Reduced tissue thyroid hormone levels in fatal illness

Arem, Ridha; Wiener, Gregory; Kaplan, Sara; Kim, Han-Seob; Reichlin, Seymour; Kaplan, Michael M.

doi:10.1016/0026-0495(93)90266-q

Cited by 125 publications

(59 citation statements)

References 40 publications

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“…The changes in circulating total and free T4 and T3, together with decreased TSH, and the low T4 and T3 levels found in all the tissues studied in the present D dams are in agreement with the changes described for the nonpregnant diabetic rats (10), and for patients dying from different nonthyroidal illnesses (34), indicating that 2 weeks after the injection of STZ, the adaptive mechanisms involving decreased thyroidal secretion of thyroid hormones are fully operative.…”

Section: Introductionsupporting

confidence: 90%

Maternal Diabetes Mellitus, a Rat Model for Nonthyroidal Illness: Correction of Hypothyroxinemia with Thyroxine Treatment Does Not Improve Fetal Thyroid Hormone Status

Calvo¹,

Escobar²,

Rey³

et al. 1997

Thyroid

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Maintenance of normal maternal thyroxinemia prevents severe triiodothyronine (T3) deficiency of the fetus with primary thyroid failure (1). We have studied whether thyroxine (T4) would also protect the fetal brain when maternal hypothyroxinemia is caused by nonthyroidal illnesses. We have used the streptozotocin-induced diabetes mellitus pregnant rat as a model of maternal nonthyroidal illness. We measured the effects of diabetes mellitus, and of correction of the ensuing maternal hypothyroxinemia with T4 as compared to insulin, on maternal body weight, the outcome of pregnancy, glucose, insulin, T4, T3, reverse T3, and thyrotropin levels in the maternal and fetal circulation, as well as T4 and T3 concentrations in tissues, and iodothyronine deiodinases in liver, lung, and brain. The diabetic mothers showed changes in thyroid hormone status typical of nonthyroidal illnesses. Thyroid hormone status of the fetuses was severely affected: the total T4 and T3 pools decreased to one-third of normal values. T4 and T3 concentrations in the fetal brain were lower than normal and the expected increase in 5'-deiodinase activity was not observed. Although insulin treatment avoided or mitigated these changes, the low cerebral T3 did not improve with T4 treatment of the maternal hypothyroxinemia. Several findings indicated that treatment of the severely ill dams with T4 was actually harmful for the outcome of pregnancy. These negative effects were observed without the expected increase in the maternal or fetal T3 pools.

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Section: Introductionsupporting

confidence: 90%

Maternal Diabetes Mellitus, a Rat Model for Nonthyroidal Illness: Correction of Hypothyroxinemia with Thyroxine Treatment Does Not Improve Fetal Thyroid Hormone Status

Calvo¹,

Escobar²,

Rey³

et al. 1997

Thyroid

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“…These studies were mostly based on samples obtained from critically ill patients shortly after death. Liver T 3 and T 4 concentrations were reported to be low in samples of NTIS patients as compared with healthy controls, indicating that the liver may be deficient in THs during prolonged critical illness (87). In agreement with this are the decreased liver T 3 levels observed in a rabbit model of prolonged critical illness (88).…”

Section: Chronic Inflammation Sepsis and Critical Illnessmentioning

confidence: 69%

MECHANISMS IN ENDOCRINOLOGY: Beyond the fixed setpoint of the hypothalamus–pituitary–thyroid axis

Fliers

Kalsbeek

Boelen

2014

European Journal of Endocrinology

104

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The hypothalamus-pituitary-thyroid (HPT) axis represents a classical example of an endocrine feedback loop. This review discusses dynamic changes in HPT axis setpoint regulation, identifying their molecular and cellular determinants, and speculates about their functional role. Hypothalamic thyrotropin-releasing hormone neurons were identified as key components of thyroid hormone (TH) setpoint regulation already in the 1980s, and this was followed by the demonstration of a pivotal role for the thyroid hormone receptor beta in negative feedback of TH on the hypothalamic and pituitary level. Gradually, the concept emerged of the HPT axis setpoint as a fixed entity, aiming at a particular TH serum concentration. However, TH serum concentrations appear to be variable and highly responsive to physiological and pathophysiological environmental factors, including the availability or absence of food, inflammation and clock time. During food deprivation and inflammation, TH serum concentrations decrease without a concomitant rise in serum TSH, reflecting a deviation from negative feedback regulation in the HPT axis. Surprisingly, TH action in peripheral organs in these conditions cannot be simply predicted by decreased serum TH concentrations. Instead, diverse environmental stimuli have differential effects on local TH metabolism, e.g. in liver and muscle, occurring quite independently from decreased TH serum concentrations. The net effect of these differential local changes is probably a major determinant of TH action at the tissue level. In sum, hypothalamic HPT axis setpoint regulation as well as TH metabolism at the peripheral organ level is flexible and dynamic, and may adapt the organism in an optimal way to a range of environmental challenges.

