Download Non-toxic nodular goitre and thyroid nodules

Neuroendocrinology Letters ISSN 0172–780X
Copyright © 2002 Neuroendocrinology Letters
The problem of goitre with particular consideration
of goitre resulting from iodine deficiency (II):
NEL
R EV IEW
Management of non-toxic nodular goitre and of thyroid nodules
Andrzej Lewinski
Department of Thyroidology, Institute of Endocrinology, Medical University of Łódz; POLAND.
Department of Endocrinology, Polish Mother’s Memorial Hospital – Research Institute,
Łódz, POLAND.
Correspondence to: Prof. Andrzej Lewinski
Department of Thyroidology
Institute of Endocrinology
Medical University of Lodz
Dr. Sterling St. No. 5
91-425 Lodz, POLAND
PHONE : +48 42 6322594
FA X : +48 42 6322594
E-MAIL : [email protected]
Submitted:
Accepted:
June 7, 2002
June 13, 2002
Key words:
nodular goitre; single thyroid nodules; diagnostics; treatment
Neuroendocrinology Letters 2002; 23:356–364
I N V IT ED
Abstract
pii: NEL230402R05
Copyright © Neuroendocrinology Letters 2002
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 non-toxic 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 concentrationsuppressing doses (as a therapy commonly used
in the complex treatment of differentiated thyroid
Non-toxic nodular goitre and thyroid nodules
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-T4receiving 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 L-T4, 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.
According to La Rosa et al. [7], in cases of single,
solid thyroid nodules (scintigraphically “cold”), with
diameter ≤ 3.5 cm – with the diagnostic outcome of fineneedle aspiration biopsy (FNAB) as benign – “colloidparenchymal lesion”, an administration of L-T4 preparations should be regarded as the therapy of choice,
until the use of this hormone is contraindicated for
any reason. The applied treatment should keep serum
TSH concentration at levels < 0.3 mU/L, however, not
around the values typical for overt hyperthyroidism
(i.e., below 0.03 mU/L). Nodules with volumes >10
mL (i.e., of diameter >2.7 cm) will, most probably, not
decrease in size after such treatment, thus their volumes should be monitored until increase. L-T4 ought
to be administered in cases of such nodules only when
their further growth is observed.
In the course of treatment with L-T4 preparations,
the different types of response to this hormone can be
observed, namely:
1) The nodule volume is getting reduced, what becomes
visible after 4–8 months of treatment. The therapy
with L-T4 preparations should be continued until
further reduction of nodular volume is observed. At
this stage, the therapy may be discontinued; it may
be restarted if nodule size increases again.
2) Nodule size does not change in the course of L-T4
treatment. In this case, resistance to administered
L-T4 need not yet be suspected, as this agent may
prevent further increase of nodule size. The therapy may be restarted if further increase of nodule
is observed. However, if the nodule increases in size
in the course of L-T4 treatment, it should unquestionably be withdrawn.
3) The nodule volume increases in the course of
L-T4 therapy. Since non-neoplastic changes almost
never increase during therapy with L-T4 preparations, administered in TSH-suppressing doses,
the observed nodule enlargement is an unequivocal
indication to surgery [7].
It should be added that potassium iodide (KI) administration (especially in case of goitres resulting from
iodine deficiency) may be advantageous in patients
with small nodules, with diagnosed contraindications
to L-T4 therapy. Administration of KI in combination
with L-T4 may also be effective [7, 8].
Cooper [9] provides recommendations and protocols,
concerning the treatment of benign thyroid nodules
with L-T4, based on nodule size variations (enlargement, stability, decrease), either in result of TSHsuppressive therapy with L-T4 preparations or in the
course of untreated patient’s observation. As an initial
assumption does the author regard the known observation (almost always true) that nodule size decrease,
either in result of L-T4 therapy or spontaneous, may
be approached as manifestation of benign character of
nodular change.
For simplification, all the patients were divided by
Cooper into the following two groups: 1) women before
menopause and men, 2) postmenopausal women [9]
(Fig.1).
In both premenopausal women and in men with single thyroid nodule diagnosed by FNAB (performed at
the beginning of management) as benign lesion, Cooper recommends a 12-month suppressive therapy with
L-T4, administered in such doses as to maintain TSH
concentrations at the level < 0.1 nU/L [9]. If the nodule
does not respond to the therapy, the thyroid hormone
preparation is withdrawn and the patient is submitted
to further observation. If, however, nodule enlargement
is observed in the course of thyroid hormone administration, either diagnostic FNAB is to be repeated or
Neuroendocrinology Letters No.4, August 2002, Vol.23 Copyright © 2002 Neuroendocrinology Letters ISSN 0172–780X
357
Andrzej Lewinski
Figure 1. Recommendations for therapy for benign nodular disease [9].
immediate surgical intervention is to be considered.
