Rheumatologisch-osteologische Aspekte bei Schilddrüsenerkrankungen

Zusammenfassung

Erkrankungen der Schilddrüse führen nicht selten zu Symptomen vonseiten des Bewegungsapparats und sind andererseits häufig mit verschiedenen entzündlich-rheumatischen Erkrankungen assoziiert. Eine erhöhte Prävalenz von autoimmunen Schilddrüsenerkrankungen wird vor allem bei Patienten mit primärem Sjögren-Syndrom, rheumatoider Arthritis, juveniler chronischer Arthritis, systemischer Sklerose, systemischem Lupus erythematodes und Fibromyalgie beobachtet. Dabei besteht offenbar kein Zusammenhang zwischen der Schilddrüsenfunktion und der Koinzidenz mit entzündlich-rheumatischen Erkrankungen. Andererseits werden verschiedene unspezifische rheumatische Symptome bei Schilddrüsenfunktionsstörungen unabhängig vom Vorliegen einer entzündlich-rheumatischen Erkrankung beobachtet. Dazu zählen eine milde, nicht erosive Arthritis, Polyarthralgien und Myalgien bei autoimmuner Thyreoiditis. Bei Hyperthyreose tritt gehäuft eine Periarthritis humeroscapularis auf. Wesentlich seltener kommt es, insbesondere bei lange bestehender endokriner Orbitopathie, zu einer Akropachie. Insbesondere bei Asiaten wird die thyreotoxische periodische Paralyse, welche mit Hypokaliämie einhergeht, beobachtet. Typische Manifestationen der Hypothyreose sind das Karpaltunnelsyndrom und die Myopathie, welche häufig mit CK-Erhöhung einhergeht und differenzialdiagnostisch gegenüber der Polymyositis abzugrenzen ist. Eine außerordentlich wichtige Manifestation von Schilddrüsenfunktionsstörungen am Bewegungsapparat ist die Hyperthyreose-assoziierte Osteoporose. Pathogenetisch führt sowohl ein Überschuss an Schilddrüsenhormonen (T3) als auch ein Mangel an TSH zu einem verstärkten Knochenumbau mit negativer Bilanz. Bei manifester Hyperthyreose kann der Knochenmasseverlust 12 – 15 % betragen. Risikofaktoren für die Entwicklung einer Osteoporose bei latenter Hyperthyreose sind höheres Alter, Menopause, eine TSH-Suppression über lange Zeiträume sowie die Kombination mit weiteren Osteoporose-Risikofaktoren. Im Rahmen der Differenzialdiagnose der Osteoporose sollte daher eine latente oder manifeste Hyperthyreose immer ausgeschlossen werden. Die frühzeitige Therapie der Hyperthyreose stellt eine effektive Prophylaxe des Knochenmasseverlusts dar. Unter T 4-Therapie sollte eine TSH-Suppression aus Sicht des Knochenstoffwechsels vermieden werden. Falls eine TSH-Suppression erforderlich ist, wie bei Zustand nach Schilddrüsenkarzinom, ist eine prophylaktische Gabe von Bisphosphonaten zu bedenken.

Abstract

Thyroid diseases are often associated with symptoms of the locomotive system on one hand and with various rheumatic diseases on the other. An increased prevalence of autoimmune thyroid diseases is observed in primary Sjögrens syndrome, rheumatoid arthritis, juvenile chronic arthritis, systemic sclerosis, systemic lupus erythematosus and fibromyalgia. A strong pathogenetic relationship between thyroid function and the co-existing rheumatic disease is lacking. On the other hand, various unspecific rheumatic symptoms are observed frequently in hyperthyroidism and hypothyroidism. These include mild non-erosive arthritis, polyarthralgia and myalgia in autoimmune thyroiditis and adhesive capsulitis of the shoulder in hyperthyroidism. Especially in patients with long-lasting Graves disease with orbitopathy, thyroid acropachy can occur. About 2 % of Asian people with thyrotoxicosis may suffer from thyrotoxic periodic paralysis. Typical manifestations of hypothyroidism are carpal tunnel syndrome and hypothyroid myopathy which is associated with elevated creatine kinase and should be considered in differential diagnosis of polymyositis. A very important manifestation of thyroid disease is osteoporosis in hyperthyroidism. Both an excess of thyroid hormone and a deficiency of thyroid-stimulating hormone are involved in high bone turnover and bone loss. In hyperthyroid subjects, a reduction of 12 – 15 % in bone mineral density has been shown. Risk factors for bone loss in subclinical hyperthyroidism are older age, menopausal state, a long-lasting TSH suppression and the combination with other risk factors for osteoporosis. Overt and subclinical hyperthyroidism should be considered in the differential diagnosis of osteoporosis in general. An early treatment of hyperthyroidism is effective in the prevention of bone loss. With regard to bone metabolism, a TSH-suppression during T 4-therapy should be avoided if possible. If TSH suppression is indicated, the prophylactic use of bisphophonates should be considered.

