1
Q
Different types of thyroid disorders
A
- Hypothyroidism –failure of the thyroid grand to produce enough thyroid hormone to meet the metabolic demands of the body
(2nd only to DM as most common endocrine) - Hyperthyroidism – overproduction and release of thyroid hormone
- Nodular Thyroid Disease
2
Q
Functions of the thyroid
A
- Growth/maturation
- Cell respiration
- Energy expenditure- thyroid hormone increases tissue thermogenesis and basal metabolic rate (BMR)
- Turnover of vitamins/hormones
3
Q
Describe the anatomy of the thyroid and principal regulatory mechanism
A
- 2 lobes joined by an isthmus
- Anterior and caudal to the larynx
- Hypothalamic –pituitary-thyroid negative feedback system (principal regulatory mechanism)
4
Q
Explain thyroid physiology
A
- Hypothalamus secretes thyrotropin releasing hormone (TRH) which travels via the hypo-physeal portal system to the pituitary where it stimulates TSH
- In turn, TSH stimulates thyroid hormone synthesis, thyroid growth, and release of thyroid hormones (T4 and T3)
- Then, TSH secretion is inhibited by thyroid hormones
5
Q
Who is high risk for developing thyroid disease?
A
- Elderly
- Women with a family history of thyroid disease
- Prior thyroid dysfunction
- Patients with suggestive symptoms
- Patients with an abnormal thyroid on exam
- Type 1 diabetes, Addison Disease
- Personal history of autoimmune disorder
6
Q
Describe the different thyroid hormones
A
- T4 – thyroxine. Note: free T4 is preferred over total T4 because T4 binds to specific proteins in serum. Free T4 is the metabolically active form of T4 not affected by binding factors.
- T3 – triiodotyronine (80% produced by peripheral conversion of T4 mostly in liver and kidney). Measurement of T3 is of little clinical utility because it can remain stable/normal even when TSH and T4 are abnormal.
- rT3 – reverse T3 (inactive)
7
Q
Abnormal thyroid exam findings
A
- Asymmetry
- Enlargement
- Scar
- Distinct nodules
- Displacement of trachea
- Hoarseness
- Venous Dilation
8
Q
What are the recommendations for routine screening for thyroid disorders?
A
- Screening of asymptomatic individuals is controversial
- Two strategies:
~Screening all individuals over a certain age
~Screening only those with clinical risk factors - Universal screening for thyroid dysfunction is suggested in pregnant women or those hoping to become pregnant
- No recommendation to screen in non-pregnant women and asymptomatic individuals due to the absence of data showing any benefit
9
Q
What acute changes in patient status would cause you to want to screen for thyroid disorder?
A
- Substantial hyperlipidemia or a change in the lipid pattern
- Hyponatremia (often resulting from inappropriate production of antidiuretic hormone)
- Macrocytic anemia
- High serum muscle enzyme concentrations
10
Q
How do you screen for thyroid disease?
A
- TSH most sensitive and specific as initial test this is what you test first
- Reflex Testing: (only test for TSH, automatically adds other tests in abnormal)
~TSH normal – no further testing
~Increased TSH – add free T4
~Decreased TSH – add free T4, FT3
11
Q
What are some thyroid antibodies we can test for?
A
Thyroglobulin Antibodies Thyroid Peroxidase (TPO) Antibodies
Measure antibodies to confirm the presence of autoimmune disease
12
Q
What are the common signs and symptoms of hypothyroidism?
A
- Fatigue/Lethargy*
- Cold Intolerance*
- Constipation
- Weight gain
- Menorrhagia
- Infertility
- Depression
- Arthralgia, myalgia
- Difficulty concentrating
- Weakness
- Hoarseness
- Hypothermia
- Dry skin
- Goiter
- Diastolic Hypertension
- Edema
- Delayed relaxation phase of DTR
- Bradycardia
- Brittle Nails
- Cognitive Impairment
13
Q
What are the severe signs and symptoms of hypothyroidism?
A
- Sleep Apnea
- Carpal tunnel Syndrome
- Hyponatremia
14
Q
What are different ways to classify hypothyroidism?
A
- Time of onset (acquired or congenital)
- Level of involvement
~Primary – results from disease within the gland
~Secondary – much less common; often consequence of pituitary disease: low TSH is misleading - Severity – overt or subclinical
Environmental iodine deficiency is the most common cause of hypothyroidism worldwide
15
Q
What is the most common type of thyroid disease?
A
Hashimoto’s
- Autoimmune thyroiditis (testing for antibodies helps understand autoimmune processes happening in body)
- Accounts for majority of all acquired primary hypothroidism
- Most common in middle aged women (estimated to be 5-10x more common in women)
- More common in patients with other autoimmune disease
- Goiter may or may not be present
16
Q
What are some other causes of hypothyroidism?
