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Background: Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands., Methods: We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients., Results: The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion., Conclusions: Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of steroidogenic cells in the hyperplastic adrenals. Thus, the hypercortisolism associated with bilateral macronodular adrenal hyperplasia appears to be corticotropin-dependent. (Funded by the Agence Nationale de la Recherche and others.).

Hyperglycemia is commun in critically ill patients without previously known diabetes. Hyperglycemia occurring in these patients is mainly a consequence of stress associated to complex glucose metabolism abnormalities which have deleterious effects on tissues and vascular function. Several epidemiologic and intervention studies had established that hyperglycemia is related to morbidity and mortality. Maintenance of normoglycemia with intensive insulin therapy seems to decrease morbidity and mortalities in severe acute illnesses. However the benefit of most of these intervention trials remain controversial mainly in stroke, myocardial infarction and severe sepsis. Moreover strict normoglycemia required to obtain an optimal benefit increases the risk of hypoglycaemia which may be particularly harmful in patients in critical state.

Pheochromocytoma is a rare cause of secondary hypertension which may have protean clinical presentations. Noteworthy, it may be revealed or complicated by cardiovascular symptoms such as arrythmia, cardiomyopathy, acute coronary syndrome and cardiogenic shock. These cardiac manifestations of pheochromocytoma may delay diagnosis and must be known in order to provide the best chance at early detection. In some cases pheochromocytoma may be associated to a large apical dyskinesia of the left ventricule apex, tako-tsubo-like which is a reversible acute myocardiopathy. These acute cardiologic manifestations appear to be induced by a toxic effect of elevated catecholamine levels.

The thyroid gland is a very rare location of metastasis and the metastatic involvement of the thyroid is mostly asymptomatic. The authors report one of the first cases of pulmonary adenocarcinoma associated with painful metastatic involvement of the thyroid gland. Temporary hyperthyroidism was noted, followed, two months later, by clinically and biologically proven hypothyroidism with positive antithyroglobulin antibodies. The suspect goiter was detected by diffuse hyperfixation on 18-FDG PET Scan and the ultrasonography revealed two hypoechogenic nodules. The fine needle biopsy confirmed the metastatic origin of these nodules. The evolution after five cycles of chemotherapy by cisplatine and docetaxel was marked by a complete regression of the thyroid metastasis and an improvement in the thyroid function.

Objectives: Subclinical hypothyroidism defined by the presence of elevated TSH levels but normal free T4 level is a common situation. Its consequences on health are yet on debate and the interest of a precocious treatment remains surrounded by controversy., Key Points: The relationship between subclinical hypothyroidism and cardiovascular disease has been evaluated by several cross-sectional and longitudinal studies. Subclinical hypothyroidism has direct but subtle effects on the heart function, on the peripheral vascular resistance, and is associated with a mild elevation of LDL-cholesterol levels; all abnormalities may be partly reversed by a thyroxine supplementation. Data of the literature give insufficient evidence as to whether subclinical hypothyroidism is an independent cardiovascular risk factor. However treatment of subjects with TSH levels up or near to 10 mU/l would probably be beneficial in the prevention of cardiovascular disease., Future Prospects: Based on observational and interventional studies there are some arguments on the benefit of euthyroidism restoration only in patients with TSH levels superior to 10 mU/l.

Pituitary metastases are rare and generally asymptomatic. We studied 5 patients with pituitary metastases from lung cancer, illustrating the different clinical features. These metastases were in these cases symptomatic with the manifestation being diabetes insipidus or visual field defect. Histological subtypes from our five patients were as well small cell or non small cell lung cancer. After diagnosis of pituitary metastasis, prognosis seems to be linked to the histological subtype and the stage of lung cancer, rather than to the presence of such metastases.

