Transplanted beta cell response to increased metabolic demand. Changes in beta cell replication and mass.

We determined the capacity of transplanted beta cells to modify their replication and mass when stimulated by changes in metabolic demand. Five groups of Lewis rats were studied: group 1 (Tx-Px) had a 95% pancreatectomy 14 d after transplantation of 500 islets; group 2 (Px-Tx) had a 95% pancreatectomy 14 d before transplantation of 500 islets; group 3 (Tx) was transplanted with 500 islets; group 4 (Px) had a 95% pancreatectomy; and group 5 (normal) was neither transplanted nor pancreatectomized. Blood glucose was normal in Tx-Px and Tx groups at all times. Px-Tx and Px groups developed severe hyperglycemia after pancreatectomy that was corrected in Px-Tx group in 83% of rats 28 d after transplantation. Replication of transplanted beta cells increased in Tx-Px (1.15 +/- 0.12%) and Px-Tx (0.85 +/- 0.12%) groups, but not in Tx group (0.64 +/- 0.07%) compared with normal pancreatic beta cells (0.38 +/- 0.05%) (P < 0.001). Mean beta cell size increased in Tx-Px (311 +/- 14 microns2) and Px-Tx (328 +/- 13 microns2) groups compared with Tx (252 +/- 12 microns2) and normal (239 +/- 9 microns2) groups (P < 0.001). Transplanted beta cell mass increased in Tx-Px (1.87 +/- 0.51 mg) and Px-Tx (1.55 +/- 0.21 mg) groups compared with Tx group (0.78 +/- 0.17 mg) (P < 0.05). In summary, changes in transplanted beta cells prevented the development of hyperglycemia in Tx-Px rats. Transplanted beta cells responded to increased metabolic demand increasing their beta cell mass.

Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice.

In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant. We studied the evolution of beta cell replication and mass after transplantation of insufficient, minimally sufficient, or excessive islet tissue. Streptozocin diabetic C57BL/6 mice received 150 or 300 syngeneic islets under the kidney capsule and normal mice received 300 islets. In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant. In contrast, 150 islets were insufficient to achieve normoglycemia; beta cell replication was increased initially but not by 18 or 30 d despite persistent hyperglycemia, and beta cell mass fell progressively. When islets were transplanted into normal recipients, beta cell replication remained normal but beta cells underwent atrophy and mass in the graft was substantially reduced. Therefore, with a successful islet transplant, in diabetic mice beta cell replication and mass remain constant. In contrast, when insufficient islet tissue is transplanted an initial increase in beta cell replication can not compensate for a decline in beta cell mass. When excessive islet tissue is transplanted, beta cell mass is reduced despite normal beta cell replication.

[Systemic toxicity caused by local anesthetics after peripheral nerve blocks]. / Toxicidad sistémica por anestésicos locales tras bloqueos de nervios periféricos.

Peripheral nerve blocks have aroused increasing interest in recent years, leading to a rise in the rate of complications. At the same time noteworthy technical advances have been made in areas such as nerve stimulation and ultrasound imaging, and local anesthetics have become safer. Nevertheless, the risk of anesthetic-related systemic toxicity, which manifests with neurological symptoms that tend to be forerunners of cardiovascular ones, can not be ignored. We report 2 cases of systemic toxicity due to the use of a mixture of local anesthetics during nerve blocks for outpatient surgery.

Beta-cell growth and mass are preserved in long-term syngeneic islet transplantation in streptozocin-induced diabetic Lewis rats.

We determined beta-cell replication and mass in basal and stimulated conditions in long-term transplanted islets. Three groups of streptozocin-induced diabetic Lewis rats were transplanted with 1,000 islets (500 islets under left and right kidney capsules). At 2 (Tx-2), 5 (Tx-5), or 9 (Tx-9) months after transplantation, one of the two grafts (basal) was harvested; 14 days later, the contralateral graft (stimulated) was also harvested. Normoglycemia was achieved and maintained in all transplanted rats, although the capacity to respond to a glucose challenge deteriorated slightly 9 months after transplantation. Beta-cell replication remained stable in Tx-2, Tx-5, and Tx-9 basal grafts and was similar to replication in a control group of nontransplanted rats (0.28 +/- 0.06%); replication increased in Tx-2 (0.90 +/- 0.23%, P < 0.05) and Tx-9 (0.72 +/- 0.09%, P < 0.05) stimulated grafts. Beta-cell mass in basal grafts was similar to the initially transplanted mass (1.24 +/- 0.06 mg) and increased in stimulated grafts in Tx-2 (1.91 +/- 0.38 mg, P < 0.05) and Tx-5 (1.73 +/- 0.27 mg, P = 0.01) groups, compared with basal grafts, and in Tx-2 and Tx-9 groups (1.92 +/- 0.30 mg, P < 0.05), compared with initially transplanted mass. Therefore, beta-cell replication and mass were preserved up to 9 months after syngeneic transplantation, and beta-cells maintained the capacity to respond to increased metabolic demand, suggesting that replication is not a limiting factor in the survival of transplanted islets.

