Management of Thyroid Disease - c.ymcdn.com · Management of Thyroid Disease: Too much, too little, masses Fitzgerald Health Education Associates, Inc. 1 ... –=>50% increase during

Management of Thyroid Disease: Too much, too little, masses

1 Fitzgerald Health Education Associates, Inc.

Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC

President, Fitzgerald Health Education Associates, Inc.,

North Andover, MAFamily Nurse Practitioner,

Greater Lawrence (MA) Family Health CenterEditorial Board Member

The Nurse Practitioner Journal, The Prescribers Letter, American Nurse Today

Member, Pharmacy and Therapeutics CommitteeNeighborhood Health Plan, Boston, MA

Objectives

• Upon completion of this program, the participant will be able to:

–Discuss the pathophysiology of common thyroid disorders.

– Identify expected laboratory findings in common thyroid disorders including TSH, free T4, total T4, T3, and antithyroid antibodies.

Fitzgerald Health Education Associates, Inc. 2


• Upon completion of this program, the participant will be able to: (cont.)

–Discuss treatment options for the person with select thyroid disorders including thyroid masses.

Objectives (continued)

Thyroid Disorders

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References

• American Association of Clinical Endocrinologist Medical Guidelines for Clinical Practice: Hyperthyroidism and Hypothyroidism, available at https://www.aace.com/publications/guidelines

• American Thyroid Association: Topics Related to Hypothyroidism, available at

http://www.thyroid.org/thyroid-guidelines/hypothyroidism/topics/


Key Concepts in Thyroid Disease

• The thyroid produces two hormones, thyroxine (T4) and triiodothyronine (T3). These hormones act as cellular energy release catalysts and influence the function and health of every cell in the body.


In HypothyroidismLess Cellular Energy Release

Area affected Change noted

Skin Thick, dry

Reflexes

“Hung up” patellar reflex, slow arc out, slower arc back,

overall hyporeflexia esp Achilles tendon

Mentation “Can’t make sense, thoughts too slow.”

Weight change Small gain


In HypothyroidismLess Cellular Energy Release

(continued)


Stool pattern Constipation

Menstrual issue Menorrhagia

Heat/cold perception Easily chilled


Hypothyroidism: Common Etiology

Condition Comment

Hashimoto thyroiditis Autoimmune in nature

Post radioactive iodine (RAI) treatment

S/P Graves’ disease, thyroid cancer treatment

Select medication use Lithium, amiodarone, interferon, others


In Hyperthyroidism

Excessive Cellular Energy Release


Skin Smooth, silky

Reflexes Hyperreflexia

Mentation“Can’t make sense,

mind racing”


In Hyperthyroidism

Excessive Cellular Energy Release (continued)


Weight Loss

Stool patternFrequent, low volume, loose

Menstrual issue Oligomenorrhea

Heat/cold tolerance Heat intolerance


Hyperthyroiditis: Common Etiology

Condition Common etiology

Graves’ disease

Multisystem presentation

Toxic adenoma

Metabolically active lesion

ThyroiditisViral, autoimmune, post partum, often transient


Exophthalmus in Graves' Disease


Thyroid Test

Test Evaluates Comment

Thyroid stimulating hormone (TSH)NL=0.4-4.0 mIU/L

True population distribution= 0.5-1.5 mIU/L range with M=1.18 mIU/L

Hypothalamic-pituitary-thyroid axis function, reflects

anterior pituitary lobe’s ability to detect amount of circulating free thyroxine

Per American Thyroid Association, single most reliable test to

diagnose all common forms of hypo- and hyperthyroidism, particularly in the ambulatory setting


Thyroid Test (continued)

Test Evaluates CommentFree T4 (FT4, free thyroxine)

NL=0.5-1.3 ng/dL (6-16.7 pmol/L )

Unbound, metabolically active portion of thyroxine

About 0.025% of all T4

Total T4 (total thyroxine)

NL=4.5-12.0 mcg/dL (57.9-154.4 nmol/L)

Reflects the total of the protein-bound and free thyroxine

Often altered in the absence of thyroid disease but with the use of select medications (exogenous estrogen {HT, OC}, methadone) and presence of clinical conditions such as pregnancy, chronic hepatitis




Free T3

NL=0.2-0.5 ng/dL (3.5-7.7 pmol/L)

Unbound, metabolically active portion of triiodothyronine (T3)

When compared to T4 (prodrug for T3), T3 is about 4 X more

metabolically active.

