SOAP. – Thyroid Disease – SỔ TAY LÂM SÀNG

Thyroid Disease

Julie Adkins, Jill C. Cash, Mellisa A. Hall, Cheryl A. Glass, Angelito Tacderas, and Jenny Nelson Mullen

Hyperthyroidism

Definition

A.Hyperthyroidism is a condition in which the thyroid hormone exerts greater than normal responses. Hyperthyroidism may be subclinical and may not be easily recognized or exhibit overt symptoms. The most common hyperthyroid conditions are Graves’ disease and toxic multinodular goiter. The American Thyroid Association recommends that adults be screened for thyroid disease beginning at age 35 and every 5 years thereafter. However, Medicare at this time does not cover the charges for a screening thyroid test in an asymptomatic patient.

Incidence

A.Overall incidence of Graves’ disease is one in 200 people (5 per 1,000). Graves’ disease is responsible for 60% to 80% of cases of thyrotoxicosis. Overall prevalence in the United States is 1.2% with an incidence of 20 to 50 to 100,000 (pertinent to environmental and region etiologies). It is most common in adults between 20 and 50 years of age.

B.Female gender:

1.Higher in women than men by 8:1 ratio.

2.The Nurses’ Health Study II reported the 12-year incidence among women 25 to 42 years of age as 4.6/1,000 (460/100,000). Hyperthyroidism in the elder population is not common.

3.Older women: 4% to 5% incidence.

4.Graves’ disease is more common in younger women.

5.Toxic nodular goiter is more common in older women.

C.Elderly: Toxic multinodular goiter, also referred to as toxic adenoma of the thyroid (called Plummer disease if single nodule). This occurs in 15% to 20% of patients with thyrotoxicosis. Associated with atrial fibrillation, tachycardia, muscle wasting, and weakness.

TABLE 24.6 Androgen Excess Society Screening and Treatment Requirements for Impaired Glucose Tolerance (IGT)

BMI, body mass index; DM, diabetes mellitus; OGTT, oral glucose tolerance test; PCOS, polycystic ovarian syndrome.

Source: Salley, K. E. S., Wickham, E. P., Cheang, K. I., Essah, P. A., Karjane, N. W., & Nestler (2007). Glucose intolerance in polycystic ovary syndrome–a position statement of the Androgen Excess Society. Journal of Clinical Endocrinology and Metabolism, 92(12): 4546–4556.

D.Symptomatology incidence:

1.Ophthalmopathy is more common in smokers.

2.Atrial fibrillation 10% to 25% incidence and is more common in the elderly.

3.Autoimmune thyroid diseases have a peak incidence in people aged 20 to 40 years.

Pathogenesis

A.Hyperthyroidism is one form of thyrotoxicosis in which an excess of hormone is excreted by the thyroid gland. The diseases that can cause hyperthyroidism include Graves’ disease, toxic multinodular goiter, thyroid cancer, and increased secretion of the thyroid-stimulating hormone (TSH). Thyrotoxicosis not related to hyperthyroidism may be subacute thyroiditis, ectopic thyroid tissue, and ingestion of excessive thyroid hormone. Postpartum thyroiditis can precipitate a short-term mild hyperthyroidism, which has an onset at 2 to 6 months postpartum. Severe thyrotoxicosis of any cause is called thyrotoxic crisis or storm.

B.In Graves’ disease, the normal feedback mechanisms that regulate hormone secretion are taken over by some abnormal thyroid-stimulating mechanism. Thyroid autoantibodies of the immunoglobulin G (IgG) class are present in more than 95% of patients with Graves’ disease. The hyperfunctioning of the thyroid gland causes suppression of TSH and thyrotropin-releasing hormone (TRH). There are profound increases in iodine uptake and thyroid gland metabolism, which are believed to be the causes of the gland enlargement. The resulting increase in the level of circulating thyroid hormone is responsible for the thyrotoxic symptoms.

C.In the condition called toxic multinodular goiter, the thyroid gland enlarges in response to some bodily need such as puberty, pregnancy, iodine deficiency, and immunologic, viral, and genetic disorders. As TSH levels rise, the gland enlarges; when the condition demanding increased thyroid hormone resolves, TSH levels usually return to normal and the gland slowly assumes its original size.

Predisposing Factors

A.Graves’ disease:

1.Women in the second through fifth decades of life.

