Hypothalamic-pituitary-adrenal axis function following intravitreal triamcinolone acetonide injection.

To evaluate the pituitary-adrenal axis function by means of the adrenocorticotropic hormone (ACTH) stimulation test following a single intravitreal injection of triamcinolone acetonide (IVTA). Prospective comparative clinical interventional study. Twenty-eight patients (28 eyes) received a single IVTA (4 mg in 0.1 ml) for macular edema. The basal cortisol level and the response to 1 µg adrenocorticotropic hormone stimulation were determined on the morning before IVTA injection and at 1 day and 1, 2, and 4 weeks after IVTA injection. Results were compared with those obtained from a control group of 50 healthy subjects. All patients in the study had normal basal cortisol and normal response to ACTH challenge before receiving IVTA. 1 day following IVTA, basal cortisol was suppressed in one patient in the study group. Fasting serum cortisol levels at 1, 2, and 4 weeks after IVTA injection were normal in all patients in the study group. 1 day following IVTA, the peak response to ACTH at 30 min was blunted in four patients (14.3 % of the study group, p = 0.05) and the cortisol response at 60 min was suppressed (p = 0.009). 1 week following IVTA, the response to ACTH challenge was blunted in only one patient. A single IVTA injection may be associated with impaired hypothalamic-pituitary-adrenal function in some patients during the first 24 h following IVTA.

Melatonin dysregulation, sleep disturbances and fatigue in multiple sclerosis.

BACKGROUND: Sleep disruption and fatigue are common in Multiple Sclerosis (MS). Melatonin is one of the major regulators of sleep-wake cycle. The role of melatonin in MS-related sleep disturbances and fatigue as well as the interaction between melatonin and Interferon beta (IFN-ß) treatment were the subject of this study. OBJECTIVE: To assess the influence of IFN-ß treatment on melatonin secretion, fatigue and sleep characteristics in patients with MS. METHODS: 13 MS patients and 12 healthy controls participated. Fatigue was evaluated using the Fatigue Impact Scale (FIS), sleep was assessed by actigraphy and day/night levels of 6-sulphatoxy-melatonin (6-SMT) in urine were determined using a highly specific ELISA assay. RESULTS: Naïve MS patients demonstrated significantly decreased levels of 6-SMT and disrupted circadian regulation of its secretion, which were increased with IFN-ß treatment, in association with improved fatigue. Sleep Efficiency was significantly lower in the MS group compared to controls. CONCLUSION: Our findings suggest dysregulation of Melatonin secretion in MS, which may be influenced by IFN-ß treatment. The results call for further characterization of the role of neuro-hormones such as melatonin in MS, and their cross-regulation with immune-mediators.

Effects of successful parathyroidectomy on metabolic cardiovascular risk factors in patients with severe primary hyperparathyroidism.

OBJECTIVE: To evaluate the effect of parathyroidectomy on metabolic abnormalities associated with cardiovascular disease in patients with primary hyperparathyroidism (PHPT). METHODS: Thirty-four patients with PHPT (aged 51.0 ± 11.8 years, mean ± standard deviation) underwent assessment before and 1 year after successful parathyroidectomy. A control group of 42 normocalcemic healthy subjects, matched for age and body mass index, was also examined at baseline. We measured serum lipids, glucose, insulin, uric acid, calcium, parathyroid hormone, C-reactive protein, and bone density. Insulin resistance index was evaluated by homeostasis model assessment, and the presence of metabolic syndrome was determined. Because of multiple tests, the level of statistical significance was set at .01. RESULTS: After parathyroidectomy, there was a decrease in diastolic blood pressure (P<.02) and in serum concentrations of uric acid (P<.04) and insulin (P<.009). No difference was observed in rates of metabolic syndrome in patients before and 1 year after parathyroidectomy (23.5% versus 17.6%; P>.46). Insulin resistance index values were also unchanged from before to after parathyroidectomy (1.3 ± 0.9 and 1.1 ± 0.9, respectively; P>.68). A substantial increase in spine bone density (5%; P<.05) was noted postoperatively. Multivariate logistic regression analysis, after adjustment for age and body mass index, revealed that parathyroidectomy did not lead to a significant decrease in likelihood of cardiovascular risk-odds ratio (OR), 1.82; 95% confidence interval (CI), 0.53 to 6.21 (P>.34) for the metabolic syndrome and OR, 0.82; 95% CI, 0.17 to 3.88 (P>.8) for the insulin resistance index. CONCLUSION: In this study, surgical treatment had no beneficial effect on cardiovascular risk, as assessed by the metabolic syndrome and insulin resistance markers in patients with PHPT 1 year after parathyroidectomy.

