The Endocrine Society:

ENDOCRINOLOGY & METABOLISM NEWS
J Clin Endocrinol Metab 2008 93: 17a-18a [Full Text] [PDF]  

Special Features:

Shlomo Melmed

UPDATE:Update in Pituitary Disease
J Clin Endocrinol Metab 2008 93: 331-338 [Abstract] [Full Text] [PDF]  
This review of pituitary medicine highlights papers published in 2006-2007 relating to key translational and clinical discoveries.

Andréa Trevas Maciel-Guerra, Maricilda Palandi de Mello, Fernanda Boechers Coeli, Marcelo Lima Ribeiro, Márcio Lopes Miranda, Antonia Paula Marques-de-Faria, Maria Tereza Matias Baptista, Suzana Guimarães Moraes, and Gil Guerra-Júnior

CLINICAL CASE SEMINAR:XX Maleness and XX True Hermaphroditism in SRY-Negative Monozygotic Twins: Additional Evidence for a Common Origin
J Clin Endocrinol Metab 2008 93: 339-343; first published December 4 2007 as doi:10.1210/jc.2007-1115 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
In a rare case of 46, XX monozygotic twins deficient in the sex-determining region on the Y chromosome gene (SRY), one is an XX male and the other has XX ovotesticular disorder of sex development, indicates that both phenotypes can reflect the same disorder of gonadal development.

Katrina Bolar, Andrew R. Hoffman, Thomas Maneatis, and Barbara Lippe

EXTENSIVE CLINICAL EXPERIENCE:Long-Term Safety of Recombinant Human Growth Hormone in Turner Syndrome
J Clin Endocrinol Metab 2008 93: 344-351; first published November 13 2007 as doi:10.1210/jc.2007-1723 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
In this study of recombinant human growth hormone (rhGH) efficacy and safety for treatment of with Turner syndrome in 5,220 children and adolescents, there were 117 serious adverse events, including certain adverse effects associated with rhGH therapy, including intracranial hypertension, slipped capital femoral epiphysis, scoliosis, and pancreatitis. There were ten new-onset malignancies, the significance of which is unclear in patients without risk factors.

Bert Bakker, James Frane, Henry Anhalt, Barbara Lippe, and Ron G. Rosenfeld

EXTENSIVE CLINICAL EXPERIENCE:Height Velocity Targets from the National Cooperative Growth Study for First-Year Growth Hormone Responses in Short Children
J Clin Endocrinol Metab 2008 93: 352-357; first published November 13 2007 as doi:10.1210/jc.2007-1581 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Novel height velocity targets are presented for the first-year growth response to GH. They serve as practical tool for clinicians who treat patients with short stature of different etiologies. A height velocity below the mean -- 1 SD on these plots should be considered a "poor response." The plots can help to identify patients who may benefit from GH dose adjustment, compliance assessment, or questioning the original diagnosis.

Chirag G. Patil, Daniel M. Prevedello, Shivanand P. Lad, Mary Lee Vance, Michael O. Thorner, Laurence Katznelson, and Edward R. Laws, Jr.

EXTENSIVE CLINICAL EXPERIENCE:Late Recurrences of Cushing’s Disease after Initial Successful Transsphenoidal Surgery
J Clin Endocrinol Metab 2008 93: 358-362; first published December 4 2007 as doi:10.1210/jc.2007-2013 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
After initial successful transsphenoidal surgery, one-quarter of patients with Cushing's disease recur during long-term follow-up, suggesting the need for continued clinical and biochemical follow-up.

Christophe E. M. De Block, Ivo H. De Leeuw, and Luc F. Van Gaal

CLINICAL REVIEW:Autoimmune Gastritis in Type 1 Diabetes: A Clinically Oriented Review
J Clin Endocrinol Metab 2008 93: 363-371; first published November 20 2007 as doi:10.1210/jc.2007-2134 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Patients with type 1 diabetes have a higher prevalence of autoimmune gastritis and pernicious anemia. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of these two diseases in type 1 diabetes patients.

