Thyroid Disease Flashcards
1
Q
describe the anatomy of the thyroid gland
A
- 2 lobes on either side of the thyroid cartilage
- joined by isthmus- occurs at level of the cricoid cartilage
2
Q
describe the hypothalamic-pituitary-thyroid axis
A
Thyrotropin-releasing hormone (TRH), secreted by the hypothalamus, stimulates the anterior pituitary gland to release thyroid-stimulating hormone (TSH) which, in turn, stimulates release of thyroid hormones, or thyroxines (T3 and T4), from the thyroid gland.
-T3 exerts its effects on target organs by binding to DNA receptors in the nucleus. Both T3 and T4 exert negative feedback on the hypothalamic pituitary axis, regulating secretion of TRH and TSH.
3
Q
what is T3
A
- the biologically active form of thyroxine
- exerts its effects on target organs by binding to DNA receptors in the nucleus
- exerts neg. feedback on hypothalamic pit. axis, regulating secretion of TRH and TSH
4
Q
Describe TH metabolism
A
- dietary iodine is converted to iodide in the stomach and taken up by follicular cells of the thyroid
- Iodide is used to iodinate tyrosine molecules on thryoglobulin (Tg)*
- The iodinated tyrosines take on two forms, monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are coupled to form T3 or T4*
- T3 and T4 are released from Tg by peroxisomes
- TSH stimulates proteolytic breakdown of thyroglobulin to release T3 and T4
- these rxns are catalyzed by thyroid peroxidase (TPO)
5
Q
___ stimulates proteolytic breakdown of thyroglobulin (Tg) to release T3 and T4
A
TSH
6
Q
tyrosine-rich protein
A
thyroglobulin (Tg)
7
Q
Thyroid hormones exert their effects by __
A
binding to nuclear receptors in the cells of target organs
8
Q
Is T3 or T4 more metabolically potent?
A
T3
- but T4 is secreted from thyroid in far greater quantity
20: 1
9
Q
Most T3 is produced where/how
A
outside of the thyroid by conversion of T4 to T3
10
Q
most thyroxine circulates in its ___ form
-only the___ form of thyroxine is biologically available
A
bound- bound mostly to thyroxine-binding globulin (TBG)
free
11
Q
80% of T3 is produced ___
A
outside of the thyroid by conversion from T4 (mostly in the liver)
12
Q
___% T3 and T4 is bound to plasma proteins
A
Most (~99%)
- mainly bound to thyroxine-binding globulin (TBG)
- *only unbound form is biologically available
13
Q
what organ systems can TH (T3, T4) effect?
A
- cardiac
- liver
- skeletal muscle
- kidney
- brain
*Thyroid hormones impact basal metabolic rate and exert various effects on several organ systems
14
Q
How do thyroid hormones effect the cardiac system
A
- O2 consumption
- contractility
- vascular resistance
- cardiac output
*exaggerated effects w/ hyperthyroidism and decreased w/ hypo
15
Q
How do thyroid hormones effect the liver
A
- clearance
- protein synthesis
*exaggerated effects w/ hyperthyroidism and decreased w/ hypo
16
Q
How do thyroid hormones effect the brain
A
- cognitive fxn
* exaggerated effects w/ hyperthyroidism and decreased w/ hypo
17
Q
How do thyroid hormones effect the kidney
A
- clearance rates
- blood flow
*exaggerated effects w/ hyperthyroidism and decreased w/ hypo
18
Q
How do thyroid hormones effect skeletal muscles
A
- O2 consumption
- Contractility
- Protein synthesis
- Blood flow
*exaggerated effects w/ hyperthyroidism and decreased w/ hypo
19
Q
Relevant PMH when assessing for thyroid disease
A
- past thyroid diseases
- family hx
- sx of hyper/hypo
- autoimmune disorders (ex. DM1)
20
Q
What labs do you draw when you suspect thyroid disorder
A
- Screen with TSH
- 3rd generation assay - T4
- T3 resin uptake
- Free T4
- Total T3
- Thyroid Antibodies
21
Q
what is the ultrasensitive gold-standard screening test for thyroid dysfunction?
