The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:920-923 (2005)
© 2005 The Gerontological Society of America
Goiter in Adult Patients Aged 55 Years and Older: Etiology and Clinical Features in 634 Patients
Juan J. Díez
Department of Endocrinology, Hospital La Paz, Madrid, Spain.
Address correspondence to Juan J. Díez, Department of Endocrinology, Hospital Ramón y Cajal, Carretera de Colmenar, km 9, 28034 Madrid, Spain. E-mail: mibarsd{at}infomed.es
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Abstract
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Background. Goiter is common in older people, although the frequency of the different causes of goiter has not been well defined. Our aim has been to assess the frequency of the diverse etiologies of goiter in adult patients aged 55 years and older, and evaluate the relationships between etiology and age, sex, and goiter features.
Methods. We performed a descriptive, cross-sectional study in ambulatory patients in the setting of an endocrinology clinic. Six hundred thirty-four patients (544 women, 85.8%) with goiter, aged 55–91 years, were studied.
Results. Causes of goiter were nontoxic multinodular goiter (325 patients, 51.3%); toxic multinodular goiter (151 patients, 23.8%); solitary thyroid nodule (62 patients, 9.8%); toxic adenoma (32 patients, 5.0%); Graves' disease (27 patients, 4.3%); Hashimoto's thyroiditis (25 patients, 3.9%); simple goiter (8 patients, 1.3%); thyroiditis (3 patients, 0.5%); and thyroid-stimulating hormone-secreting pituitary adenoma (1 patient, 0.2%). Patients with multinodular goiter had greater thyroid size and longer time of evolution than those patients with uninodular disease. Most of the symptoms and signs associated with goiter were dependent on thyroid size and time of evolution. Age and sex conditioned the presence of retrosternal goiter and tracheal deviation, and previous therapy was related to retrosternal goiter and local symptoms. However, etiology was not associated with the presence of any symptom.
Conclusion. Nontoxic and toxic multinodular goiter are the main etiologies of goiter in patients aged 55 years and older. Thyroid size is the main factor influencing the appearance of signs and symptoms, although age and sex are related with the presence of retrosternal goiter and tracheal deviation.
THYROID gland diseases are common clinical problems associated with aging (1–3). An early study by Mortensen and colleagues (4) reported an increase of human thyroid weight with age. Further evaluations of the thyroid gland at autopsy (5) or using ultrasonography (6–9) have demonstrated that aging is accompanied by a high prevalence of goiter, especially in areas of low iodine intake (6,8,10–13). A recent survey has shown that the prevalence of goiter in the elderly population has reached figures as high as 74.2% in patients aged 55–75 years and 54% in patients aged 76–84 years. The prevalence of nodular goiter was 25% and 21% in both groups of patients, respectively (14).
Nevertheless, series of elderly patients with goiter are not easily available (15). We performed this cross-sectional study with the aim of assessing the relative frequency of the diverse etiologies of goiter in adult patients aged 55 years and older. We have also assessed the relationships between the etiology of goiter and age and sex of patients, thyroid size, duration of disease, and the presence of signs and symptoms.
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METHODS
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Patients
A descriptive cross-sectional study including ambulatory patients aged 55 years and older complaining of goiter was carried out from October 1994 through March 2001. Patients were divided into groups A (55–64 years), and B (65 or more years). A detailed clinical history, review of the previous case record, and complete physical examination were performed in every patient. To assess the degree of goiter, the modified World Health Organization classification was adopted (16,17).
A total of 634 consecutive patients (544 women, 90 men) were studied. Mean age of women (66.0 ± 8.0 years) was significantly higher than that of men (63.5 ± 7.3 years; p =.006). Most patients have stage 1a (54.7%) or 1b (28.1%) goiter. Sex distribution was not different in patients classified according to thyroid size (Table 1).
Design
For every patient, we collected stage and etiology of goiter, duration of the disease since diagnosis, and used therapies. We also registered the presence or absence of the following clinical signs or symptoms: retrosternal goiter, tracheal deviation (in X-ray films or computed tomography scan), subjective local symptoms (dyspnea, dysphagia, dysphonia, pain, or discomfort) and growth during the last year. Usual clinical, analytical, and morphological (ultrasonography, thyroid scan) procedures were used for etiological diagnosis. Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured by using immunoenzymatic assays, and thyroid peroxidase autoantibodies (TPOAb) were measured by Enzymun-Test (Boehringer Mannheim, Germany) as previously described (18).
Statistical Analysis
Results are expressed as mean ± standard deviation for normally distributed data, and as median (range) for nonparametric data. Categorical variables are described as percentages. For comparisons of means, the Student t test, Mann–Whitney U test, Wilcoxon signed-rank test, or repeated measures analysis of variance were used, as necessary. For ratio comparisons, the chi-square test or Fisher's exact test was used. A model of logistic regression was used to assess the presence of symptoms as a function of several variables. Differences were considered significant when p <.05.
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RESULTS
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Etiology of Goiter
Nontoxic multinodular goiter (51.3%) was the most frequently found etiology, followed by toxic multinodular goiter (23.8%) (Table 2). Etiology and age were related (p =.003). Age of patients with toxic multinodular goiter (68.4 ± 8.3 years) was similar to that of patients with toxic adenoma (66.3 ± 7.9 years), but was significantly higher than that of patients with nontoxic multinodular goiter (65.6 ± 7.7 years; p <.001) and solitary nodule (63.1 ± 6.9 years; p <.001).
Thyroid Size
Etiology was related to thyroid size. Patients with nontoxic and toxic multinodular goiter exhibited large goiters (stages 2 and 3) in 20.3% and 20.5% of cases, respectively, whereas this percentage was lower in other categories. Patients with Graves' disease tended to have small goiters. No relationships were found between thyroid size, age, and sex.
