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Biomedical subjects

A Tabarin

Publications and source records attributed to A Tabarin.

At least 73 records · Page 4Linked to original sources
PubMed1992

Results of long-term continuous subcutaneous octreotide administration in 14 patients with medullary thyroid carcinoma.

OBJECTIVE: Treatment by octreotide has been suggested in medullary thyroid carcinoma patients with post-surgery metastases. The purpose of this study was to evaluate if the tumoral regression could be improved by a high dose and by prolonged octreotide treatment. DESIGN: Fourteen thyroidectomized patients were studied. All patients had persistently elevated plasma calcitonin levels with normal or elevated carcino-embryonic antigen levels. Five hundred micrograms/day of octreotide were administered by continuous subcutaneous infusion for 90 days. MEASUREMENTS: Plasma calcitonin and carcino-embryonic antigen levels were determined at days -30, -20, -2, -1, 0, +30, +60, +90, +120; morphological extension was evaluated every month. RESULTS: Continuous infusion of octreotide did not induce any significant decrease of calcitonin levels, or any morphological improvement, and had no major undesirable effect. However, in 4/14 patients calcitonin levels fell during treatment (-43, -50, -15, -20%), and in 9 patients calcitonin increased (+22 to +130%) after cessation of therapy. CONCLUSION: Biological or morphological parameters of medullary thyroid carcinoma are not significantly improved in a large series of patients treated by octreotide.

Adult↗
PubMed1992

Comparative value of plasma ACTH and beta-endorphin measurement with three different commercial kits for the etiological diagnosis of ACTH-dependent Cushing's syndrome.

Recent reports suggest that, contrary to radioimmunoassays (RIA), immunoradiometric assays (IRMA) artifactually decrease plasma ACTH levels in patients with the ectopic ACTH syndrome. Discrepancies between RIA and IRMA results may provide a means of discriminating this entity from Cushing's disease. We have compared the results of these two techniques, together with those of a beta-endorphin assay, in 17 patients with Cushing's disease, 9 with the ectopic ACTH syndrome and 30 controls. ACTH-RIA and ACTH-IRMA levels in patients with Cushing's disease were similar (17.5 +/- 2.5 vs 15.1 +/- 2.8 pmol/l) and were correlated (rs = 0.59, p less than 0.01). ACTH-RIA levels in patients with the ectopic ACTH syndrome were higher than ACTH-IRMA levels (27.3 +/- 2.9 vs 14.5 +/- 2.5, p less than 0.01) and these did not correlate. The ACTH-RIA and ACTH-RIA/ACTH-IRMA ratio levels in patients with the ectopic ACTH syndrome were higher than those of patients with Cushing's disease (p less than 0.01), but they overlapped with these in 27 and 31% of cases respectively. Plasma beta-endorphin level was higher in patients with the ectopic ACTH syndrome than in patients with Cushing's disease (81.9 +/- 19.4 vs 26.4 +/- 5.6 pmol/l, p less than 0.01) and was correlated with ACTH only in patients with Cushing's disease. The overlap in beta-endorphin and beta-endorphin/ACTH-IRMA molar ratio levels between the two groups were 19 and 27% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Multihormonal response to corticotropin-releasing hormone in inferior petrosal sinus blood of one patient with Cushing's disease: comparison with in vitro secretion of the tumoral corticotropes.

A multihormonal response to CRH during inferior petrosal sinus sampling in patients with Cushing's disease has recently been described. Whether it reflects multihormonal secretion by the corticotropic adenoma, or secretion by non-tumorous adjacent cells via paracrine mechanisms remains debatable. We have compared the effect of CRH on ACTH, GH, PRL and TSH secretion during inferior petrosal sinus sampling with its effect on the in vitro secretion of the corticotropic adenoma after excision in one case of Cushing's disease. Before CRH injection in vivo results show significant central-peripheral gradients for all hormones but only ACTH lateralized to the side of the tumor. After CRH administration, the petrosal concentrations of all hormones increased preferentially on the side of the adenoma resulting in significant intersinus gradients: 8.1 for ACTH, 2.0 for GH, 1.8 for PRL and 1.5 for TSH. In vitro results: the adenoma cells were immunostainable for ACTH only. In culture, they secreted ACTH only. Addition of CRH to the culture induced a mean increase of 160% in ACTH secretion but GH, PRL and TSH remained undetectable. Our results favor the hypothesis that the multihormonal response to CRH seen during inferior petrosal sinus sampling in Cushing's disease reflects a paracrine stimulation of the adjacent non-tumorous pituitary cells by the corticotropic adenoma.

