Computerised intrapartum diagnosis of fetal hypoxia based on fetal heart rate monitoring and fetal pulse oximetry recordings utilising wavelet analysis and neural networks.

OBJECTIVE: To develop a computerised system that will assist the early diagnosis of fetal hypoxia and to investigate the relationship between the fetal heart rate variability and the fetal pulse oximetry recordings. DESIGN: Retrospective off-line analysis of cardiotocogram and FSpO2 recordings. SETTING: The Maternity Unit of the 2nd Department of Obstetrics and Gynaecology, Aretaieion Hospital, University of Athens. POPULATION: Sixty-one women of more than 37 weeks of gestation were monitored throughout labour. METHODS: Multiresolution wavelet analysis was applied in each 10-minute period of second stage of labour focussing on long term variability changes in different frequency ranges and statistical analysis was performed in the associated 10-minute FSpO2 recordings. Self-organising map neural network was used to categorise the different 10-minute fetal heart rate patterns and the associated 10-minute FSpO2 recordings. MAIN OUTCOME MEASURES: Umbilical artery pH of < or = 7.20 and Apgar score at 5 minutes of < or = 7 formed the inclusion criteria of the risk group. RESULTS: After using k-means clustering algorithm, the two-dimensional output layer of the self-organising map neural network was divided into three distinct clusters. All the cases that mapped in cluster 3 belonged in the risk group except one. The sensitivity of the system was 83.3% and the specificity 97.9% for the detection of risk group cases. CONCLUSIONS: A relationship between the fetal heart rate variability in different frequency ranges and the time in which FSpO2 is less than 30% was noticed. Fetal pulse oximetry seems to be an important additional source of information. Computerised analysis of the fetal heart rate monitoring and pulse oximetry recordings is a promising technique in objective intrapartum diagnosis of fetal hypoxia. Further evaluation of this technique is mandatory to evaluate its efficacy and reliability in interpreting fetal heart rate recordings.

Mucin-like carcinoma-associated antigen (MCA) during normal pregnancy.

OBJECTIVE: To assess the usefulness of Mucin-like carcinoma-associated antigen (MCA) in monitoring pregnant patients with breast cancer. STUDY DESIGN: Maternal serum (MS) and amniotic fluid (AF) antigen values were measured by an enzyme immunoassay in 30 pregnant women during the second trimester, in 28 during the third and in 26 at parturition. Sera only from 26 women in the first trimester and from 26 healthy, non-pregnant women (controls) were also analyzed. RESULTS: Maternal serum MCA concentrations increased significantly with gestational age (p<0.0001). The frequency of elevated serum values was 5% in the first, 35% in the second and 100% in the third trimester and at parturition. Antigen values in AF were markedly higher than those in MS (p<0.0001) and increased also significantly with advancing gestation (p<0.0001). A strong correlation was observed between MS and AF antigen values (r=0.77, p<0.0001). Maternal serum values at parturition were dependent on the mode of delivery, being higher in the cases who delivered vaginally, compared to those delivered by elective caesarean section (p<0.006). CONCLUSION: Our data suggest that pregnancy affects significantly maternal serum MCA. Consequently, MCA seems to be a non-reliable marker in monitoring pregnant patients.

[Pituitary metastases. 3 cases]. / Les métastases hypophysaires. 3 observations.

