Endocrine and Metabolic Aspects of OSA

Obstructive sleep apnea (OSA) is characterized by repeated spells of apnea.Collapsibility of hypopharynx due to multiple factors involving pharyngeal dilatormuscles and deposition of fat or fluid in the surrounding soft tissues are importantcontributing factors in its pathogenesis. OSA commonly affects obese individuals.Males are more commonly affected than the females probably due to the disturbingeffect of testosterone on sleep.The impact of OSA on human health include disturbances in endocrine and metabolicsystem affecting hypothalamic-pituitary-gonadal axis, adrenocorticotrophic-cortisolaxis, growth hormone, antidiuretic hormones and insulin resistance. There is atendency for predisposition of the metabolic syndrome or its components includingglycemic dysregulation, hypertension, hyperlipidemia and physical parameters relatedto adiposity. On the other hand, several endocrine disorders such as hypothyroidism,growth hormone excess, polycystic ovarian disease and testosterone replacement areassociated with increased prevalence of OSA.There is limited information on the effect of treatment of OSA by continuous positiveairway pressure (CPAP) on the endocrine and metabolic disturbances. There is a needto conduct randomized controlled trials using CPAP therapy in patients with OSA andto study its cause and effect relationship with endocrine and metabolic disturbances

Sleep and Endocrinology: Hypothalamic-pituitary- adrenal axis and growth hormone

The supra-chiasmatic nucleus (SCN) is the primarily biological clock determining thecircadian rhythm. The neurons of the nucleus making this clock have inherent rhythmand set in biological day and night. These periods usually corresponds to day/night, andindirectly to sleep-wakefulness cycle, in most individuals. Retino-hypothalamic tractcarrying photic information from the retina provides the most important input tomaintain the inherent rhythm of the SCN. The rhythmic discharges from the SCN tovarious neurons of the central nervous system, including pineal gland andhypothalamus, translate into circadian rhythm characteristic of several hormones andmetabolites such as glucose. As a result there is a pattern of hormonal changesoccurring during cycle of sleep wakefulness. Most characteristic of these changes aresurge of melatonin with biological night, surge of growth hormone-releasing hormone(GHRH)􀀁at onset of sleep and surge of corticotropin-􀀁releasing􀀁hormone􀀁(CRH)during late part of the sleep. The cause and effect relationship of the hypothalamicreleasing hormones and their target hormones on various phases of sleep includinginitial non rapid eye movement (NREM) phase at onset of sleep, and rapid eyemovement (REM) phase near awakening, is an upcoming research area. Sleepelectroencephalogram (EEG) determining the onset of NREM and REM sleep is animportant tool complimenting the studies assessing relationship between varioushormones and phases of sleep. The slow wave activity (SWA) corresponds to theintensity of sleep at its onset during the biological night of an individual. Besides,GHRH and CRH, several other peptide and steroid hormones such as growthhormone (GH), its secretagogues, ghrelin, neuropeptide Y, estrogen anddehydroepiandrosterone sulfate are associated or have the potential to change phases ofsleep including initial slow wave-NREM sleep

Plasma adrenocorticotropin (ACTH) values and cortisol response to 250 and 1 μ g ACTH stimulation in patients with hyperthyroidism before and after carbimazole therapy: Case-control comparative study

Context: Although the production and metabolic clearance rate of cortisol is increased during thyrotoxic state, the net effect on adrenocortical reserves is not clear. Objective: We assessed circulating ACTH levels, cortisol binding globulin (CBG), and adrenocortical reserves in hyperthyroid patients (before and after carbimazole therapy) and healthy controls. Design and Setting: This was a case-control investigative study in a tertiary care setting. Patients and Methods: Plasma ACTH and free cortisol index (FCI; serum cortisol/CBG) were measured in 49 consecutive patients with hyperthyroidism and 50 controls. ACTH1-24 stimulation tests (250 and 1 μ g) were carried out in the first 29 patients and 15 controls. Peak FCI less than the mean -3 SD of healthy controls was considered subnormal. ACTH1-24 stimulation tests were repeated in 24 patients in the euthyroid state. Results: The mean basal plasma ACTH and FCI were higher and CBG was lower in thyrotoxic patients in comparison with controls. The peak cortisol was less than 18 μ g/dl in 10 of 29 and 14 of 29 on 250 and 1 μ g ACTH1-24 stimulation. Peak FCI was subnormal only in three of 27 (11.1%) and two of 21 (7.4%) on 250 and 1 μg ACTH1-24 stimulation, respectively. The mean plasma ACTH, basal FCI, and subnormal peak FCI (two of the three) normalized after euthyroidism. Plasma ACTH and FCI did not correlate with severity of thyrotoxicosis. Conclusions: Up to 11% of thyrotoxics have subnormal peak FCI on ACTH1-24 stimulation. Such changes occur despite high basal plasma ACTH and FCI. Use of FCI, rather than total cortisol, is required for the interpretation of cortisol values in thyrotoxicosis due to the variation in CBG

