Hypovitaminosis D and bone mineral metabolism and bone density in hyperthyroidism.

Little is known about the impact of concomitant vitamin D deficiency on bone mineral density in hyperthyroidism. Therefore, we evaluated bone mineral measures in vitamin D-deficient and sufficient patients with hyperthyroidism. Thirty newly diagnosed consecutive patients with hyperthyroidism were included. Blood samples were used for measurement of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D [25(OH) D], and parathyroid hormone (PTH). Bone mineral density (BMD) was measured at the hip, spine, and forearm. The patients were divided into vitamin D-deficient (< 25 nmol/L) and vitamin D-sufficient groups (≥ 25 nmol/L). Eight (26.6%) patients had 25(OH) D levels less than 25 nmol/L, with mean ± standard deviation (SD) level of 16.5 ± 3.2 (vitamin D-deficient group 1), and the remainder had a mean ± SD of 46.0 ± 13.5 nmol/L (vitamin D-sufficient group 2). Serum-intact PTH levels were significantly higher in group 1 compared with those in group 2 (31.2 ± 16.3 vs 18.0 ± 13.1 pg/mL; p=0.041). In the vitamin D-deficient group, the mean BMD T-scores were in the osteoporotic range at hip and forearm (-2.65 ± 1.13 and -3.04 ± 1.3) and in the osteopenia range at lumbar spine (-1.83 ± 1.71). However, in vitamin D-sufficient group, the mean BMD T-scores were in the osteopenia range (-1.64 ± 1.0, -1.27 ± 1.6, and -1.60 ± 0.7) at hip, forearm, and lumbar spine, respectively. The mean BMD Z-scores were also significantly lower in vitamin D-deficient group compared with those in vitamin D-sufficient group. Finally, BMD values (gm/cm(2)) at the hip and forearm were significantly lower in the vitamin D-deficient group compared with those in the vitamin D-sufficient group. In conclusion, hyperthyroid patients with concomitant vitamin D deficiency had lower BMD compared with vitamin D-sufficient patients.

Prolonged (3-month) mycological cure rate after boric acid suppositories in diabetic women with vulvovaginal candidiasis.

OBJECTIVE: Patients with diabetes mellitus (DM) are at increased risk of vulvovaginal candidiasis (VVC) due to C. glabrata. In our previous study we had shown that patients with diabetes mellitus and VVC show an overall superior mycological cure rate (74% versus 51%) with boric acid therapy at 15th day as compared to fluconazole. Present study was carried out to assess long term response to boric acid in diabetic women with VVC. MATERIAL AND METHODS: Subjects included 40 consecutive diabetic women (type 2 DM=26 and type 1 DM=14) who had achieved mycological cure (high vaginal swab culture negativity) on day 15 of therapy following single-dose oral-150 mg fluconazole (n=21) or 600 mg of boric acid suppositories given daily for 14 days (n=19). At third month of follow up, patients were assessed for signs and symptoms of VVC and a repeat HVS was collected for fungal culture. HbA1c was measured to assess glycaemic control. RESULTS: The mean age, BMI, HBA1c and frequency of various Candida species isolated at initial diagnosis were comparable in the fluconazole and boric acid treatment groups. Fifteen of 21 (71.4%) and 12 of 19 (63.1%) women who achieved mycological cure at 15 day remain cured at three months in the fluconazole and boric acid treated groups, respectively (P=0.83). With 74% mycological cure at 15th day, this would indicate that on an average only 46.6% of diabetic women with VVC would remain cured at 3 months after a course of 14 days boric acid therapy. Most of the patients relapsed with no change in Candida species. The demographic profile and mean HbA1c (8.6+/-2.2 versus 8.8+/-2.4%, P=0.83) were comparable in patients with (n=27) and without mycological cure (n=13). CONCLUSION: The results of the current study indicating comparable mycological cure rate at 3 months between fluconazole and boric acid treated patients would support use of boric acid in the acute management of VVC in view of its superior short term response in diabetic women with C. glabrata infections. However, there is need to explore other therapeutic regimens which are effective in achieving long term mycological cure in diabetic women with VVC.

Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis.

OBJECTIVE: A large proportion of vulvovaginal candidiasis (VVC) in diabetes is due to non-albicans Candida species such as C. glabrata and C. tropicalis. Observational studies indicate that diabetic patients with C. glabrata VVC respond poorly to azole drugs. We evaluated the response to oral fluconazole and boric acid vaginal suppositories in diabetic patients with VVC. RESEARCH DESIGN AND METHODS: A total of 112 consecutive diabetic patients with VVC were block randomized to receive either single-dose oral 150-mg fluconazole or boric acid vaginal suppositories (600 mg/day for 14 days). The primary efficacy outcome was the mycological cure in patients with C. glabrata VVC in the two treatment arms. The secondary outcomes were the mycological cure in C. albicans VVC, overall mycological cure irrespective of the type of Candida species, frequencies of yeast on direct microscopy, and clinical symptoms and signs of VVC on the 15th day of treatment. Intention-to-treat (ITT; n = 111) and per-protocol (PP; n = 99) analyses were performed. RESULTS: C. glabrata was isolated in 68 (61.3%) and C. albicans in 32 (28.8%) of 111 subjects. Patients with C. glabrata VVC showed higher mycological cure with boric acid compared with fluconazole in the ITT (21 of 33, 63.6% vs. 10 of 35, 28.6%; P = 0.01) and PP analyses (21 of 29, 72.4% vs. 10 of 30, 33.3%; P = 0.01). The secondary efficacy outcomes were not significantly different in the two treatment arms in the ITT and PP analyses. CONCLUSIONS: Diabetic women with C. glabrata VVC show higher mycological cure with boric acid vaginal suppositories given for 14 days in comparison with single-dose oral 150-mg fluconazole.

Pattern of Candida species isolated from patients with diabetes mellitus and vulvovaginal candidiasis and their response to single dose oral fluconazole therapy.

OBJECTIVE: Patients with diabetes mellitus are at increased risk of vulvovaginal candidiasis (VVC). Besides Candida albicans, they often have infection due to non-C. albicans Candida species such as C. glabrata. Oral single dose fluconazole (150 mg) is commonly used to treat VVC in non-diabetic individuals with response rate varying from 70 to 90%. However, there is paucity of related information in diabetic women with VVC. Present study has been conducted to systematically assess the effect of fluconazole therapy among diabetic patients with clinically symptomatic VVC. METHODS: Study subjects included 85 consecutive patients with diabetes mellitus (type 2=70 and type 1=15) and 62 non-diabetic women who had clinical signs and symptoms of VVC and in whom evidence of candidiasis was documented by presence of yeast on direct microscopy followed by culture. Single dose fluconazole (150 mg) was given orally to all the subjects in a supervised manner. Subjects were reassessed on 14th day after fluconazole therapy and a repeat high vaginal swab was taken for direct microscopy and fungal culture. Total glycosylated haemoglobin (HbA1) was measured to assess glycaemic control. RESULTS: There were no significant differences in the frequency of pruritus (55.9 vs. 56.7%), vaginal discharge (63.8 vs. 69.0%), dyspareunia (25.0 vs. 20.0%), and percentage yeast positivity (67.5 vs. 54.7%) between diabetic and control groups before the start of fluconazole therapy. Following fluconazole therapy, vaginal discharge on examination and yeast positivity on direct microscopy continued to remain positive in higher percentage of subjects in the diabetic group as compared to non-diabetic subjects (52.5 vs. 36.4%; P =0.22 and 50.7 and 29.0%, respectively, P =0.07, respectively). Overall 67.1% of patients with diabetes and 47.3% of controls continued to show persistence of Candida growth on high vaginal swab culture following fluconazole treatment (P=0.042). Candida glabtara was the most common species isolated in patients with diabetes mellitus and its frequency was significantly higher in them when compared to control group (54.1 vs. 22.6%, P<0.001). C. albicans was the most common species isolated in controls. Species-specific response to fluconazole showed that 81.3% of patients in the diabetic group and 78.6% of the non-diabetic controls continued to show fungal growth when C. glabrata was the organism grown (P=0.99). However, in case of C. albicans, 45.4% of the patients in the diabetic group and only 21.5% of the controls had persistent Candida growth following fluconazole therapy (P=0.22). CONCLUSION: Overall only one third of patients with diabetes mellitus and VVC respond to single dose 150 mg of fluconozole therapy. Limited response in the clinical symptoms and culture negativity following single dose fluconazole therapy in diabetic subjects with VVC is explained by the high prevalence of C. glabrata in them. The present study involved only 85 patients and majority of them had type-2 diabetes mellitus. There is need to perform similar study in large number of diabetics subjects including patients with type-1 diabetes mellitus and assess various alternative treatment protocol which are also effective in C. glabrata infection.