OBJECTIVE: Review cases with hyothalamo-hypophyseal metastases which raise complex therapeutic situations. PATIENTS AND METHODS: Files of patients hospitalized from 1992 to 1996 at the Cochin Hospital Endocrinology unit were compared with data reported in the literature. RESULTS: We had patients with pituitary metastases from breast cancer and 69 cases have been reported in the literature: 72 patients, 57% men and 43% women, mean age 57.2 +/- 12.3 years. The primary tumor was identified in 58.3% of the cases. The primary cancer was unknown and revealed by the pituitary metastasis in 41.7% of the cases. The primary tumor was a breast cancer in 31.9% of the cases, and lung cancer in 30.5%. The main clinical signs were vision disorders (40.3%) and diabetes insipisus (29.1%). The principal differential diagnosis was hypophyseal adenoma. Short term prognosis was not good. DISCUSSION: These data are in agreement with the older literature excepting the high prevalence of primary cancers revealed by pituitary metastasis, probably a result of progress in hypophyseal exploration techniques. CONCLUSION: The prevalence of pituitary metastasis will continue to increase with longer survival in cancer patients. Metastasis should thus be entertained as a possibility in patients with a hypothalamo-hypophyseal tumor, particularly after the age of 59, in order to hasten diagnosis and provide early treatment.

[Hepatic ischemia and hypophyseal macroadenoma]. / Ischémie hépatique et adénome macro-hypophysaire.

We report the first case of recurrent hepatitis secondary to a pituitary macroadenoma in a 55-year old man. Liver ischemia is thought to be the main consequence of episodes of acute adrenal insufficiency. Sudden acute adrenal insufficiency was due to enlargement of the sella content secondary to several microhemorrhages in the macroadenoma.

[POEMS syndrome with primary adrenocortical insufficiency]. / Syndrome de POEMS avec insuffisance surrénalienne primaire.

BACKGROUND: POEMS syndrome is a multisystem disorder. It usually presents as severe polyneuropathy and monoclonal gammapathy associated with endocrinopathies, organomegaly, skin hyperpigmentation. CASE REPORT: A patient with POEMS syndrome developed primary adrenocortical deficiency revelated by asthenia and hyperpigmentation. Hydrocortisone replacement therapy produced a rapidly beneficial effect on asthenia and hyperpigmentation. DISCUSSION: Although asthenia and skin pigmentation are common in POEMS syndrome, adrenocortical deficiency is seldom reported. This endocrinopathy might be underestimated in POEMS patients. We suggest systematic screening with a rapid ACTH test in all POEMS patients in order to detect underlying adrenal deficiency.

[Diabetes insipidus with a hypothalamo-hypophyseal morphologic anomaly during a pregnancy]. / Diabète insipide avec anomalie morphologique hypothalamo-hypophysaire au cours d'une grossesse.

BACKGROUND: Diabetes insipidus is uncommon in pregnancy. Despite physiological modifications in hydroelectrolytic balance during normal pregnancy, the capacity of the kidney to concentrate urine is preserved, partially due to lower vasopressin secretion. CASE REPORT: A young woman developed diabetes insipidus during the third trimester of normal pregnancy. The disease regressed totally after delivery. However, magnetic resonance imaging revealed a persistent expansive intrasellar image with a high-intensity signal. DISCUSSION: Onset of diabetes insipidus is usually rapidly progressive in pregnancy. Occurring generally during the third trimester in normal pregnancies, diabetes insipidus is generally well tolerated and responds to dDAVP, usually without pituitary abnormally, and regresses after delivery. Two types are distinguished: partially latent diabetes insipidus occurring during pregnancy and due to a central rather than nephrogenic origin; and excessive vasopressinase activity leading to diabetes insipidus usually associated with liver anomalies and high frequency of pre-eclampsia. During normal pregnancy, the size of the anterior pituitary increases and the normal high-intensity signal in the posterior pituitary seen on MRI usually regresses or disappears. In diabetes insipidus, the posterior pituitary hypersignal image generally disappears, reflecting reduced vasopressin storage. Few observations of diabetes insipidus occurring during pregnancy have been reported with morphological explorations. Most have described a "normal" aspect of the pituitary, specifically in the post partum period. In our patient, the weak vasopressin response to the end of water restriction at post partum when the diabetes insipidus symptoms had disappeared would suggest partial central diabetes insipidus revealed by pregnancy. Other pathologies involving this region could also be involved due to the unusual and persistent sellar image, with an expansive process showing a high intensity signal on MRI. An asymptomatic craniopharyngioma cyst was hypothesized and would be more compatible with the observed symptoms.

[Failure of synthcen to diagnose corticotropin insufficiency]. / Pièges de l'épreuve au synacthène immédiat dans l'insuffisance corticotrope.

It is commonly believed that a normal cortisol response to exogenous ACTH (synacthen test) reliably indicates, with the exception of states of acute ACTH deprivation, the integrity of hypothalamic-pituitary-adrenocortical function. Published evidence has shown that the synacthen test is not sensitive enough to reveal partial ACTH deficiency leading to a subnormal ACTH response to stress. We report a patient who maintained a normal response to exogenous ACTH stimulation despite symptomatic chronic ACTH deficiency in unstressed conditions. A normal cortisol response in the synacthen test does not therefore exclude the possibility of clinically relevant ACTH deficiency.

[Thyroid hormone production and its regulation]. / Hormonogenèse thyroïdienne et sa régulation.

Thyroid gland fulfills two functions. On one hand, it synthesizes and builds up stocks of thyroid hormones in thyroglobulin molecules of the colloid in its follicles, such as they can maintain the hormonal secretion during several days and even weeks. To do this, it captures and concentrates plasma iodide through a specific membrane transporter and it oxidizes iodide through the action of thyroperoxidase and H2O2. This makes it able to bind to tyrosine residus of thyroglobulin. Then, the iodotyrosines can form the thyroid hormones (T4 and T3) by a coupling reaction. On the other hand, thyroid secretes the hormones after internalization and proteolysis of thyroglobulin. All the steps of synthesis and secretion are regulated by pituitary TSH, through a negative feed-back action of T4 and T3. Thus, any increase or decrease of circulating thyroid hormones induces the opposite modification of TSH. In addition, an important fraction of plasma and tissue T3 is produced through the extrathyroidal monodeiodination of T4 by enzymes (5' deiodases) which are regulated by the nutritional status and by thyroid hormones.

[Medical treatment of secretory hypophyseal adenomas]. / Traitement médical des adénomes hypophysaires sécrétants.

The main indication for medical treatment of the secretory pituitary adenomas is macroprolactinoma. In this case, bromocriptine therapy obtains better results than surgery, by a life-long administration. New dopaminergic drugs with better tolerance and a longer half-life than bromocriptine will probably improve compliance to treatment. Besides, somatostatin analogs, especially the slowly-released preparations, administrated once or twice per month, often obtain normalization of hormonal production in GH (growth hormone) or TSH (thyrotropin) secreting adenomas after surgical failure and are used in complement to radiotherapy.

[Assay of salivary cortisol. An interesting method for exploring the adrenal cortex]. / Le dosage du cortisol salivaire. Une méthode intéressante d'exploration de la corticosurrénale.

AN INTERESTING METHOD FOR PATIENTS AND PHYSICIANS: Measurement of salivary cortisol has not modified the investigation of hospitalized patients but offers very original possibilities for exploring outpatients. REPEAT MEASUREMENTS AND STIMULATION TESTS: As for serum cortisol levels, repeat measurements or stimulation tests are required for reliable evaluation of salivary cortisol. SEVERAL APPLICATIONS: Salivary cortisol level can be an appropriate tool in screening for adrenal insufficiency, using the short ACTH injection test, evaluating hypercorticism through the circadian cycle of cortisol and overnight dexamethasone suppression test either at the physician's office or in the patient's home. In addition, long-term follow-up is possible for outpatients investigated or treated for Cushing's syndrome.

[Magnetic resonance imaging in Cushing disease. Prediction of surgical results]. / Imagerie par résonance magnétique dans la maladie de Cushing. Prédiction des résultats opératoires.