Matthew C. Riddle

COMMENTARY:Starting and Advancing Insulin for Type 2 Diabetes: Algorithms and Individualized Methods Are Both Necessary
J Clin Endocrinol Metab 2008 93: 372-374; first published December 11 2007 as doi:10.1210/jc.2007-2576 [Full Text] [PDF] [FREE Author Manuscript (PDF)]  

Editorials:

Ole Schmitz

The GLP-1 Concept in the Treatment of Type 2 Diabetes—Still Standing at the Gate of Dawn?
J Clin Endocrinol Metab 2008 93: 375-377 [Full Text] [PDF]  

Sara A. DiVall and Fredric E. Wondisford

TRH Testing in Its Infancy
J Clin Endocrinol Metab 2008 93: 378-379 [Full Text] [PDF]  

Endocrine Care:

Agneta Nordenskjöld, Gundela Holmdahl, Louise Frisén, Henrik Falhammar, Helena Filipsson, Marja Thorén, Per Olof Janson, and Kerstin Hagenfeldt

Type of Mutation and Surgical Procedure Affect Long-Term Quality of Life for Women with Congenital Adrenal Hyperplasia
J Clin Endocrinol Metab 2008 93: 380-386; first published November 20 2007 as doi:10.1210/jc.2007-0556 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
This follow-up of 62 women with congenital adrenal hyperplasia reveals that their overall quality of life is affected by both the type of mutation and their childhood operative procedure. Overall, the women are less satisfied with their genitals, whether operated or not, with half experiencing vaginal stenosis. This report suggests that indications for clitoroplasty should be restrictive, and medical, surgical, and psychological treatment should be centralized.

Cathie J. Bloem and Annette M. Chang

Short-Term Exercise Improves β-Cell Function and Insulin Resistance in Older People with Impaired Glucose Tolerance
J Clin Endocrinol Metab 2008 93: 387-392; first published November 13 2007 as doi:10.1210/jc.2007-1734 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
In older people with impaired glucose tolerance, short-term exercise improved both insulin resistance and {beta}-cell function. These effects could not be explained by changes in body weight or fasting lipid, leptin, adiponectin or catecholamine levels.

Joshua H. Petit, Beverly M. K. Biller, Torunn I. Yock, Brooke Swearingen, John J. Coen, Paul Chapman, Marek Ancukiewicz, Marc Bussiere, Anne Klibanski, and Jay S. Loeffler

Proton Stereotactic Radiotherapy for Persistent Adrenocorticotropin-Producing Adenomas
J Clin Endocrinol Metab 2008 93: 393-399; first published November 20 2007 as doi:10.1210/jc.2007-1220 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Radiotherapy is often employed for patients with corticotroph adenomas persisting after transspenoidal surgery. A study of stereotactic single day proton radiotherapy for patients with postoperative recurrence of Cushing's disease or Nelson's syndrome shows that 58% of achieved a complete response after a median of 62 months. Follow-up is warranted to assess late radiation-related sequelae.

Eleanor M. Gurnell, Penelope J. Hunt, Suzanne E. Curran, Catherine L. Conway, Eleanor M. Pullenayegum, Felicia A. Huppert, Juliet E. Compston, Joseph Herbert, and V. Krishna K. Chatterjee

Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial
J Clin Endocrinol Metab 2008 93: 400-409; first published November 13 2007 as doi:10.1210/jc.2007-1134 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
A 12-month study of dehydroepiandrosterone replacement for primary adrenal insufficiency finds improved femoral neck bone mineral density and lean body mass but no significant benefit with fatigue and cognitive or sexual function.

David A. van Tijn, Jan J. M. de Vijlder, and Thomas Vulsma

Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants
J Clin Endocrinol Metab 2008 93: 410-419; first published November 13 2007 as doi:10.1210/jc.2006-2656 [Abstract] [Full Text] [PDF] [Supplemental Data] [FREE Author Manuscript (PDF)]  
TRH testing can play a pivotal role in evaluation of TSH deficiency in young infants with congenital hypothyroidism. Abnormal test results, especially a type 3 response (slightly delayed, but excessive increase and delayed decrease in TSH), indicate the need for prompt assessment of hypothalamic-pituitary function and morphology, as the majority of these patients have multiple pituitary hormone deficiencies.