A
- Surgical removal of thyroid gland
- Thyroid ablation by radioactive iodine
- External irradiation of head and neck for non-thyroid related malignancies ( i.e. lymphoma)
- Drugs (amiodarone, lithium, interferon and Sunitinib, a tyrosine kinase inhibitor for renal cell CA)
- Pituitary and hypothalamic disorders (ie. Pituitary adenoma)
17
Q
What is the gold standard for diagnosing hypothyroidism & what is the normal range?
A
- Thyroid stimulating hormone (TSH) is considered gold standard
- TSH will be increased (reference range is 0.4 to 5 mIU/L). Some experts argue that upper limit should be up to 2.5-3
- May be accompanied by decrease in serum thyroxine (T4) level
- Consider testing for thyroid autoantibodies – anti-thyroid peroxidase autoantibodies (in patients with subclinical disease or if goiter is present)
US if structural abnormality
18
Q
How do we commonly treat hypothyroidism & what dosage?
A
Levothyroxine (synthetic T4) is most common choice
- Typical adult requires about 1.6 mcg/kg/day
- Initiate dose at 112 mcg daily for 70 kg adult
- Older adults and patients with ischemic heart disease should be started at 25-5 mcg daily and titrated slowly
- Half-life 6-7 days
19
Q
What are some alternative treatments for hypothyroidism?
A
- Thyroid USP (Armour Thyroid) – dessicated beef or pork thyroid gland *not systematically studied
- Liothyronine (Cytomel) – Synthetic T3 often added to levothyroxine when mood and memory problems persist Half-life 18 hrs – difficult to monitor
ATA/AACE joint guidelines report not enough evidence to support the use of this combination (T3/T4) therapy
20
Q
How often do you monitor and follow up with patients being treated for hypothyroidism?
A
- Thyroid hormones have a narrow therapeutic index
- Frequent dose adjustments and monitoring are necessary when initiating treatment
- TSH every 6 weeks until normal level achieved
- Then, yearly TSH or whenever symptoms of hypo or hyperthyroidism occurs
- In pregnant women, monitor TSH and free T4 levels every 4 weeks for the first half of pregnancy and at least once between 26-32 weeks’ gestation (Levothyroxine needs may increase by 50% in pregnancy)
21
Q
What are some special considerations with dosing and prescribing levothyroxine in hypothyroidism?
A
- Small changes in levothyroxine do not produce measurable changes in hypothyroid symptoms or well being
- TSH target for treatment of hypothyroidism should not differ from the general reference range
- Thyroxine absorption is decreased by iron, calcium carbonate, PPIs , and sucralfate
- Advise patients to separate administration of these meds by at least 4 hours.
- Malabsorption disorders (can be given IV if needed at 70-80% of oral dose)
- Coumadin, Phenobarbital, Tegretol, Rifampin, and oral hypoglycemic agents increase elimination of thyroxine
22
Q
What are some alternative causes of persistent symptoms of hypothyroidism when TSH in normal range?
A
- Adrenal Insufficiency
- Chronic Kidney Disease
- Depression/Anxiety/Somatoform Disorder
- Liver Disease
- Obstructive Sleep Apnea
- Viral Infection (Mono, HIV)
- Vitamin D deficiency
- Anemia
- B12 deficiency
- Iron deficiency
23
Q
What is considered subclinical hypothyroidism & what do you do when your patient has it?
A
- Characterized by slight increase in TSH levels and normal T3 and T4 levels with the presence or absence of symptoms
~TSH 6-10 may not develop hypothyroidism
~TSH >10 most progress to overt hypothyroidism - Prevalence 3.1%-8.5% in the general population
- More prevalent in women, and more frequent in Whites and Mexican Americans than Blacks.
- 4%/year develop hypothyroidism
24
Q
What are some potential consequences of subclinical hypothyroidism?
A
- Coronary artery disease
- Increased cholesterol
- Neuropsychiatric disease
25
At what TSH levels are we recommended to treat?
- TSH> 10 microIU/ml OR
- TSH 5-10 PLUS a goiter or positive antibodies
- A low initial dose of levothyroxine 25 – 50 mcg daily
26
How do you manage SCH in elderly?
- Elderly patients with mildly elevated TSH may be improperly diagnosed with SCH because age adjusted ranges of TSH are not routinely used in clinical practice.
- Consider repeating level in 6-12 months prior to initiation of therapy
- Risk vs benefit of therapy should be considered
- Studies on the relationship of SCH and clinical outcomes such as CV risk, dyslipidemia and renal function in older adults are conflicting
- Careful patient selection and close monitoring are critical
27
What is a severe, often fatal, manifestation of hypothyroidism?