Adenoma↗
PubMed1992

[Biological and developmental aspects of macronodular adrenal hyperplasia in Cushing's disease].

The pathophysiology of macronodular adrenocortical hyperplasia (MNH) associated with Cushing's diseases remains debatable. Some authors have claimed that MNH represents an autonomous condition that has to be treated by surgical adrenalectomy while others advocate the use of pituitary surgery. We have compared the biochemical features, before and after pituitary surgery, between 7 cases of MHN and 22 cases of diffuse hyperplasia (DH) associated with Cushing's disease. In addition, the diameter of the adrenal nodules after surgery was evaluated in 6 cases. The mean ACTH level in MNH and DH subjects was similar. Dexamethasone suppressibility and the stimulatory effect of metyrapone on ACTH secretion were less in MNH than in DH subjects, suggesting a greater degree of adrenal autonomy in the former. The cortisol responses to metyrapone and CRF tests suggested an increased responsiveness of the adrenals to endogenous ACTH in the MNH group. Only one MNH patient had biochemical features suggesting a primary adrenal disease. The use of a sensitive ACTH assay and the results of inferior petrosal sinus sampling identified the ACTH-dependency of the disease. A short to medium term remission of the disease was obtained in all cases of MNH and in 87% of cases of DH after surgery. The diameter of the adrenal nodules significantly decreased in only 43% of cases. Our results suggest that the adrenal autonomy in MNH is incomplete and that, despite the persistence of the adrenocortical nodules, the disease can be cured with pituitary microsurgery in most cases.

Adrenal Glands↗
PubMed1991

[Macronodule associated with bilateral adrenal hyperplasia. A rare misleading cause of primary aldosteronism (two cases)].

Aldosterone-producing adrenal adenoma and bilateral hyperplasia are the two predominant subtypes of primary aldosteronism. Their recognition is based essentially on adrenal CT scan and on measurements of plasma aldosterone and 18-hydroxycorticosterone (18-OHB) concentrations in response to postural testing. We report 2 cases of primary aldosteronism associated with a unilateral hyperplastic macronodule resembling an aldosterone-producing adenoma on CT scan. Plasma aldosterone and 18-OHB concentrations were consistent with this diagnosis in one patient. In the light of these two cases and of those previously published, the investigations needed for the etiological diagnosis of primary aldosteronism are discussed.

18-Hydroxycorticosterone↗
PubMed1991

Histiocytosis X of the hypothalamus.

An unusual case of cutaneous and hypothalamic histiocytosis X (HX) is reported. The hypothalamic involvement occurred as a tumor that mimicked a chiasm glioma on computed tomography angioscanning. Magnetic resonance imaging after gadolinium injection localized the tumor within the third ventricle floor. The HX origin of the tumor was confirmed by histological examination of hypothalamic biopsies obtained by transventricular endoscopy. The results of endocrine evaluation were consistent with anterior panhypopituitarism resulting from a multiple releasing-hormone secretory defect, but there was no diabetes insipidus. This unusual endocrine aspect has not been previously described in the field of hypothalamic HX. Lastly, the tumor was insensitive to low dose megavoltage radiation therapy. This unusual case stresses the superiority of magnetic resonance imaging over computed tomography scanning in the assessment of suprasellar tumors and emphasizes the usefulness of transventricular endoscopy in these cases.

Female↗
PubMed1991

Use of ketoconazole in the treatment of Cushing's disease and ectopic ACTH syndrome.

Ketoconazole, an imidazole derivative which inhibits adrenal steroidogenesis, has been used with success for the metabolic control of Cushing's disease. Few data are available about the use of ketoconazole in the management of the ectopic ACTH syndrome. We have used ketoconazole in eight patients: four patients with Cushing's disease, two patients with overt and two with occult ectopic ACTH syndrome. Among patients with Cushing's disease, reversible hypoadrenalism occurred once. All had full clinical and biochemical regression of the disease for more than 6 months with 400-1200 mg ketoconazole per day. Patients with ectopic ACTH syndrome received 1200 mg ketoconazole per day for at least 2 months. Partial biochemical regression was observed in two and a secondary escape to adrenal blockade in two others. These findings further indicate that ketoconazole is a valuable tool for the metabolic control of Cushing's disease. On the contrary, in ectopic ACTH syndrome, this aim can be impossible to reach with ketoconazole although the reasons for its ineffectiveness remain to be determined.

ACTH Syndrome, Ectopic↗
PubMed1991

Spontaneous and corticotropin-releasing factor-induced cytosolic calcium transients in corticotrophs.