Diminished fraction of blockable ATP-sensitive K+ channels in islets transplanted into diabetic mice.

The reasons for the poor outcome of islet transplantation in diabetic patients are not well known; a better understanding of the pathophysiology of transplanted islets is needed. To study the mechanism coupling secretagogue stimuli with insulin release in transplanted islets, we determined the effects of glucose, tolbutamide, and carbamylcholine on the beta-cell membrane potential and cytosolic calcium concentrations ([Ca2+]i) of islets syngeneically transplanted into normal and streptozocin-induced diabetic mice. In both groups, normoglycemia was maintained after transplantation. Islets transplanted into normal recipients showed similar changes in beta-cell membrane potential and [Ca2+]i oscillations to those in control islets. In contrast, when islets were transplanted into diabetic mice, bursts of electrical activity were triggered at lower glucose concentrations (5.6 mmol/l) than in control islets (11 mmol/l), and maximal electrical activity was achieved at lower glucose concentrations (11 mmol/l) than in control islets (22 mmol/l). When membrane potential was plotted as a function of glucose concentration, the dose-response curve was shifted to the left. Compared with control islets, glucose-induced [Ca2+]i oscillations were broader in duration (22.3 +/- 0.6 s vs. 118.1 +/- 12.6 s; P < 0.01) and higher in amplitude (135 +/- 36 nmol/l vs. 352 +/- 36 nmol/l; P < 0.01). Glucose supersensitivity was attributed to a resting decrease in the fraction of blockable ATP-sensitive K+ (K+(ATP)) channels in transplanted islets that maintained normoglycemia with a limited beta-cell mass.

Trends and outcomes after prenatal diagnosis of congenital cardiac malformations by fetal echocardiography in a well defined birth population, Atlanta, Georgia, 1990-1994.

OBJECTIVES: In this study we used a population-based approach to assess the impact of fetal echocardiography on a well defined birth population with nearly complete ascertainment of cardiac defects. BACKGROUND: Although fetal echocardiography is being used more frequently in the prenatal diagnosis of congenital cardiac malformations, its impact on the diagnosis and surveillance of cardiac defects has not been described in defined populations. METHODS: All stillborn and live-born infants with diagnosed cardiac defects and whose mothers resided in the metropolitan Atlanta area from January 1990 through December 1994 were ascertained through an established birth defects surveillance system. All fetuses with cardiac defects diagnosed prenatally by a pediatric of cardiac defects, diagnostic trends and adverse fetal outcomes were described. RESULTS: We identified 1,589 infants with congenital cardiac malformations, for a live-birth prevalence rate of 8.1/1,000 (95% confidence interval [CI] 7.8 to 8.6). Overall, 97 (6.1%) of these cases of cardiac malformations were diagnosed prenatally. The proportion of cardiac defects diagnosed prenatally rose from 2.6% in 1990 to 12.7% in 1994, a nearly fivefold increase. The proportion of cardiac defects diagnosed prenatally during the study varied by the type of defect, from a low of 4.7% for atrial septal defects to a high of 28% for hypoplastic left heart syndrome. Prenatally diagnosed cardiac malformations were associated with a high incidence of infant mortality (30.9%, 95% CI 2.4 to 5.4) and fetal wastage (17.5%, 95% CI 6.2 to 11.3). CONCLUSIONS: These data show that fetal echocardiography is being used increasingly in the prenatal diagnosis of congenital cardiac malformations in metropolitan Atlanta. Few pregnancy terminations were reported as a result of such diagnoses. However, the study had limited power (10%) to detect a meaningful decrease in birth prevalence rates for congenital heart disease. In addition, survival of infants was not improved after prenatal diagnosis with fetal echocardiography.

Minimum number of islets required to maintain euglycemia and their reduced immunogenicity after transplantation into diabetic mice.

