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Therapeutic Use of Cannabis and Cannabinoids: A Review

Author/s: 
Michael Hsu, Arya Shah, Ayana Jordan, Mark S Gold, Kevin P Hill

Importance: Approximately 27% of adults in the US and Canada report having ever used cannabis for medical purposes. An estimated 10.5% of the US population reports using cannabidiol (CBD), a chemical compound extracted from cannabis that does not have psychoactive effects, for therapeutic purposes.

Observations: Conditions for which cannabinoids have approval from the US Food and Drug Administration include HIV/AIDS-related anorexia, chemotherapy-induced nausea and vomiting, and certain pediatric seizure disorders. A meta-analysis of randomized clinical trials reported a small but significant reduction in nausea and vomiting from various causes (eg, chemotherapy, cancer) when comparing prescribed cannabinoids (eg, dronabinol, nabilone) with placebo or active comparators (eg, alizapride, chlorpromazine; standardized mean difference [SMD], -0.29 [95% CI, -0.39 to -0.18]). A meta-analysis of randomized clinical trials among patients with HIV/AIDS reported that cannabinoids had a moderate effect on increasing body weight compared with placebo (SMD, 0.57 [95% CI, 0.22 to 0.92]). Evidence-based guidelines do not recommend the use of inhaled or high-potency cannabis (≥10% or 10 mg Δ9-tetrahydrocannabinol [Δ9-THC]) for medical purposes. High-potency cannabis compared with low-potency cannabis use is associated with increased risk of psychotic symptoms (12.4% vs 7.1%) and generalized anxiety disorder (19.1% vs 11.6%). A meta-analysis of observational studies reported that 29% of individuals who used cannabis for medical purposes met criteria for cannabis use disorder. Daily inhaled cannabis use compared with nondaily use was associated with an increased risk of coronary heart disease (2.0% vs 0.9%), myocardial infarction (1.7% vs 1.3%), and stroke (2.6% vs 1.0%). Evidence from randomized clinical trials does not support the use of cannabis or cannabinoids for most conditions for which it is promoted, such as acute pain and insomnia. Before considering cannabis or cannabinoids for medical use, clinicians should consult applicable institutional, state, and national regulations; evaluate for drug-drug interactions; and assess for contraindications (eg, pregnancy) or conditions in which risks likely outweigh benefits (eg, schizophrenia or ischemic heart disease). For patients using cannabis or cannabinoids for treatment of medical conditions, clinicians should discuss harm reduction strategies, including avoiding concurrent use with alcohol or other central nervous system depressants such as benzodiazepines, using the lowest effective dose, and avoiding use when driving or operating machinery.

Conclusions and relevance: Evidence is insufficient for the use of cannabis or cannabinoids for most medical indications. Clear guidance from clinicians is essential to support safe, evidence-based decision-making. Clinicians should weigh benefits against risks when engaging patients in informed discussions about cannabis or cannabinoid use.

Keywords 
medical marijuana cannabis

Lung Cancer in Nonsmoking Individuals: A Review

Author/s: 
Cian Murphy, Tej Pandya, Charles Swanton

Importance: Lung cancer in nonsmoking individuals (defined as people who have smoked fewer than 100 cigarettes in their lifetime) accounts for 15% to 20% of all lung cancer cases worldwide. In the US, the annual incidence of lung cancer in nonsmoking individuals is 14.4 to 20.8 per 100 000 person-years in females and 4.8 to 12.7 per 100 000 person-years in males.

