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Persistent non-response despite protocol compliance suggests pituitary hyporesponsiveness, which requires endocrine evaluation

Additional factors include autonomic dysregulation, small fiber neuropathy, as well genetic and epigenetic predispositions such as polymorphisms in the catechol-O-methyltransferase well as alterations in pain processing pathways (Siracusa et al

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However, this combination also comes with unique considerations and requires close monitoring by healthcare professionals