Spontaneous and CRF-stimulated changes in the cytosolic free calcium concentration ([Ca2+]i) were studied in two types of corticotrophs: 1) cultured human ACTH-secreting pituitary adenoma cells (hACTH cells), and 2) identified small ovoid corticotrophs cultured from normal rat pituitaries. [Ca2+]i was monitored in individual corticotrophs by dual emission microspectrofluorimetry using indo-1 as the intracellular fluorescent Ca2+ probe. In hACTH cells, [Ca2+]i measurements were carried out in combination with electrophysiological recordings obtained using whole cell patch-clamp techniques. It was shown that a single spontaneous Ca(2+)-dependent action potential led to a marked transient increase in [Ca2+]i in human tumoral corticotrophs. Spontaneous fluctuations in [Ca2+]i were also observed in unpatched corticotrophs whether derived from human pituitary tumors or normal rat tissue. Based on their striking kinetic features and their sensitivity to external Ca2+, we suggest that these spontaneous [Ca2+]i transients were the consequence of action potential firing. Under separate voltage-clamp (patch-clamp) conditions, tumor corticotrophs showed two Ca2+ current components: a low threshold, rapidly inactivating (T-type) current, and a higher threshold, slowly inactivating (L-type) current. The dihydropyridine Ca2+ channel blocker PN 200-110 (100 nM) abolished the L-type current without affecting the T-type current, while the inorganic Ca2+ channel blocker Cd2+ (200 microM) suppressed both Ca2+ currents. The Na+ channel blocker tetrodotoxin (5 microM) did not affect inward currents in tumor corticotrophs. Both L- and T-type voltage-gated Ca2+ channels were involved in controlling [Ca2+]i transients in both tumor and normal corticotrophs, inasmuch as Cd2+ (200 microM) abolished [Ca2+]i) transients, while PN 200-110 (100 nM) greatly diminished, but did not completely abolish, [Ca2+]i transients. The latter did not appear to depend on a voltage-dependent Na+ influx, since they were unaffected by tetrodotoxin (5 microM). Corticotrophs generate [Ca2+]i transients in response to the hypothalamic secretagogue CRF by acting on their membrane excitability. Indeed, we demonstrated in combined fluorescent and electrophysiological experiments that CRF (100 nM) had a coordinate action on human tumoral corticotrophs comprised of a modest depolarization and an increase in the frequency of both action potentials and subsequent [Ca2+]i transients. A coincident increase in the peak amplitude of the [Ca2+]i transient and after hyperpolarization was also observed in some CRF-stimulated cells. CRF (100 nM) evoked qualitatively similar [Ca2+]i patterns in human tumoral and normal rat corticotrophs not subjected to patch-clamping.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease.

Inferior petrosal sinus blood sampling for ACTH measurement (IPSS) is used for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative location of pituitary microadenomas. Intermittent ACTH secretion from pituitary adenomas may result in insignificant differences between petrosal and peripheral ACTH levels at the time of sampling. Thus, pituitary stimulation during IPSS may improve the procedure. The aim of the study was to evaluate the usefulness of CRH injection in combination with IPSS. Twenty-two patients with Cushing's disease (CD; 5 macroadenomas, 16 microadenomas, and 1 corticotroph hyperplasia) and 5 patients with ectopic ACTH syndrome were studied. Bilateral IPSS was successfully carried out on 25 patients. Patients with ectopic ACTH syndrome had, before and after CRH injection, central to peripheral ACTH gradients below 1.7. Four patients with CD had basal gradients below 1.4. After CRH administration all patients with CD had gradients above 3.2. Despite correct location of central catheters, the predicted location of pituitary microadenomas was erroneous in 41% of the cases. It was not improved after CRH injection. In conclusion, the combination of CRH injection with IPSS was useful for the differential diagnosis of ACTH-dependent Cushing's syndrome, as it increased the discrimination of the procedure. On the contrary, it was useless for the preoperative location of pituitary microadenomas, which was poorly predicted by IPSS.

ACTH Syndrome, Ectopic↗
PubMed1991

[Isolated osteoporosis in a case with Cushing's disease: development after treatment].

The unusual case of a 37 year old woman with Cushing's disease in whom the only feature of hypercortisolism was a clinically asymptomatic osteoporosis is presented. After successful treatment of the disease, serial bone biopsy examinations and bone mineral density measurements (BMD) were performed up to 31 months. 27 months after cessation of hypercortisolism, BMD remained unchanged and histomorphometric examination showed no improvement of the osteopenia in addition to focal osteomalacia. Despite 5 months of calcium and vitamin D therapy, BMD did not improve. This case report emphasizes the importance of routine evaluation of adrenal function in unexplained isolated osteoporosis. Long-term follow-up studies, leaded in a large number of patients are necessary to elucidate the course of osteoporosis in Cushing's syndrome and the usefulness of a specific treatment.

