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J P Luton

Publications and source records attributed to J P Luton.

At least 19 recordsLinked to original sources
PubMed1992

[Cushing syndrome during pregnancy. New diagnostic methods used in 3 cases of adrenal cortex carcinoma].

Cushing's syndrome during pregnancy is most often caused by an adrenal cortical tumour; it is a rare event which bears poor foetal and maternal prognoses. We report 3 cases of adrenal cortex carcinoma diagnosed during pregnancy (after 24, 27 and 28 weeks respectively of amenorrhea) and revealed by local tumoral signs in 2 cases and by pulmonary embolism in the third. Because hair growth was moderate and weight gain as well as high blood pressure had mistakenly been attributed to the pregnant state, these clinical features of hypercortisolism has only lately been related to tumoral secretion. The hypercortisolic state was firmly established by comparing the patients' urinary cortisol levels (677, 941 and 2,167 micrograms/day) and 20-hour salivary cortisol levels (9.9, 15 and 25.3 micrograms/ml) with values obtained in women at the same stage (88 +/- 11.4 micrograms/day and 2.31 +/- 0.25 micrograms/ml). The aetiological diagnosis was made by the finding of a highly increased salivary testosterone levels (50, 34 and 95 pg/ml; normal = 8.6 +/- 4 pg/ml), and by magnetic resonance imaging which showed unilateral adrenal masses of 3, 8 and 20 cm in diameter respectively. These 3 cases illustrate the difficulty of the clinical diagnosis of hypercortisolism during pregnancy. Assessment of the unbound steroids and magnetic resonance imaging are the most useful methods for an early diagnosis, thus preventing the severe complications which may otherwise reveal this rare pathological condition.

Adrenal Cortex Neoplasms↗
PubMed1992

[Bilateral adrenal tumoral formation. Regressive spontaneous evolution].

A case of bilateral adrenal tumoral formation associated with Addison's disease is reported, and the possible cause of this association is discussed. The short-term deleterious course of metastatic malignancies, hemopathies or severe infections when left without specific treatment, and the long-term course of our patient's tumoral pathology excluded these diagnoses. The spontaneous regression of a bilateral pseudotumoral mass was suggestive of 2 causes: haematoma or tuberculosis. Haematoma was unlikely in the absence of causal factors, and this, combined with the slow regression of the adrenals, made tuberculosis the most probable diagnosis. The few similar cases found in the literature are reviewed.

Addison Disease↗
PubMed1992

Expression of the neuroendocrine cell marker 7B2 in human ACTH secreting tumours.

OBJECTIVE AND DESIGN: Pro-opiomelanocortin gene expression is a ubiquitous phenomenon which takes place not only in the pituitary but also in many normal and tumoral non-pituitary tissues. However, the clinical features of the ectopic ACTH syndrome are rarely encountered. To further investigate this problem we examined series of normal human pituitaries and endocrine tumours evaluating the tissue content of pro-opiomelanocortin peptides, and the state of neuroendocrine differentiation as indicated by the biochemical marker 7B2. PATIENTS AND MEASUREMENTS: Tissue concentration of 7B2, pro-opiomelanocortin products (joining peptide and beta-endorphin) were measured in 13 pituitary corticotrophic adenomas and 13 non-pituitary tumours associated with the ectopic ACTH syndrome (five out of 20 bronchial carcinoid tumours, two out of 19 phaeochromocytomas, one out of 11 medullary thyroid carcinomas, three pancreatic and two thymic carcinoid tumours). Molecular weight forms of immunoreactive 7B2 and 7B2 RNA messenger were determined using Western and Northern blot analysis respectively. RESULTS: In all tissues examined, concentrations of immunoreactive beta-endorphin (fmol/mg tissue wet weight) showed widely distributed values from less than 0.7 to 1,340,000, which were correlated (r = 0.975, P less than 0.01) with that of immunoreactive joining peptide, another pro-opiomelanocortin fragment. In the 13 non-pituitary tumours associated with the ectopic ACTH syndrome, immunoreactive beta-endorphin concentrations ranged from 8.6 to 548,000, whereas in normal and tumoral pituitaries they varied from 16,600 to 364,800, and 5000 to 1,340,000, respectively. Immunoreactive 7B2 was detected in 67 of 68 neuroendocrine tumours. Tissue concentrations (fmol/mg tissue wet weight) of immunoreactive 7B2 varied from 135 to 1787 in pituitary tumours; from less than 0.5 to 555 in bronchial carcinoids; from 21.7 to 793 in phaeochromocytomas; from less than 1.6 to 948 in medullary thyroid carcinomas. Western blot analysis showed a predominant molecular weight form of immunoreactive 7B2 at 22 kDa. Northern blot analysis of RNA extracted from ACTH secreting pituitary and non-pituitary tumours showed a predominant signal hybridizing at 1.5 kb with a 7B2 probe. CONCLUSION: These results show that all ACTH secreting tumours have biochemical markers for neuroendocrine differentiation. Tissue concentrations of pro-opiomelanocortin peptides are variable, being extremely high in the most benign tumours and low in those with an aggressive growing pattern, and are not correlated with the biochemical neuroendocrine markers.

