- 1. Presenter : DR. A.B.M. KAMRUL HASAN MD Final Part (EM)
Bangabandhu Sheikh Mujib Medical University
2. Irwin Klein, MD; Sara Danzi, PhD Circulation.
2007;116:1725-1735 doi: 0.1161/CIRCULATIONAHA.106.678326 3.
Cellular mechanisms of thyroid hormone action Effects of thyroid
hormone on cardiovascular hemodynamics Clinical manifestations of
thyroid diseases from a cardiovascular perspective Changes in
thyroid hormone metabolism that arise from acute MI and chronic
congestive heart failure 4. Classic feedback loop mechanism: T4
& T3 regulate pituitary synthesis and release of TSH A highly
sensitive TSH assay- initial test Suggestion about narrowing TSH
reference range especially upper limit at which hypothyroidism may
be present TSH>20 mIU/L: overt hypothyroidism TSH 3-20 mIU/L:
milder or subclinical hypothyroidism Suppressed TSH 25 mmHg at rest
& >30 mmHg during exercise): Often unknown origin A link to
thyroid disease (both hyper- & hypothyroidism) has been
identified Thyroid disease should be considered in DD of Primary
pulmonary HTN 13. Fractional clearance of LDL by liver: No. of LDL
receptors LDL receptor activity Catabolism of cholesterol into bile
T3 negatively regulates liver specific enzyme cholesterol 7-
hydroxylase Overt Hypothyroidism: Hypercholesterolemia Marked LDL
& Apolipoprotein B Changes are also evident in subclinical
hypothyroidism 90% of hypothyroid patients had hypercholesterolemia
Prevalence of overt hypothyroidism in patients with
hypercholesterolemia is 1.3-2.8% 14. Palpitations Anginal chest
pain Exercise intolerance Atrial fibrillation Exertional dyspnea
Cardiac hypertrophy Systolic hypertension Peripheral edema
Hyperdynamic circulation Congestive heart failure Cardiac output
increased by 50-300% of normal: combined effect of increased
resting HR, contractility, blood volume & EF with a decrease in
SVR Cerebrovascular ischemic symptoms has been reported in young
patients with Graves disease Routine TSH in cardiac & cerebral
ischemic symptoms 15. Prevalence: 2-20%, with age (15% in patients
>70 yrs) 40,628 patients in the Danish National Registry: 8.3%
developed AF Male gender, ischemic or valvular heart disease or CHF
increased risk Subclinical hyperthyroidism carry same relative risk
In unselected patients who present with AF, 60 yrs) with AF of
longer duration less likely to revert If AF persists after chemical
euthyroidism is achieved, electrical or pharmacological
cardioversion should be attempted Majority can be restored to sinus
rhythm & will remain so for a prolonged period of time Addition
of Disopyramide (300mg/d) lets such patents to maintain sinus
rhythm 19. Paradoxical finding- ?high-output failure, does not
accurately apply Exaggerated sinus tachycardia or AF can produce LV
dysfunction & HF Preexistent ischemic or hypertensive heart
disease Mitral valve prolapse: increased incidence, causing LA
enlargement & AF High prevalence of pulmonary artery HTN: some
similar signs Exercise intolerance & Exertional dyspnea: may be
due to pulmonary compliance or respiratory & skeletal muscle
function 20. Common CV signs & symptoms are: Bradycardia Mild
hypertension (diastolic) Narrowed pulse pressure Cold intolerance
Fatigue 21. Expression of Sarcoplasmic reticulum Ca2+-ATPase
Expression of Phospholamban (inhibitor of SR Ca2+-ATPase) Slowing
of the isovolumic relaxation phase of diastolic function 22. Effect
Impaired cardiac contractility & diastolic function Increased
systemic vascular resistance Decreased endothelial derived
relaxation factor Increased serum cholesterol Increased C-reactive
protein Increased homocysteine Diastolic HTN Accelerated
atherosclerosis Increased risk of CAD Increased risk of stroke
RESULTS IN Prolongation of QT interval Ventricular arrhythmias
Protein rich pericardial and/or pleural effusion 23. Poses some
challenge In young healthy patients: full replacement dose of
L-thyroxine of 1.6 g/kg/d can be initiated at the outset In older
patients: start low (25 to 50 g/d) and go slow (increase the dose
no more rapidly than every 6 to 8 weeks) A predictable improvement
in thyroid and CV functional measures Concerns that restoration of
the heart to a euthyroid state might adversely affect underlying
ischemic heart disease are largely unfounded Patients with
atherosclerotic cardiovascular disease more often improve, rather
