DESIGN:The hormonal serum marker for the presence and course of patients with medullary thyroid cancer (MTC) is the mature calcitonin (CT) peptide. Other CALC-1 gene products such as the 116-amino acid polypeptide prohormone, procalcitonin, as well as its component calcitonin precursors (CTpr) may also be increased in their sera. We performed a study to evaluate the clinical utility of serum levels CTpr in these patients.METHODS:Twenty-one patients with MTC (9 males, 12 females; 23-76 years of age) were evaluated. The diagnosis was confirmed by histologic examination, except for 2 (a proven RET mutation plus an abnormal pentagastrin-stimulated CT level). Nine patients had postoperative hypercalcitoninemia and 3 of these died. The specific assay for mature CT was a commercial immunoradiometric assay (hCT-IRMA); the immunoluminometric assay for CTpr (B.R.A.H.M.S Diagnostica, Berlin, Germany) detects intact procalcitonin and the free CT:CT carboxypeptide-1.RESULTS:All patients had detectable serum CTpr. These levels considerably exceeded those of mature CT, averaging 7.6-fold greater. CTpr levels correlated positively with mature CT (r = 0.61; p < 0.001). After pentagastrin administration, there was a parallelism of response between the two assays. Whenever there were known metastases, CTpr increased markedly.CONCLUSION:This study demonstrates the universal presence of CTpr in the blood of patients with MTC. The measurement of these peptides may offer a new dimension to the clinical evaluation of this malignancy.

Background Medullary thyroid carcinoma is a rare tumour derived from the thyroid parafollicular calcitonin-secreting cells. Calcitonin is a very specific marker of this cancer that allows preoperative diagnosis. Serum calcitonin assay is particularly useful to define the postoperative state of patients (cured, apparently cured, not cured) and, because of its great sensitivity, it has a major place in the postoperative follow-up.Objective To identify, among patients thyroidectomized for medullary thyroid carcinoma (MTC), the characteristics of authentic recurrent MTC [re-elevation of stimulated serum calcitonin (CT) level measured by a sensitive immunoradiometric assay, after postoperative normalization].Patients and methods We first collected, through the national registry of the French Calcitonin Tumour Study Group (GETC), patients who had undergone a total thyroidectomy with or without lymph node surgery and who were not cured at the last followup visit. Among 453 such patients included in the database, 15 patients met the criteria for authentic recurrence as defined in previous studies: they had been first considered as cured during the 6 months following the initial surgical procedure (basal and pentagastrin-stimulated serum calcitonin level less than or equal to 10 ng/l) but had a secondary rerise of their pentagastrin-stimulated calcitonin level, over 10 ng/l. Eight of them even had an undetectable (<2 ng/l) immediate postoperative CT, confirming the initial postoperative cure. The characteristics (age, nature of disease, stage at surgery and type of node dissection) of these 15 patients were studied.Results According to the Tumour Node Metastasis classification, nine patients were T1 and, among them, five patients had had complete lymph node surgery without any evidence of nodal metastases; (NO). The recurrence was 3.22.2 years (range: 0.7-7.5) after the initial surgery.Conclusions 3.3% of patients not cured at the last visit had a recurrent MTC. This recurrence occurred whatever the stage, and even if the primary surgery for MTC was a priori complete. These results emphasize the need for a regular biochemical follow-up because recurrence may appear many years after the initial surgery.

Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting endocrine tumor. Although plasma CT level is a specific and sensitive marker of MTC, its preoperative usefulness in predicting tumor size and postoperative CT normalization has not been documented. From a nationwide database set up by the French CT Tumor Study Group, 226 MTC patients were selected according to the following criteria: preoperative CT level determination by an immunoradiometric assay (normal value, < 10 pg/mL) within the 6 months prior to surgery, total thyroidectomy and diagnosis of MTC ascertained by histological report including tumor size. Patients were 129 females and 97 males (female/male ratio, 1.3). One hundred and twelve patients (49.6%) had the sporadic variety of the disease, 74 (32.7%) had multiple endocrine neoplasia 2A, three (1.3%) had multiple endocrine neoplasia 2B, and 37 (16.4%) had familial MTC. Median age at diagnosis was 44.8 yr (range, 4.9-80.1 yr). Complete neck dissection was performed in 159 patients (70.4%). Postoperative CT normalization was ascertained by negative response of CT to pentagastrin stimulation (< 10 pg/mL) in 94 patients. Seventy-one patients were considered as not cured because of residual tumor tissue and/or elevated CT levels. Median tumor size was 11.0 mm (range, 0.2-80.0 mm), significantly larger in females (15.0 vs. 8.0 mm, P < 0.05), and in sporadic forms (15.0 vs. 7.0 mm, P < 0.05). Tumor size was significantly correlated (r2 = 0.52, P < 0.01) with preoperative CT levels, the relationship being more straight in familial (r2 = 0.71) than in sporadic (r2 = 0.36) forms. Furthermore, preoperative CT levels under 50 pg/mL appeared to be predictive of postoperative CT normalization (44 of 45 patients). However, higher CT levels did not mean absence of postoperative CT normalization (50 of 120 patients). We conclude that low preoperative CT levels are predictive of tumor size and postoperative CT normalization.