ACTH Syndrome, Ectopic↗
PubMed1992

Monoclonality of corticotroph macroadenomas in Cushing's disease.

The pathophysiological mechanism of pituitary ACTH oversecretion in Cushing's disease remains unclear. The question of whether a collection of corticotroph cells is a primary pituitary event or is driven by increased production of hypothalamic corticotropin releasing factor is still debated. Establishing whether or not there is a clonal nature of such pituitary lesions has important conceptual and practical implications. Clonal composition of corticotroph cell adenomas was determined by X chromosome inactivation analysis using a DNA probe, M27 beta, which detects a multiallelic polymorphism in 90% of females. A first digestion by PstI reveals the polymorphism. A second digestion by MspI or its methylation sensitive isoschizomer HpaII, distinguishes the active from the inactive copy. DNA was extracted from 11 corticotroph macroadenomas responsible for Cushing's disease or Nelson's syndrome. Eight of the 11 female patients were heterozygous for the locus and included in the study. Blood leukocytes were available for 5 females and were used as controls. All 8 tumors demonstrated a monoclonal pattern while the 5 leukocyte DNA were polyclonal. Ours results show that a somatic modification plays an important role in the pathogenesis of corticotroph macroadenomas allowing monoclonal expansion of a genetically aberrant cell.

Adenoma↗
PubMed1992

Cushing's syndrome and pregnancy: aetiologies and prognosis in twenty-two patients.

OBJECTIVE: The association of an active Cushing's syndrome and pregnancy is a rare event which raises specific diagnostic difficulties and bears poor maternal and foetal prognoses. We report our series of 22 patients. PATIENTS: Age range was 19-34 (mean +/- SEM = 27.3 +/- 1.5) the onset of hypercorticism occurred before the pregnancy (n = 2), during the pregnancy (n = 15) or in the early post-partum (n = 5). The diagnosis was made during the pregnancy of 4 patients and in the post-partum of 18. RESULTS: Cushing's syndrome was revealed by the local manifestations of an adrenocortical tumour in 3 patients and by the clinical features of hypercorticism in 19 patients: mainly morphological changes (n = 19), high blood pressure (n = 12), and/or accelerated hair growth (n = 7). Aetiological distribution was noteworthy by the unusual predominance of primary adrenocortical tumours (n = 16) especially adrenocortical carcinomas (n = 8). Cushing's disease was present in only 4 patients and in 2 an ectopic ACTH secretion was observed. This association implied a high rate of complications for the mother: high blood pressure (n = 12), diabetes (n = 3), preeclampsy (n = 3) and pulmonary embolism (n = 1) and for the infant: prematurity (n = 16), hypotrophy (n = 4), adrenal insufficiency (n = 1), virilization (n = 1), stillbirth (n = 1). During their pregnancy 18 patients had a symptomatic treatment while only 4 patients (3 with adrenocortical carcinoma and one with an ACTH-secreting phaeochromocytoma) had a unilateral adrenalectomy. CONCLUSION: This condition is difficult to recognize: the diagnosis of Cushing's syndrome may be obscured by normal hormonal modifications of the pregnant state; it also forbears particular severity because of maternal and foetal complications, the unusual prevalence of malignant tumours and the particular difficulty in curing or merely controlling the hypercorticism.

Adrenal Cortex Neoplasms↗
PubMed1992

[Pheochromocytoma, first manifestation of Von Hippel-Lindau disease: a possibility to be considered].

Von Hippel-Lindau (VHL) disorder is an autosomal dominant disease characterized by the almost constant development of hemangioblastomas in the central nervous system (cerebellum, spinal cord and retina). In addition, various types of tumors including renal cell carcinomas, pancreatic cysts and pheochromocytomas are frequently observed in VHL gene carriers. Linkage of the VHL locus to the RAF-1 oncogene on the short arm of chromosome 3 (3p25-26) has been recently reported. Pheochromocytoma is of particular interest because of the risk of inaugural malignant hypertensive crisis but especially because of a great degree of interfamily variability (from 0 to 92% of affected members in previously reported large kindreds). We have studied a French series of 25 pheochromocytoma (11 males, 14 females) in VHL affected patients. Twenty pheochromocytoma (80%) occurred in a familial context, whereas 5 (20%) were consistent with "apparent sporadic cases". The mean age at pheochromocytoma diagnosis was 27 years (5-55 years). Bilateral tumours have been documented in 13 cases (52%). The prevalence of pheochromocytoma revealing VHL was 14 out 25 (56%). In these cases, VHL diagnosis was considered up to 25 years later. In 6 cases (2 deceased) pheochromocytoma was the only manifestation of VHL. Thus, search for VHL must be systematic in the presence of pheochromocytoma, in the interest of the patients themselves and of potential at-risk family members (prevention of hypertensive crisis linked to latent tumours). Basic check-up (neurological and somatic examination, ophthalmoscopy, familial inquiry) may be completed with cerebral CT scan or MRI and abdominal ultrasonography followed, if positive or doubtful, by abdominal MRI or selective angiography.