OBJECTIVES: The purpose of the study is to determine if pituitary Magnetic Resonance Imaging (MRI) can predict the outcome of transsphenoidal surgery in patients with Cushing's disease. METHODS: Fifty four patients were divided in three groups according to MRI findings: those with a well circumscribed focal lesion clearly separated from the cavernous sinus (group 1, n = 24), those with adenomas in close contact with the cavernous sinus (group 2, n = 18), and those with no identified lesion (group 3, n = 12). RESULTS: The adenoma is found on the predicted side in 97,6% of the cases with positive MRI. A histologically proven adenoma is found in 96, 100 and 33% of the cases in groups 1, 2 and 3, with successful outcome in 91, 94 and 58% of the patients respectively. In group 2, surgery failed in a patient in whom tumoral tissue surrounded the internal carotid artery, but succeeded in two other cases in whom a MRI involvement of the cavernous sinus was suspected. CONCLUSION: We confirm the excellent localization value of MRI. Failure due to cavernous sinus involvement can be predicted only when MRI shows that the adenomatous tissue surrounds the carotid artery. In cases of negative MRI, the outcome is less favorable.

[Differentiated thyroid carcinomas manifesting as toxic adenoma]. / Carcinomes thyroïdiens différenciés se manifestant comme un adénome toxique.

BACKGROUND: Hot thyroid nodules are generally benign. We report two exceptional cases of thyroid carcinomas mimicking toxic adenomas. CASE REPORTS: A 35-year-old man and a 55-year-old woman had thyroid carcinoma behaving as an autonomously hyperfunctioning nodule. DISCUSSION: Only twenty similar cases have been reported in the literature. While a hot nodule on radio-iodine scan is unlikely to be malignant, the possibility of carcinoma should not be overlooked. Surgery should therefore be the preferred treatment of toxic adenoma.

[Lymphocytic hypophysitis: a reality]. / Hypophysite lymphocytaire: une réalité.

Lymphocytic hypophysitis is a rare entity; we report here three cases. This condition usually occurs in women during pregnancy or in the post-partum period. Pituitary enlargement is associated with complete or partial hypopituitarism. The difficulty in diagnosis is well illustrated by our cases and results from the similarity between the clinical and biological signs of adenoma and hypophysitis. Circulating antipituitary antibodies are not constantly found and are nonspecific, evidence only of the autoimmune nature of hypophysitis. Thus the diagnosis has to be undertaken in all suspected cases in pregnant women or during the post-partum period. The clinical course may be very long, emphasizing the need for rigorous long-term observation. The pituitary gland is commonly enlarged and homogenous in lymphocytic hypophysitis, but in our third case the enlargement was heterogeneous with associated cyst formation. We suggest that the inflammatory process could have been maintained by the presence of cysts. Finally, corticosteroids are the therapy of choice in the inflammatory stage and should be undertaken as soon as the diagnosis has been established. Regular surveillance is required.

Overnight dexamethasone suppression test: comparison of plasma and salivary cortisol measurement for the screening of Cushing's syndrome.

The overnight 1-mg dexamethasone suppression test is a very good screening test for subjects suspected of having Cushing's syndrome. To simplify the procedure, we evaluated the 1-mg dexamethasone suppression test with measurement of salivary cortisol. We performed this test with plasma and salivary cortisol measurements in 27 patients with Cushing's syndrome and 64 normal controls. The sensitivity and specificity of plasma cortisol measurements were 100% and 87%, respectively, for a cut-off point of 100 nmol/l, in accordance with previous studies. The results of salivary cortisol showed the absence of overlap between the two groups, with a sensitivity and specificity of 100% for a cut-off point of 2.8 nmol/l. On a larger series, however, one might occasionally miss the diagnosis of a patient with Cushing's syndrome. Therefore, we favor a cut-off point of 1.9 nmol/l, the sensitivity remaining at 100% and the specificity being 94%. In conclusion we recommend the overnight dexamethasone suppression test with measurement of salivary cortisol as a screening test for Cushing's syndrome.

[Riedel's thyroiditis and lymphoma. Diagnostic difficulties]. / Thyroïdite de Riedel et lymphome. Difficultés diagnostiques.

