Hypothyroidism PDF

Hypothyroidism Hypothyroidism Thyroid Gland Underac0ve thyroid o Endocrine 0ssue that wraps around the front of the trachea Low T3, T4 o Largest endocrine gland High TSH o Consists of two lateral lobes connected by a median 0ssue mass (isthmus) § T3 Triiodothyronine (most ac0ve thyroid hormone) § T4...

Hypothyroidism Hypothyroidism Thyroid Gland Underac0ve thyroid o Endocrine 0ssue that wraps around the front of the trachea Low T3, T4 o Largest endocrine gland High TSH o Consists of two lateral lobes connected by a median 0ssue mass (isthmus) § T3 Triiodothyronine (most ac0ve thyroid hormone) § T4 Thyroxine § Calcitonin (decrease amount of calcium in the blood, when too high) o Gland consists of groups of thyroid follicles surrounded by connec,ve ,ssue capsules o Follicles are composed of a space, filled with the glycoprotein colloid, enclosed by a layer of follicular cells § First layer is the follicular cells, with the inner layer being the colloid § Colloid synthesizes the hormone § Follicular cells secrete thyroid hormone into blood § Parafollicular cells (C cells) secrete calcitonin Thyroid Hormone Synthesis Hypothalamus ini0ates synthesis of hormone Releases TRH (Thyrotropin releasing hormone) TRH to pituitary gland via pituitary stalk (blood) Anterior Pituitary releases TSH (Thyroid s0mula0ng hormone) TSH goes to Thyroid TSH binds to receptor of thyroid follicular cells In the follicular cell: o Thyroglobulin ac/vity § Thyroglobulin made in ER of follicular cell § Thyroglobulin sent from follicular cell to colloid via exocytosis o Iodide ac/vity § Iodine (exists in body as Iodide via liver conversion) § Follicular cells have high iodide stored but prefer iodide in blood — Na enters follicular cell from blood (ac,ve facilitated diffusion) — Energy of Na entering allows iodide to enter via “Sodium-Iodide Symporter” § Iodide in follicular cell enters colloid via Pendrin channel In the Colloid: What are the two func.ons of follicular cells? o TPO (thyroid peroxidase) oxidizes iodide to iodine -ER makes thyroglobulin o 2 func0ons of TPO: -Store iodide and take up iodide from blood § Oxida0on of iodide to iodine § Coupling of Iodine to thyroglobulin What is the basic unit of thyroid hormone? — 3 iodine = T3 -Tyrosine — 4 Iodine = T4 -Tyrosine allows iodine and thyroglobulin to When the body needs thyroid hormone: bind via TPO Follicular cells will release T3/T4 o T3/T4 enters follicular cell via endocytosis from colloid What are the two func.ons of TPO? o T3/T4 structure is broken via lysosomal enzyme, creates Free T3, Free T4 -oxida.on of iodide to iodine o Will leave follicle cell and enter bloodstream thru MCT channel -coupling iodine w/ thyroglobulin Hypothyroidism 2 classifica0ons (Primary and Secondary) Primary: destruc0on of thyroid and Iodine deficiency Secondary: dysfunc0on of hypothalamus and/or pituitary gland Follicular cells make thyroglobulin in the ER, then exocytosed into colloid o Combined with iodine, thyroglobulin produces thyroid hormones T3 and T4 o Primary hypothyroidism → NO THYROGLOBULIN bc destruc0on of thyroid follicles → inadequate produc0on of thyroid hormones Iodine deficiency is the most common cause of hypothyroidism due to low intake of iodine (esp third world countries) Primary hypothyroidism → low T3 and T4 with very high TSH low T3 and T4 signals hypothalamus to increase TSH What is the most common hypothyroidism: Primary Primary Hypothyroidism 3 main causes of thyroid destruc,on: o Autoimmune thyroid destruc0on (Thyroidi,s) o Infec0ous thyroid destruc0on o Iatrogenic