Recent developments in thyroid hormone metabolism: Interpretation and significance of measurements of reverse T3, 3,3′T2, and thyroglobulin

doi:10.1016/0026-0495(78)90028-8

Metabolism

Volume 27, Issue 5, May 1978, Pages 615-630

https://doi.org/10.1016/0026-0495(78)90028-8 Get rights and content

Abstract

The development of specific radioimmunoassays has allowed measurements of 3,3′,5′-triiodothyronine (reverse T₃), 3,3′-diiodothyronine (3,3′T₂), and thyroglobulin to be performed in serum and in various biologic fluids both in normal and in altered states of thyroidal economy. The physiology, kinetics, and metabolic actions of reverse T₃, 3,3′T₂ and thyroglobulin are reviewed. Presently, it appears that reverse T₃ and 3,3′T₂ measurements in amniotic fluid and cord serum may potentially be useful in diagnosing fetal or neonatal thyroid dysfunction, and serum thyroglobulin measurements appear to be important as a measure of the efficacy of treatment of patients with differentiated thyroid carcinoma.

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The examination and understanding of thyroid function perturbations in the intensive care unit (ICU) setting is often difficult, because the changes reflect apparent alterations in the ability to measure thyroid hormone parameters and homeostatic modulations in thyroid hormone metabolism accurately. Present concepts suggest that patients in the ICU setting are catabolic and that decreased extrathyroidal conversion of T4 to T3 decreases unnecessary energy expenditure. These alterations in thyroid function in a euthyroid, systemically ill patient are referred to as the euthyroid sick syndrome.8, 9, 10, 18, 49, 50, 51, 52, 53 There are selected patients in the ICU who actually have biochemically perturbed thyroid function, either hypothyroidism or hyperthyroidism, in addition to the typical changes of the euthyroid sick syndrome. It is usually difficult to discern these patients from the larger population of euthyroid patients, partly because the usual clinical manifestations of hyper- or hypothyroidism overlap with the signs and symptoms of euthyroid patients who have altered results of thyroid function tests. Further, there is no absolute gold standard clinical or biochemical measurement that can be used to differentiate these two groups of patients. The purposes of the present article are to review the typical thyroid hormone alterations in the euthyroid sick syndrome and to discuss methods of differentiating this syndrome from pathologic thyroid dysfunction that requires specific thyroid therapy. The purpose of assessing thyroid function in a given patient is to assess the systemic metabolic action of thyroid hormones at the cellular level. Indeed, serum thyroid hormone measurements, no matter how accurate, may not be proportional to thyroid hormone action at the cellular level.
Sensitive thyrotrophin (third generation) assays that are capable of detecting .01 μU/mL of thyroid stimulating hormone (TSH) have been extremely helpful in this setting and have largely supplanted the need for performing a thyrotrophin releasing hormone (TRH) test.43, 44 Assuming a normal pituitary gland, a serum TSH measurement in an ambulatory (noncritically ill) patient is the best measure of thyroid hormone action at the cellular level; an elevated TSH concentration shows hypothyroidism and a decreased or undetectable TSH level demonstrates hyperthyroidism. In patients in the ICU, these general principles apply, albeit with several important caveats that are discussed farther on.
Metabolism of monoiodotyrosine in lower vertebrates: with emphasis on snakes
1983, Comparative Biochemistry and Physiology -- Part B: Biochemistry and
- 1.
  1. A survey was made on the monoiodotyrosine deiodinating activities in the liver and kidney of 2 species of Teleosts, 1 Urodele, 1 Anura, 2 species of Chelonia, 2 species of Lacertilia, 6 species of Ophidia and 1 Aves. With the exception of some snakes, monoiodotyrosine deiodinating activities in the liver are present in all animals and in the kidney of the Teleosts and Urodele.
- 2.
  2. In vivo and in vitro metabolism of M¹²⁵IT in the thyroid tissue of the rat snake, Ptyas korros revealed labelled DIT, T₄.
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  3. This study support our earlier suggestion that snakes have a defective peripheral iodotyrosine deiodinating system, which seems to be susceptible to some factors like temperature and season of sacrifice.
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1979, Clinics in Endocrinology and Metabolism
The changes which occur in endocrine physiology in the course of normal ageing are rather specific and involve either interesting interplays of endocrine glands and their target organs or changes in hormone degradation rates. Two of the critical ‘life-support’ endocrine circuits — pituitary-adrenal cortex and pituitary-thyroid — evince changes with age that are secondary to decreased hormone degradation in peripheral tissues; basal circulating hormone levels are maintained and responses to stress are intact. A third critical axis — the β-cell — shows a change in sensitivity. Islet cell perception of hyperglycaemia is depressed (‘glucoreceptor defect’) and insulin output is appropriately low in the face of modest glucose challenge. Target organ sensitivity to insulin, on the other hand, is probably normal. In contrast, sensitivity of the osmoreceptor is heightened in the aged, and ADH secretion is increased (relative to younger subjects) in response to elevated plasma osmolality. This change is appropriate to decreased renal tubular sensitivity to ADH. Changes with age in the pituitary-ovarian axis are wellknown, and may be paralleled in men, albeit far less dramatically, in terms of circulating androgen and gonadotrophin levels.
It is not possible, from these observations, to discern a common denominator which can be regarded as ‘characteristic’ of endocrine gland ageing. Attempts to describe endocrine gland ageing globally — for example, as a function of altered hormone feedback thresholds in the hypothalamus — have, so far, been unconvincing. On the other hand, studies in animals of peripheral tissue hormone receptors, while incomplete, suggest rather generalized age-related changes. Except for indirect evidence regarding insulin, very little is known in man regarding receptor changes with ageing.
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The effect of T3 and reverse T3 administration on muscle protein catabolism during fasting as measured by 3-methylhistidine excretion
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Since recent studies have indicated that measurement in urine of the amino acid, 3-methylhistidine, accurately reflects the extent of muscle catabolism, and because it has been suggested that thyroid hormones may influence muscle breakdown, especially during fasting, the effect of T3 and reverse T3 (rT3) administration on the excretion of 3-methylhistidine was examined in obese subjects during fasting. The mean (± SE) 3-methylhistidine excretion in patients fed an egg protein diet (devoid of meat protein) was 256 ± 35 μmoles/day and decreased to 190 ± 14 μmoles/day during fasting. T3 administration (100 μg/day × 5 days) increased 3-methylhistidine excretion to 304 ± 37 μmoles/day during its ingestion and to 485 ± 46 μmoles/day in the T3 posttreatment interval. T3 doses of 10 μg every 4 hr (q4h) for the first 6 days of fasting also appeared capable of increasing 3-mehis excretion whereas 5 μg T3 q4h administered during the first 6 days of fasting did not increase 3-mehis excretion. Reverse T3 administration (80 μg q6h) during fasting was associated with a mean 3-methylhistidine of 130 ± 13 μmoles/day, a value no higher than in patients fasted alone. These observations suggest that: (1) skeletal muscle catabolism decreases during fasting; and (2) pathophysiologic doses of T3 (60 μg/day or more), but not reverse T3, enhance muscle catabolism during fasting.
Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism?
2019, Frontiers in Endocrinology