About 20% of circulating (T3) is from the thyroid, rest as a result of conversion of T4

to T3




Total T3

NL=95-190 ng/dL (1.5-2.9

pmol/L)

Reflects the total of the protein bound and free triiodothyronine

See comments on total T4




Antiperoxidase (antimicrosomal) antibodyNL=Depends on

lab method, from negative to <1:1000

An antibody against peroxidase, an enzyme

held within the thyroid

Also known as thyroid peroxidase (TPO) antibody (TPO Ab) test,

thyroid peroxidase autoantibody test, antimicrosomal antibody test and antithyroid antibody


American Thyroid Association: Thyroid Function Tests

Available at

www.thyroid.org/blood-test-for-thyroid/


Measuring TSH and FT4?

• “When thyroid status is stable and hypothalamic-pituitary function is intact, serum TSH measurement is more sensitive than free T4 (FT4) for detecting mild (subclinical) thyroid hormone excess or deficiency.”


Measuring TSH and FT4? (continued)

• “The superior diagnostic sensitivity of serum TSH reflects the log/linear relationship between TSH and FT4 and the exquisite sensitivity of the pituitary to sense free T4 abnormalities relative to the individual’s genetic free T4 set-point.”

– Source: www.aacc.org/sitecollectiondocuments/nacb/lmpg/thyroid/thyroid-fullversion.pdf


Measuring TSH and FT4? (continued)

• “Serum FT4 measurement is a more reliable indicator of thyroid status than TSH when thyroid status is unstable, such as during the first 2-3 months of treatment for hypo- or hyperthyroidism.”

– Source: www.aacc.org/sitecollectiondocuments/nacb/lmpg/thyroid/thyroid-fullversion.pdf


True or false?

• TSH levels peak in the evening and are lowest in the afternoon.

• TSH varies with physiologic conditions such as illness, psychiatric disorders and low energy intake.


Thyroid Test ResultsLow Thyroxine (FT4)=High TSH

• Example–TSH=84 mIU/L (0.4-4.0 mIU/L)

–Free T4=3 pmol/L (10-27 pmol/L)

• Etiology–Untreated hypothyroidism

– Inadequate thyroxine dose


From Levothyroxine PI

• “Synthetic T4 is identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C15H10I4N NaO4 • H2O, molecular weight of 798.86 g/mol (anhydrous)…” – Source-www.rxabbvie.com/pdf/synthroid.pdf


From Levothyroxine PI(continued)

• T ½

– In hypothyroid state=9-10 d

– In euthyroid state=7 d

– In hyperthyroid state=3-4 d

• How many T ½ to reach steady state? Eliminate drug from the body?


Intervention in Hypothyroidism

• Calculating anticipated levothyroxine dose

–1.6 mcg/kg/day in adults

–1.0 mcg/kg/day in elderly

–4.0 mcg/kg/day in children

–=>50% increase during pregnancy

• Increase levothyroxine dose by =>33% as soon as pregnancy is confirmed.


True or false?

• When calculating the levothyroxine dose for a patient, ideal body weight (IBW) should be used for the person who is obese.

• For the person who is underweight, actual body weight should be used.


Therapy is usually initiated in patients under the age of 50 years with full replacement.

• For those patients who are older than 50 years, or in younger patients with a history of cardiac disease, a lower initial dosage is indicated, starting with 0.025 to 0.05 mg of levothyroxine daily, with clinical and biochemical reevaluations at 6- to 8-week intervals until the serum TSH concentration is normalized.


What about desiccated porcine thyroid preparations?

Source: American Thyroid Association Treatment Guidelines for Patients with Hypothyroidism,

available at http://thyroidguidelines.net


T4/T3 Combinations

• Desiccated thyroid preparations (T4/T3 combination, porcine origin such as Armour® Thyroid, Nature-Throid®, Bio-Throid®, Westhroid®)

–1 grain=60-65 mg thyroid USP=100 mcg levothyroxine

–Thyroid USP 60-120 mg per day for typical adult daily dose


Per American Thyroid Association (ATA)

• “Biological and synthetic thyroid hormone preparations containing both T4 and T3 are also not currently recommended for therapy since they produce fluctuating and often elevated T3 concentrations, although their use is not necessarily contraindicated.”