Seasonal variation of heavy metals in Subarnarekha River at Jamshedpur, East Singhbhum, Jharkhand

The present investigation is aimed at assessing the amount of heavy metals andcurrent water quality standard along the Subarnarekha river in Jharkhand. Three samples were collected along the stretches of Subarnarekha basin during the period : Jan-Dec, 2015, on the first week of every month. The concentrations Cu, Pb, Ni, Zn, Cr, Co, Sr, Cd and Fe were determined using inductively coupled plasma mass spectrometry for seasonal fluctuation, source apportionment and heavy metal pollution indexing. The results demonstrated that concentrations of the metals showed significant seasonality. To assess the composite influence of all the considered metals on the overall quality of the water, heavy metal pollution indices were calculated. The deterioration of water quality and enhanced concentrations of certain metals in the Subarnarekha River near industrial and mining establishments may be attributed to anthropogenic contribution from the industrial and mining activities of the area. Various physicochemical parameters like pH, TDS, EC, DO, BOD, Total Hardness, Total alkalinity sodium, potassium, calcium, magnesium etc. were also analysed. Eight parameters namely pH, Dissolved Oxygen, Biochemical Oxygen Demand, Nitrate, Phosphate, Total Dissolved Solids and Faecal Colliform were considered to compute Water Quality Index (WQI) based on National Sanitation Foundation studies and discussed

Ectopic pituitary adenoma with an empty sella

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Prevalence of thyroid autoimmunity in sporadic idiopathic hypoparathyroidism in comparison to type 1 diabetes and premature ovarian failure

Context: Thyroid autoimmunity is the most common coexistent endocrinopathy in type 1 diabetes (T1D), Addison's disease, and premature ovarian failure (POF). Although the role of autoimmunity is being investigated in patients with sporadic idiopathic hypoparathyroidism (SIH), there is little information on coexistent thyroid autoimmunity. Objective: Our objective was to assess the prevalence of thyroid peroxidase autoantibodies (TPOAb) and thyroid dysfunction in patients with SIH and its comparison with that in T1D, POF, and Hashimoto's thyroiditis (HT) and age- and sex-matched healthy controls (for SIH). Design and Setting: We conducted a case control study in a tertiary care setting. Patients and Methods: Subjects were consecutive patients with SIH (n = 87), T1D (n = 100), POF (n = 58), and HT (n = 47) and healthy controls (100 females and 64 males). Serum free T3, free T4, TSH, and TPOAb (normal ≤ 34 IU/ml) were measured by electrochemiluminescence assay. Subjects with 1) serum TSH at least 5 μ U/ml along with TPOAb more than 34 IU/ml; 2) TSH at least 10 μ U/ml but normal TPOAb titers; or 3) Graves' disease were considered to have thyroid dysfunction. Results: TPOAb positivity (>34 IU/ml) in females was 14.6% in SIH, 24.1% in POF, and 42.1% in T1D compared with 76.6% in HT and 9% in healthy controls. The frequencies of TPOAb positivity and thyroid dysfunction in patients with SIH were comparable to those in control and POF groups, but significantly less than in T1D and HT groups. Conclusion: The frequencies of TPOAb and thyroid dysfunction were not significantly higher in patients with SIH than in healthy controls, unlike in patients with T1D and POF

Pattern of 25-hydroxy vitamin D response at short (2 month) and long (1 year) interval after 8 weeks of oral supplementation with cholecalciferol in Asian Indians with chronic hypovitaminosis D

