Follow-up Of Medullary Thyroid Carcinoma Research Articles

Serum Biochemical Markers for Medullary Thyroid Carcinoma: An Update.

Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC. A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers. The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management. Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.

An initial disturbing finding in the follow-up of medullary thyroid carcinoma after surgery- in the Vth laterocervical compartment may represent a positive course of the disease. Case Report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Calcitonin: current concepts and differential diagnosis.

Calcitonin (CT) is most effectively produced by the parafollicular cells of the thyroid gland. It acts through the calcitonin receptor (CTR), a seven-transmembrane class II G-protein-coupled receptor linked to multiple signal transduction pathways with its main secretagogues being calcium and gastrin. It is clinically used mostly in the diagnosis and follow-up of medullary thyroid carcinoma (MTC). Hypercalcitoninemia can be attributed to primary (e.g. CT-secreting tumor) or secondary (e.g. due to hypercalcemia) overproduction, underexcretion (e.g. renal insufficiency), drug reaction (e.g. β-blockers), or false-positive results. In clinical practice, elevated basal calcitonin (bCT) is indicative, but not pathognomonic, of MTC. Current literature leans toward an age as well as gender-specific cutoff approach. bCT >100 pg/ml has up to 100% positive prognostic value (PPV) for MTC, whereas bCT between 8 and 100 pg/ml for adult males and 6 and 80 pg/ml for adult females should be possibly further investigated with stimulation calcitonin (sCT) tests. Calcium is showing similar efficacy with pentagastrin (Pg) sCT; however, the real value of these provocative tests has been disputed given the availability of new, highly sensitive CT immunoassays. Anyhow, evidence concludes that sCT <2 times bCT may not be suggestive of MTC, in which case, thyroid in addition to whole body workup based on clinical evaluation is further warranted. Moreover, measurement of basal and stimulated procalcitonin has been proposed as an emerging concept in this clinical scenario. Measuring bCT levels in patients with thyroid nodules as a screening tool for MTC remains another controversial topic. It has been well established, though, that bCT levels raise the sensitivity of FNAB (Fine Needle Aspiration Biopsy) and correlate with disease progression both pre- and postoperatively in this situation. There have been numerous reports about extrathyroidal neoplasms that express CT. Pancreatic, laryngeal, and lung neuroendocrine neoplasms (NENs) are most frequently associated with hypercalcitoninemia, but CT production has also been described in various other neoplasms such as duodenal, esophageal, cutaneous, and paranasal NENs as well as prostate, colon, breast, and lung non-NENs. This review outlines the current biosynthetic and physiology concepts about CT and presents up-to-date information regarding the differential diagnosis of its elevation in various clinical situations.

Procalcitonin measured by three different assays is an excellent tumor marker for the follow-up of patients with medullary thyroid carcinoma.

Procalcitonin (PCT) has been suggested as a tumor marker in patients with medullary thyroid carcinoma (MTC). Clinical application data in long term follow-up are missing. 210 serum samples of 169 consecutive patients with MTC (92 sporadic, 77 hereditary, 158 postoperative follow-up, 11 preoperative) were collected between 2018 and 2020. Postoperative patients were stratified into three groups according to their disease status at the end of follow-up: cured (n=51, calcitonin (CT) levels<limit of quantitation), minimal residual disease (n=55, detectable CT and no metastases provable by imaging methods), metastatic disease (n=52). In five patients CT and PCT were measured while on therapy with tyrosine kinase inhibitors (TKI). CT was analyzed by the Roche ECLIA, PCT by three assays from Roche, PES, Abbott. The mean±SD values seen with the three PCT assays in the MTC response groups, cured: <0.06, 0.016±0.007, 0.014±0.007ng/mL, minimal residual disease: 0.511±0.800, 0.389±0.687, 0.341±0.614ng/mL, metastatic disease 109±202, 60.4±110, 63.3±115ng/mL correlate well with the CT results in these groups: cured <1.0pg/mL, minimal residual disease 91.3±121.5pg/mL, metastatic disease 14,489±30,772pg/mL. There was a significant correlation (p<0.001) between the three PCT assays (Roche/PES r=0.970, Roche/Abbott r=0.976, Abbott/PES r=0.995). In the course of treatment with TKI both CT and PCT reflected clinical state. Preoperative PCT in hereditary MTC has the same diagnostic validity than CT. PCT measured with three different immunoassays is as good as the standard tumor marker CT in the follow-up of MTC but has a superior analytical stability.

