Thyroid Nodules: Diagnosis and Treatment in Primary Care

Background: Thyroid nodules are very common, with a prevalence of more than 75% among persons over age 60 in Germany, yet more than 80% of them remain asymptomatic and undetected. Only a small fraction of thyroid nodules pose a relevant risk to health; these include carcinomas of the thyroid gland (prevalence 0.027%) and functionally autonomous adenomas (clinically relevant prevalence 0.34%).

Methods: Systematic literature searches based on the PICO scheme or exploratory key questions were carried out during the development of an S3-level clinical practice guideline for the management of patients with thyroid nodules in primary care. The quality of the pertinent guidelines and studies was assessed with standardized instruments. Selected findings are described in this article.

Results: Most thyroid nodules are discovered incidentally. Further diagnostic evaluation by the primary care physician is generally only indicated if the patient is symptomatic, has a family history of thyroid cancer, or has a low TSH (thyroid-stimulating hormone) level. Ultrasonography should be performed in targeted and standardized fashion (TIRADS classifications) and cascading diagnostic studies should be avoided. If the nodule is considered potentially malignant, the patient should be referred to a specialist. The indications for treatment include symptoms due to compression, esthetic impairment, or functionally relevant autonomous adenomas. Pharmacotherapy with the goal of shrinking the nodule(s) is now obsolete, and other measures can only be carried out after specialized referral.

Conclusion: Rational, patient-centered approaches are needed in primary care so that overdiagnosis and overtreatment can be avoided and appropriate care provided as efficiently as possible. The diagnostic evaluation is focused on the meticulous selection of patients who must be referred to a specialist. For most thyroid nodules, no treatment is indicated.

Cite this as: Schübel J, Stahl A, Feldkamp J, Werner F, Uebel T, Voigt K: Thyroid nodules: Diagnosis and treatment in primary care. Dtsch Arztebl Int 2025; 122: 341–7. DOI: 10.3238/arztebl.m2025.0067

The prevalence of thyroid nodules is high in Germany and increases with age (1, 2, e1). More than 75% of persons over age 60 can be assumed to have thyroid nodules (1). Only few of these nodules are diagnosed and, once detected, become a potential medical problem. Most of the thyroid nodules (approximately 80%) remain unnoticed (3), since they only rarely become symptomatic as the result of their size or position (4). In most patients diagnosed with thyroid nodules, the diagnosis is made based on an incidental finding, for example after a computer tomography of the neck, magnetic resonance imaging of the cervical spine or ultrasound screening (incidentaloma). Those affected then see their primary care physician for further counselling, workup and follow-up examinations.

The majority of thyroid nodules are benign or will never cause clinical problems, even in the case of malignancy; only a very small fraction has a relevant adverse impact on the health of affected individuals (5, e1, e2).

There are two preventable dangerous clinical courses, which, although rare, require the special attention of the primary care physician as they should not be missed: prognostically relevant thyroid carcinomas and autonomously functioning adenomas.

Prognostically relevant thyroid carcinomas

Among selected patients with thyroid nodules greater than 1 cm in diameter, the risk of malignancy is 1.1% (6). The risk in the general population is likely to be significantly lower. The population-based prevalence of thyroid cancer in adults with thyroid nodules—and thus its occurrence in the primary care setting—can be estimated from the data shown in Table 1 and is 0.027%.

Table 1

Calculated frequencies of preventable dangerous clinical courses in patients with thyroid nodules in the primary care setting

With a long-term survival rate of 80% to 100% if diagnosed and treated, papillary carcinomas are only rarely categorized as prognostically relevant. Autopsy studies have demonstrated that numerous latent papillary carcinomas were present in thyroid glands of deceased patients which were never detected while these patients were alive and apparently never became symptomatic (7, e2). With an age-standardized incidence of 3/100 000 men and 7.5/100 000 women per year, diagnosed thyroid carcinomas are very rare in Germany (5). There are various subtypes which differ significantly with regard to their respective prognosis and treatment options (eTable 1). Compared to papillary thyroid cancer, follicular, medullary and anaplastic thyroid carcinomas are associated with significantly higher mortality risks.

eTable 1

Overview of the subtypes of thyroid cancer

Autonomously functioning adenomas

Autonomously functioning thyroid adenomas are usually asymptomatic. They only take a preventable dangerous course, if they produce hormones at systemically relevant levels, i.e. if they lead to hyperthyroidism (toxic adenomas). It can be assumed that overall autonomously functioning adenomas are common, but a large proportion (about two thirds) of them remain undetected and are of only minor clinical relevance (8). With a prevalence of hyperthyroidism of 0.2% to 1.3%, which in 16% to 50% of cases is caused by toxic adenomas (9), the estimated prevalence of clinically relevant autonomously functioning adenomas in the population is 0.34% (Table 1). There is a significant discrepancy between the abundance of harmless thyroid nodules and the rarity of dangerous nodules in the general population. Thus, the challenge for primary care physicians is to identify those among the multitude of patients with thyroid nodules for whom further diagnostic workup and/or treatment of these nodules will do more good than harm. From a public health perspective, the focus is particularly on the efficient use of limited financial and human resources.

