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Flashcards in L87- Thyroid Disorders Deck (42):

What cells are found in the Thyroid Gland? 

Follicular (epithelial) cells - thyroid hormone synthesis

Endothelial cells

Parafollicular Cells or C- Cells = make Calcitonin





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? 


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


Bradycardia, Heartblock, prolonged QT


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


What is Subcliical Hypothyroidism? 

Elevated TSH (between 5-10) and normal T4/T3



What are some complications to mom and baby when have Hypothyroidism in pregnancy? 

Danger in Hashimotos? 

MAternal - preeclampsia, anemia, hemorrhage, Central Ventricular dysfunction, abortion, abruption

Fetal - low birth weight, impaired cognitive development, fetal mortality


High TPO titers confer higher risk of Abortion in Hashimotos 


What is the treatment goal for hypothyroidism in pregnancy? What if not enough TH? 

GOAL TSH 0.2-3.5 mlU/L

NEED enough in the first trimester or else Cretinism


What are most common causes of Hyperthyroidism? Who gets them? 

GRAVES DISEASE MOST COMMON - peak incidence 20s-40s

Toxic Multinodular Goiter (MNG) - peak incidence > 50 yo

Toxic Adenoma - peak incidence 30-40

Females > MAles 


How do symptoms of Hyperthyroidism manifest differently in older vs younger patients? 

Young PAtients - symptoms of sympathetic activation, anxiety, hyperactivity, tremor

Older Patients - manifest CV symptoms like Dyspnea, AFIB w/ unexplained weight loss 


What are the symptoms and signs of Hyperthyroidism? 

Symptoms: Anxiety, sweating, tremor, heat intolerance, weakness, Diarrhea, hyperactivity, palpitations, weight loss, dyspnea, insomnia, menstraul abnormalities

Signs: hyperactivity, weight loss, hair loss, Tachycardia or Atrial Arrhtyhmia, Systolic HTN, Warm - smooth skin, Proximal Myopathy, Exophthalmos, Emotional Lability, Hyperactive reflexes


Labs in Primary Hyperparathyroidism? 

Overproduction of T4/T3 w/ low levels of TSH


Causes of Hyperthyroidism that lead to Low TSH and HIGH RAIU



Toxic Aneoma

Chorionic Gonadotropin-induced

TSH receptor mutations


causes of hyperthyroidism that lead to Low TSH and LOW RAIU

Iodine-induced hyperthyroidism

Amiodarine associated - due to excess iodine release


Struma Ovarri? 

Teratoma that has functional Thyroid carcinoma


What is the most common cause of Thyrotoxicosis? What are the signs/symptoms/associations? What do you see on RAIU?

Grave's Disease!!!

Thyroid-Stimulating Immunoglobulin (TSI)- antibodes that bind TSH receptor resulting in growth of thyroid cells and increased function

RAIU: Diffuse Increased uptake!

Signs/Symptoms: - Pretibial Myxedema - swelling over anterir shin

- Thyroid Eye disease

- Increased pigmentation and Vitiligo


Another cause of primary hyperthyroidism is Multinodular Goiter. Desecribe what's happening there and where you see it? Presentaiton? 

2 or more thyroid nodules secreting excess TH 

- RAUI shows multiple hyperfuncitoning nodules 

- Potentiated by drugs w/ Iodine - Radiocontrast or Amiodarone

- can have insidious onset and present in older patients as Apathetic Hyperthyroidism: WEight loss, AFIB, Depression


What is a Toxic Adenoma? Who gets it? Treatment?

Single Hyper-functioning nodule

seen in pts 30-40 yo 

usually BENIGN

RAIU shows 1 nodule uptake and remainder or thyroid gland is suppressed

Treatment is RAdioablation or surgery


What is the relationship between Beta-HCG and TSH? Why is this good normally? and When/why is it bad? 

TSH and BETA-HCG have Alpha Subunit Homology and so B-HCG acts on the TSH receptor to stimulate TH production

Normally occurs in pregnancy bc need increased TH; resolves in normal pregnancy by 14 weeks and associated w/ Hyperemesis Gravidarum or Twins 

Bad when seen w/ Trophoblastic or germ cell tumors, familial gestational hyperthyroidism



Clinical Symptoms of Thyroid Storm? 