When nodule size decreases (what can be found in palpation or following sonographic imaging), Cooper [9]
suggests to provide the patient with an option between
such L-T4 dose reduction as to maintain TSH concentration at lower normal values, however, with perspective of chronic (without any time limits) administration of this hormone, and therapy withdrawal, followed
by observation. In the course of his recommendations,
Cooper emphasizes that, in contrast to the data on multinodular goitre, there is no reliable information on
clinical consequences of L-T4 withdrawal in case of thyroid nodules which had primarily decreased in result of
TSH suppression by this hormone. Clinical experience
indicates that some of the nodules are getting enlarged,
while other remain stable.
In postmenopausal women, Cooper [9] recommends
6–12-month observation period without therapy, following FNAB indicating benign character of lesion. If,
after this period: 1) the nodule remains the same or
decreases in size, treatment is still withdrawn; 2) the
nodule size enlarges, L-T4 therapy is applied for 12
months in doses to maintain TSH concentration below
the normal values, at the same time, above the threshold of detectability by sensitive methods (>0.1 mU/L
and <0.5 mU/L); 3) the nodule size enlarges in the
course of L-T4 therapy, either repeated FNAB or surgical intervention is recommended [9].
After a 12-month application, the L-T4 therapy is
withdrawn, regardless whether effective or not. If,
after L-T4 withdrawal, nodule enlargement is observed,
the therapy is restarted, using L-T4 dose to maintain
TSH concentration at the lower normal limit; chronic
L-T4 administration is continued for an undetermined
(unlimited) period of time.
Having analysed the above considerations, Cooper
[9] recommends an extreme care in the management of
elderly postmenopausal women – with decreased estrogen concentrations – in order to protect them from complications in the cardiovascular system or from bone
mass loss.
358
According to Ridgway [10], the following management is to be applied in patient with diagnosed single,
solid, and cytologically benign nodule (FNAB should be
the first diagnostic step!) and with normal thyroid function:
1) the patient should undergo a 12-month observation,
without L-T4 therapy. At the end of the 1st year
of observation, the patient should be submitted to
thorough examinations, oriented towards the presence of thyroid disease symptoms; the thyroid function and nodule size should be assessed in ultrasonographic imaging [10].
2) If: A) nodule size have not changed or have decreased
spontaneously, the observation without treatment
should be continued; B) the nodule has increased
in size, FNAB should be repeated; C) the performed
biopsy has revealed either malignant process or suspicious change, the patient should be submitted to
surgical intervention.
All other patients, in whom nodule enlargement has
been diagnosed, should be treated with L-T4 preparations, administered in doses high enough to suppress
serum TSH concentration to levels within the range
of 0.1–0.5 mU/L. The observation and treatment with
L-T4 preparation should be continued for subsequent
year. If the nodule increases in size during L-T4 therapy, surgical intervention is necessary. Patients with
neither growing nor diminishing nodules during L-T4
therapy should continue receiving this hormone.
Even if the algorithm, as proposed by Ridgway [10],
is not perfect, it eliminates suppressive treatment with
L-T4 preparations in patients, in whom either spontaneous involution or no enlargement of nodular changes
is observed. This approach limits the application of L-T4
preparation in suppressive doses only to patients in
whom therapeutic advantages are possible, i.e., patients
with nodule enlargement (Fig. 2). The goal of such
approach to this problem is not nodule size reduction,
as much as the prevention of its enlargement and of
certain symptoms associated with enlargement process;
Non-toxic nodular goitre and thyroid nodules
Figure 2. Decision making for treatment of patients with benign thyroid nodules [10].
in other words, the point is to prevent clinically overt
disease (tumour enlargement) rather than to treat subclinical disease, which, according to Ridgway [10], is the
presence of nodule, neither varying in size nor causing
any clinical symptoms (except of its very presence). On
the other hand, the acceptance of the hypothesis that
suppressive treatment with L-T4 prevents the enlargement of benign nodules in the thyroid gland, is fairly
easy. At the same time, it is very difficult to prove
the efficacy of this treatment in controlled prospective
studies.
Summing up, despite many reports, no unequivocal
standards of management have been developed with
respect to the therapy of single, non-toxic thyroid nodules or of multinodular goitre with L-T4 preparations.
In the background of treating single thyroid nodules with L-T4 preparations, a number of questions can
be raised, concerning the appropriate diagnostics of
the thyroid gland, i.e., such diagnostics which should
always be performed prior to the treatment, assessing
the possibility of its application. At present, there are
no doubts that ultrascan (US)-guided FNAB is the first
and the most important step in the preoperative diag-
nostics of structural changes in the thyroid gland.
