Thyroid Update Dr. D. Zatelny BaSc, MD, FRCPC

Objectives Review practical primary care management of 3 common thyroid conditions through a case based approach Encourage discussion !

Case 1 PMHx: depression Meds: BCP FMHx: father had MI age 52 yrs. 26 yr old married executive secretary referred for possible hypothyroidism PMHx: depression Meds: BCP FMHx: father had MI age 52 yrs. mother had Graves disease HPI: Patient c/o fatigue and weight gain She is concerned she may be hypothyroid

Case 1 O/E BP 112/66 HR =74 bpm BMI = 30 Labs: Hb = 116 eye exam normal thyroid exam normal Labs: Hb = 116 ferriten = 9 sTSH = 6.2

What would you do next?

Case 1 After discussion with patient she elects to repeat her bloodwork in 3-4 months including FT4 and TAb Patient presents 2 months later concerned she may be pregnant

Case 1 LABS: Bhcg +ve sTSH = 5.8 FT4 = 15 TPOAb =1:764 TGAb = 1:66

Pregnancy & the Thyroid Pregnancy is a stress test for the thyroid

Pregnancy & the Thyroid The gland increases 10% in size Production of FT4 & FT3 increases by 50%, Due to the impact of placental hCG, sTSH decreases throughout pregnancy with the lower limit of normal in the 1st trimester being poorly defined

RECOMMENDATION The following reference ranges are recommended: 1st trimester, 0.1–2.5 mIU/L; 2nd trimester, 0.2–3.0 mIU/L; 3rd trimester, 0.3–3.0 mIU/L.

OH and SCH in pregnancy OH is defined as a TSH > 2.5 in conjunction with a decreased FT4 or a TSH >10.0 irrespective of the FT4 levels SCH is defined as a TSH between 2.5 and 10 mIU/L with a normal FT4

Adverse Outcomes Associated with OH in Pregnancy OH in pregnancy has consistently been shown to be associated with an increased risk of adverse pregnancy complications, as well as detrimental effects upon fetal neurocognitive development Specific adverse outcomes include increased risk of premature birth, LBW, miscarriage and gestational hypertension

Adverse Outcomes Associated with SCH in Pregnancy “the majority of scientific evidence suggests SCH is associated with increased risk of adverse pregnancy outcomes” “an association between maternal SCH and adverse fetal neurocognitive development is biologically plausible though not clearly demonstrated”

RECOMMENDATION The recommended treatment of maternal hypothyroidism is LT4 It is strongly recommended not to use other thyroid preparations such as T3 or desiccated thyroid.

RECOMMENDATION Hypothyroid patients on LT4 who are newly pregnant should increase their dose of LT4 by ~25%–30% One simple suggestion for patients is to increase LT4 from once daily dosing to a total of nine doses per week TSH should be monitored approximately every 4 wks during the first half of pregnancy and once between 26 – 32 wks gestation

Postpartum Pearls

Who is at risk for developing postpartum thyroiditis? Any woman with: Autoimmune disorders (such as Type1 dm) Positive anti-thyroid antibodies History of previous thyroid dysfunction including previous postpartum thyroiditis Family history of thyroid dysfunction

Postpartum Thyroiditis Is the occurrence of thyroid dysfunction in the first year post partum in women euthyroid prior to pregnancy In its classical form, transient thyrotoxicosis is followed by transient hypothyroidism with a return to the euthyroid state by the end of the first postpartum year The thyrotoxic phase occurs 1-4 months after delivery and lasting for 1-3 months The hypothyroid phase, typically occurs 4-8 months after delivery and may last up to 9 –12 months. 1/3 of patients wil only have a thyrotoxic or hypothyroid phase Approximately 20% of those that go into a hypothyroid phase will remain hypothyroid.

RECOMMENDATION During the thyrotoxic phase of PPT, symptomatic women may be treated with beta blockers Propranolol at the lowest possible dose is the treatment of choice ATDs are not recommended for treatment of the thyrotoxic phase of PPT

RECOMMENDATION Women who are symptomatic during the hypothyroid phase of PPT should have their sTSH level retested in 4–8 wks or start on LT4 Women who are asymptomatic during the hypothyroid phase of PPT should have their TSH level retested in 4–8 wks

Case 2 56 yr old divorced firefighter referred for goitre PMHx: hypertension PSHx: hernia, vasectomy Meds: micardis 80 mg od FMHx: adopted HPI: Patient noted to have a goitre on routine physical exam

Case 2 O/E BP 142/86 BMI = 26 HR = 76 thyroid: exam otherwise normal visible fullness over left lobe on palpation well circumcribed nodule measuring approximately 2 cm no lymphadenopathy exam otherwise normal

Thyroid Nodule Guidelines Clinical risk factors predicting malignancy include: history of neck radiation family history of thyroid cancer age < 30 yrs or > 60 yrs male gender rapid growth of nodule voice hoarseness

What would you do next?

Thyroid U/S U/S should be performed in all patients with known or suspected thyroid nodules Various U/S features have been associated with a higher likelihood of malignancy hypoechogenicity increased intranodular vascularity irregular margins microcalcifications abnormal lymph nodes

RECOMMENDATION Measure sTSH in the initial evaluation of a patient with a thyroid nodule. If the serum TSH is subnormal, a thyroid scan should be performed to rule out a “hot nodule”

Case 2 Labs: sTSH = 2.2 U/S: The thyroid gland is nodular in appearance. The largest nodule in the right lobe measures .9 x .6 x .5 cm. There is a dominant nodule in the left lobe measuring 2.4 x 1.4 x 1.2 cm. Cervical lymph nodes appear normal. Impression: Multinodular goitre with a dominant nodule in the left lobe.

