What are the signs, symptoms, and treatment options for hypothyroidism, especially in women over 50 with a family history of thyroid disorders?

Hypothyroidism: Signs and Symptoms

Classic Clinical Presentation

Hypothyroidism presents with nonspecific symptoms that reflect the body's decreased metabolic rate, making diagnosis challenging but critical, especially in women over 50 who face the highest risk. 1, 2

Cardinal Symptoms

• Fatigue and lethargy are the most common presenting complaints, resulting from decreased cellular metabolism 1, 3
• Weight gain occurs despite normal or decreased appetite, caused by reduced fat-burning rate 1
• Cold intolerance develops from decreased heat production by the body 1, 3
• Constipation results from slowed gastrointestinal motility 1, 3
• Dry skin (xeroderma) is a frequent dermatologic manifestation 1, 3

Additional Common Manifestations

• Mental impairment and cognitive dysfunction, including difficulty concentrating and memory problems 3, 4
• Depression is frequently present and may be the primary complaint 3
• Irregular menses in premenopausal women 3
• Hoarseness from vocal cord edema 3
• Myalgias (muscle aches) and generalized weakness 3
• Edema, particularly periorbital and peripheral 3
• Bradycardia (slow heart rate) 3

Physical Examination Findings

• Firm, irregular thyroid gland on palpation, particularly with Hashimoto's thyroiditis (the most common cause in the United States) 3, 4
• Delayed ankle reflexes are a characteristic finding 4
• Dry, coarse skin 1
• Periorbital edema 3

Critical Diagnostic Pitfalls in Women Over 50

Symptoms in older women are often more subtle and easily attributed to aging or menopause, leading to delayed diagnosis. 2, 5

• Hypothyroidism affects 4-10% of women, with prevalence increasing significantly with age 3, 4
• Symptoms overlap with perimenopausal/postmenopausal changes, making clinical recognition more difficult 2
• One in 300 persons in the United States has hypothyroidism, with higher rates in females and older individuals 4

Cardiovascular and Metabolic Complications

• Hypertension can develop or worsen from hypothyroidism 4
• Hyperlipidemia (elevated cholesterol) is common and may be the presenting finding 3, 4
• Increased cardiovascular disease risk, particularly concerning in postmenopausal women already at elevated risk 2

Severe Untreated Disease Consequences

• Heart failure can develop from prolonged untreated hypothyroidism 1, 5
• Myxedema coma represents life-threatening severe hypothyroidism 1, 5
• Psychosis may occur in severe cases 5
• Infertility and increased miscarriage risk 1, 4
• Hyponatremia (low sodium) 5
• Hyperprolactinemia (elevated prolactin) 5

Diagnostic Approach

TSH measurement is the single most important diagnostic test—do not rely on clinical symptoms alone for diagnosis. 3, 4

• Serum TSH is the best laboratory assessment of thyroid function, with sensitivity above 98% and specificity greater than 92% 6, 4
• Free T4 measurement confirms the diagnosis when TSH is elevated 4
• Confirmation of diagnosis must be based on laboratory tests, not symptoms, as clinical presentation is too nonspecific 3

Treatment Overview

Levothyroxine is the standard treatment and is highly effective when properly dosed. 7, 3, 4, 5

Initial Treatment Strategy

• For women over 50 without cardiac disease: Start levothyroxine at approximately 1.6 mcg/kg/day 8
• For women over 70 or with cardiac disease: Start at 25-50 mcg/day and titrate gradually to avoid cardiac complications 8
• For TSH >10 mIU/L: Initiate treatment regardless of symptoms, as this carries approximately 5% annual risk of progression to overt hypothyroidism 8

Monitoring Requirements

• Recheck TSH every 6-8 weeks after any dose adjustment until stable 8, 7
• Once stable, monitor TSH every 6-12 months or when clinical status changes 8, 7
• Target TSH range is 0.5-4.5 mIU/L for primary hypothyroidism 8

Special Considerations for Women Over 50 with Family History

• Aggressive case-finding is warranted in older women, even without overt symptoms 2
• Women with family history of thyroid disorders have increased risk and should maintain high clinical suspicion 6
• Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts 4.3% annual progression risk versus 2.6% in antibody-negative individuals 8
• Postmenopausal women face compounded risks of osteoporosis and cardiovascular disease, making treatment particularly important 2

Critical Treatment Pitfalls to Avoid

• Approximately 25% of patients on levothyroxine are unintentionally overtreated with TSH suppression, increasing risks for atrial fibrillation, osteoporosis, and fractures 8
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism, as this can precipitate life-threatening adrenal crisis 8
• Treatment is typically lifelong—hypothyroidism is usually permanent 3
• Suboptimal dosing is common in clinical practice, requiring careful monitoring and dose adjustments 5