The control of hypertension in diabetic hypertensive patients prevents micro and macroangiopathy complications. Our prospective study was designed to evaluate the level of treatment of hypertension in type II diabetic patients at the time of referral to our endocrinology unit and after a mean follow-up of 9.2 months. Five hundred and sixty four patients (sex ratio: 1.15, mean age of 56 +/- 13, mean BMI of 28 +/- 15, mean duration of diabetes of 11.3 +/- 9.9) were referred to our unit. Among these, 42% had an antihypertensive drug (58% under monotherapy, 42% under combinations) and 92% had a documented history of CHD. Glycemic and blood pressure controls were stable during follow-up. HbA1c remained unchanged (8.95% at admission, 8.8% at 9 months) BP decreased from 143/84 +/- 26/13 mmHg to 142/82 +/- 23/13 mmHg. Fifty six percent reached a BP goal of 140/90 mmHg whereas 42% achieved a BP goal of 130/85 mmHg at 9 months compared to respectively 56% and 39% at admission. A multivariate logistic regression analysis showed that initial value of SBP (p < 0.0001), age (p < 0.0001), BMI (p = 0.006), HbA1c (p = 0.018) were independent factors of non control of hypertension. In conclusion, follow-up of hypertension diabetic patients would be focussed on identified and modifiable factors.

The control of hypertension in diabetic hypertensive patients prevents micro and macroangiopathy complications. Our prospective study was designed to evaluate the level of treatment of hypertension in type II diabetic patients at the time of referal to our endocrinology unit and after a mean follow-up of 9.2 months. Five hundred and sixty four patients (sex ratio: 1.15, mean age of 56+/-13, mean BMI of 28+/-15, mean duration of diabetes of 11.3+/-9.9) were referred to our unit. Among these, 42% had an antihypertensive drug (58% under monotherapy, 42% under combinations) and 92% had a documented history of CHD.Glycemic and blood pressure controls were stable during follow-up. HbA1c remained unchanged (8.95% at admission, 8.8% at 9 months) BP decreased from 143/84+26/13 mmHg to 142/82+/-23/13 mmHg. Fifty six percent reachead a BP goal of 140/90 mmHg whereas 42% achieved a BP goal of 130/85 mmHg at 9 months compared to respectively 56% and 39% at admission. A multivariate logistic regression analysis showed that initial value of SEP (p<0.0001), age (p<0.0001), BMI (p=0.006), HbA1c (p=0.018) were independent factors of non control of hypertension.In conclusion, follow-up of hypertension diabetic patients would be focussed on identified and modifiable factors.

Medullary carcinoma of the thyroid (MTC) is a rare tumour derived from thyroid C cells with serum calcitonin as a specific and sensitive marker. MTC is inherited in 25% of cases, with an autosomal dominant transmission, age-related penetrance and variable expressivity. MTC is an obligatory component of multiple endocrine neoplasia type 2 (MEN2), which comprises three well defined syndromes: MEN2A, which may be associated with pheochromocytoma and/or hyperparathyroidism; the much rarer MEN2B, which occurs early and is accompanied by developmental abnormalities; while in contrast, familial MTC (FMTC) is not associated with any endocrinopathy. The RET proto-oncogene is the causative gene of the MEN2 syndromes and mutations in this gene are found in >90% of inherited cases, allowing easier and more reliable family screening than pentagastrin stimulation tests. Nevertheless, the correlation between the genotype and the different clinical phenotypes is not perfect. The prognosis of MTC depends on its staging at presentation, and the early appearance of cervical lymph node metastases emphasizes the need for extensive surgery, although many patients still do not normalize calcitonin levels post-operatively, and they remain a challenge for the further management.

