Post-Thyroidectomy Endocrine Dysregulation State (PTEDS): A Multidomain Clinical Syndrome Framework

Abstract

Objective: Many patients continue to experience symptoms after thyroidectomy even when their labs suggest that levothyroxine replacement is adequate and thyroid function is normal. This study introduces and characterizes Post-Thyroidectomy Endocrine Dysregulation State (PTEDS) as a proposed multidomain clinical syndrome that may explain the gap between biochemical euthyroidism and ongoing functional impairment after thyroid removal.

Materials and Methods: We developed a systems-based conceptual model using an extensive review of peer‑reviewed literature from PubMed, Scopus, Web of Science, and Google Scholar. Key search terms included thyroidectomy, levothyroxine replacement, persistent hypothyroid symptoms, tissue T3 deficiency, deiodinase activity, neurocognitive dysfunction, hypoparathyroidism, and quality of life. Evidence from physiology, biochemistry, and clinical studies was synthesized into four core endocrine domains: thyroid hormone regulation, neuroendocrine adaptation, metabolic regulation, and calcium–parathyroid physiology. Symptom clustering was then applied to identify reproducible clinical phenotypes and to propose diagnostic criteria.

Results: Five recurring clinical domains were identified: thyroid axis instability, neurocognitive dysfunction, affective–autonomic dysregulation, metabolic inflexibility, and calcium–neuromuscular dysregulation. Estimated prevalence was highest for thyroid axis instability (87%), followed by neurocognitive dysfunction (74%), metabolic inflexibility (71%), affective–autonomic dysregulation (68%), and calcium–neuromuscular dysfunction (42%). These domains frequently overlapped; the most common pattern combined thyroid instability with neurocognitive symptoms. A three-level severity scale (mild, moderate, severe) was defined according to the number of domains involved and the degree of functional limitation.

Conclusion: PTEDS offers a plausible multidimensional framework to describe persistent symptoms in post‑thyroidectomy patients who appear biochemically euthyroid. Recognizing PTEDS may encourage clinicians to move beyond TSH-only monitoring and toward more personalized, tissue‑focused, and symptom‑oriented approaches to postoperative endocrine care.