Below, there is an algorithm proposed by Greenspan
[11] in the widely-recognized manual of endocrinology
(Fig. 3). This point of view has been confirmed by the
most eminent authorities, including clinical consultants, dealing with thyroid diseases, and specialists in
thyroid pathomorphology [7, 9, 10, 11, 12, 13, 14, 15, 16,
17, 18, 19, 20, 21, 22, 23, 24, 25, 26].
Some authors try to prove the preoperative usefulness of large needle aspiration biopsy (LNAB) of the
thyroid gland, reporting that it improves the diagnostic efficacy of FNAB in cases of microfollicular nodules
[27]. We do not share the view. At the same time – with
respect to the thyroid gland – we warn against possible
complications from the use of large needle.
The chief point of good diagnostic algorithm is its
simplicity, clearness, and high diagnostic efficacy, comparable in each diagnostic case. Unfortunately, not all
algorithms fulfil the above conditions; the algorithm
of management in cases of thyroid nodules in children
and adolescents, proposed by Foley and Peter [28] is a
negative example, being extremely complicated, casting
many doubts and raising many objections.
Figure 3. Decision matrix for workup of a thyroid nodule [11].
Neuroendocrinology Letters No.4, August 2002, Vol.23 Copyright © 2002 Neuroendocrinology Letters ISSN 0172–780X
359
Andrzej Lewinski
Figure 4. Diagnostic algorithm in case of goitre [29, 35].
For already quite a long time, we present an opinion that no different diagnostic algorithms are necessary for children and adults, with respect to nodular
goitre, thyroid neoplasms, and thyroiditis. Diagnostic
algorithm, having a universal application, should be as
simple as possible and independent of patients’ age.
There is no doubt in cases of nodular goitre, thyroid
neoplasms and thyroiditis that the universal and simple
algorithm, reported a number of times in Polish medical literature (see below), proves true in practice [29, 30,
31, 32, 33, 34, 35] (Fig.4). This algorithm is based on
either similar or identical assumptions as other algorithms, developed in many centres all over the world
[9, 10, 11, 36, 37, 38], and can effectively be used in the
diagnostics of the above mentioned diseases, regardless
of patient’s age.
The above mentioned diagnostic algorithm [29,35] is
applied in cases of:
1. single thyroid nodule;
2. multinodular goitre (in this case it is extremely useful to apply “power Doppler” or “colour Doppler” US
methods, in order to properly select the dominating
nodule or a few dominating nodules, which should
subsequently be subjected to a FNAB in order of the
potential possibility of malignancy; the most suspicious are those lesions which are characterized by
the biggest blood flow rate;
3. increased consistency of the gland, detected by palpation (suspicion of the autoimmune thyroid disease);
4. goitre with distinctive pain during palpation;
5. focus/foci of changed acoustic density, impalpable,
especially those with diameter above 10 mm, both
in the enlarged and in normal thyroid gland; these
lesions are called “incidentalomas”, which term appears to be more proper – from the logic point of
view – than “impalpable nodules”.
There are also separate algorithms of diagnostic management (Fig.5), used with regards to impalpable le-
360
sions and identified in US imaging as foci of changed
acoustic density (cf point no.5 above) [39]. Lesions of
this type are referred to as “incidentalomata”. As mentioned before, these, incidentally found lesions in the
thyroid gland, are submitted to cytological diagnostics,
depending on the degree of risk of malignant neoplasm
in patient, the nature of the sonographic image of analysed focus, and on the lesion diameter [19,39,40,41].
Especially, the last criterion may be subject of controversy.
Following the generally accepted views, the differences in the incidence of particular types of pathological changes, observed in the thyroid gland in childhood (distribution of diagnoses) in comparison with
data obtained in adult patients, however fairly characteristic, do not justify any different diagnostic management in children from that accepted for adults [34, 39,
42, 43, 44, 45, 46, 47, 48, 49, 50].
The main differences concerning pathological changes
of the thyroid in children and adolescents are as follows:
1) before the age of 18, hyperplastic lesions, both neoplastic and non-neoplastic, more often occur as a
single tumour of the thyroid gland, especially nodular goitre in children is often manifested in the clinical picture as single hyperplastic nodule, raising
false suspicion of adenoma or even follicular carcinoma;
2) chronic thyroiditis in childhood presents with different morphological and clinical pictures, when
compared to those in adult patients. In aspirates
from the thyroid gland, affected by this process,
distinctive oncocytic metaplasia of follicular epithelium is extremely rare, despite of the cellular material, sometimes exceptionally rich in lymphocytes.