Richard S. Legro, Jaimey G. Pauli, Allen R. Kunselman, Juliana W. Meadows, James S. Kesner, Richard J. Zaino, Laurence M. Demers, Carol L. Gnatuk, and William C. Dodson

Effects of Continuous Versus Cyclical Oral Contraception: A Randomized Controlled Trial
J Clin Endocrinol Metab 2008 93: 420-429; first published December 4 2007 as doi:10.1210/jc.2007-2287 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
A comparison of cyclic to continuous oral contraception over 24 weeks finds no reduction in bleeding days between the two treatments, but lesser patient symptoms and greater suppression of the ovary and the endometrium with continuous therapy.

Esther M. M. Ooi, Gerald F. Watts, Paul J. Nestel, Dmitri Sviridov, Anh Hoang, and P. Hugh R. Barrett

Dose-Dependent Regulation of High-Density Lipoprotein Metabolism with Rosuvastatin in the Metabolic Syndrome
J Clin Endocrinol Metab 2008 93: 430-437; first published November 20 2007 as doi:10.1210/jc.2007-0854 [Abstract] [Full Text] [PDF] [Supplemental Data] [FREE Author Manuscript (PDF)]  
A study of men with metabolic syndrome treated with rosuvastatin finds a dose-dependent increase in plasma high-density lipoprotein (HDL) cholesterol and apolipoprotein-I (LpA-I) concentrations, suggesting that a reduction in plasma triglycerides with remodeling of HDL particles and reduction in LpA-I catabolism may be the mechanisms of action involved for this drug.

Esben Thyssen Vestergaard, Christian Born Djurhuus, Jakob Gjedsted, Søren Nielsen, Niels Møller, Jens Juul Holst, Jens Otto Lunde Jørgensen, and Ole Schmitz

Acute Effects of Ghrelin Administration on Glucose and Lipid Metabolism
J Clin Endocrinol Metab 2008 93: 438-444; first published November 27 2007 as doi:10.1210/jc.2007-2018 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
In this small cross-over study, ghrelin increased plasma glucose and serum nonesterified fatty acids by inducing insulin resistance in skeletal muscle and lipolysis. These ghrelin effects appear to be direct ones, although small contributions by growth hormone and cortisol cannot be ruled out.

R. W. J. Leunissen, P. Oosterbeek, L. K. M. Hol, A. A. Hellingman, T. Stijnen, and A. C. S. Hokken-Koelega

Fat Mass Accumulation during Childhood Determines Insulin Sensitivity in Early Adulthood
J Clin Endocrinol Metab 2008 93: 445-451; first published November 27 2007 as doi:10.1210/jc.2007-1543 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Low birth weight and postnatal catch-up growth have been associated with increased risk of adult type 2 diabetes. In 136 young adults, adult fat mass is the only significant predictor of insulin sensitivity, not birth length and birth weight. After correction for age, gender, and adult body size, insulin sensitivity was significantly lower, but the glucose disposition index was no different.

Ruben H. Willemsen, Sandra W. K. de Kort, Danielle C. M. van der Kaay, and Anita C. S. Hokken-Koelega

Independent Effects of Prematurity on Metabolic and Cardiovascular Risk Factors in Short Small-for-Gestational-Age Children
J Clin Endocrinol Metab 2008 93: 452-458; first published November 20 2007 as doi:10.1210/jc.2007-1913 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
A comparison of preterm and term short small-for-gestational-age (SGA) children reveals divergent effects on cardiovascular risk factors between the two groups. Preterm SGA children had a higher systolic and diastolic blood pressures, but lower body fat percentage and higher insulin secretion and glucose disposition index than term SGA children.

Koichiro Azuma, Zofia Rádiková, Juliet Mancino, Frederico G. S. Toledo, Ernestine Thomas, Cyrous Kangani, Chiara Dalla Man, Claudio Cobelli, Jens J. Holst, Carolyn F. Deacon, YanLing He, Monica Ligueros-Saylan, Denise Serra, James E. Foley, and David E. Kelley

Measurements of Islet Function and Glucose Metabolism with the Dipeptidyl Peptidase 4 Inhibitor Vildagliptin in Patients with Type 2 Diabetes
J Clin Endocrinol Metab 2008 93: 459-464; first published November 27 2007 as doi:10.1210/jc.2007-1369 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
The mechanisms by which the DPP-4 inhibitor vildagliptin lowers fasting plasma glucose and postprandial plasma glucose in patients with type 2 diabetes are not clear. This study shows that vildagliptin improves islet function in these patients by enhancing glucose responsiveness of insulin secretion, increasing postprandial suppression of glucagon, augmenting peripheral glucose utilization, and increasing glucose clearance.