Background: The overprevalence of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in women remains unexplained. Microchimerism pathogenicity has been discussed in some systemic diseases. We tested history of pregnancy as a risk factor for GCA., Methods: Prospective, multicenter case-control study with multiple, age-matched, control groups. Patients have been included in 40 different centers. The first control group has been randomly selected in the general population, consecutive hospitalized patients in two geographically distant departments of internal medicine made up the second and third ones., Results: Three hundred and fifteen patients (249 GCA and 66 PMR), 242 general population controls, 333 in the first hospitalized control group, and 355 in the second, have been included in the 1991-1998 period. Pregnancy has been constantly protective against GCA/PMR (Wilcoxon rank sum test: P = 0.0001, 0.0005, and 0.054, respectively, for the three control groups), more particularly for parity equal or greater than 4 (OR = 0.32, 95% CI: 0.18-0.57, P = 0.00003; OR = 0.44, 95% CI: 0.26-0.74; P = 0.0009, and OR = 0.42; 95% CI: 0.25-0.71, P = 0.0006, respectively). In multivariate analysis, risk for GCA on pre-existing degenerative, vascular disease is decreased by half for each pregnancy (OR = 0.49, 95% CI = 0.27-0.90, P = 0.022)., Conclusion: Contrary to the initial hypothesis, multiparity is a protective factor against GCA. Mechanism is unknown.

DEFINING THE PROBLEM: Sub-clinical hypothyroidism, defined as a moderate and isolated increase in TSH levels, is a common syndrome and is the first phase of a progressive disease. However its treatment remains controversial. Some anamnestic, clinical and biological (anti-thyroperoxidase antibodies) parameters contribute in identifying the patients most likely to progress towards overt hypothyroidism. WHAT CAN BE EXPECTED OF TREATMENT? Several clinical studies have described cardiovascular, neuromuscular and lipid disorders in these patients, but administration of levothyroxine has provided varying results and does not enable the distinction between a pharmacological-like intrinsic effect of the thyroid hormone and the true benefits imputable to the correction of TSH, in the absence of any large interventional study. More studies are required to better identify the patients who will benefit most from hormone replacement.

The effects of smoking on the thyroid gland have been studied for years. The consequences of smoking on thyroid function and size are however still controversial. It is accepted that an increase in serum thyiocyanate, a potent inhibitor of iodine transport, may contribute to the development of thyroid dysfunction, particularly in geographical areas with borderline iodine deficiency. In the general population, smoking is associated with normal thyroid hormone levels, with a tendency to lower TSH levels and enlargement of thyroid size. There is an increased risk of developing over thyroid disease. The relationship between smoking and relapse of Graves' disease and the incidence and severity of Graves' ophthalmopathy are constantly reported. Smoking also has a potent nodular goitrigenic effect in low iodine areas. Despite the fact that smoking decrease both thyroid secretion and thyroid hormone action, hypothyroidism does not appear to be more frequent. Smoking does however increase the metabolic effects of hypothyroidism. Active and passive smoking have proven deleterious effects on the fetal thyroid. Paradoxically, there is evidence of reduced risk for thyroid cancer in smokers.

BACKGROUND: To date, only case reports or small studies have documented the syndrome of food-cobalamin malabsorption in specific populations of patients or situations. In this paper, we present the data from 80 unselected patients with cobalamin deficiency related to food-cobalamin malabsorption. METHODS: We studied 80 patients with well-established food-cobalamin malabsorption who were extracted from an observational cohort study (1995-2000) of 127 consecutive patients with cobalamin deficiency and who were followed in a department of internal medicine. RESULTS: The median age of patients was 66 years and the female to male ratio was 1.2. The mean hemoglobin level was 113+/-27 g/l (range 32-159 g/l) and the mean erythrocyte cell volume was 95.4+/-12.3 fl (range 55-140 fl). Mean serum vitamin B12 and homocysteine levels were 153+/-74 pg/ml (range 35-200 pg/ml) and 20.6+/-15.7 μmol/l (range 8-97 μmol/l), respectively. The main clinical findings noted were peripheral neuropathy (46.2%), stroke (12.5%), confusion or dementia (10%), asthenia (18.7%), leg edema (11.2%), and digestive disorders (7.5%). The commonest associated conditions were atrophic gastritis (39%) with evidence of Helicobacter pylori infection (12.2%) and alcohol abuse (13.7%). Three patients had Sjögren's syndrome and one had systemic sclerosis. Ten percent of all patients were on long-term metformin (10%) and 7.5% on acid-suppressive drugs. Correction of the serum vitamin B12 levels and hematological abnormalities was achieved equally well in all patients treated with either intramuscular or oral crystalline cyanocobalamin. CONCLUSION: This study suggests that food-cobalamin malabsorption may be the leading cause of vitamin B12 deficiency in adults. As other studies have also reported, the condition is often associated with neuro-psychiatric findings and with several other conditions. Oral and parenteral cobalamin appear to be equally effective in correcting serum B12 levels and hematological abnormalities and, in many cases, they also relieve symptoms.

Purpose: Unexplained inflammatory syndrome is a frequent and worrying condition in Internal Medicine. However, the long-term clinical outcome of these patients cannot be inferred from the literature. The aim of this study is to describe the long-term follow-up and the prognosis of a group of patients hospitalised for an inflammatory syndrome and discharged without causal diagnosis., Methods: This retrospective study was carried out on 46 patients, 15 men and 31 women, aged 21 to 90 years, hospitalised between 1992 and 1999. Data concerning the hospital stay were obtained from the patients' medical record. Follow-up was performed by consulting the treating physician., Results: The prognosis of these patients is fairly good. In one third of the cases, the inflammatory syndrome resolved spontaneously (n = 13). In the second third, a definite diagnosis was established after discharge (n = 14) and consisted mainly of chronic inflammatory diseases (n = 9), cured with a specific treatment. In the remaining third (n = 12), the inflammatory syndrome persisted, in clinically asymptomatic patients., Conclusion: These results suggest that the persistence of an inflammatory syndrome is not a poor prognostic factor. Thus we propose for patients discharged with an undiagnosed persistent inflammatory syndrome despite thorough investigations, a simple clinical and biological follow-up instead of repeated etiological investigations.

Persistant hypocalcemia occurring after surgical treatment of severe primary hyperparathyroidism may be due to transient or permanent hypoparathyroidism but also to a bone disease. We report three cases of hypocalcemia after surgery of large parathyroid adenoma or hyperplasia in women. Plasma calcium, phosphate and PTH levels are in accordance with Hungry Bone Syndrome (HBS). HBS is related to both excessive bone demineralization and turn over. It is a major importance to distinguish HBS from surgical hypoparathyroidism in order to start early the appropriate treatment given for a long period.

Fibromyalgia is a syndrome characterized by chronic musculoskeletal pain and fatigue without biological detectable disturbances. The mechanisms of this disease are unknown. It has been postulated that it can be the consequence of a chronic stress mediated mainly through the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system. These fields have been extensively studied. Results were scattered and non convincing. A reduction of growth hormone and IGF-1 levels described in a third of patients has led to a double blind random clinical trial with biogenetic growth hormone. Results were equivocal . Other hormonal systems are grossly normals and circadian rhythms are unaltered. Despite some arguments in favour of a CRH neurons hyperactivity, these results are not able to consolide a particular physiopathological mechanism and to argument for a new therapeutic approach. Many of the abnormalities may be the consequence of psychological disturbances.

Objectives: To compare the clinical, biochemical, radiological features and the outcome of elderly and young patients with tuberculosis., Methods: Between 1980 and 1997, 83 patients diagnosed as having tuberculosis were treated in two departments of Internal Medicine and Geriatrics. They were divided into 42 young (< 65 years) and 41 elderly (> or = 65 years) patients and differences in presentation between the two groups were analysed., Results: A past history of tuberculosis was found in 10% of young and in 18% of elderly patients (p = 0.43). Cancer was more often associated with tuberculosis in elderly patients (2% vs 15%, p = 0.09). The sites of disease were similar in both groups with 2/3 of pulmonary infection. Comparison of the presenting symptoms showed no significant difference for weight loss (52% vs 66%, p = 0.31), fever (52% vs 56%, p = 0.90) and cough (33% vs 32%, p = 1). The skin testing was positive for the majority of the young adults (84% vs 58%, p = 0.11). The commonly observed biochemical abnormalities in elderly patients were an increased erythrocyte sedimentation rate (49 vs 69 mm/h: p = 0.03) and lymphocytopenia (1724 vs 1059/microliter, p < 0.01). There was no significant difference in radiographic findings between both groups with miliary tuberculosis in about 10% of patients. During the first three months of treatment, the mortality was especially high (22%) for the elderly patients., Conclusions: Comparison of the clinical and radiological features of tuberculosis in internal medicine showed no significant difference in young and elderly patients.

