A Crossover Study Evaluating Effect of Timing of Levothyroxine on Thyroid Hormone Status in Patients of Hypothyroidism.

OBJECTIVE: Current literature shows a definite benefit of fasting state Levothyroxine administration. However, superiority of any specific timing is not yet established. Our study was designed to compare the effect of timing of levothyroxine administration, morning versus evening dose, on thyroid profile control in patients of hypothyroidism. METHODOLOGY: :A randomized double-blind crossover study was performed on 60 patients with primary hypothyroidism, euthyroid on stable levothyroxine regime of 100 µg daily, randomized into two sequence groups, morning dose first (AB sequence) versus evening dose first (BA sequence) with switch over after 6 weeks. Primary endpoints were change in thyroid function tests. RESULTS: There was an insignificant rise in TSH in morning dose first group (AB) at 6 weeks which reduced significantly in evening dose, [2.36(1.11) to 2.45(1.19) mIU/L (p=0.56)], [2.07(0.99) (p=0.006)] respectively. Levothyroxine evening dose first group (BA) showed significant reduction of TSH levels at 6 weeks followed by non significant increase [2.63(0.96) to 1.85(1.35) mIU/L, (p=0.002)], [2.14(1.16), (p=0.15)]. Group AB showed mild followed by significant rise in FT4 at 6 and 12 weeks respectively, [1.06(0.30) to 1.14(0.33) ng/dl (p=0.18)], [1.24(0.36) (p=0.008)]. FT4 of BA sequence significantly increased at 6 weeks followed by mild increase, [1.10(0.29) to 1.20(0.28) ng/dl (p=0.01)] [1.23(0.31) ng/dl (p=0.58)]. FT3 of AB revealed initial reduction (p=0.87), followed by significant rise (p=0.02). Group BA showed a significant rise (p=0.04) in FT3 followed by fall (p=0.63). CONCLUSION: Bedtime dosing of Levothyroxine showed improved thyroid hormone status control and could be a viable option in treatment of patients with hypothyroidism.

Comparing the efficacy and safety profile of sitagliptin versus glimepiride in patients of type 2 diabetes mellitus inadequately controlled with metformin alone.

OBJECTIVE: To compare the efficacy and safety of sitagliptin and glimepiride in treatment of patients with type 2 diabetes mellitus inadequately controlled with metformin alone. RESEARCH DESIGN AND METHODS: In an 18 week, randomized parallel group interventional trial, 50 subjects who were only on metformin as antidiabetic agent, with inadequate glycemic control, were randomized to either sitagliptin 50/100mg or glimepiride 1/2 mg per day. Dose of drugs was adjusted after 4 weeks if glycemic control was not reached. RESULTS: At 18 weeks both groups (sitagliptin and glimepiride) produced significant (P < 0.001) reduction in HbA1C (-0.636% and -1.172% respectively), with 12% patients in sitagliptin group and 36% patients in glimepiride group achieving target HbA1C. Reduction was also significant (P < 0.001) in both groups in FPG (-15.49 mg and -29.84 mg respectively) and 2HPPG (-34.28 mg and -44.83 mg respectively). Sitagliptin group showed net decrease in bodyweight by 0.102 kg whereas glimepiride group showed net increase in body weight by 0.493 kg. Incidence of hypoglycemia was 4% in sitagliptin group and 8% in glimepiride group. CONCLUSION: In this study addition of sitagliptin and glimepiride to metformin monotherapy, produced significant improvement in glycemic control. Benefits were more with glimepiride in comparison to sitagliptin. Sitagliptin was well tolerated, with lower risk of hypoglycemia than glimepiride, and produced weight loss as compared to weight gain with glimepiride.

Burden of organochlorine pesticides in blood and its effect on thyroid hormones in women.

Man has utilized a wide variety of pesticides to combat the crop pests and vectors of human diseases. However, in this process, he has overlooked the darker side of these noxious chemicals, the concentrations of which have reached the environment and pose serious threats, such as mutagenesis, teratogenesis, carcinogenesis and endocrine dysfunction in various components of the ecosystem. The present study was planned to assess the burden of organochlorine pesticides and their influence on thyroid function in women. The study included a total of 123 women from Jaipur City who visited the Thyroid clinic in SMS Medical College and Hospital. One hundred women showed normal thyroid hormone levels while the remaining 23 women had depleted T4 and high TSH levels. The qualitative and quantitative estimation of organochlorine pesticides was carried out by gas chromatography. Out of the analyzed pesticides, the concentration of p,p'-DDT and its metabolites was higher in all the subjects, but dieldrin was found to be significantly high in the hypothyroid women. The correlation analysis for dieldrin and depleted T4 levels in hypothyroid women elicited an inverse relationship between them.

