Hypothyroidism, Subacute Thyroiditis Flashcards by Denisse Tiangco

A disease state caused by insufficient circulating thyroid hormone

Hypothyroidism

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Thyroid hormone deficiency caused by thyroid gland destruction or dysfunction

Primary hypothyroidism

Ex: Hashimoto’s thyroiditis

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Most common cause of hypothyroidism

Hashimoto’s thyroiditis

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Thyroid hormone deficiency caused by pituitary insufficiency
TSH deficiency occurs in the context of other anterior pituitary hormone deficiencies
Isolated TSH deficiency is rare

Secondary hypothyroidism

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Thyroid hormone deficiency caused by hypothalamic disease or disruption of hypothalamic pituitary portal blood flow
TRH deficiency usually occurs in the context of other hypothalamic hormone deficiencies
Isolated TRH deficiency is very rare

Tertiary hypothyroidism

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Elevated serum TSH

Normal free T4

Subclinical hypothyroidism

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Autoimmune Hashimoto’s thyroiditis
Epidemiology

Incidence
Mean age
Sex

Risk

Other predisposing factors

W 400: 100,000
M 100: 100,000

60 years
Prevalance increases with age

Rarely seen in children

Common in Japanese
High iodine diet

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Most common cause worldwide of hypothyroidism

Iodine deficiency

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Most common cause of hypothyroidism in iodine-sufficient regions

Autoimmune Hashimoto’s Thyroiditis

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Autoimmune disorder with genetic and environmental susceptibilities

Characterized by marked lymphochytic infiltration
atrophy of the thyroid follicles
absence of colloid
fibrosis

Leading to thyroid gland destruction

Hashimoto’s thyroiditis

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Thyroid-cell destruction is believed to be primarily mediated by

CD8+ cytotoxic T cells

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CD8 cytotoxic t cells destroy their targets by

Perforin induced cell necrosis

Granzyme B-induced apoptosis

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Thyroid cells are rendered susceptible to apoptosis because of cytokines

IL - 1
TNF
IFN

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End stage of Hashimoto’s thyroiditis

More extensive fibrosis
Less pronounced lymphocytic infiltration
Absence of thyroid follicles

Atrophic thyroiditis

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Primary Hypothyroidism etiology

Surgical: thyroidectomy
Radiation for iodine treatment in hyperthyroidism
External radiation of neck for lymphoma
Drugs 
Congenital
Infiltrative disorders

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Congenital causes of Primary Hypothyroidism

Thyroid agenesis or dysgenesis
Dyshormogenesis
TSH receptor mutations (inactivating)
Maternal antithyroid hormone therapy (transient)
Maternal TSH receptor antibodies (treatment)

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Drugs that cause hypothyroidism

Amiodarone
Lithium
Antithyroid drugs
Interferon alpha

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Cause of transient hypothyroidism

Silent thyroiditis (postpartum thyroiditis)
Subacute thyroiditis
Shortly after iodine treatment or subtotal thyroidectomy for Grave’s disease

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Hypothyroidism symptoms and signs

Fatigue
Generalized weakness
Dry skin
Cold intolerance
Hair loss
Difficulty concentrating/poor memory 
Constipation
Weight gain with poor apetite
Dyspnea
Hoarse voice
Menorrhagia (later in the clinical course, oligo or ameno)
Paresthesia
Impaired hearing

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Signs of hypothyroidism

Dry coarse skin; cool peripheral extremities
Puffy face, hands, feet (myxedema)
Diffuse alopecia
Bradycardia
Nonpitting peripheral edema
Delayed tendon reflex relaxation
Carpal tunnel syndrome
Serious cavity effusions

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Most common symptom of hypothyroidism

Fatigue and generalized weakness

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Most common sign of hypothyroidism

Dry, coarse skin, cool peripheral extremities

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Laboratory manifestations of hypothyroidism

Normochromic, normocytic anemia
Hypercholesterolemia
Hyponatremia (in advanced hypothyroidism)
Hyperprolactinemia
Elevated creatine phosphokinase level
Hypoglycemia (myxedema coma)

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The first-line diagnostic test for hypothyroidism and patient screening

Serum thyrotropin TSH

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An elevated TSH level should be confirmed by

repeated measurement of TSH with FT4

When evaluating thyroid function in suspected hypothalamic/pituitary disease, TSH measurement

is inadequate

May be useful to define underlying cause of primary hypothyroidism although not required in all settings

measurement of antithyroid antibodies

If a patient has sustained hypothyroidism after extensive exclusion of other potential causes, it is presumed to be

autoimmune in origin

Primary hypothyroidism Initial Test

TSH If normal, exclude primary thyroid abnormality If elevated, confirm by repeat TSH and FT4

Primary hypothyroidism thyroid function profile

Elevated TSH | Low FT4

Subclinical hypothyroidism

Elevated TSH | Normal FT4

TSH normal and pituitary disease suspected but low free T4 level

assess for possibility of medication effects or sick euthyroid syndrome

TSH level normal and pituitary disease suspected Normal free T4

Excludes secondary and tertiary causes of hypothyroidism

Secondary or Tertiary Hypothyroidism Lab profile

TSH level: highly variable usually normal | FT4: LOW

Present in 90-95% of patients with autoimmune hypothyroidism 40-80% of patients with Grave’s Useful in predicting progression of subclinical to overt hypothyroidism

