Quarterly individual outpatients lifestyle counseling after initial inpatients education on type 2 diabetes: the REDIA Prev-2 randomized controlled trial in Reunion Island.

AIMS: This study aimed to describe the 1-year evolution of type 2 diabetes (T2D) patients who attended inpatients education, and to assess whether quarterly outpatients counseling visits by nurses and dietitians can improve metabolic control and health-related behaviours. METHODS: Following in-hospital educational sessions, 398 adult T2D patients were randomized to either attend quarterly individual lifestyle counseling visits by a nurse and a dietitian (intervention group), or receive the usual care (control group). Primary (HbA(1c)) and secondary endpoints (fasting blood glucose, lipids, body mass index, waist circumference, fat mass, blood pressure, diet, physical activity) were assessed at baseline and at 12 months. RESULTS: HbA(1c) changes from baseline to 12 months were -1.74±2.64% (P<0.0001) for the intervention group and -2.02±2.57% (P<0.0001) for the control group. There was no statistically significant difference between the intervention group (n=153) and the controls (n=166) for any of the clinical and biological outcomes. In both groups, total energy and fat intakes decreased significantly from baseline levels. Also, no difference was found between the groups for any dietary outcome. A slight enhancement in sports activity was observed in the intervention group, but the difference between the two groups did not reach statistical significance, and no difference was found concerning any other physical activity scores. CONCLUSION: In this study of adults with T2D, patients significantly improved their metabolic control, and dietary and exercise habits, 1 year after receiving intensive inpatients education, whereas subsequent quarterly outpatients counseling visits with nurses and dietitians have not demonstrated any superiority compared with the usual care.

Mutant WD-repeat protein in triple-A syndrome.

Triple-A syndrome (MIM 231550; also known as Allgrove syndrome) is an autosomal recessive disorder characterized by adrenocorticotropin hormone (ACTH)-resistant adrenal insufficiency, achalasia of the oesophageal cardia and alacrima. Whereas several lines of evidence indicate that triple-A syndrome results from the abnormal development of the autonomic nervous system, late-onset progressive neurological symptoms (including cerebellar ataxia, peripheral neuropathy and mild dementia) suggest that the central nervous system may be involved in the disease as well. Using fine-mapping based on linkage disequilibrium in North African inbred families, we identified a short ancestral haplotype on chromosome 12q13 (<1 cM), sequenced a BAC contig encompassing the triple-A minimal region and identified a novel gene (AAAS) encoding a protein of 547 amino acids that is mutant in affected individuals. We found five homozygous truncating mutations in unrelated patients and ascribed the founder effect in North African families to a single splice-donor site mutation that occurred more than 2,400 years ago. The predicted product of AAAS, ALADIN (for alacrima-achalasia-adrenal insufficiency neurologic disorder), belongs to the WD-repeat family of regulatory proteins, indicating a new disease mechanism involved in triple-A syndrome. The expression of the gene in both neuroendocrine and cerebral structures points to a role in the normal development of the peripheral and central nervous systems.

Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome.

Triple A syndrome (Allgrove syndrome, MIM No. 231550) is a rare autosomal recessive disorder characterised by ACTH-resistant adrenal insufficiency, achalasia of the cardia, and alacrimia. The triple A gene has been previously mapped to chromosome 12q13 in a maximum interval of 6 cM between loci D12S1629 and D12S312. Using linkage analysis in 12 triple A families, mostly originating from North Africa, we confirm that the disease locus maps to the 12q13 region (Zmax = 10.89 at theta = 0 for D12S1604) and suggest that triple A is a genetically homogeneous disorder. Recombination events as well as homozygosity for polymorphic markers enabled us to reduce the genetic interval to a 3.9 cM region. Moreover, total linkage disequilibrium was found at the D12S1604 locus between a rare allele and the mutant chromosomes in North African patients. Analysis of markers at five contiguous loci showed that most of the triple A chromosomes are derived from a single founder chromosome. As all markers are located in a 0 cM genetic interval and only allele 5 at the D12S1604 locus was conserved in mutant chromosomes, we speculate that the triple A mutation is due to an ancient Arabian founder effect that occurred before migration to North Africa. Since we also found linkage disequilibrium at D12S1604 in two patients from Southern Europe (France and Spain), the founder effect might well extend to other Mediterranean countries. Taking advantage of a YAC contig encompassing the triple A minimal physical region, the triple A gene was mapped to a 1.7 Mb DNA fragment accessible to gene cloning.

