[Evaluation of an immunoradiometric assay for succinylated ACTH]. / Evaluationdudosageimmunoradiométrique de l'ACTH succinylée.

A new immunoradiometric assay for succinylated ACTH using 3 monoclonal antibodies has been developed by Immunotech (I-IRMA). It was compared to a commercial immunoradiometric assay of ACTH (Nichols Institute, N-IRMA). The functional sensitivity of I-IRMA assay was estimated at 1.5 ng/L. The comparison of both methods on plasma samples withdrawn at 8 h from 47 normal subjects showed a good correlation coefficient (r = 0.83; P < 0.001). The 24-hours secretion profiles obtained by both methods were similar in 14 normal subjects. Nevertheless, the I-IRMA mean values were about 30% lower than the corresponding N-IRMA values. This difference increased to 50% when the ACTH concentrations were low, as it the case at 24 h or during the dexamethasone suppression test. During insulin hypoglycemia stimulation test, the two procedures gave similar values. Both methods applied to a pathologic population gave similar result to those obtained on normals. In 10 patients bearing corticotroph adenomas, the profiles of ACTH secretions during 24 h were similar using both methods. The I-IRMA values were lower about 30% than N-IRMA values during the base state or after the 8 mg-dexamethasone suppression test. This difference was also observed in 6 patients with corticotroph insufficiency. In conclusion, the comparison of N-IRMA and I-IRMA methods showed the validity of the new succinylated-ACTH assay which is more efficient in the lower range of ACTH concentration. This significant decrease in the sensitivity threshold may be useful in the establishment of the cure criteria in Cushing disease.

[Immunohistochemical detection of calcitonin, ACTH, beta-MSH, beta-endorphin and somatostatin in medullary carcinoma of the thyroid. Immunoperoxidase study (PAP, ABC) of 10 cases]. / Détection immunocytochimique de calcitonine, d'ACTH, de beta MSH, de beta-endorphine et de somatostatine dans les carcinomes médullaires de la thyroïde. Etude en immunoperoxydase (PAP, ABC) de 10 cas.

Ten cases of Medullary carcinoma of Thyroid gland (MCT) were examined (two familial, eight sporadic) in patients with increased serum calcitonin levels and ranging age from 31 to 87 years. Immunocytochemical reactions were performed using Peroxidase-Antiperoxidase (PAP) complex and/or Avidin-Biotin-Peroxidase complex (ABC) by light microscopy on fixed tumorous specimens (10 cases) and additionally by electron microscopy (3 cases). The tumors displayed light microscopic features typical of MCT. The cells were polyhedral, angular or fusiform and showed high affinity for Grimelius stain. Large deposits of amyloid were Congo red stained and disclosed a green birefringence in polarized light. In the familial cases sections of non-tumorous thyroid tissue showed C cell hyperplasia. Electron microscopic studies revealed intracytoplasmic secretory granules and amyloid fibrils. The immunoperoxidase technique demonstrated calcitonin in the tumor cells in all the cases, with a weaker staining than in para-and intra-follicular C cells of adjacent non tumorous tissue and than in C cells hyperplasia foci, when present. Immunoreactive tumor cells were also observed with anti SRIF in 4 cases, with anti-ACTH and anti-beta MSH in 3 cases, and with anti-beta endorphin in 2 cases. These results are discussed with a review of the literature.

[Plasma tumor markers (calcitonin and carcinoembryonic antigen) in medullary thyroid cancers]. / Les marqueurs tumoraux plasmatiques (calcitonine et antigène carcino-embryonnaire) au cours des cancers médullaires thyroïdiens.

The authors have studied 43 patients operated on for medullary thyroïd carcinoma. Plasma calcitonin was measured regularly in all patients, while carcinoembryonic antigen assay was performed in only 30 patients. Calcitonin assay was found to be useful for preoperative diagnosis of medullary carcinoma, and the level of plasma calcitonin appeared to be roughly correlated with tumor extension. After surgery, simultaneous assay of calcitonin and carcinoembryonic antigen was performed, in order to obtain more accurate information concerning the evolution and prognosis of the disease. In most cases in which no metastatic lymph nodes had been discovered at operation, the level of the two markers rapidly fell to undetectable values. It was observed that in patients with lymph node involvement, cervico-mediastinal radiation treatment did not change the slow and progressive evolution of the disease. However, a rapid increase in titre of carcinoembryonic antigen occurred simultaneously with the discovery of metastases, even when calcitonin levels did not dramatically change.

[Diagnosis of familial medullary cancers]. / Dépistage des cancers médullaires familiaux.