Schlüsselwörter

Schilddrüsenerkrankungen - rheumatische Manifestationen - Osteoporose

Key words

thyroid diseases - rheumatoid manifestations - osteoporosis

Literatur

• 1 Abe E, Marians R C, Yu W. et al . TSH is a negative regulator of skeletal remodeling.  Cell. 2003;  115 151-162
• 2 Abe E, Sun L, Mechanick J. et al . Bone loss in thyroid disease: role of low TSH and high thyroid hormone.  Ann N Y Acad Sci. 2007;  1116 383-391
• 3 Antonelli A, Delle Sedie A, Fallahi P. et al . High prevalence of thyroid autoimmunity and hypothyroidism in patients with psoriatic arthritis.  J Rheumatol. 2006;  33 2026-2028
• 4 Artuso V, Roiter I. A rare hyperthyroid sindrome.  Minerva Endocrinol. 2004;  29 71-75
• 5 Atzeni F, Doria A, Ghirardello A. et al . Anti-thyroid antibodies and thyroid dysfunction in rheumatoid arthritis: prevalence and clinical value.  Autoimmunity. 2008;  41 111-115
• 6 Bassett J H, Williams G R. The molecular actions of thyroid hormone in bone.  Trends Endocrinol Metab. 2003;  14 356-364
• 7 Batal O, Hatem S F. Radiologic case study. Thyroid acropachy.  Orthopedics. 2008;  31 98-100
• 8 Bauer D C, Ettinger B, Nevitt M C. et al . Study of Osteoporotic Fractures Research Group. Risk for fracture in women with low serum levels of thyroid-stimulating hormone.  Ann Intern Med. 2001;  134 561-568
• 9 Bazzichi L, Rossi A, Giuliano T. et al . Association between thyroid autoimmunity and fibromyalgic disease severity.  Clin Rheumatol. 2007;  26 2115-2120
• 10 Biondi B, Palmieri E A, Klain M. et al . Subclinical hyperthyroidism: clinical features and treatment options.  Eur J Endocrinol. 2005;  152 1-9
• 11 Brinkane A, Crickx L, Bergheul S. et al . Hyperthyroid rheumatism. Review of the literature and a case report.  Presse Med. 2003;  32 836-838
• 12 Cakir M, Samanci N, Balci N. et al . Musculoskeletal manifestations in patients with thyroid disease.  Clin Endocrinol. 2003;  59 162-167
• 13 Faber J, Galløe A M. Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis.  Eur J Endocrinol. 1994;  130 350-356
• 14 Faber J, Jensen I W, Petersen L. et al . Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women.  Clin Endocrinol. 1998;  48 285-290
• 15 Garton M, Reid I, Loveridge N. et al . Bone mineral density and metabolism in premenopausal women taking L-thyroxine replacement therapy.  Clin Endocrinol. 1994;  41 747-755
• 16 Harel L, Prais D, Uziel Y. et al . Increased prevalence of antithyroid antibodies and subclinical hypothyroidism in children with juvenile idiopathic arthritis.  J Rheumatol. 2006;  33 164-166
• 17 Hase H, Ando T, Eldeiry L. et al . TNFalpha mediates the skeletal effects of thyroid-stimulating hormone.  Proc Natl Acad Sci U S A. 2006;  103 12 849-12 854
• 18 Hsieh C H, Kuo S W, Pei D. et al . Thyrotoxic periodic paralysis: an overview.  Ann Saudi Med. 2004;  24 418-422
• 19 Ikeda F, Nishimura R, Matsubara T. et al . Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation.  J Clin Invest. 2004;  114 475-484
• 20 Innocencio R M, Romaldini J H, Ward L S. Thyroid autoantibodies in autoimmune diseases.  Medicina. 2004;  64 227-230
• 21 Jacobs-Kosmin D, DeHoratius R J. Musculoskeletal manifestations of endocrine disorders.  Curr Opin Rheumatol. 2005;  17 64-69
• 22 Jara L J, Navarro C, Brito-Zerón Mdel P. et al . Thyroid disease in Sjögren’s syndrome.  Clin Rheumatol. 2007;  26 1601-1606
• 23 Kohriyama K, Katayama Y, Tsurusako Y. Relationship between primary Sjögren’s syndrome and autoimmune thyroid disease.  Nippon Rinsho. 1999;  57 1878-1881
• 24 Kerimović-Morina D. Autoimmune thyroid disease and associated rheumatic disorders.  Srp Arh Celok Lek. 2005;  133 (Suppl 1) 55-60
• 25 Kumeda Y, Inaba M, Tahara H. et al . Persistent increase in bone turnover in Graves’ patients with subclinical hyperthyroidism.  J Clin Endocrinol Metab. 2000;  85 4157-4161
• 26 Kung A W. Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge.  J Clin Endocrinol Metab. 2006;  91 2490-2495
• 27 Lakatos P. Thyroid hormones: beneficial or deleterious for bone?.  Calcif Tissue Int. 2003;  73 205-209
• 28 Lazarus M N, Isenberg D A. Development of additional autoimmune diseases in a population of patients with primary Sjögren’s syndrome.  Ann Rheum Dis. 2005;  64 1062-1064