Granulomatous angiitis of the central nervous system associated with herpes zoster.

Granulomatous angiitis of central nervous system (CNS) is a rare inflammatory disease of blood vessels mostly confined to CNS. We describe a case which presented with right sided hemiplegia with aphasia, after herpes zoster ophthalmicus. CT scan and MRI brain showed a large left sided infarct in the left middle cerebral artery (MCA) territory. MRI angiography revealed narrowing and thinning of left internal carotid artery (ICA) and to a lesser extent, left MCA suggestive of granulomatous vasculitis. Herpes zoster is often associated with major CNS involvement and a vascular etiology was previously postulated. Recent pathological reports suggest that cerebral angiitis secondary to herpes virus infection may be more common than realised.

An open study to evaluate the efficacy of artemether in severe falciparum malaria.

An open clinical trial was conducted in 30 patients of severe falciparum malaria with heavy parasitaemia (parasitized erythrocytes above 5%). Artemether (methyl ether of dihydroartemisinin-active principle isolated from Chinese plant Qinghaosu) was administered as 80 mg intramuscular injection twice on first day and then single dose of 80 mg intramuscular on 2nd to 5th day. The trial could be completed in 28 patients and two patients expired. In our observation falciparum malaria affected the young adults in their most productive period of life i.e. 25-44 yrs. All patients became afebrile by the 4th day with fever clearance time approximately 31.92 +/- 15.30 hr. Twenty-five patients (83.33%) became parasite free by 5th day with mean parasite clearance time approximately 47.04 +/- 19.95 hr. Deranged liver function and renal profile was observed in 63% and 50% patients respectively. Two patients, who died had very high degree of parasitaemia (50% and 16%) with cerebral malaria. One died due to multiorgan failure and other due to massive hematemesis and shock. The type of response achieved by artemether therapy was analysed as per WHO criteria suggested for chloroquine resistance. S response was observed in 25 patients (cure rate 83.33%). Two patients (6.66%) patients showed R II response, one patient (3.33%) showed R III response and R I response was not observed in any patient. No significant side effects were noted. This pilot study demonstrated that intramuscular artemether is a useful addition to antimalarial drugs in this era of multidrug resistant P. falciparum malaria showing high clinical potency with virtually no side effect.

Antihypertensive efficacy and tolerability of once-daily sustained-release diltiazem alone and in combination with ramipril in hypertension.

This study assessed once-daily (OD), sustained-release (SR) diltiazem alone and in combination with ramipril in essential hypertension. Fifty patients with supine diastolic blood pressure (DBP) > or = 95-< or = 114 mm Hg were entered into the active treatment phase of the study after 2 weeks of placebo run-in. Sustained-release diltiazem 180 mg OD was administered for 2 weeks, then optimally titrated, at 2 week intervals, to SR diltiazem 240 mg OD and then SR diltiazem 180 mg + ramipril 2.5 mg OD to achieve supine DBP < or = 90 mm Hg. After 4 weeks of diltiazem monotherapy (SR diltiazem 180 mg or 240 mg OD) mean supine DBP was reduced from 102.84 +/- 3.81 mm Hg to 90.15 +/- 5.02 mm Hg (P < 0.01) and mean supine heart rate was reduced from 85.15 +/- 11.02 bpm to 77.62 +/- 11.45 bpm (p < 0.01). Diltiazem monotherapy reduced supine DBP to < or = 90 mm Hg in 35/45 (77.77%) patients. Combination therapy (SR diltiazem 180 mg + ramipril 2.5 mg OD), received by non-responders to diltiazem monotherapy, reduced supine DBP to < or = 90 mm Hg in 3/10 (30%) patients. Sinus bradycardia was observed in one patient. Sustained-release diltiazem alone and in combination with ramipril reduce blood pressure in a dose related manner and is well tolerated.