Hypovitaminosis D is common in Asian Indians. Physicians often prescribe 1500 μ g (60 000 IU) cholecalciferol per week for 8 weeks for vitamin D deficiency in India. Its efficacy to increase serum 25-hydroxy vitamin D (25(OH)D) over short (2 months) and long (1 year) term is not known. We supplemented a group of twenty-eight apparently healthy Asian Indians detected to have low serum 25(OH)D (mean 13.5 (sd 3.0) nmol/l) on screening during January-March 2005. Serum parathyroid hormone (PTH) level was supranormal in 30 % of them. Oral supplementation included 1500 μ g cholecalciferol per week and 1g elemental Ca daily for 8 weeks. Serum 25(OH)D, total Ca, inorganic P and intact (i) PTH were reassessed in twenty-three subjects (twelve females and eleven males) who had follow up at both 8 weeks and 1 year. At 8 weeks the mean 25(OH)D levels increased to 82.4 (SD 20.7) nmol/l and serum PTH normalized in all. Twenty-two of the twenty-three subjects had 25(OH)D levels>49.9 nmol/l. At 1 year, though the mean 25(OH)D level of 24.7 (SD 10.9) nmol/l was significantly higher than the baseline, all subjects were 25(OH)D deficient. Five subjects with supranormal iPTH at baseline showed recurrence of biochemical hyperparathyroidism. Thus, with 8 weeks of cholecalciferol supplementation in Asian Indians with chronic hypovitaminosis D, mean serum 25(OH)D levels would be normalized and serum PTH value would be reduced to half. However, such quick supplementation would not maintain their 25(OH)D levels in the sufficient range for 1 year. For sustained improvement in 25(OH)D levels vitamin D supplementation has to be ongoing after the initial cholecalciferol loading

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

Prevalence of clinical remission in patients with sporadic idiopathic hypoparathyroidism

Background: Remission of disease activity is a characteristic feature of autoimmune endocrine disorders such as Graves' disease, Addison's disease and occasionally in patients with premature ovarian failure. Autoimmunity is also implicated in sporadic idiopathic hypoparathyroidism (SIH) with clinical remission of disease reported in three cases. Objective: To assess the rate of remission in patients with sporadic idiopathic hypoparathyroidism and review the cases reported so far. Subjects and methods: Subjects included 53 patients (M:F, 24:29) with SIH who had been symptomatic for at least 1 year (range 1-31 years). They were treated with calcium and 1-α -(OH)D3/cholecalciferol therapy and had a mean duration of follow up of 5.0 ± 3.2 years. Treatment was withdrawn in two stages in the patients who maintained normal levels of serum total calcium during the preceding year of treatment. In stage-1, the dose of therapy was reduced to half and subsequently all treatment was stopped (stage 2) in those patients who maintained normal serum total calcium levels on the reduced dose. Remission of SIH was defined as maintenance of normal serum total (≥ 2.12 mmol/l) and ionized calcium, inorganic phosphorus and serum intact parathyroid hormone (iPTH) for at least 3 months after withdrawal of calcium and 1-α -(OH)D3/cholecalciferol therapy. Calcium sensing receptor autoantibodies (CaSRAb) were determined by Western blot. Results: Two of the 53 patients (3.8%) with SIH stayed in remission for 1 year after complete withdrawal of therapy. CaSRAb was absent in both the cases. The clinical features, age at onset and duration of hypocalcaemic symptoms in cases with remission were comparable to those who did no show remission. Conclusion: Sporadic idiopathic hypoparathyroidism is not irreversible as is widely believed and spontaneous remission of disease may occur in 3.8% of patients

Prevalence and functional significance of 25-hydroxyvitamin D deficiency and vitamin D receptor gene polymorphisms in Asian Indians

Background: Recent studies show a wide prevalence of hypovitaminosis D in Asian Indians. Objective: The objective was to assess the functional significance of 25-hydroxyvitamin D [25(OH)D] deficiency, vitamin D receptor (VDR) gene, and parathyroid hormone (PTH) gene polymorphisms in relation to bone mineral density (BMD) in urban Asian Indians. Design: Serum total calcium, inorganic phosphorus, alkaline phosphatase, 25(OH)D, intact PTH, and BMD at lumbar spine, proximal femur, and forearm were measured in 105 adult subjects. The genotyping related to VDR (BsmI, FokI, and TaqI) and PTH (BstBI and DraII) gene single-nucleotide polymorphisms was carried out by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The mean serum 25(OH)D concentration in the whole cohort was 9.8 ± 6.0 ng/mL, which was inversely related with serum intact PTH values (P = 0.042). Ninety-nine (94.3%) of the 105 subjects had vitamin D deficiency with 25(OH)D concentrations < 20 ng/mL. The age- and body mass index (BMI)-adjusted BMD value at the hip was higher in subjects with serum 25(OH)D values > 9.0 ng/mL than in those with values ≤9.0 ng/mL (0.893 ± 0.114 compared with 0.839 ± 0.112 g/cm2, respectively; P = 0.001). The mean forearm and spine BMD values in subjects with TT (VDR, TaqI) or bb (PTH, BstBI) genotypes were significantly higher than the values in subjects with Tt genotype and BB or Bb genotype, respectively. Conclusion: Functionally significant 25(OH)D deficiency affecting BMD at the hip region is prevalent in urban Asian Indians. However, variation in BMD at the spine and forearm is related to VDR and PTH gene polymorphisms rather than to vitamin D status, at least in this hypovitaminotic D population