In streptozocin (SZ)-induced diabetic mice, 200 islets, but not 50 islets, consistently restore euglycemia within 1 week of transplantation. To determine the minimum number of islets sufficient to maintain euglycemia in a diabetic mouse, we first transplanted 50 and 150 syngeneic islets simultaneously into the right (RK) and left kidney (LK), respectively, and then removed the LK 1 week post-transplantation. The remaining 50 islets maintained euglycemia in 8 of 11 mice with normal intravenous glucose tolerance tests (IVGTT). Protection of 50 islets for at least 7 days was necessary because removal of the 150 islets at 5 or 3 days resulted in a much lower incidence of persistent euglycemia. Similarly, 25 islets were capable of maintaining euglycemia in 2 of 9 mice once hyperglycemia was reversed by split-transplantation of 25 (RK) and 175 (LK) islets. To examine if 50-islet allografts survive longer than 200-islet allografts, we split-transplanted 50 DBA/2 islets in the RK and 150 islets of either B6 (syngeneic), DBA/2 (allogeneic), or C3H/He (third party allogeneic) mouse origin in the LK in 3 groups of diabetic C57BL/6 (B6) mice. The survival of 50 DBA/2 islets in each group after removal of the LK on day 7 was compared to that of 200 DBA/2 islets in control B6 mice. Maximum prolongation of allograft survival was obtained with 50 DBA/2 islets that were split-transplanted with syngeneic B6 islets. These results clearly demonstrate that 50 islets are sufficient to maintain normal glucose tolerance once euglycemia is induced by transplantation of a larger number (i.e., 200) of islets and that 50 islet allografts are much less immunogenic than 200-islet allografts.

Kawasaki disease and the T-cell antigen receptor.

We investigated the evidence for an infectious etiology of Kawasaki disease (KD), an acute vasculitis of unknown etiology, by assessing the effects of KD on the T cell antigen receptor variable beta region families (V beta). Using 3-color flow cytometry, we studied KD patients pre- and post-intravenous gamma globulin (IVIG) therapy and at > 40 days post therapy, additionally comparing them to matched pediatric control patients (PCC) and their own healthy parents (one parent/KD child). Of all the V beta families examined, only V beta 2 exhibited statistically significant differences, between the pre- and post-IVIG samples and preIVIG and parent samples. No associations were found between V beta 2 findings and T cell memory, activation, or adhesion markers. For 2 KD patients, 4 parents, and 1 PCC participant, > 15% of resting CD8+ lymphocytes and > 15% of blastic CD8+ lymphocytes expressed a single V beta family, which varied by individual, without similar expansions in the CD4+ cell populations. One of the participants with this abnormality was the only one with significant cardiac abnormalities. For all participants with the V beta abnormality, other T-cell abnormalities were extensive and involved both CD4+ and CD8+ cells. We suggest that V beta 2 changes do occur in KD, as previously reported. However, these may not be involved in disease pathogenesis. Other V beta changes also occur. Those occurring in parents may reflect asymptomatic reinfection with an infectious agent causing KD. Further, some KD patients may have restricted cytotoxic T-cell responses to that as yet unidentified agent; this restricted response may be associated with more severe cardiac involvement.

Acute pulmonary hemorrhage in infants associated with exposure to Stachybotrys atra and other fungi.

BACKGROUND: A geographic cluster of 10 cases of pulmonary hemorrhage and hemosiderosis in infants occurred in Cleveland, Ohio, between January 1993 and December 1994. STUDY DESIGN: This community-based case-control study tested the hypothesis that the 10 infants with pulmonary hemorrhage and hemosiderosis were more likely to live in homes where Stachybotrys atra was present than were 30 age- and ZIP code-matched control infants. We investigated the infants' home environments using bioaerosol sampling methods, with specific attention to S atra. Air and surface samples were collected from the room where the infant was reported to have spent the most time. RESULTS: Mean colony counts for all fungi averaged 29 227 colony-forming units (CFU)/m3 in homes of patients and 707 CFU/m3 in homes of controls. The mean concentration of S atra in the air was 43 CFU/m3 in homes of patients and 4 CFU/m3 in homes of controls. Viable S atra was detected in filter cassette samples of the air in the homes of 5 of 9 patients and 4 of 27 controls. The matched odds ratio for a change of 10 units in the mean concentration of S atra in the air was 9.83 (95% confidence interval, 1.08-3 X 10(6)). The mean concentration of S atra on surfaces was 20 X 10(6) CFU/g and 0.007 x 10(6) CFU/g in homes of patients and controls, respectively. CONCLUSION: Infants with pulmonary hemorrhage and hemosiderosis were more likely than controls to live in homes with toxigenic S atra and other fungi in the indoor air.