Glycaemic control and microvascular complication among patients with youth onset diabetes in India using differing types of insulin and methods of glucose monitoring.

We assessed whether insulin types and monitoring methods were relevant to glycaemic control, microvascular complications as well as costs of management in 208 patients with youth onset diabetes in India. The type of insulin and monitoring method used made no difference to the glycaemic and complication status. Cost considerations support bovine insulin use along with urine glucose monitoring as an appropriate approach to diabetes self care in developing countries.

Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism.

OBJECTIVE: The pathogenesis of sporadic idiopathic hypoparathyroidism is unclear. The calcium sensing receptor (CaSR) plays a pivotal role in extracellular calcium homeostasis and is the candidate autoantigen in hypoparathyroidism associated with autoimmune polyglandular endocrinopathy syndrome. We therefore looked for antibodies (Ab) against the CaSR in patients with sporadic idiopathic hypoparathyroidism and their association, if any, with the major histocompatibility complex (MHC) class II human leukocyte antigen (HLA)-DR haplotypes. METHODS: The subjects included 51 patients with sporadic idiopathic hypoparathyroidism and 45 healthy controls. Investigations included computerised tomography, serum calcium, phosphorus, thyroxine, TSH, cortisol, intact parathyroid hormone (iPTH), ACTH and thyroid peroxidase (TPO) and adrenal antibodies. The CaSRAb were assayed in patients' sera by Western blot. Genotyping of the HLA-DR locus was performed using PCR and sequence-specific oligonucleotide probes. RESULTS: Intracranial calcification and cataract were present in 76.5% and 41.1% of the patients respectively and 62.7% had convulsions. Autoantibodies against the 168 kDa CaSR protein were demonstrated in the serum of 49.0% of the patients and in 13.3% of the controls (P<0.001). Pre-incubating serum samples from the CaSRAb-positive patients with parathyroid membrane produced a 90% decrease in the band intensity. HLA-DRB1*01 and DRB1*09 alleles were significantly associated with idiopathic hypoparathyroidism (relative risk of 7.8, P=0.001). The frequency of HLA-DRB1*09 and DRB1*10 alleles tended to be higher in patients positive for the CaSRAb. There was no significant difference in the frequency of occurrence of convulsions, cataract, intracranial calcification, calcium:phosphorus ratio, and iPTH levels between patients with and without CaSRAb. CONCLUSION: 49.0% of the patients studied had serological evidence of organ-specific autoimmunity against the CaSR protein. The occurrence of CaSRAb and the HLA-DR associations imply an autoimmune component to the disease, but the primary role of the CaSRAb in the pathogenesis of the disease needs to be assessed further.

Cytologic characterization of postiodization residual goiter in schoolchildren by fine needle biopsy.