Moreover, the course of chronic thyroiditis in children more rarely leads to the development of persistent hypothyroidism;
3) It should also be kept in mind that the diagnostics of
structural lesions of the thyroid gland in childhood
Non-toxic nodular goitre and thyroid nodules
Figure 5. Algorithm for evaluation and treatment of thyroid incidentaloma [39].
is affected by a higher risk of finding congenital malformations and developmental disorders which can
manifest themselves as pathological lesions exceptionally difficult to be characterized;
4) it is a well-known fact that papillary carcinoma –
in countries with high or normal iodine supplementation, during the recent years also in Poland – is
the most frequently observed malignant neoplasm
of the thyroid gland; in children, it stands for more
than 90% of all cases of this carcinoma; it is also
most frequently found in adults, standing for 75%
of all carcinoma cases in Poland;
5) it is characteristic that the follicular type of papillary thyroid carcinoma in children is almost as frequently observed as the classic microscopic form of
this neoplasm, while the third position in this ranking is occupied by the type with diffuse sclerosis.
Still, however, despite the above mentioned differences
of child age, we claim that there is no need nor any
justification for the diagnostic algorithm of detecting
structural lesions in the thyroid gland to be different
for children and adults.
It appears from the diagnostic algorithms, concerning cases of thyroid nodules in children and adolescents, as presented by Foley and Peter [28], and, generally, in all the patients, independently of age, as
proposed by Castro and Gharib [38] (Fig. 6), that the
selection of diagnostic procedures, including also the
role of US-guided FNAB, depends on the functional
status of the thyroid gland.
In my opinion, the data from literature on the occurrence of malignant neoplastic lesions in the thyroid
gland of hyperthyroid patient (e.g., the diagnosis of cancer in “hot” nodule), although not very frequent (the
coexistence rate of a few percent), justify to initiate the
diagnostic process from FNAB – also in case of nodules
in hyperthyroid patients and in euthyroid patients with
autonomously-functioning thyroid nodules (AFTN).
In earlier reports, thyroid scintigraphy was proposed to select thyroid nodules into high-risk nodules
and low-risk nodules (“cold” vs. “warm” or “hot”);
FNAB was recommended only in case of “cold” nodules
Figure 6. Diagnostic algorithm in patients with thyroid nodules [38].
Neuroendocrinology Letters No.4, August 2002, Vol.23 Copyright © 2002 Neuroendocrinology Letters ISSN 0172–780X
361
Andrzej Lewinski
Figure 7. Decision matrix for the work-up of the thyroid nodules [51].
[36, 51] (Fig. 7). However, the same authors decided to
start the diagnostic process from FNAB in cases of single, quickly growing nodules [36] or, in their subsequent
published reports, they modified their approach to the
problem, suggesting FNAB to be the first step in the
diagnostic process [11] (the respective algorithm see
Fig. 3, as shown before).
Following our opinion, the occurrence of nodular disease enforces the physician to start diagnostics from
US-guided FNAB, regardless of the functional status of
the thyroid gland.
If the reason of FNAB delay or – in other words – of
shifting FNAB to a more backward position in the diagnostic algorithm is fear of negative psychological effects
(in the child’s perception) of the biopsy, performed with
the use of needle and syringe, we represent the opinion that this fear is an inappropriate consideration of
health of the little patients. Many authors share our
view on the significant role of FNAB as the first diagnostic study in case of thyroid nodules in children [43, 44],
especially, that thyroid nodules – however much more
rare in children than in adults – bear a several times
higher risk of malignant process [42].
In descriptions of actual diagnostic procedures, concerning the treatment of thyroid nodules, after FNAB
– performed as diagnostic study of the first order –
many authors allow a possibility of periodic observation
of the nodules without drug administration or recommend L-T4 as initial management – in order to assess
the response of nodule to suppressive therapy. Shortterm administration of L-T4 in high doses may, in this
case, be treated as a specific diagnostic tool, verifying
if the examined nodule can be regarded as benign; the
nodules which shrink are approached as not malignant [52, 53]. Subsequent diagnostic procedures are
performed only when the nodule enlarges, either spontaneously or despite L-T4 administration [7, 9, 10].
362
A separate comment is required for the application
of thyroid scintigraphy in the diagnostics of structural
lesions in the thyroid gland in its typical anatomical
position, i.e., in the anterior part of the neck. Scintigraphy of the thyroid gland is a valuable study which can
find applications both in the diagnostics and in treatment of thyroid diseases, especially neoplastic. However,
its usefulness consists in the visualisation of iodineuptaking tissue with untypical location (thyroid cancer
metastases, thyroid malformations, ectopic thyroid tissue, aberrant goitre) than of nodules localised within
the thyroid gland in its anatomically typical location.