Duration of Disease
Duration of goiter was not related with age. Men showed a time of evolution shorter than that observed in women (2.0 [0.5–6.0] vs 5.0 [2–11.8] years; p <.001). Duration was more prolonged (p <.001) in patients with nontoxic multinodular goiter (6 [2–13] years) and toxic multinodular goiter (5 [1–12] years) than in patients with solitary nodule (2 [1–7] years) and toxic adenoma (3 [0.3–6.8] years).
Treatment
Periodic observation was used in a great number of patients (386, 60.9%). There were 248 patients (39.1%) who had received any kind of previous therapy, mainly thyroid hormones in patients with euthyroid or hypothyroid goiters, and radioiodine, thionamides, or surgery in patients with hyperthyroid goiters. There was no relationship between the existence of previous therapy and age, sex, and goiter size (data not shown).
Signs and Symptoms
Table 3 shows the number of patients with signs and symptoms and the relationships between these symptoms and sex, age, thyroid size, and previous therapy. A significant relationship between the four main etiologies of goiter and the presence of signs and symptoms was found (Table 4).
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Table 3. Signs and Symptoms Associated With Goiter in Patients Classified in Groups of Sex, Age, Thyroid Size, and Previous Therapy.
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Table 4. Number and Percentage of Patients With Signs or Symptoms Associated With Goiter in Each of the Four Main Etiologic Groups.
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Because the presence of symptoms was related to etiology, sex, age, thyroid size, and previous therapy, and the etiology was also related to age and thyroid size, we performed models of logistic regression to study the dependence of each symptom as a function of several independent variables (Table 5). Results of these analyses showed that: (a) sex and age were related to the presence of retrosternal goiter and tracheal deviation; (b) time of evolution was related to retrosternal goiter, tracheal deviation, and growth; and (c) existence of previous therapy was related to retrosternal goiter and local symptoms. Thyroid size significantly influenced the presence of all symptoms. Etiology was a nonsignificant variable in this model.
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Table 5. Results of Logistic Regression Analysis to Study the Influence of Six Covariates on the Appearance of Signs and Symptoms Associated With Goiter.
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DISCUSSION
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Our results show that nontoxic and toxic multinodular goiters are by far the most prevalent etiologies of goiter in patients aged 55 years and older. The mechanisms leading to the genesis of uninodular or multinodular goiters include iodine deficiency, chronic TSH stimulation, genetic influences, growth factors, growth-stimulating immunoglobulins, and goitrogens (19–22). The progression from euthyroidism to hyperthyroidism has been well characterized in older people, and usually develop over a period of years (13). Mutations of TSH receptor gene have been also involved in the pathogenesis of some cases of thyroid autonomy (23–25). These facts are especially relevant in the aged population. In fact, toxic multinodular goiter is the most frequent cause of thyrotoxicosis in older people, especially in iodine-deficient areas (12,13,17,26).
The prevalence of chronic autoimmune thyroiditis increased with age (1,11). In the study by Cavaliere and colleagues (14), evidence of autoimmune thyroiditis was found in 6.5% of the population. We found a lower percentage of patients with autoimmune thyroiditis because of the high proportion of patients with nodular goiters.
Our findings also show that etiology and thyroid size are significantly related, as patients with multinodular disease usually exhibit larger goiters than those found in patients with uninodular disease. A long-standing goiter that sometimes leads to local symptoms of pressure is considered to be characteristic of elderly patients with multinodular goiter (16,26). Our data agree with this view, because patients with multinodular disease had a longer disease duration than did patients with uninodular disease. One explanation for this finding might be that multinodular goiters grow more slowly than do uninodular goiters. However, our data show that goiter growth was present in 30.2% of patients with nontoxic multinodular goiter and in 31.3% of those with toxic adenoma. Only patients with a solitary thyroid nodule seem to exhibit growth in a clearly lower percentage of cases. Another explanation could be that patients with uninodular disease would exhibit fewer signs and symptoms than would patients with multinodular goiters. Again, this seems only true for patients with solitary nodules (Table 4), because 53.1% of the patients with toxic adenoma exhibit symptoms, and this percentage was about 48% in patients with multinodular disease.
Less than half of our patients exhibited signs and symptoms usually associated with goiter (27). The frequency of symptoms has been found to be related to thyroid size in some surveys (11). We tried to relate the presence of symptoms with other clinical variables. The presence of retrosternal goiter and tracheal deviation seemed to be associated with male sex and older age. In fact, logistic regression analysis confirmed these associations and also demonstrated that the main factors influencing the appearance of symptoms were thyroid size and duration of disease. Patients who were treated by periodic observation were more prone to develop retrosternal goiter and local symptoms than were those who received any kind of therapy. On the contrary, the etiology of goiter was not related to the presence of symptoms, thus indicating that the different distribution of the signs and symptoms found in patients classified according to the etiology is mainly due to differences in thyroid size, duration of disease, previous therapy, sex, and age, but not to the etiology itself.
Summary
Patients with multinodular disease tended to present with larger size and longer time of evolution than did patients with uninodular disease. Thyroid size is the main factor influencing the appearance of signs and symptoms, although age and sex are significantly related to the presence of retrosternal goiter and tracheal deviation.
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Acknowledgments
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We thank Ms. I. Pérez Aqueche, Ms. R. Amill, and Ms. A. Mora Castellano (Roche Farma Especialidades) for their valuable bibliographical assistance.
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Footnotes
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Decision Editor: John E. Morley, MB, BCh
Received January 15, 2004
Accepted February 10, 2004
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Abstract
Methods