What would you do next?

FNAB FNA is the most accurate and cost-effective method for evaluating thyroid nodules FNA is not recommended for subcentimeter nodules unless clinical or U/S suggests high risk Only solid nodules >1 cm should be evaluated, since they have a greater potential to be clinically significant cancers

FNAB In the presence of two or more thyroid nodules > 1 cm, those with suspicious U/S features should be aspirated It is rarely necessary to biopsy more than 2 nodules If a thyroid scan is available, do not biopsy “hot areas” FNA is reported as one of six diagnostic categories

FNAB Diagnostic Category Risk of Malignancy Nondiagnostic, 1 – 4% Benign 0.3% Follicular lesion , undetermined significance 5 – 15% Follicular or Hurtle cell neoplasm 15 – 30% Suspicious for Malignancy 60 – 75% Malignant 97 – 99%

Case 2 FNAB: consistent with a follicular lesion, undetermined significance Options: Repeat U/S in 6 – 18 mos. and repeat FNAB if size has increased > 20% in 2 dimensions Surgical excision (risk of malignancy = 5 – 15%)

Case 3 54 yr old ER nurse referred for hyperthyroidism PMHx: insomnia PSHx: wisdom teeth Meds: Ativan prn FMHx: sister had PPT HPI: Patient presents with a 3 mos history of intermittent tremor and palpitations and 2 mos history of 15 lb wt loss and heat intolerance

Case 3 O/E: LABS: eyes: mild stare, no exophthalmos mild tremor HR = 94 BMI = 24 eyes: mild stare, no exophthalmos mild tremor thyroid: visibly enlarged, on palpation enlarged to 3 x normal no nodularity, non tender LABS: FT4 = 49 FT3 = 5.6 sTSH < .01

What would you do next?

RECOMMENDATION A RAI131uptake should be performed when the clinical presentation of thyrotoxicosis is not diagnostic of GD A thyroid scan should ONLY be added in the presence of thyroid nodularity

RAI 131 Patient has a thyroid uptake which is elevated with a 24 hr uptake of 44% ( normal < 25 % )

CAUSES OF THYROTOXICOSIS Thyrotoxicosis associated with a normal or elevated RAI131 uptake Graves Disease (GD) Toxic Adenoma (TA) or Toxic MNG RARE: TSH-producing pituitary adenomas, thyroid hormone resistance Thyrotoxicosis associated with a low RAI131 uptake Painless (silent) thyroiditis, acute thyroiditis, PPT Amiodarone-induced thyroiditis RARE: Iatrogenic , factitious

Graves Disease GD is an autoimmune disorder in which TRAbs stimulate the TSH receptor on the thyroid gland, increasing thyroid hormone production. Overt thyrotoxicosis is characterized by elevated FT4 and FT3 and suppressed TSH (<0.01) Subclinical hyperthyroidism is characterized by normal FT4 and FT3 and a suppressed TSH (<0.01) There is only moderate correlation between elevation in FT4 and clinical signs /symptoms

TREATMENT Beta-adrenergic blockade should be given to elderly patients with symptomatic thyrotoxicosis or to any thyrotoxic patient with resting HR > 90 bpm or coexistent cardiovascular disease

TREATMENT Patients with overt GD should be treated with any of the following modalities: RAI131 therapy antithyroid medication thyroidectomy

RAI 131 Most patients respond to RAI131therapy with a normalization of FT4 and clinical symptoms within 4–8 weeks. Hypothyroidism most commonly occurs between 2 - 6 months post treatment Since TSH levels may remain suppressed for months after hyperthyroidism resolves, the levels should be interpreted only in concert with FT4

Anti-Thyroid Drugs The goal of the therapy is to render the patient euthyroid as quickly and safely as possible. These medications do not cure GD Patients with mild disease, small goiters, and negative TRAb have a higher remission rate making the use of ATD more favorable in this group of patients Treatment may have a beneficial immunesuppressive role, but the major effect is to reduce the production of thyroid hormones and maintain a euthyroid state while awaiting a spontaneous remission

RECOMMENDATION Methimazole (Tapazole) should be used in virtually every patient who chooses ATD therapy for GD except … Propylthiouracil (PTU) is preferred during the first trimester of pregnancy and in patients with minor reactions to methimazole who refuse RAI131therapy or surgery

RECOMMENDATION If methimazole is chosen as the primary therapy for GD, the medication should be continued for approximately 12–18 months, then tapered or discontinued if the TSH is normal If a patient with GD becomes hyperthyroid after completing a course of methimazole, consideration should be given to treatment with RAI131 or surgery Low-dose methimazole treatment for > 12–18 months may be considered in patients not in remission who prefer this approach

Surgery Thyroidectomy should be considered in: patients with allergies, contraindications or non adherence with ATDs who cannot or will not pursue RAI131 second trimester pregnancy, if surgery is indicated patients with moderate to severe TAO.

Case 3 Patient elected initial treatment with RAI131 Propranolol was initiated prior to RAI131 for management of tremor, palpitations +/- insomnia Repeat bloodwork (FT4) will be done q 4-6 weeks post treatment LT4 is started once FT4 is in low normal range

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