Observations: Most lung cancers in nonsmoking individuals are histologically adenocarcinomas (60%-80%) with the remainder being squamous or adenosquamous (10%-20%) and rarely small cell lung cancer (<10%). Risk factors include exposure to passive smoking, radon exposure, air pollution, asbestos, and history of lung cancer in a first-degree family member. Therapeutically targetable genomic variants, such as EGFR mutations or ALK gene rearrangements, are more common in tumors from nonsmoking individuals compared with those with a smoking history (defined as people who currently or formerly smoked) (43% vs 11% for EGFR and 12% vs 2% for ALK). In contrast, tumor mutation burden, the number of somatic mutations in a tumor cell, is lower in lung cancer among nonsmoking individuals (0-3 mutations/megabase [Mb] vs 0-30 mutations/Mb). Similar to individuals with a history of smoking, nonsmoking individuals with lung cancer may present with wheeze, chest pain, dyspnea, hemoptysis, or symptoms attributable to metastatic disease (eg, bone pain and headache) or be diagnosed with incidentally detected disease. The US Preventive Services Task Force does not currently recommend lung cancer screening with low-dose computed tomographic scans for nonsmoking individuals, although screening guidelines vary globally. Treatment typically involves a combination of surgery, radiotherapy, and systemic therapies depending on stage, performance status, and molecular features of the tumor. Comprehensive next-generation sequencing should be performed on stage Ib to IIIa lung cancer tumor tissue from nonsmoking individuals because actionable genomic alterations, such as EGFR mutations or ALK gene rearrangements, are treated with targeted therapy such as the tyrosine kinase inhibitors osimertinib or lorlatinib, respectively. Median survival among nonsmoking individuals with advanced non-small cell lung cancer (stage IIIb or higher) and actionable genomic alterations can exceed 3 to 5 years, while survival without these genomic alterations is similar to lung cancer in people with a history of smoking (1-2 years).

Conclusions: Lung cancer in nonsmoking individuals accounts for 15% to 20% of lung cancer cases worldwide. Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with tyrosine kinase inhibitors compared with chemotherapy.

Keywords 
adenocarcinoma Carcinoma Squamous Cell tobacco Smokers smoking Early Detection of Cancer

Approach to pelvic venous disorders

Author/s: 
Andrew D Brown

Objective: To provide a practical guide to help family physicians recognize, diagnose, and manage patients with pelvic venous disorders (PeVDs), often overlooked as causes of chronic pelvic pain and varicose veins.

Sources of information: This review is based on guidelines from the American Venous Forum, the Society for Vascular Surgery, the American Vein and Lymphatic Society, the Society of Interventional Radiology, and the European Society for Vascular Surgery.

Main message: PeVDs are common, though frequently misdiagnosed, causes of chronic pelvic pain and varicose veins predominantly in female patients. These conditions arise from venous reflux or obstruction, which can cause varicose veins and venous hypertension in the renal hilum, pelvis, perineum, and lower extremities. Family physicians should recognize the clinical signs of PeVDs and use appropriate imaging to confirm diagnoses. Interventional treatments, including embolization and stenting, are effective for symptom management and improving patient outcomes.

Conclusion: Early recognition of patients with PeVDs by family physicians is crucial for timely and effective treatment. By using appropriate diagnostic tools and making timely referrals, physicians can substantially improve patients' quality of life.

Keywords 
Perineum female quality of life physicians family Radiology Interventional Varicose Veins Vascular Surgical Procedures hypertension

Pharmacologic Treatment of Perinatal Depression

Author/s: 
Emily S. Miller, S. Karlene Cunningham, Lauren M. Osborne

Approximately 1 in 7 individuals are affected by perinatal depression, defined as a depressive episode occurring during pregnancy or within 12 months after delivery. Although the diagnostic criteria are similar to those of major depressive disorder, perinatal depression may also include symptoms such as difficulty forming an emotional attachment with the fetus or infant, persistent doubts about parenting abilities, and intrusive thoughts of harm to self or infant.1 Mental health conditions are leading contributors to maternal mortality in the US; among reporting states, the rate of death from perinatal suicide ranges from 4.2 to 21.4 per 100 000 pregnancies.2 Untreated or undertreated perinatal depression increases other maternal risks, including limited engagement in care, impaired relationships, substance use, preeclampsia, and suicide, as well as fetal or neonatal risks, including preterm birth, low birth weight, and disrupted attachment with long-term developmental consequences.3 Individuals from marginalized communities, such as those who are non–English speaking, uninsured, or geographically isolated, experience a higher prevalence of perinatal depression and are at increased risk of underdiagnosis and undertreatment.3

Risk factors for perinatal depression include a personal or family history of depression, abuse, stressful life events, low socioeconomic status, adolescent or single parenthood, and pregnancy complications, such as preterm birth or pregnancy loss. Each factor individually confers only a small increase in risk, making accurate prediction based on clinical factors challenging.4 Therefore, to facilitate early identification and treatment, universal screening during and after pregnancy is recommended. The American College of Obstetricians and Gynecologists (ACOG) recently issued 2 Clinical Practice Guidelines on perinatal mental health, 1 on screening and diagnosis5 and 1 on treatment and management,3 highlighting opportunities for obstetricians to address existing health gaps.

