Thyroid tissue is made up of colloid, which includes iodinated thyroglobulin. Thyroglobulin is a big molecule that is synthesized by the surrounding follicular cells and from which thyroxine is produced and processed in colloid. Thyroid neuroendocrine cells (parafollicular or C cells) release calcitonin, a physiologically active peptide, and are situated between the follicular cells. Calcitonin can be utilized to diagnose medullary thyroid carcinoma as a biomarker.
Thyroid hormones play a significant influence in metabolic activities. Thyroxine (T4) and triiodothyronine (T3) are made from the amino acid tyrosine. T4 is the most common circulating hormone, which is converted to T3 in the peripheral nervous system, which is more potent and has a shorter half-life. The proteins thyroxine binding globulin (TBG), transthyretin, and albumin in the circulation are strongly associated with thyroid hormones. Thyroid receptors (TR) in the cell only bind to the free hormone. Thyroid receptors are divided into two types (TRα and TRβ), each of which is expressed differently in various organs. TR mutations induce thyroid hormone resistance, which is a rare condition. A set of activating and deactivating enzymes govern the local activity of thyroid hormones on tissues (de-iodinase enzymes; DIO 1, 2 and 3).
Interpreting thyroid function tests
The key to correctly interpreting thyroid findings is to comprehend the feedback axis. A classic negative feedback system exists in the thyroid gland. Thyrotropin Releasing Hormone (TRH) increases pituitary TSH secretion, which activates T3 and T4 secretion by G-protein coupled receptors in the thyroid. TRα and TRβ are responsible for T3 and T4’s peripheral effects. Since thyroid hormones have very little circadian rhythmicity and are not pulsatile, basal levels are adequate for interpretation and dynamic tests are not needed.
Thyroid disorder, which is also autoimmune in nature, causes primary hypothyroidism. Reduced circulating T3 and T4 levels, as well as a compensatory increase in TSH, characterize this condition. Secondary hypothyroidism is distinguished by low T3/T4 levels and non-elevated TSH – sometimes TSH is normal rather than low – which is triggered by TSH deficiency, which is normally caused by pituitary disease.
The most common causes are thyroid antibodies, lymphocytic infiltration, fibrosis, and atrophy, as well as gland enlargement with goitre (Hashimoto’s thyroiditis). Pregnancy may cause acute or chronic hypothyroidism after birth, which may be misdiagnosed as postpartum depression (post-partum thyroiditis). In developing nations, iodine deficiency is a preventable cause of neonatal hypothyroidism, which causes severe mental retardation (cretinism). A unusual genetic mutation in thyroid hormone synthesis can trigger hypothyroidism in children (familial thyroid dyshormonogenesis). Hypothyroidism is caused by two drugs: amiodarone and lithium. Iatrogenic hypothyroidism is caused by the intentional treatment of thyroid disease (e.g. surgery, RAI) or the inadvertent disturbance of thyroid activity caused by radiation to the head and neck region.
TSH dysfunction caused by hypothalamic–pituitary disease causes secondary hypothyroidism, which is far less frequent than primary hypothyroidism. Low fT4 and non-elevated TSH are signs of secondary hypothyroidism, which may warrant a thorough examination of the pituitary gland.
A typical fT4 with an elevated TSH is referred to as subclinical hypothyroidism. If patients are asymptomatic, therapy may not be necessary; 10–15 percent of patients’ thyroid function returns to normal after repeat monitoring. Because of the high risk of progression to frank hypothyroidism, guidelines prescribe beginning thyroxine even though patients are asymptomatic if TSH is >10 mIU/L. Treatment can also be considered in women considering birth, on a trial basis in symptomatic patients, and in patients with severe dyslipidaemia at lower levels of TSH elevation (TSH 5–10 mIU/L). Patients with healthy thyroid antibodies should have a TFT every year and make sure they don’t develop excessive hypothyroidism.