Myxedema Coma
- Rare complication of long standing disease
- Typically in elderly patient (female > male)
- Hallmark features: mental status changes including lethargy, cognitive dysfunction, and sometimes psychosis; hypothermia
- Hyponatremia
- Bradycardia
- Respiratory failure
- ICU management, endocrine consult required
28
When should you refer your hypothyroid patient?
- Patients under 18
- Pregnant women
- Patients unresponsive to therapy
- Cardiac patients
- Presence of goiter, nodule, or other structural changes in the thyroid gland
- Presence of other endocrine disease
29
What is hyperthyroidism?
Characterized by the overproduction or release of thyroid hormones plus clinical signs and symptoms
US- prevalence approximately 1.2%
30
What are the common signs and symptoms of hyperthyroidism?
```
Thyroid enlarged
Fine hand tremor
Brisk DTRs
Ecg – tachy, afib
Insomnia
Heat intolerance
Diarrhea
Weight Loss
Fatigue, muscle weakness
Palpitations
Nervousness, anxiety, irritability
Increased appetite
Exopthalmos
Amenorrhea/menstrual irregularity
```
31
What are some causes of hyperthyroidism?
- Graves’ Disease (accounts for up to 75% of cases) autoimmune disorder- remission has been reported in up to 30% of pts w/o treatment
- Toxic adenoma or single toxic nodule (3-5%)
- Toxic multinodular goiter (common in older patients in regions of iodine deficiency)
- Subacute Thyroiditis- viral- presentation: fever and pain.
- Painless Thyroiditis – postpartum, or with certain drugs- - Lithium or Amiodarone (thyroiditis occurs in 5-10% of the time)
- Excessive thyroid hormone ingestion
Overproduction of TSH (pituitary tumor)
32
What is Graves' disease?
- Autoimmune process
- Circulating immunoglobulins stimulate thyroid activity
- Antibodies active against TSH receptors which stimulates the gland to synthesize and secrete excess thyroid hormone
33
Where are toxic multinodular goiters most commonly found?
- 10 times more common in iodine deficient areas
- 5% of cases in US
- Typically patients 40 and older
34
In what patient population do we normally see toxic ademona?
Younger patients
35
What are the different types of thyroiditis?
- Subacute – post viral
| - Lymphocytic and postpartum – transient inflammatory conditions
36
How do you diagnose hyperthyroidism?
1. Serum TSH – most sensitive and specific test
- TSH level will be low or even undetectable
2. Free T4 usually elevated in addition to low TSH
3. Consider ordering a total T3 level in a patient with suspected hyperthyroidism and a normal free T4 (5% of patients with hyperthyroidism have a normal T4 and an elevated T3 early in disease)
37
What causes Graves’ opthalmopathy?
Caused by infiltration of lymphocytes into extraocular muscle tissue that results in inflammation and forward protrusion of globe
38
What is Graves’ infiltrative dermopathy?
Thickening of skin
39
What are some patient factors to consider when choosing treatment for hyperthyroidism?
- Cause and severity of thyroid dysfunction
- Age
- Size of goiter
- Comorbid conditions
GOAL – correct the hypermetabolic state with the fewest side effects and the lowest incidence of hypothyroidism
40
What are some treatment options for hyperthyroidism?
- Radioactive Iodine (TOC in US)
- Surgery (subtotal thyroidectomy)-may be most appropriate for patients with severe hyperthyroidism/large goiter who require rapid control
- Antithyroid Drugs: Methimazole and propylthiouracil
- Adjunctive Therapy: BBs for sx management- start at time of diagnosis of hyperthyroidism assuming there is no contraindication
(Atenolol 25-50mg daily)
41
How is radioactive iodine (RAI) used in patients with hyperthyroidism?
- TOC for Graves’ and toxic multinodular goiter
- Performed in a radiology setting
- Inexpensive, highly effective, easy to administer, and safe
- Administered as a capsule or oral solution
- Iodine concentrates in thyroid gland and disrupts hormone synthesis and destroys thyroid tissue within 6-18 weeks
42
What are some considerations with dosing RAI?
- Degree of destruction dependent upon dosage . . .
- Higher doses favored in elderly, patients with cardiac disease, or patients who require rapid control of symptoms
- Smaller doses more likely to achieve euthyroidism
- Within 3 months most patients develop hypothyroidism and require lifelong thyroid replacement therapy
43
How do thianomide drugs work and what are the two most common ones?
- Interfere with thyroid hormone synthesis
- Methimazole (Tapazole)
- Propylthiouracil (PTU)
44
What is the thianomide drug of choice in nonpregnant patients?
