The thyroid hormone secretory pathway--current dogmas and alternative hypotheses.
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Animals↗
Biomedical subjects
R Mornex
Publications and source records attributed to R Mornex.
Measurement of plasma methoxyamines for the diagnosis of pheochromocytoma.
Urinary methoxyamine determination is considered as the most sensitive and specific parameter for the diagnosis of pheochromocytoma. Since blood sampling is easier to perform, we developed a new HPLC method to assay metanephrine (MN) and normetanephrine (NMN) in plasma. We now report the results for total (free and conjugated) MN and NMN in 22 cases of pheochromocytoma compared to 26 healthy subjects, 33 patients with essential hypertension, 14 with miscellaneous diseases and 4 patients with renal failure. The mean normal values (mean +/- SD) were 0.40 +/- 0.10 ng/ml for MN and 0.85 +/- 0.25 ng/ml for NMN. The sum of MN+NMN was 1.25 +/- 0.28 and the range 0.9-1.9. In essential hypertension, the range of NMN+MN was 1.2-6.0. In the 4 renal failures, both MN and NMN were drastically increased. In 49 samples drawn from 22 pheochromocytomas, MN was elevated over the hypertensive range in 34 samples and NMN in 47 samples. The total MN+NMN ranged from 6.2 to 436 ng/ml; this figure was observed whatever the clinical presentation even in silent tumors or in paroxysmal forms between the crisis. After tumor removal, the values dropped rapidly. In conclusion, plasma determination of MN and NMN provides a highly sensitive and specific biological pointer for the diagnosis of pheochromocytoma in patients without renal failure.
Adrenal Gland Neoplasms↗
Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma.
The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months. Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases. The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed in 9 patients (60%). No complete remission of the disease was observed. Seven patients died during the study, among whom 4 never responded to the treatment. Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months. Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months. All patients with a hormonal response had objective improvement in clinical status and blood pressure. There was no clear-cut relationship between the cumulative dose and the responses. The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued. This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.
3-Iodobenzylguanidine↗
Lipolytic and ketogenic fluxes in human hyperthyroidism.
The effect of hyperthyroidism on lipolytic and ketogenic fluxes was determined by measuring simultaneously (stable isotope methodology) glycerol, nonesterified fatty acids (NEFA), and ketone body (KB) kinetics in euthyroid and hyperthyroid subjects. In the postabsorptive state hyperthyroid patients had normal concentrations of insulin and glucagon, but increased concentrations (P less than 0.01) and turnover rates (P less than 0.01) of glycerol, NEFA, and KB. The ratio of NEFA appearance rate to glycerol appearance rate was decreased in hyperthyroid subjects (2.34 +/- 0.23 vs. 3.15 +/- 0.22; P less than 0.05), indicating that intracellular cycling between triglycerides and fatty acids was increased. The percentage of NEFA flux used for KB production, calculated from NEFA disappearance rates and KB appearance rates, was increased in hyperthyroid patients (21.20 +/- 2.75% vs. 13.37 +/- 0.63%; P less than 0.05), suggesting a diversion during hyperthyroidism of hepatic fatty acid metabolism toward ketogenesis. However, when the plasma NEFA levels of control subjects were raised by the infusion of a triglyceride emulsion to levels comparable to those observed in hyperthyroid patients their percentage of NEFA flux used for ketogenesis rose to values slightly higher (26.30%) than those of hyperthyroid subjects. In conclusion, 1) hyperthyroidism results not only in increased lipolysis, but also in enhanced triglyceride-fatty acid cycling, which could contribute to the excessive energy expenditure; and 2) the increased KB production of hyperthyroid patients results more from an increase in NEFA availability than from a direct stimulation of hepatic ketogenesis.
Adult↗
[New techniques for investigation of human nutrition].
Accurate determination of energy requirement and nutrients metabolism is essential to improve physiological knowledge and for physiopathological purpose in human nutrition. This evaluation is an absolute necessity for food industry. Energy expenditure could be precisely determined by indirect calorimetry or doubly labeled water technic. Nutrients metabolism (kinetics?) and substrates turn-over studies are now accessible without health hazard using tracers labelled with stable isotopes. These three methods are the basic tools for the new Research Nutrition Center which are now in progress.