Color-flow doppler sonography in patients with subclinical thyroid dysfunction.

OBJECTIVE: To assess the value of color-flow Doppler sonography (CFDS) in evaluating intrathyroidal blood flow and velocity in patients with subclinical thyroid dysfunction. METHODS: In this prospective study, patients with subclinical hypothyroidism, patients with subclinical hyperthyroidism, and euthyroid patients without known thyroid autoimmune disease who served as controls were included. Subclinical thyroid dysfunction was defined as normal se-rum free thyroxine (FT4) and free triiodothyronine (FT3) in the presence of high (subclinical hypothyroidism), or low-suppressed (subclinical hyperthyroidism) serum thyrotropin (TSH) levels. Serum FT4, FT3, TSH, and antibodies to thyroid peroxidase and thyroglobulin were measured in all participants. In addition, TSH receptor antibody levels were determined in patients with subclinical hyperthyroid-ism. All participants underwent conventional sonography and CFDS. Mean peak systolic velocity (PSV) and resistive index were obtained from multiple extranodular thyroid parenchyma samplings and inferior thyroid artery measurements. RESULTS: The study population included 27 patients with subclinical hypothyroidism, 15 patients with subclinical hyperthyroidism, and 20 euthyroid patients. Patients with subclinical hypothyroidism had significantly higher mean intrathyroidal PSV values than control patients (19.9 +/- 5.6 cm/s vs 15.7 +/- 4.4 cm/s; P = .008), whereas patients with subclinical hyperthyroidism had significantly higher mean PSV values than control patients at the inferior thyroid artery level (29.7 +/- 10.7 cm/s vs 21.9 +/- 6.8 cm/s; P = .014). Compared with control patients, a greater proportion of patients with subclinical hypothyroidism and patients with subclinical hyperthyroidism had marked CFDS patterns (78% vs 15% [P<.001] and 53% vs 15%; [P<.001], respectively). A significant association was found between positivity for thyroid autoantibodies and intense CFDS patterns. No correlation was found between TSH or thyroid hormone levels and CFDS pattern or blood flow velocity. CONCLUSION: We have demonstrated that significantly increased thyroid blood flow velocity and vascularity are already present in patients with mild thyroid dysfunction.

Beclomethasone dipropionate enema in ulcerative colitis: Is it safe?

Objective: To evaluate the pituitary-adrenal axis (PA axis) reserve in patients with ulcerative colitis (UC) treated with steroid enemas, we performed 1mug ACTH test.Methods: Patients with UC (n=8) given beclomethasone dipropionate enema (Betnesol) for 4 weeks. Fasting serum cortisol and the response at 30 and 60 minutes following an IV 1mug ACTH injection were determined after 2 weeks of Betnesol enemas. Patients were retested, one month after discontinuation of enemas.Results: Fasting and peak cortisol responses to ACTH were suppressed in six patients. Additional patient had suppressed fasting cortisol and another patient had blunted response to ACTH. One month off Betnesol enema, basal and peak cortisol response to ACTH were normal in all but one patient.Conclusion: Betnesol enemas are associated with severe suppression of the PA axis in almost all patients. Caution is required in patients with UC after withdrawal of rectal steroids as adrenal insufficiency can occur.

Prevalence of subclinical hypothyroidism in women with type 2 diabetes.

BACKGROUND: Subclinical hypothyroidism is a common thyroid disorder. Although there is a recognized association between thyroid disease and diabetes mellitus, there is no definite answer as to whether screening for subclinical hypothyroidism is necessary in patients with type 2 diabetes. The objective of the present study was to evaluate the prevalence of subclinical hypothyroidism in women with type 2 diabetes. MATERIAL/METHODS: Four hundred ten women with type 2 diabetes (aged 59.6+/-10.9 years) and 125 women without diabetes (aged 51.8+/-15.8 years) were studied. Subclinical hypothyroidism was defined as a thyroid stimulating hormone level above the upper normal limit together and a normal free thyroxine level. Measurements of lipids, glycosylated hemoglobin, and antithyroid antibody levels were also performed. RESULTS: After excluding patients with previous thyroid disease, the prevalence of subclinical hypothyroidism was similar between patients with diabetes and control subjects (5.4% vs 7.9%, respectively) (P=0.32). When patients with known thyroid disease were included, the prevalence of subclinical hypothyroidism between groups was similar (9% in diabetes vs 8% in control subjects) (P=0.75). Across all participants, positivity for antithyroid antibody was significantly higher in patients with subclinical hypothyroidism than in euthyroid subjects. CONCLUSIONS: The similar prevalence of subclinical hypothyroidism in women with type 2 diabetes and women without diabetes suggests that routine screening of thyroid function in patients with type 2 diabetes is unwarranted.

