The Effect of Starvation on the Concentration and Binding of Thyroxine and Triiodothyronine in Serum and on the Response to TRH

Portnay, G. I.; O’Brian, John T.; Bush, Jo Ellen; Vagenakis, Apostolos G.; Azizi, Fereidoun; Arky, Ronald A.; Ingbar, Sidney H.; Braverman, Lewis E.

doi:10.1210/jcem-39-1-191

Cited by 242 publications

(86 citation statements)

References 4 publications

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“…However, the implications of the prolonged hospitalization of the low birth wt infants are self-evident, in view of the well-known effect that malnutrition and caloric deprivation have on lowering circulating levels of IGF-I (8-10) and that illness has on reducing serum T4 concentrations (1 1). Caloric deprivation not only lowers IGF-I but also alters thyroid hormone metabolism in human volunteers, as manifested by striking decreases in serum T3 without changes in T4 (12,13). However, the latter hormone is reduced in a variety of acute and chronic disorders (14); and because malnutrition is a frequent accompaniment of disease, it is ver) likely that both T3 and T4 are diminished.…”

Section: Discussionmentioning

confidence: 99%

The Relationship of Insulin-Like Growth Factor-I to Total Thyroxine in Normal and Low Birth Weight Infants

Mitchell

Hermos

Feingold³

et al. 1989

Pediatr Res

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ABSTRACT. IGF-I concentrations were determined by RIA in eluates of dried blood collected on filter paper from infants who ranged in age from 3 to 21 d. The infants were separated into normal (>2.5 kg) and low (~2 . 5 kg) birth wt groups and further subdivided on the basis of normal (>83.7 nmollliter) or low (<64.4 nmollliter) levels of thyroxine. Both the normal and low birth wt groups whose blood thyroxine was in the normal range had similar mean IGF-I values during the 1st wk of life that were significantly higher ( p c 0.05) than those of either the normal or low birth wt groups whose thyroxine concentrations were below normal. Infants older than 1 wk of age with normal birth wt and normal thyroxine levels had signifi- T4, ThyroxineDespite the intense interest in the potential growth-promoting role of IGF-I in the newborn during the perinatal period, the precise relationship of this peptide to growth and development remains unclear. Previous studies in preterm infants have demonstrated low concentrations of IGF-I compared to concentrations seen in adults but that nonetheless correlated positively with birth wt (1, 2). The determinant(s) of these low concentrations of IGF-I in the preterm infant remains unresolved.During the tenure of our newborn screening program for hypothyroidism, we have been impressed by substantial numbers of low birth wt infants who exhibit abnormally low levels of circulating total T4 but who have normal thyroid function, as reflected by normal free T4 and TSH measurements. In view of these observations, we wondered whether IGF-I concentrations also correlated with total T4; and if so, did this confound the relationship between IGF-I and low birth wt. Therefore, we measured IGF-I and T4 levels in blood specimens from normal and low birth wt infants. These studies have taken advantage of our recently described procedure for measuring IGF-I in whole blood collected on filter paper (3). MATERIALS AND METHODSStandardized filter paper forms (S&S 903, Schleicher & Schuell, Inc., Keene, NH) impregnated with whole capillary blood from 3-to 2 1-d-old infants were used in the study after all routine procedures had been completed by the Newborn Screening Laboratory. Specimens from newborns were randomly selected for analysis on the basis of T4 concentration and birth wt. Although the threshold for the low T4 range in our screening program is 83.7 nmol/liter, we regard values between 64.4 and 83.7 nmol/liter to be borderline low. For the purpose of this study, we elected to use only those specimens with unequivocally low T4 concentrations (c64.4 nmol/liter). Because information on gestational age was unavailable from the forms, infants were separated into those of normal (>2.5 kg) and low (c2.5 kg) birth wt. Measurement of IGF-I was performed on filter paper blood specimens from 141 normal birth wt infants with normal T4 (>83.7 nmol/liter), 46 normal birth wt infants with low T4, 84 low birth wt infants with normal T4, and 92 low birth wt infants with low T4.Filter paper specimens, when not in u...

