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Prolonged pulsatile exogenous GnRH allows differentiation between hypothalamic and pituitary causes of hypogonadotrophic hypogonadism and is able to induce ovulation and pregnancy in most of women with hypothalamic amenorrhea (HA). When compared with human menopausal gonadotropin, GnRH appears to be a more efficient therapy of HA but yields inferior results in chronic anovulatory patients with persistent LH secretion. Pulsatile GnRH following a GnRH-analog suppression represents a new promising treatment of infertile women with polycystic ovarian syndrome. However such a combined therapy is time-consuming and only permits to attempt 3 to 4 stimulated cycles during a year. Therefore the successful preliminary reports need to be confirmed by a further randomized study.

The aim of therapeutic research is to find out an effective medication against the disease without any dangerous toxic action. The delicate problem is that very often the dose of drug confines with toxicity. The solutions are numerous: transformation of supports, change of the introduction route, adaptation of the concentration. It has been realised that, in certain disease, continuous infusion of medication was much more effective than repeated intermittent injections. The general technic of drug contribution by a pump supposed a drug reservoir with sufficient volume to prevent the frequent manipulations, a source of energy assuring the circulation of the drug and a control of the speed of the drug delivery. These attempts are not exceptional in our practice, being very often utilized in the treatment of difficult diabetes by insulin infusion, the thrombosing diseases be heparin infusion, some forms of diffused cancers by specific chemotherapeutic agents, acute polyhormonal insufficiencies... It is also possible to use infusion pumps in intensive cares with administration of antibiotics, of antalgic drugs, in cardiology for the management of atrial fibrillation, atrial and/or ventricular tachycardias, etc. The most common are the portable pumps and the implantable.

Methods for detection and characterization of episodic fluctuations in circulating hormone levels are frequently used for endocrine investigations, related to the physiological importance of the pulsatile nature of hormone secretion in modulating target-cells response. Several sophisticated methods of pulse analysis have been recently developed and validated, aiming to minimize the false-positive and false-negative error rates. The present report mainly devoted to the clinician aims to analyze and discuss the main features of the most widely used methods for pulse detection.

Diabetic cheiroarthropathy (DCA) or pseudosclerodermatous hand of the diabetic is characterized by nonpainful limited extension of the proximal metacarpophalangeal and/or interphalangeal joints with spontaneous flexum of the fingers. The mechanism of lesion formation is poorly known but apparently associates neurogenic, vascular and cutaneous phenomena. Fifteen patients with DCA (9 men, 6 women; range 20-74 years) were studied by capillaroscopy, photoplethysmography and skin biopsy. Eleven had type 1 diabetes and 4 type 2 over periods ranging from 1 to 42 years (mean 19.9 years). Diabetic retinopathy was noted 10/15 times, nephropathy 5/15 times and neuropathy of the lower limbs 13/15 times. All patients had at least one of these abnormalities. In capillaroscopy, "Shoal of fish" features of diabetic microangiopathy were found only 4 times, but minor dystrophy was noted in 12 cases. In digital photoplethysmography, a drop in digital systolic pressure or an increase in pulse time was noted in 5 cases. The Hillestad test was less than or equal to 2 in 8 patients. Histological study showed constant dermal collagenous fibrosis in diseased skin, which was also found in normal skin in 6/13 patients. PAS staining showed a thickening of vascular basal membrane 14/15 times in diseased skin and 11/13 times in normal skin. The relation between DCA and microangiopathy is discussed in terms of collagen metabolism abnormalities observed during diabetes.

Precise recordings of reactive (post-hyperglycaemic) hypoglycaemia were ensured by continuous blood glucose monitoring during oral glucose tolerance tests. The definition of hypoglycaemia was limited to the following criteria: absence of chemical diabetes; fall in blood sugar to less than 30% of the fasting level or to less than 2.50 mmol/l (0.45 g/l); development of clinical signs of hypoglycaemia. An infusion of somatostatin over 4 hours slowed down the initial rise in blood sugar during the first 90 minutes and the rise was prolonged throughout the infusion whatever its duration. The maximum glycaemia reached was 13.3 mmol/l (2.40 g/l) at the 250th minute. Interruption of the infusion led to a rapid fall in blood sugar to a level identical (2.1 and 2.5 mmol/l) with and without somatostatin respectively. Somatostatin infusions, while frankly diabetogenic in certain circumstances, do not prevent reactive hypoglycaemia but rather delay its onset.