Moreover, if any fears, associated with the use of
radioactive isotopes in the diagnostics (among others,
of the thyroid gland), had any justification, this would
much more concern children, especially small, than
adults.
Summing up this issue, we believe that, in certain
algorithms, the scintigraphic examination of the thyroid is not necessarily included [28, 54].
Following the results of the “North American Survey”, dedicated to members of the American Thyroid
Association), American endocrinologists apply scintigraphy of this organ three times less frequently than
their European colleagues [55, 56].
Also worth emphasising is the much less importance
of sonographic imaging of the thyroid gland among
American authors than it is in Europe [10, 13, 55, 56].
The simpler are all standards of management, diagnostic and therapeutic, the better they are in practice.
They should also be legible for physicians who are not
specialists in a given medical branch. In the actual reality, an addition to the diagnostic algorithm of, for example, scintigraphic examination, what may be regarded
necessary by physician not specialising in endocrinology, will certainly prolong the time of diagnostics, delaying cytological examination by several months.
Non-toxic nodular goitre and thyroid nodules
On the margin of considerations on the design of
all diagnostic algorithms, a rather important problem
emerges, namely, whether it would be justified that the
calculus of probability, determining the risk of pathological change, affected the shape of diagnostic scheme.
This can be illustrated by the following example: papillary thyroid carcinoma may grow in the gland multifocally and not in the form of single tumour. Therefore,
should there be any arbitrarily determined borderline
of the lesion, imaged in sonographic examination,
above which FNAB should be performed? This last
problem may be regarded as specific self-criticism [32,
33], although, on the other side, we have to admit that
also other authors recommend in their algorithms arbitrarily determined borderlines for the size of diagnosed
lesions [39, 40].
In summary, it should be stated that the main goal
of the preoperative diagnostics of thyroid tumours is
the quickest and the most accurate selection of cases
which should be surgically treated. The same goal is
assumed by the preoperative cytological diagnostics of
multinodular goitre [57]. Such an understanding of this
issue raises two important questions:
1) is it possible to select high-risk patients on the basis
of knowledge of cancer pathogenesis and its epidemiology?
2) can our knowledge in this respect be applied for the
prevention of cancer?
At the end, I would like to emphasise that any evaluation of thyroid cytology, as well as any other diagnostic
and/or therapeutic procedures, concerning thyroid nodules, should be adjusted to the level of iodine consumption by the population in a given geographic territory
[58, 59]. Moreover, it should be remembered that the
aspiration process, even with thin needle, may change,
however slightly, the volume of thyroid nodules, what
complicates the interpretation of L-T4 therapy efficacy
in suppressing TSH concentrations [18].
Below, I would like to present the classification of
cytological diagnoses, developed for practical use in my
research group [34, 50].
Groups of cytological diagnoses:
GROUP I – The cytological picture is characteristic
enough to make an unequivocal diagnosis of specific disease entity:
– undifferentiated carcinoma
– papillarry carcinoma
– subacute granulomatous thyroiditis
– suppurative acute thyroiditis
GROUP II – Cytological picture with accurate clinical
data allows to distinguish a definite disease entity:
– medullary carcinoma
– malignant lymphoma
– cyst
– nodular goitre
– metastatic neoplasm
– chronic thyroiditis (i.e., Hashimoto’s disease)
GROUP III – Cytological picture and clinical data
allow to draw the differential-diagnostic circle:
– follicular neoplasm – follicular tumour
– oncocytic tumour
– benign tumour – benign lesion
– chronic inflammatory reaction
GROUP IV – The outcome is confined to a description
of aspirated material, sometimes with additional
remarks on further diagnostic-therapeutic management but no definite diagnosis can be made.
GROUP V – Cytological picture unequivocally indicates that the punctured structure/lesion is not
pathologically changed thyroid:
– lymph node
– salivary gland
– parathyroid
– muscular tissue
– fat tissue
– tracheal elements [ciliary (respiratory) epithelium]
– teratoma
The last report, the results of which I would like to
present, should not find improper applications; it was
proved not so long ago that alcohol consumption was
associated with lower incidence of goitre and of single
thyroid nodules [60]. It is difficult to say whether this is
an optimistic perspective but, just at this point, I would
like to finish this short review of prevailing opinions on
the conditions for the diagnostics and therapy of thyroid nodules with L-T4 preparations.
REFERENCES
1 Lewinski A, Pawlikowski M, Cardinali D. Thyroid growth-stimulating and
growth-inhibiting factors. A review. Biol Signals 1993; 2:313–351.