Keywords 
Pharmacology Perinatal Depression Major Depressive Disorder abuse depression

Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults: A Review

Author/s: 
Herbert Tilg, Salvatore Petta, Norbert Stefan, Giovanni Targher

Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction–associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers.

Observations The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (≥50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor β-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis.

Conclusions A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis.

Keywords 
liver disease steatotic liver disease MASLD Steatohepatitis

Online Unsupervised Tai Chi Intervention for Knee Pain and Function in People With Knee Osteoarthritis: The RETREAT Randomized Clinical Trial

Author/s: 
Shiyi Julia Zhu, Rana S. Hinman, Rachel K. Nelligan

Importance: Tai chi is a type of exercise recommended for knee osteoarthritis, but access to in-person tai chi can be limited.

Objective: To evaluate the effects of an unsupervised multimodal online tai chi intervention on knee pain and function for people with knee osteoarthritis.

Design, setting, and participants: The RETREAT study was a 2-group superiority randomized clinical trial enrolling participants who met clinical criteria for knee osteoarthritis in Australian communities from August 2023 and November 2024.

Interventions: Participants in the control group received access to a purpose-built website containing information about osteoarthritis and exercise benefits. Participants in the intervention group received the My Joint Tai Chi intervention comprising access to the same website plus tai chi information, a 12-week unsupervised video-based Yang-style tai chi program, and encouragement to use an app to facilitate program adherence.

Main outcomes and measures: Changes in knee pain during walking (Numeric Rating Scale; range 0-10 with higher scores indicating greater pain) and difficulty with physical function (Western Ontario and McMaster Universities Osteoarthritis Index; range 0-68 with higher scores indicating greater dysfunction) during 12 weeks. Secondary outcomes included another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, fear of movement, self-efficacy, balance confidence, positive activated affect, sleep quality, global improvement, and oral medication use.

Results: Of 2106 patients screened, 178 met inclusion criteria and were randomized, 89 (mean [SD] age, 61.0 [8.7] years; 66 female [74%] and 23 [26%] male participants) to the control group and 89 (mean [SD] age, 62.1 [7.3] years; 59 [66%] female and 30 male [34%] participants) to the tai chi intervention. Of the total, 170 (96%) completed both of the primary outcomes at 12 weeks. The tai chi group reported greater improvements in knee pain (control, -1.3; tai chi, -2.7; mean difference, -1.4 [95% CI, -2.1 to -0.7] units; P < .001) and function (control, -6.9; tai chi, -12.0; mean difference, -5.6 [95% CI, -9.0 to -2.3] units; P < .001) compared to the control group. More participants in the tai chi than in the control group achieved a minimal clinically important difference in pain (73% vs 47%; risk difference, 0.3; 95% CI, 0.1 to 0.4; P < .001) and function (72% vs 52%; risk difference, 0.2; 95% CI, 0.1 to 0.3; P = .007). Between-group differences for most secondary outcomes favored tai chi, including another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, global improvement, pain self-efficacy, and balance confidence. No associated serious adverse events were reported.

Conclusions and relevance: This randomized clinical trial found that this unsupervised multimodal online tai chi intervention improved knee pain and function compared with the control at 12 weeks. This free-to-access web-based intervention offers an effective, safe, accessible, and scalable option for guideline-recommended osteoarthritis exercise.

Keywords 
Pain Medicine Tai Chi Knee osteoarthritis

Use of Ambient AI Scribes to Reduce Administrative Burden and Professional Burnout

Author/s: 
Kristine D. Olson, Daniella Meeker, Matt Troup

Importance: While in short supply and high demand, ambulatory care clinicians spend more time on administrative tasks and documentation in the electronic health record than on direct patient care, which has been associated with burnout, intention to leave, and reduced quality of care.

Objective: To examine whether ambient AI scribes are associated with reducing clinician administrative burden and burnout.

