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This difficulty may result from: Variable absorption due to gastrointestinal (GI) disorders, drug interactions, or food Fluctuations in consistency, with better absorption some days compared to others Missed doses or imperfect adherence Differences between generic preparations or formulations Different pharmacokinetics ( how fast a drug starts working, how long it lasts, how strong its effects are, and how often you need to take it) Because of these challenges, clinicians sometimes refer to “ refractory hypothyroidism ” when TSH remains elevated (or free T4 low) despite what seems like an adequate oral dose

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The ubiquitin–proteasome system (UPS) catalyzes the degradation of ubiquitinated intracellular proteins playing a key role on regulation of cell proliferation and survival [127]