The ophtalmic, diabetic and hormonal outcome in 16 patients treated identically for diabetic ophtalmopathy with pituitary radio-gold implants were assessed 1, 2, 5 and 10 years afterwards. Four patients (25%) died in the first 6 years, 3 of them of severe renal insufficiency which developed after pituitary implantation. Of these remaining alive at each assessment visual acuity was either stable or improved in 78%, 58%, 64% and 42% respectively, but at very low levels since at 10 years acuity was 1/10 or less in half the population. Four patients became blind, the remaining eight had a severe proliferative retinopathy with exsudates and haemorrhages but retained useful vision. Haemorrhage and new vessel formation continued to develop with the years following implantation in all patients who at the time had one on either lesion. Cataracts were removed in 6 patients, 3 and 7 years after implantation. The mean insulin requirements of the group fall from 55 to 31 units daily. The fall in growth hormone concentration, occuring in only 45% of cases, does not account for all the improvements observed. Several hormonal deficiencies developed: 2 cases of adrenal insufficiency, 3 of hypothyroïdism and 6 of hypogonadal impotence.

Prolactin-secreting adenoma is probably the most common functional pituitary tumour in type I multiple endocrine neoplasia (MEN I). The authors report on a case of gastrinoma and parathyroid adenoma associated with prolactinoma. The latter tumour was revealed by sudden pituitary apoplexy. The characteristic features of endocrine tumours in MEN 1 are discussed, and the relevant literature is reviewed. Emphasis is placed on the fact that prolactinomas are well tolerated, remain clinically silent for a long time and may be diagnosed only when dramatic symptoms suddenly appear.

We used intravenous synthetic somatostatin to stem severe bleeding from oesophagites and oesophageal ulcer associated with renal failure hyponatremia and mental confusion. The ability of somatostatin to reduce splanchnic blood flow and portal pressure and to inhibit both gastrin release and the pentagastrin-stimulated secretion of gastric acid and pepsin provides its therapeutic use in multiple alimentary bleeding. When patients is considered poor candidate for surgery, somatostatin may prove a particularly valuable alternative to conventional medical treatments. We observed no side effects, with somatostatin, during a 72 h period of treatment. Since cimetidine give rise to mental confusion in ureamia or hyponatremia, somatostatin should be looked upon with particular interest in cases of gastro-intestinal bleeding associated with renal insufficiency.

A case of type III (Arthus') hypersensitivity to insulin which occurred several years after insulin treatment was instituted is described. Its persistence even with highly purified insulins of bovine or porcine origin was suggestive of a direct reaction against insulin itself. The patient had no history of allergy and, contrary to most similar cases published, had not received intermittent insulin therapy. Using stimulation of lymphocyte blastogenesis, the authors were able to demonstrate the presence of specific antigen-mediated hypersensitivity to all insulins tested, including human insulins. The circulating immune complexes did not appear to be pathogenic, since the patient only had minimal retinopathy after 22 years of insulin-dependent diabetes. Human insulin was tolerated and proved effective in controlling both blood glucose levels and skin rashes in response to conventional insulins.

Home blood glucose monitoring is becoming increasingly popular in diabetic patients. The purpose of this work was to determine the accuracy of this technique. We have compared plasma glucose obtained in the laboratory and two reagent strips (Dextrostix and Haemoglukotest 20-800). No differences were found among visually-read values and meter-read values using either Dextrometer, Glukometer, Hypocount or Glucochek. Thus, visually-read strips seem to be sufficient for clinical purposes with best results for HGT. The performances of different meters are similar. Nevertheless must patients favoured the use of a meter because of the apparent "objectivity" of the values. Furthermore, meters provide to patients a better involvement in the management of their disease.

