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NEUROENDOCRINOLOGY LETTERS (NEL)
including Psychoneuroimmunology, Neuro
psychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL Vol.23 No.4, August 2002

REVIEW ARTICLE
Non-toxic nodular goitre and thyroid nodules

2002; 23:356–364
pii: NEL230402R05
PMID: 12195241

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The problem of goitre with particular consideration of goitre resulting from iodine deficiency (II):
Management of non-toxic nodular goitre and of thyroid nodules

Andrzej Lewinski

Department of Thyroidology, Institute of Endocrinology, Medical University of Lódz; Poland.
Department of Endocrinology, Polish Mother's Memorial Hospital – Research Institute, ódz, Poland.

Key words:
nodular goitre; single thyroid nodules; diagnostics; treatment

June 7, 2002
Accepted: June 13, 2002

ABSTRACT

The present opinions on the therapy with L-thyroxine (L-T4) of non-toxic multinodular, as well as of non-toxic thyroid nodules are rather divergent. This treatment is based on the suppression of TSH secretion from the pituitary.
There are no doubts that fine-needle aspiration biopsy (FNAB) performance is the first and – at the same time – the most significant diagnostic procedure in the case of thyroid structural lesions (nodules, goitre, thyroiditis). FNAB performance should – by all means – precede the beginning of L-T4 application for the treatment of non-toxic multinodular goitre or thyroid nodules.
The simplicity, clearness and high efficacy, with comparable results in each case, are the core of good diagnostic algorithm. Unfortunately, not all diagnostic algorithms concerning thyroid nodules and multinodular goitre fulfil these important criteria.

 

Rather divergent views have been reported, concerning the application of levothyroxine (L-T4) preparations in the therapy of single, non-toxic thyroid nodules and of multinodular nontoxic goitre; the nature of this treatment is suppression of thyrotropin (TSH) secretion from the pituitary, while TSH is a significant growth factor for thyroid follicular cells in vivo [1].
However, both early reports [2], and the latest observations [3] reveal that TSH is not required for thyroid growth initiation and promotion. Following this opinion, some reports indicate that TSH need not be the dominating growth factor, either for benign or for malignant thyroid tumours [3].
On one hand, the efficacy of L-T4 suppressing effects on nodule size reduction is not certain, while, on the other, an administration of thyroid hormones in TSH secretion-suppressing doses may lead to decrease of bone mineral density, especially in postmenopausal women [4].
Women with history of either hyperthyroidism or of L-T4 administration in TSH concentration-suppressing doses (as a therapy commonly used in the complex treatment of differentiated thyroid cancer – following total thyroidectomy and 131I application), should undergo bone mineral density evaluation, especially in sites with cortical bone prevalence (e.g., hip, forearm) and, however to a smaller extent, in areas with trabecular bone structure.
It should be emphasized that the thyroid hormone replacement therapy with maintained normal serum TSH concentration, has either a minimal or no effect on the bone mineral density (BMD) at all [4].
L-T4 administration may also be a risk factor of cardiac hypertrophy [5]. Left-ventricular hypertrophy has been observed as a result of chronic L-T4 administration in patients with no significant changes in either heart rhythm or arterial blood pressure or in left-ventricular systolic function, what suggests a direct, trophic effect of L-T4 on myocardium [5].
Recently, several prospective studies have been analysed, concerning the effects of L-T4 administered in TSH-suppressing doses for at least 6 months, on the sonographically-determined volume of single benign thyroid nodules [6]. The summary of obtained results indicates that patients, in whom the nodule volume decreased by more than 50%, stood for 26.5% in a group of 242 L-T4-administered patients, while 12.3% only among 171 patients of the control group, receiving either placebo or no treatment at all. Moreover, in the control group, there was a higher percent of patients, presenting with nodular volume increase by more than 50% (17.3%), when compared with that in the L-T4-receiving group (8.1%). Zelmanowitz et al., using cumulative metaanalysis, have drawn a conclusion that treatment with L-T4 preparations was associated with decreasing volume of thyroid nodules in 17% of patients, while in other 10% of the patients, L-T4 prevented the increase in volume of examined nodules [6]. According to the cited authors, an appropriate management should comprise a 12-month therapy with L-T4 preparations, administered in suppressive doses to premenopausal women and men – in whom no cardiovascular contraindications have been diagnosed; this treatment should then be continued with slightly smaller doses of L-T4 (relative, partial or incomplete TSH suppression), if nodular volume has decreased. Unlike in younger persons, may TSH-suppressive therapy with use of LT4, when applied in older age, induce undesirable side-effects, outweighing the actual therapeutic advantages. Moreover, there is a risk that such therapy may deteriorate the symptoms resulting from previous, suppression-resistant, endogenic foci of thyroid hormone production.

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