A
TSH
22
Q
Of the measures of thyroid hormone levels, ___ is by far the most useful
A
free T4
*Total T4, Free T3 and T3 resin uptake are all affected by changes in protein levels in the circulation and are useful only in certain situations, such as in the case of hypo- or hyper-proteinemia.
23
Q
____ are all affected by changes in protein levels in the circulation and are useful only in certain situations, such as in the case of hypo- or hyper-proteinemia.
A
Total T4, Free T3 and T3 resin uptake
24
Q
_____: Not useful for screening or for evaluation of hypothyroid states. Can be helpful in the evaluation of hyperthyroid states.
A
T3 and free T3
25
___: Affected by changes in thyroid-binding proteins
Total T4
26
what is a T3 resin uptake (T3UR)?
- Indirect measure of total T4.
- Less commonly used since there are good FT4 assays available.
- Can be helpful in hypo/hyper-protein states.
27
what thyroid antibodies can you check for thyroid disease
Anti-TPO
Anti-Thyroglobulin (TgAb)
Anti-TSH receptor
* helpful in diagnosing autoimmune thyroid disease
* poor sensitivity and specificity
28
what imaging is frequently used in assessing thyroid disease?
- nuclear medicine (thyroid scanand uptake)
- US
- FNA- US guided
29
what is a thyroid scan and uptake test
- nuclear medicine
- involves the injection of a radioactive technetium-labeled compound that accumulates in the thyroid.
- The uptake of this compound is measured at 6 and 24 hours and compared with expected normal values. The “scan” is an image of the distribution of the radio-labeled compound in the thyroid.
- Useful for evaluating nodules: “hot” (increased uptake) versus “cold” (decreased uptake)
30
what are hot and cold nodules
| and what are they commonly associated w/
Hot= increased uptake (Graves' disease)
| Cold=decreased uptake (thyroiditis)
31
when are US used for assessing thyroid disease?
- useful to characterize nodules and other lesions identified by physical exam or scanning
- monitor change in size
- distinguish solid from cystic lesions
- FNA US guided
32
The test of choice for evaluating solitary nodules in euthyroid patients
FNA
33
what are the values of high, normal, and low TSH?
High: greater than 5 mU/ml
Normal: 0.5-5 mU/ml
Low: less than 0.5 mU/ml
34
TSH is a "magnification marker"
| -what does this mean?
that small changes in circulating T4 cause proportionally larger shifts in TSH levels
35
what is the relationship between TSH and free T4?
- linear, inverse relationship
| - when T4 decreases, TSH increases
36
overt thyroid disease is characterized by:
- abnormal TSH
- abnormal free T4, T4, T3RU, T3
- classic signs and sx of either hyper or hypthyroidism
37
subclinical thyroid disease is characterized by:
-Abnormal TSH
-Normal hormones:
Free T4, T4, T3RU
T3
-Subtle or no signs and symptoms of either hyper or hypothyroidism
38
when does the ATA recommend you start screening for thyroid disease?
- beginning at age 35 and every 5 yrs thereafter
| - more aggressive/frequent screening w/ pregnancy and autoimmune disease
39
what does the USPSTF 2004 and AAFP 2004 recommend regarding thyroid screening?
USPSTF 2004
Data for screening in nonpregnant adults “inconclusive.”
AAFP 2004
No evidence to support routine screening
40
what is the prevalence of overt and subclinical hyperthyroidism?
Overt: 2-4% in women. 0.2% in men
*15% of cases occur in patients 60 or older
Subclinical: 3-6% in the general population.
