What are the complications of hypothyroidism and the recommended treatment and monitoring plan for adults?

Complications of Hypothyroidism and Management

Cardiovascular Complications

Untreated hypothyroidism causes significant cardiac dysfunction including delayed myocardial relaxation, reduced cardiac output, increased systemic vascular resistance, and diastolic heart failure, which can progress to life-threatening heart failure if left untreated. 1, 2

• Hypothyroidism increases cardiovascular event risk and can worsen pre-existing heart disease 2
• Hypertension develops due to increased systemic vascular resistance, with characteristic delayed ankle reflexes 1
• Patients may develop pericardial effusion and bradycardia 3
• The cardiac dysfunction is reversible with adequate levothyroxine treatment 1

Metabolic and Lipid Abnormalities

TSH levels >10 mIU/L are directly linked to hypertriglyceridemia and elevated LDL cholesterol, increasing atherosclerotic cardiovascular disease risk. 1

• Hypothyroidism causes insulin resistance and hyperglycemia, particularly problematic in patients with diabetes 2
• Weight gain occurs in 24-59% of patients due to metabolic slowing 2
• Treatment with levothyroxine significantly reduces total cholesterol, triglycerides, and LDL cholesterol 1

Reproductive and Pregnancy Complications

Untreated maternal hypothyroidism increases risk of preeclampsia, low birth weight, stillbirth, premature delivery, miscarriage, and permanent neurodevelopmental deficits in offspring. 1, 4, 2

• Menstrual irregularities occur in approximately 23% of patients, including oligomenorrhea and menorrhagia 2
• Disrupted ovulation and infertility are common complications 2
• Pregnant women with pre-existing hypothyroidism require 25-50% dose increases immediately upon pregnancy confirmation 1
• Target TSH <2.5 mIU/L in the first trimester to prevent fetal harm 1

Neuropsychiatric Complications

Cognitive impairment affects 45-48% of patients with hypothyroidism, manifesting as memory loss, difficulty concentrating, and "brain fog." 2, 5

• Fatigue is the most common symptom, affecting 68-83% of patients 2
• Depression and mood changes are frequent 5
• TSH suppression (<0.1 mIU/L) from overtreatment is associated with increased dementia risk 1
• Cognitive symptoms typically improve within 6-8 weeks of adequate levothyroxine replacement 1

Myxedema Coma

Myxedema coma represents severe decompensated hypothyroidism with hypothermia, hypotension, altered mental status, and carries a mortality rate up to 30% despite intensive care treatment. 2

• This is a medical emergency requiring immediate ICU admission 2
• Early recognition and aggressive treatment are essential for survival 4
• Precipitating factors include infection, cold exposure, medications, and acute illness 3

Bone and Musculoskeletal Complications

Overtreatment with levothyroxine causing TSH suppression (<0.1 mIU/L) significantly increases osteoporosis risk and fracture rates, particularly in postmenopausal women and elderly patients. 1, 6

• Women over 65 with TSH ≤0.1 mIU/L have markedly increased hip and spine fracture risk 1
• Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH 1, 6
• Patients with chronic TSH suppression should ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) intake 1

Recommended Treatment Protocol

Initial Treatment Selection

Levothyroxine monotherapy at 1.6 mcg/kg/day is the first-line treatment for overt hypothyroidism in young, healthy patients without cardiac disease. 6, 4, 5

• For patients >70 years or with cardiac disease, start at 25-50 mcg daily and titrate gradually by 12.5-25 mcg every 6-8 weeks 1, 6, 4
• Patients with long-standing severe hypothyroidism require conservative dose initiation to avoid cardiac decompensation 3
• Take levothyroxine on an empty stomach, 30-60 minutes before breakfast, at least 4 hours apart from iron, calcium, or antacids 1

Critical Safety Precaution

Before initiating levothyroxine in suspected central hypothyroidism or hypophysitis, always start physiologic dose corticosteroids at least one week prior, as thyroid hormone can precipitate life-threatening adrenal crisis. 1, 6

• Measure morning cortisol and ACTH before starting levothyroxine 1
• If cortisol is low, initiate hydrocortisone 20 mg morning and 10 mg afternoon for one week before levothyroxine 1

Monitoring Protocol

Monitor TSH and free T4 every 6-8 weeks after initiating treatment or changing dose until TSH stabilizes within the reference range of 0.5-4.5 mIU/L. 1, 6, 4, 2

• Once stable, check TSH annually or sooner if symptoms change 1, 6
• Target TSH 0.5-2.0 mIU/L for most patients with primary hypothyroidism 3
• Free T4 helps interpret ongoing abnormal TSH during therapy, as TSH may take longer to normalize 1

Dose Adjustment Strategy

Adjust levothyroxine by 12.5-25 mcg increments based on TSH results, using smaller increments (12.5 mcg) for elderly patients or those with cardiac disease. 1

• For TSH >10 mIU/L despite treatment, increase dose by 25 mcg 1
• For TSH 4.5-10 mIU/L on treatment, increase by 12.5-25 mcg 1
• Wait full 6-8 weeks between adjustments to reach steady state 1

Managing Overtreatment

If TSH <0.1 mIU/L, immediately reduce levothyroxine by 25-50 mcg to prevent atrial fibrillation, osteoporosis, and cardiovascular mortality. 1, 6

• For TSH 0.1-0.45 mIU/L, reduce by 12.5-25 mcg, particularly in elderly or cardiac patients 1
• Prolonged TSH suppression increases atrial fibrillation risk 3-5 fold, especially in patients >60 years 1
• Recheck TSH and free T4 in 6-8 weeks after dose reduction 1

Special Population Considerations

Pregnant women require immediate 25-50% levothyroxine dose increase upon pregnancy confirmation, with TSH monitoring every 4 weeks until stable, then each trimester. 1, 6

• Target TSH <2.5 mIU/L in first trimester 1
• Levothyroxine requirements typically increase 25-50% during pregnancy 1
• Never use T3-containing preparations during pregnancy, as T3 does not adequately cross the placenta 1

Patients on immune checkpoint inhibitors developing hypothyroidism should continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption. 1

• Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 monotherapy and 16-20% with combination immunotherapy 1
• Monitor TSH every 4-6 weeks for first 3 months, then every second cycle 1
• Consider treatment even for subclinical hypothyroidism if fatigue or symptoms present 1

Common Pitfalls to Avoid

• Never treat based on single elevated TSH value—30-60% normalize spontaneously on repeat testing 1, 6
• Never start levothyroxine at full replacement dose in elderly or cardiac patients—risk of myocardial infarction, heart failure, or fatal arrhythmias 1
• Never adjust doses more frequently than every 6-8 weeks before steady state is reached 1
• Never ignore suppressed TSH in patients on levothyroxine—14-21% of treated patients are unintentionally overtreated 6
• Never assume hypothyroidism is permanent without reassessment—consider transient thyroiditis, especially in recovery phase 1