• 29 Leese G P, Jung R T, Guthrie C. et al . Morbidity in patients on L-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH.  Clin Endocrinol. 1992;  37 500-503
• 30 Lin S H, Chu P, Cheng C J. et al . Early diagnosis of thyrotoxic periodic paralysis: spot urine calcium to phosphate ratio.  Crit Care Med. 2006;  34 2984-2989
• 31 Loviselli A, Mastinu R, Rizzolo E. et al . Circulating telopeptide type I is a peripheral marker of thyroid hormone action in hyperthyroidism and during levothyroxine suppressive therapy.  Thyroid. 1997;  7 561-566
• 32 Lupoli G, Nuzzo V, Di Carlo C. et al . Effects of alendronate on bone loss in pre- and postmenopausal hyperthyroid women treated with methimazole.  Gynecol Endocrinol. 1996;  10 343-348
• 33 Madariaga M G. Polymyositis-like syndrome in hypothyroidism: review of cases reported over the past twenty-five years.  Thyroid. 2002;  12 331-336
• 34 Marcocci C, Golia F, Bruno-Bossio G. et al . Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women.  J Clin Endocrinol Metab. 1994;  78 818-823
• 35 Marians R C, Ng L, Blair H C. et al . Defining thyrotropin-dependent and -independent steps of thyroid hormone synthesis by using thyrotropin receptor-null mice.  Proc Natl Acad Sci U S A. 2002;  99 15 776-15 781
• 36 Mazziotti G, Sorvillo F, Piscopo M. et al . Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma.  J Bone Miner Res. 2005;  20 480-486
• 37 Mihailova D, Grigorova R, Vassileva B. et al . Autoimmune thyroid disorders in juvenile chronic arthritis and systemic lupus erythematosus.  Adv Exp Med Biol. 1999;  455 55-60
• 38 Mudde A H, Houben A J, Nieuwenhuijzen Kruseman A C. Bone metabolism during anti-thyroid drug treatment of endogenous subclinical hyperthyroidism.  Clin Endocrinol. 1994;  41 421-424
• 39 Neeck G, Riedel W. Thyroid function in patients with fibromyalgia syndrome.  J Rheumatol. 1992;  19 1120-1122
• 40 Pamuk O N, Cakir N. The frequency of thyroid antibodies in fibromyalgia patients and their relationship with symptoms.  Clin Rheumatol. 2007;  26 55-59
• 41 Punzi L, Betterle C. Chronic autoimmune thyroiditis and rheumatic manifestations.  Joint Bone Spine. 2004;  71 275-283
• 42 Ramos-Casals M, García-Carrasco M, Cervera R. et al . Thyroid disease in primary Sjögren syndrome. Study in a series of 160 patients.  Medicine (Baltimore). 2000;  79 103-108
• 43 Raterman H G, Halm V P, Voskuyl A E. et al . Rheumatoid arthritis is associated with a high prevalence of hypothyroidism that amplifies its cardiovascular risk.  Ann Rheum Dis. 2008;  67 229-232
• 44 Rosen H N, Moses A C, Garber van J. et al . Randomized trial of pamidronate in patients with thyroid cancer: bone density is not reduced by suppressive doses of thyroxine, but is increased by cyclic intravenous pamidronate.  J Clin Endocrinol Metab. 1998;  83 2324-2330
• 45 Rosen H N, Moses A C, Gundberg C. et al . Therapy with parenteral pamidronate prevents thyroid hormone-induced bone turnover in humans.  J Clin Endocrinol Metab. 1993;  77 664-669
• 46 Sampath T K, Simic P, Sendak R. et al . Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.  J Bone Miner Res. 2007;  22 849-859
• 47 Soy M, Guldiken S, Arikan E. et al . Frequency of rheumatic diseases in patients with autoimmune thyroid disease.  Rheumatol Int. 2007;  27 575-577
• 48 Tunc R, Gonen M S, Acbay O. et al . Autoimmune thyroiditis and anti-thyroid antibodies in primary Sjogren’s syndrome: a case-control study.  Ann Rheum Dis. 2004;  63 575-577
• 49 Uzzan B, Campos J, Cucherat M. et al . Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis.  J Clin Endocrinol Metab. 1996;  81 4278-4289
• 50 Vasconcellos L F, Peixoto M C, Oliveira T N. et al . Hoffman’s syndrome: pseudohypertrophic myopathy as initial manifestation of hypothyroidism. Case report.  Arq Neuropsiquiatr. 2003;  61 851-854
• 51 Vestergaard de P, Mosekilde L. Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16,249 patients.  Thyroid. 2002;  12 411-419
• 52 Vestergaard P, Rejnmark L, Mosekilde L. Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk.  Calcif Tissue Int. 2005;  77 139-144