2 Lewinski A, Bartke A, Smith NKR. Compensatory thyroid hyperplasia
in hemithyroidectomized Snell dwarf mice. Endocrinology 1983;
113:2317–2319.
3 Derwahl M, Broecker M, Kraiem Z. Thyrotropin may not be the dominant growth factor in benign and malignant thyroid tumors. J Clin
Endocrinol Metab 1999; 84:829–834.
4 Greenspan SL, Greenspan FS. The effect of thyroid hormone on skeletal integrity. Ann Intern Med 1999; 130:750–758.
5 Ching GW, Franklyn JA, Stallard TJ, Daykin J, Sheppard MC, Gammage
M.D. Cardiac hypertrophy as a result of long-term thyroxine therapy
and thyrotoxicosis. Heart 1996; 75:363–368.
6 Zelmanovitz F, Gengro S, Gross JL. Suppressive therapy with levothyroxine for solitary thyroid nodules: a double-blind controlled clinical
study and cumulative meta-analyses. J Clin Endocrinol Metab 1998;
83:3881–3885.
7 La Rosa GL, Lupo L, Giuffrida D, Gullo D, Vigneri R, Belfiore A. Levothyroxine and potassium iodide are both effective in treating benign
solitary cold nodules of the thyroid. Ann Intern Med 1995; 122:1–8.
8 Tomaszewski W, Zygmunt A, Karbownik M, Lewinski A. Optimisation
of treatment with L-thyroxine and potassium iodide of non-toxic diffuse goitre in adults. Endocrinologia 2001; 6:47, abstract O–14.
9 Cooper DS. Thyroxine suppresion therapy for benign nodular disease.
J Clin Endocrinol Metab 1995; 80:331–334.
10 Ridgway EC. Medical treatment of benign thyroid nodules: have we
defined a benefit? Ann Intern Med 1998; 128:403–405.
11 Greenspan FS. The thyroid gland. In: Greenspan FS, Gardner DG (ed.),
Basic and Clinical Endocrinology, Lange Medical Books/McGraw-Hill,
Medical Publishing Division, New York, Toronto, 2001: 201–272.
12 Hamberger B, Gharib H, Melton LJ III, Goellner JR, Zinsmeister AR.
Fine needle aspiration biopsy of thyroid nodules: impact on thyroid
practice and cost of care. Am J Med 1982; 73:381–384.
13 Ridgway EC. Clinician’s evaluation of a solitary thyroid nodule. J Clin
Endocrinol Metab 1992; 74:231–235.
14 Gharib H, Goellner JR. Fine-needle aspiration of the thyroid: An appraisal. Ann Intern Med 1993; 118: 282–289.
15 Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med
1993; 328:553–559.
Neuroendocrinology Letters No.4, August 2002, Vol.23 Copyright © 2002 Neuroendocrinology Letters ISSN 0172–780X
363
Andrzej Lewinski
16 Hamburger JI. Extensive personal experience. Diagnosis of thyroid
nodules by fine needle biopsy: Use and abuse. J Clin Endocrinol
Metab 1994; 79:335–339.
17 Singer PA, Cooper DS, Daniels GH, Ladenson PW, Greenspan FS, Levy
EG, Braverman LE, Clark OH, McDougall IR, Ain KV, Dorfman SG.
Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. Arch Intern Med 1996; 156:2165–2172.
18 Gordon DL, Flisak M, Fisher S. Changes in thyroid nodule volume
caused by fine-needle aspiration: a factor complicating the interpretation of the effect of thyrotropin suppression on nodule size. J Clin
Endocrinol Metab 1999; 84:4566–4569.
19 Leenhardt L, Hejblum G, Franc B, Fediaevsky LDP, Delbot T, Guillouzic
DL, Menegaux F, Guillausseau C, Hoang C, Turpin G, Aurengo A. Indications and limits of ultrasound-guided cytology in the management
of nonpalpable thyroid nodules. J Clin Endocrinol Metab 1999; 84:
24–28.
20 Liel Y. The yield of adequate and conclusive fine-needle aspiration
results in thyroid nodules is uniform across functional and goiter
types. Thyroid 1999; 9:25–28.
21 Poller DN, Ibrahim AK, Cummings MH, Mikel JJ, Boote D, Perry
M. Fine-needle aspiration biopsy of the thyroid. Cancer Cytopathol
1999; 90:239–244.
22 Tambouret R, Szyfelbein W, Pitman MB. Ultrasound-guided fine-needle aspiration biopsy of the thyroid. Cancer Cytopathol 1999; 87:
299–305.