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“…The latter points to the well-known effect of GH on the activity of type I deiodinase and eventually to other important interactions among different anterior pituitary axes for optimal peripheral responses (47). It remains a matter for speculation, however, as to whether correction of the low serum-and tissue concentrations of T3 also improves clinical problems distinctively associated with prolonged critical illness (48,49), such as diminished cognitive status with lethargy, somnolence or depression; ileus and cholestasis; pleural and pericardial effusions; glucose intolerance and insulin resistance; and hyponatremia, anemia and de®cient clearance of triglycerides. So far, pioneering studies with T4 administration have failed to demonstrate clinical bene®ts within an intensive care setting, but in view of the impaired conversion of T4 to T3 this is not really surprising (50,51).…”

Section: Changes In the Chronic Phase Of Critical Illnessmentioning

confidence: 99%

Novel insights into the neuroendocrinology of critical illness

Berghe

2000

European Journal of Endocrinology

226

104

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An unexplained hallmark of prolonged critical illness is the fact that food does not prevent or reverse protein wasting, while fat is paradoxically accrued. This`wasting syndrome' often persists after the underlying disease has been resolved and thus perpetuates intensive care dependency. Although the crucial role of an intact hypothalamus±pituitary axis for homeostasis during stress is well recognized, the differences between the neuroendocrine changes observed in acute and prolonged critical illness were only recently described. Novel insights in this area are reviewed here.The initial endocrine stress response consists primarily of a peripheral inactivation of anabolic pathways while pituitary activity is essentially ampli®ed or maintained. These responses presumably provide the metabolic substrates and host defense required for survival and to delay anabolism, and thus should be considered as adaptive and bene®cial. Persistence of this acute stress response throughout the course of critical illness was hitherto assumed. This assumption has now been invalidated, since a uniformly reduced pulsatile secretion of ACTH, TSH, LH, prolactin (PRL) and GH has been observed in protracted critical illness, causing diminished stimulation of several target organs. Impaired pulsatile secretion of anterior pituitary hormones in the chronic phase of critical illness seems to have a hypothalamic rather than a pituitary origin, as administration of relevant releasing factors evoked immediate and pronounced pituitary hormone release. A reduced availability of TRH, one of the endogenous ligands of the GH-releasing peptide (GHRP) receptor (such as the recently discovered ghrelin) and, in very long-stay critically ill men, also of GHRH, appear to be involved. This hypothesis was further explored by investigating the effects of continuous i.v. infusion of GHRH, GHRP, TRH and their combinations for several days. Pulsatile secretion of GH, TSH and PRL was re-ampli®ed by relevant combinations of releasing factors which also substantially increased circulating levels of IGF-I, GH-dependent binding proteins, thyroxine and tri-iodothyronine (T3) while avoiding a rise in reverse T3. Active feedback-inhibition loops prevented overstimulation of target organs and metabolic improvement was noted with the combined infusion of GHRP and TRH. Whether this novel endocrine strategy will also enhance clinical recovery from critical illness remains to be explored.

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Reduced tissue thyroid hormone levels in fatal illness

Cited by 125 publications

References 40 publications

Maternal Diabetes Mellitus, a Rat Model for Nonthyroidal Illness: Correction of Hypothyroxinemia with Thyroxine Treatment Does Not Improve Fetal Thyroid Hormone Status

Maternal Diabetes Mellitus, a Rat Model for Nonthyroidal Illness: Correction of Hypothyroxinemia with Thyroxine Treatment Does Not Improve Fetal Thyroid Hormone Status

MECHANISMS IN ENDOCRINOLOGY: Beyond the fixed setpoint of the hypothalamus–pituitary–thyroid axis

Novel insights into the neuroendocrinology of critical illness

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