[TSH determination in central hypothyroidism]. / Le dosage de la TSH dans l'hypothyroïdie centrale.

Central hypothyroidism is one of the limitations of the use of sensitive TSH assays as first line screen in evaluating thyroid function. Studies on this subject are however scarce. The aim of the present study is to evaluate the usefulness of TSH assay before and after TRH on a large series of patients with central hypothyroidism. Fifty two patients presenting with post-partum hypopituitarism (Sheehan's Syndrome), 32 hypothyroids and 20 euthyroids were studied, as well as 21 normal females. There was no difference in TSH basal levels (TSH0) between the hypothyroid (1.43 +/- 0.98 mU/l), the euthyroid patients (1.45 +/- 0.83 mU/l) and the controls (1.32 +/- 0.58 mU/l). Delta TSH (TSH 30 mn after TRH-TSH0) was higher (p < 0.001) in the control group (8.48 +/- 3.76 mU/l) than in the euthyroid group (2.63 +/- 2.22 mU/l) that had a better (p < 0.001) response than the hypothyroid group (0.93 +/- 1.11 mU/l). Ten euthyroid patients had impaired response to TRH, while 6 hypothyroids had a normal test. This test has no advantage over basal TSH in central hypothyroidism diagnosis. TRH test gives many misleading results and have an elevated cost/benefit ratio as compared with the characteristic combination of low thyroxinemia and non elevated TSH0.

The relative roles of endemic goiter and socioeconomic development status in the prognosis of thyroid carcinoma.

BACKGROUND: It generally is accepted that the prognosis of thyroid carcinoma is more severe in areas in which goiter is endemic. It could be assumed that this prognosis also is less favorable in developing countries. METHODS: Clinical features and tumor histology of 1000 consecutive patients were studied: Patient data from the endemic area (EA) were compared with those from the nonendemic area (NEA). In addition, patients from the years 1966-1981 (P1) were compared with those from 1982-1991 (P2). It is obvious that the country's socioeconomic status and health care system improved between the two periods. RESULTS: The anaplastic and follicular types of thyroid carcinoma were more frequent in EAs (14% and 42.13%, respectively) than in NEAs (6.25% and 38.40%, respectively). The frequency of the anaplastic carcinoma during P1 (16.03%) decreased by half during P2 (7.79%), whereas the frequency of follicular carcinoma remained stable (35.85% and 40.46%, respectively). Clinically, more advanced stages (tumor size, local and distant disseminations) were observed in the study country than in developed countries. A clearcut improvement was observed during P2 whereas differences between the EA and NEAs were few. Survival rates (follicular and papillary types only) were not found to be different between EAs and NEAs (5-year survival: 81.44% and 75.32%, respectively; 10-year survival: 67.93% and 69.52%, respectively). A significant (P < 0.01) increase was observed between P1 and P2 (5-year survival: 72.69% and 84.80%, respectively; 10-year survival: 58.77% and 83%, respectively). CONCLUSIONS: Compared with endemic goiter, low socioeconomic status appeared to be the major factor accountable for the high prevalence of advanced stage cases and anaplastic carcinomas. Iodine deficiency appeared to play a specific role in the increased prevalence of follicular types of thyroid carcinoma.

Treatment of Cushing's disease by transsphenoidal, pituitary microsurgery: prognosis factors and long-term follow-up.