HLA typing has been carried out in 100 caucasions with Graves' disease and compared with 270 healthy controls. 25 HL-A antigens were characterized using a lymphocytotoxicity micro-technique. Analysis of the results reveals an increased incidence of HLA-B8 antigen (35% in patients as compared to 16.3% in controls) with a high degree of statistical significance: p = 0.0002 and corrected p (X 25) = 0.005. We did not observe a clear-cut correlation between the presence of HLA-B8 and different characteristics of the disease: sex, age of onset, familial history, exophtalmia, goiter, severity. The knowledge of the relationships between the HLA B8 gene and several auto-immune diseases is a strong argument in favor of the auto-immune nature of Graves' disease. The association between HLA B8 and Graves' disease could be explained by a close linkage between the second HLA locus and one or several Ir-IrG loci, occupied in predisposed individuals by "predisposing" alleles. In these subjects, an antigenic contact with an exogenous etiological agent would induce a pathological immune response, with production of thyroid stimulating IgG.

Pseudo-hyperkaliemia is a biochemical abnormality suspected when the blood level of K is increased, contrasting with the absence of usual symptoms of hyperkaliemia. The diagnosis is confirmed by the discrepancy between K+ blood levels which are normal if measured immediately after the blood sample is drawn, and increased if the blood sample is incubated at room temperature. In our case, the pseudo-hyperkaliemia is due to the passage of K outside the erythrocytes through increased passive membrane permeability to K. In vivo, this increased passive outflow of K seems to be compensated by an increased active inflow of K dependent on the sodium pump. This explains the absence of true hyperkaliemia and clinical symptoms. In vitro, it seems that the sodium pump is no longer able to ensure this increased activity. Therefore, the abnormality becomes overt, mirrored by a delayed increase in kaliemia.

The authors report one case of saturnism with chronic nephropathy. In a 49 years old Caucasian male, the diagnosis was suggested by the following findings. Two acute abdominal crisis associated with a severe increase in blood pressure and a slight but significant elevation in the lead concentration in blood (1 mg/l) and urine (0,42 and 0,60 mg/24 h). The chronic poisoning was explained by the high lead concentration in the drinking water used by the patient. Despite chronic renal failure, a significant lead urinary chelation was obtained after infusion of Edetate calcium disodium (8 mg/24 h). Although E.D.T.A. keep its value for diagnosis this chelating agent is less effective on lead removal than the peritoneal dialysis (15 mg over a 36 hour-period) which appears to be the most useful method for treatment in case of chronic nephropathy.

Insulin infusions given by portable pumps constitute a recent therapeutic advance in those difficult cases of diabetes mellitus which cannot be stabilized by repeated conventional injections. The different varieties of pumps, catheters and insulins used are described. The intravenous and intraperitoneal routes of administration have given results superior to those of the subcutaneous route. Short-term results are evaluated by change in blood glucose levels, medium-term results by glycosylated haemoglobin levels and various metabolic and hormonal abnormalities, and long-term results mostly by the influence of treatment on degenerative complications of diabetes. The metabolic and infectious incidents and accidents of the method as well as its psychological advantages and drawbacks are discussed.

Nutritional studies conducted in 9 patients suffering from anorexia nervosa showed a marasmus-like pattern with predominant depletion of lean body mass rather than of visceral proteins. In addition, adaptation to insufficient food intake led to a decrease in myofibrillar breakdown, as evidenced by low levels of urinary 3-methylhistidine. Low-flow enteral feeding resulted, within a few weeks, in return to normal of plasma proteins (particularly those with short half-life), while a dramatic increase in urinary 3-methylhistidine suggested acceleration of muscle protein turnover under adequate calorie-protein intake.

Spirometry, blood gases, steady state diffusing lung capacity for carbon monoxyde, ductance for carbon monoxyde were determined in 27 obeses. In 13 of them we also measured closing volume. In 80 per cent of these patients we observed a decrease in expiratory reserve volume certainly due to a shift on the right of the chest wall volume-pressure curve. In 50% of the obeses we found an arterial hypoxia, usually observed when the expiratory level was lower than closing volume. Finally in 20% of the subjects we observed a decrease in diffusing lung capacity and/or ductances probably due to an important fall in and expiratory level at the closing volume level with impairment of the distribution of ventilation.