Monitoring Thyroxine Therapy

• TSH

–No sooner than 6-8 (AACE) or 8-12 (ATA) weeks

• Long T ½

• TSH too high

–Dose too low

–Adherence

–Drug interaction

• TSH too low

–Excessive use

–Dose too high


Thyroid Test ResultsHigh Thyroxine (FT4)=Low TSH

• Example

–TSH<0.15 mIU/L (0.4-4.0 mIU/L)


• Etiology

–Hyperthyroidism

–Excessive thyroxine dose


Intervention in Hyperthyroidism at the Time of Diagnosis

• Beta adrenergic antagonist

–B1, B2 blockade if possible

• Propranolol, nadolol

• Antithyroid medication

–PTU, methimazole

• Radioactive iodine (RAI)

–Thyroid ablation


From PTU PI

• “PTU inhibits synthesis of thyroid hormone by interfering with the incorporation of iodine into thyroglobulin; it also inhibits the formation of iodothyronine. Besides blocking hormone synthesis, it also inhibits the peripheral deiodination of thyroxine to triiodothyronine (liothyronine).”


FDA Advisory on PTU

• FDA is notifying healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil in adult and pediatric patients.

– Source: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm162701.htm


From Methimazole PI

• “Methimazole inhibits synthesis of thyroid hormone by interfering with the incorporation of iodide into tyrosyl. Methimazole also inhibits the formation of iodothyronine.”


From Methimazole PI(continued)

• There have been rare reports of fulminant hepatitis, hepatic necrosis, encephalopathy, and death. Symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.) should prompt evaluation of liver function.


Subclinical HypothyroidismElevated TSH, NL Free T4

• Example

–TSH=8.9 mIU/L (0.4-4.0 mIU/L)


–Antithyroid antibodies=1:1,800 (<1:1,000)


Per AACE GuidelinesSubclinical Hypothyroidism

• AACE guidelines recommend treatment of patients with TSH>5 mIU/L if the patient has a goiter or if thyroid antibodies are present.

• The presence of symptoms compatible with hypothyroidism, infertility, pregnancy or imminent pregnancy would also favor treatment.

– Source: https://www.aace.com/publications/position-statements


Samantha, 47 YO Woman

• Last year’s results

–TSH=1.2 mIU/L

• 0.35-4.0 mIU/L

–FT4=14 pmol/L

• 10-27 pmol/L

• This year’s results

–TSH=6.4 mIU/L

–FT4=6 pmol/L

• Long-standing hypothyroidism

• States continues to take her levothyroxine “every day, just like clockwork”


SamanthaInterim History

• Since last visit with you, saw gyn for heavy menstrual bleeding

• Underwent endometrial ablation procedure and is quite pleased with the results


Iron Ingestion and Levothyroxine Therapy

Campbell NR, et al. Ann Intern Med. 1992;117:1010-1013.

Ferrous sulfate effect on TSH levels in patients with hypothyroidism

P<.001

0

1

2

3

4

5

6

TS

H L

evel

, µI

U/m

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Before Ingestion After Ingestion44

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LT4 Interactions

• Iron

•Calcium

•Aluminum antacids

•Sucralfate

•Soy milk

• Formation of inactive drug compound

–Separate=>2h

–Empty stomach


Medications Increasing Metabolism of Thyroid Hormone

• Phenytoin

• Phenobarbital

• Carbamazepine

• Rifampin


NTI with Many Drug-drug, Drug-nutrient Interactions

• Take your levothyroxine

–Always at the same time of day

–Empty stomach, =>½ h before or =>2 h after meal

–Separate from other meds including OTC, minerals, vitamins by =>2 h


Generic or brand?Per AACE Statement

• "Patients should be maintained on the same brand name levothyroxine product. If the brand of levothyroxine medication is changed, either from one brand to another brand, from a brand to a generic product, or from a generic product to another generic product, patients should be retested by measuring serum TSH in six (6) weeks, and the drug reiterated as needed.


Generic or brand?Per AACE Statement

(continued)

• Since small changes in levothyroxine administration can cause significant changes in TSH serum concentrations, precise and accurate TSH control is necessary to avoid potential adverse iatrogenic effects.”– Source: http://dig.pharm.uic.edu/faq/levothyroxine.aspx


Continued Fatigue

• With NL TSH and free T4

–Consider checking T3

• T4

–~40% converted in peripheral tissue to T3


Should we also give T3?

• Triiodothyronine (T3) –About 4 X as active

as T4

–Can be important to brain function


T4 and Liothyronine Sodium (Cytomel®)?