Ketoacidosis at diagnosis is predictive of lower residual beta-cell function and poor metabolic control in type 1 diabetes.

To determine the factors at diagnosis predictive of changes in residual beta-cell function and metabolic control in Type 1 diabetes, 125 patients older than 7 years of age consecutively diagnosed between March 1986 and June 1991 were followed prospectively for two years. The effect of age, gender and the presence of ketoacidosis (DKA) and islet-cell antibodies (ICA) on beta-cell function, metabolic control and insulin requirements were studied by multivariate analysis of variance (repeated measurements over time) in 90 patients who completed follow-up. DKA had an independent negative effect on residual beta-cell function over time (p = 0.001). ICA-positive patients had lower residual beta-cell function at the end of follow-up (p < 0.05), but overall differences were not significant. DKA and younger age had an independent negative influence on metabolic control (p < 0.05) and insulin requirements (p < 0.001) over time. It is concluded that residual beta-cell function in Type 1 diabetic patients two years after diagnosis was independently influenced by DKA and ICA at diagnosis. Moreover, DKA and age influenced metabolic control and could thus be used to predict those patients with rapidly deteriorating metabolic control who might benefit from a more intensive therapeutic approach.

Replication of adult pancreatic-beta cells cultured on bovine corneal endothelial cell extracellular matrix.

A valuable system has been developed to study replication of adult beta cells. Isolated islets from adult rats were partially dispersed and plated on dishes coated with extracellular matrix from bovine-corneal endothelial cells. Within 24 h islet cells attached to the matrix and formed a monolayer. The proportion of insulin-, glucagon-, and somatostatin-containing cells in the cultures was characteristic of whole islets. Function of beta cells was assessed by measuring glucose-stimulated insulin release. Insulin release from 7-day-old cultures increased 19-fold after a 16.7 mM glucose challenge indicating that beta-cell function was normal. Cellular replication in the cultures was assessed using the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). BrdU incorporation was noted in insulin-, glucagon-, and somatostatin-containing cells and also in non-endocrine cells. Among endocrine cells, the majority of BrdU labeling occurred in beta cells. Beta-cell replication potential was assessed using different concentrations of glucose. The incorporation of BrdU into beta cells was affected in a dose-dependent manner by glucose; over a 10-fold increase of beta-cell BrdU labeling was observed when glucose concentration was raised from 5.5 to 16.7 mM. The system proved advantageous for studying the replication potential of adult beta cells.

Bone mineral density in patients with type 1 diabetes mellitus.

Although osteopenia is often reported as a complication of type 1 diabetes mellitus, its frequency and severity remain unclear, and studies of bone mineral density in type 1 diabetics have yielded conflicting results. We measured bone mineral density at the lumbar spine and femoral neck in 88 Spanish adults with type 1 diabetes mellitus responsible for moderately severe complications. Mean age (+/- SD) was 28.9 +/- 8.8 years, and mean disease duration was 11.2 +/- 6.4 years. As compared to normal Spanish adults, bone mineral density was decreased in the patients at the lumbar spine (Z-score, -0.32 +/- 1.08; P < 0.001) but not at the femoral neck (Z-score, -0.21 +/- 1.03; P non-significant). The magnitude of bone loss in the diabetics was small (T-score, -0.38 +/- 1.13 at the lumbar spine and -0.37 +/- 1.08 at the femoral neck). Only three patients met WHO criteria for osteoporosis at one or both measurement sites. Patients with retinopathy (n = 37) had lower lumbar spine bone mineral density values than patients without retinopathy; however, this difference was no longer present after adjustment for age and disease duration. Bone mineral density values were similar in patients with (n = 13) and without microalbuminuria. Our findings suggest that bone loss is not a major problem in younger type 1 diabetics with short disease durations and no severe diabetic complications.

Exercise-induced bronchospasm in nonasthmatic obese children.

