Thyroid Hormone Replacement Therapy Improves Olfaction and Taste Sensitivity in Primary Hypothyroid Patients: A Prospective Randomised Clinical Trial.

Smell and taste are known to be influenced by thyroid function changes. However, many hypothyroid patients and physicians are unaware of their dysosmia and dysgeusia. The present study was performed to shed more light on the relation between hypothyroidism and olfactory loss. 32 primary hypothyroid patients and 31 controls enrolled in the prospective randomized interventional study. Newly diagnosed Primary hypothyroid patients were treated with L-thyroxine for 3-6 months. The control group was selected on the basis of the biochemical evidence of a normal thyroid function. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens ("Sniffin' Sticks", Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Smell identification, threshold, discrimination, TDI scores, bitter and sweet taste scores were significantly lower in untreated hypothyroid patients compared to controls (12.31±1.09 vs. 14.03±1.05, p<0.001; 7.09±1.15 vs. 8.89±1.12, p<0.001; 11.47±0.95 vs. 13.06±0.85, p<0.001; 30.90±2.70 vs. 35.89±2.07, p<0.001; 4.88±1.6 vs. 6.64±0.96, p<0.001; and 5.5±2.22 vs. 6.58±1.28, p=0.021) respectively. Comparison of scores at the third month of treatment and before treatment of hypothyroid patients revealed significant improvement in smell and taste functions in terms of identification, threshold, discrimination, TDI scores, bitter, sweet and salty tastes (12.31±1.09 vs. 13.84±1.22, p<0.001; 7.09±1.15 vs. 8.02±1.16, p<0.001; 11.47±0.95 vs. 12.41±1.21, p<0.001; 30.90±2.70 vs. 34.27±3.25, p<0.001; 4.88±1.6 vs. 6.06±1.4, p<0.001; 5.5±2.22 vs. 6.38±1.28, p<0.001; and 6.12±2.32 vs. 6.62±1.48, p=0.044) respectively. On correlation analysis, there was a negative correlation between TPO-Ab levels and discrimination, identification and TDI scores (r=-0.409, p=0.02; r=-0.424, p=0.016; r=-0.532, p=0.002), and also between Tg-Ab levels and identification, TDI, and bitter scores (r=-0.423, p=0.016; r=-0.468, p=0.007; r=-0.409, p=0.02) respectively. Primary hypothyroidism was found to have a negative effect on smell and taste. RAI treatment was found to be most destructive on smell and taste compared to surgical and autoimmune hypothyroidism. Treatment of hypothyroidism was positively correlated with an improvement of both senses. Thus, the future workup of patients with smell/taste loss should include investigations for thyroid functions.

Gastric carcinoma and thyroid status.

Gastric carcinoma is reported to be more frequent in geographical areas where diets are either iodine-deficient or iodine-excessive. Reports have also shown an association between thyroid diseases and some of the risk factors for gastric carcinoma. We investigated the frequency of thyroid disorders in 61 patients with gastric carcinoma compared with 55 healthy control subjects. Thyroid health was evaluated by physical examination and by measuring the serum levels of thyroid hormones and thyroid autoantibodies. More patients with gastric cancer had goitre compared with healthy controls (49.1% versus 20%, respectively). Significantly more patients with gastric cancer had non-toxic goitre compared with control subjects. There was also a significant difference in the incidence of autoimmune thyroid disease--27.8% of patients with gastric cancer versus 10.9% of control subjects were affected. These results indicate that there is a significant association between gastric cancer and thyroid disorders.

Low parathormone levels and hypercalcaemia in patients with pulmonary tuberculosis: relation to radiological extent of disease and tuberculin skin test.

AIM: We hypothesised that serum calcium (Ca) and parathormone (PTH) levels correlate with radiological extent and that there may also be a relationship between the tuberculin skin test (TST), serum Ca and PTH levels in patients with pulmonary tuberculosis (PTB). MATERIALS AND METHODS: Forty-four patients with active PTB and 33 healthy subjects were enrolled in the study. Serum Ca, PTH, magnesium and phosphate levels were measured in patients and controls and compared. Correlations were also investigated for TST values, erythrocyte sedimentation rate (ESR), the degree of radiological involvement, serum PTH and corrected Ca levels. RESULTS: There was a significant difference between the two groups for mean serum PTH and corrected Ca levels. Significant correlations were detected between radiological extent of disease and serum PTH levels, between TST values and serum PTH levels and between ESR and serum PTH levels. We suggest that abnormal Ca metabolism in PTB patients is related to the radiological extent of disease. Factors determining the radiological extent of disease, predominantly the patient's immune status, may have an important role in modulating Ca metabolism in PTB patients.

