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.


Screening

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

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

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)

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

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

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

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

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:

http://www.primarycareguidelines.com/uploads/5/8/1/0/5810751/uoft2011_thyroid.pdf

UpToDate Nov 19/2014

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Posted in 91 Thyroid, 99 Priority Topics, Endo, FM 99 priority topics

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