Thyroid Nodules: Diagnosis and Treatment in Primary Care

Abstract

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.

Information on CME

This article has been certified by the North Rhine Academy for Continuing Medical Education. The questions on this article may be found (in German) at http://daebl.de/RY95 (Deutsches Ärzteblatt’s CME portal). Their English translation may be found in the PDF version of this article. The closing date for entries is June 26, 2026.

Participation is possible at cme.aerztebatt.de

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.

	Women	Men	Total
Thyroid nodules among adults in Germany (3)	–	–	21 200 000
New cases of thyroid cancer/year (5)	4000	1800	5800
Proportion of thyroid carcinomas in thyroid nodules	0.038% (4 000/10 600 000)	0.017% (1800/10 600 000)	0,027% (5800/21 200 000)
Adults with hyperthyroidism in Germany (9)	102 000–663 000
Hyperthyroidism due to toxic adenomas (9)	16 320–331 500
Mean number of clinically relevant toxic adenomas	173 910
Proportion of relevant toxic adenomas in the adult population in Germany	0.34 % (173 910/51 000 000)

All absolute frequencies are taken from the respective references cited. The percentages (rows 4 and 8) as well as the mean reported in row 7 were calculated independently from these data.

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.

Subgroup thyroid carcinoma	Proportion of thyroid carcinomas (%) (5)		Primary treatment options (8)	Prognosis
	Women	Men
Papillary thyroid carcinoma	76	66	Depending on the stage (sub)total thyroidectomy Radioiodine therapy	Very good 10-year survival 90% (8)
Follicular thyroid carcinoma	10	13	Usually complete thyroidectomy Radioiodine therapy	Good 10-year survival >80% (8)
Medullary thyroid carcinoma	5	7	Total thyroidectomy, removal of the involved lymph nodes	Moderate 10-year survival 61–81% (e3)
Anaplastic thyroid carcinoma	2	4	Radiotherapy and chemotherapy (combined or as monotherapy)	Very poor 1-year survival <10% (e4)
Unspecific	5	6
Other morphologies	2	4

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.

PICO questions	Guideline search*1		Publication search*2
	Identified	Included	Identified (PubMed + Cochrane)	Included
Diagnosis What are the conditions under which further workup (laboratory & ancillary testing) brings benefits with regard to patient-related outcomes und preventable dangerous clinical courses?	29	9	366 + 141	35
Monitoring In which patients with thyroid nodules and at what intervals are follow-up examinations necessary, and when can they be discontinued? What kind of follow-up examinations are necessary?			167 + 141	3
Treatment concepts in primary care What concepts are used for the treatment of thyroid nodules in the primary care setting?	0	0	93 + 54	4
Pharmacotherapy Does pharmacotherapy with levothyroxine or iodine lead to a significant reduction in the volume of thyroid nodules compared to control groups without treatment?	2	2	31 + 169	1

*¹ Databases: AWMF, Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V.); G-I-N, Guidelines International Network; SIGN, Scottish Intercollegiate Guidelines Network; ETA, European Thyroid Association; ATA, American Thyroid Association AACE; American Association of Clinical Endocrinologists

*² Databases: PubMed + Cochrane

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.