Medullary thyroid carcinoma (MTC) is hereditary in 20 to 25% of cases. It is inherited as an autosomal dominant trait. MTC can be considered as a sporadic form only after a clinical and biological survey of the two parents, siblings and children of the patient, using pentagastrin stimulation test. The authors have studied 36 patients from 26 families. Hereditary MTC with different clinical features, were discovered in two kindreds. The systematic investigation leads to the discovery of 7 cases in the first family, and of 3 in the second. The treatment of the disease at the first stage of its evolution has been possible when an early diagnosis had been made, such as in the second family.

Absence of secondary hyperparathyroidism in most patients with renal hypercalciuria.

We examined parathyroid gland function in 47 patients with idiopathic hypercalciuria in an effort to determine whether serum levels of parathyroid hormone (PTH) and/or urinary excretion of cyclic adenosine monophosphate (cyclic AMP) can discriminate between the various forms of hypercalciuria. Although we could separate our 47 patients into two groups, 21 patients with renal hypercalciuria (RH) and 15 patients with absorptive hypercalciuria (AH), there remained a group of 11 patients who did not exactly correspond to either group. Basal serum PTH was normal in the two groups: for RH, 10.32 +/- 0.93; for AH, 11.43 +/- 1.10 microliter Eq/ml. Similarly, urinary cyclic AMP did not differ between the two groups: for RH, 4.88 +/- 0.5; for AH, 4.87 +/- 0.55 nmoles/dl/min GFR. Moreover, the response of the parathyroid glands to acute hypocalcemia produced by intravenous infusion of EDTA was not different among patients with AH, RH, and control subjects. Only one patient showed a marked increase of serum PTH in response to acute hypocalcemia, and the bone biopsy revealed increased osteoclastic resorption. In conclusion, our data show that serum levels of PTH and urinary cyclic AMP do not differentiate between the various forms of idiopathic hypercalciuria. The EDTA test demonstrated that secondary hyperparathyroidism is very uncommon in these patients.

Immunohistochemical and immunoelectron-microscopic study of pituitary adenomas associated with Cushing's disease. A report of 13 cases.

Thirteen pituitary adenomas were removed from patients with Cushing's disease by the transphenoidal route. All cases demonstrated a typical histochemical and ultrastructural pattern. Immunocytochemical study by means of the immunoperoxidase technique and light or electron microscopy demonstrated 1-24/1-39 adrenocorticotropic hormone (ACTH) in all cases, lipotropin/melanotropin (beta-LPH/beta-MSH) in 10 cases, beta-endorphin in 8 cases, and an absence of calcitonin in all cases. In addition, in 2 cases tumor tissue contained a few antiprolactin immunoreactive cells. These ACTH, beta-LPH, and beta-endorphin immunoreactivities may reflect either the peptides themselves or their precursors or intermediate products. The authors also suggest a possible intermediate-lobe-like processing of beta-LPH leading to beta-endorphin production, which may act on PRL cells. In addition, no positive arguments for the existence of a common precursor for calcitonin and ACTH could be provided from this study.

Re-examination of human calcitonin radioimmunoassay.

Evaluations of human immunoreactive calcitonin (IRCT) assay have been extensively reviewed. Labelled hormone was re-purified on carboxymethyl-cellulose in order to isolate a fraction containing mainly monoiodinated calcitonin, which was found to be very stable. Two antisera with different immunochemical characteristics were used for incubation studies, one of which was incubated with unextracted and extracted plasma samples. The sensitivity of the assays was 60 pg/ml plasma. However, marked differences were observed in the results obtained by the three methods depending on the importance of the inhibitory effect of plasma on the binding of the tracer to antibodies. However, the absolute plasma IRCT level could not be related to the presence of calcitonin M, except in one case. Further studies are needed in order to ascertain the origin and the significance of the immunoreactive material which was detected in normal plasma by one antiserum.

[Hypoparathyroidism in adults (author's transl)]. / L'insuffisance parathyroïdienne de l'adulte.

The authors studied the clinical characteristics of primary and post-operative hypoparathyroidism in 39 patients. Laboratory follow-up data were compared under two different treatment programs using either AT 10 or 25 Hydroxycholecalciferol (25 OHCC). Clinical analysis revealed the atypical characteristics of primary hypoparathyroidism. From a therapeutic standpoint, AT 10 and 25 OHCC were equally effective in provoking a return to normal plasma calcium levels, except in complex cases of vitamin D resistance. 25 OHCC proved much easier to manipulate than at 10 and offered a higher security with respect tothe risk of hypercalcemia. The biological activity of 25 OHCC seems to differ from that of AT 10, especially regarding phosphorus metabolism.

Ultrastructure, biological study and culture of C-cell carcinoma of the thyroid gland.

The ultra-structural of a C-cell carcinoma of the thyroid confirms previous data: the cells are slender, with a large nucleus. The Golgi apparatus is well developed. Granules in striking abundance are seen in every part of the cytoplasm: their diameter is 85 - 250 mmu.