Two cases of Riedel's thyroiditis demonstrated the difficulties encountered in diagnosis. In the first case, subtotal thyroidectomy was performed due to compressive goiter. The intraoperative macroscopic aspect suggested Riedel's thyroiditis. The pathology report also discussed the diagnosis, despite a major lymphoid component, as dense fibrosis had multilated the thyroid parenchyma. Subsequent clinical course led to the diagnosis of lymphoma. The clinical presentation in the second case was classical with rapid increase in size of a hard thyroid gland. Histology was however atypical showing calcifications and liquid cysts within the fibrous thyroid tissue. The initial signs of Riedel's thyroiditis, a very rare disease, usually suggest neoplasia: ligneous compressive goiter with deep adherences. Histologically, there is invasive fibrous thyroiditis with highly suggestive occlusive phlebitis in certain cases. The origin of the disease remains obscure. The differential diagnosis between a sclerosing form and lymphoma is particularly important for therapeutic management.

Long-distance and long-term follow-up of a patient with intermittent Cushing's disease by salivary cortisol measurements.

Salivary cortisol is an excellent indicator of the plasma free cortisol concentration in normal and pathological situations. We took advantage of its ease of sampling, allowing multiple collections at home, to follow the course of a patient with Cushing's disease living in North Africa. This 48-year-old woman presented with a clinically moderate hypercortisolism caused by a large basophilic pituitary adenoma. Bilateral extension to the cavernous sinuses precluded surgical therapy. She went into spontaneous remission based on clinical signs as well as biochemical findings. During the following 2 years she demonstrated intermittent relapses that were treated by radiotherapy (50 Gy), followed by ketoconazole and then o-paraprime-dichloro-diphenyl-dichloroethane (Op'DDD). After a prolonged clinical remission, Cushing's syndrome again became active. Bromocriptine was started without effect and a new treatment with Op'DDD was began. Evaluation and follow-up were performed during hospitalizations and mainly through the measurements of salivary cortisol in more than 100 samples sent from North Africa by air mail to our department in Paris. Thus we were able to demonstrate intermittent overproduction of cortisol before any treatment, with periods of normal and even low values, and to follow the efficacy of therapy and to detect the relapses. We conclude that measurement of salivary cortisol is a valuable tool in difficult clinical situations such as intermittent hypercortisolism and remoteness between the patient and hospital.

ADP and ATP activate distinct signaling pathways in human promonocytic U-937 cells differentiated with 1,25-dihydroxy-vitamin D3.

We investigated the effects of purinergic P2 agonists on cell adhesion, as well as the signaling pathways involved, in U-937 human promonocytic cells differentiated to a more mature monocytic phenotype with 1,25-(OH)2-vitamin D3. In cell adhesion studies, ATP was more potent than ADP, whereas ADP showed greater efficacy. The time course of the intracellular calcium concentration ([Ca2+]i) response to ATP was biphasic (a spike followed by a plateau), whereas ADP evoked a plateau after a time lag of several seconds. The spike [Ca2+]i response evoked by ATP was due to both myo-inositol-1,4,5-trisphosphate-induced Ca2+ mobilization and influx, whereas the ADP effect was Ca2+ influx dependent. Moreover, ADP and ATP activated distinct Ca2+ influx mechanisms, as shown by Mn2+ quenching of the fura-2 signal, which was slow and long-lasting for ADP but rapid for ATP. Treatment with phorbol dibutyrate shifted the EC50 of the [Ca2+]i spike response to the right and abolished the plateau response. Accordingly, phorbol dibutyrate inhibited the ADP-evoked response but only partly inhibited the ATP-evoked Ca2+ influx. cAMP-raising agents had no effect on the [Ca2+]i spike or on Ca2+ influx but delayed or transiently inhibited the plateau phase. The plateau response thus appears to be independent of the spike response, because it can be directly evoked by ADP and undergoes distinct regulation. This suggests that ADP and ATP activate U-937 cells through distinct signaling pathways, probably involving specific receptors.