Effects of aminoguanidine and tolrestat on the development of ocular and renal structural changes in experimental diabetic rats.

Studies that researched the role of aminoguanidine and tolestat in the prevention of diabetic retinopathy and nephropathy resulted in conflicting data. We investigated the effects of these agents in the prevention of ocular and renal changes in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ in 30 rats. Ten rats that were not given STZ served as non-diabetic control (Group 1). Ten STZ-diabetic rats that were not given any treatment served as diabetic control (Group 2). Groups 3 and 4 were composed of STZ-induced diabetic rats (10 each) that were given tolrestat and aminoguanidine respectively. Eyes and kidneys were examined at the 24th week under electronmicroscopy. Cataract was observed in all six of the surviving rats in Groups 2 and 4, and in one of 6 surviving rats in group 3. Cataract development was lower in Group 3 than Groups 2 and 4. All retinal samples obtained from group 2 demonstrated a number of structural abnormalities, whereas there were no significant ultrastructural changes in groups 3 and 4. Groups 2 and 3 demonstrated mesangial proliferation and expansion, diffuse glomerular basement membrane (GBM) thickening, and focal GBM thickening in the bulb form. Group 4 demonstrated a normally appearing mesangial space, minimal diffuse but no focal GBM thickening. The urinary albumin excretion (UAE) was lower in Group 4 than the other groups. In conclusion, our results suggest that aminoguanidine may be an important agent for the prevention of renal changes, whereas tolrestat may be effective for the prevention of ocular changes in diabetes mellitus.

Effects of granulocyte-colony stimulating factor in the treatment of diabetic foot infection.

AIMS: Foot infections and the subsequent amputation of a lower extremity are the most common cause of hospitalization among patients with diabetes mellitus. Although there are several reasons for susceptibility to infection in diabetic patients, white blood cell dysfunction is considered to be an important cause for this tendency. Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophils from the bone marrow and improves neutrophil functions. Based on this knowledge, the aim of the present study was to investigate the effects of addition of G-CSF to the treatment of foot infections in diabetic patients. METHODS: Thirty diabetic patients with foot infection were included in the study. Fifteen of the patients received standard treatment consisting of local wound care and antibiotics (standard group), and the other 15 patients received G-CSF besides standard treatment (G-CSF group). The objectives of this study were to determine the time to resolution of infection, time to hospital discharge, need for surgical intervention, and the effects of G-CSF on phagocytosis and respiratory burst of neutrophils. RESULTS: Treatment with G-CSF led to significantly higher neutrophil counts on the 5th and 10th days, and at the end of treatment in the G-CSF treated group compared to the standard group. Respiratory burst of neutrophils increased significantly in both the G-CSF group (from 1.6 +/- 0.3 to 2.3 +/- 0.5, p = 0.001) and the standard group (from 2.0 +/- 0.4 to 2.3 +/- 0.4, p = 0.02) with treatment. But, while phagocytosis of neutrophils increased significantly in the G-CSF group (from 70.4 +/- 2.0 to 74.5 +/- 1.9, p = 0.004), it did not change significantly in the standard group (from 68.1 +/- 0.2 to 69.4 +/- 1.9, p = 0.3) with treatment. Duration of hospitalization (26.9 +/- 2.0 vs. 28.3 days, p < 0.05), duration of parenteral antibiotic administration (22.9 +/- 2.0 vs. 23.3 +/- 1.9 days, p < 0.05), time to resolution of infection (23.6 +/- 1.8 vs. 22.3 +/- 1.7 days, p < 0.05), and need for amputation (13.3% vs. 20%, p > 0.05) were similar between the G-CSF and the standard groups. CONCLUSIONS: Although G-CSF improves neutrophil function as well as increasing the absolute numbers, this improvement is not associated with shortening of duration of antibiotic administration, duration of hospital stay or need for amputation in diabetic foot infection.

Insulin resistance in nonobese patients with polycystic ovary syndrome.

