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British Journal of Radiology 74 (2001),486-489 © 2001 The British Institute of Radiology

Full paper

Role of radionuclide imaging in hyperthyroid patients with no clinical suspicion of nodules

N A Lacey, MRCP, FRCR1, A Jones, MRCP, FRCR1 and S E M Clarke, MSc, FRCP2

Departments of 1Radiology and 2Nuclear Medicine, Guy's & St Thomas NHS Trust, St Thomas' Street, London SE1 5RT, UK


   Abstract
Top
 Abstract
Introduction
 Patients and method
 Results
 Discussion
 References
 
The purpose of the study was to assess the role of radionuclide imaging of hyperthyroid patients with no suspicion of nodules. 99Tcm radionuclide scans performed on all 190 patients referred over a 2-year period with symptoms and thyroid function tests compatible with thyrotoxicosis were retrospectively reviewed. 73% of patients were referred by a hospital clinician and 27% were referred direct from the general practitioner. Referral letters and, where applicable, the clinical notes were reviewed and patients with suspected thyroid nodules were excluded. The results of 99Tcm thyroid scans of the 190 patients (age range 23–93 years, mean 48 years) were reviewed. 152 (80%) patients had Graves' disease, 10 (5.3%) had Graves' disease with nodules, 6 (3.2%) had Graves' disease with non-functioning nodules, 5 (2.6%) had viral thyroiditis, 5 (2.6%) had autonomously functioning nodules and 12 (6.3%) were normal studies. Therefore, 20% of patients had a diagnosis other than solely Graves' disease. These diagnoses are important with respect to clinical management. In conclusion, routine radionuclide imaging is worthwhile, as a significant proportion of patients with clinical "Graves' disease" in this study would have received incorrect treatment without the result of this scan.


   Introduction
Top
 Abstract
 Introduction
Patients and method
 Results
 Discussion
 References
 
Routine radionuclide imaging for patients referred with Graves' disease and for hyperthyroid patients without palpable nodules is not uniform practice in the UK. However, it is important that an accurate diagnosis of the cause of the hyperthyroid state is made, as this affects treatment and prognosis.

Hyperthyroidism is generally due to toxic diffuse goitre (Graves' disease), toxic nodules that are either solitary or multiple (Plummer's disease), or more rarely subacute thyroiditis. Non-functioning nodules have been shown in many studies to co-exist with any of the above conditions. The treatment for each of these conditions is entirely different. The treatment of choice for Graves' disease is a prolonged course of antithyroid drugs in the first instance, which cures approximately 50% of patients. These patients can then be further treated by radioactive iodine (131I) or surgery [1]. Plummer's disease, however, is rarely, if ever, cured by antithyroid drugs alone and therefore a long-term treatment regimen involving these drugs is both costly and may involve unnecessary side effects. The treatment of choice for Plummer's disease is 131I [2]. It is clinically important to differentiate Graves' disease from Plummer's disease, as treatment ofthe former with 131I leads to a high incidence of hypothyroidism and requires meticulous follow-up, whereas the incidence is low for the latter condition [3]. Subacute thyroiditis causes only transient hyperthyroidism and it is therefore important to recognize this diagnosis to avoid unnecessary treatment. The presence of multinodularity in a gland in which there is superimposed Graves' disease may lead to a mistaken diagnosis of Plummer's disease. Non-functioning nodules in patients with Graves' disease require clinical follow-up owing to the risk of malignant change in a nodule.

This study aimed to assess the frequency of causes of hyperthyroidism other than Graves' disease in consecutive patients referred with elevated thyroid function without clinically suspected nodules. The frequency of cold nodules and multinodular goitre was also assessed. All patients referred to Guy's Hospital Thyroid Clinic with hyperthyroidism undergo thyroid radionuclide imaging regardless of the clinical suspicion of nodules.


