In the hyperplastic (toxic) phase of diffuse multinodular goiter, are thyroid‑stimulating hormone (TSH) low, normal, or high, and are triiodothyronine (T3) and thyroxine (T4) elevated, normal, or low?

Thyroid Function Tests in Hyperplastic (Toxic) Phase of Multinodular Goiter

In the hyperplastic (toxic) phase of diffuse multinodular goiter, TSH is low or suppressed, while T3 and T4 are elevated or high-normal.

Laboratory Pattern in Toxic Multinodular Goiter

The characteristic biochemical profile shows:

• TSH is suppressed (low or undetectable) due to autonomous thyroid hormone production from hyperfunctioning nodules 1, 2
• T3 and T4 are elevated (or high-normal in early/subclinical cases), reflecting excess thyroid hormone synthesis from autonomously functioning follicles 1, 2
• Free T4 or total T3 with low or normal TSH defines the thyrotoxic state 1, 2

Understanding the Pathophysiology

The toxic phase occurs when nodules within the multinodular goiter develop autonomous function:

• Autonomous nodules produce thyroid hormone independent of TSH stimulation, leading to feedback suppression of pituitary TSH secretion 3, 4
• Activating TSH receptor mutations in hyperfunctioning nodules drive this autonomous hormone production 4
• Approximately 21% of patients with multinodular goiter demonstrate TSH unresponsiveness to TRH stimulation, representing preclinical hyperthyroidism that may progress to overt toxicity 3

Clinical Spectrum and Detection

The toxic phase presents along a spectrum:

• Early/subclinical phase: TSH may be suppressed with normal or high-normal T3/T4 levels, representing "preclinical hyperthyroidism" 3
• Overt toxic phase: Both TSH suppression and frank elevation of T3/T4 occur, with or without clinical symptoms 1, 5
• Radioiodine uptake scans demonstrate increased uptake in hyperfunctioning nodules with suppression of surrounding normal thyroid tissue 1, 6

Critical Diagnostic Pitfall

Do not confuse toxic multinodular goiter with transient thyrotoxicosis from destructive thyroiditis:

• Toxic multinodular goiter shows high radioiodine uptake in functioning nodules 1, 2
• Destructive thyroiditis shows low or absent radioiodine uptake 2
• This distinction is essential because toxic multinodular goiter requires definitive treatment (surgery or radioiodine), while destructive thyroiditis is self-limiting 1, 2, 5

Monitoring After Treatment

Following surgical treatment of toxic multinodular goiter:

• Serum T3 decreases approximately 50% and T4 decreases approximately 28% within the first 2 days postoperatively 7
• TSH responsiveness typically recovers after partial thyroidectomy, accompanied by normalization of thyroid hormone levels 3