Design, setting, and participants: This quality improvement study used preintervention and 30-day postintervention surveys to evaluate the use of the same ambient AI platform for clinical note documentation among ambulatory care physicians and advanced practice practitioners of 6 academic and community-based health care systems across the US. Clinicians were recruited by the health systems' digital health leaders; participation was voluntary. The study was conducted between February 1 and October 31, 2024.

Exposure: Use of an ambient AI scribe for 30 days.

Main outcomes and measures: The primary outcome was change in self-reported burnout, estimated using hierarchical logistic regression. Secondary outcomes of burnout evaluated were changes in note-related cognitive task load, focused attention on patients, patient understandability of notes, ability to add patients to the clinic schedule if urgently needed, and time spent documenting after hours. Outcome measures were linearly transformed to 10-point scales to ease interpretation and comparison. Differences between preintervention and postintervention scores were determined using paired t tests.

Results: Of the 451 clinicians enrolled, 272 completed the preintervention and postintervention surveys (60.3% completion rate), and 263 with direct patient care in ambulatory clinics (mean [SD] years in practice, 15.1 [9.3]; 141 female [53.6%]) were included in the analysis. The sample included 131 primary care practitioners (49.7%), 232 attending physicians (88.2%), and 168 academic faculty (63.9%). After 30 days with the ambient AI scribe, the proportion of participants experiencing burnout decreased significantly from 51.9% to 38.8% (odds ratio, 0.26; 95% CI, 0.13-0.54). On 10-point scales, the ambient AI scribe was associated with significant improvements in secondary outcomes of burnout (mean [SE] difference, 0.47 [0.12] points), note-related cognitive task load (mean [SE] difference, 2.64 [0.13] points), ability to provide undivided attention (mean [SE] difference, 2.05 [0.18] points), patient understandability of their care plans from reading the notes (mean [SE] difference, -0.44 [0.17] points), ability to add patients to the clinic schedule if urgently needed (mean [SE] difference, 0.51 [0.24] points), and time spent documenting after hours (mean [SE] difference, 0.90 [0.19] hours).

Conclusions and relevance: This multicenter quality improvement study found that use of an ambient AI scribe platform was associated with a significant reduction in burnout, cognitive task load, and time spent documenting, as well as the perception that it could improve patient access to care and increase attention on patient concerns in an ambulatory environment. These findings suggest that AI may help reduce administrative burdens for clinicians and allow more time for meaningful work and professional well-being.

Keywords 
burnout burnout, professional ambulatory care ambient AI

Online Unsupervised Tai Chi Intervention for Knee Pain and Function in People With Knee Osteoarthritis: The RETREAT Randomized Clinical Trial

Author/s: 
Shiyi Julia Zhu, Rana S Hinman, Rachel K Nelligan, Peixuan Li, Anurika P De Silva, Jenny Harrison, Alexander J Kimp, Kim L Bennell

Importance: Tai chi is a type of exercise recommended for knee osteoarthritis, but access to in-person tai chi can be limited.

Objective: To evaluate the effects of an unsupervised multimodal online tai chi intervention on knee pain and function for people with knee osteoarthritis.

Design, setting, and participants: The RETREAT study was a 2-group superiority randomized clinical trial enrolling participants who met clinical criteria for knee osteoarthritis in Australian communities from August 2023 and November 2024.

Interventions: Participants in the control group received access to a purpose-built website containing information about osteoarthritis and exercise benefits. Participants in the intervention group received the My Joint Tai Chi intervention comprising access to the same website plus tai chi information, a 12-week unsupervised video-based Yang-style tai chi program, and encouragement to use an app to facilitate program adherence.

Main outcomes and measures: Changes in knee pain during walking (Numeric Rating Scale; range 0-10 with higher scores indicating greater pain) and difficulty with physical function (Western Ontario and McMaster Universities Osteoarthritis Index; range 0-68 with higher scores indicating greater dysfunction) during 12 weeks. Secondary outcomes included another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, fear of movement, self-efficacy, balance confidence, positive activated affect, sleep quality, global improvement, and oral medication use.