Medullary thyroid carcinoma and multiple endocrine neoplasiatype 2

Medullary thyroid carcinoma (MTC) is a rare malignancy and compromises only 3 % of all thyroid carcinomas. MTC cells secret calcitonin, which serves as a sensitive tumor marker for screening and follow-up of MTC. Calcitonin screening in patients with nodular goiter allows for early diagnosis of MTC and surgical curative treatment. In 25 % of patients MTC occurs as an integral part of multiple endocrine neoplasia type 2 (MEN2), an autosomal dominant inherited tumor syndrome. It is caused by germline mutations in the RET protooncogene. In gene carriers early diagnosis and treatment through prophylactic thyroidectomy is possible. MTC is a slowly growing tumor with a good prognosis and 5and 10 year survival rates up to 80 and 60 %. In the follow-up a dynamic risk stratification allows for a personalized disease management. In symptomatic and progressive metastasizing MTC tyrosine kinase inhibitors are an effective therapy.

Macrocalcitonin Is a Novel Pitfall in the Routine of Serum Calcitonin Immunoassay.

Calcitonin (CT) is a sensitive marker of medullary thyroid carcinoma (MTC) and is used for primary diagnosis and follow-up after thyroidectomy. However, persistently elevated CT is observed even after complete surgical removal without evidence of a recurrent or persistent tumor. To investigate the presence of assay interference in the serum CT of MTC patients who are apparently without a structural disease. We studied three index MTC cases for CT assay interference and 14 patients with metastatic MTC. The CT level was measured using an immunofluorometric assay. Screening for assay interference was performed by determination of CT levels before and after serum treatment with polyethylene glycol. Additionally, samples were analyzed by chromatography on ultra-performance liquid chromatography and protein A-Sepharose. Patients with biochemical and structural disease showed CT mean recovery of 84.1% after polyethylene glycol treatment, whereas patients suspected of interference showed recovery from 2-7%. The elution profile on UPLC showed that the immunometric CT from these three patients behaved like a high molecular mass aggregate (>300 kDa). Additionally, when these samples were applied to the protein A-Sepharose, CT immunoreactivity was retained on the column and was only released after lowering the pH. For the first time, our results show the presence of a novel pitfall in the CT immunoassay: "macrocalcitonin." Its etiology, frequency, and meaning remain to be defined, but its recognition is of interest and can help clinicians avoid unnecessary diagnostic investigations and treatment during the follow-up of MTC.

Epidemiology and Clinical Presentation of Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the thyroid C cells producing mainly calcitonin (CTN) used as tumor marker. MTC occurs either sporadic (75%) or in a hereditary form (multiple endocrine neoplasia type 2, MEN2), due to germline mutations in the RET proto-oncogene. The discovery of an MTC in a patient has several diagnostic implications involving a specific strategy: preoperative evaluation of the tumor marker CTN and the extent of the disease, classification of MTC as sporadic or hereditary by DNA testing, and screening for associated endocrinopathies in hereditary MTC. Elevated CTN is a highly sensitive and specific tumor marker for diagnosis and follow-up of MTC. CTN is directly related to the tumor mass. In patients with nodular thyroid disease, diagnosis of MTC could be made by CTN determination as an indicator of tumor burden in conjunction with fine-needle aspiration. Patients with confirmed sporadic or hereditary MTC should have a total thyroidectomy and depending on the preoperative CTN value and the extent of disease additional dissection of the lymph nodes in the central and lateral neck compartment. In MEN 2 patients diagnosed by screening, the time of prophylactic thyroidectomy depends on RET mutation and CTN level.