Serenella Checchi, Annalisa Montanaro, Letizia Pasqui, Cristina Ciuoli, Valentina De Palo, Maria Celeste Chiappetta, and Furio Pacini

L-Thyroxine Requirement in Patients with Autoimmune Hypothyroidism and Parietal Cell Antibodies
J Clin Endocrinol Metab 2008 93: 465-469; first published November 27 2007 as doi:10.1210/jc.2007-1544 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Presence of autoimmune gastritis can influence the daily L-thyroxine requirement for patients with hypothyroidism. This study's findings suggest that serum parietal cell antibodies should be performed in hypothyroid patients with unexplained high L-thyroxine replacement doses.

Olivier Valkenburg, Regine P. M. Steegers-Theunissen, Huberdina P. M. Smedts, Geesje M. Dallinga-Thie, Bart C. J. M. Fauser, Egbertine H. Westerveld, and Joop S. E. Laven

A More Atherogenic Serum Lipoprotein Profile Is Present in Women with Polycystic Ovary Syndrome: A Case-Control Study
J Clin Endocrinol Metab 2008 93: 470-476; first published December 4 2007 as doi:10.1210/jc.2007-1756 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Women with polycystic ovary syndrome (PCOS) have more pronounced atherogenic serum lipid profile, with higher levels of triglycerides, cholesterol, and low density lipoprotein cholesterol, and low levels of apolipoprotein A-I.

Maria A. J. de Ridder, Theo Stijnen, and Anita C. S. Hokken-Koelega

Prediction Model for Adult Height of Small for Gestational Age Children at the Start of Growth Hormone Treatment
J Clin Endocrinol Metab 2008 93: 477-483; first published November 13 2007 as doi:10.1210/jc.2007-1381 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Growth hormone treatment is recommended for short children born small for gestational age (SGA), but the optimal dose has not been established. A prediction model for expected height at onset of puberty and of adult height in short children born SGA provides useful information about the expected long-term growth and helps determine the effective GH dose required.

Rachael E. Van Pelt, Robert S. Schwartz, and Wendy M. Kohrt

Insulin Secretion and Clearance after Subacute Estradiol Administration in Postmenopausal Women
J Clin Endocrinol Metab 2008 93: 484-490; first published November 6 2007 as doi:10.1210/jc.2007-1657 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Large clinical trials of postmenopausal women show an association of estrogen therapy with lesser incidence of diabetes. In this study, 24-hour transdermal estradiol did not alter insulin secretion or clearance in postmenopausal women. However, subacute estradiol increased glucose disposal in women who were only a few years past menopause, but decreased glucose disposal in women who were more years past menopause.

Katica Bajuk Studen and Ariel Barkan

Assessment of the Magnitude of Growth Hormone Hypersecretion in Active Acromegaly: Reliability of Different Sampling Models
J Clin Endocrinol Metab 2008 93: 491-496; first published November 20 2007 as doi:10.1210/jc.2007-1451 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Methods to measure the degree of GH hypersecretion in acromegaly patients are controversial. This study discusses the limitations of abbreviated GH sampling for these patients.

Sebastiaan Hammer, Rutger W. van der Meer, Hildo J. Lamb, Michael Schär, Albert de Roos, Jan W. A. Smit, and Johannes A. Romijn

Progressive Caloric Restriction Induces Dose-Dependent Changes in Myocardial Triglyceride Content and Diastolic Function in Healthy Men
J Clin Endocrinol Metab 2008 93: 497-503; first published November 20 2007 as doi:10.1210/jc.2007-2015 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
The physiology of triglyceride storage in tissues other than fat remains largely uncharacterized. This study in ten lean healthy men demonstrates that progressive caloric restriction induces a dose-dependent increase in myocardial triglyceride content, a dose-dependent decrease in diastolic function, and a distinct dose-independent change in hepatic triglyceride stores.