23 Marqusee E, Benson CB, Frates MC, Doubilet PM, Larsen RR, Cibas
ES, Mandel SJ. Usefulness of ultrasonography in the management of
nodular thyroid disease. Ann Intern Med 2000; 133:696–700.
24 Kelman AS, Rathan A, Leibowitz J, Burstein DE, Haber RS. Thyroid
cytology and the risk of malignancy in thyroid nodules: importance
of nuclear atypia in indeterminate specimens. Thyroid 2001; 11:
271–277.
25 Ogawa Y, Kato Y, Ikeda K, Aya M, Ohisawa K, Kitani K, Onoda N,
Ishikawa T, Haba T, Waklasa K, Hirakawa K. The value of ultrasoundguided fine-needla aspiration cytology for thyroid nodules: an assessment of its diagnostic potential and pitfalls. Surg Today 2001;
31:97–101.
26 Yang GCH, Liebeskind D, Messina AV. Ultrasound-guided fine-needle
aspiration of the thyroid assessed by ultrafast Papanicolaou stain:
data from 1135 biopsies with a two- to six-year follow-up. Thyroid
2001; 11:581–589.
27 Carpi A, Ferrari E, Sagripanti A, Nicolini A, Iervasi G, De Gaudio C,
Romani R, Di Coscio G. Aspiration needle biopsy refines preoperative diagnosis of thyroid nodules defined at fine needle aspiration as
microfollicular nodule. Biomed & Pharmacother 1996; 50:325–328.
28 Foley TP, Jr., Peter F. Thyroid nodules in children and adolescents. In:
Hochberg Z. (ed.), Practical Algorithms in Pediatric Endocrinology,
Karger AG, Basel (Switzerland), 1999, pp. 84–85.
29 Sporny S, Lewinski A. Interpretation of cytologic diagnoses of fineneedle aspiration biopsy of the thyroid gland (in Polish). Endokrynol.
Pol. – Polish J. Endocrinol. 1995; 46 (suppl. 1 to no. 3):15–36.
30 Kulig A, Lewinski A, Sporny S, Sygut J, Słowinska-Klencka D, Klencki
M, Matejkowska-Sobaniec M. The multifarious diagnostics of the thyroid lesions (in Polish). Endokrynol Pol – Polish J Endocrinol 1995;
46 (suppl. 1 to no. 3):41–52.
31 Lewinski A, Karbownik M. An outline of thyroidology – the basis for
physiology and pathology of the thyroid gland (in Polish). Endokrynol
Pol – Polish J Endocrinol 1996; 47 (suppl. 1 to no. 1):1–14.
32 Lewinski A. Early diagnostics of diseases of the endocrine glands (in
Polish). Endokrynol Pol – Polish J Endocrinol 1999; 50 (suppl. 2 to
no. 4):1–25.
33 Lewinski A. Diseases of the thyroid gland. In: Endokrynologia Kliniczna dla Ginekologa, Internisty i Pediatry (in Polish), (ed.) T.E. Romer,
Springer PWN, Warszawa 1998: 342–424.
34 Sporny S. Cytodiagnostics of Thyroid Diseases (in Polish). Habilitation Theses, Medical University of Łódz. Studio Graficzne Sobiepanski-Trocha, s.c., Łódz 1999.
35 Lewinski A. Diagnostics of thyroid carcinoma – morphological, imaging and genetic procedures. Endokrynol Pol – Polish J Endocrinol
2000; 51 (suppl. 1 to no. 3):65–75.
36 Schumann GB, Colon VF. Thyroid cytology. In: Clinican’s Guide to
Diagnostic Cytology, G.B. Schumann, V.F. Colon. Year Book Medical
Publisher, Inc., Chicago, London, 1982: 81–98.
37 Grant CS, Hay ID, Gough IR, McCarthy PM, Goellner JR. Long-term
follow-up of patients with benign thyroid fine-needle aspiration cytologic diagnoses. Surgery 1989; 106:980–986.
38 Castro MR., Gharib H. Thyroid nodules and cancer. Postgrad Med
2000; 107:113–124.
364
39 Burguera B, Gharib H. Thyroid incidentalomas. Prevalence, diagnosis, significance, and management. Endocrinol Metab Clin North Am
2000; 29:187–203.
40 Tan GH, Gharib H. Thyroid incidentalomas: management approaches
to nonpalpable nodules discovered incidentally on thyroid imaging.
Ann Intern Med 1997; 126:226–231.