Calorimetry, Indirect↗
[Localization of pheochromocytomas by 131-I-meta-iodobenzylguanidine scintigraphy].
Scintigraphy using 131I-labeled meta-iodobenzylguanidine was performed in 89 patients. A diagnosis of pheochromocytoma was indicated by urinalysis in 28 cases and confirmed histologically in the 27 patients who underwent surgery. The tumor was located using scintigraphy and computed tomography. Fourteen isolated and 6 malignant metastatic pheochromocytomas were found as well as 8 pheochromocytomas associated with genetic disease. Scintigraphy located the tumors in 22 out of 28 cases; however, 3 adrenal pheochromocytomas and 3 malignant pheochromocytomas were not detected. Radioisotope perfusion scanning was more sensitive than computed tomography for the detection of bilateral adrenal pheochromocytoma. In the only case of a multifocal tumor, a combination of scintigraphy and computed tomography located all pheochromocytomas which were later resected. The high number of patients without elevated urine catecholamines and in whom scintigraphy did not alter the diagnosis shows that his technique should be applied only after demonstration of catecholamine hypersection.
3-Iodobenzylguanidine↗
[Hyperthyroidism and glucose metabolism].
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Blood Glucose↗
Use of a new gas chromatograph isotope ratio mass spectrometer to trace exogenous 13C labelled glucose at a very low level of enrichment in man.
The use of 13C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low 13C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in 13C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-13C] glucose as tracer and analysed by this new method was found to be 10.4 +/- 0.7 mg.kg-1.min-1, a value 21% lower than that found using D-[6,6-2H2] glucose as tracer (13.1 +/- 1.1 mg.kg-1.min-1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 2H2] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g.kg.-1,1 g.kg.-1) labelled with 0.1% D-[U-13C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97 +/- 0.04 g.kg.-1 and 1.2 +/- 0.04 g.kg.-1, exogenous glucose appearance was 0.51 +/- 0.02 g.kg.-1 and 0.84 +/- 0.04 g.kg.-1, endogenous glucose production was 0.44 +/- 0.04 g.kg.-1 and 0.35 +/- 0.06 g.kg.-1 after the 0.5 and 1 g.kg.-1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Association of cutaneous myxoma, recurrent cardiac myxoma and Cushing's syndrome (Carney's complex). Description of a case and review of the literature].
The authors report the case of a rare clinical syndrome which has recently been called Carney's complex or "myxomas, spotty pigmentation and endocrine overactivity". Three components of this complex are described: cutaneous myxomas, Cushing's syndrome of unpredictable evolution treated by bilateral adrenalectomy for multiple adrenal adenoma and left atrial myxoma which recurred twice. The authors review the literature and discuss the practical implications of this new syndrome which may be familial. The role of echocardiography, the key investigation for the detection of the myxoma and follow-up of these patients who have a high risk of recurrence, is underlined.
Adrenal Glands↗
Normal brainstem auditory evoked potentials in adult hypothyroidism.
Nervous system dysfunction and hearing loss are part of the clinical picture of hypothyroidism. Several studies on visual evoked potential and two brainstem auditory evoked potential studies have shown abnormalities in this disease that are reversible with treatment. It has been suggested that visual evoked potential and brainstem auditory evoked potential could be useful to evaluate the effects of hypothyroidism on the central nervous system and to monitor the response to treatment. We recorded brainstem auditory evoked potentials in 15 adult hypothyroid patients immediately before treatment. All patients were women, ranging in age from 34 to 82 years. Fourteen also had an audiometric study. In five patients, both tests were repeated 20 to 22 months after treatment. Audiometry showed that hearing loss increased with age, suggesting that hearing loss in these patients could be secondary more to aging than to hypothyroidism. When compared to sex-matched controls of similar ages, our patients showed no statistically significant differences in brainstem auditory evoked potentials before treatment. Brainstem auditory evoked potential values were not modified in the five patients whose tests were repeated after treatment. The normality of these results raises serious objections to the clinical use of brainstem auditory evoked potential for central nervous system evaluation and therapy monitoring in adult hypothyroidism.
