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Thyroid Screening and Childhood Cognitive Function
original article
Thyroid Screening and Childhood Cognitive Function
February 9, 2012 | J.H. Lazarus
and Others

In this randomized trial, antenatal screening (at a median gestational age of 12 weeks 3 days) and treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age.

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A Man with Muscle Pain, Weakness, and Weight Loss
case records of the massachusetts
general hospital
A Man with Muscle Pain, Weakness, and Weight Loss
February 9, 2012 | E.P. Rhee,
J.A. Scott, and A.S. Dighe

A 37-year-old man was admitted to this hospital because of 12 hours of muscle pain and weakness, resulting in the inability to rise from bed. Brief episodes of similar symptoms had occurred during the past month. He reported blurred vision, gynecomastia, and weight loss.

  • CME

Interactive Feature

Bird's-Eye View of Fever
Interactive Medical Case
Bird’s-Eye View of Fever
October 13, 2011 | J.J. Ross and Others

This interactive Journal feature presents the case of a 78-year-old man with a 4-month history of worsening fatigue, generalized weakness, and anorexia, with an unintentional weight loss of 11.4 kg.

Direct the investigation of the case, test your diagnostic and therapeutic skills, and compare your performance with that of others.

GAD65 and Beta-Cell Function in Type 1 Diabetes
original article
GAD65 and Beta-Cell Function in Type 1 Diabetes
February 2, 2012 | J. Ludvigsson
and Others

This trial assessed alum-formulated glutamic acid decarboxylase, the 65-kD isoform (GAD65), a major autoantigen in type 1 diabetes. In patients with recent-onset disease, the compound did not significantly alter the loss of C peptide or improve clinical outcomes.

Worth a Second Look
clinical problem-solving
Worth a Second Look
February 2, 2012 | T.M. Berzin
and Others

A 72-year-old man presented to his physician for evaluation of fatigue and weight loss. Over the previous 8 months, the patient had lost 16 kg (35 lb) and had begun having up to 10 loose stools per day. There was no history of blood in the stool, fever, chills, or rash.

  • Comments
original article
Osteitis Fibrosa Disseminata, Areas of Pigmentation and Precocious Puberty in Females
April 29, 1937 | F. Albright and Others

In this report, the authors call attention to a syndrome characterized by multiple bone cysts, areas of pigmentation, and precocious puberty in females. The suggestion is made that the endocrine disturbance as well as the bone lesions and pigment spots may be manifestations of an underlying neurologic disturbance or of an embryologic defect.

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  • Editorial

    The Debate over Thyroid-Function Screening in Pregnancy

    Maternal hypothyroidism in pregnancy has been associated with a range of adverse outcomes, most importantly miscarriage, preterm delivery, and reduced cognitive function in offspring. In surveys, almost half the obstetricians in private practices in Maine and the majority of obstetricians in a…

    • February 9, 2012
    • Brent G.A.
    • N Engl J Med 2012; 366:562 - 563

      Maternal hypothyroidism in pregnancy has been associated with a range of adverse outcomes, most importantly miscarriage, preterm delivery, and reduced cognitive function in offspring.1 In surveys, almost half the obstetricians in private practices in ...

    • Case Records of the Massachusetts General Hospital

      Case 4-2012 — A 37-Year-Old Man with Muscle Pain, Weakness, and Weight Loss

      Presentation of Case. Dr. Ian J. Barbash (Medicine): A 37-year-old man was admitted to this hospital because of muscle pain and weakness. The patient had been well until the evening before admission, when mild diffuse myalgias developed. He awoke in the morning with diffuse muscle cramps and…

      • February 9, 2012
      • Rhee E.P., Scott J.A., Dighe A.S.
      • N Engl J Med 2012; 366:553 - 560
      • CME

      A 37-year-old man was admitted to this hospital because of 12 hours of muscle pain and weakness, resulting in the inability to rise from bed. Brief episodes of similar symptoms had occurred during the past month. He reported blurred vision, gynecomastia, and weight loss.