*Progress to overt disease 1-3% per year
41
what is the most common etiology of overt hyperthyroidism
Graves disease
42
what is the most common etiology of subclinical hyperthyroidism
over-zealous levothyroxine replacement
43
tx of subclinical hyperthyroidism
Treatment is controversial but consider in older patients with TSH less than 0.1
44
is hyper or hypo-thyroidism more commmon?
hypothyroidism
45
hyperthyroidism is ___ times more likely to occur in women and can occur throughout adulthood
10
46
sx of overt hyperthyroidism
- Tachycardia
- heat intolerance
- hyperactive reflexes
- hyperhidrosis (increased sweating)
47
how do sx of hyperthyroidism differ in older ppl (70+) and younger than 50
Older: incomplete or blunted physiologic responses, AF
Younger more: goiter, tremor, nervousness, hyperactive reflexes, increased sweating, increased appetite
48
DDX/ other causes of hyperthyroidism
1. Graves’ Disease (60-80%)
2. Hashitoxicosis
3. Toxic adenoma (Solitary hot nodule)
4. Multinodular goiter
5. Thyroiditis: post-partum, subacute
6. T3 Toxicosis
7. Rare: TSH producing pituitary tumor
49
what is Graves' disease
-an autoimmune disease in which antibodies bind to the TSH receptor and cause a TSH-like response
- Antibodies directed against TSH receptor
- Thyroid-stimulating immunoglobulins (TSI)
- Act like TSH
50
how common is Ophthalmopathy in graves disease
20-40%, severe in 5%
*less common in the modern era because of effective detection of early disease.
51
what is ophthalmopathy
an autoimmune inflammatory disorder affecting the orbit around the eye, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and bulging eyes (exopthalmos)
52
Graves’ disease occurs most commonly in who
younger women, with a peak incidence between 20 and 40 years of age
53
Goiters w/ graves disease depend on what
age-dependent
| examiner-dependent
54
what is Hashitoxicosis
Transient hyperthyroidism associated with the initial destructive phase of Hashimoto’s thyroiditis, during which the thyroid is being destroyed by an autoimmune process, spilling thyroxine into the circulation.
55
what is toxic adenoma
-a nodule that secretes excessive thyroxine and typically occurs in younger patients (solitary hot nodule)
56
who is toxic adenoma most commonly seen in
younger patients
57
- Increased T3/T4 secretion in a single nodule
| - Single nodule shows increased RAI uptake
toxic adenoma
58
what is toxic multinodular goiter
generally a disease of elderly patients and manifests as diffuse nodular enlargement of the gland
59
toxic multinodular goiter is most often seen in who
Most common in older patients with history of goiter
60
how do you evaluate for hyperthyroidism
1. check TSH and free T4
2. if TSH is low and free T4 is high=hyper, and an uptake and scan will allow you to narrow ddx
OR
2. if TSH is low but free T4 is normal--> measure T3, you need to rule out T3 toxicosis
61
High uptake with a diffuse/homongenous pattern suggests
Graves’ Disease,
62
high uptake with a single “hot” nodule suggests
toxic adenoma
63
high uptake with with multiple “hot” nodules suggests
toxic multinodular goiter
64
Low uptake suggests
acute thyroiditis or over-treatment with levothyroxine
65
what is T3 toxicosis
an uncommon condition in which T3 levels are elevated
66
Low TSH, normal FT4--> measure T3
- Normal suggests: __
- High suggests: __
normal: Subclinical, medication, pregnancy, illness
high T3: T3 Toxicosis
67
thyroid scan:
| -Patchy, nodular uptake
Hashimoto’s disease
| Nodular disease
68
tx of Graves disease
sx management w/
1. b-blockers
2. steroids
3. I131 ablation (radioactive thyroid ablation)
4. antithyroid drugs
5. surgery
69
tx of Nodular disease
sx management w/
1. I131 ablation (radioactive thyroid ablation)
2. antithyroid drugs
- Not good long term
3. surgery
70
what it the most common treatment for Graves disease in the US
Radioactive ablation with I-131
71
SE of Radioactive ablation with I-131
- minimal SE except hypothyroidsim (70%)
- most patients will require life-long supplementation with levothyroxine
- Patients require close monitoring of thyroid function tests until euthyroidism has been established
- 10% will require re-treatment with I131.
72
clincial use/indications for antithyroid drug tx for hyperthyroidism
1. Long term management of Grave’s disease.
2. Short term management of hyperthyroidism prior to I131 treatment or surgery.
3. Rarely indicated long term in the treatment of Toxic Multinodular Goiter.
73
what is the mechanism of action for antithyroid drugs
Antithyroid drugs are thionamides and work by blocking thyroid peroxidase, thus inhibiting incorporation of iodide into tyrosine residues.