Aaron. P. Brown, Jergin Chen, Ying J. Hitchcock, Aniko Szabo, Dennis C. Shrieve, and Jonathan. D. Tward

The Risk of Second Primary Malignancies up to Three Decades after the Treatment of Differentiated Thyroid Cancer
J Clin Endocrinol Metab 2008 93: 504-515; first published November 20 2007 as doi:10.1210/jc.2007-1154 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
The overall risk of secondary cancers is slightly increased for thyroid cancer survivors compared to that of the U.S. general population, with this risk modified by age at diagnosis, radioisotope use, and latency period.

Paula M. L. Skidmore, Aedin Cassidy, Ramasamyiyer Swaminathan, J. Brent Richards, Tim D. Spector, and Alex J. MacGregor

Relation of Birth Weight, Body Mass Index, and Change in Size from Birth to Adulthood to Insulin Resistance in a Female Twin Cohort
J Clin Endocrinol Metab 2008 93: 516-520; first published November 20 2007 as doi:10.1210/jc.2007-1424 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
This study in female twins investigating the relationship between birth weight, body mass index, and change in body size over life and insulin resistance suggests that postnatal growth is more important than fetal growth in the development of insulin resistance.

Sandi Powell, Deqiong Ma, and Graeme Jones

Determinants of Skeletal Age Deviation in a Cross-Sectional Study
J Clin Endocrinol Metab 2008 93: 521-526; first published December 4 2007 as doi:10.1210/jc.2007-1139 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Skeletal age deviation in children has been associated with fracture history, which is more prevalent in children with a delay in skeletal age versus chronological age. This cross-sectional study of 640 children aged 7-17 years indicates that predictors of lower skeletal age deviation include lower bone free lean and fat masses, weaker grip strength, and histories of smoking and inhaled corticosteroid use.

Héctor F. Escobar-Morreale, Raul Sanchón, and José L. San Millán

A Prospective Study of the Prevalence of Nonclassical Congenital Adrenal Hyperplasia among Women Presenting with Hyperandrogenic Symptoms and Signs
J Clin Endocrinol Metab 2008 93: 527-533; first published November 13 2007 as doi:10.1210/jc.2007-2053 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
This study finds a 2% prevalence of nonclassic congenital adrenal hyperplasia among Spanish women presenting with hyperandrogenic complaints and recommends lowering the cut-off value basal serum 17- hydroxyprogesterone level for diagnosis from 2.0 to 1.7 ng/mL.

Ada Igwebuike, Brian A. Irving, Maureen L. Bigelow, Kevin R. Short, Joseph P. McConnell, and K. Sreekumaran Nair

BRIEF REPORT:Lack of Dehydroepiandrosterone Effect on a Combined Endurance and Resistance Exercise Program in Postmenopausal Women
J Clin Endocrinol Metab 2008 93: 534-538; first published November 20 2007 as doi:10.1210/jc.2007-1027 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Combined endurance and resistance training in postmenopausal women for twelve weeks improves body composition, physical performance, and cardiometabolic risk, and addition of dehydroepiandrosterone does not potentiate these effects.

Stefan Fischli, Stefan Jenni, Sabin Allemann, Marcel Zwahlen, Peter Diem, Emanuel R. Christ, and Christoph Stettler

BRIEF REPORT:Dehydroepiandrosterone Sulfate in the Assessment of the Hypothalamic-Pituitary-Adrenal Axis
J Clin Endocrinol Metab 2008 93: 539-542; first published November 6 2007 as doi:10.1210/jc.2007-1780 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Individuals with hypothalamic-pituitary-adrenal (HPA) insufficiency have lower age- and gender-adjusted dehydroepiandrosterone sulfate (DHEA-S) levels than those with normal HPA function. DHEA-S measurement could be of diagnostic value in assessing HPA integrity especially in younger patients and in patients with pituitary macroadenoma.

Other Original Articles:

Peter Plomgaard, Christian P. Fischer, Tobias Ibfelt, Bente K. Pedersen, and Gerrit van Hall

Tumor Necrosis Factor- Modulates Human in Vivo Lipolysis
J Clin Endocrinol Metab 2008 93: 543-549; first published November 20 2007 as doi:10.1210/jc.2007-1761 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Many chronic diseases are characterized by systemic inflammation, insulin resistance, and dyslipidemia, all of which involve cytokines. In this study, administration of recombinant TNF-{alpha} to healthy young male volunteers increased whole body lipolysis by 40%, while having no effect on skeletal muscle fat metabolism.