Objective: Certain liver test abnormalities have been described in adult Still's disease. The objective of the present study was to analyze their type and frequency., Patients: In a 10 year retrospective study, patients were included if they fulfilled Kahn's and/or Yamaguchi's diagnostic criteria (median follow-up: 6.5 years)., Results: Twelve patients were selected. The median age was 25 years old and the sex ratio H/F was 2.7. Fever was present in 100% of patients and hepatomegaly in 41%. Liver test abnormalities were identified in 92% of patients: moderate cytolysis (level of transaminases between 2 and 5 N) (83%), severe cytolysis (level of transaminases > 5 N) (17%), cholestasis (elevated levels of GGT and/or alkaline phosphatase) (75%), and an increase in the LDH level (41%). All these liver abnormalities resolved spontaneously or during treatment (83%), within a median of 18 days., Conclusion: Our study confirms the high frequency of liver test abnormalities (> 2/3 of the patients) in adult Still's disease. These abnormalities are generally moderate and asymptomatic (3/4 of the cases), but severe cytolysis may exist. This emphasizes the need to consider a diagnosis of adult Still's disease in the presence of fever and elevated transaminase activity.

Since very little is known about the clinical expression of Lyme borreliosis in Western Europe, a 3-year prospective study was conducted that included all patients seen for suspected Lyme borreliosis at the Strasbourg University Hospital in northeastern France. The diagnosis of Lyme borreliosis was made on the basis of the presence of erythema migrans or on the basis of another suggestive clinical manifestation and laboratory confirmation. A total of 132 patients, 70 women and 62 men, mean age 54 years, had Lyme borreliosis according to these criteria. Within this study group, 77% of the patients were regularly exposed to tick bites and 64% could remember one. Erythema migrans, the most frequent clinical manifestation, occurred in 60% of the patients and was the only sign of Lyme borreliosis in 40%. Lymphocytoma and acrodermatitis chronica atrophicans were rare (1 and 3 patients, respectively). Nervous system involvement (mainly radiculoneuropathy), the second most common clinical manifestation, was found in 40% of the patients and was the only sign of Lyme borreliosis in 22%. Musculoskeletal involvement was present in 26% of the patients and was an isolated finding in 14%. During the study period, no patient was diagnosed with Lyme carditis. There was serological evidence of Lyme borreliosis in 75% of the cases and direct evidence of borrelial infection in 10 (7.5%). The results show that the clinical expression of Lyme borreliosis in northeastern France is similar to that in other European countries but different from that in North America.

Objective: Adult celiac disease is a genetically determined condition resulting from intolerance to gluten. This familial disease is associated with HLA B8 DR3 and is characterized by cytotoxic T-lymphocyte reaction in the digestive wall leading to a maladsorption syndrome. Adult celiac disease would be an expression of a silent disease already present in childhood., Patients and Methods: We conducted a retrospective study in 19 patients. Diagnosis was established in a department of internal medicine in adulthood. We analyzed histological findings and the clinical history and course., Results: The age curve at diagnosis peaked at 22 years and 67 years. Female sex predominated. Average delay to diagnosis was 3.1 years. The patients were admitted for reasons other than digestive disorders in 17 out of 19 cases. Careful history taking did however disclose subtle digestive signs. The principal manifestations were hematological disorders such as chronic anemia, abnormal liver function tests, and poor control of associated diseases. Type 1 diabetes mellitus was the main associated disease (4/19). Patients with prolonged nutritional deficiencies experienced serious situations., Conclusion: Adult celiac disease is a clinical variant suggesting the presence of other non-digestive disorders. Specific antibodies should be assayed in patients with even minimal signs of deficiency in order to identify associated diseases. The principal cause of mortality is digestive T-cell lymphoma. A gluten-free diet is essential to control the course of this chronic disease.

Prolonged corticosteroid treatment is considered to be the main cause of adrenal insufficiency (AI). AI is due to adrenal atrophy caused by the inhibition of ACTH secretion. Risk factors for AI after corticosteroid treatment remain unknown. Various functional tests, particularly the "standard" Synacthene 250 microg, demonstrate frequent abnormal responses in these patients. However, these abnormalities are not predictive of the risk of AI in particular in case of stress. More recent tests (CRH, "low dose" Synacthene) need to be further evaluated in this situation. Several recent studies in animals and in humans have demonstrated that the need for glucocorticoid coverage during a surgical stress has been greatly overestimated and that maintenance of the usual daily dose seems to be sufficient and safe in most patients with minor surgical stress. Revision of guidelines for more important surgical stress or for other medical conditions in patient treated with glucocorticoids is necessary.