   Patients and method
Top
 Abstract
 Introduction
 Patients and method
Results
 Discussion
 References
 
The patient group was selected by reviewing all 99Tcm scans performed for thyrotoxicosis over a 2-year period. By assessing the referral forms and notes, as appropriate, for these patients, it was possible to select those that had been referred with a clinical diagnosis that either stated Graves' disease or that provided a history of signs and symptoms compatible with a diagnosis of Graves' disease. Patients were excluded who, on clinical examination or other imaging modalities, had prior evidence of thyroid nodules. In each case it was noted whether the referral for the scan came direct from the general practitioner (GP) or from a hospital clinician to assess whether unsuspected nodules are less common in the hospital referral group. Note was also made of whether the patient had elevated thyroid function tests and whether the patient was being treated with carbimazole.

Before imaging, a clinical history was obtained, with particular reference to symptoms that would make thyroiditis more likely, for example a painful goitre. A full drug history was also taken and a standard protocol was followed to prepare the patient for the scan. Ultrasound was performed if medical staff were available.

Imaging was performed 20 min after an intravenous injection of 80 MBq of sodium 99Tcm pertechnetate, using a gamma camera with a high resolution collimator. Data were acquired with a 128 x 128 matrix and a zoom factor of 2.67–4.0. Imaging acquisition was terminated at 100 k counts or after 900 s of imaging, whichever occurred first.

Tracer uptake by the thyroid gland at 20 min was also calculated as a percentage of the dose injected, allowing for decay and correcting for background. The normal range applied was 0.5–4.0%. This result was helpful in calculating the dose of subsequent radioactive iodine treatment.

Graves' disease was diagnosed in a diffusely enlarged thyroid gland with a high uptake of tracer throughout. Viral thyroiditis was diagnosed on the background of thyroid function tests and signs and symptoms compatible with thyrotoxicosis but an uptake scan showing a homogeneous distribution of tracer throughout both lobes of the thyroid and reduced tracer uptake. Autonomously functioning thyroid nodules show a focal area of increased uptake, with suppressed uptake in the rest of the gland. Nodularity was detected as areas of non-homogeneity in tracer uptake.


   Results
Top
 Abstract
 Introduction
 Patients and method
 Results
Discussion
 References
 
Results were reviewed in 190 patients (Table 1Go). 140 of these patients were female and 50 were male, giving a female to male ratio of 2.8:1. The age range of the patients was 23–93 years, with a mean age of 48 years. A diagnosis of Graves' disease was confirmed on 99Tcm thyroid scans in 152 patients. Varying diagnoses were made on the remaining 38 patients, including viral thyroiditis, autonomously functioning thyroid nodules, Graves' disease with areas of multinodularity and Graves' disease with non-functioning nodules. Some patients were found to have scans with normal uptake with some nodularity. 20% of a total of 190 patients were therefore shown to have a diagnosis other than solely Graves' disease, all of which were important in the future management of the patient.


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  		Table 1. Results of radionuclide imaging in hyperthyroid patients

 
All patients had elevated thyroid function tests. Interestingly, the vast majority of patients in whom nodules were found were taking carbimazole, which is known to diminish the uptake associated with solitary or multiple toxic nodules (Table 2Go). 60% of patients diagnosed with solely Graves' disease were taking carbimazole. This could potentially have lead to an underestimate of the presence of nodules in these patients.


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  		Table 2. Referral details and clinical information obtained for patents in the study

 
All patients who underwent an ultrasound examination at the time of the isotope scan had the presence or absence of their nodules confirmed (Table 2Go). Of the six patients with decreased areas of uptake consistent with cysts or cold nodules, subsequent ultrasound imaging showed all these to be solid nodules. Fine needle aspiration was performed on two of the six patients and showed benign histology in both cases. No further evaluation was performed on two patients because they were elderly and had severe concurrent disease. However, one of these showed no evidence of thyroid-related disease 4 years after the isotope scan. Ultrasound in one patient showed multiple nodules in the suspicious area with no obvious nodule to biopsy, and one patient was transferred to another hospital that has subsequently closed. The patient with multiple small nodules has been followed clinically and has remained well for 5 years following her initial scan.