In obesity resistant to traditional low calory diets, the authors alternated short periods of moderate low calory intake (600 to 1,000 calories) with periods of very restrictive low calory intake (230 to 300 calories). The results of this method are analysed in 105 patients. This method permits loss of weight in difficult cases of obesity, both during intensely low calory diets and during less severe low calory diets. This technique is well accepted by the patients and is less monotonous than very unbalanced multi-fractionated diets or with prolonged courses of fasting. The results are all the more satisfactory when the patient is young, when the obesity is recent and marked, which does not, however, exclude its efficacy in long-standing cases of obesity.

Our aim was to evaluate the possible role of prostaglandins (PG) on renal calcium excretion in humans through the PG inhibitory effects of indomethacin. Renal calcium excretion was evaluated by a technique of impulse analysis which gives a specific index of tubular calcium transport. Several parameters were derived from this specific transport function W(t): 1) the fractional excretion of filtered calcium as % of total dose (FECa % TD); 2) the peak excretion rate; 3) the mean transit time (MTT, min). The aforementioned parameters were determined in 7 healthy subjects in basal conditions and again after 10 days of treatment with 100 mg indomethacin daily. FECa was significantly (P less than 0.02) higher with indomethacin (8.18 +/- 0.97) than under basal conditions : (5.02 +/- 0.57). The peak excretion rate and MTT remained unchanged after indomethacin. These results indicate that indomethacin increases renal calcium excretion. As indomethacin did not produce any significant change in glomerular filtration rate (125 +/- 7 ml/min before v.s. 129 +/- 9 after) one can assume that PG play a role in tubular calcium reabsorption. However the mechanism remains to be elucidated : direct action of mediated through the cyclic AMP system.

Eight patients with giant cell arteritis (6 with Horton's disease and 2 with polymyalgia rheumatica) were investigated for abnormalities in glycoregulation, previously reported in Horton's disease, using oral glucose tolerance tests with measurement of insulinaemia and C-peptide response to glucagon to evaluate pancreatic function. The results were compared with those obtained in an age and weight matched population of patients with inflammatory syndromes of other origins. All patients with giant cell arteritis had abnormal glucose tolerance tests, with diabetes mellitus in 6 and impaired glucose tolerance in 2. Insulinaemias at all stages of the test, insulin response areas and basal C-peptide values were elevated; C-peptide response to glucagon was normal. Similar results were observed in patients with other inflammatory syndromes. It is concluded that glycoregulation disorders are not incidental in giant cell arteritis, that the normal pancreatic function seems to exclude immune pancreatic vasculitis, and that the abnormal glycoregulation is probably due to insulin-resistance. Since these abnormalities cannot be explained by the patients' advanced age alone, the part played by the inflammatory syndrome, which was common to both groups, is discussed. Its responsibility for inducing insulin-resistance may account for the fact that corticosteroids, which are rapidly effective against giant cell arteritis, normalise oral glucose tolerance tests.

Eight female patients are studied, four of them without hyperthyroidism. The following were measured before and after surgery = hormonal iodine by column, serum concentrations of T T3, AF T3, TSH, total T3 distribution space, T3 pool size T3 fractional turnover rate. T T3 is measured in the serum of peripheral venous blood, nodular venous blood and of jugular venous blood of the opposite side of the adenoma. Before surgery, the mean of T T3 in patients with hyperthyroidism is increased in serum obtained from brachial and not nodule venous blood. Are also increased AF T3 and T3 production rate. In patients without hyperthyroidism, T T3, AF T3 are increased in two subjects only, but T3 production rate is rised among three of them. After surgery the previous values are not different with normal values. These data are in good agreement with the hypothesis that, in patients without thyrotoxicosis, there is an increase in T3 production from not nodular goiter. There phenomena may explain unresponsiveness to TRH test and inactivity of normal thyroid. Absence of hyperthyroidism may be due to a lack of sensitivity of peripheral tissues to the increase of T3.