Purpose: New hypotheses have recently been developed on vitamin B12 deficiency and the frequently observed occurrence in the elderly subject of food cobalamin malabsorption, i.e., the non-dissociation of B12 and its carrier protein (ND B12), and the possibility of rectifying this imbalance by oral crystalline B12 supplementation. The aim of this study was therefore to confirm these hypotheses in a series of patients aged over 75 years with anemia due to B12 deficiency., Methods: A retrospective study was carried out over a 5-year period on patients aged over 75 years presenting with megaloblastic anemia (hemoglobin [Hb] < 12 g/dL) and vitamin B12/cobalamin deficiency (B12 < 160 pg/mL)., Results: Twenty cases were analyzed. The average age of the patient population was 82.5 +/- 6 years, and the F/M sex ratio was 1:2. Mean Hb levels were 7.9 +/- 2.4 g/dL, mean serum B12 levels were 83 +/- 24 pg/mL, and mean homocysteinemic levels were 35 +/- 27 mumol/L. The diagnosis was as follows: food cobalamin malabsorption/ND B12 (n = 10), Biermer's disease/pernicious anemia (n = 5), malabsorption due to pancreatic insufficiency (n = 1), and low dietary B12 levels (n = 1). Disorders associated with ND B12 were: atrophic gastritis and Helicobacter pylori infection (n = 6), antacid or biguanide intake (n = 3), alcohol abuse (n = 2), or idiopathic syndrome (n = 2). In the patients who were followed up (n = 10), i.m. (n = 5) or oral (n = 5) administration of crystalline B12 resulted in the correction of hematological abnormalities., Conclusion: In the elderly subject, food cobalamin/ND B12 malabsorption appears to be the main cause of B12 deficiency, and is frequently associated with atrophic gastritis. In these cases, administration of oral crystalline B12 may be an efficient means of treating this disorder.

The purpose of this study is to describe sex and geographic differences in apolipoproteins (apo) A-I and B and lipoprotein(a) [Lp(a)] concentrations in elderly Europeans. Subjects were 2164 elderly participants of the SENECA study from different regions of Europe. Sera for apo A-I, apo B, and Lp(a) measurement were available for 1703 individuals. In men, mean values ranged from 1.38 to 1.79 g/l for apo A-I, 1.03-1.36 g/l for apo B, and 0.26-0.67 g/l for Lp(a). In women, mean values ranged from 1.54 to 1.98, 1.20-1.51, and 0.26-0.68 g/l for apo A-I, apo B, and Lp(a), respectively. A comparison of northern (Norway, Denmark, Netherlands), middle (France, Switzerland), and southern (Portugal, Spain, Italy, Greece) communities showed a less atherogenic profile in the south, including lower LDL cholesterol, apo B, TC/HDL cholesterol ratio, and apoB/apo A-I ratio. Men, but not women, also had significantly higher HDL cholesterol and apo A-I concentrations in the South. Paradoxically, Lp(a) concentrations were generally high among all elderly and were significantly higher in the southern communities. These data show that the elderly in Europe are very heterogeneous with respect to plasma lipoproteins, including apo A-I, apo B, and Lp(a).

Staphylococcus aureus was isolated as the predominant or only isolate from cultures of stools of 60 patients over 2 years in a university hospital, leading to the collection of 114 isolates. Diarrhea was observed in 90% of the patients. Ninety-eight percent of the patients had received antibiotics in the month before the diarrhea. Ninety-two percent of the S. aureus isolates were methicillin resistant. S. aureus was encountered with antibiotic-associated diarrhea among 47 quite elderly patients affected or not affected by a gastrointestinal disease. Among the antimicrobial treatments, cessation of the previous therapy when possible or rapid application of oral vancomycin therapy was the most appropriate. Analysis of total DNA by pulsed-field gel electrophoresis revealed 27 different SmaI pulsotypes distributed in 15 clusters. The pulsotypes never differed for related isolates from a single patient, even if they originated from patients with bacteremia. S. aureus was not isolated as the predominant isolate in cultures of stools of 57 patients who received an antimicrobial treatment for more than 5 days without diarrhea. Occurence of production of both enterotoxin A and the bicomponent leucotoxin LukE-LukD by the S. aureus isolates was significantly different from that by random isolates. The results strongly suggest that when predominant in stool samples, S. aureus should be considered a possible etiologic agent for some cases of antibiotic-associated diarrhea.