Ultrasound screening for thyroid nodules in primary care
Population	All pts with nodules >1 cm: 41% of age group 20–93 years in Germany (3) → 28 700 000 (N)
Prevalence of thyroid cancer	1% (6)
Number of ill persons	287 000
Number healthy persons	28 413 000
	Sensitivity (e5) ACR-TIRADS (≥ 5) (10): 0,5; EU-TIRADS (≥ 4) (11): 0,93; Kwak-TIRADS (≥ 4b) (12): 0,94
	n tested true positive	n tested false negative
ACR-TIRADS (≥ 5) (10)	143 500	143 500
EU-TIRADS (≥ 4) (11)	266 910	20 090
Kwak-TIRADS (≥ 4b) (12)	269 780	17 220
	Specificity (e5) ACR-TIRADS (≥ 5) (10): 0,94; EU-TIRADS (≥ 4) (11): 0,57; Kwak-TIRADS (≥ 4b) (12): 0,61
	n tested true negative	n tested false positive
ACR-TIRADS (≥ 5) (10)	26 708 220	1 704 780
EU-TIRADS (≥ 4) (11)	16 195 409	12 217 591
Kwak-TIRADS (≥ 4b) (12)	17 331 930	11 081 070
Predictive values
	Positive predictive value (What proportion of those who test positive are actually ill?)	Negative predictive value (What proportion of those who test negative are actually healthy?)
ACR-TIRADS (≥ 5) (10)	8%	> 99%
EU-TIRADS (≥ 4) (11)	2%	> 99,5%
Kwak-TIRADS (≥ 4b) (12)	2%	> 99,5%
Which number of patients (n) would need to be referred to further diagnostic workup based on positive test results?
ACR-TIRADS (≥ 5 Pkt.) (10)	1 848 280
EU-TIRADS (≥ 4) (11)	12 484 501
Kwak-TIRADS (≥ 4b) (12)	11 350 850

ACR American College of Radiology; N, total number; n, number in subgroup;

pts, patients; TIRADS, Thyroid Imaging Reporting and Data System

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 (13–15, 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.

Malignancy criterion	Sensitivity
Solidity	10–34% (21)
Hypoechoicity	30–87% (21)
Irregular margins	37% (21)
Microcalcifications	5–69% (21)
Taller-than-wide shape (anteroposterior > laterolateral)	15–53% (25)
Signs of extrathyroidal spread:
Characteristic associated lymphadenopathy
Invasion of adjacent structures

Table 4. Dignity evaluation based on ultrasound criteria using the established Thyroid Imaging Reporting and Data System (TIRADS) classification systems.

Assessment/ estimated malignancy risk	Kwak 2011*1 (12)	ACR TI-RADS*2 (10) American College of Radiology	EU-TIRADS (11) (European Thyroid Association)	ATA guidelines (21) (American Thyroid Association)	K-TIRADS (22) (Korean Society of Thyroid Radiology)	Perros 2014 (23)
Without suspicion of malignancy < 3 %	No suspicious ultrasound features	Up to 2 points	Cysts	Cysts Partly cystic nodules without suspicious ultrasound features	Cysts Partly cystic nodules with comet-tail artefacts; spongiform	Halo, isoechoic /mildly hyperechoic Cystic changes +/- ring-down artifact (colloid) Micro-cystic /spongiform Peripheral eggshell calcification Peripheral vascularity
Low suspicion of malignancy1.7–10%	4a: 1 suspicious ultrasound feature 4b: 2 suspicious ultrasound features	3 points	Solid nodules isoechoic or hyperechoic, spongiform nodules	Solid nodules, isoechoic, hypoechoic, spongiform Partly cystic nodule with eccentric solid area WITHOUT microcalcification, irregular margin, taller-than-wide shape, or extrathyroidal spread	Partly cystic or solid nodule, isoechoic, hyperechoic WITHOUT microcalcifications, taller-than-wide shape, irregular margin	Homogenous, hyperechoic (marked), solid, halo (follicular lesion), hypoechoic, dubious echoic foci, cystic change, mixed/central vascularity
Increased suspicion of malignancy 10–70%	4c: 3–4 suspicious ultrasound features	4–6 points	Hypoechoic solid nodule WITHOUT microcalcifications, irregular margin, extrathyroidal spread	Hypoechoic solid nodule with smooth margins WITHOUT microcalcifications, taller-than-wide shape or extrathyroidal spread	Hypoechoic, solid nodules without further highly suspicious features or partially cystic or iso-/hyperechogic nodules with at least 1 highly suspicious feature	Solid, hypoechoic (compared to thyroid gland); solid, very hypoechoic (compared to muscle) Interrupted peripheral calcification, hypoechoic, lobulated margin
High suspicion of malignancy >70–90%	5 suspicious ultrasound features	≥ 7 points	Nodules with ≥ 1 of the following features: microcalcifications, irregular margin, extrathyroidal spread, marked hypoechoicity	Solid hypoechoic nodules or solid hypoechoic part of a partially cystic nodule with ≥ 1 suspicious features	Solid hypoechoic nodule with ≥ 1 highly suspicious features	Solid, hypoechoic, lobulated/irregular outline, microcalcification, solid, hypoechoic, lobulated/irregular outline, globular calcification, intranodular vascularity; shape (taller > wide), associated lymphadenopathy

