Neuropsychiatric and Cognitive Sequelae of Severe Hypothyroidism: Insights into Endocrine–Brain Interactions

Severe hypothyroidism can disrupt neurocognitive and affective functioning through alterations in cerebral metabolism, neurotransmission, and immune signaling. While somatic features often guide diagnosis, presentations dominated by psychiatric and cognitive symptoms—particularly in young adults—are rare and prone to misattribution.

We describe a 29‑year‑old male with autoimmune comorbidities who developed progressive anxiety, cognitive slowing, and depressive symptoms over several months. Lacking classic hypothyroid stigmata, his presentation was initially attributed to academic stress, prompting initiation of venlafaxine. Routine laboratory screening revealed profound hypothyroidism (TSH >90 μIU/mL, markedly reduced free T4) secondary to Hashimoto’s thyroiditis. Full‑dose levothyroxine replacement led to rapid physical improvement and resolution of cognitive slowing within six weeks. Residual mood symptoms improved following antidepressant titration.

This case underscores the critical role of endocrine–brain interactions in psychiatric practice and raises consideration of the historically described but underrecognized syndrome of “myxedema madness.” It also illustrates how autoimmune vulnerability may heighten neuropsychiatric risk in endocrine disorders.

Clinicians should maintain a high index of suspicion for thyroid dysfunction in patients with atypical, treatment‑resistant, or diagnostically ambiguous psychiatric presentations. Incorporating thyroid screening into psychiatric evaluations can prevent prolonged morbidity and facilitate full functional recovery. Broader clinical awareness is essential for timely recognition and integrative management of endocrine‑related neuropsychiatric syndromes.