Increased circulating T3 and T4, as well as suppressed TSH due to negative feedback, characterize primary hyperthyroidism. Rare circumstances or assay intervention should be addressed if TSH is not inhibited in the sense of hyperthyroidism. In this case, the clinical picture is critical in determining whether Subclinical hypothyroidism exists.
The sympathetic nervous system is overactive in hyperthyroidism, resulting in a variety of symptoms. Weight loss (often accompanied with a rise of appetite), insomnia and irritability, nausea, heat aversion, palpitations, and resting tremor are all common symptoms. Pruritus, elevated bowel frequency and loose movements, menstrual discomfort, and decreased fertility are all typical hyperthyroidism symptoms.
Resting tachycardia (sinus rhythm or atrial fibrillation), warm peripheries, resting tremor, hyper-reflexia, and lid lag are all common symptoms of hyperthyroidism. Because of increased sympathetic tone in the upper eyelid, lid lag may occur in any cause of hyperthyroidism. Graves’ condition is characterized by lid retraction and proptosis. Hypertension and a flow murmur are possible symptoms of a hyperdynamic circulation. Patients with hyperthyroidism frequently appear anxious and hyperkinetic (the so-called “thyroid affect”).
Thyroid eye disorder is one of the specific clinical symptoms of Graves’ disease. Skin alterations (dermopathy) characterized by pre-tibial myxoedema, as well as nail changes similar to clubbing, are more uncommon extra-thyroidal symptoms (thyroid acropachy). Cross-reactivity with TSH receptors in the back of the orbit and on the skin causes these symptoms.
Thyroid enlargement is referred to as goitre. Graves’ disease goitres are usually flat, symmetrical, and vascular, and palpation and auscultation also reveal a rush and bruit. The vascularity of nodular goitres is lower, and dominant nodules can be clinically palpable. There may be a single nodule or several nodules.
Thyroid disease and the heart
Hyperthyroidism may manifest as a heart attack or stroke. Supraventricular tachycardia (SVT) or rapid atrial fibrillation is the most frequent acute presentation (AF). Thyrotoxic cardiomyopathy, which is more prevalent in Graves’ disease, is seen in a smaller percentage of patients. Thyroid storm is an uncommon medical emergency characterized by high-output heart dysfunction and agitation. It has a high mortality rate which necessitates a lot of treatment.
T3, T4 and TSH
Hyperthyroidism is characterized by elevated free T4 (fT4) and free T3 (fT3) levels, as well as undetectable TSH levels. T3 toxicosis is described as an increase in fT3 without a decrease in TSH. Subclinical hyperthyroidism is described by a normal fT4/fT3 ratio and a suppressed TSH, indicating autonomous thyroid function. The occurrence of elevated fT4 and fT3 in the absence of TSH suppression is rare and needs further study.
Thyroid antibodies may validate Graves’ disease, which could be clinically noticeable on inspection. Thyroid peroxidase antibodies (TPO) are autoimmune thyroid disorder non-specific markers. TSH antibody activating antibodies are more specific and can be useful in specific health conditions, such as breastfeeding, as well as confirming a Graves’ disease diagnosis.
Thyroid ultrasound (US) will help confirm nodular thyroid disorder, but it can’t tell you how active the thyroid gland is. Nuclear imaging (technetium or iodine uptake isotope scan) aids in the diagnosis of hyperthyroidism by determining the role of the thyroid gland and thus the cause of hyperthyroidism. In Graves’ disease, uptake increases uniformly, but in nodular disease, uptake increases only in the autonomous nodule (s).
Factors affecting thyroid results
Non-thyroidal disease (‘sick euthyroid syndrome’) may affect TFTs, causing central TSH suppression in most cases, but any pattern of outcomes can be observed. TFTs are better assessed in the outpatient environment, when patients are in good health, rather than during acute infection or hospitalization. Thyroid function can also be affected by medication (e.g., lithium and amiodarone) and pregnancy.
- Vargatu I. (2016). WILLIAMS TEXTBOOK OF ENDOCRINOLOGY. Acta Endocrinologica (Bucharest), 12(1), 113