Thyroid function affects the muscle, joints and bone ... - USJ
-
Upload
khangminh22 -
Category
Documents
-
view
0 -
download
0
Transcript of Thyroid function affects the muscle, joints and bone ... - USJ
Presentation Summary:
Thyroid function affects the muscle, joints and bone health.
Hypothyroidism induces a metabolic myopathy and therefore a wide spectrum of symptoms related to
muscle impairment. Hypothyroid arthropathy involves most commonly the knees, hands and wrists and is
characterized by non-inflammatory effusions.
Hyperthyroidism is one of the secondary causes of osteoporosis, as it induces bone resorption, a negative
calcium balance, and yields an increased fracture risk. Thyroid acropatchy is associated with auto-
immune thyroid disease and manifests as clubbing and swelling of the fingers and toes, and rarely affects
distal joints.
Finally, new biologic therapies for rheumatic diseases, such as adalimumab, were recently found to be
associated with subacute thyroiridtis.
Musculo-skeletal Manifestations of Thyroid Disorders
Marlene Chakhtoura, MD, MScAssistant Professor of Medicine
Calcium Metabolism & Osteoporosis Program
American University of Beirut-Medical Center
Prevalence of Hypothyroidism Worldwide
Taylor Nat Rev Endo 2018
Prevalence of overt hypothyroidism in the general population Europe: 0.2% - 4.2% USA : 0.3% - 3.7% (depending on the definition used and population studied)
Countries in white represent no data available
Prevalence of Hyperthyroidism Worldwide
Taylor Nat Rev Endo 2018
A meta-analysis of European studies estimated a mean prevalence rate of 0.75% for males and females combined and an incidence rate of 51 cases per 100,000 per year
Countries in white represent no data available
Risk factors for Thyroid Dysfunction
Risk factor Hypothyroidism Hyperthyroidism
Female sex + +
Iodine deficiency or excess + +
Auto-immune diseases + +
Genetic risk factors + +
Selenium deficiency + +
Drugs + +
Smoking - +
Alcohol - NA
Taylor Nat Rev Endo 2018
(-) reduced risk; (+) increased risk
Thyroid Auto-immunity and Rheumatoid Arthritis
Pan Endocrine 2015
Systematic review and meta-analysis until 201413 Case control studies
TgAb: Thyroglobulin antibody; TPOAb: Anti-peroxidase antibodies
Thyroid Disorders and Systemic Lupus Erythematosus
-Systematic review and meta-analysis -Search until 2017-Observational studies on thyroid dysfunction and SLE (ACR criteria)-10 studies, both genders -Mean age 26-50 y
Thyroid dysfunction N of studies
OR (SLE vs control)
Hypothyroidism 8 2.93 (95% CI, 1.81–4.75)
Subclinicalhypothyroidism
5 5.67 (95% CI, 3.50– 9.18)
Hyperthyroidism 9 Non significant
Subclinical hyperthyroidism
4 Non significant
Luo Lupus 2018
Outline
• Thyroid hormones and the musculo-skeletal system
• Thyroid Myopathy
• Thyroid Arthropathy and Acropachy
• Osteoporosis • Subclinical and clinical thyroid disease
• Subacute thyroiditis
• Take home messages
Outline
• Thyroid hormones and the musculo-skeletal system
• Thyroid Myopathy
• Thyroid Arthropathy and Acropachy
• Osteoporosis • Subclinical and clinical thyroid disease
• Subacute thyroiditis
• Take home messages
Thyroid hormones and the musculo-skeletal system
Role of T3:-Regulates glucose uptake (GLUT4)-Stimulates oxidative pathways by increasing mitochondrial biogenesis and oxygen consumption-Regulates non-enzyme coding genes involved in muscle function-Involved in myogenesis and muscle differentiation -Connective tissue metabolism (GAG)
Sindoni Rev Endocr Metab Disord 2016; Bloise J Endo 2018
Skeletal muscle
Thyroid hormones and the musculo-skeletal system
Bassett Endocr Rev 2013
Is mediated by specific membrane transporter proteins, including monocarboxylate transporter (MCT) 8 and MCT10, the organic anion transporter protein-1c1 (OATP1c1), and the nonspecific L-type amino acid transporters 1 and 2 (LAT1, LAT2)
Outline
• Thyroid hormones and the musculo-skeletal system
• Thyroid Myopathy
• Thyroid Arthropathy and Acropachy
• Osteoporosis • Subclinical and clinical thyroid disease
• Subacute thyroiditis
• Take home messages
Hypothyroid Myopathy
• Prevalence 20-80% in retrospective studies
• Myopathy may precede biochemical hypothyroidism or occur simultaneously
• Usually proximal myopathy, rarely axial and pelvic muscle involvement, typical of polymyositis
• Elevated CK 57-90%
• Serum CK values correlated positively with serum TSH and negatively with serum FT3 and FT4, and therefore correlated with the severity of biochemical hypothyroidism, but not with the clinical severity of the muscular symptoms.