Rachel Courtney, Paul M. Stewart, Melvin Toh, Marie-Noella Ndongo, Roberto A. Calle, and Boaz Hirshberg

Modulation of 11β-Hydroxysteroid Dehydrogenase (11βHSD) Activity Biomarkers and Pharmacokinetics of PF-00915275, a Selective 11βHSD1 Inhibitor
J Clin Endocrinol Metab 2008 93: 550-556; first published November 6 2007 as doi:10.1210/jc.2007-1912 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
11{beta} hydroxysteroid dehydrogenase type 1 (11{beta}HSD1) inhibition is a promising treatment target for type 2 diabetes. However, there is no direct assay to assess liver enzyme function. By assessing prednisolone generation and urinary corticosteroid metabolite levels, this study suggests that PF-00915275 is a selective 11{beta}HSD1 inhibitor.

Dick C. Chan, Minh N. Nguyen, Gerald F. Watts, and P. Hugh R. Barrett

Plasma Apolipoprotein C-III Transport in Centrally Obese Men: Associations with Very Low-Density Lipoprotein Apolipoprotein B and High-Density Lipoprotein Apolipoprotein A-I Metabolism
J Clin Endocrinol Metab 2008 93: 557-564; first published November 13 2007 as doi:10.1210/jc.2006-2676 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
A study of insulin-resistant and centrally obese men defines the disrupted kinetics of apolipoprotein (apo) C-III, a major risk factor for cardiovascular disease, including elevated plasma apoC-III, due to elevated VLDL-apoC-III production and reduced VLDL- and HDL-apoC-III catabolism, as well as disturbances in VLDL-apoB and HDL-apoA-I metabolism.

Maria Nesterova, Ioannis Bossis, Feng Wen, Anelia Horvath, Ludmila Matyakhina, and Constantine A. Stratakis

An Immortalized Human Cell Line Bearing a PRKAR1A-Inactivating Mutation: Effects of Overexpression of the Wild-Type Allele and Other Protein Kinase A Subunits
J Clin Endocrinol Metab 2008 93: 565-571; first published December 4 2007 as doi:10.1210/jc.2007-1902 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Aberrant cyclic AMP signaling has been linked to adrenocortical and other endocrine tumors. Using an immortalized cell line from a Carney complex patient bearing a PRKAR1A-inactivating mutation, this study demonstrates that a balance between protein kinase A (PKA)-I and -II is critical for induction and promotion of tumorigenesis in tissues bearing PRKAR1A mutations. Increased RI b expression led to inhibition of proliferation, whereas RII{beta} a introduction promoted increased proliferation, aneuploidy, and cell cycle changes.

Lonneke J. M. van Nimwegen, Jitschak G. Storosum, Regje M. E. Blumer, Gideon Allick, Henk W. Venema, Lieuwe de Haan, Hiske Becker, Therese van Amelsvoort, Mariette T. Ackermans, Eric Fliers, Mireille J. M. Serlie, and Hans P. Sauerwein

Hepatic Insulin Resistance in Antipsychotic Naive Schizophrenic Patients: Stable Isotope Studies of Glucose Metabolism
J Clin Endocrinol Metab 2008 93: 572-577; first published November 20 2007 as doi:10.1210/jc.2007-1167 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Patients with antipsychotic naive schizophrenia or schizoaffective disorder are more likely to have hepatic insulin resistance, which cannot be explained by an increase in visceral fat mass or differences in plasma free fatty acids, glucoregulatory hormones, plasma adiponectin or plasma retinol-binding protein 4 concentrations.

Sridevi Devaraj, Mohan R. Dasu, Jason Rockwood, William Winter, Steven C. Griffen, and Ishwarlal Jialal

Increased Toll-Like Receptor (TLR) 2 and TLR4 Expression in Monocytes from Patients with Type 1 Diabetes: Further Evidence of a Proinflammatory State
J Clin Endocrinol Metab 2008 93: 578-583; first published November 20 2007 as doi:10.1210/jc.2007-2185 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
This study further links atherosclerosis and type 1 diabetes (T1DM) with higher levels of inflammatory biomarkers and increased monocyte activity by identifying in T1DM patients increased monocytic expression of the toll-like receptors 2 and 4.

