AI Thyroid Hormone Physiology Review PDF

**Endocrine II** **Thyroid Hormone - Physiology Review** This excerpt explains the synthesis and function of Thyroid Hormones, primarily focusing on T3 (Triiodothyronine) and T4 (Thyroxine). - **Production:** Both T3 and T4 are produced by follicle cells within the thyroid gland. - **T4...

**Endocrine II** **Thyroid Hormone - Physiology Review** This excerpt explains the synthesis and function of Thyroid Hormones, primarily focusing on T3 (Triiodothyronine) and T4 (Thyroxine). - **Production:** Both T3 and T4 are produced by follicle cells within the thyroid gland. - **T4 Dominance:** 90% of the thyroid hormone secreted is T4. - **Half-life:** T4 has a longer half-life, meaning it stays in the body longer than T3. - **Conversion:** Although initially more abundant, T4 is gradually converted into T3 as it travels to target cells. - **Activity:** Despite being less abundant initially, T3 is the more biologically active form of thyroid hormone. This means it has a stronger effect on the body\'s metabolic processes. **Physiological Effects** - **Regulation of Transcription:** Thyroid hormones influence the production of proteins within cells. This is achieved by influencing the process of transcription, which is the first step in making proteins from DNA.  - **Stimulates Metabolism:** They increase metabolic rate, meaning they speed up the body\'s chemical reactions involved in energy production.  - **Development:** They are crucial for the normal development and function of the nervous system, particularly during the early stages of life. They also support the growth-promoting effects of growth hormone. - **Catecholamine Sensitivity:** Thyroid hormones enhance the sensitivity of cells to catecholamines, which are hormones like adrenaline and noradrenaline that regulate stress responses and other essential bodily functions. **Feedback and regulation of T3/T4** --------------------- page16image60626832 --------------------- **Negative Feedback Mechanism** ------------------------------------------  ------------------------------------------ ------------------------------------------------------------- page18image59980416 ------------------------------------------------------------- **TRH (Thyrotropin-releasing hormone):** This hormone is secreted by the hypothalamus, a region in the brain that controls many bodily functions. It triggers the release of TSH from the pituitary gland. - **TSH (Thyroid-stimulating hormone):** This hormone is produced by the anterior pituitary gland, which sits at the base of the brain. TSH acts directly on the thyroid gland, stimulating it to produce and release T3 and T4. This is a negative feedback loop. Higher levels of T3 and T4 in the bloodstream inhibit the release of TRH and TSH, thus slowing down thyroid hormone production. Conversely, when T3 and T4 levels are low, TRH and TSH secretion increases, stimulating more thyroid hormone production. This keeps thyroid hormone levels within a healthy range. **Hyperthyroidism** - **Hyperthyroidism:** This occurs when the body\'s tissues are exposed to excessive amounts of thyroid hormone. - **Etiologies:** The section then lists the possible causes (etiologies) of hyperthyroidism:  1. **Primary Hyperthyroidism** This refers to problems originating in the thyroid gland itself.  - **Genetic Predisposition:** Certain genetic mutations, especially in the TSH receptor protein, can lead to increased thyroid hormone production.  - **Thyroiditis:** Inflammation of the thyroid gland. Subacute thyroiditis is a temporary condition, while postpartum thyroiditis develops after childbirth. Silent thyroiditis often goes unnoticed. - **Toxic Nodular or Multinodular Goiter (Plummer Disease):**These are lumps or nodules in the thyroid gland that produce excess thyroid hormones. - **Thyroid Adenomas:** Benign tumors in the thyroid gland.  - **Thyroid Cancer:** Malignant growths in the thyroid gland. 2. **Secondary Hyperthyroidism** This is caused by increased TSH secretion from the anterior pituitary gland.  - **TSH-secreting pituitary adenomas:** These are tumors in the pituitary gland that produce excessive amounts of TSH, leading to increased thyroid hormone production. - **Special Cases:** These are specific examples of secondary hyperthyroidism: - **[Graves Disease:]** This is an autoimmune condition where the body produces antibodies that stimulate the thyroid gland to produce excess hormones.(70%) - **Overdose of Thyroid Medication (Thyrotoxicosis):** Taking too much thyroid hormone medication can also cause hyperthyroidism. **Pathophysiology hyperthyroidism** - **Primary hyperthyroidism:** The thyroid gland itself is overly active, leading to increased T3 and T4 production. This increased hormone levels suppress TSH production by the pituitary gland through a negative feedback mechanism. page23image60355792 - **Secondary hyperthyroidism:** An overactive pituitary gland releases excessive TSH, which then stimulates the thyroid gland to produce excess T3 and T4.  **\ ** **Clinical Consequences** **Due to increased T3/T4**: This refers to symptoms directly associated with elevated thyroid hormone levels: - **Increased metabolic rate:** The body\'s chemical reactions speed up, leading to increased energy expenditure, weight loss, and potentially heat intolerance. - **Increased neuromuscular activity:** The muscles become more active, leading to tremors, restlessness, and an overall heightened state of energy.  - **Increased SNS stimulation:** The sympathetic nervous system, which controls the \"fight or flight\" response, is stimulated. This can cause rapid heartbeat, increased blood pressure, anxiety, and sweating. **Due to increased TSH:** This is primarily related to secondary hyperthyroidism, where increased TSH from the pituitary gland can lead to: - **Goiter:** An enlarged thyroid gland, which is often associated with secondary hyperthyroidism, as the constant stimulation by elevated TSH causes the gland to grow in size. **Graves' Disease** **Secondary Hyperthyroidism** **Autoimmune** This is an autoimmune disease where the body\'s immune system [mistakenly] attacks the thyroid gland and produces antibodies called thyroid stimulating immunoglobulins (TSI). **Pathophysiology (Graves')** - **TSI Overproduction:** Instead of attacking the thyroid gland, these TSI antibodies mimic the actions of TSH, the normal hormone that stimulates thyroid hormone production. - **TSI Stimulation:** The excessive presence of TSI leads to overstimulation of the thyroid gland, resulting in increased secretion of T3 and T4.  - **TSH Suppression:** The high levels of T3 and T4 in the bloodstream feedback to inhibit the pituitary gland from producing additional TSH, resulting in suppressed TSH levels. **Clinical Consequences (Graves')** - **Problems due to hyperthyroidism:** This part reiterates the general consequences of hyperthyroidism mentioned earlier, which include increased metabolic rate, neuromuscular activity, and SNS stimulation. - **Goiter:** A goiter, or an enlarged thyroid gland, is a common feature in Graves\' disease. This is due to the continuous stimulation of the thyroid gland by **TSI**, which acts like **TSH**. - **Effects on ocular tissue:** This is a characteristic symptom of Graves\' disease, affecting about 95% of patients.  - **Degeneration of extraocular muscles:** The muscles controlling eye movement can weaken and degenerate, leading to eye strain and blurred vision. - **Edematous fluid accumulation in orbit:** Excess fluid can accumulate in the eye socket, causing protrusion of the eyeballs (exophthalmos) and other visual disturbances. **Hypothyroidism** This happens when the thyroid gland is not functioning properly, leading to low levels of T3 and T4. 1. **Primary Hypothyroidism:**  This refers to problems originating in the thyroid **[gland itself]:** **[Loss of Thyroid Tissue]:** The thyroid gland may shrink or be destroyed, making it unable to produce sufficient thyroid hormones.  - **Iodine Deficiency:** Iodine is an essential component of thyroid hormones. A lack of iodine can impair their production.  - **Congenital Lack of Thyroid Tissue:** This is a condition present at birth where the thyroid gland is underdeveloped or absent.  - **Hashimoto\'s Thyroiditis:** This is an autoimmune disease where the immune system attacks the thyroid gland, causing it to malfunction and decrease hormone production. **\ ** 2. **Secondary Hypothyroidism** **t**his refers to **problems in the pituitary gland**, which usually produces **TSH** to stimulate the thyroid gland: **Failure of Pituitary:** The pituitary gland might fail to produce enough TSH, leading to decreased thyroid hormone production. This can happen due to various reasons:  - **Stroke to Hypothalamus or Pituitary:** Damage to these brain regions can affect the pituitary gland\'s ability to produce TSH. - **Pituitary Tumor:** Benign or cancerous tumors in the pituitary gland can interfere with TSH production.  - **Postpartum Pituitary Necrosis:** Rarely, the pituitary gland can become damaged after childbirth. **Pathophysiology Hypothyroidism** **Primary Hypothyroidism** The malfunctioning thyroid gland secretes less T3 and T4. This low hormone level triggers the pituitary gland to produce more TSH in an attempt to stimulate the thyroid. However, the thyroid gland is unable to respond effectively.  page34image60619808 **Secondary Hypothyroidism:**  The pituitary gland itself is not functioning properly, producing less TSH. This leads to a chain reaction where less TSH reaches the thyroid, resulting in reduced thyroid hormone production (T3 and T4). **General** - **Myxedema:** This is a condition characterized by swelling (edema) in tissues. It occurs when collagen in connective tissues is replaced by other proteins and complex sugars (mucopolysaccharides), which hold onto water, causing swelling and fluid retention.  - **Water Retention:** The complex formed by these proteins and sugars traps water, leading to the characteristic edema seen in myxedema. **Clinical consequences** **Due to decreased T3/T4:** This refers to the symptoms directly caused by low thyroid hormone levels: - **Decreased metabolic rate:** The body's chemical reactions slow down leading to decreased energy expenditure, weight gain, and potentially cold intolerance. - **Decreased neuromuscular activity:** Muscles become less active leading to fatigue, slowness of movement, and overall decreased energy. - **Decreased SNS activity:** The sympathetic nervous system is less active, resulting in a slower heart rate, decreased blood pressure, and potential for depression. **Due to increased TSH:** This focuses on a consequence related to the pituitary gland's attempt to compensate for low thyroid hormone (T3 and T4) levels: Decreased iodine Decreased T3/T4 Increased TSH Follicle growth + accumulation of thyroglobulin - **Goiter:** An enlarged thyroid gland can occur in **primary hypothyroidism from Iodine deficiency,** specifically in cases of iodine deficiency. This happens because the thyroid gland is constantly stimulated by high TSH to try and produce more hormones, but it cannot due to the lack of iodine. **Cortisol -- Physiology Review** - **Cortisol:** This hormone is the primary glucocorticoid, meaning it mainly regulates glucose metabolism and has anti-inflammatory effects. - **Adrenal Cortex:** Cortisol is secreted by the adrenal cortex, part of the adrenal glands located near the kidneys.  The adrenal cortex also makes other important hormones like **aldosterone** (regulates blood pressure and salt balance) and **androgens** (male sex hormones). - **Survival During Stress:** Cortisol is crucial for survival during periods of extreme stress. It helps maintain blood sugar, conserve energy, and suppress the immune system.  **Physiological Effects** - **Glucose Metabolism:** Cortisol elevates blood sugar levels by decreasing glucose uptake in tissues and stimulating gluconeogenesis, the production of glucose from non-carbohydrate sources. - **Protein Metabolism:** It promotes protein breakdown in muscle and collagen, making amino acids available for gluconeogenesis.  - **Lipid Metabolism:** Cortisol stimulates fat breakdown (lipolysis) in limbs and promotes fat storage (lipogenesis) in the face and trunk. - **Immune and Inflammatory Responses:**  1. It decreases the number and activity of immune cells like T-cells, B-cells 2. It decreases the number macrophages, and neutrophils 3. reduces the release of inflammatory mediators. - **Catecholamine Responsiveness:** Cortisol can enhance the responsiveness of cells to catecholamines, like adrenaline, allowing for a more robust stress response. **Feedback and Regulation of Cortisol** ------------------------------------------  ------------------------------------------ -------------------------------------------------------------- page47image60745264 -------------------------------------------------------------- - **RH/CRF (Corticotropin-releasing hormone/factor):** This hormone is secreted by the hypothalamus, a region in the brain that controls many vital functions. It acts as a trigger for the release of ACTH from the pituitary gland.  - **Hypothalamus:** The hypothalamus acts as the control center for hormone release, responding to changes in stress levels and other signals. When stress is detected, it releases CRH/CRF, which initiates a chain of events leading to cortisol production. **ACTH, or Adrenocorticotropic hormone**: is released by the anterior pituitary gland, which is located at the base of the brain. This hormone is responsible for stimulating the adrenal cortex, which is the outer layer of the adrenal glands situated on top of the kidneys.  **Hypercortisolism** This refers to abnormally high levels of cortisol in the body. 1.**Primary Hypercortisolism (Cushing syndrome):** This occurs when the **adrenal cortex is overactive** (**[gland]**), producing too much cortisol.  - **Hyperfunction of adrenal cortex:** This indicates that the adrenal gland itself is working abnormally.  - **Ectopic cortisol production:** In some cases, the excess cortisol production might come from a tumor in a different part of the body, not the adrenal gland (ectopic). **2.Secondary Hypercortisolism (Cushing disease):** This happens when the **pituitary gland** produces too much ACTH, which in turn causes the adrenal gland to overproduce cortisol. **Etiologies (Cause)** **Primary Hypercortisolism:** - **Adrenal adenomas or carcinomas:** These are tumors in the adrenal gland. Adenomas are benign, whereas carcinomas are malignant.  - **Non-adrenal tumor:** Some tumors in other body parts can produce cortisol.  - **Cortisol-like Medications:** Long-term use of high doses of medications like hydrocortisone or prednisone can also lead to this. **Secondary Hypercortisolism:** - **Pituitary adenomas:** Tumors in the pituitary gland can cause excessive ACTH secretion.  - **Non-pituitary tumor:** Some tumors can also produce ACTH. **Pathophysiology Hypercortisolism** **1.Primary Hypercortisolism** In this type, the adrenal cortex is overactive, leading to increased cortisol production. The high cortisol then provides a negative feedback loop, suppressing the pituitary gland's production of ACTH. This means that even though the adrenal gland is overproducing cortisol, ACTH levels are usually lower in this condition. page52image60355376 **2.Secondary Hypercortisolism** This arises from an overactive pituitary gland producing excessive ACTH. This elevated ACTH stimulates the adrenal cortex to produce more cortisol and, in some cases, excess androgens. So in this type, both ACTH and cortisol levels are elevated. a. **Androgen Production:** Secondary hypercortisolism can lead to androgen production because ACTH also stimulates the production of androgens, which are male sex hormones. **Clinical consequences** **Due to Cortisol Excess** - **Hyperglycemia:** Excess cortisol promotes glucose production and decreases its uptake by cells, leading to high blood sugar levels. - **Collagen Breakdown:** Cortisol promotes protein breakdown, including collagen, which can weaken tissues and bones. - **Increased SNS Activity:** Cortisol boosts the sympathetic nervous system (SNS) activity, leading to increased heart rate, blood pressure, anxiety, and alertness. - **Immunosuppression:** Cortisol suppresses the immune system, making the body more susceptible to infections. - **Physical Body Changes:** Excess cortisol can cause weight gain, especially in the face, abdomen, and upper back, leading to a "moon-shaped" face, \"buffalo hump\" on the upper back, and central obesity. Furthermore, it can lead to thin extremities, as the cortisol promotes protein breakdown in limbs. **Due to Increased ACTH in Secondary Hypercortisolism:** **Remember secondary has androgens!** - **Hyperpigmentation of Skin:** Increased ACTH can darken the skin in certain areas, especially in areas with skin folds or creases. - **Hirsutism/Acne/Male Pattern Baldness:** Elevated ACTH can also increase androgen production, leading to excessive hair growth (hirsutism), acne, and male pattern baldness in women. **Hypocortisolism (Addison Disease)** Also known as **[adrenocortical insufficiency or Addison disease]**, this condition occurs when the adrenal cortex, the outer layer of the adrenal glands, doesn't make enough cortisol.  **Primary Hypocortisolism:**  This arises from problems directly affecting the adrenal cortex (**[gland)]** **Adrenal cortex atrophy or destruction:** The adrenal gland can shrink or be damaged, impairing its ability to produce cortisol. (decrease cortisol and aldosterone)   - **Autoimmune destruction of adrenal cortex:** The immune system can mistakenly attack the adrenal cortex, leading to its destruction.  - **Familial adrenal insufficiency:** A rare genetic condition where the body cannot properly respond to ACTH due to mutations in the ACTH receptors or defects in the ACTH signaling pathway. - **Tuberculosis:** This infection can sometimes damage the adrenal glands. **Secondary Hypocortisolism:** This arises from **[problems with the pituitary gland]**, which is responsible for producing ACTH. - **Anterior pituitary hypofunction:** The pituitary gland might not be working properly due to various reasons, including tumors, strokes, or other issues. **Special case - Suppression of ACTH:**  If someone is taking exogenous glucocorticoids (medications like prednisone), their body\'s own ACTH production is suppressed. If these **[medications are stopped abruptly]**, the adrenal glands may take some time to resume normal function, leading to temporary hypocortisolism. **Pathophysiology** **Primary Hypocortisolism**  **Secondary Hypocortisolism** This arises from an underactive pituitary gland, producing less ACTH. This leads to a chain reaction where less ACTH is produced, leading to reduced thyroid hormone production (T3 and T4). page65image60698192 **Clinical Consequences** **Due to Cortisol Deficiency:** - **Hypoglycemia:** Low cortisol levels interfere with glucose production and utilization, resulting in low blood sugar. - **Decreased SNS Activity:** Hypocortisolism affects the sympathetic nervous system (SNS), leading to decreased heart rate, blood pressure, and a general lack of energy. **Due to Aldosterone Deficiency:** - **Inability to Conserve Sodium and Water:** Aldosterone is a hormone that regulates sodium and water balance. Its deficiency leads to sodium loss and water retention, resulting in low blood pressure and dehydration. - **Impaired Renal Secretion of Potassium and Hydrogen Ions:** Aldosterone also plays a role in regulating kidney function. Low aldosterone impairs the kidney\'s ability to excrete potassium and hydrogen ions, leading to potentially dangerous electrolyte imbalances. **Due to Increased ACTH in Primary Hypocortisolism:** - **Hyperpigmentation of Skin:** While the adrenal glands are unable to produce cortisol, the pituitary gland may still produce ACTH in an attempt to stimulate them. This elevated ACTH can cause a darkening of the skin, particularly in areas exposed to sun or friction (skin folds and creases). The quote attributed to Addison (1855) describes the characteristic bronzing or darkening of the skin seen in Addison\'s disease.