Improvement in metabolic indices including thyroid hormones via enhanced absorption of nutrients by Teduglutide in short bowel syndrome.

INTRODUCTION AND IMPORTANCE: Short bowel syndrome is characterized by maldigestion and malabsorption resulting in deficiencies of multiple nutrients including vitamins and minerals. Most subjects required parental elimination for survival. GLP-2 RA Teduglutide was recently approved for treatment of short bowel syndrome especially for those requiring parenteral support. Our intent in reporting this subject is to demonstrate the utility of Teduglutide in improving multiple metabolic indices in presence of short bowel syndrome. CASE PRESENTATION AND CLINICAL DISCUSSION: 66-year-old Caucasian female presented with a history of short bowel syndrome and associated vitamin deficiencies, hypothyroidism requiring large dose (300 µg) of levothyroxine, diarrhea and liver cirrhosis. Upon starting teduglutide the subject saw improvement in her symptoms. Moreover, daily dose of Levothyroxine required a gradual decrease to maintain desirable serum concentrations of Free T4, Free T3 and TSH. Serum levels of several vitamins attained greater than therapeutic concentrations requiring dosage reductions. Also notable was the improvement in her liver function tests, remission from ascites and episodes of hepatic encephalopathy and regeneration of liver nodules. CONCLUSION: Following administration of GLP2 therapy, an adult subject with short bowel syndrome with concurrent hypothyroidism and multiple vitamin deficiencies, demonstrated a marked improvement in her metabolic parameters resulting in reduction in daily medication doses along with improvement in manifestations of liver cirrhosis.

Low 25-Hydroxyvitamin D in Primary Hyperparathyroidism: Enhanced Conversion Into 1,25-Hydroxyvitamin D May Not Be "True" Deficiency.

Vitamin D deficiency is reported in individuals with primary hyperparathyroidism (PHP). However, decreased 25OHD may be attributed to enhanced conversion into 1,25-hydroxyvitamin D [1,25(OH)D]. To examine vitamin D metabolism in individuals with PHP, serum calcium, PTH, 25OHD, and 1,25(OH)D levels were determined in 210 adults: 102 with PHP, 40 with normal 25OHD, and 68 with vitamin D deficiency. Concentrations were redetermined in 37 individuals with PHP following vitamin D supplementation and 43 patients postsurgery. Comparisons were conducted by Student's t test and ANOVA. Correlations were assessed between PTH and 25OHD, 1,25(OH)D, and 1,25(OH)D/25OHD in individuals with PHP. Calcium, PTH, and 1,25(OH)D were higher (p < 0.001) in individuals with PHP (11.4 ± 0.4, 116 ± 21, 79 ± 6) than in individuals with normal 25OHD (9.6 ± 0.2, 49 ± 5, 57 ± 6) and vitamin D deficiency (9.3 ± 0.2, 62 ± 6, 32 ± 4). Compared with individuals with normal 25OHD (47 ± 5), 25OHD was lower (18 ± 3), but not different from subjects with vitamin D deficiency (15 ± 2). In individuals with PHP, vitamin D2 supplementation induced rises in 1,25(OH)D and calcium without lowering PTH, whereas postsurgery, calcium, PTH, 25OHD, and 1,25(OH)D normalized. Finally, in individuals with PHP, significant correlations (p < 0.01) were documented between PTH and calcium (r = 0.74), 25OHD (r = -0.43), 1,25(OH)D (r = 0.52), and 1,25(OH)D/25OHD (r = 0.46); and between 1,25(OH)D/25OHD and calcium (r = 0.47). Subnormal 25OHD in most individuals with PHP may be attributed to enhanced conversion to 1,25(OH)D-not "true" vitamin D deficiency-although in some patients, both PHP and vitamin D deficiency coexisted. Moreover, vitamin D supplementation exaggerated hypercalcemia in individuals with PHP. © 2020 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

MORE THAN MEETS THE EYE IN A PATIENT WITH PCOS: ANDROGEN-SECRETING GRANULOSA CELL OVARIAN TUMOR IN A VIRILIZED WOMAN WITH POLYCYSTIC OVARIAN SYNDROME (PCOS).

