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⇱ JAMA

JAMA

Current Issue: May 22, 2026 - Volume 335 - Issue 23
ISSN: 0098-7484
Frequency: Undetermined

  • JAMA

    June 09, 2026: 335(22):1915-1916

  • Amyotrophic Lateral Sclerosis

    June 09, 2026: 335(22):1970-1982

    Importance

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness due to degeneration of upper motor neurons in the brain and lower motor neurons in the brainstem and spinal cord. It affects approximately 25 000 individuals in the United States.

    Observations

    Amyotrophic lateral sclerosis is characterized by progressive painless muscle weakness that typically begins in a focal region of the body, such as limb muscle weakness causing hand weakness or foot drop (65%), cranial muscle weakness causing speech or swallowing problems (20%-25%), or axial muscle weakness causing bent posture (5%-10%), and spreads to other body regions over time. The disease usually manifests with dysfunction indicative of both upper motor neurons (causing muscle stiffness and spasticity) and lower motor neurons (causing weakness, fasciculations, atrophy, and flaccidity). After onset, weakness spreads through the musculature and typically causes death due to respiratory muscle weakness. Among people with ALS, approximately 85% have sporadic ALS, which is not associated with known environmental or genetic factors, and 15% have familial ALS. Amyotrophic lateral sclerosis is diagnosed based on clinical features, which can be supported by results of electromyography. More than 60 genes have been associated with ALS, and most are autosomal dominant. Pathogenic variants in chromosome 9 open reading frame 72 (C9orf72) are found in 40% of all familial ALS cases, and pathogenic variants in superoxide dismutase 1 (SOD1) are found in 20% of patients with familial ALS. Patients with ALS survive a mean of 3 to 5 years after diagnosis, and there are currently no curative therapies. Clinical care primarily focuses on symptom management and quality of life. Three US Food and Drug Administration (FDA)–approved disease-modifying therapies are available in the United States. Riluzole and edaravone are oral medications that slow ALS progression by up to 2 to 4 months, and tofersen is an intrathecally administered gene therapy for patients with SOD1 gene variants. Specialized multidisciplinary teams, comprising neurologists, nurses, therapists, dietitians, and social workers, are associated with improved survival (4-7 months) and quality of life.

    Conclusions and Relevance

    Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disorder of upper and lower motor neurons. No curative therapies exist. Two oral medications, riluzole and edaravone, are approved by the FDA and modestly decrease disease progression in sporadic ALS. Tofersen, an intrathecally administered gene-based therapy, is also FDA approved and slows disease progression in patients with SOD1 pathogenic gene variants.

  • Hypothyroidism

    JAMA. November 18, 2025: 334(19):1750-1760

    Importance

    Hypothyroidism is a disease of thyroid hormone deficiency. The prevalence ranges from 0.3% to 12% worldwide, depending on iodine intake, and it is more common in women and older adults. Untreated hypothyroidism can cause serious health complications such as heart failure and myxedema coma.

    Observations

    Hashimoto thyroiditis (an autoimmune disease) is the cause of primary hypothyroidism in up to 85% of patients with hypothyroidism living in areas with adequate nutritional iodine levels. The risk of developing hypothyroidism is associated with genetic factors (having a first-degree relative with hypothyroidism), environmental factors (iodine deficiency), undergoing neck surgery or receiving radiation therapy, pregnancy in the setting of underlying autoimmune thyroid disease, and with the use of certain medications (eg, immune checkpoint inhibitors and amiodarone). Patients with hypothyroidism may have nonspecific symptoms due to metabolic slowing, including fatigue (68%-83%), weight gain (24%-59%), cognitive issues (45%-48%) such as memory loss and difficulty concentrating, and menstrual irregularities (approximately 23%) such as oligomenorrhea and menorrhagia. Hypothyroidism can cause insulin resistance and hyperglycemia in patients with diabetes, increase the risk for cardiovascular events, such as heart failure, and negatively affect female reproductive health, causing disrupted ovulation, infertility, and increased risk of miscarriage. Untreated hypothyroidism may progress to severe hypothyroidism with decompensation (myxedema coma), which is a condition associated with hypothermia, hypotension, and altered mental status that requires treatment in an intensive care unit and has a mortality rate of up to 30%. Hypothyroidism is diagnosed based on biochemical testing; a high thyrotropin (TSH) level and a low free thyroxine (T4) level indicate overt primary hypothyroidism. Screening for hypothyroidism is not recommended for asymptomatic individuals. Targeted testing is recommended for patients who are considered high risk (eg, patients with type 1 diabetes). First-line treatment for hypothyroidism is synthetic levothyroxine to normalize thyrotropin levels. Initial dosages should be tailored to patient-specific factors. Lower starting doses should be used for older patients or those with atrial fibrillation and coronary artery disease. Thyrotropin monitoring should be performed 6 to 8 weeks after initiating levothyroxine treatment, or when changing the dose, and then annually once the thyrotropin level is at goal to avoid overtreatment or undertreatment, both of which are associated with cardiovascular health risks.