74
commonly used anti-thyroid med
1. propylthiouracil (PTU)-- TID dosing
| 2. methimazole (MMI)--1x day dosing
75
when is propylthiouracil (PTU) preferred
in pregnancy and nursing, for severe hyperthyroidism and thyroid storm
76
what antithyroid drug is generally considered safer in non-pregnant patients.
MMI
*lower incidence of major side effect
77
what is the efficacy of antithyroid drug tx in Graves disease
- Virtually all patients will become euthyroid with ATD treatment
- Usually euthyroid within 6-12 weeks.
- Typically treat 12-24 mos., then taper.
- Remission in only 40-50% of patients.
- High doses allow shorter time to euthyroidism, but are not associated with higher remission rates
78
Thionamides are very effective in achieving normal thyroid hormone levels but only ___ % of patients given a one to two year course remain in remission following drug cessation. The rest will require ___
40-50%
ablation
79
Side effects of ADT
Minor (1-15%)
- Rash (most common)
- Fever
- urticaria
- joint pain
- abnormal taste
- Transient transaminase elevation (15-30% PTU)
Major:
- Severe fulminant hepatitis (rare but higher w/ PTU)
- Agranulocytosis (severe leukopenia) (.2-.5%)
- Vasculitis
*severe fulminant hepatitis and agranulocytosis (severe leukopenia) can be fatal (rare)
80
what are the stages of thyroiditis
hyper--> hypo--> recovery
-typically presents as clinical hyperthyroidism, due to inflammation of thyroid follicular cells, followed by a period of hypothyroidism, as cellular function recovers to the point where the patient is euthyroid.
81
types of thyroiditis
1. subacute granulomatous thyroiditis
| 2. subacute lymphocytic thryoiditis
82
what is the presentation of subacute granulomatous thyroiditis
- Painful, tender, often follows a viral illness
- Abrupt onset of thyrotoxicosis (50 %) due to inflamed gland
- Hyperthyroidism typically lasts 3-6 weeks
- Euthyroid by 6-12 months
83
complications of subacute granulomatous thyroiditis
- Hyperthyroidism typically lasts 3-6 weeks
- 10-15 % have persistent hypothyroidism
- Must be distinguished from Graves’: RAI uptake helpful
84
tx of subacute granulomatous thyroiditis
1. NSAIDS to start, prednisone if no improvement after 1 week (for pain and inflammation)
2. Beta-blockers can be used to treat hyperthyroid symptoms
3. Treatments are supportive and do not alter course
85
Subacute lymphocytic thyroiditis is most commonly seen when
post-partum
86
presentation of Subacute lymphocytic thyroiditis
- Painless
- Sporadic or Post-partum
- Most likely autoimmune
87
tx for Subacute lymphocytic thyroiditis
tx is for hypo- or hyperthryroidism
88
what drugs are known to induce thyroiditis
amiodarone, interleukin, interferon
89
If you suspect thyroiditis and there is pain and/or tenderness of the gland, it is likely ___
subacute granulomatous thyroiditis.