Lymphocytic hypophysitis (LH) is a new clinico pathological entity, first described in 1962 by Goudie [46]. With recent advances in radiological investigation and technical refinements of trans-sphenoidal surgery, LH cases are being reported with increasing frequency. A total of 145 cases have been reported to date, 102 of them since 1990, with 121 histologically proven. LH is an autoimmune endocrinopathy characterized by an extensive infiltration of the anterior pituitary gland by chronic inflammatory cells, which can cause pituitary expansion and a variable degree of hypopituitarism closely mimicking the features observed in pituitary adenoma. Involvement of the neurohypophysis rarely occurs in LH. The disease mostly occurs at the end of gestation or during the early post partum, but not exclusively: 23 cases of men and 13 cases of menopausal women have been reported in the literature. When no diagnosis is made, the sometimes insidious clinical course can progress towards hypopituitarism and can result in a lethal outcome. Better known since the last five years, clinical management remains a question of debate. Up to now, the majority of cases of adenohypophysitis were surgically treated leading to severe secondary endocrine deficiencies. Recently some authors (including in one personal case report) reported a new approach with corticosteroid therapy, which was successful in reversing the hypophy-seal mass and the pituitary endocrine insufficiency. Lymphocytic hypophysitis is a recently individualized autoimmune endocrinopathy, similar to Hashimoto's thyroi-ditis. The frequency of the disease is probably underestimated and some cases of idiopathic pituitary insufficiency of adults or primary idiopathic empty sella syndrome might be related to previously ignored LH. Pathological definition

Medullary thyroid carcinoma is a rare disease which originates from the secretion of calcitonin by thyroid parafollicular cells. Sporadic (75%) and inherited (25%) forms of the disease are encountered. Familial forms (termed multiple endocrine neoplasia type IIa, IIb, or familial medullary thyroid carcinoma) may or may not be associated with other endocrinopathies such as pheochromocytoma and/or hyperparathyroidism.Circulating forms of calcitonin, a marker of the disease, are heterogeneous in blood, thus explaining why assays lead to different results according to the method used.Family screening is much easier, as germ line mutations of the proto-oncogene RET have recently been identified in inherited forms of the disease. Treatment includes extensive surgery. This, and prophylactic thyroidectomy in gene carriers, is discussed. Prognosis is much better nowadays, but precise follow-up has to be instituted.

BACKGROUND: Once genetic testing accurately identifies MEN 2 gene carriers, affected children are given the opportunity to undergo thyroidectomy at the earliest stages of the C-cell disease. OBJECTIVE: To define reliable parameters by which to identify the best moment for thyroidectomy in patients who are carriers of the MEN 2 gene. PATIENTS AND METHODS: Seventy-one MEN 2/FMTC gene carriers, collected through the national register of the French Calcitonin Tumours Study Group, were evaluated. All the patients included were younger than 20 years of age and underwent total thyroidectomy. Basal and pentagastrin-stimulated calcitonin were assayed using an immunoradiometric method (sensitivity less than 2pg/ml). Calcitonin measurement was evaluated on the basis of histopathological findings in surgical thyroid specimens. RESULTS: We found C-cell hyperplasia or medullary thyroid carcinoma in all the 71 gene carriers - even for the youngest patients - and nodal metastases were present in four cases. Calcitonin measurement (basal or pentagastrin-stimulated) detected C-cell disease preoperatively in all patients. Six of the 71 patients were not surgically cured: one had nodal metastases, one had an advanced staged disease and four had an incomplete nodal dissection or had not undergone lymph node surgery. CONCLUSIONS: Determination of calcitonin forms an integral part of the management of MEN 2 gene carriers. Thyroidectomy is undisputably indicated when basal calcitonin is abnormal. When basal calcitonin is undetectable, a pentagastrin-stimulated increase in calcitonin to more than 10 pg/ml indicates an early thyroidectomy to cure the patient.

. Sur le plan chirurgical : Le pheochromocytome s'il est depiste doit dans tous les cas etre opere avant le cancer medullaire de la thyroide (CMT). Le traitement de ce dernier consiste en unbe thyroidectomie totale avec dissection complete du compartiment central du cou. Ce curage sra complete par un curage jugulocarotidien bilateral au moindre doute. Un âge different selon les cas : Chez les sujets a risque, l'âge de la thyroidectomie a tendance a etre de plus en plus precoce. Dans la NEM 2B, la severite du pronostic justifie l'intervention du CMT des que la mutation est connue. Pour la NEM 2A, l'expression biologique precoce du CMT, conduit a operer vers l'âge de 6 ans. Pour le F-CMT, le pronostic et l'allure evolutive sont variables, car ils s'accompagnent d'une grande variete de mutations sur le proto-oncogene RET. Celles situees sur les exons 13, 14 et 15 semblent evoluer plus tardivment vers la cancerisation. Dans l'avenir : Le rescensement des cas de NEM 2 tel qu'il se fait depuis 1983 au sein du GETC permettra de mieux definir dans l'avenir chirurgical en cas de depistage ; pour le moment la thyroidectomie totale avec curage central reste obligatoire. le pronostic des neoplasies endocriniennes multiples de type 2 sera sans nul doute transforme par le depistage moleculaire, mais la surveillance post-operatoire de la calcitonine sous pentagastine, de meme que la recherche du pheo restent imperatives.