Sindoni Rev Endocr Metab Disord 2016
Hypothyroid Myopathy
Presentation Definition
Asymptomatic hyper-CKemia Persistent and asymptomatic high serum creatine kinase (CK)
Myalgia Muscle pain (Painful cramps, fatigue and exercise-intolerance)
Myoedema Mounding of muscle tissue after finger pressure
Muscular pseudohypertrophy
Increased muscle volume not related to muscle fiber hypertrophy
Proximal myopathy Symmetrical weakness of proximal upper and/or lower limbs
Rhabdomyolysis Massive and acute muscle fiber lysismassive pain and weakness
Rare syndromes Acute compartment syndromeHoffman’s syndromeKoche – Debre’ – semelaigne syndrome
Sindoni Rev Endocr Metab Disord 2016
Hypothyroid Myopathy Diagnosis:• Electromyography (EMG) can demonstrate low/small amplitude potentials
which could help with diagnosis. • Normal in 50% of the patients and does not preclude the diagnosis
Treatment:• Thyroid hormone replacement restoration of normal thyroid function,
gradual resolution of most neuromuscular symptoms is noted in most of the patients.
• CK levels fall quickly with thyroxine replacement with a few weeks and could resolve even before TSH comes to a normal range.
surrogate to monitor response to treatment in the initial stages• Myopathic symptoms can take up to 6 months to resolve.
Expert opinion to supplement by T4 and T3• Most of the symptoms resolve within a year of adequate hormone
replacement.Fariduddi StatPearls 2019
Myopathy in thyroid disease
Duyff J Neurol Neurosurg Psychiatry 2000
Prospective cohort Adults with newthyroid dysfunctionEvaluation:-Clinically-Dynamometry -Electrodiagnosis
Resolution in 79% at
6.9 (4) months
At 1 year, weakness
in 21%, confirmed in
13%
Resolution in ALL
at 3.6 (2.3)
months
Thyrotoxic Periodic Paralysis• Age 20-40 y; Men > Women; Asian> Western
• Presentation: recurrent, transient episodes of muscle weakness, mild to complete flaccid paralysis; proximal >distal
• Triggers: carbohydrates, alcohol, exercise
• Biochemical evidence of hyperthyroidism (Graves Disease being the most common) and hypokalemia (may be normal if during the recovery phase), and other electrolytes (Ph, Mg) imbalance
• Etiology: Increased Na/K-ATPase pump activity and number
• Treatment: K replacement and definitive treatment of thyroid disease
Kung JCEM 2006
Outline
• Thyroid hormones and the musculo-skeletal system
• Thyroid Myopathy
• Thyroid Arthropathy and Acropachy
• Osteoporosis • Subclinical and clinical thyroid disease
• Subacute thyroiditis
• Take home messages
Thyroid and Joint Disease
• Carpal tunnel syndrome
• Arthralgia and joint effusion
• Crystal deposition
• Thyroid Acropachy
Hypothyroidism and Carpal Tunnel
Shiri Muscle Nerve 2014
Carpal Tunnel diagnosed by nerve conduction assessment in the majority of the studies
Hypothyroid Arthropathy
• Predilection for epiphyseal involvement in hypothyroid individuals with secondary skeletal abnormalities (femoral head, tibial plateau, or digital phalanges)
• Characteristics of arthropathy:
• Non-inflammatory effusion
• Elevated synovial fluid viscosity
• Knee, hand, and wrist involvement
McLean Sem Arth Rheuma 1995
Hypothyroid Arthropathy
• Several bone and joint abnormalities have been described in hypothyroid patients:• Epiphyseal dysgenesis • Slipped capital femoral epiphysis• Aseptic necrosis • Erosive osteoarthritis• Gout and Pseudogout (to follow)
• Thyroid hormone replacement leads to clinical and a dramatic radiographic improvement
McLean Sem Arth Rheuma 1995
Hypothyroidism and Chondrocalcinosis
McLean Sem Arth Rheuma 1992
Few small studies assessed this associationAll had low power Problems in design (selection and assessment of the control group)
CC: chondrocalcinosis, PA: pyrophosphate arthropathy (PA)
Hypothyroidism and Gout
Study Results
Singh 2018Medicare database N = 1,572,874
Gout VS controls: HR of incident hypothyroidism 1.76 (1.72, 1.80)*
Bruderer 2017UK-based Clinical Practice Research DatalinkN=136,318
Hypothyroid VS euthyroid**:OR of gout 1.12 (95% CI 1.05–1.20)
LT4 replacement VS no replacement**:OR of gout 1.54 (95% CI 1.24–1.92)
No significant association with hyperthyroidism
Might be explained by the fact that thyroid hormones influence serum urate levels through regulation of GFR. Hypothyroidism whose kidney function was normal should not be at an increased risk of developing incident gout, although not confirmed in sub-group analysis
*adjusted for medications and co-morbidities; ** adjusted for BMI, smoking, alcohol, co-morbidities
Thyroid Acropachy
• Thyroid acropachy is one of the extrathyroidal manifestations of autoimmune thyroid disease, Graves Disease.
