Verband tussen serum schildklierhormoonbalans en schildkliervolume bij patiënten die worden behandeld met levothyroxine

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Verband tussen serum schildklierhormoonbalans en schildkliervolume bij patiënten die worden behandeld met levothyroxine

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Verband tussen serum schildklierhormoonbalans en schildkliervolume bij patiënten die worden behandeld met levothyroxine als monotherapie voor hypothyreoïdie

Sawako Takahashi, Mitsuru Ito, Yuzuki Masaki, Mikiko Hada, Mizuho Minakata, Kazuyoshi Kohsaka, Tomohiko Nakamura, Toshihiko Kasahara, Takumi Kudo, Eijun Nishihara, Shuji Fukata, Mitsushige Nishikawa, Takashi Akamizu and Akira Miyauchi
Center for Excellence in Thyroid Care, Kuma Hospital, Hyogo 650-0011, Japan


thyroid volume (TV)
levothyroxine (LT4 )
free triiodothyronine (FT3)
Hashimoto thyroiditis (HT)



Abstract
Veel eerdere onderzoeken, waaronder de onze, hebben gemeld dat athyreotische patiënten die levothyroxine (LT 4 ) gebruiken, relatief lage serum-vrije trijoodthyronine (FT 3 ) -spiegels hebben, terwijl patiënten met grote struma-ziekten vaak hoge serum-FT 3- spiegels hebben.

Hier hebben we Hashimoto-thyroïditis (HT) -patiënten op LT 4 onderzocht om de relatie tussen schildkliervolume (TV) en schildklierhormoonstatus te bestuderen bij hypothyreoïdiepatiënten op LT 4 .

We onderzochten retrospectief 408 euthyroid HT-patiënten die werden behandeld met LT 4 voor hypothyreoïdie; verdeelde ze volgens TV en vergeleken serumniveaus van vrij thyroxine (FT 4 ) en FT 3 en de FT 3 / FT4- ratio in elke patiëntengroep met die in euthyroid-gematchte controlegroep.

We evalueerden ook de associatie tussen serum FT 3- niveau en FT 3 / FT 4- ratio en tv onder HT-patiënten op LT 4 .
Bij patiënten met TV <15 ml waren serum FT 3- spiegels significant lager dan die bij controles.
Bij patiënten met TV 15-80 ml waren serum FT 3- spiegels gelijk aan die bij controles.
Bij patiënten met TV ≥80 ml serum FT 3 niveaus waren significant hoger dan die in de controlegroep.
Het serum FT 3- niveau ( r = 0,35, p <0,01) en FT 3 / FT 4ratio ( r = 0,42, p <0,01) vertoonde een positieve correlatie met tv.

Tv's bij HT-patiënten op LT 4 veroorzaakten verschillen in de serum-schildklierhormoonbalans, aangezien een toenemend volume het serum FT 3- niveau en de FT 3 / FT 4- ratio verhoogt .

De balans van het schildklierhormoon in serum bij HT-patiënten met kleinere schildklierhormonen was vergelijkbaar met die bij athyreotische patiënten.
Milde thyrotropinesuppressie met LT 4 is nodig om bij dergelijke patiënten normale FT 3- spiegels te bereiken .



Een klein gedeelte uit het artikel;
T3 level in hypothyroid patients on LT4


THE TWO MAJOR THYROID HORMONES in the body are triiodothyronine (T3 ) and thyroxine (T4 ).
Approximately 20% of T3 is produced from the thyroid gland via two pathways, as follows: coupling of monoio‐ dotyrosine and diiodotyrosine (DIT) and conversion of T4 to T3 by type 1 and type 2 iodothyronine deiodinases (D1 and D2, respectively).

