Thyroid Disease – 2011 UofT FM Guideline & Uptodate

Overview

Hypothalamus –> TRH – pituitary gland –> TSH, which controls the production of T3 & T4 from the thyroid gland. T3/T4 affects protein synthesis by affecting gene transcription and mRNA stabilization. They play an important role in regulating tissue metabolism and development.

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Screening

• Those with risk factors & presents with non-specific signs & symptoms
• Asymptomatic adults don’t require routine screening.

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Risk Factors

1. Hx of autoimmune disease, eg. DM1
2. Hx of neck irradiation
3. Drug therapies (Lithium, amiodarone)
4. Family Hx of thyroid dz
5. women >50yo or in the period of up to 6mo post-partum

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Signs & symptoms

Hypothyroidism

1. Wt gain, constipation
2. hair loss, dry skin, cold intolerance
3. bradycardia / diastolic HTN
4. lethargy, cognitive impairment, depression
5. goiter
6. Menstrual irregularities (menorrhagia)

Hyperthyroidism

1. Wt loss, hair loss
2.  heat intolerance, diaphoresis, clammy hands
3. palpitations / tachycardia / atrial fibrillation / HTN / widened pulse pressure
4. nervousness / tremor / anxiety
5. goiter
6. menstrual irregularities (amenorrhea / oligomenorrhea)
7. proximal muscle weakness

Red Flags for thyroid cancer

1. Male gender, extremes in age (<20yo or > 65yo)
2. Rapid growth of nodule
3. Symptoms of local invasions: dysphagia, neck pain, hoarseness
4. Hx of radiation to the head or neck
5. Family Hx of thyroid cancer or polyposis (Gardner’s syndrome)

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Investigation

TSH – no further testing if normal

• ↑TSH – free T4 added to determine the degree of hypothyroidism
• ↓TSH – free T3 and T4 added to determine the degree of hyperthyroidism
• TSH and free T4 if pituitary or hypothalamic disease suspected (eg, a young woman w/ amenorrhea + fatigue).
• free T4 if convincing symptoms of hyper- or hypothyroidism despite a normal TSH result.

ANTITHYROID ANTIBODIES

• Routine measurement of antithyroid antibodies is not necessary for the assessment of thyroid function.
• Serum antithyroid peroxidase antibodies need not be measured in patients with overt primary hypothyroidism because almost all have chronic autoimmune thyroiditis.
• Thyroglobulin (Tg), 
• Thyroid peroxidase (TPO), 
  • useful to predict the likelihood of progression to permanent overt hypothyroidism in patients with subclinical hypothyroidism.
• The (thyrotropin)TSH receptor antibodies (TRAb) – confirm graves: 3 types- stimulating, blocking, or neutral
  • Unnecessary for establishing the cause of hyperthyroidism if a radioiodine uptake has been obtained.
  • May be useful when a radioiodine uptake is unavailable or contraindicated (eg, to distinguish Graves’ hyperthyroidism from postpartum thyroiditis in a nursing mother).
  • Useful for assessing the likelihood of remission after a course of antithyroid drugs in patients with Graves’ disease.

• a thyroid u/s if PE suggests nodularity
• Thyroid uptake scan to differentiate causes of a hyperthyroid state

Serum TSH	Serum Free T4	Serum T3	Assessment
Normal hypothalamic-pituitary function
Normal	Normal	Normal	Euthyroid
Normal	Normal or high	Normal or high	Euthyroid hyperthyroxinemia
Normal	Normal or low	Normal or low	Euthyroid hypothyroxinema
Normal	Low	Normal or high	Euthyroid: triiodothyronine therapy
Normal	Low normal or low	Normal or high	Euthyroid: thyroid extract therapy
High	Low	Normal or low	Primary hypothyroidism
High	Normal	Normal	Subclinical hypothyroidism
Low	High or normal	High	Hyperthyroidism
Low	Normal	Normal	Subclinical hyperthyroidism
Abnormal hypothalamic-pituitary function
Normal or high	High	High	TSH-mediated hyperthyroidism
Normal or low*	Low or low-normal	Low or normal	Central hypothyroidism