    • Original Article

      Antenatal Thyroid Screening and Childhood Cognitive Function

      Active secretion of thyroid hormone in the fetus does not start until about 18 to 20 weeks' gestation. Studies in animals suggest that until fetal hormone secretion begins, the fetus is dependent on circulating free thyroxine (T4) in the mother for growth and development, including central nervous…

      • February 9, 2012
      • Lazarus J.H., Bestwick J.P., Channon S., et al.
      • N Engl J Med 2012; 366:493 - 501
      • CME

      In this randomized trial, antenatal screening (at a median gestational age of 12 weeks 3 days) and treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age.

    • Clinical Practice

      Delayed Puberty

      Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage. A 14-year-old…

      • February 2, 2012
      • Palmert M.R. and Dunkel L.
      • N Engl J Med 2012; 366:443 - 453
      • CME
      • Full Text Audio

      Puberty is considered delayed when it has not yet occurred at an age that is 2 to 2.5 SD later than average (traditionally, 14 years in boys and 13 years in girls). Constitutional delay of growth and puberty (CDGP) is the most common cause. Management of CDGP is discussed.

    • Images in Clinical Medicine

      Insulin-Induced Lipohypertrophy

      Figure 1.

      • February 2, 2012
      • Landau S.
      • N Engl J Med 2012; 366:e9
      • Free Full Text

      A 55-year-old man with a 31-year history of type 1 diabetes mellitus presented for a routine clinical evaluation, his first in two decades. His insulin regimen consisted of a combination of neutral protamine Hagedorn (NPH) and rapid-acting insulin. In the ...

    • Clinical Problem-Solving

      Worth a Second Look

      Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 72-year-old man presented to his…

      • February 2, 2012
      • Berzin T.M., Greenberger N.J., Levy B.D., Loscalzo J.
      • N Engl J Med 2012; 366:463 - 468

        A 72-year-old man presented to his physician for evaluation of fatigue and weight loss. Over the previous 8 months, the patient had lost 16 kg (35 lb) and had begun having up to 10 loose stools per day. There was no history of blood in the stool, fever, chills, or rash.

      • Original Article

        GAD65 Antigen Therapy in Recently Diagnosed Type 1 Diabetes Mellitus

        The clinical onset of type 1 diabetes is manifested by the effects of inadequate insulin secretion due to the immunologic destruction of pancreatic-islet beta cells. Despite replacement therapy with exogenous insulin, type 1 diabetes is associated with substantial morbidity and mortality. Even…

        • February 2, 2012
        • Ludvigsson J., Krisky D., Casas R., et al.
        • N Engl J Med 2012; 366:433 - 442

          This trial assessed alum-formulated glutamic acid decarboxylase, the 65-kD isoform (GAD65), a major autoantigen in type 1 diabetes. In patients with recent-onset disease; the compound did not significantly alter the loss of C peptide or improve clinical outcomes.

        • Perspective

          Assessing Supplement Safety — The FDA's Controversial Proposal

          Recently, a well-respected dietary-supplement company in Utah announced the recall of Zotrex, a sexual enhancement supplement labeled as containing "Ophioglossum polyphyllous." The problem with Zotrex was twofold: not only is no species of ophioglossum (adder's tongue) an established dietary…

          • February 2, 2012
          • Cohen P.A.
          • N Engl J Med 2012; 366:389 - 391
          • Audio

          By law, dietary supplements whose ingredients were not sold in the United States before 1994 require demonstration of a “reasonable expectation of safety” — a currently unenforced requirement. Will the FDA's proposed new guidance in this area be adequate?

