L87- Thyroid Disorders Flashcards
What cells are found in the Thyroid Gland?
Follicular (epithelial) cells - thyroid hormone synthesis
Endothelial cells
Parafollicular Cells or C- Cells = make Calcitonin
Fibroblasts
Lymphocytes
Adipocytes
Describe the Biosynthetic pathway of Thyroid Hormone Synthesis.
ACtive Uptake of Iodide –> Oxidation of I to I2
Organification of Tyr –> Conversion to MIT and DIT
MIT + DIT = T3
DITx2 = T4
Exocytosis and transport w/ TBG (T4 3x more exported than T3 so that can control w/ peripheral metabolism of T4 to T3 in tissues where you need it)
What converts Thyroxine in the periphery?
Deiodinases
D2 converts T4 to T3 as does D1 in the periphery
D3 converts T4 to rT3 (inactive) which is the direct deactivation pathway and can be seen in severe stress
Describe Thyroid Hormone action on bone, CV, Liver, Fat, Brain, and GI.
Bone: Activation of Osteoclasts
CV: Increases CO and Blood Volume; Decreases Systemic vascular resistance
Liver: Regulates lipid metabolism
Fat: Lipid storage, lipolysis, adipocyte proliferation
Brain: Stimulates Axonal growth and development
GI: Bowel irregularity
Clinical Presentation of Hypothyroidism?
Variable presentation from asymptomatic to Comatose - Myxedema Coma !!!
Hypothermia, slowed speech and movements
fatigue, weight gain, pallor, yellowing of skin, dry skin and hair loss
joint pain, Macroglossia, edema
Cold Intolerance
Decreased SBP and Increased DBP
Bradycardia and Pericardial Effusion
Hyporeflexia w/ delayed relaxation
Primary Hypothyroidism - Labs? Causes of Primary Hypothyroidism?
Labs: low or normal low T4/T3 and elevated TSH due to loss of negative feedback
Acquired Etiologies: Hashimoto’s Thyroiditis, post-Ablative, Iodine Deficiency - endemic goiter, Transient post-thyroiditis, Drug induced (amiodarone or sunitinib), or drugs block synth/release T4 (Lithium, sulfonamides, Amiodarone), Infiltrative diseasese
Congenital Etiologies: Thyroid agenesis/dysplasia, TSH receptor defects, Iodide Transport or utilization defect - Pendre’s Syndrome etc
What is Pendred’s Syndrome?
Iodide tranpsort or utilization defect (NIS or pendrin mutations) that causes Primary Hypothyroidism and Sensorineural Deafness
Hashimoto’s - who gets it? What causes it/what do you see? What are you at increased risk for? What’s it associated w/?
Autoimmune destruction of Thyroid gland w/ Lymphocytic infiltration and fibrosis
Women > ME, Familial predisposition
Thyroid Autoantibodies - TPO and Thyroglobulin Antipodies
Association/Component of APS-2
5% risk of Thryoid Cancer
What are some causes of central aka secondary Hypothyroidism? What Labs would you see? Test to determine source?
Labs: Low TSH bc pathology of Hypothal or Pituit and Low T4/T3
Acquired causes: Pituitary or hypothalamic disorders, Da problems, Bexarotene (retinoid X receptor Agonist)
Congenital Causes: TSH deficiency or receptor defect
TRH stimulation test can determine between Pituitary or Hypothalamic
Another cause of Hypothyroidism can be resistance to TH. What happens here? Manifestations?
TR-Beta gene mutation and so can’t respond to T3
Clinical Manifestations: Goiter, Tachycardia, Elevated levels of hormones - can be confused w/ TSH producing tumor
Labs: Elevated TSH and variable T3/4
What tumors can cause consumptive hypothyroidism?
Hemangiomas or Hemangioendotheliomas
- rapid destruction of thyroid hormone due to D3 over-expression in tumors to use all available thyroxine
What is Myxedema Coma? Who gets it? Precipitating Factors?
Endocrine Emergency - severe long-standing hypothyroidism leading to depressed mental state
- Occurs in old women in winter? Accompanied by Hypothermia
Precipitating Factors: Loss of adaptive mechanisms to maintain homeostasis in the face of CVA, Trauma, Infection, CNS depressants, Raw Bock Choy?, Cold
*Hypothermia can mask infection!
What are the Signs and Symptoms of Myxedema Coma?
ALTERED MENTAL STATUS - Hallmark Feature: Disorientation, paranoia, depression, hallucination
Hypothermia
Bradycardia, Heartblock, prolonged QT
Hypotension
Hyponatremia - increase ADH
Hypoventilation - Hypoxia and Hypercapnse
Seizures due to resulting hyponatremia, hypoglycemia or hypoxemia
What are labs you can get for all causes of hypothyroidism?
TSH or T4
- Total T4 = Free and Protein bound (TBG, albumin, transthyretin)
MEasurement of Thyroid Antibodies - TPO and TgAb
Thyroid Function tests in Primary vs Central Hypothyroidism vs REsistance?
Primary: Elevated TSH, Low/Normal T4/T3, TPO/TBAg positive in Hashimotos
Central: TSH Low/Normal, T4/T3 Low
TH Resistance: TSH high and T4/T3 high
TSH Normally .5-4.5
What is the goal of medical management in Hypothyroidism? How do you achieve that? What do you use?
Goal: Normalize serum TSH levels so treat w/ Thyroid hormone replacement
Drugs: Levothyroxine (T4 Analogue AKA Synthroid, Levoxyl etc)
or can give Liothyronine (cytomel) which is T3