Medullary thyroid cancer diagnosis: An appraisal

Since its first description in 1951, a timely diagnosis of medullary thyroid carcinoma (MTC) may represent a diagnostic challenge in clinical practice. Several contributions have been addressed to the treatment and follow-up of MTC, but review articles focused on the diagnostic problems of this cancer in clinical practice are sparse. As a delayed diagnosis and an inadequate initial treatment may severely affect the prognosis of this thyroid malignancy, the appropriate use and the correct interpretation of the available diagnostic tools for MTC are of crucial importance. The purpose of the present article is to provide an easy-to-use guide reviewing the main issues of MTC diagnosis: (1) basal serum calcitonin; (2) stimulated serum calcitonin; (3) additional serum markers for MTC; (4) ultrasound and other imaging techniques; (5) fine-needle aspiration (FNA) cytology; (6) calcitonin measurement on FNA washout; (7) rearranged during transfection (RET) mutations; and (8) scope of the problem.

Interpretation of serum calcitonin in patients with chronic autoimmune thyroiditis

Calcitonin (CT) is an important clinical marker for the diagnosis and follow-up of medullary thyroid carcinoma, although it is not absolutely specific. Some authors have reported C-cell hyperplasia in a number of thyroid specimens affected by Hashimoto's thyroiditis. The association between thyroiditis and hypercalcitoninemia is still controversial because some authors have reported low CT levels. The aim of this study is to evaluate the basal CT values in patients with and without thyroid autoimmunity. From May 2005 to February 2010, 1073 patients underwent ultrasonography-guided fine-needle aspiration cytology at the Thyroid Center of Sapienza University of Rome, with evaluation of basal serum FT4, FT3, TSH, and antithyroid peroxidase (anti-TPO) antibodies as well as CT levels. Forty-one patients presented a basal CT level above the reference upper limit. The mean serum CT was significantly lower in women than in men (4.28 ± 6.63 vs 7.50 ± 25.50 pg/ml; P<0.01). Basal serum CT was not significantly higher in patients showing anti-TPO Ab positivity (4.71 ± 6.46 vs 4.84 ± 13.11 pg/ml; P>0.05). Importantly, the rate of 'suspicious' CT values (above the 10 pg/ml cutoff) was not significantly different between patients with or without thyroid autoimmunity (3.9 vs 3.0%). Patients with hypercalcitoninemia suffering from chronic autoimmune thyroiditis should undergo the same clinical evaluation procedure as patients do without thyroid autoimmunity.

Medullary thyroid carcinoma in a patient with Hashimoto's thyroiditis diagnosed by calcitonin washout from a thyroid nodule

Serum calcitonin is a tumor marker used in the diagnosis and follow-up of medullary thyroid carcinoma. Calcitonin washout evaluation is a new method used for suspicious thyroid nodules and lymph nodes. Limited clinical data are present about the efficacy of this method. A 61-year-old female patient with known Hashimoto's thyroditis and an 8-mm hypoechoic nodule was presented with one previously benign fine-needle aspiration cytology (FNAC). On referral to our department, she had a moderately high-serum calcitonin level, and we repeated the FNAC that was reported as nondiagnostic. We performed FNAC for the third time together with calcitonin washout evaluation from the thyroid nodule. The FNAC was again nondiagnostic, but the calcitonin washout level from the thyroid nodule was 152.569 pg/mL. Total thyroidectomy was performed, and the diagnosis was confirmed as medullary thyroid carcinoma. Calcitonin washout evaluation may be a useful method in the differential diagnosis of patients with thyroid nodules having moderately high-serum calcitonin levels.

La TEP-TDM à la 18F-Dopa aurait-elle un rôle dans le suivi postopératoire des patients atteints de carcinome médullaire de la thyroïde ? Résultats préliminaires de l’expérience strasbourgeoise et revue de la littérature