The frequency, degree, and pattern of bronchial reactivity to exercise were compared in 13 obese and 14 control children, ages 6 to 10 years, with no history of asthma. Spirometry was performed before and every three minutes after a seven-minute exercise challenge on a treadmill. There were 11 obese children and 6 controls who had at least a 15% fall in at least one of three monitored pulmonary function parameters (P < .05). The group mean percentage falls in FEV1 and FEF25%-75% were significantly greater in the obese group than in the controls. The pattern of bronchospasm, occurring soon after the exercise challenge, is consistent with that found in the known asthmatic population. A significant correlation was found between triceps skin-fold thickness and degree of fall in FEF25%-75% (r = .55, P < .005). This study demonstrated that significantly greater frequency and degree of bronchospasm of the smaller airways occur in obese children, partially related to the amount of subcutaneous fat. Whether exercise-induced bronchospasm leads to exercise avoidance and obesity or whether obesity causes or enhances bronchial hyperreactivity to exercise requires further study.

[Study of thyroid function parameters and thyrotropin in general non-thyroid diseases]. / Estudio de los parámetros de función tiroidea y de la tirotropina en la enfermedad general no tiroidea.

The changes in the parameters of thyroid function and thyrotropin (TSH) have been evaluated in 5 groups of patients with general non-thyroid disease (GNTD): acute severe bacterial infection (16 patients), acute myocardial infarction (22 patients), diabetic ketoacidosis (24 patients), non-ketotic hyperosmolar decompensation (8 patients), protein-calorie undernutrition (12 patients), without associated conditions or drug therapies that might have modified the thyroid hormones. These patients were evaluated at the beginning of their GNTD and after recovery. Thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) were measured by radioimmunoassay (RIA), the TBC index by competitive analysis, the free T4 by a labeled T4 analogue and T4 by immunoradiometric analysis (IRMA). In all patients similar changes in thyroid hormones and in IRMA were found, and they returned to normal after recovery; the changes were most marked in diabetic ketoacidosis, followed by hyperosmolar decompensation and by undernutrition. When the 5 groups were evaluated together, T3 was the most commonly low value (57.3%), followed by T4 and TBC index (26.8%), free T4 (20.7%) and the free T4 index (10.9%). The level of rT3 was increased in 39% of cases. Baseline TSH was, initially, 1.05 +/- 1.05 microU/ml, and 1.36 +/- 0.85 microU/ml after recovery (p less than 0.001). It was only found to be suppressed in one patient (a female with diabetes mellitus and Graves disease); in 17 cases it had borderline values between 0.1 and 0.4 microU/ml, and in the remaining patients it was normal. GNTD induces profound changes in the thyroid functional parameters, with reductions below their normal range, including the analogue measured T4 and low TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

[Limitations of joint mobility in patients with type 1 diabetes mellitus]. / Limitación de la movilidad articular en pacientes con diabetes mellitus tipo I.

BACKGROUND: To assess limitation of joint mobility in patients with type I diabetes mellitus and to evaluate its relation with retinopathy, joint mobility was prospectively assessed in 96 diabetic patients and 68 healthy controls. METHODS: Joint mobility was explored with the praying maneuver and the measurement in mobility degrees of the third and fifth metacarpophalangeal joints, wrists and elbows. The degree of metabolic control was assessed with the mean glycosylated hemoglobin in the last two years. Retinopathy was investigated with direct funduscopy. The results were statistically evaluated with chi-square and Student's t tests and the linear coefficient. RESULTS: A reduced joint mobility was found in 41 diabetics and 5 controls (p less than 0.0001). The reduction in joint mobility was related with the patients' age but not with the degree of metabolic control. 85% of diabetics with joint involvement had retinopathy of some degree. CONCLUSIONS: A limited joint mobility is a common complication of type I diabetes mellitus. The demonstration of this abnormality in diabetic patients might represent a first and simple marker of microangiopathy.

[Value of basal cortisol and ACTH in the immediate postoperative period of hypophyseal surgery in non-ACTH secretory adenomas]. / Interés del cortisol y de la ACTH basales en el postoperatorio inmediato de cirugía hipofisaria en adenomas no secretores de ACTH.