Methods

For this review, we used the results of systematic literature searches that were performed as part of the development of a guideline. Publications in German and English from 2012 to 2023 were included. Key questions based on the PICO framework were used to select pertinent publications (eTable 2). The quality of the pertinent guidelines and studies were assessed using standardized instruments (AGREE-2, CASP), the results were systematically grouped and presented in evidence tables by PICO questions and exploratory questions in order to structure and derive recommendations for diagnosis and treatment. For detailed information about the methods used, please refer to the eSupplement. This article summarizes selected results of these searches.

eTable 2

Overview of the systematic searches

The diagnosis of thyroid nodules in primary care

When a thyroid nodule is first diagnosed, the primary factor relevant for the decision on further workup is whether the nodule was symptomatic or merely an incidental finding. Further diagnostic testing not only has potential benefits but it also harbors risks, such as: triggering diagnostic cascades und repeated follow-up examinations that place a burden on those affected and their caregivers; resulting invasive investigations or inadequate treatments, which, in turn, can be associated with complication risks. The patient-relevant benefits (symptom alleviation, improvements of quality of life and/or prognosis) have to be evaluated with regard to associated risks and need to be addressed in a doctor-patient discussion.

The above-mentioned very low prevalence rates of preventable dangerous clinical courses in the primary care setting generally result in low pre-test probabilities for the standard diagnostic tests, irrespective of the at times good sensitivity and specificity of the individual tests. One consequence of this is that the positive predictive value of diagnostic tests is very low in the primary care setting and thus the method is less reliable there than in the specialist care setting (Table 2). Since medical decisions take both the aspect of individual patient-oriented responsibility and responsibility for society as a whole into account, the use of diagnostic tests should generally be considered carefully, taking the care setting into account. Given the heterogeneous, unselected patient population in primary care, other decision criteria and strategies are required there compared to the management of preselected patients in the specialist care setting. Carcinomas of the thyroid gland are rare in all age groups (5); more aggressive forms of thyroid cancer are more likely to occur among older people than among younger people. Thus, a risk-adapted rather than primarily age-dependent diagnostic strategy is advisable in primary care.

Table 2

Overview of the effect of test qualities of ultrasonography in the low prevalence range

Medical history and clinical examination

If in the primary care setting thyroid nodules are asymptomatic with no abnormalities detected on clinical examination, no further diagnostic evaluation is usually needed.

There is little research into the relationship between thyroid nodules and the symptoms they cause. Symptoms such as dyspnea, dysphagia and hoarseness for weeks without other correlated findings are reasons for further diagnostic workup in primary care (13, 14, 15, e6), since these are often caused by large thyroid nodules (>3.5 cm) (e7). It is also recommended to carry out further diagnostic testing in the case of known hereditary tumor syndromes, first-degree relatives with thyroid cancer and after neck radiation (16). Suspicious palpable neck lymph nodes or painful sensitivity to pressure of the thyroid gland are red flags for compromising nodules or malignancy and require further diagnostic workup, as does clinical evidence of hyperthyroidism (17, e8).

Laboratory tests

As part of the general differential diagnostic workup of a thyroid nodule, it is initially relevant for determining thyroid function to measure the level of thyroid-stimulating hormone (TSH) in order to rule out a decompensated autonomously functioning (toxic) adenoma. If TSH levels are within the age-related reference range (18), testing for further laboratory parameters is unnecessary in the primary care setting (16, 19).

Calcitonin is regarded a sensitive (83– 100%) and specific (94–100%) tumor marker for detection of medullary thyroid cancer (20). However, the difficulty of diagnostic testing in the low-prevalence primary care setting can be very well illustrated using this parameter: Based on 20 million adults with thyroid nodules and only about 400 diagnosed medullary thyroid cancers per year, the number needed to screen is 20,000,000/400 = 50,000 people in the primary care setting. This is further compounded by the low positive predictive value of just 7.7% (20) as well as the high pre-analytical error rate due to the instability of the peptide hormone. Thus, measuring calcitonin levels is not a suitable method for routine testing in primary care. If after history taking and clinical examination, the primary care physician thinks that the abnormality of the findings make it necessary to rule out a medullary carcinoma, a referral of the patient for further specialist care with a corresponding query is advisable.