90
thyroiditis evaluation:
+ pain/tenderness
History of radiation or trauma
radiation or traumatic thryoiditis
91
thyroiditis evaluation:
+ pain/tenderness
No history of radiation or trauma
subacute granulomatous thyroiditis
92
thyroiditis evaluation:
no pain/tenderness
meds associated w/ thyroiditis
drug induced thyroidits
93
```
thyroiditis evaluation:
no pain/tenderness
post-partum--> check ___ level
high or normal: __
low: __
```
TSH
High or normal: post-partum or Hashimoto's
Low: Post-partum vs Graves’ (RAI uptake to distinguish)
94
thyroiditis evaluation:
no pain/tenderness
no meds associated w/ thyroiditis
no post-partum
Hashimoto's vs Subacute lymphocytic thyroiditis
95
thyroid nodules are most commonly seen in who
more common in women (4x more common)
(4-7 % of the population, but U/S studies suggest much higher incidence
96
A palpable swelling in an otherwise normal thyroid
thyroid nodule
97
sx of thryoid nodules
Most persons with nodules are euthyroid, asymptomatic and are typically discovered on thyroid palpation
98
thyroid nodules suggestive of malignancy
hard, fixed lesion, cervical lymphadenopathy, size greater than 4cm, hoarseness
*most are benign, only 5% are malignant
99
evaluation of thyroid nodule on PE
1. check TSH
2. if Euthyroid--> FNA
3. if hyperthyroid--> Scan and uptake
- Cold nodule: FNA
- hot nodule: surgery vs radioactive iodine
*hot nodules are very unlikely to be malignant
100
what is the prevalence of hypothyroidism and subclinical hypothyroidism
hypo- 5% in the general population
-10-20% in women over age 60
subhypo- 4-8% in the general population
-9-16% in women over age 60
101
what is considered subhhypothyriodism
elevated TSH with normal free T4
102
what percentage of subclinical hypothyroidism progress to overt disease?
20-40%
103
clinical sx of hypothyroidism
1. Weakness (99%)
2. Skin changes (dry or coarse skin) (97%)
3. Lethargy (91%)
4. Slow speech (91%)
5. Eyelid edema (90%)
6. Cold sensation (89%)
7. Decreased sweating (89)
8. Cold skin (83%)
9. Thick tongue (82%)
10. Facial edema (79%)
11. Coarse hair (76%)
12. Skin pallor (67%)
13. Forgetfulness (66%)
14. Constipation (61%)
104
ddx of primary hypothyroidism (95%)
1. Idiopathic (probably “burned out” thyroid from old Hashimoto)
2. Hashimoto thyroiditis
3. Surgically absent thyroid
4. Post radioactive ablation
5. Iodine deficiency
6. Other
* *always consider depression when you are thinking of hypothyroidism
105
ddx of secondary hypothyroidism
1. congenital hypopituitarism
2. pituitary/hypothalamic
secondary involve hypothalamic-pit. axis and are rare
106
what sx do depression and hypothyroidism have in common?
1. Mood
2. poor Concentration
3. decreased Libido
4. change in Appetite
5. Fatigue
6. Sleep disorder
7. Wt gain
107
what sx do hypothyroidism have that depression doesn't have and vise-versa
hypothyroid:
- bradycardia
- lipid disorder
- cold intolerance
- hair/skin changes
- goiter
- delayed DTRs
Depression:
- Delusions
- Suicidal ideation
- insomnia
- increased appetite
108
what percent of pts in colorado taking thyroid medications have abnormal TSH?
40%
**we in health care are not doing well in this area
109
what is the treatment of hypothyroidism
-Levothyroxine (T4): 1.6 mg/kg/day
- Be very cautious – Elderly, Cardiac disease
- T3 – no data to support this
*check TSH every 6-8 weeks until TSH level has stabilized between 1-2 mlU/L
110
what is the goal TSH when treating hypothyroidism
1-2 mlU/L (more stringent than normal screening range of 5-5 mIU/L)
* except thyroid CA patients
- monitor every 6-8 weeks after dose or brand changes bc Half-life = 7 days
111
what is the half-life and therapeutic range of levothyroxine
half-life = 7 days
Therapeutic range: 1-2 mlU/L (more stringent than normal screening range of 5-5 mIU/L)
112
common causes of TSH variability in patients on levothyroxine
1. patient compliance
2. Changes in thyroid hormone preparation
3. Malabsorption syndromes
4. Drug interactions: impaired levothyroxine absorption or altered metabolism
113
subclinical hypothyroidism is associated with:
1. Progression to overt hypothyroidism
2. Cardiac abnormalities: decreased function, increased risk CAD
3. Mild “symptoms” of hypothyroidism.
4. Hyperlipidemia
114
what is the Tx of subclinical hypothyroidism
- Treatment has become very controversial.
- “Not routinely recommended in patients with TSH 4.5-10”
*no studies that demonstrate clear benefit to treating at this stage