Transsphenoidal pituitary microsurgery is considered as the best treatment of Cushing's disease. However, some recent studies reported disappointing results, leading their authors to suggest the possibility of returning to a first line adrenalectomy treatment. The aim of this study was to evaluate long-term results of transsphenoidal surgery in Cushing's disease, with special interest in factors that could affect the surgical outcome on the one hand and particular attention to surgical endocrine effects on the other. Fifty consecutive patients (34 females, 16 males, mean age 29.64 +/- 1.52 yr) were studied. The median post-operative follow-up was 71.5 months (range 25-219). Clinical, biological, surgical and pathological data between the success and failure groups were compared. Criteria of cure were: normal urinary free cortisol excretion, circadian cortisol rhythm and low dose dexamethasone test. Recovery of corticotroph and somatotroph functions were followed using the insulin test. Particular attention is given to clinical evolution in evaluating other pituitary functions. T4 or FT4, prolactin, E2 in women, testosterone in men, were measured. TRH and LHRH tests were not systematically performed. Only two parameters differed significantly between the cured and failure groups: the size of the adenomas was smaller and the pathological confirmation of the adenoma more frequent in the cured group. One patient had permanent corticotropic failure while two other had impaired response to hypoglycemia with normal cortisol basal levels. No acquired hypothyroidism nor hypogonadism were observed except in a patient who underwent two operations and radiotherapy. Recovery of GH function was slow. Definitive short stature was observed in all the patients whose disease began before the age of 16. Two patients had permanent diabetes insipidus. In conclusion, the most favorable prognosis in transsphenoidal surgery for Cushing's disease is observed in case of microadenoma confirmed by pathological examination. With this treatment, we obtained satisfactory results in Cushing's disease with minimal complications and no necessity of life-long endocrine substitutive therapy.

[Hypothalamic-pituitary-adrenal function in primary hypothyroidism]. / Fonction hypothalamo-hypophyso-surrénalienne au cours de l'hypothyroïdie primaire.

OBJECTIVES: Hypothyroidism is known to lead to a certain degree of functional insufficiency of the adrenal gland by affecting both the hypophyseal axis and peripheral metabolism of cortisol. This study was conducted to evaluate hypothalamic, pituitary, and adrenal function in a homogeneous group of patients with long-standing major hypothyroidism. METHODS: Forty-five patients (32 females, 13 males; mean age 42.9 +/- 9.6 years; range 20-59) with major primary hypothyroidism known to be long-standing (> 1 year in 1 and for an undetermined duration of several years in all the others) were included. Twenty-nine age-matched subjects served as controls. Insulin-induced hypoglycaemia and oral metyrapone tests were performed before and after treatment had induced euthyroidism. Plasma ACTH and cortisol were measured every 20 min for 2 hours during the hypoglycaemia test and ACTH before and after the last dose of metyrapone. Plasma cortisol levels were determined before and 30 min after injection of tetracosactide. RESULTS: Baseline ACTH and cortisol were not different in patients and controls and were unchanged by treatment. ACTH and cortisol response to hypoglycaemia were weaker in patients with ongoing hypothyroidism (p < 0.05 vs controls) and improved significantly (p < 0.05 vs baseline) after treatment. Adreno-cortical response to exogenous ACTH stimulation was weaker in patients with hypothyroidism (p < 0.05 vs controls) and returned to normal after treatment. CONCLUSIONS: Modifications of the hypothalamic-pituitary-adrenal system resulting from hypothyroidism were minimal and evidenced only by dynamic exploration. Levels returned to normal after adequate treatment and the deficit restricted to the hypothalamus and pituitary might also involve the adrenal gland.

The sella turcica in Sheehan's syndrome: computerized tomographic study in 54 patients.

A CT scan study of the sella turcica and its contents was conducted in patients with Sheehan's syndrome with a search for correlation between the radiological data and the degree of endocrine insufficiency on one hand, and the time course of the disease on the other. Fifty-four patients with Sheehan's syndrome were included: 32 with complete anterior hypopituitarism, 22 with at least one spared pituitary function. Subgroups of equal size were obtained with a cut-off of 9 years evolution. The CT scan appearance of the pituitary was never normal in Sheehan's syndrome. The sella turcica was totally empty in 39 patients. A pituitary remnant was visible in 15 patients, more frequently in those with incomplete hypopituitarism (p less than 0.005) and those with short evolution (p less than 0.025). The size of this pituitary residue never exceeded one third of the normal pituitary gland. The pituitary stalk was always visualized. On the other hand, the size of the fossa was significantly (p less than 0.001) smaller in the patients, as compared to a 12-female control group, matched for age and number of pregnancies. Among the patients there was no difference when considering the disease duration nor the degree of hypopituitarism. An empty or partially empty sella of normal or reduced size is a constant feature of Sheehan's syndrome. The presence of a pituitary remnant is inversely correlated to the duration and extension of the disease. Arachnoid herniation alone does not induce a dilatation of the fossa.

Aldosterone in panhypopituitarism: dynamic studies and therapeutic effects in Sheehan's syndrome.