Aim Retrospective study to assess the value of fluorine-18 dihydroxyphenylalanine ( 18F-Dopa) positron emission tomography (PET)/computed tomography (CT) in the post-surgical follow-up of patients with history of medullary thyroid carcinoma (MTC) and biological suspicion of disease relapse. A review of the literature was also performed. Patients and methods Ten patients (23–71 years) with MTC previously treated by surgery were examined by at least one 18F-Dopa PET/CT. All patients presented with elevated serum calcitonin (130–9076 ng/l) and/or CEA (1.2–518 ng/ml) levels. 3D whole body PET/CT was performed 45 and 120 minutes after intravenous injection of 4 MBq/kg of 18F-Dopa. Scintigraphic images were visually interpreted. For quantitative analysis, maximum standardized uptake value (SUV max) per focus was employed. PET results were compared with histological findings and/or with the results of all other imaging procedures. Results Seven patients (70%) had a positive 18F-Dopa PET/CT. Twenty-five focal tracer accumulations were described. Histopathological confirmation of metastatic disease was obtained in four of the seven patients with pathologic 18F-Dopa PET/CT. No scintigraphic abnormalities were evidenced in the three other patients, whose conventional morphological imaging procedures were also negatives. Delayed PET/CT examinations didn’t increase sensitivity. No correlation between 18F-Dopa PET/CT results and both serum calcitonin and CEA levels was achieved. Conclusion Our results are in accordance with the existing literature, showing the potential role of 18F-Dopa PET/CT in the clinical management of patients with history of MTC and biological suspicion of relapse during post-surgical follow-up. Prospective studies including larger patient series are necessary to confirm the future place of 18F-Dopa PET/CT in follow-up of MTC.

Clinical Value of 18-Fluorine-Fluorodihydroxyphenylalanine Positron Emission Tomography/Computed Tomography in the Follow-Up of Medullary Thyroid Carcinoma

18-Fluorine-fluorodihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET) is a sensitive method for detecting medullary thyroid carcinoma (MTC). The advent of PET/computed tomography (CT) has enabled more sensitive and specific lesion identification using various tracers in many other tumors. The aim of this study was therefore to test the hypothesis that combined (18)F-DOPA PET/CT more accurately detects MTC lesions than each modality does alone. Twenty-eight consecutive (18)F-DOPA PET, CT, and (18)F-DOPA PET/CT scans of patients followed up for sporadic MTC or multiple endocrine neoplasia 2 syndrome-associated MTC were reviewed retrospectively in randomized sequence by two blinded readers, one a nuclear medicine physician and the other a radiologist, with extensive experience interpreting such images. Of 18 lesions detected concurrently by the three modalities, PET identified all as positive for MTC, but was unable to definitively localize 4 (22%) lesions. CT could definitively localize all 18 lesions, but could not definitively diagnose or exclude MTC in 6 (33%) lesions. Further, CT falsely identified as MTC-negative one lesion that was judged to be MTC-positive by both PET and PET/CT. Only PET/CT scans accurately characterized and localized all 18 lesions. On a per patient basis, the sensitivity of (18)F-DOPA PET/CT for MTC was 74% and the specificity, 100%. In the present series, no truly MTC-positive (18)F-DOPA PET/CT case was found in patients with basal human calcitonin (hCt) levels under 60 pg/mL, and conversely, no truly MTC-negative PET/CT case was found in patients with basal hCt over 120 pg/mL. Between hCt concentrations of 60 and 150 pg/mL true-negative, false-negative, and true-positive scans all were obtained. (18)F-DOPA PET/CT had 100% sensitivity and specificity when hCt at the time of scanning was over 150 pg/mL, the threshold at which the 2009 American Thyroid Association guidelines recommend performing additional imaging including (18)F-DOPA PET/CT. (18)F-DOPA PET/CT allows for a more accurate diagnosis and localization of MTC lesions than do (18)F-DOPA PET or CT alone. Supporting the recent American Thyroid Association recommendations on additional imaging in MTC, (18)F-DOPA PET/CT appears to have 100% sensitivity in patients with hCt over 150 pg/mL.

Spurious hypercalcitoninemia in patients with nodular thyroid disease induced by heterophilic antibodies

Serum calcitonin is the most useful tumor marker for the diagnosis and follow-up of medullary thyroid carcinoma (MTC). Spurious hypercalcitoninemia caused by heterophilic antibody interference (HAI) is rarely found in patients without MTC. We studied 2 patients with hypercalcitoninemia and thyroid nodules, but no evidence of MTC on fine-needle aspiration cytology. We performed calcium stimulation tests, measured serum calcitonin with another calcitonin kit, performed dilution tests, and remeasured serum calcitonin after applying heterophilic blocking tubes. In a 31-year-old woman with no response to the calcium stimulation test, serum calcitonin was <5 pg/mL using another kit. After we applied heterophilic blocking tubes, the serum calcitonin level decreased to normal range. We concluded that patient had spurious hypercalcitoninemia. In a 63-year-old woman, all tests revealed that the patient had true hypercalcitoninemia. The patient underwent total thyroidectomy that revealed MTC. We suggest that patients suspected for spurious hypercalcitoninemia should undergo further investigation due to HAI.