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Recent developments in thyroid hormone metabolism: Interpretation and significance of measurements of reverse T3, 3,3′T2, and thyroglobulin

Abstract

Metabolism

Lancet

J Pediatr

J Pediatr

Lancet

Lancet

Lancet

Lancet

Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects

J Clin Invest

A radioimmunoassay for measurement of 3,3′,5′-triiodothyronine (reverse T3)

J Clin Invest

Radioimmunoassay of 3,3′,5′-triiodo-L-thyronine (reverse T3) in human serum and its application in different thyroid states

Z Klin Chem Klin Biochem

A radioimmunoassay for 3,3′,5′-triiodo-L-thyronine in unextracted serum: Method and clinical results

J Clin Endocrinol Metab

A radioimmunoassay for 3,3′,5′-1-triiodothyronine (reverse T3): Assessment of thyroid gland content and serum measurements in conditions of normal and altered thyroidal economy and following administration of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH)

J Clin Endocrinol Metab

On the metabolism of 3,3′-diiodothyronine and 3,3′,5′-triiodothyronine

Endocrinology

The recovery of 3:5:3′-triiodothyroacetic acid and 3:3′-diiodothyronine from rat kidney after injection of 3:5:3′-triiodothyronines

Endocrinology

I. Hormone biosynthesis and metabolism: Nature and metabolism of thyroid hormones

Recent Prog Horm Res

Thyroid hormone physiology and biochemistry: Triiodothyronine in relation to thyroid physiology

Recent Prog Horm Res

Determination of triiodothyronine concentration in human serum

J Clin Invest

Triiodothyronine radioimmunoassay

J Clin Invest

An improved radioimmunoassay of triiodothyronine in serum: Its application to clinical and physiological studies