To appreciate the aldosterone secretion status in panhypopituitarism, the steroid response to stimulation was studied in a homogeneous group of 20 female patients presenting with global hypopituitarism. Specific effects of glucocorticoid and thyroid hormone deficiencies were also assessed by studying the same patients before and after cortisol (F) and cortisol plus thyroid hormone (F + T) substitution. The patients were submitted to two stimulation tests before and after each treatment: the orthostasis test (O-T) and the furosemide test (Furo-T). The results obtained in the 3 situations were compared, each patient serving as her own control. Comparison was also established with the results obtained in healthy women serving as control group. Basal plasma aldosterone levels in the untreated patients were not significantly different from those of the control group (5.43 +/- 0.51 vs 7.16 +/- 0.80 ng/100 ml, mean +/- SEM). They were significantly lower after F (3.91 +/- 0.42) and F + T substitution (3.31 +/- 0.23) than those of untreated patients and controls. Response to both stimulations was blunted in the untreated patients (O-T: 14.10 +/- 2.81; Furo-T: 9.78 +/- 1.35) as compared to the control group (O-T: 26.46 +/- 4.67; Furo-T: 23.96 +/- 3.30). F treatment did not improve the response to either tests, (O-T: 11.42 +/- 2.55; Furo-T: 10.32 +/- 1.23). F + T treatment normalized the orthostasis response (20.83 +/- 3.59) and increased the response to furosemide which remained, however, lower (15.28 +/- 1.83) than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidiuretic function in Sheehan's syndrome.

Twenty patients with postpartum hypopituitarism underwent a dehydration test followed by the administration of synthetic arginine-vasopressin (DDAVP; desmopressin). Panhypopituitarism was confirmed by hormonal assays in the basal state and after stimulation with combined luteinising hormone releasing hormone-thyrotrophin releasing hormone-insulin. All the patients were given replacement therapy with hydrocortisone and thyroid hormones. Results were compared with those in 12 normal women. Urinary concentrating ability was diminished in the patients as compared with the controls (maximum urine osmolality 688 (SEM 23) mmol (mosmol)/kg in the patients v 967 (SEM 29) mmol/kg in the controls). Also the change in urine osmolality after administration of desmopressin was greater in the patients (+9.55 (SEM 1.98)% in the patients v 2.49 (SEM 0.96)% in the controls). Partial diabetes insipidus is apparently common in Sheehan's syndrome. This association should be borne in mind when managing these patients, especially those in acute failure.

Arginine-vasopressin in postpartum panhypopituitarism: urinary excretion and kidney response to osmolar load.

The response to an osmolar load (750 ml 2.5% NaCl solution iv preceded by 500 ml water by mouth) was studied in 20 patients with Sheehan's syndrome and 12 normal women. Sodium and osmolality were determined in plasma and urine and arginine-vasopressin (AVP) was measured by RIA in urine. The test was performed in each patient when untreated (group P), after hydrocortisone replacement alone (group F), and combined hydrocortisone and thyroid hormone replacement (group F+T). After the osmolar loading, maximum urinary osmolality in the patients was lower than in the normal women and remained unaffected by both hydrocortisone alone and hydrocortisone and thyroid hormone. Comparison of the mean hourly urinary volume before and after NaCl infusion demonstrated an increase in group P, a decrease in group C, and no change in groups F and F+T. Although free water clearance became negative in all groups, values in groups P, F, and F+T were constantly above that of group C. None of the patients in groups P and F had a significant rise in urine AVP excretion during or after NaCl infusion. Those in group F+T had a slight AVP response which was less than in normal women. Impaired response of AVP to an osmolar load appears to be a constant feature of Sheehan's syndrome even without overt diabetes insipidus.

The renin-angiotensin system in panhypopituitarism: dynamic studies and therapeutic effects in Sheehan's syndrome.