We report the case of a 46-year-old man whose Graves' disease relapsed 5 years after its first appearance. At the time of relapse thyrotropin (TSH) receptor antibodies were very high, as was radioactive uptake in the left lobe of the thyroid. After thyroidectomy, histological analysis of the specimen showed evidence of treated Graves' disease, and there were signs of subacute thyroiditis in the right lobe. The clinical and immunologic characteristics of this observation are discussed as well as the hypothesis explaining the succession of an inflammatory and autoimmune thyroid disease.

UNCOMMON MALIGNANCY: Adrenocortical carcinoma is a very rare malignancy with poor prognosis. Median survival ranges from 12 to 25 months. Most clinicians recommend aggressive surgical management of either local or recurrent and metastatic disease. ANTICORTISOL AGENTS: Mitotane, the most tested agent against inoperable and metastatic adrenocortical carcinoma, procures overall response rates of 20 to 25%, but recent data do not support its use in the adjuvant setting., Chemotherapy: The efficacy of cytotoxic chemotherapy is low but new agents or associations (with platinum salts), new concepts (dose-intensification, MDR (the chemoresistance gene) reversing agents) may be useful and five some hope in this difficult disease., Radiotherapy: The role of radiation therapy must be developed.

Iodine is a raw material for the thyroid production of hormone which is on the major external control of TSH. The thyroid adaptation to iodine deficiency consists in an increasing iodine concentration from the circulation, an enhancing iodination of the tyrosyl residues in thyroglobulin, a decreasing iodine storage associated to a better recycling of non hormonal iodine and thyroid hyperplasia to provide more synthetic possibilities. Genetic variation and environmental factors explain the wide variation of individuals response to iodine deficiency resulting in a high prevalence of goiter, a mild TSH level increase or overt hypothyroidism. At long term iodine deficiency may have severe pathological consequences and induce neuropsychological deficits in school-children. A policy of iodine supplementation mainly by iodized salt must be undertaken in many areas in the world. Effects of an iodine excess on thyroid function are variable depending upon the underlying thyroid disorder and ambient iodine intake. The most subjects remain euthyroid by mechanisms of autoregulation based on an inhibition of thyroid hormone synthesis and a decrease in the thyroid iodide trap. Euthyroid individuals from high iodine intake areas or those with a history of lymphocytic thyroiditis, treated Graves' disease or subtotal thyroidectomy develop hypothyroidism. On the other hand iodine induced hyperthyroidism is more common in areas of iodine deficiency and in older patients with nodular goiter.

Pituitary stimulation tests are widely used to explore hypophyseal adenomas. There are few disadvantages, although a few cases of pituitary necrosis have been published. We report a new case with a dramatic outcome. A 30-year-old man with clinical signs of acromegalia and major visual disorders was found to have a voluminous macro-adenoma of the pituitary gland. Thirty minutes after beginning the stimulation test, the patient complained of major headache and experienced persistant vomiting for several hours. Brain magnetic resonance imaging the next day did not reveal evidence of pituitary necrosis. Sudden onset coma occurred one hour later. The CT scan demonstrated hemorrhagic necrosis of the adenoma. The patient died despite emergency surgery. Due to the risk of hemorrhagic necrosis of a pituitary adenoma, baseline assays may be sufficient for diagnosis in patients with clinical signs highly suggestive of pituitary oversecretion, especially when a voluminous tumor is involved. Rigorous clinical surveillance is required after stimulation tests.

Objective: To compare actual food intake of elderly people in Europe and further identify food patterns, which mediate favourable or unfavourable nutrient intakes from cluster analysis of pooled data., Design: Cross-sectional analysis of food patterns of participants of the SENECA follow-up study (1993)., Setting: Twelve traditional European towns., Subjects: Men (n = 647) and women (n = 710) aged 74-79 y in 1993., Methods: Food intake data were assessed using the same validated dietary history technique in all SENECA towns. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables., Results: A northern and southern European eating pattern emerged. The southern food pattern appeared to be the most healthful being rich in grain, vegetables, fruit, lean meat and olive oil. The north-south gradient did, however, not systematically segregate into the same clusters. All dietary profiles were represented in all sites. The four dietary profiles, identified by cluster analysis, were: 'Lean and green eaters': high carbohydrate and vitamin C intake, 'gourmands': high intake of energy and nutrients, 'milk drinkers': high intake of calcium and vitamin B2 and 'small eaters': marginal energy and nutrient consumption. Marital status, education, smoking, health status and physical activity level differed between clusters., Conclusions: A north-south gradient of food patterns was identified. The southern diet agreed better with guidelines for healthy eating. A sufficient energy intake seemed, however, to be necessary for an adequate nutrient intake, beside a good choice of food types.

