What is hypothyroidism, particularly in women over 50 years old?

Hypothyroidism Definition

Hypothyroidism is a clinical condition characterized by deficient production of thyroid hormones (thyroxine/T4 and triiodothyronine/T3) by the thyroid gland, resulting in a slowed metabolic state that affects multiple organ systems. 1, 2

Biochemical Classification

Hypothyroidism is diagnosed based on laboratory parameters rather than symptoms alone:

• Overt (clinical) hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) with low free T4 levels 3, 2
• Subclinical hypothyroidism is defined as elevated TSH (typically >4.5 mIU/L) with normal free T4 and T3 concentrations 3, 4
• The normal TSH reference range is 0.45-4.5 mIU/L, though this shifts upward with advancing age 4, 5

Etiology and Pathophysiology

Hypothyroidism can be classified by anatomic origin:

• Primary hypothyroidism results from abnormality in the thyroid gland itself, accounting for the vast majority of cases 3
• Hashimoto thyroiditis (autoimmune thyroiditis) causes up to 85% of primary hypothyroidism in iodine-sufficient areas 2, 5
• Secondary (pituitary) or tertiary (hypothalamic) hypothyroidism results from hypothalamic or pituitary disease, also called central hypothyroidism 3, 6

Clinical Manifestations in Women Over 50

The presentation varies significantly with age and sex:

• Most common symptoms include fatigue (68-83%), cold intolerance, weight gain (24-59%), constipation, dry skin, voice changes, and cognitive issues (45-48%) such as memory loss and difficulty concentrating 1, 7, 2
• Menstrual irregularities occur in approximately 23% of affected women, including oligomenorrhea and menorrhagia 2
• Symptoms result from decreased metabolic rate—weight gain occurs due to decreased fat-burning, cold intolerance from decreased heat production 8
• In women over 50, the prevalence is substantially higher, affecting up to 20% of women over 60 years 5

Epidemiology

• The prevalence ranges from 0.3% to 12% worldwide depending on iodine intake 2
• Clinical hypothyroidism affects approximately 1 in 300 people in the United States 7
• Women are disproportionately affected compared to men 5, 7
• The prevalence increases substantially with age, particularly in postmenopausal women 5, 7

Risk Factors Specific to This Population

Women over 50 face elevated risk due to:

• Advanced age substantially increases hypothyroidism risk 5
• Postmenopausal status represents a higher-risk period for thyroid dysfunction 5
• Family history of thyroid disease increases risk due to genetic predisposition 5
• Previous hyperthyroidism treatment may result in hypothyroidism 5
• History of head and neck radiation can damage thyroid tissue 5

Consequences of Untreated Disease

Untreated hypothyroidism carries serious morbidity and mortality risks:

• Cardiovascular complications include cardiac dysfunction, heart failure, and increased risk of cardiovascular events 2, 5
• Elevation in total and LDL cholesterol increases cardiovascular disease risk 5
• Myxedema coma represents severe decompensation with hypothermia, hypotension, altered mental status, requiring ICU treatment with mortality up to 30% 2, 1
• Insulin resistance and hyperglycemia can develop in patients with diabetes 2
• Infertility, disrupted ovulation, and increased miscarriage risk affect reproductive health 2

Diagnostic Approach

• Diagnosis is based on biochemical testing, not symptoms alone, as symptoms are nonspecific and overlap with other conditions 1, 7, 8
• High TSH with low free T4 indicates overt primary hypothyroidism 2
• Population screening is not recommended for asymptomatic individuals, but targeted testing is appropriate for high-risk patients 2, 7

Treatment Principles

• Levothyroxine monotherapy is the standard first-line treatment to normalize TSH levels 7, 2, 3
• Treatment typically requires lifelong hormone replacement therapy 8
• Initial dosing should be tailored to patient-specific factors—lower starting doses (12.5-50 mcg daily) for patients over 60 years or with cardiac disease 7, 4
• TSH monitoring should occur 6-8 weeks after initiating or changing levothyroxine dose, then annually once at goal 2, 4
• With appropriate treatment, symptoms can be effectively managed and most patients lead normal, healthy lives 8