OBJECTIVE: Granulosa cell ovarian tumors are known to secrete estrogen. Herein we report a patient presenting with primary amenorrhea and virilization with markedly high androgen levels, all thought to be disproportional to be attributed to polycystic ovary syndrome (PCOS) alone. Bilateral oophorectomy revealed a rare androgen-secreting granulosa cell ovarian tumor and bilateral cysts (PCOS) both contributing to manifestations. METHODS: Description of a case and discussion of the literature. RESULTS: A 25-year-old female presented with primary amenorrhea, male pattern baldness and hirsutism of the face and chest, clitoral hypertrophy, cystic acne on the chest and shoulders, and type 2 diabetes. Diagnosis of PCOS was made at age 13 years. The concurrent presence of congenital adrenal hyperplasia was also considered. She was receiving metformin, oral contraceptives, and/or spironolactone with no improvement in manifestations at presentation to the endocrine clinic. She reported several elevated serum testosterone and androstenedione levels. Diagnosis of PCOS was established by the presence of enlarged cystic ovaries on ultrasound examination. The patient reported worsening manifestations including progression of diabetes despite therapy with metformin. She shaved her face, chest, and breasts daily for cosmetic reasons. Laboratory testing demonstrated markedly elevated total testosterone level (234 ng/dL), and normal cortisol and adrenocorticotropic hormone levels. Dexamethasone suppression and human chorionic gonadotropin stimulation indicated ovaries as a probable source of excessive circulating androgen levels. A computed tomography scan of the abdomen and pelvis showed multiple cysts in both ovaries, the largest being 1.9 cm in the right ovary. Due to the severity of manifestations, the patient was counseled to undergo fluoroscopically guided blood sampling of bilateral adrenal and ovarian veins, which confirmed both ovaries to be the source of the excess androgen production with a greater contribution by the right ovary. The patient underwent bilateral oophorectomy. Pathologic examination confirmed the presence of bilateral polycystic ovaries as well as an androgen-secreting granulosa cell tumor in the right ovary which apparently contributed to greater androgen levels in a right ovarian venous blood sample. Peripheral venous androgen levels normalized promptly after bilateral oophorectomy. Gradual resolution of clinical manifestations followed. CONCLUSION: A unique presentation of granulosa cell ovarian tumor with concurrent PCOS contributing to the extremely excessive production of androgens in a young woman manifesting primary amenorrhea and masculinization at the onset of puberty with marked gradual resolution of manifestations following bilateral oophorectomy.

Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese.

CONTEXT: Lowering of body mass index (BMI) to ≥25 kg/m2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI < 27 kg/m2) subjects with IGM. OBJECTIVE: Assessment of IS and insulin resistance (IR) in L and obese (Ob; BMI ≥ 27 kg/m2) subjects with euglycemia (N), PreDM, and new onset DM2. SUBJECTS: Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. METHODS: Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. RESULTS: All indices of IS and IR were lower (P < 0.05) in L than corresponding Ob groups (P < 0.05). Moreover, decline in IS and rise in IR were progressive from N to PreDM (P < 0.05) and DM2 (P < 0.05) in both groups. However, the declines in IS were greater (P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher (P < 0.05) than declines in IS in ObPreDM and ObDM2. CONCLUSION: In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.

Case of diabetic ketoacidosis as an initial presentation of Cushing's syndrome.

SUMMARY: Diabetic ketoacidosis (DKA) is commonly encountered in clinical practice. The current case is a unique and rare presentation of DKA as the initial manifestation of Cushing's disease secondary to ACTH-secreting pituitary adenoma. Appropriate management as elaborated in the article led to total remission of diabetes as well as the Cushing's disease. LEARNING POINTS: DKA is a serious and potentially life-threatening metabolic complication of diabetes mellitus.Some well-known precipitants of DKA include new-onset T1DM, insulin withdrawal and acute illness.In a patient presenting with DKA, the presence of a mixed acid-base disorder warrants further evaluation for precipitants of DKA.We present a rare case of DKA as an initial manifestation of Cushing's disease secondary to ACTH-producing pituitary adenoma.

Elevated fructosamine levels in acquired immunodeficiency syndrome.

OBJECTIVE: To investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer. METHODS: We assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (PAO2) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests. RESULTS: Fasting serum glucose was not significantly different between the men with AIDS (87 +/- 4 mg/dL) and the healthy male volunteers (84 +/- 6 mg/dL); however, A1C (6.9 +/- 0.2%) and serum fructosamine levels (288 +/- 15 micromol/L) were significantly higher (P<.01) in the patients with AIDS than in the normal subjects (A1C, 5.6 +/- 0.1%; fructosamine, 204 +/- 14 micromol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P<.01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin <12 g/dL) or hypoxia (PAO2 <95 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 +/- 3 mg/L) and the normal subjects (22 +/- 4 mg/L). CONCLUSION: On the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent.

Deleterious outcomes after abrupt transition from insulin glargine to insulin detemir in patients with type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Iowa Care (Iowa Medicaid), USA, switched insulin glargine to insulin detemir in subjects with diabetes mellitus without the approval of healthcare providers. This study set out to examine the impact of transition on parameters of diabetes management in type 1 diabetes. METHODS: This was a retrospective review of the records of subjects with type 1 diabetes up to August 2007 in whom transition occurred. Subjects completing 6 months of insulin detemir therapy were included. Twenty-four subjects switching from insulin glargine to insuline detemir (group 1) fulfilled the duration with insulin detemir. Glycaemic control (glycosylated haemoglobin [HbA1c]), bodyweight, daily insulin dose (units), total and insulin glargine or insulin detemir and rapid-acting insulin aspart and hypoglycaemic events during the last 4 weeks, pre-switch and again at 6 months post-switch were assessed. Records of 21 age-matched subjects and continuing insulin glargine for 6 months (group 2) were examined. Subjects switched from insulin glargine to insulin detemir in the same daily dose. The daily doses of insulin detemir and aspart in group 1 were adjusted by telephone weekly based on blood glucose monitoring until stabilization occurred. Subjects were followed up in the outpatient clinic every 3 months. RESULTS: Subjects in group 1 changed to insulin detemir twice a day because of a significant rise in hypoglycaemia with the daily dose used once a day. Glycaemic control remained stable on continuing insulin glargine; HbA1c 7.6+/-0.3 to 7.8+/-0.3%, while it worsened on switching to insulin detemir; HbA1c 7.9+/-0.6 to 8.8+/-0.8 despite a higher daily dose; insulin detemir 46+/-9 U/day versus pre-switch insulin glargine 36+/-8 U/day and group 2 insulin glargine 35+/-6 U/day; and greater total insulin dose: 80+/-12 U/day versus 68+/-10 pre-switch and group 2 insulin glargine 62+/-10 U/day (p<0.05 for all comparisons). Bodyweight and hypoglycaemic events were not significantly different pre- and post-switch. CONCLUSION: Switching to insulin detemir from glargine is likely to result in lapse of glycaemic control despite a higher daily insulin dose, increased number of injections and need for frequent evaluations.

Starting insulin in type 2 diabetes: Overcoming barriers to insulin therapy.

BACKGROUND: Several barriers to insulin therapy are encountered by both the providers and the patients with type 2 diabetes mellitus. These barriers include the fear of the needles i.e. number of injections as well as number of times of self blood glucose monitoring, fear of hypoglycemia and weight gain as well as the convenience, compliance and the cost. However, most of these patients are likely to require insulin therapy with increasing duration of the disorder because of the progressive cell failure. Therefore the most important aspect of insulin therapy must revolve around the regimen most suitable and acceptable because of its ability in overcoming these barriers while being effective in attaining and maintaining desirable glycemic control. METHODS: Recently published studies using different regimens with combinations of various oral agents and insulins in patients with type 2 DM and manifesting lapse of glycemic control when treated with various oral agents are discussed. Specific attention is paid to the capacity of each individual regimen in overcoming aforementioned barriers. RESULTS: Comparative analysis amongst various insulin regimens shows that combination of metformin, and glimeperide with SC administration of basal insulin Lantus required the least daily dose of insulin with least consequential hypoglycemia as well as weight gain. Moreover, the number of injections as well as the number of times of self blood glucose monitoring, were lesser with this regimen with better compliance and more convenience in comparison to other combination insulin regimens. CONCLUSION: The insulin regimen with fewest barriers consists of one SC injection of basal insulin lantus in combination with oral agents. However, to be effective, oral agents must include a secretogogue i.e. glimeperide in addition to a sensitizer i.e. metformin and not multiple sensitizers without a secretogogue. Moreover, this regimen apparently is also the most preferred by the patients, and is cost effective.

Serum thyrotropin in Graves' disease: a more reliable index of circulating thyroid-stimulating immunoglobulin level than thyroid function?

OBJECTIVE: To assess the relationship between serum thyrotropin (thyroid-stimulating hormone or TSH) on one hand and thyroid-stimulating immunoglobulin (TSI), free thyroxine (T4), and triiodothyronine (T3) levels on the other in Graves' disease, inasmuch as TSH may be suppressed in the presence of TSI because TSI may bind to the TSH receptor on the thyroid gland membrane and thus eliminate the need for circulating TSH for stimulating the thyroid gland. METHODS: We determined serum TSI levels in 37 women and 13 men with Graves' disease, stratified into 4 groups on the basis of serum TSH levels irrespective of serum free T4 and T3 levels. Our reference ranges were 0.72 to 1.74 ng/dL for free T4, 80 to 200 ng/dL for T3, and 0.4 to 4.0 micro/mL for TSH. RESULTS: Mean serum TSI concentrations were highest (215% +/- 28%) in patients with undetectable TSH levels (<0.03 micro/mL) and lowest (103% +/- 9%) in those with supernormal TSH concentrations (>4.0 micro/mL). TSI levels were intermediate in the other study groups: 157% +/- 16% in patients with subnormal though detectable TSH levels (0.03 to 0.39 micro/mL) and 125% +/- 12% in those with normal TSH levels (0.4 to 4.0 micro/mL). Moreover, a progressive decline in TSI levels with increasing serum TSH concentrations was noted, along with a significant negative correlation (r = -0.45; P<0.01) between serum TSI and TSH concentrations. Finally, relationships between free T4 and T3 levels on one hand and TSI or TSH levels on the other were not significant, with a considerable variability in free T4 and T3 levels being noted in individual study groups. CONCLUSION: Serum TSH is frequently suppressed after treatment with antithyroid drugs or radioiodine (131I), irrespective of clinical thyroid function as expressed by increased, normal, or decreased free T4 and T3 concentrations. In an individual patient with Graves' disease, the serum TSH level may be more reflective of the circulating TSI concentration than is thyroid gland function as expressed by free T4 and T3 concentrations and therefore may be as reliable a predictor of remission as TSI.

Role of thyrotropin in metabolism of thyroid hormones in nonthyroidal tissues.

T(4) conversion into T(3) in peripheral tissues is the major source of circulating T(3). However, the exact mechanism of this process is ill defined. Several in vitro studies have demonstrated that thyrotropin facilitates deiodination of T(4) into T(3) in liver and kidneys. However, there is a paucity of in vitro studies confirming this activity of thyrotropin. Therefore, this study was conducted to examine the influence of thyrotropin on thyroid hormone metabolism in nonthyroidal tissues. We assessed T(4), T(3), reverse T(3) (rT(3)), and T(3) resin uptake (T(3)RU) responses up to 12 hours at intervals of 4 hours in 6 thyroidectomized female mongrel dogs rendered euthyroid with LT(4) replacement therapy before and after subcutaneous (SC) administration of bovine thyrotropin (5 U) on one day and normal saline (0.5 mL) on another in a randomized sequence between 08:00 and 09:00 am. Euthyroid state after LT(4) replacement was confirmed before thyrotropin administration. Serum T(4), T(3), rT(3), and T(3)RU all remained unaltered after SC administration of normal saline. No significant alteration was noted in serum T(3)RU values on SC administration of thyrotropin. However, serum T(3) rose progressively reaching a peak at 12 hours with simultaneous declines being noted in both serum T(4) and rT(3) concentrations (P < .05 vs prethyrotropin values for all determinations). The changes after SC administration were significantly different (P < .001) in comparison to those noted on SC administration of normal saline. Thyrotropin may promote both the conversion of T(4) to T(3) and metabolism of rT(3) into T(2) in nonthyroidal tissues via enhancement of the same monodeionase.

Comparative efficacy of glimepiride and/or metformin with insulin in type 2 diabetes.

BACKGROUND AND AIMS: The data regarding comparison of efficacy of metformin with glimepiride, newest Sulfonylurea, or with the use of both drugs in combination with insulin is rare in the literature. Therefore, we assessed the daily insulin dose, hypoglycemic events and body weight on achieving desirable glycemic control after addition of insulin, to glimepiride 8 mg and/or metformin 2500 mg, in subjects with type 2 DM manifesting lapse of glycemic control. METHODS: S.C. insulin Novolog Mix [70/30], pre-supper was initiated in 12 subjects on metformin, 14 subjects on glimepiride, and 12 subjects receiving both drugs, with HbA1C > 7.5% and eight subjects receiving placebo. Insulin dose was increased by 4 U at weekly interval until fasting blood sugar [FBS] between 6.6 and 8 mM/l was attained and then further titrated by 2 U every week to attain and maintain FBS between 4.5 and 6.7 mM/l over the next 4 months. The comparisons were conducted between these groups for HbA1C, the daily insulin dose, body weight noted at the end of this study period as well as the hypoglycemic episodes per patient during the last 4 weeks of the study period. RESULTS: HbA1C levels were < 7.0% in all subjects at the end of the study. The daily insulin dose (units), total and per kg/BW was significantly lower [p < 0.001] with metformin (51 +/- 5, 0.51 +/- 0.10), glimepiride (40 +/- 4, 0.42 +/- 0.09) as well as with both drugs (23 +/- 7, 0.21 +/- 0.07) in comparison to placebo (82 +/- 10, 0.82 +/- 0.12). The insulin dose was also significantly lower [p < 0.05] in subjects on both drugs than subjects receiving them individually. Weight gain was less [p < 0.001] with metformin [2.5 +/- 0.74 kg], glimepiride [2.3 +/- 0.7 kg], and both drugs [2.2 +/- 0.61 kg] in comparison to placebo [5.2 +/- 1.4 kg] whereas the hypoglycemic episodes were lesser with metformin (3.8 +/- 1.2) and glimepiride (3.3 +/- 0.9) and least with both drugs (2.5 +/- 0.6) in comparison to placebo (5.2 +/- 1.0). CONCLUSION: Glimepiride and metformin are effective individually in achieving a glycemic goal with a less daily insulin dose, weight gain, and hypoglycemic episodes in comparison to insulin monotherapy in subjects with type 2 diabetes mellitus with further marked reduction in these parameters when used concurrently.

Cost-effective management of hyperglycemia in patients with type 2 diabetes using oral agents.

Diabetes exacts an enormous toll on health care resources, with extremely high costs attributable to care of diabetes patients in proportion to the afflicted population. Though individual treatment strategies are required for each patient, newer long-acting sulfonylureas may be the initial drugs of choice, as they may be the only oral agents that inhibit the processes inducing hyperglycemia--hepatic glucose production and glucose utilization by the tissues--by improving insulin secretion and insulin resistance. Sulfonylureas also represent the most cost-effective therapeutic option, alone or in combination with other oral agents or insulin. The newer long-acting agents, glimepiride and glipizide GITS, may be more attractive among sulfonylureas, due to their greater insulin-sparing property, fewer hypoglycemic events, weight neutrality, and once-daily dosing. Glimepiride may be preferred due to its safety profile, especially for the elderly and those with hepatic and/or renal dysfunction.

Effects of glimepiride on insulin secretion and sensitivity in patients with recently diagnosed type 2 diabetes mellitus.