Adult↗
[Effects of VIP (vasoactive intestinal peptide) on plasma membrane ATPases from rat enterocytes].
We studied the effect of VIP on the ATPase activities from basolateral membranes prepared from rat enterocytes. Under the standard conditions of assay for membrane ATPases (millimolar ATP concentration) VIP has no effect, neither on the Na, K ATPase activity (ouabain sensitive) nor on the Mg ATPase activity (ouabain insensitive). These results suggest that short-term effects of VIP on ionic permeability and metabolism of enterocytes, are not mediated through modifications of the Na/K ratio by the Na, K ATPase or through modifications of another membrane ATPase activities.
Adenosine Triphosphatases↗
Dawn phenomenon in type 1 (insulin-dependent) diabetic adolescents: influence of nocturnal growth hormone secretion.
In order to reassess the role of growth hormone in the dawn phenomenon, we studied eight C-peptide negative diabetic adolescents, who are likely to exhibit important nocturnal growth hormone surges. The insulin infusion rate necessary to maintain euglycaemia was predetermined in each patient from 22.00 hours to 01.00 hours, and then kept constant until 08.00 hours resulting in stable free insulin levels. Blood glucose rose from 4.3 +/- 0.7 mmol/l at 01.00 hours to 7.1 +/- 1.1 mmol/l at 08.00 hours (p less than 0.01) secondary to an increased hepatic glucose production. All the subjects presented an important growth hormone secretion, ranging from 20 to 66 ng/ml (peak values) and from 3619 to 8621 ng.min.ml-1 (areas under the curve). The insulin infusion rate selected for each patient was positively correlated with the nocturnal growth hormone secretion (area under the curve) (r = 0.87, p less than 0.01). On the other hand, there was no relationship between the nocturnal growth hormone secretion and the magnitude of the early morning blood glucose rise (r = -0.48, p greater than 0.2). We conclude that, in Type 1 (insulin-dependent) diabetic adolescents, the dawn phenomenon exists but is moderate despite important growth hormone surges; the nocturnal growth hormone secretion influences the nocturnal insulin requirements but not the dawn phenomenon itself, if insulinisation is adequate.
Adolescent↗
[Treatment of malignant pheochromocytoma by 131-I-metaiodobenzylguanidine].
Twelve patients (2 with only bone metastases, 3 with only soft tissues metastases and 7 with bone and soft tissues metastases) were treated with 131-I-MIBG (specific activity: 20 mCi/mg), 100 to 200 mCi every 3-6 months. A dosimetric study was carried out before each administration. The follow-up ranged from 6 to 24 months and the number of doses ranged from 1 to 8, with 1.85-9 GBq per administration and a cumulative activity of 1.85-62. 2 GBq according to patients. The cumulative absorbed activity ranged from 850 to 9700 cGy. The following side effects were observed: a bone marrow hypoplasia (1 patient) and a transient increase in catecholamines (3 patients). The treatment was successful in 7 patients (3 with soft tissue metastases, 3 with bone and soft tissue metastases and one with bone metastases). This success consisted in clinical improvement and a decrease greater than 50% of hormonal values in the 7 patients and a decrease greater than 50% of tumoral masses in only 3 patients. No complete remission was obtained at this stage of the study. The disease recurred in 1 patient after a year of partial remission. There was no clear-cut relation between the number of doses and the results. This study shows that 131-I-MIBG can give encouraging though limited results.
3-Iodobenzylguanidine↗
[Diagnostic strategy in acquired diseases of the thyroid].
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Humans↗
[Biological criteria of isolated Graves' ophthalmopathy].
The diagnostic value of biological tests, especially the thyroid stimulating immunoglobulin (TSI) assay, was studied in 29 patients with endocrine Graves' ophthalmopathy without hyperthyroidism. In 21 patients the presence of biological abnormalities (L-T3 suppression test, TRH test, presence of antithyroid antibodies) indicated that the ophthalmopathy was related to Graves' disease. The remaining 8 patients were free of any biological abnormality. The contribution of the TSI assay to the pathophysiological diagnosis of ophthalmopathy is poor. These immunoglobulins were detected in 12 out of 29 cases, but they were associated with the above-mentioned abnormalities in all but 3 of these 12 cases.