*¹ Suspicious ultrasound features: solidity, hypoechoicity, microlobulation, irregular margin, (micro-) calcifications, taller-than-wide shape

*² Points: Composition: cystic or almost completely cystic, spongiform: 0 points; mixed cystic and solid: 1 point; solid or almost completely solid: 2 points; Echogenicity: anechoic: 0 points; isoechoic or hyperechoic: 1 point; hypoechoic: 2 points; very hypoechoic: 3 points; Shape: wider than deep: 0 points; taller than wide: 3 points; Margin: smooth: 0 points; lobulated or irregular: 2 points; extrathyroidal spread: 3 points; Echogenic foci: no or large comet tails: 0 points; macrocalcifications: 1 point; peripheral calcifications: 2 points; microcalcifications: 3 points

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::

Figure.

This nodule located dorsally in the thyroid lobe grows primarily into the depth (“taller than wide“). In primary care, it is common to encounter such growth patterns which follow the normal direction of goiter expansion. In such a case, this feature is not suspicious of malignancy, whereas it is treated as suspicious for thyroid cancer in the TIRADS systems.

In a German study, such a configuration was found in 17% of all thyroid nodules.

(From: [e17], reprinted with the kind permission of NUK-Verlag)

• 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.

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, 27–29).Here, neither nodule size nor nodule growth can be used as reliable criteria for differentiating between malignant and benign thyroid nodules (30–33): 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.

eBox. Scintigraphy.

If in patients with thyroid nodules TSH levels are low, referral for scintigraphy is useful in order to detect autonomously functioning areas. Normal or elevated TSH levels usually rule out the presence of a—functional and clinically relevant—autonomously functioning nodule. In individual cases, autonomously functioning adenomas can be functionally relevant even if TSH levels are in the low-normal range, in particular in geriatric patients with cardiovascular disease. If clinical abnormalities (e.g., unexplained weight loss, atrial fibrillation, heart failure) are present, it is possible that there nevertheless is a clinically relevant thyroid functional autonomy (provided thyrotoxicosis factitia has been ruled out). In this case, scintigraphy should be considered. For asymptomatic patients with functionally not relevant autonomously functioning adenomas, this has not diagnostic or therapeutic consequences.

Given that hyperfunctioning (“hot”) nodules are usually benign, scintigraphy is also considered an indirect method for ruling out malignancy. As a general rule, this group of patients should not receive further diagnostic workup to determine the dignity of the nodule (e9). In Germany, up to 25% of all thyroid nodules are “hot“ (e10), of these more than 50% without TSH suppression (e11). In this subgroup, again more than 50% have ultrasound criteria indicative of increased or high suspicion of malignancy (e12). As these would lead to unnecessary further diagnostic workup, thyroid scintigraphy should be performed to rule out a “hot” nodule prior to any planned fine-needle aspiration biopsy.

“Cold” nodules are only detected using scintigraphy if they measure more than 1 cm in diameter. Among “cold” nodules, the likelihood of thyroid cancer (regardless of prognosis) is 2% to 5% (e13), somewhat higher in studies carried out in specialized centers (8, e9). Therefore, the nuclear medicine S1-level guideline recommends examining all thyroid nodules larger than 1 cm in diameter using scintigraphy (e14). However, since the absolute malignancy risk of “cold“ nodules is still low, especially for prognostically relevant clinical courses, routine referral of all patients with thyroid nodules larger than 1 cm to scintigraphy is not justified. Scintigraphy is both at the individual patient and overall economic level not justified. In primary care, it is advisable to refer patients with findings suspicious of malignancy to appropriate specialists (Table 4). These specialists then decide whether or not further diagnostic workup is required.

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).