        • Correspondence

          Staphylococcus aureus Reactivation Osteomyelitis after 75 Years

          To the Editor: In 1934, a 10-year-old girl was hospitalized at the Children's Hospital of Boston for 1 1/2 years for Staphylococcus aureus osteomyelitis of the left femur. This was the preantibiotic era, so she did not receive any antibiotic therapy at that time but, instead, underwent multiple…

          • February 2, 2012
          • N Engl J Med 2012; 366:481 - 482
          • Free Full Text

          In this case report, Staphylococcus aureus was found to persist in an 85-year-old woman 75 years after the successful treatment of osteomyelitis during her childhood.

        • Review Article

          Mechanisms of Disease: Iron Overload in Human Disease

          Iron-overload disorders are typically insidious, causing progressive and sometimes irreversible end-organ injury before clinical symptoms develop. With a high index of suspicion, however, the consequences of iron toxicity can be attenuated or prevented. Some iron-overload disorders are quite common…

          • January 26, 2012
          • Fleming R.E. and Ponka P.
          • N Engl J Med 2012; 366:348 - 359
          • CME

          Iron is both essential and toxic. The authors review how the body absorbs, uses, and loses iron and explore both common and unusual causes of iron overload and treatment of the resulting disorders.

        • Clinical Implications of Basic Research

          Closing the Iron Gate

          Genetic hemochromatosis is a prevalent iron-overload disease resulting from inadequate production of the iron-regulatory hormone hepcidin. Recently, Preza and colleagues developed an oral, biologically active hepcidin mimic that offers a new experimental approach to treating hemochromatosis and…

          • January 26, 2012
          • Andrews N.C.
          • N Engl J Med 2012; 366:376 - 377

            Ferroportin permits the uptake of dietary iron by cells of the intestinal epithelium into the circulation. Hepcidin targets ferroportin for lysosomal destruction. A recent study shows that an engineered minihepcidin reduces levels of iron in the serum and liver.

          • Original Article

            Brief Report: A Mutation in the Thyroid Hormone Receptor Alpha Gene

            Thyroid hormones have diverse actions, which include regulation of skeletal growth, maturation of the central nervous system, cardiac and gastrointestinal function, and energy homeostasis. In addition, thyroid hormones control their own production by feedback inhibition of hypothalamic thyrotropin…

            • January 19, 2012
            • Bochukova E., Schoenmakers N., Agostini M., et al.
            • N Engl J Med 2012; 366:243 - 249

              On whole-exome sequencing, a child with clinical hypothyroidism but borderline-abnormal thyroid hormone levels was found to have a heterozygous nonsense mutation in THRα, encoding a mutant protein inhibiting wild-type receptor action in a dominant negative manner.

            • Original Article

              Bone-Density Testing Interval and Transition to Osteoporosis in Older Women

              Current osteoporosis management guidelines– recommend routine bone mineral density (BMD) screening with the use of dual-energy x-ray absorptiometry (DXA) scans for women 65 years of age or older, but no guidelines specify an osteoporosis screening interval that is based on data from longitudinal…

              • January 19, 2012
              • Gourlay M.L., Fine J.P., Preisser J.S., et al.
              • N Engl J Med 2012; 366:225 - 233
              • CME

              This study analyzed the transition from normal BMD or osteopenia to osteoporosis; in women 67 years of age or older, the time for 10% to develop osteoporosis was approximately 15 years for normal BMD or mild osteopenia at baseline, 5 years for moderate osteopenia, and 1 year for advanced osteopenia.

            • Clinical Implications of Basic Research

              Diabetic Stem-Cell “Mobilopathy”

              Hematopoietic stem-cell (HSC) transplantation remains the primary curative treatment for patients with a variety of hematologic cancers. Transplantation of either autologous or allogeneic stem cells requires the acquisition of sufficient numbers of HSCs to ensure rapid and consistent trilineage…

              • December 29, 2011
              • DiPersio J.F.
              • N Engl J Med 2011; 365:2536 - 2538

                Obtaining hematopoietic stem cells (HSCs) for transplantation depends on effective egress of HSCs from bone marrow into the peripheral circulation on induction. This process is impaired in a mouse model of diabetes and in patients undergoing autologous transplantation.

