{"id":"7bc4e3bd-aae5-5dd8-b562-0675ac08f9c6","stable_key":"availability:thyroid-local-hormone-metabolism:2","predicate":"can_change","statement":"Restriction-related changes in deiodinase activity can change local thyroid-hormone metabolism.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Biochemical mechanism with experimental and clinical context; source-derived unverified synthesis.","direction":"context_dependent","is_public":true,"mechanism_event_id":"ec83cdfa-da36-5d53-8800-6a1252d2b3c9","mechanism_event_label":"Restriction-related changes in deiodinase activity can change local thyroid-hormone metabolism.","subject":{"id":"f36696c0-fc20-5777-b298-36395846ffea","slug":"deiodinases","display_name":"DIO1 / DIO2 / DIO3","entity_type_key":"protein_family"},"object":{"id":"cb036857-cb52-50d7-b656-9ca2a3cf98a0","slug":"thyroid-hormone-metabolism","display_name":"Local thyroid-hormone metabolism","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ec83cdfa-da36-5d53-8800-6a1252d2b3c9","stable_key":"availability:thyroid-local-hormone-metabolism:2","event_type":"availability_dependent_change","label":"Restriction-related changes in deiodinase activity can change local thyroid-hormone metabolism.","description":"Selenium restriction affects deiodinase expression or activity in a particular tissue. Mechanistic synthesis; deiodinase responses and clinical consequences are tissue- and context-dependent.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f36696c0-fc20-5777-b298-36395846ffea","slug":"deiodinases","display_name":"DIO1 / DIO2 / DIO3","entity_type_key":"protein_family"},"role":"condition_input","stoichiometry":null,"state_label":"Selenium restriction affects deiodinase expression or activity in a particular tissue.","sequence_order":0,"notes":""},{"entity":{"id":"cb036857-cb52-50d7-b656-9ca2a3cf98a0","slug":"thyroid-hormone-metabolism","display_name":"Local thyroid-hormone metabolism","entity_type_key":"cellular_process"},"role":"affected_component","stoichiometry":null,"state_label":"Selenium restriction affects deiodinase expression or activity in a particular tissue.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Selenium restriction affects deiodinase expression or activity in a particular tissue.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Mechanistic synthesis; deiodinase responses and clinical consequences are tissue- and context-dependent.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Normal serum TSH neither directly measures local T3 generation nor establishes hidden clinical tissue hypothyroidism. Combined iodine deficiency is a distinct context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4b6cd166-38dd-5799-9693-d403b5a429ed","evidence_kind":"source_passage","locator":"lines 319-327","start_line":319,"end_line":327,"excerpt":"DIO1, DIO2, and DIO3 are selenoproteins. Selenium restriction can therefore affect deiodinase biology and local thyroid-hormone metabolism.\n\nselenium restriction\n     ↓\nchanges in deiodinase expression/activity\n     ↓\nchanges in local T4 ↔ T3 / rT3 metabolism\n\nSerum TSH does not directly measure tissue-specific T3 generation. At the same time, a normal TSH should not be taken as proof that a neuron or other tissue is clinically “hypothyroid.” The degree of clinically important tissue-level decoupling in ordinary nutritional selenium deficiency is not captured by a single validated threshold.","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}}],"relations":[],"conflicts":[],"corrections":[{"id":"7dbe08d6-7f96-521e-9e98-d363f1a52f6e","title":"Local thyroid metabolism cannot diagnose hidden tissue hypothyroidism","kind":"qualification","status":"qualified","why":"The earlier draft states that apparently euthyroid laboratory results can conceal a hypothyroid neuron. The new reference distinguishes local metabolism from proof of clinically important tissue hypothyroidism.","resolution":"Keep tissue-specific deiodinase biology while avoiding a diagnosis from normal TSH or an unvalidated selenium threshold.","created_at":"2026-09-17 05:59:32","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/7dbe08d6-7f96-521e-9e98-d363f1a52f6e","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1747,"end_line":1752,"papers":[{"paper_key":"rat-thyroid-1997","title":"Effects of selenium and iodine deficiency on thyroid hormone concentrations in the central nervous system of the rat","url":"https://pubmed.ncbi.nlm.nih.gov/9100558/","doi":null,"year":1997,"model":"Adult Wistar rats; single/combined selenium/iodine deficiency; brain assays","summary":"Local metabolism experiments do not establish a clinical diagnostic rule for humans with normal TSH."}]},"sides":[{"conflict_id":"7dbe08d6-7f96-521e-9e98-d363f1a52f6e","ordinal":0,"label":"Earlier statement","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":129,"end_line":129,"quote":"This is why severe Se deficiency **decouples local tissue thyroid status from serum TSH.** You can look euthyroid on labs and be hypothyroid inside a neuron.","claim_id":null,"source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":[]},{"conflict_id":"7dbe08d6-7f96-521e-9e98-d363f1a52f6e","ordinal":1,"label":"New reference qualification","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":319,"end_line":327,"quote":"DIO1, DIO2, and DIO3 are selenoproteins. Selenium restriction can therefore affect deiodinase biology and local thyroid-hormone metabolism.\n\nselenium restriction\n     ↓\nchanges in deiodinase expression/activity\n     ↓\nchanges in local T4 ↔ T3 / rT3 metabolism\n\nSerum TSH does not directly measure tissue-specific T3 generation. At the same time, a normal TSH should not be taken as proof that a neuron or other tissue is clinically “hypothyroid.” The degree of clinically important tissue-level decoupling in ordinary nutritional selenium deficiency is not captured by a single validated threshold.","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]}]}],"research":null}