- Methimazole (Tapazole)
- Once daily dosing, rapid efficacy
- Give in conjunction with beta bockade for first 4-8 weeks
- Monitor clinical status and monthly free T4 levels
- Duration of treatment usually 12-18 months
- Relapse in 50-60% of patients usually within 3-6 months of cessation of drug therapy
45
What is the preferred thianomide drug for pregnant women?
Propylthiouracil (PTU)
Preferred for pregnant women
Starting dose 100mg TID
Maintenance dose 100-200 mg/day
46
What are some side effects of propylthiouracil (PTU)?
- Agranulocytosis is most serious complication and presents with sudden fever or sore throat
- Minor side effects – rash, fever, elevated liver enzymes
- Arthritis/poly-arthralgia syndrome
47
What is the most common type of thyroid surgery and how does it work?
Subtotal thyroidectomy
- Preserves some thyroid tissue and reduces the incidence of hypothyroidism to 25% (recurrent hyperthyroidism occurs in 8% of patients)
48
On who do we perform total thyroidectomy?
Severe disease or large goiters in whom recurrences would be largely problematic
49
When is surgery indicated for Graves' disease?
Surgery for Graves’ Disease is the least popular choice of endocrinologists except for patients with obstructive goiters, intolerance or contraindication to the other treatment options or if there was a coexisting suspicious
50
What is the prognosis & risks associated with hyperthyroidism?
- Good with appropriate treatment
- Even with aggressive treatment some manifestations of the disease are irreversible
~Ocular
~Cardiac
~Psychologic
- Increased all-cause mortality risk
- Increased incidence of cardiac and cerebrovascular disease
- Increased incidence of hip fractures
- Remember to screen for osteoporosis and atherosclerotic disease
51
How often are thyroid nodules malignant and what is the prognosis?
- Vast majority are benign
- Often incidental finding on exam or radiology study
- 4-6.5% malignant
- Most have excellent prognosis – worst prognosis if older or more invasive cancer
- High resolution US (cystic vs. solid)
- Scintigraphy: radioiodine uptake
~Functional status – “hot” vs. “cold”
52
How is thyroid cancer diagnosed?
- FNA – fine needle aspiration (gold standard)
- High resolution US (cystic vs. solid)
- Scintigraphy: radioiodine uptake
~Functional status – “hot” vs. “cold”
53
What components of the HPI are concerning for or contribute to likelihood of thyroid nodules?
- Age
- Rate of neck mass growth
- Anterior neck pain
- Dysphonia, dysphagia, or dyspnea
- Previous head or neck irradiation
- Symptoms of hypothyroidism or hyperthyroidism
- Personal or family history of thyroid cancer
- Use of iodine containing drugs or supplements
54
What are some important components of the physical exam when assessing thyroid nodules?
Careful focused exam of thyroid and lymph nodes
- Thyroid volume and consistency
- Location, consistency, size and number of nodules
- Neck tenderness or pain
- Cervical lymphadenopathy
55
When should a thyroid US be performed?
In all patients with a suspected thyroid nodule
- Assesses size and location of nodules
- Evaluate adjacent neck structures
56
What labs should be ordered for patients with thyroid nodules?
- TSH
- If TSH elevated, then free T4 and thyroid peroxidase antibodies (TPOAb)
- IF TSH decreased, then free T4 and free T3
57
How does a thyroid scintigraphy work?
- To check the function of the thyroid gland, radioactive iodine is given and then a picture is taken to evaluate the glands ability to concentrate the iodine. (24 hrs)
- Tell you if thyroid is functioning or not – “cold” nodule doesn’t absorb radioactive iodine, more indicative of cancer, “hot” nodule soak up iodine, less risk for cancer
- Not done often anymore - now if nodule large enough, biopsy
58
What is recommended by American Thyroid Association thyroid cancer guidelines (2015) as the procedure of choice to evaluate suspicious nodules?
Fine Needle Aspiration
- Should be US guided
- Decision to biopsy is based on US features and size of nodule
~> 10 mm – need FNA
~If < 10 mm but suspicious US findings present-
need FNA
~If < 5 mm- monitor
- If cytology suggests cancer refer to surgeon
59
How do you manage benign thyroid nodules?
- Typically no surgery needed
- Periodic US monitoring of benign nodules initially at 6-12 months, then yearly
- If nodule increases in size then may need to repeat FNA
- These patients should be under the care of endocrine or ENT
60
What is the cause, s/sx, and tx of thyroid storm?
- Acute, life threatening, hypermetabolic state
- Patient presents with severe tachycardia, hypertension, hyperthermia, and CNS dysfunction
- Precipitated by infection, trauma, surgery, pregnancy, DKA, RAI treatment, thyroid hormone ingestion
- Refer to emergency department
- Rx – PTU or methimazole ; beta blockade (inderal); glucocorticoids; antipyretics
Primary Care Exam 3
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