              • Case Records of the Massachusetts General Hospital

                Case 40-2011 — A 52-Year-Old Man with Weakness, Infections, and Enlarged Adrenal Glands

                Presentation of Case. Dr. Liana K. Billings (Medicine): A 52-year-old man was admitted to this hospital because of weakness and swelling in his legs. The patient had been in his usual health until 9 months earlier, when leg edema and weakness developed, associated with weight gain. His physician…

                • December 29, 2011
                • Tritos N.A., Schaefer P.W., Stein T.D.
                • N Engl J Med 2011; 365:2520 - 2530
                • CME

                A 52-year-old man was admitted to this hospital because of weakness, leg swelling, and hypokalemia. During the hospital course, multiple infections were diagnosed and imaging studies revealed enlarged adrenal glands. A diagnostic procedure was performed.

              • Review Article

                Mechanisms of Disease: Proprotein Convertases in Health and Disease

                Secretory proteins, such as hormones, enzymes, and receptors, constitute a broad group of biochemically active molecules that are essential for cellular function. Post-translational processing of their precursor molecules, which occurs through endoproteolytic cleavage, results in the formation of…

                • December 29, 2011
                • Artenstein A.W. and Opal S.M.
                • N Engl J Med 2011; 365:2507 - 2518

                  Proteases that process larger precursor proteins into smaller functional proteins are involved in a wide range of physiologic processes. Derangements in the function of these enzymes play a role in many diseases.

                • Original Article

                  Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1 Diabetes

                  An impaired glomerular filtration rate (GFR) is the final common pathway of diabetic kidney disease. Once the GFR is impaired, cardiovascular disease events and progression to end-stage renal disease occur at unacceptably high rates, even with proven medical management.– This underscores the need…

                  • December 22, 2011
                  • The DCCT/EDIC Research Group
                  • N Engl J Med 2011; 365:2366 - 2376
                  • CME

                  Persons with type 1 diabetes are at high risk for kidney disease. In this study, intensive diabetes therapy administered early in the course of type 1 diabetes reduced the long-term risk of an impaired glomerular filtration rate.

                • Clinical Practice

                  Primary Hyperparathyroidism

                  Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage. A 62-year-old…

                  • December 22, 2011
                  • Marcocci C. and Cetani F.
                  • N Engl J Med 2011; 365:2389 - 2397
                  • CME
                  • Full Text Audio

                  This article reviews the differential diagnosis and management of primary hyperparathyroidism. For most patients, parathyroidectomy (usually by a minimally invasive approach) is recommended, but surveillance is an option for asymptomatic patients who meet certain criteria.

                • Images in Clinical Medicine

                  Ectopic Cushing's Syndrome

                  Figure 1.

                  • December 22, 2011
                  • Flohr F. and Geddert H.
                  • N Engl J Med 2011; 365:e46
                  • Free Full Text

                  A 23-year-old man presented with a 1-year history of diabetes mellitus, hypertension, and hypogonadism and a weight gain of 22 kg. Abdominal striae were present on physical examination (Panel A). An endocrine evaluation showed a corticotropin-dependent ...

                • Original Article

                  CPAP for the Metabolic Syndrome in Patients with Obstructive Sleep Apnea

                  Obstructive sleep apnea is a highly prevalent but underrecognized clinical problem. The Wisconsin Sleep Cohort Study estimated a prevalence of 24% among men and 9% among women in that state. In an urban setting in northern India, the prevalence of obstructive sleep apnea and the obstructive sleep…

                  • December 15, 2011
                  • Sharma S.K., Agrawal S., Damodaran D., et al.
                  • N Engl J Med 2011; 365:2277 - 2286

                    Patients in this randomized, double-blind trial in India were treated for the obstructive sleep apnea syndrome with 3 months of continuous positive airway pressure (CPAP) or sham CPAP. CPAP therapy lowered blood pressure and ameliorated metabolic abnormalities.

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