Objective: To describe the serum total cholesterol, lipoprotein cholesterol and triglyceride concentrations in elderly people from the SENECA follow-up study and report on longitudinal changes in these lipid concentrations over a four-year follow-up period., Design: Longitudinal study including baseline measurements taken in 1988/1989 which were repeated in 1993., Subjects: In 1993 lipid concentrations were assayed in blood serum collected from 1181 elderly men and women, born from 1913 to 1918 and living in twelve small towns in ten European countries and one town in the USA. 1062 of these subjects had also participated in the baseline study., Results: Mean concentrations ranged from 4.91 to 6.72 mmol/l for total cholesterol, 1.15 to 1.64 mmol/l for HDL cholesterol, 3.04 to 4.47 mmol/l for LDL cholesterol and 1.03 to 1.79 mmol/l for triglycerides. Thirty-two per cent of European men and 18% of women had plasma total cholesterol concentrations below 5.16 mmol/l; 32% of men and 56% of women had HDL cholesterol concentrations exceeding 1.42 mmol/l. Total- and HDL-cholesterol concentrations, and the HDL:total cholesterol ratio were higher in women than in men. Despite large variations between towns no clear north-south gradient was observed. Yet, lowest values for LDL cholesterol tended to be located in the south, while the highest values for LDL cholesterol showed up in the north. Comparisons between the 1989 and 1993 surveys revealed a significant decrease in total cholesterol and an increase in the HDL:total cholesterol ratio without significant variation in HDL cholesterol or triglyceride concentrations., Conclusion: Though serum lipid concentrations varied widely across Europe, a marked decline in total cholesterol values along with an increase in the HDL:total cholesterol ratio occurred across the SENECA towns.

Objective: To assess longitudinal changes in intakes of energy and macronutrients in elderly Europeans., Design: Longitudinal study including a dietary assessment in 1988/1989, which was repeated in 1993., Setting: Serial data were collected in nine European towns: Belgium: Hamme (H/B); Denmark: Roskilde (R/DK); France: Haguenau (H/F) and Romans (R/F); Italy: Padua (P/I); the Netherlands: Culemborg (C/NL); Portugal: Vila Franca de Xira (V/P); Spain: Betanzos (B/E) and Switzerland: Yverdon (Y/CH). In other centres dietary intake data were collected in 1993 only: Portugal: Coimbra (C/P); Poland: Marki (M/PL); Northern Ireland: Ballymoney-Limavady-Portstewart (BLP/NI/UK) and United States: Mansfield (Connecticut) (M/CT/USA)., Subjects and Methods: Using standardized methodologies, data were collected from a random stratified sample of elderly men and women born between 1913 and 1918. In 1993 dietary intake data were collected from 1125 subjects by a modified validated dietary history method., Results: Over the 4-year study period, a decline in mean energy intake of one MJ or less per day was observed in most towns, which was significant (P < 0.01) in only four of the towns. The within- and between-centre variation of change was large. Overall, a slight decline was reported for all macronutrients and with the exception of protein, large within and between centre variations were observed in both men and women., Conclusion: Intake of energy and macronutrients was found to decline with age. This may be of special concern for small eaters.

The consequences of aging function are appreciated in various ways. In fact most of the thyroid hormone abnormalities described in the elderly are secondary to associated disease or treatments. Health and nutritional status seem to be more determinant than age. However, there is an increased prevalence of dysthyroidism in the elderly. Symptoms may be misleading and induce severe general repercussions. Mild or occult forms of dysthyroidism characterized by abnormal TSH levels with normal free thyroid hormone levels are not uncommon. Their clinical significance and their prognosis without treatment are still unresolved. The frequency of dystrhyroidism during old age and the possibility of a specific treatment may be in favour of a screening by a systematic TSH determination in elderly patients.

