Thyroid Gland Physiology
The microscopic structure of a mammalian thyroid gland consists of :
1. Follicular cells that form spherical structure (follicles) that store the thyroid hormones. The stored hormones have a homogenous microscopic appearance that is called colloid (Figure_1). The follicular cells are involved in the synthesis, storage and release of thyroid hormones.
2. Parafollicular cells that are located near the follicles and secrete calcitonin (Figure_2)
There is a classic “feedback” loop mechanism whereby levothyroxine (T4) and triiodothyronine (T3) regulate pituitary synthesis and release of thyrotropin, a thyroid-stimulating hormone (TSH) (Figure_3)
T4 and T3 are synthesized by the thyroid gland in response to TSH (Figure_4).
The thyroid gland primarily secretes T4 ( ~ 85%), which is converted to T3 in the liver, kidney, and skeletal muscle. The heart lacks the enzymes that convert T4 to T3, and T3 is transported into the myocyte. T3 exerts its cellular actions through binding to thyroid hormone nuclear receptors.
Thyroid hormone effects on the heart and peripheral vasculature include decreased SVR and increased resting heart rate, left ventricular contractility, and blood volume (Figure_5).
Thyroid Hormones & Normal ECG
Variation in thyroid hormone levels in the general population, even within the normal range, are associated with various ECG changes e.g. a positive linear association between serum total T4 level and heart rate in men, and a U-shape association between T4 and PR interval in men and women. TSH level was positively associated with QRS interval in men, while a U-shape association between TSH and QRS was observed in women.
What is meant by the terms thyrotoxicosis and hyperthyroidism?
Thyrotoxicosis is a hyper-metabolic state caused by elevated circulating levels of free T3 and T4. Thyrotoxicosis can be subclinical, clinical or extreme ("thyroid storm").
Because the most common cause is hyper-function of the thyroid gland, the terms thyrotoxicosis and hyperthyroidism are often used interchangeably. However thyrotoxicosis can be due to excessive release of preformed thyroid hormone (e.g. in thyroiditis) or excessive thyroid hormone production by a extra-thyroidal source.
The causes of thyrotoxicosis are:
Hyper-function of the thyroid gland associated with:
- Diffuse hyperplasia of the thyroid caused by Graves disease (accounts for 85% of cases)
- Multi-nodular goitre
- Adenoma of the thyroid
- Increased release of thyroid hormone from a inflamed thyroid gland
- Pituitary adenomas that secrete TSH
- Thyroxine medication
- Ovarian teratoma that secretes thyroid hormone
Graves disease (diffuse toxic goitre) is an autoimmune disease in which autoantibodies against the thyroid-stimulating hormone receptors inappropriately stimulate the thyroid gland with ensuing excessive production and release of thyroid hormones. Graves disease is associated with various autoimmune diseases such as pernicious anemia, vitiligo, type 1 diabetes mellitus, autoimmune adrenal insufficiency, systemic sclerosis, myasthenia gravis, Sjögren syndrome, rheumatoid arthritis, and systemic lupus erythematosus
Thyroid storm is a rare and potentially fatal complication of hyperthyroidism. It typically occurs in patients with untreated or partially treated thyrotoxicosis who experience a precipitating event such as surgery, infection, or trauma. Patients typically appear markedly hyper-metabolic with high fevers, tachycardia, nausea and vomiting, tremulousness, agitation, and psychosis. It is a clinical diagnosis, and several scoring systems have been devised to help with the diagnosis
Hyperthyroidism and the Heart
- Exercise intolerance (muscle weakness ± inability to increase heart rate and ejection fraction)
- Exertional dyspnoea
- Anginal chest pain
- Increased resting heart rate
- Increased cardiac output
- Increased myocardial oxygen demand
- Decreased systemic vascular resistances
- Systolic hypertension
- Peripheral oedema
- Congestive cardiac failure (This seems paradoxical given the increased cardiac contractility and increased cardiac output)
- Graves’ and Hashimoto’s diseases may be associated with an increased prevalence of mitral valve prolapse
- Angina (can develop in persons with with normal coronary arteries)
- Coronary artery vasospasm
- Left ventricular hypertrophy
- Pulmonary hypertension
- ? Association with Moyamoya disease (anatomic occlusion of the terminal portions of internal carotid arteries, usually occurring in in Asian women)
ECG Changes in Hyperthyroidism
- Sinus tachycardia
- Increased amplitude of P wave and T wave
- Prolonged PR interval
- Shortened QT interval
- The prevalence of AF in hyperthyroidism is 7-8 %, which increases with age to a peak of ~ 15 % in persons 70 years or older. Subclinical (mild) hyperthyroidism carries the same relative risk for atrial fibrillation as does overt disease
- In unselected patients with atrial fibrillation the incidence of thyrotoxicosis is less than 1 %.
- In patients with hyperthyroidism advancing age rather than the presence of atrial fibrillation is the main risk factor for systemic or cerebral embolism
- ST segment elevation with normal coronary angiography
- Atrioventricular block
Thyrotoxicosis and Fat Freddy's Cat (FFC)
FFC is a maniacal cat who was part of the world of the Fabulous Furry Freak Brothers, an alternative culture comic drawn by Gilbert Sheldon in the 1960s and 1970s.
First described in 1980, feline hyperthyroidism is currently the most frequently diagnosed feline endocrinopathy, with a prevalence of 2% across cats of all ages.
Hypothyroidism and the Heart
ECG Changes in Hypothyroidism
- Sinus bradycardia
- T wave flattening
- T wave inversion
- ST segment depression
- Low QRS voltages
- QTc is usually normal but may be prolonged. There are case reportsof torsades de pointes in persons with hypothyroidism and prolonged QTc interval
- Ventricular late potentials (a risk factor for ventricular arrhythmia) have been observed on signal-averaged ECG
- Accelerated atherosclerosis
- Increased risk of coronary artery disease
- Ventricular septal hypertrophy
- Diastolic hypertension
- Increased systemic vascular resistance
- Impaired cardiac contractility
- Diastolic dysfunction
- Decreased cardiac output
In older patients with hypothyroidism the principles of treatment are to start low (dose) and go slow (only increase the dose every 6 to 8 weeks). Concerns that restoration of the heart to a euthyroid state might adversely affect underlying ischaemic heart disease are largely unfounded.
About 30% of patients with congestive heart failure have low T3 levels. The decrease in serum T3 is proportional to the severity of the heart disease. The low T3 syndrome is defined as a fall in serum T3 accompanied by normal serum T4 and TSH levels, and the syndrome results from impaired hepatic conversion of T4 to the biologically active hormone, T3. The heart is relatively deficient in the presence of enzymes that convert T4 to T3.
Hypothyroidism is the most commonly diagnosed endocrinopathy in dogs.
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