The majority of patients with nodules and thyroiditis were referred from the hospital clinician rather than GPs (Table 2Go). These patients are therefore likely to have had histories taken and examinations performed by specialists. In no case of thyroiditis were there suspicious clinical features stated in the referral. Therefore, if ultrasound alone had been used, these cases would have been missed as the ultrasound was normal in all of these cases. Although patients in which there was a clinical suspicion of nodules were excluded from the study, 23 out of the total of 190 patients were found to have nodules. These nodules were all confirmed by ultrasound if this was performed. However, ultrasound alone would not have diagnosed Graves' disease in those who had nodules as well as Graves' disease.


   Discussion
Top
 Abstract
 Introduction
 Patients and method
 Results
 Discussion
References
 
This study aimed to analyse consecutive requests for radionuclide thyroid scanning in patients in whom a clinical diagnosis of Graves' disease had been made and in patients in which no palpable nodules were present. In particular, the incidence of conditions that required a different treatment regimen than that used for Graves' disease was sought. These included Plummer's disease, carcinoma, Graves' disease in a multinodular gland and viral thyroiditis. Ultrasound alone cannot diagnose Graves' disease in multinodular goitre or thyroiditis, and cannot identify functionality of nodules.

The practice of routine radionuclide thyroid imaging of all patients referred for hyperthyroidism is controversial. The results of all patients referred with hyperthyroidism were analysed in a previous study [4], which showed that the vast majority of patients were confirmed as having Graves' disease, but there was a significant number of patients with other diagnoses, including 12% with autonomously functioning nodules (Plummer's disease), 3% with Graves' disease in a multinodular gland, while the remainder had either viral thyroiditis or iodine-induced thyrotoxicosis. Only 20% of the patients with Plummer's disease had palpable nodules and therefore 80% of cases would have remained undiagnosed without a "routine" scan in those patients without a clinical suspicion of nodularity. However, the conclusion of a study in Leeds [5] was that thyroid scanning was of little use when the referral identified a diffuse goitre. Only two patients out of a total of 50 had a toxic hot nodule that led to a change of management. However, on closer scrutiny of the data used for this study, only seven patients fitted the eligibility criteria for this present study of clinical Graves' disease with no suspected nodules. Therefore, the discrepancies of the result may be owing to this small sample size.

Autonomously functioning thyroid tissue can occur as a solitary nodule or as multiple nodules (classic Plummer's disease), with the mass and rate of secretion of this tissue determining the thyroid status of the patient. These nodules are independent of thyroid stimulating hormone (TSH) for growth and function and appear as increased uptake areas or are "hot", with suppression of uptake in the remainder of the gland on the radionuclide scan. The diagnosis of autonomously functioning thyroid nodules is important, as the treatment is different from that of Graves' disease. Antithyroid drugs such as carbimazole, which can be curative in Graves' disease only control the secretion of thyroxine in Plummer's disease and do not cure the condition. Mistreatment is therefore not only expensive, inappropriate and inconvenient for the patient, but can also expose the patient to the risk of the side effects of these drugs, including nausea, headache, rashes, pruritis, arthralgia and, more seriously, alopecia or agranulocytosis [6]. A more permanent treatment is preferable, with either radioactive iodine (131I) or surgery in hyperthyroid patients, especially in the elderly in whom cardiac complications are more common [7]. In these patients, the radioisotope scan has an added benefit as the uptake value allows the dose of 131I to be calculated.

The incidence of concurrent hyperthyroidism and thyroid cancer has been relatively frequent in several surgical studies. In one study [8], thyroid cancer was found in thyroidectomy specimens of 8% of 25 patients with toxic adenoma, 6% of the 33 patients with Graves' disease and 5% of the 138 patients with toxic nodular goitre. In a different study [9], malignancy was found in the thyroidectomy specimens of 4 out of 18 patients with toxic diffuse goitre, with a thyroid nodule also present and 2 out of 68 patients with just a toxic diffuse goitre. No mention is made of radionuclide imaging findings in either of these studies. However, these studies confirm that nodules should be evaluated carefully to rule out malignancy [10].

It is also necessary to exclude subacute granulomatous or viral thyroiditis as a cause of hyperthyroidism before planning treatment. Scintigraphic findings in subacute thyroiditis include low uptake in mild cases and markedly suppressed or absent uptake in extensive disease owing to both the disruptive effect of the inflammation and the ensuing hyperthyroidism [11]. Treatment of the transient hyperthyroid symptoms seen in this condition should be symptomatic, as hypothyroidism may result from the condition itself and therefore definitive treatment with 131I or surgery is contraindicated.