2.Familial autoimmune thyroid disease.

3.Concomitant disorders believed to be autoimmune.

4.Increase in trisomy 21.

5.Higher incidence in smokers.

B.Toxic multinodular goiter:

1.Advanced age.

2.Recent exposure to iodine-containing medications (amiodarone and/or radio-contrast dye).

3.Long-standing simple goiter.

4.Conditions such as puberty, pregnancy, iodine deficiency, and immunologic, viral, or genetic disorders.

Common Complaints

A.Graves’ disease:

1.Prominence/protrusion of the eye (exophthalmos).

2.Prominent stare.

3.Visual changes:

a.Diplopia.

b.Photophobia.

c.Eye irritation: Gritty feeling or pain.

d.Eyelid retraction, proptosis, periorbital edema, and conjunctival redness.

B.Weight loss with no change in diet or an increase in appetite.

C.Anorexia (may be prominent in the elderly).

D.Weakness and fatigue.

E.Tachycardia.

F.Decreased tolerance to heat, diaphoresis, and palmar erythema.

G.Thinning scalp hair.

H.Onycholysis: Fingernail separation from the nail bed.

I.Smooth, warm, moist, thin skin. In some adults and the elderly skin might have peau d’orange appearance and difficult to pinch.

J.Heart palpitations (atrial fibrillation).

K.Bowel symptoms:

1.Increase in frequency and loose bowel movements (not diarrhea).

2.Constipation (more frequent in the elderly).

L.Systolic hypertension (HTN):; signs of heart failure (edema, rales, tachypnea, jugular venous distension).

M.Neurological: Fine tremors extremities/digits, hyperkinesia, hyperreflexia.

Other Signs and Symptoms

A.Goiter: Approximately 50% of patients will not have an enlargement of the thyroid gland. Elderly patients are less likely to have a goiter. Thyroid/neck tenderness with/without thyroid bruits.

B.Periorbital edema.

C.Flushing, warm skin.

D.Fine hand tremors.

E.Dyspnea (especially elderly).

F.Exertional fatigue/exercise intolerance.

G.Insomnia.

H.Irritability.

I.Nervousness.

J.Mood swings.

K.Inability to concentrate.

L.Depression and apathy (elderly).

M.Menses (oligomenorrhea or amenorrhea).

N.Impotence and decreased libido in men.

O.Gynecomastia.

P.Galactorrhea (TSH-mediated hyperthyroidism).

Q.Atrial dysrhythmias (atrial fibrillation), left ventricular dilation (common in elderly).

R.Urinary frequency, polyuria and nocturia.

S.Osteopathy/thyroid acropachy: Subperiosteal bone formation and swelling of metacarpal bones (most common in older adults).

T.A combination of these noted symptoms should lead to the assessment of hyperthyroidism.

Subjective Data

A.Identify when symptoms began, duration, and any change or progression.

B.Identify whether the patient has noticed enlargement of the thyroid gland, difficulty swallowing, or change in voice.

C.Assess for change in weight over the past 3 months, past 6 months, and last year. Ask the patient whether his or her appetite has changed.

D.Explore the patient’s family history of thyroid problems.

E.Obtain the patient’s medical history of associated diseases (especially those of autoimmune pathogenesis: pernicious anemia, type 1 diabetes mellitus (DM), myasthenia gravis, rheumatoid arthritis, ulcerative colitis).

F.Review the patient’s medication history, including amiodarone, interferon alpha, levothyroxine (overdose), expectorants, and health food supplements containing seaweed.

G.Ask the patient to identify any changes in bowel habits, loose (nondiarrhea) stools, frequency of bowel movements, or constipation.

H.Ask about moods, changes in concentration, feelings of restlessness, nervousness, anxiety, and change in sleep habits.

I.Assess for any cardiac symptoms, such as palpitations, chest pain, shortness of breath, and decreased tolerance for activities previously done.

J.Ask whether the patient has noticed any swelling or puffiness anywhere.

K.Determine whether the patient has experienced changes in vision and/or eye irritation.

L.Assess for hand tremors, increase in the moistness and coolness of the skin, flushing, and blushing.

M.Ask the patient to identify any menstrual changes or whether the patient has had a recent pregnancy, or is in the postpartum period.

N.Review for a recent history of a viral infection.