Adolescent↗
PubMed1991

[Bilateral Leydig cell tumor of the ovary in a woman with congenital adrenal hyperplasia. The first reported case].

A 26-year-old woman with congenital adrenal hyperplasia (CAH) due to 11 hydroxylase deficiency complained of infertility. Clinical examination disclosed no evolutive virilizing features. Basal serum levels of delta 4 androstenedione and testosterone, under hydrocortisone suppressive therapy, where elevated at 4.72 and 2.84 ng/ml respectively (N: 1.2 to 2.2 and 0.2 to 0.6) leading to the discovery of a right ovarian tumor. Post-operative evaluation (8 months later) revealed dexamethasone-sensitive hyperandrogenism and a coincidental large left ovarian tumor. Three months after the second surgical procedure, the patient became pregnant and gave birth to a non-virilized girl. At microscopic examination both tumors were typical Leydig cell tumors of the ovary containing crystals of Reinke. This is the first case of bilateral and macroscopic Leydig cell tumor ot the ovary in a woman with congenital adrenal hyperplasia. Relationships between hilus cell tumors and steroid cell tumors of the adrenocortical type are discussed.

Adrenal Hyperplasia, Congenital↗
PubMed1991

Proopiomelanocortin gene expression in normal and tumoral human lung.

Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation.

Carcinoid Tumor↗
PubMed1990

[Nodular adrenomegalies in congenital adrenal hyperplasia in adults. Implications].

The presence of adrenal nodules in patients with congenital adrenal hyperplasia seems to be relatively frequent but is seldom reported. We observed such nodular formations in 3 women and 2 men aged from 19 to 71 years. Four patients had enzyme deficiency revealed in childhood (3 were deficient in 21-hydroxylase and 1 in 11-hydroxylase); the fifth patient had a virilizing form of an unrecognized 21-hydroxylase deficiency. In 3 patients the nodular formations had a diameter of 10 millimetres or less. In the other 2 patients the diameter was greater than 30 millimetres, and an adrenocortical adenoma was found at surgery. In one case a preoperative increase of medical treatment resulted in partial regression of the nodules. Our findings show that young subjects may have adrenal nodules, and their dependence on ACTH is discussed. We also discuss the possible influence of these nodules on the difficulty of medical treatment, the need for a life-long therapy and the necessity to look for a congenital adrenal hyperplasia when confronted with an "incidentaloma".

Adenoma↗
PubMed1990

Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy.

Adrenocortical carcinoma is a rare tumor, and only limited information is available about its natural history and the effects of therapy. We studied 105 patients (75 female and 30 male; mean age, 46 years) with adrenocortical carcinoma who were referred to us between 1963 and 1987. The average duration of symptoms before diagnosis was 8.7 months. At the time of diagnosis, 68 percent of the patients had endocrine symptoms, and 30 percent had distant metastases. Hormonal studies showed that 79 percent of the tumors were functional. Eighty patients underwent surgery, and 59 also received the adrenal cytotoxic agent mitotane. The median disease-free interval after surgery was 12.1 months (range, 1 to 175). Tumor dissemination occurred in 82 percent of the patients, most commonly to the lung, liver, and adjacent organs. The median survival time was 14.5 months (range, less than 1 to 175), and the five-year survival was 22 percent. Age over 40 years and the presence of metastases at the time of diagnosis were the only factors recognized as indicating a poor prognosis. Mitotane controlled hormonal secretion in 75 percent of the patients. Eight mitotane-treated patients had partial tumor regression, but the drug did not have a significant effect on survival. We conclude that adrenocortical carcinoma carries a poor prognosis. Mitotane therapy may offer transient benefits, particularly in controlling endocrine symptoms.

Adrenal Cortex Hormones↗
PubMed1990

Pituitary-like proopiomelanocortin transcripts in human Leydig cell tumors.