FEVER and profuse sweating 

Altered MS - agitation, delirium, psychosos, coma

Tachyarrthythmia - sinus, AFIB, Tachypnea



GI dysfunction and Jaundice




When is Thyroid storm seen? What are some precipitating factors? 

Graves and TMG

PRecipitating factors

- surgery or trauma


Iodine load - like CT scan w/ IV contrast




What is the cause of SEcondary Hyperthyroidism? What labs do you see? PResentation? RAIU scan? Treatment? 

TSH-Producing Pituitary Adenoma

Labs: Normal/elevated TSH and Elevated T3/T4 (similar to TH resistance) 

Presentation: Bitemporal Hemianopsia, HA, Goiter, Hyperthyroid

Majority are MACROADENOMAs and 25% co-secrete GH and Prolactin!!! 

High uptake on RAIU scan! 

Treatment: surgery and somatostatin analogues


What can cause transient TH excess and what do you see? Treatment? 

Thyroiditis - inflammation causes release of a bunch of TH all at once

Low TSH and Low Uptake on Scans

Following viral illness get Painful Thyroid + Hyperthyroidism as it gets inflamed and just dumps all stored colloid

Tx: Beta Blockers, NSAIDS, Prednisolone but no need for antithyroid drugs 


What do you see in Post-Partum Thyroiditis? 

several weeks after delivery get transient thyrotoxicosis followed by hypothyroidism and recover

RAIU uptake low bc destruction of gland 


What is Subclinical Hyperthyroidism and who gets treated for it? 

Low/Suppressed TSH w/ normal T4/T3 - assays for TSH more sensitive than for normal T4/T3

No symptoms but higher incidence low bone density 

should really be named Mild Hyperthyroidism 

TREAT IN POST-MENOPAUSAL WOMEN - improves bone density and cardiac function 


Low or suppressed TSH < 0.4 mIU/L


Lab testing for All hyperthyroidism? differences in etiologies and labs?

TSH, T4 and T3

*High T3 suggestive of Grave's Disease

TSI and TSH receptor Antibody (TRAb)

Hyperthyroidism: Low TSH, T4 and/or T3 elevated, and can have Antibodies

TSH-Producing Pituitary Adneoma: TSH normal or elevated, T4 and/or T3 elevated

TH resistance: TSH high and T3/T4 high 


Imaging for Thyroid diseases - what do you use? 

Thyroid US - for nodules, drug induced, or increased Vascularity seen in Grave's

MRI Brain for pituitary lesions

Thyroid Uptake and Scan:

- high uptake = Graves (diffuse), Toxic MNG, Toxic Adenoma

- Low uptake = Thyroiditis, Iodine-induced hyperthyroidism 


How id Thyroid Scintigraphy used? Relation to TSH? 

Used to determine etiology of Hyperthyroidism by using radioisotopes of Iodine (I-123) or Tech-99 which are taken up by the Follicular cells

Thyroid takes up Iodine under influsence of TSH 


Graves: whole thyroid dark bc TSH stimulation to take up everywhere

Toxic MNG/Adenoma: nodules or adenoma dark and then rest is light bc no TSH to the rest of the thyroid

Thyroiditis: no TSH bc suppressed so less uptake 


What are the management goals and treatments used for Hyperthyroidism? 

GOAL: Normalize serum TSH 

Beta Blockers (non-selective) to help w/ symptoms - Propanolol (blocks peripheral T4 to T3 conversion) 

Antithyroid Drugs inhibit synthesis of TH: Methimazoe and TPU

Radio-Ablation w/ I-133

Surgery to take out and then use Levothyroxine replacement


Grave's Disease and Hyperthyroidism need to be treated in pregnancy or else get what maternal/fetal complications? 


Complications of treatment? 

Maternal - preeclampsia, anemia, hemorrhage, spontaneous abortion

Fetal - low birth weight, fetal goiter, fetal neonatal hyperthyroidism or hypothyroidism, and death


Treatment can cause liver disease so need to monitor LFTs and TFTs every 2 weeks! 


What are complications of Untreated Hyperthyroidism? 

AFIB and Stroke

Osteoporosis and broken hip

Maternal/Fetal Complications in pregnancy

Thyroid Storm