THYROID DISORDERS

Hyperthyroidism

Prepared by : Stephanie N. Ammari

Resources : Davidson , Medstudy

Normal Physiology

THYROID FUNCTION TESTS

• TFTs include TSH, FT4, and sometimes FT3 .

• When screening for primary thyroid disease: start with a TSH to

detect abnormalities of thyroid function (both hyper- and

hypothyroidism) .

• If the TSH is high, then order a FT4 to assess for hypothyroidism.

• If the TSH is low, then order a FT 3 + FT 4 to assess for

hyperthyroidism .

OTHER THYROID TESTS

1. Radioactive iodine uptake (RAIU) .

2. Thyroid scan (also called "scintigraphy").

3. Ultrasound .

4. Biopsy (Fine needle aspiration (FNA) is a biopsy method used to

evaluate a thyroid nodule ) .

• The thyroid RAIU and scintigraphy scan are essential in

determining the cause of hyperthyroidism and are never

used in the workup of a hypothyroid patient.

• RAIU produces a number , the scan produces a picture.

Hyperthyroidism ( thyrotoxicosis )

• The most common cause of hyperthyroidism is autoimmune

Graves disease .

Other causes :

1. toxic multinodular goiter (MNG)

2. toxic adenomas .

3. thyrotoxicosis due to chronic autoimmune thyroiditis

(hashitoxicosis).

• Transient illnesses not associated with long-term primary

hyperthyroid disease :

Subacute and postpartum thyroiditis .

Symptoms

• Anxiety and restlessness

• Irritability

• Insomnia

• Impaired concentration (even confusion or psychosis)

• Weight loss despite normal diet

• Diarrhea

• Heat intolerance

• Alopecia

• Dyspnea

• Menstrual irregularities (oligo- or amenorrhea, impaired fertility)

• In males: gynecomastia, decreased libido, impaired spermatogenesis, and/or erectile dysfunction

Physical Exam

• Warm skin .

• The "hyperthyroid stare"( exophthalmos) .

• Lid-lag & lid retraction .

• Hypertension .

• Increased heart rate .

• Atrial fibrillation or ectopy in up to 20% of patients (more

common in elderly) .

• Thyroid Acropachy .

• In Goiter : diffuse enlargement of thyroid gland

Graves Disease

• The thyrotoxicosis results from the production of

immunoglobulin G (IgG) antibodies directed against the

TSH receptor on the thyroid follicular cell, which stimulate

thyroid hormone production and proliferation of follicular

cells, leading to goitre in the majority of patients.

• These antibodies are termed thyroid-stimulating

immunoglobulins or TSH receptor antibodies (TRAb) and

can be detected in the serum of 80–95% of patients with

Graves’ disease.

Graves Disease

• Graves’ disease has a strong genetic component.

• Genomewide association studies have identified

polymorphisms at the MHC, CTLA4, PTPN22, TSHR1

and FCRL3 loci as predisposing genetic variants .

• A suggested trigger for the development of thyrotoxicosis

in genetically susceptible individuals may be infection with

viruses or bacteria.

Specific Graves disease physical findings :

1. A diffuse, soft, symmetric goiter (but not always) .

2. Ophthalmopathy : Exophthalmos and periorbital edema

with impaired extraocular movements diplopia,

corneal ulcerations, visual impairment.

3. Dermopathy: Pretibial myxedema .

4. Immune-mediated hematologic abnormalities, such as

pernicious anemia and idiopathic thrombotic purpura.

Treatment is rarely required but in severe

cases topical glucocorticoids may be

helpful.

This infiltrative dermopathy

occurs in fewer than 5% of

patients with Graves’ disease

It takes the form of raised pink-

coloured or purplish plaques on the

anterior aspect of the leg, extending

on to the dorsum of the foot . The

lesions may be itchy and the skin

may have a ‘peau d’orange’

appearance with growth of coarse

hair; less commonly, the face and

arms are affected.

Diagnosis

• clinical exam + TFTs + thyroid uptake scan (TUS).

TSH is low (usually < 0.01 mU/L) .

FT3 and FT4 are elevated (rarely, only FT3 is

increased with normal FT4) .

the TUS shows increased diffuse uptake.