Ultrasonography

Being a noninvasive, fast and cost-effective diagnostic modality, ultrasonography is commonly used to diagnose and monitor thyroid nodules. Technological advances in ultrasound equipment are one reason why the prevalence of thyroid nodules statistically appears to be increasing (e1). As a general rule, the potential benefits and harms of an ultrasound scan of the thyroid gland should be carefully weighed up together with the patient prior to the examination. If an ultrasound examination is performed without medical indication, it increases the likelihood of false-positive findings. This is largely due to the high a priori probability of negative findings, but may also be related to the level of experience of the examiner. Primary care physicians must be aware that performing an ultrasound scan always increases the probability of abnormal but ultimately clinically irrelevant findings (Table 2). However, such findings then lead to a diagnostic cascade of further examinations, label those affected as “ill“ and cause uncertainty. Thus, a new diagnosis of asymptomatic thyroid nodules generally has no health benefits for patients.

If the thyroid ultrasound is performed in a primary care setting, the ultrasound description of the thyroid nodule should be based on relevant criteria which allow to assess the risk of malignancy (Table 3). Due to low sensitivities, none of these criteria is sufficient on its own to evaluate the dignity of a nodule (21). If abnormalities are detected regarding two or more criteria, the probability of predicting malignancy increases. Therefore, using a classification system when evaluating thyroid nodules is useful for creating comparability, systematically determining the further procedure and discussing it with the patients. For this purpose, Thyroid Imaging Reporting and Data System (TIRADS) classification systems are a useful approach. By assessing various ultrasound criteria, they help to determine the malignancy risk which can then be used to conclude the usefulness of further diagnostic studies (e.g., by fine-needle aspiration) (Table 4).

Table 3

Suspicious ultrasound criteria in the diagnosis of thyroid nodules and sensitivities

Table 4

Dignity evaluation based on ultrasound criteria using the established Thyroid Imaging Reporting and Data System (TIRADS) classification systems

However, the fact that the probabilities of malignancy calculated by the established TIRADS classification systems cannot be applied uncritically to the primary care setting, because the data on which they are based comes from tertiary centers with a very high proportion of thyroid cancer cases, is an obstacle to their application in primary care. The malignancy probability associated with the category cannot be taken from the respective classification system and applied to primary care, since the significantly lower prevalence rates in primary care inevitably imply a significantly lower risk of malignancy for one and the same sign. Using the criterion “taller than wide” (Figure) as an example, it was shown that the risk of malignancy in the primary/secondary care setting is approximately 10 times lower than in the TIRADS studies which were conducted in the tertiary/university care setting (24, 25). The workup of thyroid nodules in primary care must therefore be carried out in a differentiated manner and also include (risk) factors identified in the patient’s history in the decision-making process::

• If the medical history is unremarkable (e.g., incidentaloma detected during carotid Doppler ultrasound) and in the absence of a malignancy risk, no further follow-up ultrasound examinations are required.
• If the initial ultrasound scan determines a low risk of malignancy, a single follow-up examination may be performed after three to five years. However, if the actual malignancy probability is less than 5% (11, 12), it is also explicitly justifiable to jointly decide against follow-up examinations—malignancies only very rarely manifest themselves at a later point in time (6). Here, it is important that the treating physicians engage in a transparent and open risk communication with those affected in order to jointly evaluate the scope of managing the findings (26).
• If aspects in the patient’s medical history raise concerns (e.g., dysphagia) and there is only a minor or no malignancy risk detected by ultrasound, it is not necessary to perform further ultrasound follow-up examinations. If no correlation between the thyroid nodule findings and the symptoms is found, a symptom-oriented workup is indicated which should not be limited to the thyroid gland.
• Ultrasound findings indicating an increased or high risk of malignancy may be a reason to involve specialists in the care of the patient.

Figure

This nodule located dorsally in the thyroid lobe grows primarily into the depth (“taller than wide“).

However, given the above-mentioned uncertainty associated with ultrasound-based malignancy evaluations in primary care, medical history and clinical factors should also be taken into account when making this decision. Where appropriate, this overall context may be used to determine the urgency of the referral. If, after weighing up the advantages and disadvantages in a discussion with the patient, a joint decision is made against an urgent specialist referral, it is recommended to perform a follow-up ultrasound after one year at the latest, depending on the clinical course, but earlier, if the patient develops symptoms that may be related to the nodule.

If a thyroid nodule has already been regularly followed up with no change to the evaluation, discontinuation of the follow-up scans is justified as it is unlikely that this nodule poses a relevant health risk (6, 27, 28, 29).Here, neither nodule size nor nodule growth can be used as reliable criteria for differentiating between malignant and benign thyroid nodules (30, 31, 32, 33): Contrary to medical experience with many other diseases, both criteria do not correlate with thyroid nodule malignancy risk, according to the available evidence.

