thyroid

Question 1

Thyrotoxicosis:

Answer 1

Thyrotoxicosis: hypermetabolic state caused by elevated circulating levels of free T3 and T4

– Most commonly from hyperthyroidism
– Can also be from excessive release of preformed thyroid hormone (e.g., in thyroiditis)

– Extrathyroidal source

Question 2

most common causes of hyperthyroidism

Answer 2

1. Diffuse hyperplasia (Graves disease)
2. Hyperfunctioning (“toxic”) multinodular goiter
3. Hyperfunctioning (“toxic”) adenoma

Question 3

What are the primary causes of hyperthyroidism?

Answer 3

Primary:

1. Diffuse hyperplasia (Graves disease)
2. Hyperfunctioning (“toxic”) multinodular goiter
3. Hyperfunctioning (“toxic”) adenoma
4. Iodine‐induced hyperthyroidism
5. Neonatal thyrotoxicosis associated with maternal Graves disease

Question 4

Secondary causes of hyperthyroidism

Answer 4

Secondary:
– TSH‐secreting pituitary adenoma (rare)

Question 5

Disorders of THYROTOXICOSIS thare ARENT associated with hyperthyroidism?

Answer 5

1. Granulomatous (de Quervain) thyroiditis (painful)
2. Subacute lymphocytic thyroiditis (painless)
3. Struma ovarii (ovarian teratoma with ectopic
4. thyroid)
5. Factitious thyrotoxicosis (exogenous thyroxine intake)

Question 6

Name the 4 cardiac symptoms related to thyrotoxicosis

Answer 6

1. Tachycardia, palpitations, and cardiomegaly common
   
   1. From elevated cardiac contractility and cardiac output
      
      1. response to increased peripheral oxygen requirements
2. Arrhythmias particularly atrial fibrillation
   
   1. occur frequently esp. in older patients
3. Congestive heart failure in those with preexisting cardiac disease
4. Thyrotoxic or hyperthyroid cardiomyopathy
   
   1. Reversible left ventricular dysfunction and “low‐output” heart failure

Question 7

Answer 7

hyperthyroidism

Question 8

Advanced age and co‐morbidities may blunt features that typically bring younger patients to attention

Answer 8

apathetic hyperthyroidism

Question 9

most useful single screening test for hyperthyroidism. how is the test subsequently confirmed?

Answer 9

TSH, followed by free T4 (will be increased)

Question 10

how would you test for a secondary cause of hyperthyroidism?

Answer 10

1. Rare secondary cause is pituitary‐associated): TSH levels are either normal or raised
2. Thyrotropin‐releasing hormone (TRH) stimulation test
   
   1. ​A normal rise in TSH after administration of TRH excludes secondary hyperthyroidism

Question 11

Radioactive iodine test for

1. grave’s
2. toxic adenoma
3. thyroiditis

Answer 11

1. Diffusely increased uptake in the whole gland (Graves disease)
2. Increased uptake in a solitary nodule (toxic adenoma)
3. Decreased uptake (thyroiditis)

Question 12

Treatments for hyperthyroidism

Answer 12

1. B blockers to tx symptoms
2. thionamide to block hormone synthesis
3. iodine to prevent release of thyroid hormone

Question 13

Causes of Primary Hypothyroidism

Answer 13

1. Causes of Primary Hypothyroidism
   
   1. Autoimmune: Hashimoto thyroiditis
   2. Iodine deficiency
   3. Iatrogenic (postablative): surgery, radioiodine therapy, external radiation
   4. Drugs: Lithium, iodines, p‐aminosalicylic acid

Question 14

drugs associated with primary hypothyroidism

Answer 14

Lithium, iodines, p‐aminosalicylic acid

Question 15

The RARE causes of primary hypothyroidism and secondary causes

Answer 15

1. Rare
   
   1. Thyroid hormone resistance syndrome (THRB mutations)
   2. Congenital biosynthetic defect (dyshormonogenetic goiter)
   3. Genetic defects in thyroid development (PAX8, FOXE1, TSH receptor mutations)
2. Secondary
   
