Are There Variances Of Calculated Free Testosterone Attributed To Variations In Albumin And Sex Hormone-Binding Globulin Concentrations In Men?

ObjectiveCalculated free testosterone (cFT) is determined from total testosterone (TT), sex hormone binding globulin (SHBG), and albumin (Alb) levels using mathematical formulae. Variations in cFT due to changes in SHBG or Alb have not been investigated. We evaluated potential cFT variances determined with fixed Alb (4.3 g/dL) and measured Alb, and the point at which low SHBG and Alb combinations produced significant cFT variance.MethodWe analyzed 11,176 data points from 5,797 men. cFT values with fixed versus actual Alb values were evaluated and compared. cFT levels were theoretically determined for all possible combinations of TT, SHBG, and Alb (8,343,552 combinations). Agreement between the 2 measures was assessed with Lin’s concordance coefficient.ResultsMean Alb was 4.06 ± 0.32 g/dL. Mean SHBG was 39.0 ± 23.6 nmol/L. A fixed Alb of 4.3 g/dL did not produce significant variance for most cFT evaluations. Accuracy decreased when Alb was ≤3.5 g/dL in combination with SHBG ≤30 nmol/L, and this occurred in 1.2% of all data points.ConclusionA fixed Alb of 4.3 g/dL is acceptable for most clinical evaluations. If Alb is <3.5 g/dL and SHBG is <30 nmol/L, the variance increases, and a free testosterone (FT) measurement by equilibrium dialysis is warranted for better accuracy. (Endocr Pract. 2013;19:236-242)     

A Single-Center Open-Label Study To Investigate The Efficacy And Safety Of Repeated Subcutaneous Injections Of Lanreotide Autogel In Patients With Acromegaly Previously Treated With Octreotide

ObjectiveTo evaluate the efficacy of lanreotide Autogel, a depot preparation of a long-acting somatostatin analogue, in patients with acromegaly who were previously treated with octreotide.MethodsIn a prospective single-center, open-label, comparative study, 13 patients were switched from octreotide treatment (baseline) to lanreotide Autogel therapy at a fixed dosage of 90 mg/4 wk. After 6 injections, the dosage was titrated to 60, 90, or 120 mg/4 wk, on the basis of growth hormone (GH) levels, for a further 6 injections. Mean GH and insulinlike growth factor-I (IGF-I) levels were determined at baseline, during treatment (to 48 weeks), and up to 8 weeks after the last injection.ResultsThere was no significant change in the proportion of patients with GH and IGF-I control from baseline to week 48 (GH, 85% to 89%; IGF-I, 46% to 62%). Mean GH levels changed little from baseline, but mean IGF-I levels were significantly lower after 32 weeks (P < .05) and 48 weeks (P < .02). Data collected at 6 and 8 weeks after the last injection suggested that the efficacy of lanreotide Autogel can persist for longer than 4 weeks.ConclusionThis small study suggests that lanreotide Autogel is at least as effective as octreotide in the control of acromegaly and may last for longer than the recommended 4 weeks. It appears to be a useful alternative to long-acting octreotide in the treatment of acromegaly. (Endocr Pract. 2010;16:191-197)     

Cell Cycle And The Concept Of Physiological Age With Special Reference To Pyruvate Kinase Activity In Wi-38 Cells

Wi-38 Cells Were Synchronized By Mitotic Collection And Periodically Assayed For Pyruvate Kinase Activity. The Kinetics Of The Synchronous Cohort Were Determined By Continuous Labelling Index And By Mitotic Index. The Experimental Data Were Analysed By Computer Using A State Vector Model To Yield The Probability Density Functions For Phase Transit Times And For Cell Physiological Ages. Pyruvate Kinase Activity For These Cells As A Function Of Physiological Age Was Then Examined Using The Computer Model. Considering Dna Synthesis, Pyruvate Kinase Activity And Mitosis To Be Markers Of Physiological Age, It Was Found That A Model Which Assumes That A Cohort Of Synchronized Cells Desynchronizes Irreversibly And Uniformly From One Age Marker To The Next Is Incompatible With The Experimental Data. For Example, The Times Over Which Cells Entered The S Phase Were Too Widely Distributed To Be Consistent With The Mitotic Index Data. Also, For Pyruvate Kinase Activity To Be A Function Of Physiological Age Alone, The Cell Ages Were Probably Too Dispersed To Be Compatible With The Experimental Enzyme Data. Alternative Models For Cell Physiological Ageing Are Presented, Which Are Compatible With The Experimental Data.     

Pharmacokinetics And Relative Bioavailability Of Absorbed Testosterone After Administration Of A 1.62% Testosterone Gel To Different Application Sites In Men With Hypogonadism

ObjectiveTo determine the pharmacokinetics, bioavailability, and safety of a new formulation (1.62%) of testosterone gel that produces eugonadal serum testosterone levels with use of a lower amount of gel than the currently available 1% gels.MethodsIn an open-label, randomized, 3-way crossover study, 36 male patients with hypogonadism applied 5 g of 1.62% testosterone gel (81 mg of testosterone) once daily to the abdomen, to the upper arms/shoulders, or alternating between both sites per an established schedule for7 days. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured and used to compare the pharmacokinetics and bioavailability of the 3 treatments.ResultsEach application method produced average serum testosterone concentrations within the eugonadal range (300 to 1,000 ng/dL), and steady-state testosterone concentrations were achieved after 2 days of gel application to either the abdomen or the upper arms/shoulders. When testosterone gel was applied to the abdomen, approximately 30% to 40% lower bioavailability (based on area under the serum concentration-time curve from 0 to 24 hours) was observed in comparison with application to the upper arms/shoulders. The 1.62% testosterone gel was found to be safe and well tolerated in men with hypogonadism.ConclusionAlthough lower testosterone bioavailability was observed after abdominal application of 1.62% testosterone gel in comparison with application to the upper arms/shoulders, application to either site yielded eugonadal levels of serum testosterone. (Endocr Pract. 2011;17:574-583)     

Transculturalization Recommendations For Developing Latin American Clinical Practice Algorithms In Endocrinology Proceedings Of The 2015 Pan-American Workshop By The American Association Of Clinical Endocrinologists And American College Of Endocrinology

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.Abbreviations:A1C = glycated hemoglobinAACE = American Association of Clinical EndocrinologistsACE = American College of EndocrinologyBG = blood glucoseBMI = body mass indexCPA = Clinical Practice AlgorithmCPG = Clinical Practice GuidelineCVD = cardiovascular diseaseDXA = dual-energy X-ray absorptiometryEDC = endocrine-disrupting compoundFBG = fasting blood glucoseFNA = fine-needle aspirationHCP = health care professionalLA = Latin AmericaPAACE = Pan-American AACESU = sulfonylureaT2D = type 2 diabetestDNA = transcultural Diabetes Nutrition AlgorithmTSH = thyroid-stimulating hormoneWC = waist circumferenceWHO = World Health Organization