Thyroid radionuclide imaging is also helpful in identifying those patients with Graves' disease superimposed on a multinodular gland as opposed to those with a toxic nodular goitre that would require radioactive iodine treatment. Diagnosis of nodules is important as they need to be followed up to assess cancer risk. Prominent or suspicious non-functioning nodules should undergo fine needle aspiration to exclude malignancy [12, 13]. Follow-up is therefore recommended in patients with multinodular goitre with superimposed Graves' disease. Once euthyroid status is achieved, yearly evaluation with TSH determination and thyroid palpation is usually sufficient for small goitres. Surgery is the treatment of choice if the goitre is large and local compression symptoms occur.

An unexpected finding of this study was that most of the unsuspected nodules were found in patients referred direct from hospital clinicians rather than from GPs. These patients are likely to have had histories taken and examinations performed by specialist physicians experienced in feeling for nodules. This confirms that imaging is required before a diagnosis of Graves' disease is made. Ultrasound confirmed the presence of nodules in all those patients in whom it was performed, but ultrasound alone would not have diagnosed the Graves' disease when this was superimposed on a multinodular goitre, and thyroiditis cannot be diagnosed by ultrasound alone. It was also interesting to note that no symptoms of thyroiditis were mentioned in those found to have this disease. This demonstrates the importance of routine isotope imaging in these patients.

This study has shown that routine thyroid radionuclide imaging is helpful in identifying patients with an unsuspected cause of hyperthyroidism other than Graves' disease. There is a definite change of clinical management in a percentage of patients at our centre as a result of these scans.

Received for publication May 25, 2000. Revision received January 2, 2001. Accepted for publication February 19, 2001.


   References
Top
 Abstract
 Introduction
 Patients and method
 Results
 Discussion
 References
 

  1. Vanderpump MPJ, Ahlquist JAO, Franklyn JA, Clayton RN. Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism. BMJ 1996;313:539–43.[Free Full Text]
  2. Franklyn JA. The management of hyperthyroidism. N Engl J Med 1994;330:1731–9.[Free Full Text]
  3. Miller JM. Hyperthyroidism from the thyroid follicle autonomous function. Clin Endocrinol Metab 1975;7:177–97.
  4. Fogelman I, Cooke SG, Maisey MN. The role of thyroid scanning in hyperthyroidism. Eur J Nucl Med 1986;11:397–400.[Medline]
  5. Tindall H, Griffiths AP, Penn ND. Is the current use of thyroid scintigraphy rational? Postgrad Med J 1987;63:869–71.[Abstract]
  6. British National Formulary. British Medical Association and Royal Pharmaceutical Society of Great Britain. 1996;9:298.
  7. Thomas CG Jr, Croom RD III. Current management of the patient with autonomously functioning nodular goitre. Surg Clin North Am 1987;67:315–28.[Medline]
  8. Terzioglu T, Tezelman S, Onaran Y, Tanakol R. Concurrent hyperthyroidism and thyroid carcinoma. Br J Surg 1993;80:1301–2.[Medline]
  9. Pacini F, Elisei R, Di Cosgio GC, et al. Thyroid carcinoma in thyrotoxic patients treated by surgery. J Endocrin Invest 1988;11:107–12.[Medline]
  10. Carnell NE, Valente WA. Thyroid nodules in Graves' disease: classification, characterization and response to treatment. Thyroid 1988;8:571–6.
  11. Roddie ME, Kreel I. Endocrine disease. In: Grainger RG, Allison D, editors. Grainger and Allison's diagnostic radiology: a textbook of medical imaging, (3rd Edn). London: Churchill Livingstone, 1997: 1306.
  12. Hurley DL, Gharib H. Evaluation and management of multinodular goitre (review). Otolaryngol Clin North Am 1996;29:527–40.[Medline]
  13. Hurley DL, Gharib H. Thyroid nodular disease: is it toxic or non-toxic, malignant or benign. Geriatrics 1995; 50: 24–6, 29–31.



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