BACKGROUND: The aim of this study was to evaluate the usefulness of basal cortisol and ACTH in the immediate postoperative period of pituitary surgery as indicators of definitive adrenocorticotropin function. METHODS: Twenty-one patients with pituitary, non producers of ACTH, adenomas, three microadenomas and 18 macroadenomas treated by adenomectomy by a trans-sphenoidal route were respectively studied. The basal cortisol and ACTH were compared in the first week following surgery with the definitive results obtained after one month by dynamic tests (stimulation with ACTH or insulin hypoglycemia). RESULTS: The six patients with secondary adrenal failure (AF) in the definitive evaluation had lower basal cortisol in the immediate postoperative period than the patients with AF (135.3 +/- 225.3 nmol/l versus 473.6 +/- 147.2 nmol/l; p < 0.05). The values of ACTH were also lower (2.3 +/- 1.6 nmol/l versus 4.8 +/- 3.4; p < 0.05). In all the patients with definitive AF except one, the basal cortisol in the first week was lower than 130 nmol/l and in those who did not present AF it was greater than 220 nmol/l. CONCLUSIONS: In the immediate postoperative period after pituitary surgery cortisol is a good indicator of definitive adrenocorticotropin function. This parameter may identify the patients requiring posterior substitutive treatment.

[Pituitary apoplexy: analysis of endocrine function in 17 cases]. / Apoplejía hipofisaria: análisis de la función endocrina en 17 casos.

BACKGROUND: From a neurological standpoint, pituitary apoplexy (PA) is a well defined syndrome. There are few systematic studies addressing pituitary hormone secretion after a PA episode. The aim of the present study was to assess the frequency and degree of endocrine dysfunction due to PA. METHODS: In 17 consecutive patients, the secretion of growth hormone (GH), the pituitary-adrenal axis status, thyrotropin (TSH), prolactin and gonadotropins (LH, FSH) were evaluated after the administration of insulin, thyrotropin releasing hormone (TRH) and gonadotropin-releasing hormone (LHRH) after an episode of PA. 20-90 days after surgery the measurements were repeated. Antidiuretic hormone (ADH) was measured by plasma/urine osmolality after water deprivation and, in some cases, by administration of hypertonic saline. RESULTS: The most commonly found deficiency was that of GH (84%), which in two cases resulted in cure of acromegaly, followed by that of LH (78%). Pituitary-adrenal dysfunction was improved in two patients after surgery. In all cases except one there was a reduced secretion of at least two hormones. If serum prolactin was reduced, the rest of pituitary function was usually impaired. In one case, permanent diabetes insipidus developed after PA. The prevalence of PA in pituitary adenomas was 9%. CONCLUSIONS: Pituitary hormone secretion after a PA episode is almost invariably impaired. This impairment may be reversed after surgery. Hypoprolactinemia is an indicator of pituitary hypofunction.

[Thyroid function parameters and TSH in patients treated with anticonvulsant drugs]. / Estudio de los parámetros de función tiroidea y de la TSH en pacientes tratados con fármacos anticonvulsionantes.

Several antiepileptic drugs change the serum levels of thyroid hormones by different mechanisms, of these diphenylhydantoin being the most known. This study was carried out on 96 patients in order to analyse the effects of long-term treatment with phenobarbital (N = 29), carbamazepine (N = 21), sodium valproate (N = 11), diphenylhydantoin (N = 6) and a combination of them all at therapeutic doses. We observed a decrease of T4 seric levels and free T4 index (in 25 and 14 patients respectively, under normal levels) free T4 normal, T3 normal, decreased rT3, and normal TSH in all groups being more noticeable in patients treated with diphenylhydantoin, carbamazepine, phenobarbital and lastly, sodium valproate. It is a different situation from a general non-thyroid disease, where there is a decrease of T3 and where the antiepileptic drugs of different chemical structure induce changes in seric levels of thyroid hormones. The basal TSH is the best measurement to reflect the euthyroidism of these patients.

Salivary testosterone as an index of antiandrogen therapy in hirsutism.

The purpose of this study is to examine whether salivary testosterone (ST) in hirsute women treated with antiandrogen therapy can be considered a good parameter for the evaluation of clinical response. Twenty-three hirsute women, four with polycystic ovarian disease and 19 with idiopathic hirsutism were treated with cyproterone acetate and ethynyl-oestradiol with levonorgestrel in a reverse sequential regime for three months. Basal ST from hirsute women was 0.18 +/- 0.11 nmol/L (normal values 0.03-0.17) and a decrease to 0.11 +/- 0.06 was observed in the first month of treatment, to 0.1 +/- 0.059 after two months and to 0.11 +/- 0.06 after three months, all of them significantly different from basal values (p < 0.05). We found a relationship between ST decrease and the clinical response to antiandrogen therapy. On the basis of these results we suggest that ST values could be a good index for the follow-up of antiandrogen therapy in hirsute women.