• Ophthalmopathy is almost always present with dermopathy.
• Acropachy is present in extreme forms of dermopathy and may present with clubbing and swelling of the fingers and toes, with or without periosteal reaction of the distal bones; more rarely, acropachy may present with articular manifestation of distal joints
Gul Arthritis Rheumatol 2016 Fatourechi JCEM 2002
Thyroid Acropachy• In a series of 40 patients with thyroid dermopathy associated with acropachy
Fatourechi JCEM 2002
Strong association with smoking
No specific treatment for acropachy of thyroid.Immunosuppressive therapy are directed at associated ophthalmopathy and dermopathy.
Outline
• Thyroid hormones and the musculo-skeletal system
• Thyroid Myopathy
• Thyroid Arthropathy and Acropachy
• Osteoporosis • Subclinical and clinical thyroid disease
• Subacute thyroiditis
• Take home messages
Hypothyroidism and Bone Health
• Hypothyroidism per se is unlikely to be related to fracture risk, whereas long term supraphysiological replacement with thyroid hormones may result in an increased risk of fracture
• Subclinical hypothyroidism and fracture/BMD: No association
Bassett Endocr Rev 2013
Effect of excess thyroid hormones on bone
• Hyperthyroidism shortens the bone remodeling cycle
a high bone turnover state with increased bone resorption and formation rates (favoring more the former)
• The frequency of initiation of bone remodeling is also increased.
• The duration of bone formation and mineralization is reduced to a greater extent than the duration of bone resorption.
• This leads to reduced bone mineralization, a net 10% loss of bone per remodeling cycle, and osteoporosis
Bassett Endocr Rev 2013
Subclinical hyperthyroidism and BMD
Individual participant data analysis systematic review
5,458 individuals (median age 72 years, 49.1% women), median follow-up of 6.7 years
Studies quality good to excellent
PROSPERO CRD42015019814; Segna JAMA Int Med 2018
Data adjusted for age, sex, body mass index (BMI), diabetes mellitus, smoking, and menopausal status.
Site N (SH/NL) Annualized %Δ BMD, vs euthyroid
Femoral Neck
283/4700 −0.18 (−0.34; −0.02) I2 0.0%
Total hip 232/4122 Non significant
Lumbar spine 163/2974 Non significant
Subclinical hyperthyroidism and BMD
Individual participant data analysis systematic review
5,458 individuals (median age 72 years, 49.1% women), median follow-up of 6.7 years
Shyper 5%
PROSPERO CRD42015019814; Segna JAMA Int Med 2018
Data adjusted for age, sex, body mass index (BMI), diabetes mellitus, smoking, and menopausal status.
