L87- Thyroid Disorders Flashcards Preview

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Flashcards in L87- Thyroid Disorders Deck (42):
1

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

2

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)

3

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 

4

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

5

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 

6

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 

7

What is Pendred's Syndrome? 

Iodide tranpsort or utilization defect (NIS or pendrin mutations) that causes Primary Hypothyroidism and Sensorineural Deafness

8

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

9

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

10

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

11

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

12

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! 

13

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

14

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

15

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 

16

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

17

What is Subcliical Hypothyroidism? 

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

 

18

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 

19

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

20

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 

21

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 

22

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

23

Labs in Primary Hyperparathyroidism? 

Overproduction of T4/T3 w/ low levels of TSH

24

Causes of Hyperthyroidism that lead to Low TSH and HIGH RAIU

Graves

TMNG

Toxic Aneoma

Chorionic Gonadotropin-induced

TSH receptor mutations

25

causes of hyperthyroidism that lead to Low TSH and LOW RAIU

Iodine-induced hyperthyroidism

Amiodarine associated - due to excess iodine release

26

Struma Ovarri? 

Teratoma that has functional Thyroid carcinoma

27

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

28

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

29

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

30

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

 

31

Clinical Symptoms of Thyroid Storm? 

FEVER and profuse sweating 

Altered MS - agitation, delirium, psychosos, coma

Tachyarrthythmia - sinus, AFIB, Tachypnea

CHF 

HTN

GI dysfunction and Jaundice

Tremors 

Goiter

32

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

Graves and TMG

PRecipitating factors

- surgery or trauma

INFECTION MOST COMMON

Iodine load - like CT scan w/ IV contrast

Parturition

Burns

33

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

34

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 

35

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 

36

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

37

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 

38

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 

39

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 

SEE PICTURE

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 

A image thumb
40

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

41

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! 

42

What are complications of Untreated Hyperthyroidism? 

AFIB and Stroke

Osteoporosis and broken hip

Maternal/Fetal Complications in pregnancy

Thyroid Storm