What happens when the thyroid gland releases too little thyroid hormone?

Thyroid Hormone Deficiency: Consequences and Management

When the thyroid gland releases too little thyroid hormone (hypothyroidism), it leads to significant health consequences including cardiovascular complications, cognitive impairment, metabolic dysfunction, and reduced quality of life that require appropriate hormone replacement therapy to prevent morbidity and mortality. 1

Pathophysiology of Hypothyroidism

Hypothyroidism occurs when the thyroid fails to produce adequate amounts of thyroxine (T4) and triiodothyronine (T3). This condition disrupts the normal hypothalamic-pituitary-thyroid axis:

• The pituitary gland, which has the highest density of T3 receptors, responds to low thyroid hormone levels by increasing thyroid stimulating hormone (TSH) secretion 2
• TSH normally regulates iodine uptake and all subsequent steps in thyroid hormone biosynthesis 3
• In hypothyroidism, despite elevated TSH, the thyroid cannot produce sufficient hormones

Clinical Manifestations

Hypothyroidism affects multiple body systems:

Cardiovascular Effects

• Altered cardiac output
• Adverse lipid profiles
• Increased cardiovascular risk 1

Metabolic Effects

• Weight gain
• Cold intolerance
• Fatigue
• Constipation

Neurological/Cognitive Effects

• Cognitive impairment
• Depression
• Memory problems

Other Effects

• Dry skin
• Hair loss
• Hoarseness
• Menstrual irregularities

Diagnostic Approach

Diagnosis relies on laboratory testing:

• Elevated TSH with low free T4 indicates primary hypothyroidism
• Low or inappropriately normal TSH with low free T4 suggests central (secondary) hypothyroidism 4
• Serum TSH is not a sensitive indicator of iodine status 3

Treatment Considerations

Levothyroxine Replacement

• Weight-based dosing of approximately 1.6-1.8 mcg/kg/day is common for complete replacement 1
• Target TSH range is approximately 0.4-4.5 mIU/L for most patients 1
• Regular monitoring every 6-12 months once stable

Special Populations

• Elderly patients (>65 years): Maintain higher TSH targets and consider more frequent monitoring due to increased cardiac risk 1
• Pregnant patients: Require trimester-specific reference ranges 1
• Patients with diabetes: May experience worsened glycemic control even with optimal levothyroxine doses 1

Complications of Untreated Hypothyroidism

Untreated or undertreated hypothyroidism can lead to:

• Persistent hypothyroid symptoms
• Adverse lipid profiles
• Increased cardiovascular risk
• Potential cognitive effects 1
• In severe cases, myxedema coma (life-threatening)

Nutritional Considerations

Adequate micronutrient status is essential for thyroid function:

• Iodine deficiency is a major cause of hypothyroidism globally 3
• Iron deficiency impairs thyroid metabolism 3
• Selenium is required for conversion of T4 to T3 3

Common Pitfalls in Management

• Overtreatment risks: Excessive levothyroxine can cause iatrogenic hyperthyroidism, leading to:

  • 3-fold increased risk of atrial fibrillation with TSH <0.1 mIU/L 1
  • Accelerated bone mineral density loss, particularly in postmenopausal women 1
  • Increased fracture risk in patients over 65 years 1

• Monitoring challenges:

  • Failure to adjust dose when needed
  • Not recognizing drug interactions that affect levothyroxine absorption
  • Overlooking central hypothyroidism due to misinterpretation of biochemical changes 4

• Dose adjustment: When TSH falls below normal range, reduce dose by 12.5-25 mcg 1

Proper diagnosis and management of hypothyroidism is essential to prevent the significant morbidity and mortality associated with this common endocrine disorder.