Results: Of 2106 patients screened, 178 met inclusion criteria and were randomized, 89 (mean [SD] age, 61.0 [8.7] years; 66 female [74%] and 23 [26%] male participants) to the control group and 89 (mean [SD] age, 62.1 [7.3] years; 59 [66%] female and 30 male [34%] participants) to the tai chi intervention. Of the total, 170 (96%) completed both of the primary outcomes at 12 weeks. The tai chi group reported greater improvements in knee pain (control, -1.3; tai chi, -2.7; mean difference, -1.4 [95% CI, -2.1 to -0.7] units; P < .001) and function (control, -6.9; tai chi, -12.0; mean difference, -5.6 [95% CI, -9.0 to -2.3] units; P < .001) compared to the control group. More participants in the tai chi than in the control group achieved a minimal clinically important difference in pain (73% vs 47%; risk difference, 0.3; 95% CI, 0.1 to 0.4; P < .001) and function (72% vs 52%; risk difference, 0.2; 95% CI, 0.1 to 0.3; P = .007). Between-group differences for most secondary outcomes favored tai chi, including another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, global improvement, pain self-efficacy, and balance confidence. No associated serious adverse events were reported.

Conclusions and relevance: This randomized clinical trial found that this unsupervised multimodal online tai chi intervention improved knee pain and function compared with the control at 12 weeks. This free-to-access web-based intervention offers an effective, safe, accessible, and scalable option for guideline-recommended osteoarthritis exercise.

Keywords 
Knee osteoarthritis kinesiophobia Tai Chi

Superficial Vein Thrombosis: A Review

Author/s: 
Gregory Piazza, Darsiya Krishnathasan, Nada Hamade

Importance: Superficial vein thrombosis (SuVT) is characterized by thrombus in the superficial veins, typically in the lower or upper extremities, and has an estimated annual incidence of 64 to 131 per 100 000 person-years. Approximately 10% of patients with SuVT progress to deep vein thrombosis (DVT) or pulmonary embolism (PE).

Observations: Endothelial injury (caused by infection or intravenous devices), venous stasis (such as from chronic venous insufficiency or prolonged immobility), and hypercoagulability (due to cancer or pregnancy) are pathophysiologic factors associated with SuVT. Clinical risk factors for lower extremity SuVT are similar to those of DVT and PE and include pregnancy, varicose veins, and active cancer. The incidence of SuVT is greater in females than males (78-167 compared with 49-116 per 100 000 person-years). In contrast with lower extremity SuVT, upper extremity SuVT is primarily caused by indwelling intravenous catheters. Patients typically present with a tender, red, palpable cord under the skin in the upper or lower extremity. D-dimer testing has a sensitivity of approximately 48% to 74.3% and, therefore, is not reliable for excluding SuVT. Approximately 25% of patients with lower extremity SuVT present with concomitant DVT, likely because risk factors for SuVT and DVT are similar and because SuVT can extend into deep veins. In people without classic symptoms and signs of SuVT, ultrasonography can establish the presence and extent of the thrombus. Management may include elastic compression stockings and nonsteroidal anti-inflammatory drugs. For patients with SuVTs that are at least 5 cm long or those with persistent or worsening symptoms despite several days of conservative therapy, treatment includes anticoagulation with fondaparinux 2.5 mg. Alternative anticoagulation treatment includes rivaroxaban 10 mg once daily and low-molecular-weight heparins (eg, enoxaparin 40 mg once daily), which may reduce subsequent venous thromboembolic events. SuVT located within 3 cm of a deep vein should be treated with therapeutic doses of anticoagulation such as direct oral anticoagulants.

Conclusions and relevance: SuVT typically presents as a tender, painful, palpable cord under the skin. Management may include elastic compression stockings, nonsteroidal anti-inflammatory drugs, and systemic anticoagulation with fondaparinux 2.5 mg or rivaroxaban 10 mg. SuVTs within 3 cm of a deep vein should be treated with therapeutic dose anticoagulation.

Keywords 
surgery vascular surgery Venous Thromboembolism Cardiology anticoagulants

Hypothyroidism: A Review

Author/s: 
Layal Chaker, Maria Papaleontiou

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.

Keywords 
Endocrinology Thyroid Disorders hypothyroidism Reproductive Health
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