Infertility and bilateral adrenal tumors.

An infertile man who presents with azoospermia and bilateral adrenal tumors reveals an XX karyotype and congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hysterectomy and bilateral oophorectomy performed in infancy and lack of treatment resulted in full masculinization.

Biomarkers of hypercoagulability and inflammation in primary hyperparathyroidism.

BACKGROUND: Severe primary hyperparathyroidism (PHP) has been associated with increased cardiovascular morbidity. Hypertension, dyslipidemia and impaired glucose metabolism were demonstrated in severe PHP, with improvement after surgery in these variables. Such an association in mild PHP is not known. The study was conducted to determine biomarkers of hypercoagulability and inflammation for cardiovascular disease in patients with primary hyperparathyroidism. MATERIAL/METHODS: Patients (n=35) without CVD were evaluated. Patients were subdivided into two groups, severe (n=15) and mild (n=20) hyperparathyroidism, based on disease severity and whether they had indications for surgery. Results were compared with those obtained in 25, age and weight matched controls. Participants were examined in the hospital endocrine clinic and had measurement of fasting blood levels of calcium, phosphate, alkaline phosphatase, PTH, C-reactive protein, Serum IL-6, D-dimers, Fibrinogen, plasminogen activator inhibitor 1 [PAI-1], and white blood cells (WBC) count. RESULTS: PAI-1 was significantly higher in symptomatic patients (41.4 g/L +/-20) vs. controls (32.5 g/L +/-13.0); (p=0.009). Levels of fibrinogen, d-dimers, IL-6, CRP and leukocytes were similar in patients and controls. Across all subjects PAI-1 was significantly correlated with PTH levels (f=8.44;p=0.005). CONCLUSIONS: Patients with severe primary hyperparathyroidism have increased risk for cardiovascular disease, mainly due to the effect of PTH and also the duration and severity of disease. Elevated PAI-1 levels may imply that hypercoagulability may be involved in the pathogenesis of CVD in these patients.

Thyroid dysfunction in patients with systemic lupus erythematosus (SLE): relation to disease activity.

We examined the prevalence of thyroid dysfunction and the production of anti-thyroid antibodies (ATA) in patients with systemic lupus erythematosus (SLE) and assessed the association between ATA production and SLE disease activity status. Seventy-seven patients who met the American College of Rheumatology classification criteria for SLE participated in the study. Fifty-two individuals served as a control group. Demographic, clinical information and SLE disease activity (SLEDAI) status were collected from all patients. The sera of all participants were tested for free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin (ATg) and anti-thyroid peroxidase (TPO). A SLEDAI score of > or =6 was considered clinically significant. The results of the thyroid function tests and ATA were compared between the study group and the control group. ATA levels were compared between the patients with a SLEDAI score of > or =6 to those with a SLEDAI score of <6. Hypothyroidism was detected in 11.6% of SLE patients compared to 1.9% in the control group. None of the patients or controls had evidence of hyperthyroidism. No statistically significant difference was observed in the levels of ATg or TPO between the study group and the control group. No correlation was found between ATA levels and the degree of the disease activity. Among the different variables tested in this study, hypothyroidism was the only significant abnormal finding in SLE patients. No association was found between the SLEDAI score and the prevalence of ATA production. Larger controlled, longitudinal studies are necessary to confirm these findings and elucidate the role played by ATA in the pathogenesis of thyroid dysfunction in SLE patients.

Serum thyroglobulin levels after fine-needle aspiration of thyroid nodules.

OBJECTIVE: To investigate whether a minor insult to the thyroid gland attributable to fine-needle aspiration (FNA) or external thyroid palpation can cause a release of serum thyroglobulin (Tg) into the circulation. METHODS: We determined serum Tg levels before and at 60 minutes and 15 days after FNA in 25 patients with thyroid nodules. Results were compared with those obtained in 25 patients with thyroid nodules, in whom serum Tg concentrations were determined before and 60 minutes after palpation of the thyroid, and in 15 healthy subjects without thyroid disease, who had no thyroid palpation and no FNA, from whom 2 blood specimens were obtained 60 minutes apart. All participants had normal results of thyroid function tests and no detectable antithyroglobulin or thyroid peroxidase antibodies. RESULTS: After FNA, 22 of 25 patients had significant elevation of serum Tg concentrations. The Tg levels returned to baseline values 15 days after FNA. In 4 of the 25 patients with thyroid nodules who had palpation of the thyroid, a significant increase in serum Tg levels was elicited. None of the 15 healthy subjects with normal thyroid glands (and with no FNA or thyroid palpation) had significant Tg elevations. CONCLUSION: FNA causes a significant increase in serum Tg concentrations, which may persist for 15 days. Therefore, Tg assay should not be scheduled prematurely after FNA.