Adolescent↗
High voltage orbital radiotherapy and surgical orbital decompression in the management of Graves' ophthalmopathy.
We report on 2 groups of patients with Graves' ophthalmopathy. A group of 21 patients was treated by high voltage (18 MV) orbital radiotherapy combined with mean doses of corticoids. The results were good or excellent in 12 patients (mean score 6.62 before and 4.0 after, soft tissues greater than proptosis greater than extraocular muscle involvement), without any complications from irradiation. Patients undergoing surgery initially presented less severe symptoms, even 7 patients treated after corticoid and/or radiotherapy failure. The results were satisfactory in all patients (mean score 5.1 before and 2.4 after, proptosis greater than soft tissues greater than extraocular muscle involvement). Both methods showed results within 3 months, and they can be combined.
Eye Diseases↗
Postnatal development of TRH and TSH rhythms in the rat.
We previously observed that under a 12-hour light/12-hour dark schedule (lights off at 19.00 h), adult male Sprague-Dawley rats showed a circadian rhythm for serum thyroid-stimulating hormone (TSH) with a zenith near midday. In the present work, the ontogenesis of serum TSH rhythm was determined as well as pituitary TSH variations. In addition, hypothalamic and blood TRH were measured in these rats aged 15, 25, 40 and 70 days when sacrificed. As from the first age studied (15 days), a hypothalamic thyrotropin-releasing hormone (TRH) circadian rhythm was present. The mesor and the amplitude of this hypothalamic TRH rhythm increased while the rats were growing up, in contrast with the decrease observed for these parameters as far as blood TRH circadian rhythm is concerned. The time of the acrophase moved from 17.32 h in the 15-day-old rats to 13.57 h in the 70-day-old rats, being constantly in phase opposition with the blood TRH acrophase. The low amplitude pituitary TSH circadian rhythm detected in the young rat disappeared in the adult while, in contrast, the serum TSH rhythm became consistent to reach the well-characterized circadian midday peak in the 70-day-old rats.
Aging↗
Effect of epinephrine on the relationship between nonesterified fatty acid availability and ketone body production in postabsorptive man: evidence for a hepatic antiketogenic effect of epinephrine.
The effect of epinephrine (EPI) on the transformation of nonesterified fatty acids (NEFA) into ketone bodies (KB) in normal subjects was determined by measuring simultaneously NEFA ([1-13C]palmitic acid) and KB ([3-13C]- or [3,4-13C2]acetoacetate) kinetics at different NEFA levels in the presence of basal (control test) or increased (EPI infusion test) EPI concentrations. During the control test the initial (postabsorptive state) concentrations and turnover rates of NEFA and KB were 476 +/- 47 (+/- SEM) and 4.30 +/- 0.17 mumol kg-1 min-1 (NEFA) and 126 +/- 17 and 2.49 +/- 0.07 mumol kg-1 min-1 (KB). The fraction of NEFA converted into KB was between 11.5-14.6%. Raising NEFA levels to about 650 mumol L-1 (iv infusion of a triglyceride emulsion) resulted in an increase in this fraction to between 26-30.3% (P less than 0.01). When NEFA concentrations were next abruptly raised to high levels (near 3 mmol L-1) by heparin injection this fraction returned to near the initial values (15-19.2%). During the EPI infusion test the initial (postabsorptive) concentrations and turnover rates of NEFA and KB as well as the fraction of NEFA converted into KB (10.5-11.5%) were comparable to the initial values of the control test. Intravenous infusion of EPI (10 ng kg-1 min-1) raised NEFA between 600 and 750 mumol L-1, comparable to values during the triglyceride test, but the fraction of NEFA converted into KB remained between 8.2-12% (P less than 0.05 vs. control test); when NEFA then were raised to even higher values (near 2.5 mmol L-1) by the infusion of a triglyceride emulsion and the injection of heparin, this fraction decreased to between 4-8% (P less than 0.05 vs. initial values of the EPI test and P less than 0.05 vs. the control test). In conclusion, 1) the fraction of NEFA converted into KB appears to depend in part on the NEFA concentration; and 2) the net effect of EPI infusion was to decrease the fraction of NEFA converted into KB.
Absorption↗