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Causes of Hypothyroidism

Primary:

1. Chronic autoimmune thyroiditis (Hashimoto’s)
2. Transient: painless thyroiditis, postpartum thyroiditis, subtotal thyroidectomy, following tx of Grave’s thyroidectomy, subacute thyroiditis
3. Infiltrative: fibrous thyroiditis, sarcoidosis
4. medications
5. Iatrogenic – thyroidectomy, radioactive iodine Tx

Secondary

1. Pituitary lesion causing TSH deficiency
2. Hypothalamic lesion causing TRH deficiency

Causes of Hyperthyroidism

Primary

1. Autoimmune: Graves’ dz, Hashimoto’s (Hashitoxicosis – rare)
2. Toxic multinodular goiter
3. Toxic adenoma
4. Exogenous thyroid hormone intake
5. Postpartum thyroiditis
6. Neoplastic (usually metastatic thyroid cancer – very rare)
7. Drug-induced (amiodarone)

Secondary

1. TSH-producing pituitary adenoma
2. Other: Gestational hyperthyroidism (with hyperemesis gravidarum), trophoblastic dz

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Management & Monitoring

Hypothyroidism

Synthroid (Levothyroxine LT4) 

• Start at 50mcg daily & increase incrementally
• Take on empty stomach to improve absorption
• Check TSH 6 weeks after initiation & change in dose or clinical status
• Check annually once normalized

Hyperthyroidism

Antithyroid meds

PTU (propylthiouracil) 

• Initiate at 100mg tid for hyperthyroidism; higher dosages for thyrotoxicosis
• Maintenance dose usually 50-150mg/day

Methimazole

• initiate at 5-20 mg tid for 4-6 weeks then re-evaluate; reduced by 1/3 once T4 or T3 have returned to normal
• Maintenance dose: 5-15mg daily or div tid
• cutis aplasia in early pregnancy (therefore avoid in T1)

Both may cause vasculitis, hepatitis (PTU > methimazole), agranulocytosis

Radioactive Iodine (RAI)

• one time pill, curative, may require 2nd dose
• Pt required to follow radioactive precautions for one week after administration
• Hypothyroid long-term, can worsen Grave’s orbitopathy (especially in smokers)
• Can’t use in pregnancy, should not be pregnant for 5-12 months after Tx

Thyroidectomy

• Curative, invasive, requires life-long levothyroxine Tx.
• Rare c/i of hypoparathyroidism & recurrent laryngeal nerve damage

Beta-blocker

• needed for short-term Tx of symptoms until the above Tx take effect
• usually Atenolol 25-50mg od, or propranolol 20-40mg bid-qid 
• Monitoring
• Recheck TSH after 6-12 weeks, as pituitary secretion may be suppressed for several months
• Thyroid status may be assessed using fT4 –
• CBC not routinely done, only if s/sx of agranulocytosis

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Subclinical Hypothyroid dz with elevated TSH and normal fT4

• Monitor TSH annually in untreated pt
• Tx if
  • TSH >10mU/L
  • Elevated TSH < 10mU/L with the following
    • Goitre
    • Pregnancy
    • Strong family hx of autoimmune dz
    • Elevated TPO (thyroid peroxidase) antibodies

Subclinical Hyperthyroidism with suppressed TSH and normal fT4 (less common)

• TSH q6-12 month
• Tx if pt have A fib and/or osteoporosis

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Thyroid Dz in Pregnancy

• Maternal hypothyroidism is associated with decreased IQ in newborns
• TSH screening in all women with a goiter or strong family Hx of thyroid dz who are planning pregnancy or who are in early pregnancy
• TSH may be suppressed as a normal finding in pregnancy; hyperthyroidism may be ruled out with a normal fT4
• TSH target = 0.5-2.5mU/L in the 1st trimester & 0.5-3mU/L in the 2nd and 3rd trimester
• Synthroid requirements may increase 50% during pregnancy
• Post-pregnancy, most women need a reduction in synthroid dose
  • screening for post-partum thyroiditis at 3 & 6 months in women at increased risk (positive anti-TPO ab)

Reference:

UpToDate Nov 19/2014