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Section: Discussionmentioning

confidence: 99%

The Relationship of Insulin-Like Growth Factor-I to Total Thyroxine in Normal and Low Birth Weight Infants

Mitchell

Hermos

Feingold³

et al. 1989

Pediatr Res

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“…Indeed, the decrease in the concentration of circulating T 3 relative to that of T 4 and an increase in rT 3 concentrations in fasting humans was one of the earliest indications that the peripheral metabolism of thyroid hormones could be modulated by physiological or physiopathological events (Portnay et al 1974). Nevertheless, the complex physiopathological mechanisms responsible for these systemic changes remain poorly understood (Warner & Beckett 2010).…”

Section: Fasting and Nonthyroidal Illness Syndromementioning

confidence: 99%

Type 1 iodothyronine deiodinase in human physiology and disease

Maia

Goemann²,

Meyer³

et al. 2011

Journal of Endocrinology

196

123

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Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T 4 ) molecule, thus producing either the active form triiodothyronine (T 3 ; activation) or inactive metabolites (reverse T 3 ; inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T 3 production contributes to a portion of plasma T 3 in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T 3 concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

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“…The noncalorigenic product of T4 monodeiodination 3,3'-5'-triiodothyronine (reverse T3, rT3), is generated from inner ring deiodination. A decrease in the serum concentration of T3 (6)(7)(8)(9)(10) and the production of T3 from T4 (11)(12)(13) have been demonstrated in man under a variety of circumstances. An increase in serum rT3 concentration almost always occurs in these states (9,10,14,15), probably due to a decrease in rT3 clearance rather than enhanced rT3 production (11,16,17).…”

Section: Introductionmentioning

confidence: 99%

The Role of Sulfhydryl Groups on the Impaired Hepatic 3′,3,5-Triiodothyronine Generation from Thyroxine in the Hypothyroid, Starved, Fetal, and Neonatal Rodent

Harris¹,

Fang²,

Hinerfeld³

et al. 1979

J. Clin. Invest.

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A B S T R A C T The role of nonprotein sulflhydryl groups (NPSH) in the decreased in vitro hepatic 3',3,5-triiodothyronine (T3) generation from thyroxine (T4) in the starved, hypothyroid, fetal and 1-to 4-d-old neonatal rat and dwarf mouse was assessed. NPSH were measured in fresh 25% liver homogenates prepared in 0.1 M P04/10 mM EDTA buffer. As 516 4-d-old neonates, but had little or no effect in the fetal and hypothyroid rat and dwarf mouse. Liver homogenates stored for 6 mo at -20°C lost their capacity to generate T3 from T4. NPSH concentrations in the frozen homogenates decreased progressively with increasing storage and were absent by 6 mo. 5'-Deiodinase activity correlated with NPSH concentration in the stored homogenates (r = 0.95, P < 0.005). Addition of DTT partially restored hepatic T3 generation in the frozen homogenate. It is concluded that NPSH are important for the action of the liver 5'-deiodinase. The decreased hepatic T3 generation in the starved rat is associated with decreased NPSH but not with a decrease in the absolute quantity of 5'-deiodinase because provision of sulfhydryl groups restored hepatic T3 generation to normal. In contrast, the decreased hepatic T3 generation in the adult hypothyroid rodent and in the fetal rat is probably due to a decrease in the enzyme concentration per se. In the 1-and 4-d neonatal rat, the decrease in hepatic T3 generation is secondary to a decrease in NPSH and the deiodinating enzyme.

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The Effect of Starvation on the Concentration and Binding of Thyroxine and Triiodothyronine in Serum and on the Response to TRH

Cited by 242 publications

References 4 publications

The Relationship of Insulin-Like Growth Factor-I to Total Thyroxine in Normal and Low Birth Weight Infants

The Relationship of Insulin-Like Growth Factor-I to Total Thyroxine in Normal and Low Birth Weight Infants

Type 1 iodothyronine deiodinase in human physiology and disease

The Role of Sulfhydryl Groups on the Impaired Hepatic 3′,3,5-Triiodothyronine Generation from Thyroxine in the Hypothyroid, Starved, Fetal, and Neonatal Rodent

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