thyroid destruc0on Autoimmune Thyroid Destruc2on (Hashimoto, Postpartum, Riedel’s) Hashimoto’s Thyroidi0s o Most common cause of hypothyroidism in the US o An0bodies against thyroglobulin (an,-TG) and Thyroid peroxidase (an,-TPO) o An0bodies (+) in Hashimoto’s o HLA DR-3 and HLA DR-4 gene muta0ons alters immune func0on resul0ng in an0bodies o Progressive deple0on of thyroid epithelial cells due to auto immune destruc0on § CD8+ cytotoxic T cell mediated process § Cytokine-mediated process by CD4 § An,-thyroid an,body dependent cell-mediated cytotoxicity § Will lead to destruc0on of follicular cells o Gross: Hashimoto thyroid will be pale tan (normal is dark red/brown) o Histologic: lymphocy0c infiltrate, oncocy0c change of follicular epithelium Postpartum Thyroidi0s o Occur postpartum within or < 1 year of child birth o An0bodies against Thyroid peroxidase (an,-TPO) only o An0bodies (+) in postpartum o Not permanent, thyroid follicle cells regenerate o Known as TRANSIENT hypothyroidism (Hashimoto is a permanent destruc.on) Riedel’s Thyroidi0s o Known as IgG4 systemic diseases o IgG4 an0body produc0on o Characterized by developing fibro,c ,ssues at the thyroid gland § ~ 30% can have hypothyroidism o IgG4 an0bodies can be present in other systemic dz: § Autoimmune pancrea00s § Aor00s § Retroperitoneal fibrosis o Fibrosis of the thyroid gland causes compression of nearby structures such as recurrent laryngeal nerve (hoarseness), trachea (stridor) and esophagus (esophageal dysphagia- fluid cannot move in and out) Infec2ous Thyroid Destruc2on DeQuervain’s Theory o Rare, not common o Viral upper respiratory tract infec0on o Symptoms: Low grade fever, muscle aches, painful joints, runny nose, conges0on and sore throat o Painful thyroid Goiter o Along with elevated erythrocyte sedimenta0on rate (ESR) § RBC sink faster = High inflamma0on o Known as TRANSIENT hypothyroidism Iatrogenic Thyroid Destruc2on Thyroidectomy o Recent thyroid surgery o NO PRODUCTION of thyroid hormones o Clear scar in the neck Wolff-Chaikoff Effect o Caused by large inges,on of iodine § Intake of long term amiodaron § Undergoing radio-iodine therapy o Large amount of iodine inhibit TPO o No conversion of thyroglobulin into thyroid hormones → hypothyroidism o NOT due to thyroid destruc0on, instead it is due to large inges0on of iodine Secondary Hypothyroidism Dysfunc,onal hypothalamus and/or pituitary gland o CANNOT produce TRH, and/or TSH o No s0mula0on to TSH receptor on thyroid follicle cells o Low produc,on of thyroid hormones Secondary hypothyroidism → low T3 ,T4 and low TSH (important for diagnosis) Pituitary dysfunc0on: o Pituitary adenoma o Sheehan Syndrome Pituitary Adenoma Macroadenoma: large tumor on pituitary gland Pathophysiology: o TRH is produced by the hypothalamus o TRH is supposed to run through the hypophyseal portal system o Presence of tumor: Blood vessel compressed, signal of TRH can’t reach pituitary and can't trigger to make TSH o Low TSH produc,on Mass effect causes o Intercranial headache o Bitemporal hemianopia § Loss of vision on outer half of eye (par0al blindness) § Tumor right over op0c chiasm (bc pituitary gland located in between) Sheehan Syndrome Postpartum hypopituitarism due to necrosis of the pituitary gland Caused by massive hemorrhage during or aWer delivery (> 1 L within 24 hours) Pathophysiology: o Blood loss causes severe hypovolemia, leading to decreased blood pressure o Reduced perfusion to various 0ssues, including pituitary gland (hypopituitarism) § Necrosis of Pituitary gland § Reduc,on of TSH and other important hormones