O.Review recent trauma to the neck (significant trauma can cause thyrotoxicosis).

Physical Examination

A.Check temperature, if indicated; pulse (tachycardia); respirations (dyspnea); blood pressure (blood pressure; systolic HTN); and weight.

B.Inspect:

1.Observe overall appearance: Does the patient have any difficulty with breathing, including dyspnea, or difficulty swallowing from tracheal obstruction secondary to a large goiter?

2.Note eyelid retraction, lid lag, and exophthalmos. The clinician may see periorbital edema and an elevated upper eyelid, which leads to decreased blinking and a staring quality in Graves’ disease.

3.Note tremors that are best demonstrated from outstretched hands.

4.Inspect the skin for temperature and texture.

5.Inspect the fingernails for the following:

a.Onycholysis, also known as Plummer’s nails (loosening of the nails from the nail beds).

b.Softening of the nails.

6.Inspect scalp/hair.

C.Auscultate:

1.Auscultate the thyroid for bruits.

2.Auscultate the heart and pulse rate. Patients with subclinical hyperthyroidism frequently present with atrial fibrillation.

3.Auscultate the carotid arteries for bruits.

4.Auscultate bowel sounds.

D.Palpate:

1.Palpate the neck and thyroid for nodules, thrills, and enlargement. Depending on the etiology of the hyperthyroidism, the thyroid may range from normal to massive (Graves’ disease or toxic multinodular goiter). Palpation of the thyroid can induce the gland to release increased hormone; be alert for signs and symptoms of thyroid storm.

2.If the thyroid is tender and painful to palpation, granulomatous thyroiditis may be the etiology of hyperthyroidism.

3.Palpate the heart for thrills.

4.Palpate extremities for edema. Pretibial myxedema is noted in Graves’ disease.

E.Neurologic examination:

1.Assess deep tendon reflexes (DTRs).

2.Tests for lid lag:

a.Have the patient follow your finger as it moves up and down.

b.Have the patient look down and observe if sclera can be seen above the iris.

3.Have the patient stick out the tongue to observe for presence of tremors.

Diagnostic Tests

A.TSH, free thyroxin (T4), triiodothyronine (T3; see Table 24.7).

B.Radioactive iodine (131I) uptake (RAIU), if needed. If the patient has ophthalmopathy, clinical symptoms of hyperthyroidism, and a diffusely enlarged thyroid gland, the RAIU test is not necessary to confirm Graves’ disease. Pregnancy and breastfeeding are absolute contraindications to radionuclide imaging. When nodules have difficulty absorbing iodine, they will appear cold and biopsy is in order to rule out cancer. If nodules are overproducing hormones, it will appear darker and is called hot. Thyroid nodules increase with age: approximately 95% are benign and 5% are malignant.

C.Consider additional laboratory testing:

1.Complete blood count (CBC; may have normochromic, normocytic

2.Serum ferritin (may be high).

3.Thyroglobulin (Tg) cancer marker.

4.Thyroid peroxidase (TPO) antithyroid microsomal antibody to detect autoimmune disorder of thyroid.

D.If T4 and T3 are high, but TSH is normal or high, a pituitary MRI should be ordered to look for a pituitary mass.

E.An echocardiogram should be considered if an irregular heart rate and signs of heart failure are noted on examination.

F.Microscopic for Plummer’s/toxic multinodular goiter: Hyperplastic nodules with discrete fibrous capsule. Nonfunctioning nodules with degenerative changes of fibrosis, calcifications, and old/new hemorrhage.

G.Molecular/cryogenics: Monoclonal or polyclonal.

Differential Diagnoses

A.Hyperthyroidism:

1.Graves’ disease.

2.T3 toxicosis.

3.T4 toxicosis.

4.Thyroid adenoma.

5.Drug-induced hyperthyroidism, that is, iodine-rich amiodarone.

6.Subclinical hyperthyroidism.

7.TSH-induced hyperthyroidism (TSH-secreting pituitary adenoma).

8.Hyperthyroidism during pregnancy.

9.Hashitoxicosis (combination of Hashimoto and thyrotoxicosis), rare autoimmune thyroid disease.

10.Dyshormonogenetic goiter of diffuse changes (compared to focal changes) in toxic multinodular goiter.

B.Cardiovascular disease (CVD) such as coronary artery disease (CAD) and heart failure.