To gain insight in the influence of the pituitary gland on the renin-angiotensin system plasma renin substrate (PRS) and the response of PRA to stimulation were studied in a homogeneous group of 20 female patients with the same etiology and degree of pituitary failure, before treatment (group P), after hydrocortisone substitution (group F), and after hydrocortisone and thyroid hormone treatment (group F + T). All patients were studied before and after each treatment by response to two stimulatory tests, acting through two different pathways; orthostasis test (O-T) and the furosemide test (Furo-T). Results were compared between groups, each patient serving as her own control, and with those obtained in a 12 healthy women control group (group C). The diet contained about 85 meq Na/day. Compared to group C (O-T response, 5.97 +/- 0.54 ng ml-1 h-1; Furo-T response, 6.71 +/- 0.82 ng ml-1 h-1; mean +/- SEM), PRA response to both tests was blunted in group P (O-T: 2.48 +/- 0.46, P less than 0.001; Furo-T: 3.02 +/- 0.53, P less than 0.001) and remained so in F (O-T: 2.18 +/- 0.40, P less than 0.001; Furo-T: 2.52 +/- 0.28, P less than 0.001), In group F + T, the response to both tests was greater than in P and F (O-T, 6.61 +/- 1.19; Furo-T, 4.36 +/- 0.44; 0.001 less than P less than 0.05). However, whereas the response to orthostasis is entirely normalized, the response to a diuretic remained significantly smaller than in group C (P less than 0.01). These improvements were observed without significant change in PRS concentration which remained low. We conclude that panhypopituitarism is accompanied by an altered renin angiotensin system. Basal levels of PRS and PRA are low and unresponsive to adequate stimulation. Whereas glucocorticoid therapy alone is without effect on this hyporeninism, addition of thyroid hormones completely normalized the response to orthostasis and significantly improved furosemide response.

[Effects of arginine and growth hormone, administered in vivo and in vitro, on the oxygen consumption of rat liver hemogenates]. / Effets de l'arginine et de l'hormone croissance administrées "in vivo" et "in vitro" sur la consommation d'oxygène d'homogénats de foie de rat

Effects of arginine aspartate, arginine chlorhydrate, potassium aspartate, with equal arginine base and aspartate ion available for all there compounds, growth hormone, and association of these different substances, are studied on rat hepatic homogenates oxygen consumption during 7 to 12 h, after injection to rats 1 h before sacrifice (A.A.: 0.50 g, C.A.: 0.34 g, A.K.: 0.22 g, STH: 2 U.I.), or "in vitro" adjunction to the preparation (A.A.: 0.125 g, C.A.: 0.085 g. A.K.: 0.055 g. STH: 0.5 U.I./0.25 g of liver). 1) "In vivo", arginine (endogenous STH secretion stimulation) is active: A.A. (+23% to +96% from 1 h to 8 h, p is less than 0.01), C.A. (+49% from 5 h to 8 h, p is less than 0.01), whereas potassium aspartate is inactive. "In vitro", aspartate is active: A.K. (+24% to +147% from 4 h to 12 h, (p is less than 0.01), A.A. (+56% to +53% from 7 h to 12 h, p is less than 0.01), whereas arginine without aspartate: C.A. is inactive. 2) Exogenous STH is active "in vivo" (+111% from 5 h to 8 h, p is less than 0.01) and "in vitro" (+31% from 4 h to 7 h, p is less than 0.01). 3) Association A.A. + STH (endogenous STH + exogenous STH) when given "in vivo", dose not produce any additive effect the tissue Vo2 release (+91% from 5 h to 8 h, p is less than 0.01) does not differ from STH and A.A. Aspartate added to STH "in vitro" enhances STH effects: (A.A. + STH: + 44% to +114% from 4 h to 12 h, p is less than 0.01, A.K. + STH: 73% to + 152% from 4 h to 12 h, p is less than 0.01).

[The effects of arginine and growth hormone on the nitrogen balance of rats]. / Effets de l'arginine et de l'hormone de croissance sur le bilan d'azote du rat

Intramuscular administration effects of arginine aspartate (AA : 0,50 g a day for 4 days), arginine chlorhydrate (CA : 0.34 g a day for 4 days), potassium aspartate (AK : 0.22 g a day for 4 days) with equal arginine base and aspartate ion supply for all products, bovine growth hormone (STH : 2 U.I. a day for 4 days), and the association of these substances, are studied on 6 rats, during a 74 days nitrogen balance period. Arginine (endogenous STH secretion stimulation) produces a greater nitrogen retention with AA (+ 184%, p less than 0.01) than CA (+ 71% p less than 0.10). A.K. had no effect. With exogenous STH, effect is important (+ 248%, p less than 0.01) but does not significantly differ from AA. STH + A.A. and STH + C.A. associations (exogenous and endogenous STH) produce a very marked nitrogen retention (+ 282% and + 252%, p less than 0.01) which, however, does not significantly differ from STH when given alone.