Clinical characteristics and prognosis of 80 patients (53 women and 27 men) with sporadic medullary thyroid carcinomas (MTC), less than 1 cm in size (micro-MTC), operated on between 1971 and 1996 are reported (73 total and 7 partial thyroidectomies). These patients, obtained from a national database of 899 patients with MTC, were compared with 357 cases of sporadic MTC greater than 1 cm and 149 subjects with familial MTC less than 1 cm (familial micro-MTC). Median age at surgery was 52.5 years, a distribution similar to larger sporadic MTC. Micro-MTC was identified due to elevated calcitonin (47.5%), clinically identified lymph node (10.0%.), distant metastases (6.3%) or pathologic finding at surgery (36.2%). Diarrhea and/or flushing were observed in 6 patients including 4 with clinically identified lymph node. Among patients who had lymphnode dissection at surgery (68.8%), lymph node involvement with tumor was observed in 30.9%, and was significantly more frequent in multifocal (7/11) than in unifocal micro-MTC (p < 0.03). All sporadic micro-MTC were unilateral. Survival rate was 93.9% +/- 4.4% (SE) at 10 years, greater than that observed in sporadic macro-MTC (p = 0.04). Normal postoperative basal calcitonin (CT) was obtained in 71.1% of micro-MTC patients versus 33.6% in sporadic macro-MTC (p < 0.01). Sporadic micro-MTC is much more frequent than expected, 15% of MTC in our series. Although specific survival rate and percentage of biological cure in micro-MTC are significantly better than for larger tumors, the frequency of lymph node involvement, however, justifies an aggressive surgical approach including total thyroidectomy and bilateral central lymph node dissection.

Germline mutations of the RET proto-oncogene are responsible for multiple endocrine neoplasia type 2, including multiple endocrine type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma. The relationship between specific mutations and syndromic features has been established. In particular, the risk for pheochromocytoma and hyperparathyroidism (HPT) in MEN 2A patients is clearly associated with the presence of the RET mutation at a specific position, i.e. at codon 634. Also, a correlation between a specific mutation, C634R, and the development of HPT has been suggested but is still controversial. To further investigate the relationship between specific mutations of codon 634 and the development of HPT, we studied a population of 188 individuals, carrying mutations at codon 634, namely C634R (65 patients belonging to 10 families), C634Y (80 patients belonging to 11 families), or the less frequent codon 634 mutations [i.e. C634S, C634F, C634G, or C634W (43 patients belonging to 9 families)]. In this series of patients, we defined an overall HPT prevalence of 19.1% and found that this prevalence did not vary significantly, with respect to the nature of the mutation. However, irrespective of the particular mutation, the prevalence of HPT showed a high interfamilial variability. The statistical model that best fitted with the observed data was in favor of the heterogeneity of the risk for HPT, with 40% of the families showing an HPT risk of 34% and 60% of the families showing an HPT risk of 9%. In addition, our study clearly demonstrated that HPT could be an early component of the disease and provided the first estimate of age-specific and mutation-specific HPT penetrance in individuals with mutations of codon 634 of the RET proto-oncogene.