    Conclusions and Relevance

    Hypothyroidism may be associated with fatigue, weight gain, memory loss, difficulty concentrating, cardiovascular disease such as heart failure, menstrual irregularities, infertility, and increased risk of miscarriage. Levothyroxine is the first-line treatment to normalize the thyrotropin level and improve clinical manifestations due to hypothyroidism.

  • Osteoporosis

    JAMA. September 9, 2025: 334(10):894-907

    Importance

    Osteoporosis is characterized by low bone mass, increased bone fragility, and increased susceptibility to fracture, which is associated with substantial morbidity, mortality, and economic costs. Worldwide, 1 in 3 women and 1 in 5 men older than 50 years of age experience osteoporotic fractures in their lifetime.

    Observations

    Risk factors for osteoporosis include older age, female sex, prior fractures, prior falls, low body weight, history of hip fracture in a parent, glucocorticoid use, cigarette smoking, excess alcohol consumption, certain comorbidities (eg, inflammatory bowel disease, rheumatoid arthritis, and chronic liver and kidney disease), and low level of bone mineral density (BMD; measured by dual-energy x-ray absorptiometry). The fracture risk assessment algorithm combines these clinical risk factors and BMD measurement to estimate the 10-year absolute fracture risk for hip, spine, shoulder, and forearm fractures. For patients at high risk of fracture, such as those with a T score of –2.5 or less (equivalent to a bone mass that is ≥2.5 SDs below that of young adults) for BMD, history of vertebral or hip fracture, multiple fractures, or high 10-year absolute fracture risk (eg, ≥20%), antiresorptive agents (bisphosphonates or, if contraindicated, denosumab) are recommended to reduce vertebral fractures (risk difference, −52 [95% CI, −95 to −18 per 1000 person-years]) and hip fractures (risk difference, −6 [95% CI, −11 to −1 per 1000 person-years]). Anabolic medications (teriparatide, abaloparatide, and romosozumab) should be considered in very high-risk individuals (eg, recent vertebral fractures, hip fracture with a T score of ≤−2.5 for BMD), followed by an antiresorptive agent. The use of fracture liaison services (comprehensive inpatient or outpatient management program for patients after a fracture) was shown to increase medication initiation and adherence by 38% compared with 17% for patients who did not receive fracture liaison services (risk difference, 20% [95% CI, 16% to 25%]) and these benefits may reduce the rates of subsequent fracture. Patients are recommended to follow appropriate intake of calcium (1000 to 1200 mg) and vitamin D (600 to 800 IU) guidelines and to pursue a regimen of muscle resistance exercises (eg, squats, push-ups) and balance exercises (eg, heel raises, standing on 1 foot).

    Conclusions and Relevance

    Osteoporosis is a common condition among older adults that leads to increased susceptibility to fracture, which is associated with substantial morbidity and mortality. Antiresorptive agents such as bisphosphonates or denosumab are recommended for patients at high fracture risk. Anabolic treatment with parathyroid hormone analogs (such as teriparatide and abaloparatide) and sclerostin inhibitors (such as romosozumab) can be considered for very high-risk individuals.