C.GI disorders such as irritable bowel syndrome, ulcerative colitis, and Crohn’s disease.

D.Cancer: Testicular germ cell tumors.

E.Neurologic disorder.

F.Hydatidiform mole (molar pregnancy).

G.Psychological disorder.

Plan

A.General interventions:

1.Carefully assess for complications of hyperthyroidism (cardiac, ophthalmologic, GI, musculoskeletal, and psychological); address each area identified.

2.Patients with tachycardia, palpitations, tremors, anxiety, and eyelid lag can be treated with a beta-adrenergic antagonist for some relief from those symptoms until they become euthyroid.

3.For infiltrative dermopathy over the lower extremities, occlusive wraps on the affected side are recommended.

4.Only 5% of patients with Graves’ disease develop severe ophthalmopathy. An initial ophthalmologic exam is recommended as baseline, with follow-up determined by the ophthalmologist.

B.Patient teaching:

1.Patients taking propylthiouracil (PTU) or methimazole (MMI) should be instructed to immediately report any side effects, including rash, hives, fever, jaundice, abdominal pain, and clay-colored stools.

2.Less than 1% of patients develop agranulocytosis, but all patients should be instructed to call the provider immediately if a fever, sore throat, or joint ache develops because of their susceptibility to serious infection.

3.Patients receiving radioactive iodine (RAI) should be informed that they most likely will need to take lifelong hormone replacement after the RAI treatment is completed.

4.Teach safety measures to guard against the possibility of fractures due to bone density loss secondary to hyperthyroidism. Get a baseline bone density scan (DEXA scan).

5.Inform patients that an episode of serious depression may follow successful treatment of hyperthyroidism.

6.No special diet is required; however, patients should be told to avoid herbal supplements and sushi that contains seaweed.

C.Medical–surgical management:

1.RAI is a common choice of therapy for adults. It is administered in capsule form or in water:

a.One dose is usually sufficient; however, a second dose may be given if necessary.

b.Permanent hypothyroidism requiring lifelong hormone replacement is the only notable complication.

2.A thyroidectomy is seldom used except in limited patient conditions:

a.Pregnancy—if women are noncompliant or cannot tolerate thionamides because of allergies or agranulocytosis:

b.Patients who refuse RAI therapy.

c.Refractory amiodarone-induced hyperthyroidism.

d.Patients with unstable cardiac conditions that require quick normalization of thyroid function.

D.Pharmaceutical therapy:

1.Antithyroid drugs: The choice of drugs depends on clinician experience, the severity of the disease, and patient preference. Provide titration of antithyroid drug dose every 4 weeks until thyroid function normalizes and to ensure the patient does not become hypothyroid. Graves’ disease may go into remission after treatment for 12 to 18 months, and drug therapy can be discontinued:

a.PTU:

i.Initial dose 100 to 150 mg by mouth three times daily. Dosage decrease is almost always required at 4 to 8 weeks of start.

ii.Thyroid storm: 150 to 200 mg orally every 4 to 6 hours.

iii.Except in thyroid storm, PTU is considered a second-line drug therapy. It is reserved for use in patients who are allergic to or intolerant of Tapazole (MMI) and in women who are in the first trimester of pregnancy or planning pregnancy.

b.MMI (Tapazole):

i.Adults: 20 to 40 mg/d or in divided twice-a-day dose. Maintenance doses are 2.5 to 15 mg/d.

ii.Methimazole is more potent than PTU and has a longer duration of action.

iii.Methimazole is not recommended for use in the first trimester of pregnancy.

2.RAI therapy is one of the most common treatments in adults. It is administered orally as a single dose. RAI is contraindicated in pregnancy and lactation.

3.Beta blockers such as propranolol (Inderal) are also used for hyperthyroidism.

4.Atrial fibrillation treatment is directed toward restoring a euthyroid state. Other therapies

include the following:

a.Beta blockers (unless contraindicated, including chronic obstructive pulmonary disease [COPD], and asthma).

b.Calcium channel blockers if unable to utilize beta blocker.

c.Oral anticoagulation (keeping the international normalized ratio [INR] between 2 and 3).

d.Antiarrhythmic drugs and cardioversion may be unsuccessful until euthyroid.

Follow-Up

A.Depending on the experience of the clinician, an endocrinologist best prescribes therapy, including RAI and antithyroid medication.