than worsen, with treatment 24. Low or undetectable serum TSH with
normal T4 & T3 May have no clinical signs or symptoms
Prevalence increase with age Low TSH is associated with increased
risk for CV mortality & AF Treatment is controversial Older
patients with MNG or GD: should be treated especially if they are
deemed to be at risk for cardiovascular disease 25. Affects 7-10%
of older women Frequently asymptomatic but many have symptoms of
hypo Cholesterol & CRP Risk of atherosclerosis, CAD & MI
increased The benefits of the restoration of TSH levels to normal
can be considered to outweigh the risks 26. The low T3 syndrome: a
fall in serum T3 accompanied by normal serum T4 and TSH levels
Results from impaired hepatic conversion of T4 to the biologically
active hormone, T3, by 5-monodeiodinase The cardiac myocyte has no
appreciable deiodinase activity and therefore relies on the plasma
as the source of T3 In experimental animals the low T3 syndrome
leads to the same changes in cardiac function and gene expression
as does primary hypothyroidism. Significant similarities exist
between the hypothyroid phenotype and the HF phenotype (cardiac
contractility & cardiac output, & an altered gene
expression profile) 27. 30% of patients with CHF have low T3 levels
Reduction of T3 is proportional to the severity of HF Reduced serum
T3 is a strong predictor of all-cause and CV mortality and, in
fact, is a stronger predictor than age, LV EF, or dyslipidemia It
has been suggested that T3 therapy might improve cardiac function
in this clinical situation 28. Antiarrhythmic drug with a high
iodine content (75mg iodine/200mg) Can cause either hypothyroidism
(5% to 25% of treated patients) or hyperthyroidism (2% to 10% of
treated patients) Inhibits of 5-deiodinase activity Inhibits
conversion of T4 to T3 Iodine released from amiodarone metabolism
directly inhibit thyroid gland function, if the effect persists,
lead to amiodarone-induced hypothyroidism Preexistent thyroid
disease and Hashimotos thyroiditis risk If hypothyroidism develop
with a persistent rise in TSH: L-thyroxine therapy started 29. Type
1 hyperthyroidism: iodine-induced excess thyroid hormone synthesis
underlying thyroid disorder, e.g., nodular goiter or latent GD in
regions where iodine intake is low Type 2 hyperthyroidism:
thyroiditis due to a direct cytotoxic effect of amiodarone release
of thyroid hormones transient thyrotoxicosis in a previously normal
thyroid gland Can overlap & difficult to distinguish, RIU is
low in both types Point favors Type 2 hyperthyroidism: Signs of
inflammation, elevated ESR & IL-6, modest increases in thyroid
gland size 30. ATDs effective in type 1, ineffective in type 2
thyrotoxicosis. Prednisolone is beneficial in the type 2 form Beta
blocker should be started A pragmatic approach is to commence
combination therapy with an ATD and glucocorticoid in patients with
significant thyrotoxicosis A rapid response (within 12 weeks)
usually indicates a type 2 picture and permits withdrawal of the
antithyroid therapy A slower response suggests a type 1 picture,
when antithyroid drugs may be continued and prednisolone withdrawn.
Potassium perchlorate can be used to inhibit iodine trapping in
thyroid 31. If the cardiac state allows, amiodarone should be
discontinued The course of the disease may last for anywhere
between 1 to 3 months In rare cases, surgical thyroidectomy under
local anesthesia has proven to be effective To minimize the risk of
type 1 thyrotoxicosis, thyroid function should be measured in all
patients prior to commencement of amiodarone therapy, and
amiodarone should be avoided if TSH is suppressed In general,
patients treated with amiodarone should have thyroid function
(specifically TSH) testing periodically throughout therapy 32.
Thyroid dysfunction (both hypo & hyper) virtually affects the
whole spectrum of cardiovascular hemodynamics Thyroid functional
abnormality can case a range of cardiovascular signs-symptoms and
cardiovascular diseases are also associated with derangement of
thyroid functions Restoration of normal thyroid function most often
reverses the abnormal cardiovascular hemodynamics 33. Prof. Md.
Farid Uddin Chairman, Department of Endocrinology, BSMMU Prof. M.A.
Hasanat Department of Endocrinology, BSMMU All the colleagues of my
department