TPO antibodies

Present in 5-25% of euthyroid women 2% of euthyroid men Not specific for diagnosis of autoimmune hypothyroidism not indicated for evaluation Important in management of patients with differentiated thyroid carcinoma

Thyroglobulin autoantibodies

Iodine scan in Hashimoto’s thyroiditis shows

Decreased and heterogenous tracer uptake

When secondary or tertiary hypothyroidism is suspected, this imaging may be employed

MRI of pituitary gland | MRI/CT of the brain if suprasellar process suspected

Biopsy of Hashimoto’s thyroiditis reveal

Lymphocytic infiltration Follicular destruction Fibrosis

Treatment of choice for hypothyroidism

Levothroxine

Endocrine emergency treated promptly with thyroid hormone once coexisting adrenal insufficiency is excluded

Myxedema coma

Treatment for overt hypothyroidism

Levothyroxine 1.6 microgram/kg Starting dose <60: without CV disease 50-100 in severe: lower end dose recommended

TSH should be checked once started on levothyroxine after

2 months

Goal of TSH level in hypothyroidism

1-2 mIU/L

Multiple levothyroxine products exist. TSH level should be rechecked after switching to a new product to ensure adequate dosing.

Bioequivalence

In a patient of normal body weight taking >200 ug of levothyroxine with elevated TSH and normal or high FT4 may indicate

poor compliance

Patients who miss doses can be advised to take up to

3 doses of skipped tablets at once owing to long half life

In patients with TSH >4.5 mU/L and positive TPO antibodies Subclinical hypothyroidism Patient may be started on

Levothyroxine If not started, monitor TSH anually

Levothyroxine treatment on Subclinical Hypothyroidism may improve

Left ventricle function | Lipid profile

In patients with history or high risk hypothyroidism who are contemplating pregnancy, they must be rendered

euthyroid before and throughout pregnancy

Thyroid function of pregnant patients should be evaluated once

Pregnancy confirmed | 2nd and 3rd trimester

Levothyroxine doses often need to be increased by how much in pregnancy

>/= 30-50% The dose may be returned to preconception levels postpartum

In elderly persons, dose of thyroxine may be lessened by

20% If with CAD, starting dose is 12.5-25 ug/d with similar increments every 2 months until TSH is normalized

Minor complications of surgery for hypothyroidism

``` Intraoperative hypotension Sensitivity to anesthesia Ileus Hyponatremia Central nervous dysfunction ```

Drugs that interfere with thyroid hormone absorption

``` Iron Calcium carbonate Cholestyramine Aluminum hydroxide gel Sucralfate Dietary soy ```

Medical conditions that may interfere with thyroid hormone absorption

GI maladaptive disorders | Previous small-bowel bypass surgery

Postmenopausal hormone therapy requires increase in levothyroxine by

35%

Myxedema coma treatment

Levothyroxine 500 ug T3 IV (conversion of T3 to T4 is impaired) Combined levothroxine and T3 as single initial bolus Daily doses of levothyroxine and T3

Excess T3 may provoke

arrhythmia

Supportive measures for myxedema

Treatment of precipitating factor Ventilatory support during first 48 hours Parenteral hydrocortisone (50 mg q6) is indicted for impaired adrenal reserve Hypertonic saline or intravenous glucose for severe hyponatremia or hypoglycemia Hypotonic IV avoided External warming if temperature <30 to avoid cardiovascular collapse Drug clearance may be impaired Sedatives should be avoided if possible

Complications associated with untreated hypothyroidism

``` Increased sensitivity to sedatives, analgesics and anesthetic agents Hypercholesterolemia CAD Diastolic dysfunction and hypertension Decreased sensitivty to warfarin ```

Painful inflammation of thyroid gland Self-limited Transient hyperthyroidism -> hypothyroidism -> euthyroid in a span of

``` Subacute thyroiditis De Quervain’s thyroiditis Granulomatous thyroiditis Giant cell thyroiditis Viral thyroiditis ```

Subacute thyroiditis epidemiology Age Sex Season

peaks 30-50 years Women 3x Peaks in summer

Patients with subacute thyroiditis often report with

antecedent viral respiratory infection

Subacute thyroiditis predominant HLA

HLA B35

Viruses implicated in Subacute Thyroiditis

``` Mumps Measles Influenza Coxsackie Adenovirus Echovirus ```

Painful, mildly enlarged thyroid Asymmetric Sore throat with pain to the jaw or ear Rare cause of chest pain Acute onset of hyperthyroidism Fever Fatigue Myalgia

Subacute thyroiditis

Thyrotoxic phase of Subacute Thyroiditis

T4, T3 increased | Low TSH

Ratio of T4 and T3 in Subacute Thyroiditis

T3>T4 Inc T4/T3 ratio

Hypothyroid phase of Subacute Thyroiditis

Moderately inc TSH Low T4,T3 after several weeks thyroid is depleted of stored thyroid hormone

Subacute Thyroiditis Dx Tx

Radioiodine uptake and scan to assess UTZ, FNAB not needed Symptomatic control of thyroid pain and tenderness and non-specific symptoms Mitigating the transient effects of hyperthyroidism

Thyroid cancer associated with Hashimoto’s

Primary thyroid lymphoma