Adult↗
PubMed1990

[Value of the corticoliberine test in the etiologic diagnosis of Cushing's syndrome].

Several studies have demonstrated that the corticotropin-releasing factor test (CRF) is useful for the aetiological diagnosis of Cushing's syndrome: in Cushing's disease, as opposed to ectopic ACTH secretion syndrome, the hypothalamus-pituitary-adrenal (HPA) axis can still be stimulated by CRF. In the present study, we compared the CRF test with the reinforced dexamethasone suppression test in 18 patients: 11 with Cushing's disease, 6 with ectopic ACTH secretion and 1 with adrenal gland adenoma. We obtained 2 false-negative results with the CRF test and 1 false-positive result with the dexamethasone suppression test. Our study, together with published data, suggests that the CRF test is useful in the exploration of Cushing's syndromes of uncertain origin. However, the results obtained with this test must be compared with those of other methods used to explore the HPA axis and which are still necessary.

Adolescent↗
PubMed1990

Plasma concentration of atrial natriuretic hormone during endogenous glucocorticoid hypercorticism.

In vitro studies have shown that glucocorticoids may increase atrial natriuretic-hormone (ANH) synthesis and/or release. This action of glucocorticoids has also been suggested in vivo in patients with Cushing's syndrome. However, in this circumstance, plasma AH elevation might be due to humoral disturbances associated with cortisol overproduction. We studied 16 patients with endogenous hypercorticism and 11 of them after successful treatment. Plasma levels of ANH, plasma renin activity (PRA), aldosterone, desoxycorticosterone (DOC), angiotensin II (AII), cortisol, osmolarity, sodium and potassium, urinary free cortisol (UFC), and blood pressure were measured. Before treatment the mean plasma ANH concentration in patients with Cushing's syndrome was significantly higher than in controls (11.3 +/- 2.6 vs. 4.9 +/- 2.3 pmol/l; p less than 0.001). ANH was correlated with cortisol and UFC (r = 0.715, r = 0.700; p less than 0.05). There was no significant correlation between plasma ANH, PRA, aldosterone, DOC, AII, osmolarity, sodium or blood pressure. After recovery, ANH concentration decreased in all patients and was not different from that of normal subjects (4.9 +/- 2.3 vs. 4.3 +/- 2.6 pmol/l). These results suggest that in Cushing's syndrome, ANH secretion is mainly dependent on the severity of hypercortisolism and independent of the other associated disturbances that we studied.

ACTH Syndrome, Ectopic↗
PubMed1990

The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: a comparison with the lysine-vasopressin test.

The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.

Adolescent↗
PubMed1990

[Efficacy and long-term tolerance of ketoconazole in the treatment of Cushing's disease].

Successful short term treatment of patients with Cushing's disease by Ketoconazole without adverse effects is now well established. Little data are available about prolonged treatment of this disease with ketoconazole. We report herein our experience of ketoconazole therapy in four patients with Cushing's disease treated for 9 to 38 months. One patient rapidly developed adrenal hypofunction and required transient steroid therapy adjunction. In the other patients, cortisol overproduction was reduced to normal levels within two months and their urinary free cortisol remained within the normal range throughout the study. In two patients ketoconazole dose could be decreased but had to be increased after ten months of therapy in one patient. None of the patients had clinical or biochemical signs of drug toxicity. Thus, ketoconazole seems to be a useful drug for the prolonged metabolic control of Cushing's disease. However, in this circumstance, ketoconazole daily dose adaptation can be necessary in order to maintain normal urinary cortisol levels and the ability of ketoconazole to cure Cushing's disease still remains to be determined.

Adrenocorticotropic Hormone↗
PubMed1989

[Value of the CRF test in primary and secondary adrenal insufficiency].

The ACTH and cortisol responses after CRF administration were studied in 21 patients with adrenal failure and compared with those obtained in 15 control subjects. In patients with Addison's disease, cortisol and ACTH responses were respectively abolished or excessive. In patients with secondary adrenal failure, a unique bolus injection of CRF allows the differentiation between pituitary or hypothalamic secretory defect. With regard to previous reports, the usefulness of CRF test in primary and secondary adrenal failure is stressed.

Addison Disease↗