   1. rare: Pituitary or hypothalamic failure

Question 16

cretinism

Answer 16

1. Cretinism:
   
   1. Hypothyroidism in infancy or early childhood
   2. Found where dietary iodine deficiency is endemic
      
      1. Himalayas, inland China, Africa, and other mountainous areas
   3. Much less prevalent due to iodine food supplementation
   4. Rarely from dyshormonogenetic goiter
      
      1. Genetic defects that interfere with the biosynthesis of thyroid
   5. hormone
      
      1. 0rMaternal T3 and T4 cross the placenta and are critical for fetal brain development

Question 17

Serum TSH in primary hyperthyroidism and secondary hyperthyroidism

Answer 17

serum TSH is either HIGH (rare- indicates secondary hyperthyroidism, which would be a TSH-secreting tumor) or LOW (expecte because of negative feedback in primary hyperthyroidism)

Question 18

myxedema

Answer 18

Myxedema: Hypothyroidism in older child or adult

1. Broadening and coarsening of facial features
2. Enlargement of the tongue
3. Deepening of the voice
4. Generalized fatigue, apathy, and mental sluggishness (can mimic depression)
5. Speech and intellectual functions are slowed
6. Listless, cold intolerant, and frequently overweight
7. Decreased sympathetic activity → constipation and decreased sweating
   8.

Question 19

nonpitting edema

Answer 19

myxedema- hypothyroidism in grown children or adults

Question 20

total cholesterol and LDL levels in hyperthyroidism

Answer 20

increased

Question 21

Answer 21

hypothyroidism

Question 22

account for the majority of hypothyroid cases

Answer 22

hoshimoto’s thyroiditis and postablative hypothyroidism

Question 23

Serum TSH levels: high, normal, low

Answer 23

high: either primary hypothyroidism or the rare TSH secreting pituitary adenoma causing secondary hyperthyroidism

Normal: normal or secondary hypothyroidism

low: primary hyperthyroidism

Question 24

T3 and T4 levels in hyper/hypothyroidism

Answer 24

increased in all cases of hyperthyroidism, decreased in all cases of hypthyroidism

Question 25

Hashimoto Thyroiditis: relative frequency, peak incidence, age preferences? what is it?

Answer 25

1. Hashimoto Thyroiditis 1. Most common cause of hypothyroidism in areas of the world where iodine levels are sufficient 2. Peaks between 45 and 65 yrs 3. W \>\>\> M (ratio of 10 : 1 to 20 : 1) – Can occur in children 4. Autoimmune destruction of the thyroid gland 5. **Gradual and progressive thyroid failure**

Question 26

Hashimoto Thyroiditis What causes it, genetics

Answer 26

Hashimoto Thyroiditis 1. _Most common cause of hypothyroidism in areas of the world where iodine levels are sufficient_ 2. Peaks between **45 and 65 yrs** 3. **W \>\>\> M** (ratio of 10 : 1 to 20 : 1) 4. **Can occur in children** 5. **Autoimmune destruction of the thyroid gland** 6. Gradual and progressive thyroid failure Autoantibodies 1. Anti‐microsomal 2. antithyroid peroxidase 3. antithyroglobulin 4. Strong genetic association with polymorphisms in both **CTLA4 and PTPN22** • Type 1 Diabetes is too

Question 27

Hoshimoto Morphological changes

Answer 27

1. Thyroid is typically diffusely enlarged (goitrous) 2. Prominent mononuclear inflammatory infiltrate: 1. **_Lymphocytes, plasma cells, and germinal centers_** 3. Thyroid follicles are **_atrophic/lost_** 4. Areas with **“Hürthle cell"** metaplasia 5. Epithelial cells with abundant eosinophilic, granular cytoplasm 6. Fibrosis: **_Does not extend beyond the capsule of the gland_**

Question 28

clinical course of hoshimoto

Answer 28

usually comes to attention because of painless enlargement. usually symmetric and diffuse usually produces hypothyroidism in some it is preceded by thyrotoxicosis "hyperthroidism--\> subsequent hypothyroidism" "hoshitoxicosis"

Question 29

“hashitoxicosis”

Answer 29

Disruption of thyroid follicles--\> release of thyroid hormones (“hashitoxicosis”)--\> free T4 and T3 levels elevated--\>TSH is diminished--\>radioactive iodine uptake is decreased

Question 30

1. Typically presents with painless mild hyperthyroidism and/or goitrous enlargement 1. Most common age group 2. Most common gender 3. Variant