Box. Indications for treatment of thyroid nodules.

• Local symptoms such as dyspnea and difficulty swallowing, presumably caused by local compression of neck structures

• Thyroid nodules without local symptoms that are perceived by the patient as unaesthetic and annoying

• Functionally relevant toxic adenomas of the thyroid gland

• Thyroid nodules highly suspicious of malignancy

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).

Questions on the article in issue 13/2025:

Thyroid Nodules: Diagnosis and Treatment in Primary Care

The submission deadline is 26 June 2026. Only one answer is possible per question.

Please select the answer that is most appropriate.

Question 1

1. What prevalence of thyroid nodules is reported for the population aged over 60 in Germany?

1. ≥ 25%

2. ≥ 33%

3. ≥ 50%

4. ≥ 75%

5. ≥ 85%

Question 2

Which statement about thyroid nodules is the most appropriate?

1. Only a small fraction of all thyroid nodules detected has a relevant adverse health effect on the affected individual.

2. Thyroid nodules are rarely detected as an incidental finding.

3. Only rarely do thyroid nodules remain undetected over the course of a lifetime.

4. Asymptomatic thyroid nodules are rare and primarily seen in men.

5. The initial symptom of most thyroid nodules is difficulty swallowing.

Question 3

Which of the following types of thyroid cancer has the lowest mortality risk?

1. Follicular thyroid carcinoma

2. Anaplastic thyroid carcinoma

3. Papillary thyroid carcinoma

4. Medullary thyroid carcinoma

5. Acellular thyroid carcinoma

Question 4

What does the acronym TIRADS used in the article stand for?

1. Thyroid Impact Rating and Diagnosis System

2. TSH Impact Reporting and Diagnosis System

3. TSH Imaging Reporting and Disease System

4. Thyroid Imaging Reporting and Data System

5. TSH Impact Rating and Disease System

Question 5

Which of the following aspects is mentioned as one of the reasons for the supposed increase in the prevalence of thyroid nodules?

1. The greater awareness of the topic in the general population

2. The increased exposure to environmental toxins

3. The technological advances in ultrasound scanners

4. The increasing iodine deficiency due to changes in eating habits.

5. The changed definition of the diagnosis “thyroid nodule”

Question 6

What procedure is generally recommended for the workup of thyroid nodules in primary care if the initial ultrasound examination reveals a low risk of malignancy and the overall context (medical history factors and clinical presentation) is not indicative of greater urgency?

1. One-time follow-up examination after three to five years

2. One-time follow-up after one year

3. Regular follow-ups every two years

4. Regular follow-ups every six months

5. Two follow-ups (after two and four years, respectively)

Question 7

Which of the following points is not mentioned as an indication for the treatment of thyroid nodules?

1. Local symptoms, such as dyspnea and difficulty swallowing, related to the nodule

2. Nodules that are perceived as unaesthetic and annoying by the patient

3. Functionally relevant toxic thyroid adenomas

4. Thyroid nodules highly suspicious of malignancy

5. Partially cystic or spongiform nodules

Question 8

Which statement about the pharmacotherapy of thyroid nodules is the most appropriate, according to the article?

1. Iodine monotherapy is the most effective in reducing the size of nodules.

2. Monotherapy with levothyroxine is recommended for patients who do not tolerate iodine well.

3. Monotherapy with iodine or levothyroxine is effective, whereas combination therapy (iodine and levothyroxine) is obsolete.

4. Combination therapy (iodine and levothyroxine) can significantly reduce the volume of a nodule, but this reduction is not clinically relevant.

5. Before a combination therapy (iodine and levothyroxine) is started, the two medications should first be tested each alone in sequence.

Question 9

On the basis of which laboratory parameter can a functionally decompensated (toxic) adenoma be ruled out?

1. Calcitonin level

2. TSH level

3. FSH level

4. Calcitriol level

5. TPO antibodies

Question 10

Which of the following criteria is not indicative of malignancy of thyroid nodules?

1. Hypoechogenicity

2. Irregular outline

3. Microcalcifications

4. Peripheral vascularization

5. Taller-than-wide shape