OBJECTIVE: To determine the relevance and utility of fine needle biopsy (FNB) for providing a tissue-level diagnosis during a community-based survey of postiodization residual goiter in schoolchildren in India. STUDY DESIGN: A total of 14,762 schoolchildren (56.0% girls and 44.0% boys), aged 6-18 years, with a countrywide representation, were clinically screened for the presence of goiter. FNB was performed under field conditions by means of a nonaspiration technique from both lobes of goitrous glands. The cytologic diagnosis and findings were correlated with age, sex, goiter grade and biochemical parameters of serum T4, TSH, thyroid microsomal (TMA) and thyroglobulin (TGA) antibodies. RESULTS: The overall prevalence of goiter was 23.0%, with a greater frequency in girls (27.1%) than boys (17.8%). FNB was successful in 75.6% of subjects without any significant complications. The cytologic diagnoses in 1,312 successful cases were colloid goiter (92.8%), Hashimoto's thyroiditis (4.6%), focal lymphocytic thyroiditis (1.7%) and hyperplastic goiter (0.9%). Autoimmune thyroiditis (AIT), which accounted for only 6.3% cases, showed a strikingly different age-specific prevalence between girls and boys. Serologic markers of TMA and TGA at various titers were observed to lack requisite sensitivity and specificity for establishing an accurate diagnosis of AIT. CONCLUSION: The nonaspiration technique of FNB is capable of yielding valuable diagnostic information during an epidemiologic survey of goiter. The technique can be easily performed under field conditions on children without significant complications. FNB is preferable to serologic markers for accurate diagnosis of AIT. A relatively low frequency of AIT, as observed in the present study, raises the possibility of a significant role of environmental goitrogens as the underlying pathogenetic factor in postiodization residual goiter in Indian schoolchildren.

Pituitary autoimmunity in patients with Sheehan's syndrome.

Postpartum hemorrhage (PPH) is a frequent complication of pregnancy in India. Sheehan's description of postpartum hypopituitarism promoted the belief that PPH leads to necrosis of the enlarged pituitary gland of pregnancy and hypopituitarism. However, slow clinical progression suggests factors other than ischemia in its pathogenesis. Tissue necrosis could release sequestered antigens, triggering autoimmunity of the pituitary and delayed hypopituitarism in Sheehan's syndrome. Twenty-six consecutive patients with postpartum hypopituitarism were studied, 19 with Sheehan's syndrome based on a history of PPH and hormone profile suggesting pituitary failure [mean (SD) age 32.7 +/- 6.4 yr, duration of illness 5.5 +/- 3.1 yr], and seven patients with no history of PPH, categorized as "Other." Pituitary imaging and basal T(4), TSH, cortisol, LH, FSH, 17beta-estradiol, and autoantibodies against pituitary (PitAb) and thyroid (TMA) were evaluated. Controls included 28 healthy females without prior conception (22 +/- 5 yr) and 28 with prior conception (26 +/- 5 yr). Twelve of 19 (63.1%) patients with Sheehan's syndrome and one of seven in the Other group had PitAb against the 49-kDa autoantigen; neuron-specific enolase. Four of 28 (14.2%) controls without prior conception and 5 of 28 (17.8%) controls with prior conception had PitAb positivity (P < 0.001 and <0.01 vs. Sheehan's syndrome, respectively). There was no significant difference in the mean serum hormone values and TMA positivity between patients with Sheehan's syndrome and the Other group as well as patients with or without PitAb positivity. Pituitary autoimmunity may play a role in the cause of hypopituitarism following PPH.

Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy.

OBJECTIVES: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. METHODS: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffP(oeso)), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5+/-2 months. RESULTS: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59+/-26 to 23+/-13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57+/-0.62 to 2.94+/-0.60 l), forced expiratory volume in the first second (2.21+/-0.49 to 2.45+/-0.47 l), total lung capacity (3.57+/-1.19 to 4.1+/-1.12 l), diaphragmatic movement during deep respiration (5.5+/-1.0 to 6.6+/-1.1 cm) and SniffP(oeso) (68.7+/-23 to 93.1+/-25.2 cmH(2)O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffP(oeso). CONCLUSIONS: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis.