Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of "Graves disease" treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH.
Background: Rx with SU and Metformin lowered daily dose of insulin glargine with desirable glycemia. However, Soliqua trials excluded SU and subjects with morbid obesity. Objective: Assess long term efficacy and safety of Soilqua with Glimepiride and Metformin in subjects with type 2 diabetes. Subjects: 31 adults with type 2 diabetes wre identified as currently using Soliqua via EMR. One is excluded as therapy < 3 months. A1c >7.5% with 1) Glimepiride, Metformin and Basal insulin , 2) Metformin and/or DPP 4 inhibitors and/or other SUs and /or GLP1 RA and/or Basal and/or prandial insulin. Subjects with gastroparesis, Triglycerides > 300 mg/dl and pancreatitis are excluded. Methods: Oral drugs besides Glimepiride and Metformin, Basal and prandial insulin and GLP1 RA were stopped. Glimepiride 8 mg, Metformin 1000-2000 mg were started with Soliqua daily dose pre-breakfast based on previous basal insulin dose and increased by 2 units every 3 days until AM sugar >80<130 mg/dl was attained or dose of 60 units was reached. Comparisons are conducted forBW (kg), fasting glucose (mg/dl) and A1c (%) prior to initiation of therapy and at the time of analysis. Results: BMI ranged between 22-67. Duration of diabetes is 4-24 years. Duration of therapy range, 5-47 (mean 16± 6 )months. Fasting glucose declined from 167±15 to 118± 4 and A1c dropped from 9.7±0.8 to 7.6±0.3. No severe hypoglycemia was reported. In 4 morbidly obese subjects, fasting glucose and A1c declined though not achieving desirable goals despite receiving maximal dose, 60 units. Mean daily dose of Soliqua was lower (0.38±0.08 units /kg BW compared to pivotal trials (0.44 units /kg BW). Conclusion: Soliqua is cost effective and safe in the long term in all subjects irrespective of BMI, when administered in combination with glimepiride and metformin. Moreover, it may be useful when administered with Glimepiride and Metformin in more subjects with higher BMI without attaining maximum daily dose in comparison to pivotal trials. Disclosure U. M. Kabadi: None. S. Exley: None.
Background All organizations use variable glucose criteria for diagnosis of gestational diabetes (GDM). However all involve OGTT. American college of Obstetrics and Gynecology (ACOG) and American Diabetes Association (ADA) recommend 2 step testing; 1) 1 hour glucose level on 50 gm glucose ingestion at any time during the day (1 hour OGTT) and 2) 3 hour OGTT with 100 gm glucose ingestion after overnight fast in pregnant women with glucose > 140 mg/dl during 1 hour. OGTTs require preparation with least daily intake of carbohydrate 150 gm for 3 days before testing. Many women are hesitant getting tested because of nausea, vomiting on glucose ingestion. Thus, none of the tests is convenient. Objective We examined utility of serum Fructosamine level as a screening test for diagnosis of GDM. Methods Random serum glucose and Fructosamine (mcM/l) levels as well as HbA1c (%) were determined at 24-30 weeks in 206 pregnant women, ages 24-40 years along with 1 hour OGTT and then again with 3 hour OGTT in 46 pregnant women with abnormal 1 hour OGTT and 21 age matched non-pregnant women. Continuous glucose monitoring (CGM) for 2 weeks was performed in 5 pregnant women with abnormal 3 hour OGTT and 7 non-pregnant women. Results Fructosamine levels (192± 4) were significantly lower (p<0.01) in nondiabetic pregnant women when compared with age matched non-pregnant women (224 ± 5). Cutoff serum Fructosamine concentration between groups was 205. Glucose and HbA1c were not significantly different amongst groups. Serum Fructosamine levels in 26 pregnant with abnormal 1 hour but normal 3 hour OGTT were <205, similar to nondiabetic pregnant women. Serum Fructosamine concentrations in women with abnormal 3 hour OGTT and normal CGM e.g, 70-140 mg /dl matched levels in nondiabetic pregnant women. Conclusion CGM may be the most accurate test for diagnosis of GDM. Random serum Fructosamine level may be as accurate as CGM and more accurate than both OGTTs. Importantly, it is a simple and convenient test without requiring fast, glucose ingestion or preparation. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
Background: Previous studies using basal insulin documented the lowest daily dose and least hypoglycemic events when combined with Glimepiride and Metformin while attaining desirable glycemic control. However, Pivotal trials with Soliqua excluded Glimepiride as a part of therapy as well as subjects with moderate obesity (BMI > 35kg/m2). Moreover, these trials were relatively short term. Objective: Assess long term efficacy and safety of Soliqua in combination with Glimepiride and Metformin in subjects with type 2 diabetes irrespective of BMI in ‘real world’ experience. Subjects: 30 adults with type 2 diabetes, age range 32-72 years with HbA1C >7.5% while receiving therapy with 1) Glimepiride, Metformin and Basal insulin and 2) Metformin and/or DPP 4 inhibitors and/or other SUs and /or GLP1 RA and/or Basal insulin and/or prandial insulin. Type 2 diabetes was confirmed by presence of C-peptide. Subjects with history of gastroparesis, Triglycerides over 300 mg/dl and pancreatitis were excluded. Subjects with elevated liver enzymes, over 2.5 times normal and EGFR < 30 ml/min were excluded as well. Methods: All prior therapies were discontinued. All subjects were started on Glimepiride 8 mg, Metformin 1000-2000 mg and SC Soliqua was initiated prior to breakfast with daily dose 15 or 30 units as recommended. Daily dose was increased by 2 units every 3 days until AM fasting plasma glucose of 80-130 mg/dl was attained or the dose of 60 units was reached. The stable daily dose of Soliqua was continued until the time of analysis. Comparisons were conducted between body weights (kg), fasting plasma glucose (FPG) and HbA1C prior to initiation of combination therapy (pre Rx) and every 3-6 months until the time of analysis (post Rx). Results: BMI ranged between 22-67 kg/m2. Duration of diabetes was 5-25 years. Duration of therapy with the combination therapy range, 7-56 months. Subjects were divided into 2 groups according to desirable HbA1C levels as per recommendations by ADA: 1) desirable HbA1C is < 7.0%, 2) desirable HbA1C 7-8 %. Both Fasting plasma glucose (mg/dl) and HbA1C (%) declined from 167 ± 10 and 9.7 ± 0.8 to 114 ± 4 and 7.6± 0.3 at the time of analyses (post Rx) respectively in the whole cohort. In 4 (0.13 %) morbidly obese subjects, FPG and HbA1C levels declined though not achieving desirable glycemic goals despite receiving maximal daily dose, 60 units of Soliqua. All four belonged to group 1. In the remaining 17 subjects desirable glycemic levels were attained and maintained. In group 2, desirable glycemia was reached in all 9 subjects. Symptomatic hypoglycemic events confirmed by blood sugar <70 mg/dl were reported by 4 subjects, none requiring secondary assistance. No severe hypoglycemia was reported. Mean daily dose of Soliqua was lower when compared to the pivotal trials. Conclusion: Soliqua is effective and safe in the long term in all subjects irrespective of BMI when administered in combination with Glimepiride and Metformin. Moreover, lesser daily dose required to attain desirable glycemia with this oral combination may render it to be effective without attaining maximum daily dose in subjects with higher BMIs documented in pivotal trials using Metformin alone.
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