Diagnóstico de carcinoma medular de tiroides (CMT) de forma casual tras realización de Gammagrafía 123I-Metayodobencilguanidina (123I-MIBG)

The objective of this clinical note is to emphasize diagnostic efficiency of 123I-MIBG scintigraphy in the initial diagnosis and follow-up of medullary thyroid carcinoma within MEN2. We present the case of a patient who, during a scintigraphic study with 123I-MIBG for the diagnosis of pheochromocytoma, was unexpectedly found to suffer from medullary carcinoma of the thyroid. Prior to performing the test, we proceeded to block uptake into the thyroid gland through the administration of Lugol. We carried out the scintigraphic study by intravenously injecting 370 MBq 123I-MIBG. A pathological uptake of the radiopharmaceutical compound over the right suprarenal gland, and unexpectedly, over the thyroid gland was detected, thus confirming the existence of medullary carcinoma of the thyroid in this patient, and obtaining the diagnosis of Type MEN2A polyglandular syndrome. From our experience, we can manifest the value of scintigraphy using 123I-MIBG in the diagnosis and localization of medullary carcinoma of the thyroid. Furthermore, it is indicated in patients suspected of MEN, since it makes it possible to reach a diagnosis of this kind of syndrome through the performance of just one test.

Diagnóstico laboratorial do carcinoma medular de tiróide: calcitonina basal e testes de estímulo

A calcitonina é um hormônio secretado pelas células parafoliculares tiroideanas. O diagnóstico de carcinoma medular de tiróide (CMT) pode ser suspeitado a partir do encontro de níveis aumentados de calcitonina basal ou após testes de estímulos específicos. Neste sentido, a calcitonina caracteriza-se como um importante marcador tumoral para o diagnóstico e seguimento de pacientes portadores de CMT. Neste artigo, revisamos alguns tópicos referentes à utilidade da dosagem de calcitonina basal em pacientes portadores de nódulos de tiróide para rastreamento de CMT. Comentamos a respeito dos principais testes de estímulo para secreção de calcitonina disponíveis e finalizamos com algumas observações sobre os ensaios para dosagem de calcitonina.

O Laboratório no Diagnóstico e Seguimento de Doenças Auto-Imunes e Neoplásicas de Tiróide

O laboratório é fundamental no diagnóstico das doenças auto-imunes e neoplásicas da tiróide. O teste mais importante para o diagnóstico etiológico da tiroidite de Hashimoto, doença de alta prevalência, é a determinação do anticorpo anti-tiroperoxidase (A-TPO), dosagem que pode também ser útil no diagnóstico de doença de Graves, do risco de hipotiroidismo em pacientes com hipotiroidismo sub-clínico e do risco de gestantes apresentarem tiroidite pós-parto. Outro teste útil nas doenças autoimunes é a determinação dos anticorpos anti-receptor de TSH (TRAb) naqueles casos de doença de Graves pouco sintomáticos ou quando a mesma ocorre em pacientes com bócio multi-nodular. Nas doenças neoplásicas da tiróide, a tiroglobulina (Tg) é fundamental e de alta sensibilidade no seguimento dos pacientes com câncer diferenciado da tiróide (papilífero e folicular), enquanto que a dosagem de calcitonina é obrigatória para o diagnóstico e seguimento do câncer medular da tiróide.