J Lab Clin Med

A new radioimmunoassay for plasma L-triiodothyronine: Measurements in thyroid disease and in patients maintained on hormonal replacement

J Clin Invest

Serum triiodothyronine in man

Annu Rev Med

Identification and estimation of undegraded thyroblobulin in human serum

Endocrinology

Radioimmunoassay for measurement of thyroglobulin in human serum

J Clin Invest

Elevated serum thyroglobulin: A marker of metastases in differentiated thyroid carcinomas

J Clin Invest

A radioimmunoassay for serum rat thyroglobulin: Physiologic and pharmacological studies

J Clin Invest

An assessment of daily production and significance of thyroidal secretion of 3,3′,5′-triiodothyronine (reverse T3) in man

J Clin Invest

Circulating 3,3′,5′-triiodothyronine (reverse T3) in the human newborn

J Clin Invest

Measurements of 3,3′,5′-triiodothyronine (reverse T3), 3,3′-L-diiodothyronine, T3, and T4 in human amniotic fluid and in cord and maternal serum

J Clin Endocrinol Metab

Recommendations for screening programs for congenital hypothyroidism

Report of a Committee of the American Thyroid Associations

Thyroid hormones and thyrotropin in human amniotic fluid

N Engl J Med

Compartmental models for maternal, fetal, and amniotic fluid transfer of iodide, triiodothyronine, and thyroxine in the pregnant sheep

Endocrinology

Reverse triiodothyronine and fetal thyroid status

N Engl J Med

Extrathyroidal conversion of thyroxine to 3,3′,5′-triiodothyronine (reverse T3) and to 3,5,3′-triiodothyronine (T3) in humans

J Clin Endocrinol Metab

Preoperative studies on thyroid activity: Secretion of T4, T3 and reverse T3 in normal man

T4 and T3 release from the perfused canine thyroid isolated in situ

Acta Endocrinol

Demonstration of sequential monodeiodination as the major pathway of iodothyronine metabolism

Clin Res

Opposite effects of dexamethasone on serum concentrations of 3,3′,5′-triiodothyronine (reverse T3) and 3,3′,5′-triiodothyronine (T3)

J Clin Endocrinol Metab

Reciprocal changes in serum concentrations of 3,3′,5′-triiodothyronine (reverse T3) and 3,3′,5-triiodothyronine (T3) in systemic illnesses

J Clin Endocrinol Metab

Studies on the nature of thyroidal suppression during acute falciparum malaria: Integrity of pituitary response to TRH and alterations in serum T3 and reverse T3

J Clin Endocrinol Metab

Diversion of peripheral thyroxine metabolism from activating to inactivating pathways during complete fasting

J Clin Endocrinol Metab

Recent developments in thyroid hormone metabolism: Interpretation and significance of measurements of reverse T₃, 3,3′T₂, and thyroglobulin

Conversion of thyroxine (T₄) to triiodothyronine (T₃) in athyreotic human subjects

A radioimmunoassay for measurement of 3,3′,5′-triiodothyronine (reverse T₃)

Radioimmunoassay of 3,3′,5′-triiodo-L-thyronine (reverse T₃) in human serum and its application in different thyroid states

A radioimmunoassay for 3,3′,5′-1-triiodothyronine (reverse T₃): Assessment of thyroid gland content and serum measurements in conditions of normal and altered thyroidal economy and following administration of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH)

An assessment of daily production and significance of thyroidal secretion of 3,3′,5′-triiodothyronine (reverse T₃) in man

Circulating 3,3′,5′-triiodothyronine (reverse T₃) in the human newborn

Measurements of 3,3′,5′-triiodothyronine (reverse T₃), 3,3′-L-diiodothyronine, T₃, and T₄ in human amniotic fluid and in cord and maternal serum

Extrathyroidal conversion of thyroxine to 3,3′,5′-triiodothyronine (reverse T₃) and to 3,5,3′-triiodothyronine (T₃) in humans

Preoperative studies on thyroid activity: Secretion of T₄, T₃ and reverse T₃ in normal man

T₄ and T₃ release from the perfused canine thyroid isolated in situ

Opposite effects of dexamethasone on serum concentrations of 3,3′,5′-triiodothyronine (reverse T₃) and 3,3′,5′-triiodothyronine (T₃)

Reciprocal changes in serum concentrations of 3,3′,5′-triiodothyronine (reverse T₃) and 3,3′,5-triiodothyronine (T₃) in systemic illnesses

Studies on the nature of thyroidal suppression during acute falciparum malaria: Integrity of pituitary response to TRH and alterations in serum T₃ and reverse T₃