Elisabeth Modigliani

Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma : results in 899 patients

Prognostic 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.

Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma

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.

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type IIa: Retrospective French Multicentric Study

Abstract. Primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia (MEN) type IIa is rare, occurring in 20% to 30% of the patients. The aim of this study was to evaluate clinical findings, surgical therapy, and outcome for 56 patients affected by PHPT among 249 MEN-IIa patients collected from 84 families assembled by the Groupe d’Etude des Tumeurs á Calcitonine (GETC, French Calcitonin Tumors Study Group). This retrospective study was based on cases registered by the GETC (20 participating centers) from 1969 to 1994. Characteristics of PHPT in 56 patients (31 women, 25 men) with MEN-IIa were reviewed. All but two underwent cervicotomy. The median age at diagnosis was 37.6 years. PHPT was found concomitantly with medullary thyroid carcinoma (MTC) or pheochromocytoma in 43 patients (77%). PHPT was asymptomatic in 68% of the patients. Serum calcium levels ranged from 2.20 to 3.70 mmol/L (median 2.82 mmol/L; normal 2.10–2.60 mmol/L). The number of parathyroid glands removed at surgery was 0 (n = 2), 1 (n = 24), 2 (n = 5), > 2 (n = 12), 4 (n = 11). Pathology (initial surgery) consisted of 24 adenomas, 4 double adenomas, and 25 hyperplasia. Cure after initial surgery was obtained in 89%, including a 22% incidence of hypoparathyroidism. There were 6 cases (11%) with persistent PHPT. With a mean follow-up of 6.4 years, five patients (9%) had recurrent PHPT. The results indicate that MEN-IIa-related PHPT is generally associated with mild, often asymptomatic hypercalcemia. Despite recurrences encountered 5 to 15 years after the first cervicotomy, resection of only macroscopically enlarged glands generally appears sufficient. Subtotal or total parathyroidectomy with autotransplantation is associated with a high rate of hypoparathyroidism.

Pseudotumoral Lymphocytic Hypophysitis Successfully Treated by Corticosteroid Alone: First Case Report

We report the first case of pseudotumoral lymphocytic hypophysitis successfully treated by corticosteroids without surgery. A 27-year-old woman had been monitored for chronic headache 13 months after giving birth, associated with amenorrhea and galactorrhea. Cranial magnetic resonance imaging revealed a markedly enlarged pituitary gland with a suprasellar extension; the only biochemical abnormality was a mild hyperprolactinemia. Because of a putative diagnosis of prolactinoma, bromocriptine was prescribed at a dose of 5 mg daily, soon followed by the transitory appearance of menstruation. Two years later, panhypopituitarism was present and was revealed by acute adrenal insufficiency. Magnetic resonance imaging revealed that the pituitary mass was the same as previously described, but hormonal investigation showed evidence of complete hypopituitarism and no hyperprolactinemia. Nuclear antibodies were negative as well as other autoantibodies. Human leukocyte antigen serological Class II typing was DR3/DR4. Lymphocytic hypophysitis was then suspected; in the absence of visual complication and because this patient refused surgery, corticosteroids were attempted at a daily dose of 60 mg of prednisone for 3 months, progressively decreased for the next 6 months. Under this treatment, a gradual recovery of all pituitary hormones was observed and magnetic resonance imaging showed a reduction of two-thirds in pituitary mass. Five months after the end of corticoid treatment, our patient relapsed with panhypopituitarism and an increase of pituitary volume. She underwent steroid treatment, and a biopsy was performed and confirmed the diagnosis of autoimmune hypophysitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Phaeochromocytoma in multiple endocrine neoplasia type 2 A: survey of 100 cases

OBJECTIVE We report clinical, biochemical, morphological and histological data of phaeochromocytoma in 40 French families and in apparently sporadic cases of multiple endocrine neoplasia (MEN) type 2 A (medullary thyroid carcinoma, phaeochromocytoma, with or without hyperparathyroidism).

Detection of a germline mutation at codon 918 of the RET proto-oncogene in French MEN 2B families

Multiple endocrine neoplasia type 2A (MEN2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are three dominantly inherited disorders linked to the same disease locus on chromosome 10. Two types of germline mutation of the RET proto-oncogene, which codes for a transmembrane tyrosine kinase, are associated with MEN 2. Missense mutations at cysteine residues in the extra-cytoplasmic domain are exclusively associated with MEN 2A and FMTC. In MEN 2B patients, a single point mutation at codon 918 has recently been characterized, leading to the replacement of a methionine by a threonine within the RET tyrosine kinase domain. We now report the identification of a mutation at codon 918 in the germline of 16 patients out of 18 unrelated MEN 2B families analyzed. In these families we have been able to demonstrate that, in five cases, the mutation arose de novo, and that, in one kindred, it was coinherited with the disease. These results indicate that a unique mutation at codon 918 of the RET gene is the most prevalent genetic defect causing MEN 2B, but also that rare MEN 2B cases are associated with different mutations yet to be defined.

Pseudotumoral Lymphocytic Hypophysitis Successfully Treated by Corticosteroid Alone

We report the first case of pseudotumoral lymphocytic hypophysitis successfully treated by corticosteroids without surgery. A 27-year-old woman had been monitored for chronic headache 13 months after giving birth, associated with amenorrhea and galactorrhea. Cranial magnetic resonance imaging revealed a markedly enlarged pituitary gland with a suprasellar extension; the only biochemical abnormality was a mild hyperprolactinemia. Because of a putative diagnosis of prolactinoma, bromocriptine was prescribed at a dose of 5 mg daily, soon followed by the transitory appearance of menstruation. Two years later, panhypopituitarism was present and was revealed by acute adrenal insufficiency

Linkage analysis of hereditary thyroid carcinoma with and without pheochromocytoma

SummaryThe use of polymorphic DNA segments as markers for the gene for the multiple endocrine neoplasia (MEN) syndrome, type 2a, allows the identification of family members at high risk for developing medullary carcinoma of the thyroid and other tumors, especially pheochromocytoma. Several families have also been identified in which medullary thyroid carcinoma is inherited, but pheochromocytoma is not seen. We have analysed 18 families, 9 with MEN 2A and 9 with medullary carcinoma of the thyroid without pheochromocytoma, with probes specific for the pericentromeric region of chromosome 10 and conclude that the mutations for the two presentations are closely situated. Genetic heterogeneity of the susceptibility locus was not seen among this sample of 18 families. The genetic mutation for medullary carcinoma was in disequilibrium with the marker alleles of the two closely linked probes. IRBPH4 and MCK2. These data suggest that different mutant alleles of the same gene or closely linked mutations account for the variation in penetrance of pheochromocytoma in families with hereditary, medullary thyroid carcinoma.