Una propuesta para el uso racional de la PET en oncología

This study aims to develop a Clinical Practice Guide for the rational use of the Positron Emission Tomography (PET) in Oncology, that makes it possible to approach the real existence of demand in the public health care service of Andalucía, by limiting the clinical indications, using criteria based on the existence of sufficient scientific evidence on the effectiveness and clinical impact of PET. The consensus technique was used to elaborate the Guide, gathering a group of nuclear medicine experts. Prior to this a systematic research of the scientific literature was carried out, using strict criteria for the selection of the articles, such as the evaluation of the epidemiological data, work methodology, clinical and pathological diagnosis, gold standard references and statistical analysis. In each pathology group, the existence of alternative non-invasive diagnostic techniques was assessed, comparing its effectiveness and clinical impact with the PET, and the existence of useful treatments correlated with the results of the examination was also evaluated. When it was possible, we evaluated the cost-effectiveness of the PET. Finally, the cost-effectivity of the technique was assessed and the limitation of present and future resources and the economical costs arising from the PET costs and introduction were evaluated. It was considered that the PET was indicated in the following clinical conditions: 1: Assessment of Colorectal Cancer recurrence in patients with increased levels of tumor markers and negative morphological imaging techniques. Suspicion of isolated resectable recurrence. 2: Restaging in patients with high risk melanoma. 3: Differential diagnosis of solitary pulmonary nodules. 4: Staging of non-small cell bronchial carcinoma. 5: Staging and detection of recurrences of lymphomas. 6: Restaging of head and neck cancer with possibilities of curative treatment. 7: Diagnosis of recurrences in differentiated thyroid cancer in patients with increased plasma levels of thyroglobulin and negative radioiodine scintiscan. 8: Staging and follow-up of medullary thyroid carcinoma. 9: Differential diagnosis between recurrent tumor and scar or radionecrosis in brain tumors.

Improved Diagnostic Methods in the Follow-Up of Medullary Thyroid Carcinoma by Highly Specific Calcitonin Measurements

Improved Diagnostic Methods in the Follow-Up of Medullary Thyroid Carcinoma by Highly Specific Calcitonin Measurements

Improved Diagnostic Methods in the Follow-Up of Medullary Thyroid Carcinoma by Highly Specific Calcitonin Measurements*

Calcitonin (CT) is an important tumor marker for medullary thyroid carcinoma (MTC). Recent CT assays chiefly recognize the monomeric form of CT (mCT). It was the objective of this study to examine the consequences of the higher specificity of the assay for interpretation of the postoperative CT values in MTC patients. The postoperative mCT concentration was measured in 214 patients with differentiated thyroid carcinoma (MTC excepted; non-MTC patients) to determine a reference range of mCT in totally thyroidectomized patients. Monomeric CT was also determined with a two-site chemiluminescence immunoassay (Nichols) in 94 healthy subjects and in 68 MTC patients. The mCT concentrations were below the detection limit in all examined completely thyroidectomized non-MTC patients. Basal and stimulated mCT values were also below the detection limit in 32 of the 68 MTC patients. The biochemical and imaging diagnosis of the latter patients did not give any indication of tumor recurrence. We conclude that completely thyroidectomized patients with non-MTC do not show any measurable mCT concentrations. In comparison with an unspecific CT-RIA, the more specific mCT determination by immunoluminometric assay permits a more precise differentiation between postoperative normal and pathological values and an earlier diagnosis of recurrent MTC.

Pheochromocytoma in multiple endocrine neoplasia type 2: European study

Pheochromocytoma (pheo) is the second component of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. Clinical expression is sometimes poor, and chronology between medullary thyroid carcinoma (MTC) and pheo is not well evaluated. Therefore, a retrospective study was done in eight European countries in order to precise the main characteristics of pheo in MEN 2. Data from 300 MEN 2 patients with pheo (274 MEN 2 A and 26 MEN 2 B) were obtained from cases registered by the EuroMen study group, and collected by a medical standardized questionnaire. These cases occurred between 1969 and 1992. Mean age at diagnosis of pheo was 39.5 years (range 14-68 years) in MEN 2A and 32.4 years (range 15-41 years) in MEN 2B patients. Pheo occurred first in 25.1% of the cases (2-15 years before diagnosis of MTC) and after MTC in 40.2% (2-11 years). In other cases (34.7%), MTC and pheo were diagnosed at the same time. Involvement was bilateral in 67.8% of cases. Malignancy was only 4%. Thirty-nine deaths occurred in these 300 patients, 64.1% were linked in pheo, 23.1% to MTC and 12.8% to other causes. Surgery was unilateral in 39.7% of the cases and bilateral adrenalectomy was the first procedure in 48.4%. A bilateral adrenalectomy in two steps had to be done in 11.9% of cases. In conclusion, these results justify systematic and prolonged biochemical screening of pheo during follow-up of MTC and address some questions about the best mode of surgery.