Answer 30

Subacute Lymphocytic Thyroiditis 1. **Painless** 2. Typically presents with: 3. Mild hyperthyroidism and/or – Goitrous enlargement 4. Most common in **middle‐aged pts** (can occur at any age) 5. **W\>M** 6. _Postpartum thyroiditis_: **~5% women postpartum** 1. Variant of autoimmune thyroiditis 2. Most have circulating antithyroid peroxidase antibodies or a family history of other autoimmune disorders 3. Up to 1/3 evolve into overt hypothyroidism

Question 31

distinguishing Subacute Lymphocytic Thyroiditis from Hoshimoto

Answer 31

**Lymphocytic infiltration with large germinal centers, *_p_**atchy disruption* and *collapse of thyroid follicles*** ***_No fibrosis or Hürthle cell metaplasia: differentiates it from Hashimoto thyroiditis_***

Question 32

Granulomatous Thyroiditis aka De Quervain thyroiditis age, gender, etiology, common association

Answer 32

**Granulomatous Thyroiditis aka De Quervain thyroiditis** 1. Typically affects pts **40‐50 yrs** 2. **W\> M** 3. Thought to be from an **immune response triggered by a viral infection** 1. Majority of patients have a hx of an **URI** just before the onset of thyroiditis 4. **Seasonal incidence**, with occurrences peaking in the summer 5. Self‐limited

Question 33

1. Unilaterally or bilaterally enlarged and firm 2. Capsule is intact, but may be stuck to surrounding structures 3. Histology varies and can be patchy Early: Neutrophilic microabscesses in damaged follicles – Later: aggregates of lymphocytes, macrophages, and plasma cells associated with damaged follicles * Multinucleated giant cells around colloid • Fibrosis may replace the foci of injury * Different histologic stages are sometimes found in the same gland, suggesting waves of destruction over a period of time

Answer 33

1. Unilaterally or bilaterally enlarged and firm 2. Capsule is intact, but may be stuck to surrounding structures 3. Histology varies and can be patchy **Early:** _Neutrophilic microabscesses_ in damaged follicles **Later:** aggregates of lymphocytes, macrophages, and plasma cells associated with damaged follicles _Multinucleated giant cells around colloid • Fibrosis may replace the foci of injury_ Different histologic stages are sometimes found in the same gland, suggesting waves of destruction over a period of time

Question 34

Most common cause of thyroid pain

Answer 34

granulomatous thyroiditis

Question 35

clinical course of Granulomatous Thyroiditis

Answer 35

most common cause of painful thyroid Variable enlargement of the thyroid Inflammation and hyperthyroidism are transient: diminish 2 to 6 weeks even without treatment--\> normal thyroid function after 6‐8 weeks High serum T4 and T3 levels and low serum TSH levels Radioactive iodine uptake is diminished – Unlike Graves disease

Question 36

Answer 36

hoshimoto's, would need more to differentiate it from Subacute Lymphocytic Thyroidits

Question 37

Answer 37

Granulomatous Thyroiditis

Question 38

a thyroid inflammatory condition that mimics thyroid carcinoma

Answer 38

Reidel's thyroiditis 1. **Rare** 1. Extensive fibrosis of the thyroid and 2. Surrounding structures 2. **Clinically mimics thyroid carcinoma** 1. A form of systemic autoimmune IgG4‐related sclerosing disease 3. **Can affect other organs**

Question 39

Most common cause of endogenous hyperthyroidism

Answer 39

grave's

Question 40

Most common cause of endogenous hyperthyroidism incidence, gender, age, clinical description, cause

Answer 40

Grave's Most common cause of endogenous hyperthyroidism ~ 2% of US women (W\>\>\>\>M) Peaks 20‐40 yrs 1. Triad of clinical findings: 1. **Hyperthyroidism and thyrotoxicosis** 1. associated with diffuse enlargement of the gland 2. **Infiltrative ophthalmopathy** 1. **​**resultant exophthalmos 3. Localized **infiltrative dermopathy: pretibial myxedema** 1. only in a minority of patients