Studies conducted in recent years indicate that papillary microcarcinomas (<1 cm) do not develop from benign thyroid nodules. Probably already present in childhood, they do not usually progress to lethal carcinomas (34).The development of cancer from precursor lesions, as it is known, for example, from colorectal cancer (adenoma-carcinoma sequence), does not apply to papillary carcinomas of the thyroid gland. Therefore, a single definitive workup to establish the entity of the thyroid nodule seems sufficient, and it is primarily the detection of other types of carcinomas that is crucial.

The patient’s wishes, age, comorbidities and possible consequences of treatment should be taken into account when deciding on follow-up intervals and examinations. If regular follow-up ultrasound examinations that have been carried out before are discontinued, it is important to engage in a clear, fear-reducing communication with the patient, explaining that there is no risk posed by the findings to affected individuals. If specialists have already been involved in the care of the patient, a discussion among peers should be sought in order to agree on a joint strategy and avoid different approaches to follow-up care, as this could trigger uncertainty and result in a loss of trust of the patients in their treating physicians.

Scintigraphy

Whether to use scintigraphy should also be critically examined in each individual case with the aim of identifying and avoiding unnecessary medical interventions (quaternary prevention). When primary care physicians decide for or against a nuclear medicine referral, they should above all bear in mind that conventional thyroid scintigraphy is a modality to assess of the functional activity of thyroid nodules; thus, primarily, it does not provide information on the dignity of the nodule.

A detailed discussion of the role of scintigraphy in thyroid nodules, including indications and limitations in the primary care setting, is provided in the eBox.

Box

Indications for treatment of thyroid nodules

eBox

Scintigraphy

The treatment of thyroid nodules in primary care

Since the majority of thyroid nodules encountered in primary care do not represent a disease requiring treatment, but rather an “anatomical flaw“ without clinical significance, treatment of these nodules is neither required nor useful. Only in very rare cases, their treatment is medically justified (Box).

Treatment options

For a long time, monotherapy with iodine or levothyroxine was the established treatment approach in patients with thyroid nodules. There is no evidence to support the effectiveness of iodine replacement in reducing the size of thyroid nodules. Likewise, monotherapy with levothyroxine has been considered obsolete for years now (21, 35, 36) and thus should no longer be initiated; in patients still on levothyroxine treatment, it can be discontinued.

The LISA trial conducted in Germany is the only randomized, placebo-controlled and TSH-adapted study to evaluate treatment with iodine and levothyroxine alone or in combination (37). The trial found that treatment with a combination of levothyroxine and 150 µg iodine achieved a significant reduction in thyroid nodule volume of about 17% after one year. This relative mean reduction in size corresponds to an absolute volume reduction of about 0.3 mL. Given that this reduction is of no clinical significance in patients with thyroid nodules and that there is the risk of iatrogenic hyperthyroidism primarily in geriatric patients, combination therapy is also usually not indicated.

If a primary care physician determines that a patient with thyroid nodule requires treatment, there is no treatment option with proven benefit that can be provided directly in the primary care setting. Thus, there is always a need for specialist referral (surgery, endocrinology, nuclear medicine) to plan and provide the appropriate treatment.

Conclusion

The ability to find the appropriate level of diagnosis and treatment is at the core of high-quality primary care. In particular in patients with thyroid nodules, harmless irregularities are far more common than genuine health risks. Therefore, it is important to maintain the necessary vigilance for rare but serious disease courses while avoiding unnecessary examinations and treatments. This approach reduces the burden on both patients and the healthcare system and, acting as a filter, enables the efficient use of limited resources. Targeted patient selection is the only way to maintain the necessary diagnostic accuracy and the excellence of specialists. It is precisely because of differences in patient populations why guidelines that are first and foremost aimed at primary care physicians at times arrive at different recommendations than guidelines for specialists (11, 21, 23, 36, e14).

Funding

Our review is based on searches performed during the development of the guideline of the German Society of General Practice/Family Medicine (Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin, DEGAM) “Thyroid Nodules in Adults. Recommendations on the Prevention, Diagnosis and Treatment in Primary Care (AWMF reg. no. 053–058). The guideline development was supported by the Innovation Fund of the Federal Joint Committee (Gemeinsame Bundesausschuss, G-BA) (funding code: 01VSF22009).

Conflict of interest statement

JF is the spokesperson for the Academy for Continuing Education and Training of the German Society of Endocrinology (Deutsche Gesellschaft für Endokrinologie, DGE). He is a co-author of the “Thyroid Cancer” guideline of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF).

KV was a coordinator of the DEGAM guideline “Thyroid Nodules in Adults. Recommendations on the Prevention, Diagnosis and Treatment in Primary Care.“

JS and KV are spokespersons of the DEGAM Guidelines and Quality Promotion Section.

The remaining authors declare no conflict of interest.

Manuscript received on 15 June 2024; revised version accepted on 3 April 2025

Translated from the original German by Ralf Thoene, M.D.

Corresponding author:
Dr. med. Jeannine Schübel

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