STUDYThe aim of our study was to study therapeutic results after thyroidectomy in patients positive for predictive genetic analysis and with preoperative calcitonin (CT) response to pentagastlin (Pg) < 150 pg/ml.MATERIAL AND METHODS36 patients (13 F, 23 M) were selected: 13 F-MTC from 8 families, 22 MEN 2A from 15 families and 1 MEN 2B. They were positive for direct RET mutation analysis. CT was assayed by immunoradiometric method before and after Pg. Pg test results before and after thyroidectomy, age at operation and histologic results were analysed.RESULTSMean preoperative peak CT was 82.5 +/- 34.0 pg/ml (22-133): among these 36 patients preoperative basal and peak CT were normal in 16 and 2 patients respectively. F-MTC and MEN 2A patients were different according to their preoperative peak CT levels (58.1 +/- 24.0 vs 97.6 +/- 31.3) pg/ml, p < 0.01) and age at thyroidectomy (20.4 +/- 10.5 vs 11.6 +/- 7.6 years, p < 0.01 by Mann-Whitney test). Total thyroidectomy was performed in all patients at a mean age of 14.8 +/- 9.8 years (2.5-41.7) and was associated with lymph node dissection in 30 cases. The 2 F-MTC patients with normal preoperative peak CT levels had bilateral C-cell hyperplasia (CCH) associated with uni or bilateral micro-MTC. Other patients had uni or bilateral micro MTC except 4 who had isolated CCH without carcinoma. The age of two MEN-2A and 1 MEN 2B patients with micro-MTC ranged from 2.5 to 4.7 yr. Micro MTC was present in 100% of MEN-2A cases after the age of 10 yr. There were no lymph nodes metastases. During postoperative survey, the last PG tests (n = 33) were performed 27.5 months (1-92) after thyroidectomy: peak CT values were always < 10 pg/ml.IN CONCLUSIONThyroidectomy should be performed at a very young age in RET mutation carriers, regardless of the plasma CT values. This choice is justified in NEM-2A and NEM-2B patients but must be discussed in F-MTC families with less aggressive forms of the disease.

Un element constant : II s'agit du cancer medullaire du corps thyroide. Dans cette neoplasie endocrinienne multiple de type 2 (NEM 2), hereditaire, le cancer est presque toujours precede par une hyperplasie des cellules C, qui secretent la calcitonine. Deux formes classiques : La NEM 2B, rare, s'associe a des malformations et a une ganglioneuromatose ; les pheochromocytomes (pheo) y sont de survenue beaucoup plus tardive que le cancer medullaire du corps thyroide (CMT) qui, lui, est precoce. La NEM 2A est la forme la plus frequente. La CMT s'y associe dans 50% des cas a un ou plusieurs pheo et dans 20% a une hyperparathyroide. Les pheo sont peu expressifs et compte tenu des methodes de depistage du CMT, surviennent de plus en plus souvent apres qu'on ait decouvert le CMT ; il est donc necessaire de poursuivre leur recherche indefiniement une fois le cancer medullaire opere. L'hyperparathyroidie, cliniquement paucisymtomatique est souvent decouverte lors de l'intervention. une forme de diagnostic difficile : Quant a la troisieme forme clinique de la NEM, ou forme familiale de CMT isole (F-CMT), il peut etre parfois difficile de l'affirmer ; en effet, l'expression du pheo et de l'HPT peut manquer dans la NEM 2A au moment du diagnostic de CMT. Ce troisieme cadre doit donc rester un diagnostic d'exclusion. Neanmoins en France, il realise presque 30% des cas du groupe d'etude des tumeurs a calcitonine GETC).

BACKGROUNDPrognostic factors of sporadic or inherited medullary thyroid carcinoma (MTC) are still controversial and have been assessed in old and small series. A better knowledge of these factors would improve patient management.OBJECTIVETo evaluate factors involved in the prognosis of MTC in a large series of cases, using uni‐ and multivariate analysis.DESIGN AND PATIENTSClinical, biological, surgical and epidemiological data on 899 MTC patients, diagnosed between 1952 and 1996, were collected by the French Calcitonin Tumors Study Group (GETC) with a standardized questionnaire, and processed in a national database.MEASUREMENTSSurvival and biochemical cure (i.e. normal basal post‐operative serum calcitonin levels) were analysed with Kaplan and Meier and log‐rank test statistical procedures. Data are presented as adjusted rather than observed survival, to consider only patients who died of MTC. Cox's forward‐stepping proportional hazard model was used to analyse factors with a significant influence on survival by univariate analysis.RESULTSApart from the large proportion of familial forms (43%), the general characteristics of our population were similar to those in other studies: mean age at surgery = 43.4 years; sex ratio = 1 male/1.35 female; stage I = 20.8%; stage II = 21.2%; stage III = 46.5% and stage IV = 11.5%. 863 (96%) patients underwent surgery; 43% of operated patients were biochemically cured. Adjusted survival was 85.7 ± 1.5% at 5 years and 78.4 ± 2.1% at 10 years. Multivariate analysis showed that age and stage were independent predictive factors of survival. Gender, type of surgery, type of familial form were predictive only in univariate analysis. Biochemical cure predicts a survival rate of 97.7% at 10 years. Authentic recurrence, that is subsequent elevation of calcitonin (CT) after post‐operative normalization, was found in 4.9%. In non‐cured patients (57%), survival was still good: 80.2% (±2.2%) and 70.3% (±2.9%) at 5 and 10 years, respectively. Similarly, prediction of biochemical cure was solely dependent on stage.CONCLUSIONSurvival of these medullary thyroid carcinoma patients appears better than expected even in non‐cured patients. Considering the strong impact of stage, the necessity for pre‐operative diagnosis of MTC is obvious.

