ArticleCureus2025
When Hormones Shape the Mind: Neuropsychiatric Manifestations in a Patient With Congenital Adrenal Hyperplasia and Genital Ambiguity.
Article in Cureus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can produce neuropsychiatric manifestations through cortisol deficiency, adrenocorticotropic hormone (ACTH)-driven hyperandrogenism, and the cumulative effects of long-term glucocorticoid therapy. We report a 33-year-old transgender male (sex assigned female at birth) with a history of neonatal genital ambiguity surgically corrected and lifelong prednisolone replacement who presented with a five-day course of irritability, expansive mood, decreased need for sleep, erratic behavior, heteroaggression, and psychotic symptoms. Physical examination showed Cushingoid stigmata (moon facies, dorsocervical fat pad, centripetal adiposity, violaceous striae, and acral edema). Initial management included continuation of divalproex and clozapine; lithium was discontinued due to renal dysfunction and clinical worsening. Endocrine evaluation demonstrated low morning cortisol with elevated ACTH, markedly increased total and free testosterone with low-normal gonadotropins, and severe hypothyroidism, findings consistent with primary adrenal insufficiency and adrenal-origin hyperandrogenism in the setting of CAH. Given persistent manic psychosis and limited pharmacologic options, modified electroconvulsive therapy (ECT) under anesthesia and muscle relaxation was initiated (12 bilateral sessions) without complications, with progressive stabilization of mood, attenuation of psychotic content, and normalization of sleep-wake cycles. The patient was discharged in improved condition with endocrine and psychiatric follow-up, including thyroid replacement and reassessment of glucocorticoid strategy. This case underscores the diagnostic interplay between endocrine dysregulation and affective pathology, the importance of multidisciplinary coordination (psychiatry, endocrinology, and clinical genetics), and the therapeutic value of transfer energy capacitive and resistive (TECAR) when conventional mood-stabilizing regimens are constrained by medical comorbidity. Early recognition and targeted hormonal optimization may reduce iatrogenic risk and improve neuropsychiatric outcomes in adults with CAH.
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