Biomedical subjects
Publications and source records attributed to G Sassolas.
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Nine somatotropic adenomas identified by histological and immunocytochemical methods were studied in vitro during 40 days. The spontaneous release of GH decreased at various rates according to adenomas. A decrease in the size, number of secretory granules and in immunoreactivity with anti-hGH serum were also noted. When cortisol was added (350 nM), the GH secretion sustained for a longer time or even increased at its initial level. The effect of GRF (hpGRF1-44NH2, 10(-8)M) on GH release was tested by 3 hours incubation at 6-9 days of culture. The increase in GH varied from 106 to 420% compared to the basal release. It was similar to in vivo release in 3 out of 6 cases. The highest responses were found in densely granulated and strongly immunoreactive adenomas. The effect of GRF on the GH synthesis was studied by continuous incubation of GRF (10(-8)M) from the 10th the 40th day of culture. The quantity of GH in the culture medium was never higher than in culture mediums without GRF. No change in GH concentrations in mediums with or without cortisol was found when TRH (2.5, 10(-6)M) or TRH + GRF was added. No change in morphological and immunocytochemical cell characteristics were noted either with or without GRF. Thus, the variability of GH response to GRF in somatotropic adenomas in culture seems to be related to their morphofunctional heterogeneity. Under our experimental conditions, GRF stimulates the release of stored GH in tumoral cells but does not seem to stimulate its synthesis.
The authors have developed an indirect immunofluorescence technique for histochemical detection of thyroglobulin and have tested it on 66 tissue sections. Fluorescence reflecting the presence of thyroglobulin was elicited in 57 samples of differentiated thyroid tissue, including healthy or hyperfunctional tissue and primary or metastatic papillary or follicular carcinomas. Thyroglobulin was found to be distributed heterogeneously between different areas and different cells. It may occupy the whole cell, the apex, the colloid substance and sometimes extracellular spaces. No fluorescence was present in non-thyroid tissues. This technique could be applied mainly to the diagnosis of thyroid carcinomas, where 25 metastases have been examined by this method, and to clear cell carcinomas. In these two cases, thyroglobulin appeared to be a good marker of tumoral tissue.
This report describes the histologic, immunocytochemical, and ultrastructural study of a multihormonal carcinoid tumor of the pancreas, secreting a growth hormone releasing factor (GRF) which provoked acromegaly. The patient presented a nonfamilial multiple endocrine neoplasia, type 1. The absence of radiologic signs of a pituitary adenoma in conjunction with elevated plasma levels of pancreatic polypeptide, glucagon, somatostatin, as well as growth hormone (GH), led to the discovery of the tumor. Its surgical excision produced a rapid disappearance of most of the clinical and biologic disorders. No immunoreactive GH was found in the tumor using radioimmunoassay and immunocytochemistry. In contrast, three peptides with GH-releasing activity were extracted and characterized. Immunocytochemistry showed that the GRF-reactive cells, together with rare somatostatin-storing cells, made up areas which demonstrated a medullary pattern of growth with extracellular amyloid deposits. Under electron microscopic examination, actively secreting cells were observed which carried endocrine granules of 100 to 150 nm in diameter. The other regions of the tumor presented a different type of growth and were composed of pancreatic polypeptide-, glucagon-, or somatostatin-reacting cells. Cells immunostained with antisera raised against beta-endorphin were also noted. These data suggest that GRF may be a new biologic marker for pancreatic endocrine tumors.
The temporal organization of plasma melatonin, cortisol, growth hormone (GH) and prolactin secretion was examined in healthy rested controls and in patients suffering from episodic cluster headache. Eleven patients with typical cluster headache (10 men, 1 female) and 8 male controls were studied over a 24-h period: blood was collected at 2-h intervals during the day and at 1-h intervals at night. Plasma melatonin, cortisol, GH and prolactin levels were determined by radioimmunoassay. Most of the cluster headache patients showed a decrease in nocturnal melatonin secretion and the melatonin rhythm was even completely abolished in one patient. Chronobiological analysis of the cluster headache patients' 24-h plasma melatonin profile showed a significant decrease in amplitude and mesor: these were 58.7 pg/ml and 34.4 pg/ml respectively in control subjects, versus 18.7 pg/ml and 17.6 pg/ml for the patients. In addition, patients showed a significant phase-advance in their melatonin rhythm. For cortisol, the rhythm appeared slightly blunted in the cluster headache group and was significantly phase-advanced. The plasma prolactin profile showed no significant alteration, but for plasma GH the nocturnal peak was advanced in some patients; in the absence of sleep recording, however, no conclusion could be drawn. Results from this study suggest a neuroendocrine dysregulation in cluster headache in the endogenous clock which controls the pineal rhythmicity.
