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
- Hx of autoimmune disease, eg. DM1
- Hx of neck irradiation
- Drug therapies (Lithium, amiodarone)
- Family Hx of thyroid dz
- women >50yo or in the period of up to 6mo post-partum
Signs & symptoms
Hypothyroidism
- Wt gain, constipation
- hair loss, dry skin, cold intolerance
- bradycardia / diastolic HTN
- lethargy, cognitive impairment, depression
- goiter
- Menstrual irregularities (menorrhagia)
Hyperthyroidism
- Wt loss, hair loss
- heat intolerance, diaphoresis, clammy hands
- palpitations / tachycardia / atrial fibrillation / HTN / widened pulse pressure
- nervousness / tremor / anxiety
- goiter
- menstrual irregularities (amenorrhea / oligomenorrhea)
- proximal muscle weakness
Red Flags for thyroid cancer
- Male gender, extremes in age (<20yo or > 65yo)
- Rapid growth of nodule
- Symptoms of local invasions: dysphagia, neck pain, hoarseness
- Hx of radiation to the head or neck
- 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:
- Chronic autoimmune thyroiditis (Hashimoto’s)
- Transient: painless thyroiditis, postpartum thyroiditis, subtotal thyroidectomy, following tx of Grave’s thyroidectomy, subacute thyroiditis
- Infiltrative: fibrous thyroiditis, sarcoidosis
- medications
- Iatrogenic – thyroidectomy, radioactive iodine Tx
Secondary
- Pituitary lesion causing TSH deficiency
- Hypothalamic lesion causing TRH deficiency
Causes of Hyperthyroidism
Primary
- Autoimmune: Graves’ dz, Hashimoto’s (Hashitoxicosis – rare)
- Toxic multinodular goiter
- Toxic adenoma
- Exogenous thyroid hormone intake
- Postpartum thyroiditis
- Neoplastic (usually metastatic thyroid cancer – very rare)
- Drug-induced (amiodarone)
Secondary
- TSH-producing pituitary adenoma
- 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:
Click to access uoft2011_thyroid.pdf
UpToDate Nov 19/2014
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