The remaining 80% of T3 is derived from the conversion of T4 to T3 in extrathyroidal tissues. In contrast, 100% of T4 is secreted by the thyroid gland through the coupling of two DIT moieties [1].
Some previous studies including ours have reported normal serum thyrotropin (TSH) levels associated with mildly low serum free triiodothyronine (FT3 ) levels in patients on levothyroxine (LT4 ) monotherapy for athyr‐ eotic or atrophic conditions after total thyroidectomy or fter radioiodine treatment for Graves’ disease [2-5].
In addition, we have reported that the presence of the rem‐ nant thyroid tissue was associated with normal FT3 levels in patients treated with LT4 who underwent hemithyroi‐ dectomy [6] or radioiodine treatment for Graves’ disease [5]. In contrast, we documented that Hashimoto thyroid‐ itis (HT) patients with increased thyroid volume (TV) tended to present with high serum FT3 levels, low free thyroxine (FT4 ) levels, and high FT3 /FT4 ratios [7, 8].
Thus, TV may be an important factor affecting thyroid hormonal balance, including serum FT3 levels and FT3 /FT4 ratios. In the present study, we investigated the thyroid hormone balance among HT patients during LT4 mono‐ therapy for hypothyroidism who presented with a variety of TVs, and we elucidated the relationship between TV and thyroid hormone status in hypothyroid patients on LT4


Table 1
Baseline characteristics sub grouped by thyroid volume in patients with Hashimoto’s thyroiditis

Fig. 1
Serum levels of FT3 (A), FT4 (B) and FT3 /FT4 (C) in patients with Hashimoto thyroiditis (HT) and in euthyroid controls with intact thyroid matched by age, sex, and the measured year. The HT patients were divided into seven groups stratified by TV levels. The top, bottom, and middle lines of the boxes correspond to the 75th, 25th, and 50th percentiles (median), respectively. The whiskers extend from the minimum to the maximum. TV, Thyroid volume; FT3 , free triiodothyronine; FT4 , free thyroxine; TSH, thyrotropin.

Fig. 2 
(A) Association between serum free triiodothyronine and thyroid volume using the Pearson’s correlation coefficient test among Hashimoto thyroiditis patients. (B) Association between serum free triiodothyronine/free thyroxine ratio and thyroid volume using the Pearson’s correlation coefficient test among Hashimoto thyroiditis patients.


In the present study, the patients on LT4 with large goitrous thyroid had relatively high serum FT3 levels. It is unclear currently whether relatively high serum FT3 in such patients presents with thyrotoxicosis.
The clinical significance of the relative high serum FT3 levels in patients with large goiter should be evaluated in the future. There are some limitations in the present study.

First, the limited number of study patients, unequal group distribution, and single time point reduced the internal validity of the study.
Second, we did not evaluate bio‐ chemical markers and the symptoms reflecting thyroid function.
In addition, we did not evaluate echo pattern (low or normal) of HT patients.
Studies including meas‐ ures of these clinical parameters are thus needed to clar‐ ify the best method of managing HT patients’ thyroid function on LT4 .

LT4 has been considered the standard of care for treatment of hypothyroidism for many years.
LT4replacement therapy has three main goals:
(i) provide resolution of the patients’ symptoms and hypothyroid signs, including biological and physiologic markers of hypothyroidism,
(ii) achieve normalization of serum TSH with improvement in thyroid hormone concentrations,
and (iii) avoid overtreatment [24]. This study sug‐ gests that one of the three main goals has a pitfall.

Patients with hypothyroidism due to HT are treated with LT4 and live in a chronic condition of abnormal thyroid hormone status for their lives. Therefore, even if the thy‐ roidal dysfunction may be subtle, its long-term effects cannot be overlooked.
We analyzed a large number of HT patients on LT4 and demonstrated that their TVs caused differences in serum thyroid hormone balance. The patients with normal TSH levels had relatively high serum FT3 levels and FT3 /FT4 ratios as their goiter size increased. Thus, serum low FT3 levels in HT patients on LT4 with relatively small thyroid were consistent with those in athyreotic patients on LT4 , and serum high FT3 levels in HT patients on LT4 with relatively large thyroid were consistent with those in patients with large goitrous thyroid disease.
In the former, the possibility of mild hypothyroidism has been suggested, and mild TSH suppression with LT4 may be needed to achieve normal FT3 levels. The clinical significance of the latter is for further study. Our findings may provide novel information that could assist in the management of a large number of patients treated with LT4 for hypothyroidism.


Acknowledgments
Author contributions: M. Ito constructed the study design. S. Takahashi analyzed the data. The other co‐ authors contributed by administering patient care.
Disclosure Statement
The authors declare no competing financial interests


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