hypotension

Importance: Orthostatic hypotension is a common but underrecognized condition that increases with age and is associated with a lower quality of life, falls, and increased mortality. The frequent coexistence of supine hypertension and postprandial hypotension with orthostatic hypotension makes it a challenging condition to manage.

Observations: Testing for orthostatic hypotension should be done in patients with orthostatic symptoms (eg, vision changes and dizziness that occur only when upright and improve when seated or lying down), as well as asymptomatic patients in high-risk groups such as adults with frailty who are older than 70 years, individuals with neurodegenerative or autonomic disorders, and patients with unexplained falls. Patients with orthostatic hypotension should be screened for postprandial hypotension and supine hypertension to inform the treatment approach. Nonpharmacological strategies, such as medication review, increased salt and fluid intake, compression garments, and behavioral modifications, serve as fundamental approaches to treat orthostatic hypotension. Midodrine and droxidopa are the only US Food and Drug Administration-approved medications for orthostatic hypotension, but other medications (eg, fludrocortisone, atomoxetine, pyridostigmine) are used off label as part of an individualized treatment plan. Treatment targets in orthostatic hypotension are focused not on blood pressure measurements but on symptom relief and fall prevention.

Conclusions and relevance: All patients with orthostatic symptoms-along with other select patient groups-should be evaluated for orthostatic hypotension. Nonpharmacological treatments are first line, and medication decisions should be tailored based on clinical presentation and relevant comorbidities.

Author/s:

David Moloney, Ayman Youssef, Luis E. Okamoto

Peripheral Neuropathy: A Review

Megan George — Wed, 19 Nov 2025 22:20:00 +0000

Date Added:

November 19, 2025

Journal/Publication:

JAMA

Publication Date:

November 17, 2025

URL:

Peripheral Neuropathy: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi: 10.1001/jama.2025.19400

Keywords

neurology

neuralgia

Peripheral Nerves

MeSH

antidepressive agents

antidepressive agents, tricyclic

Charcot-Marie-Tooth Disease

blood glucose

Cisplatin

diabetic neuropathies

duloxetine hydrochloride

gabapentin

Hypesthesia

hypotension

Hypotension, Orthostatic

Reverse Transcriptase Inhibitors

Venlafaxine Hydrochloride

Peripheral Nerves

neuralgia

A review of the causes and treatment of the symptoms of peripheral neuropathy. Figure 2 and Table 1 may be particularly helpful. James W. Mold, MD, MPH

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Importance Peripheral neuropathy, defined as damage to peripheral nerves, affects approximately 1% of adults worldwide. More than 200 causes of peripheral neuropathy exist, with symptoms ranging in severity from mild toe numbness to debilitating symptoms that can require a wheelchair. Diabetes is the most common cause of neuropathy, affecting approximately 206 million people worldwide.

Observations Peripheral neuropathy is typically length-dependent, which means that symptoms appear in the longest nerve axons (toes) and progress proximally over time. Peripheral neuropathy is typically symmetric and affects sensory axons more than motor axons. Diabetic neuropathy, which is often associated with both sensory symptoms, such as pain, tingling, or numbness; mild weakness; and autonomic symptoms, such as orthostatic hypotension, accounts for more than 50% of peripheral neuropathy in Western populations. Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B12; and monoclonal gammopathies. Up to 27% of adults with neuropathy have no identifiable etiology for their neuropathy after diagnostic testing. Recommended initial testing includes blood glucose (for diabetes), serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation (for monoclonal gammopathies). First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline. Pain often persists despite medical management. At least a 50% reduction in pain was observed in 38% of those with painful diabetic peripheral neuropathy receiving 1200 mg of gabapentin daily. Combination drug therapies for neuropathic pain may provide added benefit. The prognosis of peripheral neuropathy depends on its underlying cause, but complete reversal of nerve damage is uncommon even in cases for which there are available treatments.

Conclusions and Relevance Peripheral neuropathy affects approximately 1% of adults worldwide and may cause sensory, motor, and autonomic symptoms. Diabetes is the most common cause of peripheral neuropathy in Western countries. First-line therapies for neuropathic pain include gabapentin, pregabalin, duloxetine, and amitriptyline.

Author/s:

Michelle L. Mauermann, Nathan P. Staff

Hypothyroidism: A Review

Megan George — Thu, 04 Sep 2025 20:17:56 +0000

Date Added:

September 4, 2025

Journal/Publication:

JAMA

Publication Date:

September 3, 2025

URL:

Hypothyroidism: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.13559

Keywords

PMID (1):

40900603

MeSH

A review of what we currently understand about hypothyroidism. James W. Mold, MD, MPH

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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.

Author/s:

Layal Chaker, Maria Papaleontiou

Treatment-induced neuropathy of diabetes related to abrupt glycemic control

Bethie Seay — Tue, 20 Jul 2021 05:00:00 +0000

Date Added:

July 20, 2021

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1503/cmaj.202091

MeSH

female

glycated hemoglobin a

diabetes mellitus, type 1

Autonomic nervous system diseases

blood glucose

neuropathy, painful

Peripheral nervous system diseases

pain

Retinal diseases

Humans

Aggressive management of blood glucose levels can sometimes precipitate painful peripheral neuropathy, which is usually temporary but may require treatment.

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KEY POINTS
Rapid correction of glycemic control (i.e., > 2 percentage points of hemoglobin A1c) over 3 months may lead to treatment-induced neuropathy of diabetes.

Symptoms include painful neuropathy, autonomic dysfunction, gastroparesis, early worsening of retinopathy and microalbuminuria.

Women and people with type 1 diabetes are at elevated risk of treatment-induced neuropathy of diabetes.

Management of the condition may include involvement of a dietitian, adjustment of insulin dose and use of medications to improve symptoms such as painful neuropathy, postural hypotension and gastroparesis.

Author/s:

Stainforth-Dubois, M., Mcdonald, E. G.

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control

Saige Blanchard — Fri, 21 May 2021 05:00:00 +0000

Date Added:

May 21, 2021

Journal/Publication:

New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

May 20, 2021

Issue:

Volume:

384

Pages:

1921-1930

URL:

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1901281

Keywords

PMID (1):

34010531

MeSH

blood-pressure

cardiovascular diseases

acute coronary syndrome

myocardial infarction

heart failure

hypotension

stroke

In patients at high risk for cardiovascular events, intensive BP control (target <120 systolic) reduced the rate of adverse CV events (CAD events, CVA, CHF, or death) by 0.63% per year. Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. James W. Mold, MD, MPH

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Background: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.

Methods: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.

Results: At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.

Conclusions: Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).

Author/s:

Lewis, C. E., Fine, L. J., Beddhu, S., Cheung, A. K., Cushman, W. C., Cutler, J. A., Evans, G. W., Johnson, K. C., Kitzman, D. W., Oparil, S., Rahman, M., Reboussin, D. M., Rocco, M. V., Sink, K, M., Snyder, J. K., Whelton, P. K., Williamson, J. D., Wright Jr., J. T., Ambrosius, W. T.