Proopiomelanocortin is a polypeptide precursor molecule, the processing of which generates ACTH, beta-endorphin, the beta- and gamma-lipotropins, the joining peptide, and the NH2-terminal fragment. Anterior pituitary corticotrophs are the major site of proopiomelanocortin gene expression in man and the predominant, if not sole source of circulating ACTH. Recent data have established that proopiomelanocortin gene expression also occurs in various normal nonpituitary tissues, one of the best studied being the testis. In this latter organ the dominant gene products are short transcripts of approximately 800 nucleotides, which lack the first two exons of the gene and cannot encode a complete proopiomelanocortin molecule. In this report we show that the mode of proopiomelanocortin gene expression is occasionally modified in human Leydig cell tumors: a 1,200-nucleotide mRNA species identical to that in the pituitary is produced. It results from the usual (pituitary) start site of transcription and thus can encode the complete proopiomelanocortin molecule. In two out of six tumors, large amounts of the 1,200-nucleotide transcript led to a dramatic increase of approximately 1,000-fold in proopiomelanocortin peptide concentrations as compared with the normal and peritumoral testis. Proopiomelanocortin processing in these tumors generates various peptide fragments including ACTH. These results may help to understand the mechanism of proopiomelanocortin expression in nonpituitary tumors and have implications for the more general phenomenon of ectopic hormone secretion.

Blotting, Northern↗
PubMed1990

[Ovarian tumors located in the hilus. Analysis of 126 publications of the literature].

One hundred and twenty six reported cases of ovarian tumors located in the hilus (OTLH) are analyzed. They represent a special sub group of ovarian steroid cell tumors (former "lipid cell tumors"). A number of these neoplasms are Leydig-Berger cell tumors (LBCT), which are characterized by the presence of the crystal of Reinke, a specific proteinaceous inclusion, whose detection may be improved by new available methods. Crystal-free steroid cell tumors located in the hilus are in most cases true leydigoma of the ovary whose features are indiscernible from LBCT's. They are revealed after years of evolution by signs of hyperandrogeny or post menopausal bleeding. Plasma testosterone levels are always elevated while urinary 17 keto steroid cytoplasmic values are normal in 50% of cases. Three main features distinguish ovarian tumors located in the hilus from others ovarian steroid cell tumors: the occurrence in aged women, the small size of the tumors, and the excellent prognosis.

Adolescent↗
PubMed1989

[Polyendocrinopathy combined with primary pulmonary arterial hypertension].

We report the case of a woman who had premature menopause, adrenal insufficiency and hypothyroidism by peripheral gland lesion, all most probably due to an autoimmune disorder, and who subsequently developed primary pulmonary arterial hypertension. The causes of this hypertension are ill-defined, but an autoimmune origin has often been envisaged since primary pulmonary arterial hypertension is not unfrequently associated with connective tissue diseases. Its association with an autoimmune polyendocrinopathy has only been reported, to our knowledge, on four occasions; in all 4 cases the thyroid gland was involved, and a connective tissue disease was present in 3 of them. Our case, which includes adrenal insufficiency and premature menopause is, as far as we know, unique. The possible link between these various diseases is their autoimmune nature, in which case primary pulmonary arterial hypertension would belong to the category of organ-specific autoimmune diseases. Our case supports the hypothesis that a number of isolated primary pulmonary arterial hypertensions could be of autoimmune origin.

Autoimmune Diseases↗
PubMed1989

[Primary hyperaldosteronism caused by unilateral macronodular hyperplasia].

A case or primary hyperaldosteronism due to unilateral macronodular adrenal hyperplasia is presented. This entity is exceptional: a review of the literature has yielded only three similar cases. The significance of these adrenal nodules is discussed; in particular, they are compared with the nodules found in hypertensive subjects. Their course after surgery is similar to that of Conn's adenoma.

Adrenal Gland Diseases↗
PubMed1989

Comparative assessment of ACTH and lipotropin plasma levels in the diagnosis and follow-up of patients with Cushing's syndrome: a study of 210 cases.

PURPOSE: A series of 210 patients with Cushing's syndrome was evaluated at a single center to assess the relative values of adrenocorticotropic hormone (ACTH) and lipotropin (LPH) plasma levels in the etiologic diagnosis of Cushing's syndrome and in the follow-up of treated Cushing's diseases. PATIENTS AND METHODS: These patients included 149 patients with Cushing's diseases, 20 with adrenal tumors, and 41 with ectopic ACTH/LPH syndromes. Hormone levels were measured before therapy and during the follow-up of treated Cushing's diseases. RESULTS: ACTH and LPH plasma levels were moderately elevated in Cushing's diseases, low or undetectable in adrenal tumors, and highly elevated in ectopic ACTH/LPH syndromes, but the overlap between the three etiologic groups was less for LPH than for ACTH. LPH appeared to be as sensitive as ACTH in evaluating the outcome of trans-sphenoidal surgery and in detecting the occurrence of Nelson's syndrome after bilateral adrenalectomy. CONCLUSION: Therefore, plasma LPH determinations provide a better index than ACTH measurements, probably for technical reasons as well as because of the greater stability of LPH in blood.

ACTH Syndrome, Ectopic↗