OBJECTIVES: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. METHOD: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. RESULTS: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 +/- 1.32 vs. 1.18 +/- 0.53 pg/ml, p < 0.001, and 11.63 +/- 5.37 vs. 4.98 +/- 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 +/- 14.94 vs. 73.98 +/- 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 +/- 4.98 vs. 19.56 +/- 2.21 microU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 +/- 27.8 vs. 427.8 +/- 88.9 micromol x kg(-1) x min(-1), p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = -0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = -0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. CONCLUSIONS: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.

Plasma leptin concentrations in postmenopausal women with osteoporosis.

BACKGROUND: The obese are usually protected against osteoporosis and have increased bone mineral density and plasma leptin concentrations. A recent in vitro study demonstrated that leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts, suggesting an influence of leptin on bone mass. However, little is known about the relationship between plasma leptin and bone mass in postmenopausal women with osteoporosis. OBJECTIVE: To investigate plasma leptin concentrations in postmenopausal women with osteoporosis to improve the understanding of the role of leptin in determining bone mass. METHODS: Fifty postmenopausal women with osteoporosis (ages 61.18+/-6.51 years; body mass index (BMI) 28. 91+/-3.44kg/m(2), mean+/-s.d.) and 30 age- and BMI-matched healthy postmenopausal women were included in the study. Bone mineral densities (BMD) were measured by dual energy X-ray absorptiometry. Plasma leptin concentrations were determined using an immunoradiometric assay. RESULTS: The median spine BMD value in the patient group (0.695+/-8.26g/cm(2), median+/-s.e.m.) was significantly lower than that in the control group (1.006+/-1. 29g/cm(2), median+/-s.e.m.; z=-7.454, P<0.001). The median plasma leptin concentration in the patient group (18.70+/-1.78ng/ml, median+/-s.e.m.) was not significantly different from that in the control group (22.35+/-2.20ng/ml, median+/-s.e.m.; z=-1.630, P=0. 103). Plasma leptin concentrations were correlated with BMI in both groups (r(s)=0.394, P=0.031 in controls and r(s)=0.404, P=0.004 in the patient group). There was no correlation between plasma leptin concentrations and BMD values in controls (r(s)=-0.107, P=0.575) but a weak correlation was observed in the patient group (r(s)=0.285, P=0.045). CONCLUSION: Our data suggest that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.

Relation of leptin and tumor necrosis factor alpha to body weight changes in patients with pulmonary tuberculosis.

In this study we investigated whether leptin and TNFalpha levels change with improvement in body weight with antituberculotic therapy in active tuberculosis patients. 30 patients (8 females and 22 males) with active pulmonary tuberculosis formed the patient group, and 25 sex- and age-matched healthy subjects (8 females and 17 males) served as the control group. Body weight, body mass index (BMI) and serum leptin and plasma TNFalpha levels are measured before and in the sixth month of therapy in all patients. Before the initiation of therapy, BMI of the patients was significantly lower than BMI of the controls (20.2 +/- 1.6 vs. 25.2 +/- 2.7 kg/m(2), respectively; p < 0.05). After treatment, BMI of the patients increased significantly to 21.4 +/- 1.9 kg/m(2) (p < 0.05), but was still lower than that of the controls (p < 0.05). Pretreatment serum leptin (4.5 +/- 0.9 vs. 2.1 +/- 0.2 ng/ml, respectively; p < 0.05) and plasma TNFalpha (27.9 +/- 3.4 vs. 23.9 +/- 3.0 pg/ml, respectively; p < 0.05) levels of the patients were significantly higher than those of the controls. After treatment, serum leptin levels increased to 6.7 +/- 2.2 ng/ml, but this rise was not statistically significant (p > 0.05). Treatment did not result in any significant change in TNFalpha levels, either. Delta leptin was highly related to Delta BMI in patients with tuberculosis (r = 0.68, p = 0.02). In the pretreatment period, there was a significant correlation between leptin and TNFalpha levels in the whole patient group (r = 0.78, p < 0.001), and in female (r = 0.74, p < 0.001) and male patients separately (r = 0.74, p = 0.035). In conclusion, leptin and TNFalpha may be responsible for the weight loss in pulmonary tuberculosis patients, but their levels do not change with improvement in body weight with antituberculotic treatment.