• Other common lab abnormalities:

elevated alkaline phosphatase, hypercalcemia, anemia,

and thrombocytopenia.

• Autoantibodies are generally not measured, but TSI

(thyroid-stimulating immunoglobulins) are positive in >

90% of cases of Graves disease.

Treatment

• Treat with antithyroid drugs (methimazole [MMI] or

propylthiouracil [PTU]) and/or thyroid ablation with ᶦᶟᶥ I or

surgery .

Treatment

• MMI is the preferred drug in non-pregnant patients

because of lower toxicity than PTU.

• PTU :

is still 1st line treatment for Graves disease in pregnant

patients in the 1st trimester and is still used for thyroid

storm.

PTU received a FDA boxed warning for increased risk of

death due to acute liver failure or severe liver injury .

Treatment

• The most serious side effects of PTU and MMI are hepatic

toxicity and agranulocytosis, which are rare and

unpredictable.

• LFTs and CBCs do not require monitoring.

• Check only if the patient becomes symptomatic

(jaundice, dark urine, prolonged fever/sore throat).

• Side effects almost always disappear when the drug is

promptly discontinued.

• Beta-blockers help patients with adrenergic symptoms

while waiting on the effects of PTU or MMI.

Treatment

Thyroid ablation using ᶦᶟᶦ I .

Virtually all patients are pretreated with beta-blockers,

and many patients are treated with MMI (or PTU) prior to

radioiodine ablation.

Most patients become hypothyroid months to years after

ᶦᶟᶦ I therapy.

Surgery

Surgery may be indicated in :

1. pregnancy .

2. in patients with an associated cold nodule or relapse

after radiation .

3. in some young patients with a large goiter.

# Worrisome complications of surgery are loss of all

parathyroids and damage to recurrent laryngeal nerves .

Thyroid Storm

• Storm is the 2nd thyroid emergency that is associated with

a high mortality rate (the other is myxedema coma).

• Storm is most often a precipitated event in patients known

or suspected to have undiagnosed or inadequately

treated hyperthyroidism.

• Precipitating events include surgery, infections, or an

iodine load, such as amiodarone or contrast dye.

Symptoms & Dx

• Symptoms of storm are identical to symptoms of hyperthyroidism, only more exaggerated:

Hypertension – tachycardia- congestive heart failure –fever – psychosis or delirium.

Some patients have constitutional symptoms of nausea, vomiting, and diarrhea.

Oddly, some patients develop jaundice

• Diagnose the condition with measurement of TSH and FT4: In virtually all cases, TSH is immeasurable and FT 4 markedly increased.

Thyroid storm

• Storm is characterized by a severe level of metabolic

stress that the patient can no longer tolerate.

• This severe stress results in a relative adrenal

insufficiency, even though the adrenal glands may be

functioning perfectly and secreting a large amount of

cortisol.

• Patients in storm die from cardiovascular collapse.

Tx of Thyroid Storm The most important aspect of treatment is large amounts of

glucocorticoids.

Provide supportive care in the ICU with diligent attention to volume status, temperature, and heart rate.

Give empiric broad-spectrum antimicrobial coverage until infection is excluded.

Other aspects of treatment include the following:

• Interrupt the physiologic response to excess thyroid hormone: IV propranolol or esmolol.

• Block new hormone synthesis: high-dose thionamide (PTU or MMI).

• Block release of preformed hormone from the gland: stable iodide.

• Block peripheral conversion of T4 to T3 : iodinated contrast agent, propranolol, and corticosteroids. PTU also does this (but not MMI).

Thyroiditis

# Thyroiditis is divided into the following categories:

• Acute: caused by bacterial infection of the gland (rare).

• Subacute: caused by viruses (also called

"granulomatous").

• Chronic: Autoimmune-mediated disease is the most

common cause (Hashimoto's). Painless and postpartum

thyroiditis are considered variants of "chronic."

Subacute (de Quervain’s) thyroiditis • Subacute thyroiditis is a transient inflammation of the thyroid

gland occurring after infection with Coxsackie, mumps or

adenoviruses .

• The condition can also be precipitated by drugs, including

interferon-α and lithium .