A beta-endorphin (beta END)-containing pituitary adenoma was demonstrated by immunocytochemical, biochemical, and ultrastructural methods in a 43-yr-old man who had impotence, slight testicular atrophy, and an enlarged sella turcica (grade II0), but no manifestations of Cushing's disease. Preoperative hormone data revealed hyperprolactinemia (97 ng/ml), low plasma cortisol levels without circadian rhythm, undetectable plasma ACTH, and normal plasma FSH and LH levels, with an impaired response to LRH. After hypophysectomy, these hormone levels normalized and responded normally to dynamic tests. Immunocytochemically, 30% of the tumor cells reacted only with beta END antiserum. beta END immunoreactivity was the only component revealed by RIA and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A characteristic ultrastructural aspect is also described. These findings demonstrate dissociation in the secretion of the proopiomelanocortin-derived peptides and suggest a relationship between hyperprolactinemia and tumor secretion of beta END.
Synthetic human pancreatic tumor GH-releasing hormone (hpGRH 1-44-NH2) was given by iv bolus injection to 10 normal men at doses of 75, 150, 300, and 600 micrograms. At all doses the plasma GH responses were similar in an individual subject. Among subjects, however, the responses were significantly different, with peak GH concentrations ranging between 9.0 micrograms/liter and 54.9 micrograms/liter. The GH released in response to GRH was bioactive in the Nb2 lymphoma cell multiplication assay. The circulating GH 30 and 60 min after GRH was detected in 3 molecular forms corresponding to little, big, and big-big GH. These forms averaged 50%, 30%, and 20% of the total immunoreactive GH, respectively. The mean rise of plasma somatomedin-C, from 1.86 U/ml to 2.21 U/ml 24 h after GRH, was not statistically significant. A small but statistically significant GRH dose-dependent rise in plasma PRL (mean PRL concentrations 10 min after 600 micrograms GRH, 11.13 micrograms/liter occurred consistently after GRH injection. The evidence that the GH released by GRH is bioactive supports the potential use of GRH for therapeutic applications.
The temporal organization of plasma melatonin and cortisol secretion was examined in healthy rested controls and in depressed patients: 11 patients suffering from a primary affective disorder (10 female, 1 male) and 8 male controls were studied over a 24-hr period; blood was collected at 2-hr intervals during the day at 1-hr intervals at night. Plasma melatonin and cortisol levels were determined by radioimmunoassay. In addition, melatonin was determined in plasma sampled at 3 AM in older male controls (n = 8) and in females (n = 10) at ovulation. The controls showed low or undetectable (less than 5 pg/ml) diurnal plasma melatonin levels and a very marked nocturnal rhythm (acrophase: 2.27 AM, mesor: 34.4 pg/ml, amplitude: 58.7 pg/ml). For the three control groups, no significant difference was observed in the nocturnal melatonin peak at 3 AM. The depressed patients also showed a significant melatonin rhythm but with lower amplitude (14.5 pg/ml) and mesor (19.1 pg/ml). The latter rhythm was not significantly phase-advanced with respect to the controls (acrophase at 1.18 and 2.34 AM, respectively). In 9 of the 11 patients, nocturnal melatonin secretion was less marked and frequently associated with hypercortisolemia. An additional episodic melatonin secretion was observed in the late afternoon in only two patients. In depressed patients, there was an increase in the mean cortisol secretion level (mesor at 13.6 micrograms/100 ml against 9.1 micrograms/100 ml in the controls), but the amplitude and the acrophase were not significantly modified. These data are discussed in terms of both the hypothalamus-pituitary-adrenal-epiphysis and aminergic abnormalities.
No case of cardiac tamponade due to subacute pericarditis in the course of Grave's disease has yet been reported. From the 2 cases presented here it would appear that the association is mere coincidence, the clinical manifestations of the pericarditis being probably aggravated by the hyperthyroidism which facilitates the development of oedema and serous effusions.
Somatocrinin (hp-GRF-44), a growth hormone releasing factor, stimulates acute pituitary response in a 11 years and 4 months old boy, with growth hormone deficiency. The capability of the anterior pituitary to secrete growth hormone in response to an IV injection of somatocrinin (120 micrograms 4 micrograms/kg) was documented, therefore proving the hypothalamic origin of the deficit which had been suspected because of association of diabetes insipidus and hyperprolactinemia.