BACKGROUND: The exact mechanism of the efficacy of glimepiride in the achievement of glycemic control has not yet been clearly defined. OBJECTIVE: This study was conducted to examine the influence of glimepiride on insulin secretion and sensitivity in patients with type 2 diabetes mellitus (DM) of recent onset. METHODS: This 24-week, open-label, controlled trial was conducted at the Division of Endocrinology and Metabolism, Veterans Affairs Medical Center (Phoenix, Arizona). Study participants were aged 32 to 75 years and had recent-onset (established by a short duration of symptoms 6 weeks to 6 months prior to the study) type 2 DM, or were age-matched healthy volunteers (control group). In the diabetic patients, glimepiride tablets were administered orally, initially at 2 mg once daily in the morning, with the dosage increased by 1 mg every 2 weeks until fasting plasma glucose (FPG) decreased to 6.7 mmol/L; the dosage was then maintained for the remainder of the 24-week study period. Oral glucose tolerance tests (OGTTs) were conducted in the control group and before treatment and at 24 weeks after the achievement and maintenance of glycemic control (glycosylated hemoglobin <7.0%) in the diabetic group. For OGTT, plasma insulin and glucose levels were determined after the subjects fasted overnight and then at every 15 minutes for 2 hours after glucose challenge. RESULTS: Fourteen diabetic men (mean [SEM] age, 50 [6] years; range, 32-75 years) and 10 male healthy controls (mean [SD] age, 48 [5] years; range, 30-68 years) were enrolled. In the DM group, FPG decreased significantly after treatment ( P<0.001); fasting plasma insulin was markedly elevated before treatment (P<0.001 vs controls) and decreased after treatment ( P<0.01) but did not normalize; first-phase insulin secretion was markedly inhibited before treatment ( P<0.001 vs controls) and normalized after treatment ( P<0.001) total insulin secretion significantly improved after treatment ( P<0.01) but did not normalize. Finally, the pretreatment insulin sensitivity index decreased significantly (P<0.01) after treatment and normalized in 6 of 14 patients (42.9%) with type 2 DM. CONCLUSIONS: In this study, glimepiride achieved desirable glycemic control in patients with recent-onset type 2 DM through improvement in insulin secretion and sensitivity.

Optimizing treatment of hypothyroidism.

Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.

Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus.

BACKGROUND: In subjects with type 2 diabetes mellitus, glycemic control deteroriates while patients use sulfonylurea drugs during the course of the disease. Adjunctive therapy with insulin at this stage requires a lesser daily insulin dose in comparison with insulin monotherapy while restoring desirable glycemic control. However, data regarding direct comparison between various sulfonylureas in this regard are lacking. OBJECTIVE: To examine comparative efficacies of adjunctive therapy with insulin in subjects with type 2 diabetes manifesting lapse of glycemic control while receiving various individual sulfonylurea drugs. METHODS: Four groups of 10 subjects, each presenting with glycosylated hemoglobin (HbA(1C)) >8.0% while using either tolazamide, glyburide, glipizide Gastrointestinal Therapeutic System (GITS), or glimepiride, were recruited. Two from each group were randomized to receive placebo; the others continued the same drug. Pre-supper subcutaneous 70 NPH/30 regular insulin was initiated at 10 units and gradually increased and adjusted as necessary to attain fasting blood glucose levels between 80 and 120 mg/dL and maintain the same range for 6 months. Fasting plasma glucose, plasma C-peptide, and HbA(1C) concentrations were determined prior to the addition of insulin and at the end of the study. Daily insulin dose and changes in body weight (BW) were noted at the end of the study, and the number of hypoglycemic events during the last 4 weeks of the study was determined. RESULTS: Daily insulin dose (units/kg BW), weight gain, and number of hypoglycemic events were significantly lower (p < 0.01) in subjects receiving sulfonylureas in comparison with placebo. However, the daily insulin dose alone was significantly lower (p < 0.05) with glimepiride (0.49 +/- 0.10; mean +/- SE) than with other sulfonylureas (tolazamide 0.58 +/- 0.12, glyburide 0.59 +/- 0.12, glipizide GITS 0.59 +/- 0.14). Finally, a significant correlation (r = 0.68; p < 0.001) was noted between suppression of plasma C-peptide level and the daily insulin dose among all participants. CONCLUSIONS: By lowering the daily insulin dose, sulfonylurea drugs appear to improve the sensitivity of exogenous insulin in subjects with type 2 diabetes mellitus manifesting lapse of glycemic control. Moreover, glimepiride appears to possess a greater insulin-sparing property than other sulfonylureas.