Thyreoidea i praksis Thomas Brix Endokrinologisk afd. M Odense Universitetshospital For højt og for lavt stofskifte Hvad gør vi med de ”subkliniske” tilfælde?

Klinisk mistanke og tilstande forbundet med øget risiko for hyperthyreose / subklinisk hyperthyreose ? Kliniske fund: Hjertebanken, v æ gttab, indre uro, tremor, l ø s aff ø ring. Klinisk mistanke og tilstande forbundet med øget risiko for hyperthyreose / subklinisk hyperthyreose ? Kliniske fund: Hjertebanken, v æ gttab, indre uro, tremor, l ø s aff ø ring. TSH Normalt stofskifte Normal Lav Gentag TSH. fT3, fT4, TRAb, CRP TSH under referenceområdet og normal fT 4 Hyperthyreose TSH under referenceintervallet og høj fT4 Normalisering Uændret Subklinisk hyperthyreose Normalt stofskifte Gentag efter 1-3 mdr. Hyperthyreose og subklinisk hyperthyreose

Subklinisk højt og lavt stofskifte Er det noget at bekymre sig om? Subclinical thyroid dysfunction Abnormal TSH in combination with normal T3 and T4

Hos en 54-årig kvinde, der klager over træthed finder du rutinemæssigt følgende tal: TSH 6.0 [ mU/l] T4110[ nmol/l] T3 1.67[ nmol/l] T3-reaktion 0.83[ arb.enh./l] Skal der gøres yderligere, og i givet fald hvad? Samme situation, men med følgende tal: TSH <0.01 [ mU/l] T4110[ nmol/l] T3 1.67[ nmol/l] T3-reaktion 0.83[ arb.enh./l] Skal der gøres yderligere, og i givet fald hvad? Problemstillinger? Ville det ændre noget hvis pt var 22 eller 83 år?

Subklinisk hyperthyreose (kun nedsat TSH) Knudsen et al

Subklinisk hypothyreose (kun forhøjet TSH) Knudsen et al

Collet TH et al. Arch Intern Med 2012 Consequences of subclinical hyperthyroidis mortality Selmer C et al. JCEM 2014; 99, Note: MACE covers cardiovascular death, nonfatal MI and nonfatal stroke Primary care setting

Consequences of subclinical hypothyroidism All cause mortality – impact of TSH level Rodondi et al. JAMA 2010

Consequences of subclinical hypothyroidism All cause mortality – impact of age Rodondi et al. JAMA 2010

Thyroid dysfunction and mortality seriel biochemical measurements PhenotypeAdjusted HR (95% CI) per 6 months of thyroid dysfunction Hyperthyroidism 1.09 (1.08;1.10), p < Hypothyroidism 1.03 (1.02;1.04), p < PlosOne 2014, 9 Accepting that… The association between subclinical hyperthyroidism and mortality/cardiovascular mortality is statistically significant A link between subclinical hypothyroidism amd mortality/cardiovascular mortality is questionable..

Thyroid dysfunction and risk of new onset atrial fibrillation Sawin, NEJM, 1994 Cappola AR et al. JAMA 2006 Selmer er al. BMJ 2012; 345, e7895 doi.

Risk of new onset cardiovasculare disease in thyroid dysfunction Risk estimates are adjusted for sex, age, and calendar yearSelmer C et al. JCEM 2014: 99,

Consequences of subclinical thyroiddysfunction The skeleton Bone mineral density is decreased in postmenopausal women with subclinical hyperthyroidism Foldes J et al. Ciln Endocrinol 1993 Mudde AH et al. Clin Endocrinol 1994 Question Do patients with subclinical hyper- & hypothyroidism have an increased risk of osteoporotic fracture?

Consequences of subclinical hyperthyroidism The skeleton - fracture 2014

Consequences of subclinical hyperthyroidism Cognitive function A link between subclinical hyperthyroidism in elderly people and dementia has been investigated in 6 studies. Association between subclinical hyperthyroidism and dementia in Two prospective community-based studies Two prospective community-based studies Kalmijn s et al. Clin Endocrinol 2000 & Tan ZS et al. Arch Intern Med 2008*Kalmijn s et al. Clin Endocrinol 2000 & Tan ZS et al. Arch Intern Med 2008* Two case-control studies Two case-control studies Dobert N et al. Acta Med Austriaca 2003 & van Osch LA et al. Neurology 2004 Dobert N et al. Acta Med Austriaca 2003 & van Osch LA et al. Neurology 2004 However, no association in One large cross sectional study One large cross sectional study van der Cammen et al. J Am Geriatr Soc 2003 van der Cammen et al. J Am Geriatr Soc 2003 One prospective study One prospective study de Jong FJ et al. J Clin Endocrinol Metab 2006 de Jong FJ et al. J Clin Endocrinol Metab 2006 Note Whether subjects older than 65 years with subclinical hyperthyroidism have an increased risk of dementia is uncertain

Consequences of subclinical hypothyroidism Cognitive function Overall status 5 studies in favor of an association 5 studies against an association Russel et al. Geriatric Psychiatry 2012

Consequences of subclinical hypothyroidism Lipid alterations Pearce, JCEM 2012 Clinical trials to date have not consistently shown a beneficial effect of levothyroxine treatment on serum lipid levels in subclinically hypothyroid patients 5-10%

Hos en 54-årig kvinde, der klager over træthed finder du rutinemæssigt følgende tal: TSH 6.0 [ mU/l] T4110[ nmol/l] T3 1.67[ nmol/l] T3-reaktion 0.83[ arb.enh./l] Skal der gøres yderligere, og i givet fald hvad? Samme situation, men med følgende tal: TSH <0.01 [ mU/l] T4110[ nmol/l] T3 1.67[ nmol/l] T3-reaktion 0.83[ arb.enh./l] Skal der gøres yderligere, og i givet fald hvad? Problemstillinger? Ville det ændre noget hvis pt var 22 eller 83 år?

Subclinical hyper- & hypothyroidism Progression or regression? Meyerovitch et all. Arch Intern Med 2007 Gentag blodprøverne, efter 1 og 3 mdr.

Cause of subclinical hyperthyroidism

Subklinisk thyreotoksikose Supprimeret TSH (<0.1) og normalt T3 og T4 Behandling: næsten altid Underbyggende indikationer: Tidlig menopause Hjerteanamnese Osteopeni Trykgener Stor eller voksende struma

Treatment of subclinical hyperthyroidism Radio jodThycapzol / PTU Myksødem + Myksødem + mange andre Livslang Konsekvenser af behandling?

Cause of subclinical hypothyroidism Cooper & Biondi, Lancet 2012

Subklinisk hypothyreose højt TSH og normalt T3 og T4 Behandling: Ved TSH > 10 Ved TSH mellem 4-10, ofte Underbyggende indikationer: Alder <75 år Hjerteanamnese / cholesterol Blodtryk Trykgener Stor eller voksende struma

Treatment of subclinical hyporthyroidism Eltroxin / Euthyrox Overbehandling + Overbehandling + mange andre Livslang Konsekvenser af behandling?

Consequences of subclinical hypothyroidism Cognitive function Russel et al. Geriatric Psychiatry 2012 Clinical trials to date have not consistently shown a beneficial effect of levothyroxine treatment on cognitive function in subclinically hypothyroid patients