• Add to T4?

– Liothyronine sodium, LT3 (Cytomel®) usual dose=12.5 mcg

• Short T ½

• Usual daily dose 25-75 mcg per day

–Reduce T4 dose by 50 mcg

• Inconclusive study in effectiveness but anecdotal, patient-by-patient reports


T3 Replacement Per ATA

• “After taking a tablet of Cytomel® there are very high levels of T3 for a short time, and then the levels fall off very rapidly. This means that T3 has to be taken several times each day, and even doing this does not smooth out the T3 levels properly.”– Source:

http://www.thyroid.org/patients/patient_brochures/hormonetreatment.html



Sonia35-year-old Woman

• Afebrile

• Pharynx and TM benign

• Hyperreflexia

• Tender, slightly enlarged thyroid


Sonia describes where her throat and ears hurt.


Sonia35-year-old Woman

(continued)

• TSH<0.15 mIU/L (0.15–4.0)

• Free T4=33 pmol/L (10–27)

• ESR=66 mm/hr (<15 mm/hr)

Thyroiditis: Subacute (Granulomatous) Thyroiditis

• In hyperthyroid phase

–Neck pain, a tender diffuse goiter, and elevated T4 and/or T3

• Caused by damage to thyroid follicular cells

and breakdown of stored thyroglobulin, leading to unregulated release of thyroxine (T4) and triiodothyronine (T3)



(continued)

• Duration of hyperthyroid phase

–Lasts 2–6 weeks until T4 and T3 stores are depleted• Low TSH minimizes thyroid

follicular stimulation

–Hypothyroidism often follows,

usually transient



(continued)

• Etiology

–Likely viral infection trigger

• Common report of recent URI symptoms

• Multiple case reports post

Coxsackievirus outbreaks

–Also strong association with HLA-B35

• ?Viral trigger with genetic basis


Additional More Common Thyroiditis Forms

• Subacute lymphocytic thyroiditis–Most common form of

postpartum thyroiditis

• Often presents with nervousness, poor sleep, painless thyroid, in first year postpartum, most often around month 3 after birth

–Lasts 1–2 months with self-resolution


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61

Thyroiditis Testing

• Additional evaluation

–Check anti-TPO antibodies

• More commonly positive in postpartum thyroiditis, rarely positive in granulomatous thyroiditis

• Consider thyroid scanning

–Generally increased uptake in Graves’ disease, low uptake in thyroiditis


Thyroid Scanning


American Thyroid Association: Thyroid Nodules Guideline

Available at www.thyroid.org/thyroidguidelines/revised/nodules/


Evaluation of a Thyroid Nodule

• The evaluation of a palpable thyroid nodule presents a challenge. In the absence of hyperthyroidism symptoms, the presentations of benign and malignant thyroid lesions are typically the same; the risk that any thyroid nodule is malignant is about 5%.


Evaluation of a Thyroid Nodule (continued)

• A history of head or neck irradiation, localized pain, dysphonia, hemoptysis, regional lymphadenopathy, or a hard fixed mass should raise suspicion.


Evaluation of a Thyroid Nodule (continued)

• Initial testing for a person with a thyroid nodule should include obtaining a TSH measurement. A metabolically active or “hot” nodule has a low risk of malignancy and can cause a reduction in TSH production from the pituitary. A thyroid scan can identify areas of increased uptake.


“Hot” Nodule


“Cold” Nodule


Thyroid Ultrasoundwithout and with Doppler


Evaluation of a Thyroid Nodule

• Fine needle aspiration biopsy is advised, regardless of TSH results, and is more helpful and cost-effective in arriving at a definitive diagnosis than ultrasound or thyroid scan. A properly performed fine needle aspiration biopsy has a false-negative rate of less than 5% and a false-positive rate of about 1%.


• Fitzgerald, M. A. Endocrine In Nurse Practitioner Certification Examination and Practice Preparation, Philadelphia, PA: F.A. Davis Company. Available at fhea.com/store


Additional Reference

End of Presentation

Thank you for your time and attention.

Margaret A. Fitzgerald,

DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC

www.fhea.com, e-mail: [email protected]



All websites listed active at the time of publication.

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Management of Thyroid Disease - c.ymcdn.com · Management of Thyroid Disease: Too much, too little, masses Fitzgerald Health Education Associates, Inc. 1 ... –=>50% increase during