B.Patients receiving PTU or MMI should be seen in the office every 4 to 6 weeks for evaluation and have blood drawn for serum TSH and free T4 measurements until euthyroid state is achieved and maintained.

C.Patients are usually maintained on these drugs for 1 to 2 years, with office visits every 3 months. The drug is then gradually withdrawn, and 25% to 90% of patients experience permanent remission.

D.Patients with RAI therapy should be seen in the office to monitor thyroid levels. It is anticipated that most of them will require lifelong hormone replacement medication following treatment.

E.Perform bone density screening (DEXA scan) to evaluate for osteopenia/osteoporosis.

F.Consider testing for impaired glucose tolerance (IGT).

Consultation/Referral

A.Ophthalmology consultation is recommended for patients with ophthalmologic involvement.

B.If surgery is the choice of treatment, refer the patient to an endocrinologist and a surgeon.

C.An experienced obstetrician or perinatologist should follow pregnant women.

Individual Considerations

A.Pregnancy:

1.Pregnant patients with mild hyperthyroidism may be followed with treatment.

2.If an antithyroid drug is necessary, PTU is the drug of choice in the first trimester. MMI has been associated with congenital anomalies such as tracheoesophageal fistula and choanal atresia. After the first trimester, mothers may be switched to MMI.

3.Monitor thyroid function every 4 weeks during pregnancy.

4.RAI therapy is contraindicated during pregnancy and breastfeeding.

5.Thyrotoxicosis may improve during pregnancy; however, symptoms may relapse during the postpartum period.

6.Hyperthyroidism in the third trimester may increase the risk of low birth weight.

7.Prolonged high-dose iodine therapy can cause fetal goiter.

8.Ultrasounds should be performed to evaluate for fetal hyperthyroidism, assessing for goiter, poor growth, cardiac failure, and hydrops fetalis.

B.Adults: Sympathetic activation (anxiety, hyperactivity, etc.) is seen in adult years more commonly than in the elderly population.

C.Geriatrics:

1.Older patients exhibit fewer clinical signs, but may still have the following: tachycardia, atrial fibrillation, dyspnea, fatigue, moderate to severe opthalmyopathy, and weight loss.

2.Less frequent signs in this population include atrial fibrillation, hyperactive reflexes, increased sweating, heat intolerance, tremors, nervousness, polydipsia, new onset of hoarseness, difficulty swallowing, and increased appetite.

3.Elderly women with hyperthyroidism are at increased risk for accelerated bone loss.

4.Malignancy occurs most often in patient ≤20 years old and ≥70 years of age.

5.In older adults, if TSH is low but free T4 remains within the normal limits (subclinical hyperthyroid) retest in 4 to 6 weeks. If TSH remains low, test the T3. Treat subclinical hyperthyroidism if symptoms are present and the TSH remains <0.1mlU/L after 3 to 6 months.

6.In older adults with CVD or low bone density, treat subclinical hyperthyroid if TSH is 0.1 to0.5 mlU/L (Reubin et al., 2016),

7.Target is raised for geriatrics: Serum TSH is 4 to 6 mIU/L (nonelderly it remains 0.5–4.5 mIU/L).

8.Angina pectoris and heart failure must be treated in conjunction with thyroid treatment. Medications implemented for geriatrics include beta-adrenergic blockers and Tapazole only if a definitive diagnosis was made with radioactive iodine or from the discretionary decision of an endocrinologist specific to the unique history of a patient.

9.Hyperthyroid medications may increase liver function tests in geriatrics. Discontinue medication if this occurs.

10.Beers Criteria considerations: see Individual Considerations in section Thyrotoxicosis/Thyroid Storm.

Hypothyroidism

Definition

A.Hypothyroidism is a condition in which the body does not produce enough thyroid hormone. In general, hypothyroidism is considered permanent, requiring therapy to restore a euthyroid state. The most common physical finding is a goiter. The most common worldwide cause of hypothyroidism is iodine deficiency, while the most common cause in the United States is Hashimoto thyroiditis, an autoimmune thyroid disease.

Incidence

A.The American Thyroid Association posited that 12% of the U.S. population will develop a thyroid condition in their lifetime. An estimated 20 million Americans have some form of thyroid disease, and approximately 60% of those with thyroid disease are unaware of their condition.

B.It occurs in women more than men (five to eight times higher).

