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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

Treatment-induced neuropathy of diabetes related to abrupt glycemic control

Author/s: 
Stainforth-Dubois, M., Mcdonald, E. G.

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.

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

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.

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.).

Keywords 
blood-pressure trial cardiovascular hypotension stroke
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