Thyroxine (T4) Associated Diseases and Disorders
Diseases and conditions associated with thyroxine (T₄) imbalance, covering both hypothyroxinemia (low T₄) and thyroxine excess (high T₄).
🔹 1️⃣ Thyroxine deficiency (hypothyroxinemia / hypothyroidism)–associated conditions
Occurs when serum free T₄ is below normal, leading to decreased tissue T₃ activity.
⚠️ Diseases and conditions:
✅ Congenital hypothyroidism
- Deficiency of T₄ at birth.
- If untreated: cretinism (severe intellectual disability, short stature, deaf-mutism).
✅ Primary hypothyroidism
- Most common cause: Hashimoto’s thyroiditis (autoimmune destruction of thyroid).
- Other causes: iodine deficiency, thyroidectomy, radioiodine therapy.
✅ Secondary hypothyroidism
- Pituitary failure → ↓ TSH → ↓ T₄ production.
✅ Tertiary hypothyroidism
- Hypothalamic dysfunction (↓ TRH).
✅ Subclinical hypothyroidism
- Normal T₄ but elevated TSH.
🩺 Signs & symptoms of hypothyroidism:
- Fatigue, weight gain, cold intolerance
- Bradycardia, dry skin, constipation
- Depression, slow reflexes
- In children: growth retardation, developmental delay
🔹 2️⃣ Thyroxine excess (thyrotoxicosis / hyperthyroidism)–associated conditions
Occurs when serum free T₄ (and/or T₃) is above normal, leading to excessive stimulation of target tissues.
⚠️ Diseases and conditions:
✅ Graves’ disease
- Autoimmune: TSH receptor antibodies → overstimulation → ↑ T₄/T₃ production.
✅ Toxic multinodular goiter
- Autonomous hyperfunctioning thyroid nodules.
✅ Toxic adenoma
- Single autonomous hyperfunctioning nodule.
✅ Thyroiditis (subacute, postpartum)
- Transient release of stored T₄/T₃.
✅ Exogenous thyroxine excess (factitious thyrotoxicosis)
- Overuse of levothyroxine therapy.
🩺 Signs & symptoms of hyperthyroidism:
- Weight loss, heat intolerance
- Tachycardia, palpitations
- Tremor, nervousness, anxiety
- Diarrhea, increased appetite
- Muscle wasting, hyperreflexia
- In Graves’: exophthalmos (eye bulging)
🔹 3️⃣ Other conditions related to altered thyroxine levels
✅ Sick euthyroid syndrome (non-thyroidal illness)
- Low T₃ ± low T₄ in critical illness without intrinsic thyroid disease (adaptive response).
✅ Iodine deficiency goiter
- Inadequate iodine → ↓ T₄ → compensatory thyroid enlargement.
✅ Resistance to thyroid hormone (rare)
- Normal or elevated T₄ with reduced tissue responsiveness.
🔹 Summary table:
| Imbalance | Diseases/Conditions | Key features |
| 🔻 Thyroxine deficiency | Congenital hypothyroidism, Hashimoto’s thyroiditis, iodine deficiency, secondary/tertiary hypothyroidism, subclinical hypothyroidism | Fatigue, cold intolerance, bradycardia, constipation, slowed growth (children) |
| 🔺 Thyroxine excess | Graves’ disease, toxic multinodular goiter, toxic adenoma, thyroiditis, factitious thyrotoxicosis | Weight loss, tachycardia, tremor, heat intolerance, anxiety, diarrhea |
| ⚠️ Altered T₄ without thyroid disease | Sick euthyroid syndrome, iodine deficiency goiter, thyroid hormone resistance | Variable depending on context |
✅ Key clinical principle:
- T₄ imbalance affects nearly every organ system, due to its central role in regulating basal metabolic rate, growth, development, and homeostasis.
- Clinical effects depend on whether T₄ is too low (hypometabolic state) or too high (hypermetabolic state).