Site N (SH/NL) Annualized %Δ BMD, vs euthyroid
Femoral Neck 283/4700 −0.18 (−0.34; −0.02) I2 0.0%
TSH < 0.1 54/4700 −0.59 (−0.99; −0.19) I2 0.0%
Exclusion of thyroid and bone active agents
184/3348 −0.36(−0.71; <−0.01) I2 45.9%
Age > 75 years - −0.34 (−0.52, −0.16)
In euthyroid, FN % %Δ BMD per year -0.59 (-0.63; -0.54)No effect of subclinical hypothyroidism on BMD
Subclinical hyperthyroidism and fracture
Individual particiapntsdata of 13 prospective cohorts
70 298 participants (median age 64 years; 61.3% women), a median follow-up of 12.1 years
Shyper 3%
Majority of studies were good quality
Data adjusted for age and sexSub-group analyses: trend for higher risk in men; no interaction with ageSensitivity analysis: Endogenous hyperthyroidism higher risk of hip, any and non-spine fracture No effect of subclinical hypothyroidism on fracture risk
Fracture Site N (SH/NL) HR, vs euthyroid
Hip 2082/56471 1.36 (1.13–1.64)6.0 vs 4.9 per 1000 person-years
Any fx 888/25901 1.28 (95% CI, 1.06–1.53)14.4 vs 11.2 per 1000 person-years)
Non spine fx 946/21722 Non significant
Spine fx 732/20328 Non significant
Blum JAMA 2015
TSH suppression for thyroid cancer and bone
Uzzan JCEM 1996
These results replicate findings from a previous systematic review and meta-analysis Faber et al 1994 showing that the effect of TSH suppression during LT4 treatment affects only BMD in postmenopausal women
Hyperthyroidism and Osteoporosis
Systematic review and meta-analysisSearch until 200220 studies on BMD and 5 on fxGraves or toxic adenoma; All agesTreated medically or with radioactive iodine
Z-score comparing hyperthyroid to controlsFor the treated group, time since diagnosis 5-7 years Vestergaard Thyroid 2003
Hyperthyroidism and Osteoporosis
Systematic review and meta-analysisSearch until 200220 studies on BMD and 5 on fxGraves or toxic adenoma; All agesTreated medically or with radioactive iodine
Z-score comparing hyperthyroid to controlsFor the treated group, time since diagnosis 5-7 years
Lumbar spine
Vestergaard Thyroid 2003
Hyperthyroidism and OsteoporosisSystematic review and meta-analysisSearch until 200220 studies on BMD and 5 on fxGraves or toxic adenoma; All agesTreated medically or with radioactive iodine
Z-score comparing hyperthyroid to controlsFor the treated group, time since diagnosis 5-7 years Vestergaard Thyroid 2003
Hyperthyroidism and Osteoporosis
Systematic review and meta-analysisSearch until 200220 studies on BMD and 5 on fxGraves or toxic adenoma; All agesTreated medically or with radioactive iodine
Z-score comparing hyperthyroid to controlsFor the treated group, time since diagnosis 5-7 years
Hip fracture
Vestergaard Thyroid 2003
Effect of treatment of hyperthyroidism on bone health
• Case-control study from Denmark
• 124,655 with a fracture, matched for age and gender to 373,962 form the general population
Effect of surgery limited by the very small sample size (0.2% of the population) Vestergaard Calcif Tissue Int 2005
Outline
• Thyroid hormones and the musculo-skeletal system
• Thyroid Myopathy
• Thyroid Arthropathy and Acropachy
• Osteoporosis • Subclinical and clinical thyroid disease
• Subacute thyroiditis
• Take home messages
Thyroiditis Induced by Anti-rheumatic Drugs
Drug Case reports
Infliximab Ankylosing spondylitis (1 case)
Etanercept RA (2 cases); Juvenile idiopathic arthritis (1 case)
Adalimumab RA (1 case); Psoriatic arthritis (2 cases)
Rituximab Psoriatic arthritis (1 case)
www.PubMed.com (Sept 2019)
? Drug effect or viral thyroiditis with TNF- α inhibitors? Genetic predisposition Some describe drug withdrawal when thyroiditis was developed
Outline
• Thyroid hormones and the musculo-skeletal system
• Thyroid Myopathy
• Thyroid Arthropathy and Acropachy
• Osteoporosis • Subclinical and clinical thyroid disease
• Subacute thyroiditis
• Take home messages
Take home messages …
• Thyroid hormones have direct effects on the musculo-skeletal system.
• Hypothyroid myopathy is common and has a heterogeneous presentation.
• Thyroid hormone replacement drops CK levels but muscle symptoms may take up to 6 months.
• Thyroid dysfunction (deficiency or excess) can manifest as joint disease.
• Subclinical and clinical hyperthyroidism results in bone loss and increased fracture risk (hip and all fracture); Risk increases with age.
• Screening with TSH is recommended in patients with hyperthyroidism
• Cases of sub-acute thyroiditis have been reported on disease modifying anti-rheumatic drugs.