C.It may present in up to 15% of people older than 65 years.

D.In adolescents, approximately 6% have acquired hypothyroidism.

E.Approximately 10% of patients with type 1 DM will develop chronic thyroiditis.

F.Up to 10% develop lymphocytic thyroiditis in the postpartum period (up to 10 months postpartum).

G.Approximately 1:4,000 newborns have congenital hypothyroidism (cretinism).

H.The incidence is higher in Whites (5.1%) and Mexican Americans than in African Americans (1.7%).

Pathogenesis

Hypothyroidism is caused by an insufficient production of thyroid hormones by the thyroid gland, either by a primary or a secondary cause.

A.Primary causes include decreased hormone production caused by autoimmune thyroiditis, endemic iodine deficiency, congenital defects, or decreased thyroid activity after treatment for hyperthyroidism.

B.Secondary causes are much less common but may include insufficient stimulation from the pituitary or hypothalamus and peripheral resistance to thyroid

C.The most common cause of primary hypothyroidism is chronic autoimmune thyroiditis, called Hashimoto thyroiditis. In this disease, circulating thyroid antibodies and the infiltration of lymphocytes destroy thyroid tissue. Autoimmune thyroiditis may also be a result of an inherited immune defect.

D.Acute thyroidism is a rare cause of hypothyroidism in which the cause is an acute bacterial infection. Subacute thyroiditis, a nonbacterial inflammation of the thyroid, is often preceded by a viral infection. Both of these conditions cause inflammation of the thyroid gland by lymphocytic and leukocytic infiltration into the thyroid tissue, resulting in hypothyroidism.

Predisposing Factors

A.Iodine deficiency.

B.Women older than 40 years at highest risk.

C.Presence of other autoimmune disorders (diagnosed and previously undiagnosed).

D.Recent acute bacterial or viral infection.

E.Treatment with RAI for thyroid gland problems.

F.Surgical removal of thyroid gland.

G.Exposure to external radiation.

H.Evidence of pituitary or hypothalamic disease.

I.Postpartum.

J.Type 1 (autoimmune) DM.

K.Chromosomal disorders:

1.Down syndrome.

2.Turner syndrome.

3.Klinefelter syndrome.

L.Celiac disease.

M.Drug-induced:

1.Amiodarone.

2.Interferon alpha

3.Thalidomide.

4.Lithium.

5.Stavudine.

6.Dopamine.

Common Complaints

A.Weight gain/obesity.

B.Fatigue/sluggishness.

C.Cold intolerance.

D.Constipation.

E.Dry and flaky skin.

F.Coarseness or loss of hair, inability of hair to hold a curl, hair loss at eyebrows, and reduced growth of hair.

G.Reduced growth of nails.

H.Hoarseness.

I.Memory or mental impairment, difficulty concentrating, and slowed speech or thinking.

J.Periorbital edema and facial puffiness.

K.Irregular or heavy menses and infertility.

L.Muscle aching and stiffness.

Other Signs and Symptoms

A.Asymptomatic if subclinical hypothyroidism and have no overt symptoms.

B.Delayed reflexes.

C.Elevated BP.

D.Hyperlipidemia.

E.Jaundice.

F.Painful subacute thyroiditis:

1.Sudden neck pain with sore throat, radiating to jaw and ears, and pain shifting to sides of the neck

2.Late stage: Myxedema, thick scaly skin, muscle weakness/joint pain, enlarged tongue, hearing loss, bradycardia, cardiac hypertrophy, pleural effusion, and ascites.

G.Pituitary or hypothalamic failure:

1.Loss of axillary and pubic hair.

2.Cessation of menses.

3.Postural hypotension.

H.Exercise intolerance:

I.Carpal tunnel syndrome is a common occurrence.

J.Depression.

K.Ataxia.

L.Decreased concentration/memory impairment.

Subjective Data

A.Note history of recent illness and/or pregnancy.

B.Evaluate the patient’s medical-surgical history for any treatment of hyperthyroidism, including radioactive treatment or thyroidectomy.

C.Review dietary and weight history, how much weight has been gained and over what period of time.

D.Review any changes in health status or symptoms associated with other body systems (thyroid symptoms usually involve multiple body systems).

E.Review any history of obstructive sleep apnea (OSA).

F.Assess for pain or swelling of the neck or difficulty swallowing.