Anneke J. A. H. van Vught, Arie G. Nieuwenhuizen, Robert-Jan M. Brummer, and Margriet S. Westerterp-Plantenga

Effects of Oral Ingestion of Amino Acids and Proteins on the Somatotropic Axis
J Clin Endocrinol Metab 2008 93: 584-590; first published November 20 2007 as doi:10.1210/jc.2007-1784 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Growth hormone is released in response to ingestion of an amino acid mixture as well as to hydrolyzed and intact soy protein, with concentrations in both mixtures higher than those reached with arginine and lysine alone. This result suggests that the increased serum insulin level and peak amino acid concentration, not rate of amino acid absorption, may be responsible for somatotropic effects.

Francesco Latrofa, Debora Ricci, Lucia Grasso, Paolo Vitti, Lucio Masserini, Fulvio Basolo, Clara Ugolini, Giovanni Mascia, Antonio Lucacchini, and Aldo Pinchera

Characterization of Thyroglobulin Epitopes in Patients with Autoimmune and Non-Autoimmune Thyroid Diseases Using Recombinant Human Monoclonal Thyroglobulin Autoantibodies
J Clin Endocrinol Metab 2008 93: 591-596; first published November 20 2007 as doi:10.1210/jc.2007-1199 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
The production of autoantibodies to thyroglobulin (TgAb) in autoimmune thyroid diseases (AITD) and non-AITD have not been fully characterized. Recombinant antibodies to Tg epitopes in patients with either AITD or non-AITD finds that Tg recognition is similar among patients in the same disease group cluster compared to those in a different disease group cluster. Patients with papillary thyroid carcinoma and lymphocytic filtration of the thyroid had similar responses to those of AITD patients.

Kevin R. Short, Niels Moller, Maureen L. Bigelow, Jill Coenen-Schimke, and K. Sreekumaran Nair

Enhancement of Muscle Mitochondrial Function by Growth Hormone
J Clin Endocrinol Metab 2008 93: 597-604; first published November 13 2007 as doi:10.1210/jc.2007-1814 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
A 14-hour growth hormone infusion in normal subjects, inducing a four-fold increase plasma levels, increases mitochondrial oxidative capacity and abundance of several mitochondrial genes, but does not appear to alter the rate of mitochondrial protein synthesis.

Ilaria Zamproni, Helmut Grasberger, Francesca Cortinovis, Maria Cristina Vigone, Giuseppe Chiumello, Stefano Mora, Kazumichi Onigata, Laura Fugazzola, Samuel Refetoff, Luca Persani, and Giovanna Weber

Biallelic Inactivation of the Dual Oxidase Maturation Factor 2 (DUOXA2) Gene as a Novel Cause of Congenital Hypothyroidism
J Clin Endocrinol Metab 2008 93: 605-610; first published November 27 2007 as doi:10.1210/jc.2007-2020 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Biallelic inactivation of the dual oxidase maturation factor 2 gene DUOXA2A is a novel cause of congenital hypothyroidism.

Jehad Abubaker, Zeenath Jehan, Prashant Bavi, Mehar Sultana, Sayer Al-Harbi, Muna Ibrahim, Abdulrahman Al-Nuaim, Mohammed Ahmed, Tarek Amin, Maha Al-Fehaily, Osama Al-Sanea, Fouad Al-Dayel, Shahab Uddin, and Khawla S. Al-Kuraya

Clinicopathological Analysis of Papillary Thyroid Cancer with PIK3CA Alterations in a Middle Eastern Population
J Clin Endocrinol Metab 2008 93: 611-618; first published November 13 2007 as doi:10.1210/jc.2007-1717 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
In Middle Eastern patients with papillary thyroid cancer, there is a high incidence of PIK3CA alterations and BRAF mutations, suggesting the potential for therapeutic targeting of PI3K/AKT and MAP kinases for this patient group.

