Week 2

 is the biggest gland in the neck. It is situated in the anterior (front) neck below the skin and muscle layers.  gland takes the shape of a butterfly with the two wings being represented by the left and right thyroid lobes which wrap around the trachea.  sole function of the thyroid is to make thyroid hormone. The function of the thyroid therefore is to regulate the body’s metabolism.

 The function of the thyroid gland is to take iodine, found in many foods, and convert it into thyroid hormones: thyroxine (T4) and triiodothyronine (T3).  These cells combine iodine and the amino acid tyrosine to make T3 and T4. T3 and T4 are then released into the blood stream and are transported throughout the body where they control metabolism (conversion of oxygen and calories to energy).

 Energy metabolism – Oxygen/Heat  Carbohydrate metabolism  Protein metabolism  Lipid Metabolism  Cardiovascular- increases heart rate, output, systolic volume and contractility  Beta adrenergic effects  Bone growth  GI tract motility  Erythropoietin production

The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology.  TSH, acting through the TSH receptor, is the major stimulator of thyroid cell growth, differentiation and function. Thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily that exhibit a dual role as activators or repressors of gene transcription in response to thyroid hormone (T3).

Modulate various physiological functions in many organ systems. The TRα and TRβ isoforms and TRα1 and TRβ1 isoforms. Have genomic or non-genomic effects  Genomic signaling pathway directly influences gene transcription and translation  Non-genomic pathway involves more rapid, cellular changes, some of which also regulate gene expression through more indirect signaling.

Hypothalamus: Thyrotropin- releasing hormone (TRH)  control of thyroid stimulating hormone (TSH) Pituitary: Thyroid stimulating hormone (TSH)  controls production of the thyroid hormones by binding to TSH receptors located on cells in the thyroid gland. Thyroid: triiodothyronine (T3) and thyroxine (T4)

The major serum thyroid hormone- binding proteins are: -Thyroxine-binding globulin [TBG or thyropexin],  binds thyroid hormones in circulation Transthyretin  a transport protein in the serum and cerebrospinal fluid that carries the thyroid hormone thyroxine (T4) Albumin (HAS, human serum albumin)

 Is under the control of the pituitary gland, a small gland the size of a peanut at the base of the brain.  When the level of thyroid hormones (T3 & T4) drops too low, the hypothalamus is part of the brain and produces TSH Releasing Hormone (TRH) which tells the pituitary gland to stimulate the thyroid gland (release TSH).  The pituitary gland produces Thyroid Stimulating Hormone (TSH) which stimulates the thyroid gland by binding to the TSH receptors to produce more hormones.  The pituitary senses this and responds by decreasing its TSH production.

Thyroid peroxidase antibodies (TPO). These antibodies can be a sign of:  Hashimoto disease, also known as Hashimoto thyroiditis.  This is an autoimmune disease and the most common cause of hypothyroidism. Hypothyroidism is a condition in which the thyroid doesn’t make enough thyroid hormones.  Graves’ disease.  This is also an autoimmune disease and the most common cause of hyperthyroidism. Hyperthyroidism is a condition in which the thyroid makes too much of certain thyroid hormones. Thyroglobulin antibodies (Tg).  These antibodies can also be a sign of Hashimoto disease. Most people with Hashimoto disease have high levels of both Tg and TPO antibodies. Thyroid-stimulating hormone (TSH) receptor.  These antibodies can be a sign of Grave’s disease.

• Those concerning the production of hormone (too much, or too little), • Those due to increased growth of the thyroid causing compression of important neck structures or simply appearing as a mass in the neck, • The formation of nodules or lumps within the thyroid which are worrisome for the presence of thyroid cancer, and • Those which are cancerous.

Measurement of serum thyroid-stimulating hormone (TSH): Measuring serum TSH is the best way to determine thyroid dysfunction Direct measurement of free T4 and T3: Since free thyroid hormones are available to peripheral tissues, directly measuring serum free hormones avoids the pitfalls of interpreting total levels, which are influenced by the level of the binding proteins. Thus, serum free levels more accurately diagnose true thyroid function. Measurement of thyroid autoantibodies:  Autoantibodies to thyroid peroxidase and, less commonly, to thyroglobulin are present in almost all patient’s thyroid autoimmune disease,  Thyroid peroxidase autoantibodies are usually detected in patients with Graves’ disease.  Both these antibodies are commonly measured by enzyme immunoassays Measurement of thyroglobulin:  The principle use of serum thyroglobulin is mostly used as a tumour marker test to help guide thyroid cancer treatment

There are 3 types of hypothyroidism:  Primary hypothyroidism – when your thyroid gland becomes diseased and cannot produce sufficient hormones  Subclinical hypothyroidism- early and mild form of hypothyroidism  Secondary hypothyroidism – when your pituitary gland isn’t stimulating your thyroid to produce enough hormones.

Hashimoto’s thyroiditis-most common (most common)  Iodine deficiency  Drug therapy

Non-specific. May be confused with other conditions especially in postpartum depression and elderly.  Fatigue.  Increased sensitivity to cold.  Constipation.  Dry skin.  Weight gain.  Puffy face.  Hoarseness.  Muscle weakness.

Autoantibodies: Thyroid autoantibodies are antibodies that develop when a person’s immune system mistakenly targets components of the thyroid gland or thyroid proteins, leading to chronic inflammation of the thyroid  Anti thyroid peroxidase [anti microsomal] antibodies  Anti thyroglobulin antibodies.  Anti bodies against T3 and T4 in auto immune hypothyroid disease.

Chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Diagnosis involves demonstration of high titers of thyroid peroxidase antibodies.  Diagnosis  High TSH with low Free T4/T3  High Thyroid autoantibodies

 An early, mild form of hypothyroidism, a condition in which the body doesn’t produce enough thyroid hormones.  It’s called subclinical because only the serum level of thyroid-stimulating hormone from the front of the pituitary gland is a little bit above normal. Diagnosis  Elevated TSH and Normal T4/T3 level

Diagnosis  Low levels of T4/T3 with high level of TRH

Is a specific, rare form of hypothyroid myopathy, which causes proximal weakness and pseudohypertrophy of muscles.

Primary hypothyroidism (elevated TSH and low Free T4 level) Subclinical hypothyroidism (elevated TSH and normal Free T4 level) Secondary hypothyroidism (normal or low TSH and low Free T4 level)

 Levothyroxine can cause increases in resting heart rate and blood pressure  So replacement should start at low doses in older and patients at risk for cardiovascular compromise

 Younger patients can be started at target dose usually 0.075 mg/day  Start low and go slow in elderly and high-risk patients, usually 0.025 mg/day

“Hyperthyroidism” refers to overactivity of the thyroid gland leading to excessive synthesis of thyroid hormones and accelerated metabolism in the peripheral tissues.

 Unintentional weight loss, even when your appetite and food intake stay the same or increase  Rapid heartbeat (tachycardia) — commonly more than 100 beats a minute  Irregular heartbeat (arrhythmia)  Pounding of your heart (palpitations)  Increased appetite  Nervousness, anxiety and irritability