Question 41

Pathogenesis of Grave's

Answer 41

Multiple autoantibodies but 9**0% of pts have thyroid‐stimulating immunoglobulin (TSI):** most important and specific one **TSI:** Binds to the TSH receptor and mimics its actions → release of thyroid hormones Some also have TSH receptor blocking antibodies in the circulation Can lead to hypothyroidism in a minority of pts Genetic susceptibility linked to polymorphisms in immune‐function genes **CTLA4 and PTPN22** and the **HLA‐DR3 allele**

Question 42

Answer 42

Grave's, scaloped margins and papillae w/out a fibrovascular core

Question 43

Graves 1. Thyroid gland: 2. Follicular cells: 3. Colloid: 4. Immune cells:

Answer 43

1. Thyroid gland 1. symmetrically enlarged 2. Diffuse hypertrophy and hyperplasia of thyroid 2. follicular epithelial cells 1. Follicular cells are tall and more crowded 2. Can even form small papillae that project into the lumen 1. Lack fibrovascular cores (in contrast to papillary carcinoma) 3. Colloid is pale with scalloped margins 4. Inflammatory infiltrates of 1. lymphocytes and plasma cells 2. Germinal centers are common

Question 44

Sx associated with graves Sx associated uniquely with Graves disease:

Answer 44

thyrotoxicosis, degree varies Sx associated uniquely with Graves disease: 1. **Diffuse hyperplasia of the thyroid, ophthalmopathy, and dermopathy** 2. Increased blood flow through the hyperactive gland can produce an **audible “bruit”**

Question 45

Graves: opthalmopathy, surprising reversal of thyroid function, risk for other conditions

Answer 45

Exophthalmos **may persist or progress** despite successful treatment of the thyrotoxicosis Sometimes pts spontaneously develop **thyroid hypofunction** Increased risk for other autoimmune diseases 1. Systemic lupus erythematosus 2. Pernicious anemia 3. type 1 diabetes 4. Addison disease

Question 46

Lab findings in Graves

Answer 46

Low TSH levels High free T4 and T3 levels Radioiodine shows diffusely increased uptake

Question 47

how do goiters form?

Answer 47

decreased iodine --\> decreased thyroid hormone produced --\> increased thyroid stimulating hormone -\> increased folliciular hyperplasia/hypertrophy --\> increased thyroid mass

Question 48

Sporadic Goiter: peak, preferrence, cause, clinical

Answer 48

Sporadic Goiter (less frequent) 1. Peaks at puberty or in young adult life 2. F\>\>\>\> M 3. Causes: 1. Ingestion of substances that interfere with thyroid hormone synthesis 2. Hereditary enzymatic defects that interfere with thyroid hormone synthesis 3. Mostly unknown 4. Clinical: 1. Majority are euthyroid although TSH is ususaly elevated (and T3 and T4 levels are normal) 2. Symptoms are from mass effects

Question 49

multi nodular goiter 1. how they arise 2. settings in which they arise 3. common clinical confusion 4. sporadic vs endemic

Answer 49

Simple goiter→ multi nodulargoiter 1. Recurrent episodes of hyperplasia and involution 2. Virtually all long‐standing simple goiters convert into multinodular goiters 3. Produces the most pronounced thyroid enlargements 4. Can be mistaken for neoplasms 5. Occur in both sporadic and endemic forms

Question 50

Clincai manifestations of multinodular goiter, related syndromes

Answer 50

Most symptoms are from: 1. mass effects, cosmetic concerns 2. airway obstruction, dysphagia 3. _Most pts are euthyroid_ 4. **Plummer syndrome**: autonomous nodule develops in a long‐standing goiter and produces hyperthyroidism (toxic multinodular goiter) 1. ~10% of multinodular goiters over 10 yrs 5. **superior vena cava syndrome:** compression of large vessels in the neck and upper thorax 6. Incidence of malignancy in long‐standing multinodular goiters \<5% 7. Dominant nodule can show up as a “solitary thyroid nodule” 1. Mimics a thyroid neoplasm

Question 51

multinodular goiter work up (so a patient comes into the office exhibiting a large thyroid/neck mass

Answer 51

1. radioiodine scan 1. Uneven iodine uptake and sometimes a “hot” nodule 1. From an admixture of hyperplastic and involuting nodules 2. A fine‐needle aspiration can be helpful in evaluating a dominant nodule to distinguish between hyperplasia vs neoplasm