Altered luteinizing hormone and testosterone secretion in middle-aged obese men with obstructive sleep apnea.

OBJECTIVE: To elucidate the causes for the decline in testosterone levels observed in men with obstructive sleep apnea (OSA). RESEARCH METHODS AND PROCEDURES: We determined serum luteinizing hormone (LH) and testosterone levels every 20 minutes between 7 pm and 7 am with simultaneous sleep recordings in five obese middle-aged men with OSA, in five age- and BMI-matched controls, and in six lean young healthy men. RESULTS: The mean and area under the curve (AUC) values of LH and testosterone were significantly lower in men with OSA compared with controls. Young controls had significantly more testosterone pulses of shorter interpulse duration than OSA subjects and middle-aged controls. After adjusting for age and BMI, the three groups differed in mean and AUC values of LH and testosterone. Analysis of covariance, using BMI as a covariate, revealed a statistically significant group effect on mean and AUC testosterone values (p = 0.03; p < 0.003, respectively). Eliminating young controls, there was a significant positive correlation between the amount of LH and testosterone secreted at night. After partialling out age alone and BMI alone, the mean LH and mean testosterone were still positively correlated. DISCUSSION: Thus, OSA is associated with decreased pituitary-gonadal function. The decline in testosterone concentrations is due to obesity and advanced age and to a lesser degree to sleep fragmentation and hypoxia.

Evaluation of the pituitary-adrenal axis function following single intraarticular injection of methylprednisolone.

OBJECTIVE: To determine the effects of a single session of intraarticular methylprednisolone (IA-MP) injections on the function of the pituitary-adrenal axis. METHODS: Twenty-five patients with rheumatic diseases were treated with a single IA-MP injection. The dose varied between 20 and 160 mg. The basal cortisol level and the response to 1 microg adrenocorticotropic hormone (ACTH) stimulation were determined before treatment, at 1 day, and at 1 week after IA-MP injections. Further tests were carried out for up to 6 weeks in patients with blunted cortisol response. Results were compared with those obtained in a group of 22 healthy subjects. RESULTS: Before treatment, all patients had normal basal and peak cortisol responses to ACTH (>396 nmoles/liter at 30 minutes). Reduced fasting cortisol levels (<147 nmoles/liter) were detected in 12 of 25 patients (48%) after 1 day, in 1 of 25 patients (4%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Blunted peak cortisol response (<396 nmoles/liter at 30 minutes) was observed in 1 of 25 patients (4%) after 1 day, in 3 of 25 patients (12%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Decreased fasting levels and peak cortisol responses to ACTH stimulation were more common in patients with inflammatory diseases and in those injected with 80-160 mg MP. CONCLUSION: Single-session IA-MP injection(s) are associated with systemic absorption of MP, causing impaired adrenocortical reserve. Recovery is expected in most patients after 1-2 weeks. Only a few patients exhibited suppression for up to 2 weeks. The magnitude of this suppression depends on the dose injected, and is more common in patients with inflammatory joint diseases. Caution is required if repeated large doses of IA-MP are considered in these patients.

Cardiovascular risk factors in middle-aged women with subclinical hypothyroidism.

OBJECTIVES: Overt hypothyroidism (OH) is associated with premature atherosclerosis and coronary heart disease (CHD). Recently, C-reactive protein (CRP) and total homocysteine (tHct) emerged as additional independent cardiovascular risk factors. Subclinical hypothyroidism (SH), affecting as many as 15% of middle-aged women is not known to be associated with risk for CHD. DESIGN AND MEASUREMENTS: We measured CRP and tHct levels as well as conventional cardiovascular risk markers in 44 middle-aged women with newly diagnose SH. Results were compared with those obtained in 10 patients with OH and 19 euthyroid controls. RESULTS: In SH, tHct and CRP levels were not as augmented as compared to controls. Their mean systolic and diastolic blood pressure values were increased vs. controls (p<0.04;p<0.01, respectively). Mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides, TC/HDL-C and LDL-C/HDL-C were not different in patients with SH compared to controls. Individual analysis revealed that the percentage of patients with SH having hypertension, hypertriglyceridemia, hypercholesterolemia, elevated TC/HDL-C and LDL-C/HDL-C ratios were higher than the percentage in controls. CRP positively correlated with BMI(r=0.29,p<0.02), and tHct positively correlated with age (r=0.24, p<0.05). CONCLUSIONS: Our findings suggest that subclinical hypothyroidism in middle-aged women is associated with hypertension and dyslipidemia. CRP and tHct do not appear to contribute to the increased risk for CHD in these patients.