Des mutations germinales : La connaissance depuis 1993 d'anomalies genetiques situee sur le proto-oncogene RET permet desormais le depistage familial par la recherche de la mutation. Celle-ci sera presente des la naissance chez les individus a risque alors que l'expression biologique (elevation de la calcitonine sous pentagastrine) varie avec l'âge. Dans le NEM 2B : Variete la plus rare, elle s'accompagne d'une mutation specifique sur le proto-oncogene, sur le codon 918 de l'exon 16. le carcimone medullaire de la thyroide (CMT) doit etre opere des que la mutation est connuen quel que soit le resultat du dosage de la calcitonine. Dans la deuxieme variete ou NEM 2A : Forme la plus frequente, elle peut comporter plusieurs types de mutations, dont la plus frequente se situe au niveau du codon 634 de l'exon 11. Des travaux du GETC ont permis de montrer que l'expression biologique du CMT, jugee par une elevation de la calcitonine sous pentagastrine au-dessus du taux basal (>10 pg/ml) est precoce, justifiant par consequent d'operer avant l'âge de 10 ans, afin d'eviter le stade d'envahissement ganglionnaire. Dans la troisieme forme ou CMT familial isole : des mutations ne sont actuellement retrouvees que dans 85% des cas ; de plus, il y a toute une variete possible de mutations tout au long du gene. Celles situees sur les exons 13, 14 et 15 semblent bien correspondre a un phenomene particulier, ou le F-CMT est a revelation plus tardive et l'HCC longtemps presente avant la cancerisation.

Calcitonin (CT) is the most sensitive tumor marker for medullary thyroid carcinoma available, but it lacks specificity. Chronic renal failure (CRF) is known to be associated with elevations of serum immunoreactive calcitonin. Using an immunoradiometric assay to detect only mature CT, we evaluated the basal CT level and its response to pentagastrin in 30 patients with CRF and compared these data with those obtained in 71 controls. Basal mature CT was significantly higher (p < 0.05) in patients with CRF (3.55 pg/mL) than in controls (2.00). Among these patients, 20% had basal CT levels more than 10 pg/mL with a maximum of 51 pg/mL. Peak CT values (highest value obtained 3 or 5 minutes after pentagastrin) were comparable in the two groups. Among patients with CRF, 10% had peak CT values greater than 30 pg/mL with a maximum of 53 pg/mL. In this group of patients, no correlation was found between CT (at any time during the test) and parathyroid hormone, calcium, phosphate, or creatinine clearance. Men had significantly higher CT values compared with women at each time point tested, including peak values. Patients with CRF, who have not yet undergone dialysis, have moderately elevated basal CT levels, but have normal pentagastrin-stimulated peak CT levels.

In the multiple endocrine neoplasia (MEN) type 2A and in the familial medullary thyroid carcinoma (FMTC), the recent development of genetic testing has provided new methods of identifying disease gene carriers. The use of sensitive immunoradiometric calcitonin (CT) assays led us to evaluate reference ranges of plasma CT responses after pentagastrin in healthy subjects in order to discuss the place of pentagastrin testing in the management of hereditary MTC. Basal and pentagastrin-stimulated CT concentrations were measured in 71 healthy volunteers--aged 20-67 years--and 76 genetically unaffected members of families with hereditary MTC--aged 4-61 years. In healthy subjects, CT peak values were below 30 ng/l in 68 cases and below 50 ng/l in 3 cases. In the genetically unaffected patients, CT peak values were below 15 ng/l in young patients and below 30 ng/l in patients older than 19 year excepted 5 men with stimulated CT levels ranging from 36.5 to 52 ng/l. In 2 of these 5, thyroidectomy revealed C-cell hyperplasia. Borderline test results are not sufficient to establish diagnosis of MTC and in these familial syndromes, management has to be based on the results of genetic testing. However, the determination of the upper normal limit for stimulated CT concentrations in young patients (< 15 ng/l) may help to identify the optimal moment for surgery.