• Affected patients are usually females aged 20–40 years.

• In its classical painful form, There is pain in the region of the

thyroid that may radiate to the angle of the jaw and the ears,

and is made worse by swallowing, coughing and movement of

the neck.

• The thyroid is usually palpably enlarged and tender.

• Systemic upset is common .

• Painless transient thyroiditis can also occur after viral infection

and in patients with underlying autoimmune disease.

Subacute thyroiditis

• Labs/studies:

• Initially, T3 and T4 are increased, TSH is suppressed,

and RAIU is initially decreased.

• ESR is increased but is too nonspecific to use in

diagnosis.

• Over time, temporary overt hypothyroidism develops in

some with low T4 and increased TSH.

• RAIU returns to normal. Eventually, T4 and TSH

normalize

Subacute thyroiditis

• The disorder is self-limited and usually does not require

treatment.

• For severe cases, treat inflammation as needed with ASA

or NSAIDs.

• Glucocorticoids are given as an 8-week taper in

refractory/systemic cases.

• Occasionally, a patient may need beta-blockers to

ameliorate the thyrotoxicosis symptoms or levothyroxine

for overt hypothyroidism.

• Reevaluate periodically until the patient's thyroid function

normalizes.

Postpartum thyroiditis

• is fairly common, affecting up to 10-15% of postpartum women.

• symptomatic thyrotoxicosis presenting for the first time within 12 months of childbirth is likely to be due to post-partum thyroiditis The clinical course and treatment are similar to those of painless subacute thyroiditis .

• Patients present with hyper- or hypothyroid symptoms and a painless goiter.

• ESR is normal, but many patients do have anti-TPO antibodies.

• RAIU is decreased.

• Don't hesitate to treat the hypothyroidism-or to give beta-blockers as needed for thyrotoxicosis.

• Patients universally recover but need annual follow-up because of the risk of overt hypothyroidism later.

• Post-partum thyroiditis tends to recur after subsequent pregnancies, and eventually patients progress over a period of years to permanent hypothyroidism.

Toxic Adenoma

• A toxic thyroid adenoma is a benign area of autonomous

hyperfunctioning thyroid tissue .

• Most occur as a single nodule of hyperfunctioning tissue

within normal tissue that grows slowly, eventually

becoming large enough to suppress TSH production.

• These are usually diagnosed by TFTs, which demonstrate

overproduction of FT/FT4 and suppression of TSH, and

thyroid scan (focal uptake in "hot" nodule).

Treatment of thyroid adenomas

• If the patient is hyperthyroid, use ablative treatment or

perform surgery. Antithyroid drugs do not work long term .

• For the euthyroid patient with a thyroid adenoma ….

If the thyroid adenoma is compressing underlying

structures or is cosmetically problematic, surgery is the

best treatment.

Percutaneous ethanol injection of autonomous functioning

thyroid nodules is an alternative to surgery and RAI, with

restoration of normal thyroid function in the majority of

cases .

Multinodular Goiter

• Toxic MNG .

• Nontoxic MNG .

Toxic MNG

• refers to a MNG with thyrotoxicosis.

• TSH is suppressed, and FT3 and FT4 are often

increased.

• The thyroid scan usually shows 1 or more hot nodules.

• Toxic MNG may temporarily be treated with antithyroid

medications.

• Normal treatment is ablative therapy with radioactive

iodine. This does not destroy all the nodules, but it does

destroy those that are hyperfunctioning.

• Surgery is used in cases that are refractory, or in

symptomatic cases, especially if a large goiter is

compressing surrounding structures.

Subclinical Hyperthyroidism

• a low or undetectable (TSH) level with a normal serum

free T4 and normal serum total T3 levels .

• It can be caused by increased endogenous production of thyroid

hormone (e.g., in Graves disease, toxic nodular goiter, or transient

thyroiditis), by administration of thyroid hormone to treat malignant

thyroid disease, or by unintentional excessive replacement therapy.

• The American Thyroid Association and the American Association of Clinical

Endocrinologists recommend treating patients with thyroid-

stimulating hormone levels less than 0.1 mIU per L if

they are older than 65 years or have comorbidities

such as heart disease or osteoporosis.