41 Hagag P, Strauss S, Weiss M. Role of ultrasound-giuded fine-needle
aspiration biopsy in evaluation of nanpalpable thyroid nodules. Thyroid 1998; 8:989–995
42 Rallison ML, Dobyns EM, Keating FR, Rall J, Tyler E. Thyroid nodularity in children. JAMA 1975; 233:1069–1072.
43 Raab SS, Silverman JF, Elsheikh TM, Thomas PA, Wakely PE. Pediatric
thyroid nodules: Disease demographics and clinical management as
determined by fine needle aspiration biopsy. Pediatrics 1995; 95:
46–49.
44 Degnan BA, McClellan DR, Francis GL. Results of fine needle aspiration biopsy of thyroid in children and adolescents. J Pediatr Surg
1996; 31:903–907.
45 Słowinska-Klencka D, Sporny S, Klencki M, Matejkowska-Sobaniec M,
Lewinski A. A comparative analysis of results of fine-needle aspiration biopsy of the thyroid gland with those of histopathological
studies in 70 patients, age: 7–18 (in Polish). Pediatria Pol 1996; 71:
1111–1117.
46 Khurana KK, Labrador E, Izquierdo R, Mesonero CE, Pisharodi LR. The
role of fine-needle apiration biopsy in the management of thyroid
nodules in children, adolescents, and young adults: a multi-institutional study. Thyroid 1999; 9:383–386.
47 Lewinski A, Sporny S. Significance of preoperative cytologic examination in the diagnostics of nodular thyroid disease in children. 38th
Annual Meeting of the European Society for Paediatric Endocrinology
(ESPE), 29.08–1.09.1999, Warsaw, Poland. Horm Res 1999; 51
(suppl. 2): 9, Abstract C9A.
48 Sporny S. Fine-needle aspiration biopsy of the thyroid gland in children (in Polish). Proceedings of the 10th Symposium of the Polish
Society of Paediatric Endocrinology in Zakopane (June 1–3, 2000).
Endokrynologia, Diabetologia i Choroby Przemiany Materii Wieku Rozwojowego 2000; 6 (suppl. 1):83.
49 Słowinska-Klencka D, Klencki M, Sporny S, Lewinski A. Fine-needle
aspiration biopsy (FNAB) of the thyroid in children in conditions
of changing iodine supplementation. 39th Annual Meeting of the
European Society for Paediatric Endocrinology (ESPE), Brussels, Belgium, 17–19 September, 2000. Horm Res 2000; 53 (suppl. 2): 109,
Abstract P3–374.
50 Lewinski A, Słowinska-Klencka D, Bobeff I, Sporny S, Klencki M. Nodular goitre and thyroid neoplasms in children and adults (in Polish).
Klinika Pediatryczna 2001; 9:209–216.
51 Klonoff DC, Greenspan FS. The thyroid nodules. Adv Intern Med 1982;
27:101–126.
52 Burch HB. Evaluation and management of the solid thyroid nodule.
Endocrinol Metab Clin North Am 1995; 24:663–710.
53 Gharib H, Mazzaferri EL. Thyroxine suppressive therapy in patients
with nodular thyroid disease. Ann Intern Med 1998; 128:386–394.
54 Korman E, Niedziela M. Diagnostics and treatment of nodular disease
of the thyroid gland in children and adolescents (in Polish). Standardy Medyczne 2001; 3:26–32.
55 Bennedbaek FN, Perrild H, Hegedus L. Diagnosis and treatment of the
solitary thyroid nodule. Results of a European survey. Clin Endocrinol
1999; 50:357–363.
56 Bennedbaek FN, Hegedus L. Management of the solitary thyroid nodule: results of a North America Survey. J Clin Endocrinol Metab 2000;
85: 2493–2498.
57 Tollin SR, Mery GM, Jelveh N, Fallon EF, Mikhail M, Blumenfeld W,
Perlmutter S. The use of fine-needle aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a
multinodular goiter. Thyroid 2000; 10:235–241.
58 Lewinski A, Laurberg P, Ridgway EC. State-of-the-art approach to the
diagnostics and treatment of thyroid nodules – clinical management
workshop. 11th International Congress of Endocrinology, Sydney, 29
October – 2 November, 2000, Abstract Book, Abstract No. 290, p.
82.
59 Słowinska-Klencka D, Klencki M, Sporny S, Lewinski A. Fine-needle
aspiration biopsy of the thyroid in an area of endemic goitre: influence of restored sufficient iodine supplementation on the clinical
significance of cytological results. Eur. J. Endocrinol. 2002; 146:
19–26.
60 Knudsen N, Bulow I, Laurberg P, Perrild H, Ovesen L, Jorgensen T.
Alcohol consumption is associated with reduced prevalence of goitre
and solitary thyroid nodules. Clin Endocrinol 200; 55:41–46.