CGRP (calcitonin gene-related peptide) is a potent vasodilator neuropeptide which acts on peri-arteriolar neurones and is implicated in the pathogenesis of numerous cardiovascular diseases. The synthesis of CGRP antagonists should be useful for the treatment of Raynaud's disease as well as migraine. There exists an homology between the structures of CGRP and pancreatic amylin and therefore an eventual role of CGRP in type II diabetes pathophysiology is currently being studied.

Left ventricular function indices were measured by pulsed Doppler-echocardiography in 17 young patients (mean age: 25 +/- 5) with insulin-dependent diabetes and 17 controls (identical mean age: 25 +/- 5) free of heart disease. All subjects had normal left ventricular systolic function. Twenty three per cent of diabetics showed a left ventricular filling anomaly on the basis of at least two abnormal indices. Isovolumic relaxation time was significantly prolonged in diabetics as compared with normal individuals (83 +/- 7 v. 68 +/- 9 ms, p < 0.00015). Half-pressure time was also prolonged in the patients (46 +/- 9 v. 38 +/- 6 ms, p < 0.01), the same applying to rapid filling deceleration time (158 +/- 32 v. 136 +/- 29 ms, p < 0.05). Peak rapid filling rate, the proportion of total filling accounted for by rapid filling, peak atrial systole velocity and the atrial contribution to total filling did not differ between the diabetics and controls. Systolic blood pressure was significantly higher in diabetics as compared with controls (124 +/- 8 v. 114 +/- 10 mmHg, p = 0.007), although remaining within normal limits. This would not, however, explain the differences seen between the 2 groups regarding left ventricular profile. The filling anomalies reported here were not correlated with the duration of diabetes nor with other parameters such as glycosylated hemoglobin or 24-hour microalbuminuria. Our results suggest that approximately 20 p. cent of young diabetics have sub-clinical left ventricular anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)

The performances of a new "3rd generation" chemoluminescence TSH assay (TSH ICMA) with a functional sensitivity of 0.005 mU/l were compared with those of an "ultrasensitive" TSH immunoradiometric assay (TSH IRMA) in a series of patients characterised by a TSH IRMA less than 0.20 mU/l and normal free thyroxin (T4 L) and triiodothyronine (T3 L) concentrations. The 95% cut-off value for hyperthyroidism was 0.03 for TSH ICMA and 0.05 for TSH IRMA. In a first group of 41 subjects undergoing Tc99m thyroid scan, images of multifocal increased uptake or toxic adenoma were associated with a lower TSH ICMA than in patients with a normal isotope scan. TSH ICMA was also lower than TSH IRMA (p < 0.01). At the cut-off value of 0.03 mU/l, the specificity of TSH ICMA was higher than that of TSH IRMA, but the sensitivity were identical. In a second group of 36 patients with severe non-thyroid diseases, TSH ICMA was lower than the cut-off value for hyperthyroidism in 30% of cases, while TSH IRMA was lower than the cut-off value in 40% of cases. A satisfactory concordance was observed between the two methods. In conclusion, the two TSH assays, IRMA and ICMA, provide globally comparable information in subjects with a low TSH and normal T4 L and T3 L. However, the better specificity of TSH ICMA and a smaller overlap with the frank hyperthyroid zone in patients with non-thyroid disease argue in favour of the use of this new assay method.

Treatment of primary hypothyroidism requires a long-term hormonal therapy with levothyroxine which restores a normal TSH value. In a series of 192 patients followed up for at least 3 years we tried to evaluate the variability of maintenance dosage and to analyse the factors predictive of replacement dosage. The L-T4 dosage varied from one individual to the other, from 0.6 to 3.2 micrograms/kg. The mean maintenance dosage (118 +/- 38 micrograms/day) was similar in men and women weight for weight, but it was higher in subjects aged under 60 and in those with Hashimoto's or congenital hypothyroidism. There is a positive linear relation between the equilibrium dose and the TSH value (n = 0.84; p < 0.001) and a negative relation with the L-T4 concentration (n = 0.71; p < 0.001). The yearly variation of dosage in each individual was small (about 3.5%) and of the same order as the variation of weight. We conclude that the L-T4 maintenance dosage depends on the cause of hypothyroidism, on the importance of biochemical abnormalities and on the patient's age, sex and weight. In practice, however, the necessary dosage is difficult to predict. In the equilibrium phase the need for replacements is remarkably stable. A yearly assay of baseline TSH seems to be sufficient to evaluate the quality of hormonal compensation in the absence of intercurrent events.