Paul A. Fowler, Sarah Cassie, Stewart M. Rhind, Mark J. Brewer, J. Martin Collinson, Richard G. Lea, Paul J. Baker, Siladitya Bhattacharya, and Peter J. O’Shaughnessy

Maternal Smoking during Pregnancy Specifically Reduces Human Fetal Desert Hedgehog Gene Expression during Testis Development
J Clin Endocrinol Metab 2008 93: 619-626; first published November 13 2007 as doi:10.1210/jc.2007-1860 [Abstract] [Full Text] [PDF] [Supplemental Data] [FREE Author Manuscript (PDF)]  
Maternal cigarette smoking during gestation increases cryptorchidism and hypospadias, and reduces testis size and fertility in the resulting sons. In this case-control study, the aborted male fetuses of smoking mothers had reduced expression of the Sertoli cell-specific Desert hedgehog gene; whereas the expression of 29 other reproductive and developmental genes; testosterone, hCG, LH, and cotinine levels; liver concentrations of 16 polycyclic aromatic hydrocarbons; and Leydig, Sertoli and germ cell numbers were all no different.

Johnny Deladoëy, Nicole Pfarr, Jean-Marc Vuissoz, Jasmine Parma, Gilbert Vassart, Stefan Biesterfeld, Joachim Pohlenz, and Guy Van Vliet

Pseudodominant Inheritance of Goitrous Congenital Hypothyroidism Caused by TPO Mutations: Molecular and in Silico Studies
J Clin Endocrinol Metab 2008 93: 627-633; first published November 20 2007 as doi:10.1210/jc.2007-2276 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Most cases of goitrous congenital hypothyroidism are recessively inherited and due to thyroid peroxidase gene mutations. This study reports a pedigree with pseudodominant goitrous congenital hypothyroidism due to segregation of three different mutations in the thyroid peroxidase gene, one of which, the Gln660Glu mutant, appears to be expressed, but lacks enzymatic activity.

Marco Fedi, Leon A. Bach, Samuel F. Berkovic, John O. Willoughby, Ingrid E. Scheffer, and David C. Reutens

BRIEF REPORT:Association of a Nicotinic Receptor Mutation with Reduced Height and Blunted Physostigmine-Stimulated Growth Hormone Release
J Clin Endocrinol Metab 2008 93: 634-637; first published November 27 2007 as doi:10.1210/jc.2007-1611 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
Alterations in stature and growth hormone secretion are linked with a bSer248Phe mutation on the neuronal nicotinic acetylcholine receptor. Subjects with this mutation were shorter and had a blunted response to physostigmine.

Saskia N. van der Crabben, Gideon Allick, Mariette T. Ackermans, Erik Endert, Johannes A. Romijn, and Hans P. Sauerwein

BRIEF REPORT:Prolonged Fasting Induces Peripheral Insulin Resistance, Which Is Not Ameliorated by High-Dose Salicylate
J Clin Endocrinol Metab 2008 93: 638-641; first published December 4 2007 as doi:10.1210/jc.2006-2491 [Abstract] [Full Text] [PDF] [FREE Author Manuscript (PDF)]  
In healthy fasting men, high dose of salicylate does not affect fasting-induced peripheral insulin resistance as seen in patients with type 2 diabetes, suggesting that fasting has a different mechanism of insulin resistance.

Announcements and Resources:

2nd Annual International Adrenal Cancer Symposium: Clinical and Basic Science, March 14-15, 2008, 18 AMA PRA Category I Credits
J Clin Endocrinol Metab 2008 93: 429 [Full Text] [PDF]  

International Symposium on Signal Transduction in Health and Disease on Neuroendocrinology: Basic and Clinical Aspects
J Clin Endocrinol Metab 2008 93: 526 [Full Text] [PDF]  

Endocrine-Related Resources from the National Institutes of Health
J Clin Endocrinol Metab 2008 93: 642-645 [Full Text] [PDF]  

National Hormone & Peptide Program (NHPP): New Recombinant Hormones, Hypothalamic Peptides, Natural Hormones, New Antisera, & Expanded Hormone Assay Services Available
J Clin Endocrinol Metab 2008 93: 646-648 [Full Text] [PDF]  

Patient Information Page from The Hormone Foundation:

Marcel Cedars, William Evans, and Nanette Santoro

Patient Information Page from The Hormone Foundation:Premature Ovarian Failure
J Clin Endocrinol Metab 2008 93 [Full Text] [PDF]  

Marcel Cedars, William Evans, and Nanette Santoro

Patient Information Page from The Hormone Foundation:El fallo ovárico prematuro
J Clin Endocrinol Metab 2008 93 [Full Text] [PDF]  

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