TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy

M, Ito; Miyauchi, Akira; Morita, Shinji; Kudo, Takumi; Nishihara, Eijun; Kihara, Minoru; Takamura, Yuuki; Ito, Yasuhiro; Kobayashi, Kaoru; Miya, Akihiro; Kubota, Sumihisa; Amino, Nobuyuki

doi:10.1530/eje-11-1029

Cited by 113 publications

(102 citation statements)

References 21 publications

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“…In contrast, Ito et al (33) showed that in patients who have undergone thyroidectomy, a moderately TSH-suppressive dose of L-T 4 is required to postoperatively restore serum FT 3 to the preoperative level. Interestingly, earlier studies have also indicated that L-T 4 replacement aiming at a normal serum TSH may not invariably result in an appropriate normalisation of serum FT 3 (34).…”

Section: Discussionmentioning

confidence: 94%

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Hoermann

Midgley²,

Larisch

et al. 2013

European Journal of Endocrinology

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Objective: In recognition of its primary role in pituitary-thyroid feedback, TSH determination has become a key parameter for clinical decision-making. This study examines the value of TSH as a measure of thyroid hormone homoeostasis under thyroxine (T 4 ) therapy. Design and methods: We have examined the interrelationships between free triiodothyronine (FT 3 ), free T 4 (FT 4 ) and pituitary TSH by means of i) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of L-T 4 and ii) independent mathematical simulation applying a model of thyroid homoeostasis, together with a sensitivity analysis. Results: Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH vs FT 3 and FT 4 between untreated patients and L-T 4 groups. Total deiodinase activity (G D ) was positively correlated with TSH in untreated subjects. However, G D was significantly altered and the correlation was lost under increasing L-T 4 doses. Ninety-five per cent confidence intervals for FT 3 and FT 4 , when assessed in defined TSH concentration bands, differed significantly for L-T 4 -treated compared with untreated patients. Higher doses were often needed to restore FT 3 levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including an important role of pituitary deiodinase type 2. Conclusion: The data reveal disjoints between FT 4 -TSH feedback and T 3 production that persist even when sufficient T 4 apparently restores euthyroidism. T 4 treatment displays a compensatory adaptation but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.

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Section: Discussionmentioning

confidence: 94%

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Hoermann

Midgley²,

Larisch

et al. 2013

European Journal of Endocrinology

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“…Low total or fT3 levels have been described in many LT4-treated euthyroid subjects (reviewed by Jonklaas et al) (27), with one study showing that TSH levels below the reference range were needed to restore T3 levels to presurgery levels in patients after thyroidectomy (28). Two recent crossover studies randomized hypothyroid subjects on stable LT4 doses to continued LT4 therapy versus LT3 or desiccated thyroid extract, maintaining similar TSH levels within the reference range (29,30).…”

Section: Lt4 Therapy Energy Expenditure and Body Compositionmentioning

confidence: 99%

Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition

Samuels

Kolobova

Smeraglio

et al. 2016

Thyroid

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Background: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition. Methods: This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry. Results: REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group ( p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups ( p = 0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition. Conclusions: LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.

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“…A relative T 3 deficiency may thus be present in athyreotic patients during T 4 monotherapy. Several studies (2,3,4,5) compared postoperative T 3 levels in patients on L-T 4 therapy with their own preoperative levels or those in euthyroid controls. We reported that serum T 3 levels were inappropriately low in patients who had undergone a total thyroidectomy (TT) and were on L-T 4 supplementation and that a moderately thyroid-stimulating hormone (TSH)-suppressive dose of L-T 4 was required to achieve their preoperative native serum T 3 levels (2).…”

Section: Introductionmentioning

confidence: 99%

Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients

Miyauchi

Kang

et al. 2015

European Journal of Endocrinology

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Objective: We and others recently reported that in total thyroidectomy (TT), serum triiodothyronine (T 3 ) levels during levothyroxine (L-T 4 ) therapy were low compared to the preoperative levels, suggesting that the presence of the thyroid tissue affects the balances of serum thyroid hormone levels. However, the effects of remnant thyroid tissue on these balances in thyroidectomized patients have not been established. Methods: We retrospectively studied 253 euthyroid patients with papillary thyroid carcinoma who underwent a TT or hemithyroidectomy (HT). We divided the cases into the TTCsupplemental L-T 4 (CL-T 4 ) group (nZ103); the HTCL-T 4 group (nZ56); and the HT-alone group (nZ94). We compared the postoperative serum levels of free T 4 (FT 4 ) and free T 3 (FT 3 ) and the FT 3 /FT 4 ratio in individual patients with those of controls matched by serum TSH levels. Results: The TTCL-T 4 group had significantly higher FT 4 (P!0.001), lower FT 3 (P!0.01) and lower FT 3 /FT 4 (P!0.001) levels compared to the controls. The HTCL-T 4 group had FT 4 , FT 3 and FT 3 /FT 4 levels equivalent to those of the controls. The HT-alone group had significantly lower FT 4 (P!0.01), equivalent FT 3 (PZ0.083), and significantly higher FT 3 /FT 4 (P!0.001) ratios than the controls. Conclusions: The presence of the remnant thyroid tissue was associated with different thyroid hormone balances in thyroidectomized patients, suggesting that T 3 production by remnant thyroid tissue has a substantial effect on the maintenance of postoperative serum T 3 levels.

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TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy

Cited by 113 publications

References 21 publications

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition

Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients

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