degrees. In contrast, severely ill patients showed only slight and anticipated elevations of serum TSH levels (mesor 0.93 mU/l, amplitude 0.22 mU/l, acrophase +82.4 degrees). Moreover, whereas the episodic TSH secretion in healthy individuals consisted of 5–8 pulses/24 h, mainly clustered around midnight, only one pulse of reduced amplitude was detected in two of the eight severely ill patients and no pulses in the other six. Since earlier studies have indicated that the loss of TSH pulsatility is associated with the relative insensitivity of the thyrotrophs to low thyroid hormone levels and our analytical procedures have demonstrated that 24 h pulsatile pattern of TSH closely overlapped with baseline TSH secretion, it seems reasonable to assume that low-thyroid-hormone state, deficient pulsatile TSH secretion and altered nyctohemeral TSH periodicity do not coincide by chance, but that there is a causal relationship between such abnormalities in severely ill patients. Nicola Custro, Cattedra di Patologia Medica, Via del Vespro, n.141, 90127 Palermo, Italy

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