Intravenous injection of four doses (75, 150, 300, 600 micrograms) of synthetic somatocrinin (GRF 44) greatly increases serum growth hormone concentrations in ten adult normal men in contrast to placebo. Mean peak values were identical. Plasma GH released under GRF stimulation was able to stimulate proliferation of NB2 cells.
In exceptional cases, acromegaly develops as the clinical expression of an ectopic secretion of Growth Hormone (GH) or Growth Hormone-Releasing Factor (GRF), tumorous in origin. In the present report, we describe an instance of acromegaly caused by the secretion of GRF from a voluminous pancreatic tumor. The resection of this tumor resulted in a temporary disappearance of the biological and clinical symptoms of acromegaly, which then reappeared in conjunction with a rise in plasma GRF. From this pancreatic tumor, substances displaying a potent GRF activity were isolated and characterized. Amino acid analyses revealed that they were related to 3 peptides containing respectively 44, 40 and 37 aminoacids. The largest (hp GRF (1-44)-NH2) referred as hp GRF or somatocrinin is considered to be the primary molecule. The pancreatic tumor was multisecreting as proved by high plasma levels of somatostatin, pancreatic polypeptide and glucagon, normalized after the tumor removal, taken together with the immunocytochemical demonstration of the presence of these peptides in the tissue and with the isolation of somatostatin. In contrast hypercalcemia associated with an elevated plasma level of IR-PTH was unmodified by tumor removal. Diagnosis of acromegaly as ectopic endocrine syndrome will probably be facilitated by plasma GRF radioimmunoassay, as a result of production of anti synthetic GRF antibodies.
Among 230 surgically removed pituitary adenomas, eight tumours showing immunostaining gonadotropic cells and elevated intratumours gonadotropin concentrations have been detected (frequency: 3.5 per cent.). By light microscopy the tumours were composed of agranular cells and generally PAS negative cytoplasm. The immunofluorescence technique revealed the presence of immunoreactive FSH (beta-subunit) alone in two cases, of both FSH and LH in six cases with immunoreactive beta endorphin in two of them. By electron microscopy, the cells contained an often dilated moderately or well developed rough endoplasmic reticulum, secretory granules measuring 150 nm to 200 nm which varied in electron density, and numerous microtubules. Basal plasma FSH and LH levels were simultaneously elevated in two cases; FSH levels alone were elevated in two cases; in three cases, both FSH and LH plasma values were normal. FSH and LH intratumour concentrations were simultaneously elevated in five cases; FSH alone was elevated in two cases. In all cases, the concentrations of the other hormones were negligible, except in two cases where beta endorphin concentration was elevated. The comparison of the immunocytochemical findings, the hormonal plasma levels and intratumour concentrations showed a good relationship between the immunoreactivity of the tumour and the intratumour RIA. The gonadotropic adenoma is uncommon but not rare. Its diagnosis is possible if immunocytochemical techniques are applied.
Three cases of adult males with spastic paraparesis and adrenal insufficiency are reported. The adrenal insufficiency is primary and in one case associated with Leydig cell insufficiency. Ultrastructural examination of peripheral nerve revealed abnormal cytoplasmic inclusions in Schwann cells. A decrease in the percentage of linoleate to total fatty acids was found in the sera. A child with adrenoleucodystrophy and an adult with adreno myeloneuropathy were observed in the same family. It allows adrenomyeloneuropathy to be considered as an adult form of adrenoleucodystrophy.
The changes in the levels of plasma prolactin, progesterone and oestradiol were studied in 20 women during labour and immediately after delivery. The study of these levels shows that there is a mechanism for inhibiting the galactopoietic action of prolactin. Lifting this inhibition allows the milk to come in. This inhibition is probably due to circulating steroids, but this study does not allow us to differentiate clearly between the respective roles of oestradiol and progesterone, chiefly because of their short half-life.
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An intravenous injection of synthetic LHRH (50mug) was given in 10 patients with prolactin secreting pituitary adenomas. Variations in circulating levels of gonadotrophic hormones were measured by radioimmunological estimation. The increase in blood level of luteinizing hormone was constant, low in three cases, normal in 3 and high in 4. An increase in follicle stimulating hormone (FSH) was absent in only two cases. The data obtained indicates the absence of any characteristic value of the LHRH test in the aetiological diagnosis of amenorrhoea/galactorrhoea syndromes. They represent an argument in favour of the relative character and of the functional nature of the gonadotrophic insufficiency of prolactin adenomas.
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