G.Inquire as to the patient’s history of supervoltage x-ray therapy to the neck for nonthyroid cancer or for polio.

H.Identify family history:

1.Does the patient have a first-degree relative with thyroid disease?

2.Is there a family history of any endocrine problems, including thyroid, type 1 DM, and/or receptor agonist (RA)?

I.Review the patient’s medication history for current medication, over-the-counter (OTC) medications, vitamins, or herbal supplements.

J.Review the patient’s menstrual history or history of infertility.

Physical Examination

A.Check pulse (bradycardia), respirations, BP (decreased systolic blood pressure and increased diastolic blood pressure (DBP), and weight

B.General observation:

1.Gait problems such as ataxia or rigidity and spasticity of the trunk and proximal extremities.

2.Quality of the patient’s voice (hoarseness).

3.Signs of depression, decreased concentration, or memory impairment.

C.Inspect:

1.Inspect the skin (dry/flaky) for presence of jaundice.

2.Inspect the hair (coarse, thin, and brittle) and decrease in pubic/axillary hair pattern.

3.Perform oral examination for evaluation of macroglossia (enlarged tongue).

4.Inspect the face/eye for periorbital puffiness/edema.

5.Inspect the neck for the presence of a goiter and surgical scar.

D.Auscultate:

1.Auscultate the thyroid and carotids.

2.Auscultate the heart.

3.Auscultate the lungs.

4.Auscultate the abdomen for bowel sounds in each quadrant (hypoactive).

E.Palpate:

1.Palpate the neck, thyroid gland, and lymph nodes.

2.Palpate the abdomen for presence of abdominal distension, ascites, and hepatomegaly.

3.Palpate/evaluate extremities for edema.

F.Musculoskeletal examination: Perform a detailed musculoskeletal examination:

G.Neurologic examination:

1.Check visual fields (restricted with hypothyroidism).

2.Test hearing:

a.Whisper words and have the patient repeat.

b.Use a ticking watch.

c.Use a tuning fork:

i.Weber test: Place vibrating fork on top midline of head (sound hearing equally in both ears).

ii.Rinne test: Place vibrating tuning fork on mastoid, begin counting, and ask the patient to tell you when he or she no longer hears; then quickly reposition 1/2 to 1 inch from the ear and ask the patient when he or she no longer hears (hearing should be twice as long as bone conduction).

3.Check for loss or reduction of DTRs.

4.Evaluate proximal muscle weakness/strength.

5.Test for abnormal tandem gait: Have the patient walk across the room in a heel-toe, heel-toe fashion.

6.Check for sensory loss:

a.Evaluate the first three fingers and one half of the fourth finger on testing loss of sensation from carpal tunnel syndrome.

b.Evaluate sensory loss of the feet/legs (generally symmetrical in a stocking-glove distribution).

Diagnostic Tests

A.TSH.

B.When a high TSH is noted, repeat the test and add a free T4.

C.T3 resin uptake.

D.Thyroid antibodies (see Table 24.8).

E.TSH assay (if TSH assay is elevated, it indicates hypothyroidism).

F.Thyroid scan.

G.CBC (anemia).

H.Lipid profile.

I.Ultrasound of the neck and thyroid to detect nodules (not a first-line test).

Differential Diagnoses

A.Hypothyroidism:

1.Hashimoto thyroiditis.

2.Subclinical hypothyroidism.

3.Hypothyroidism secondary to treatment/intervention for hyperthyroidism.

4.de Quervain’s thyroiditis.

5.If TSH and free T4 are both low, consider hypothyroidism secondary to pituitary or hypothalamic failure.

B.Obesity: Patients with elevated total cholesterol levels or triglyceride levels are often misdiagnosed by assuming that these symptoms are caused by obesity and high-fat diets.

C.Depression.

D.Ischemic heart disease.

E.Nephrotic syndrome.

F.Cirrhosis.

G.Side effects/adverse effects of medications.

H.Constipation.

I.Sleep apnea/sleep disorder.

J.Fibromyalgia.

K.Infectious mononucleosis.

Plan

A.General interventions:

1.The American Thyroid Association clinical practice guideline for detection of both subclinical and symptomatic hypothyroidism recommends that all adults aged 35 and older be screened for hypothyroidism every 5 years to identify thyroid disease in the early stages. However, Medicare does not cover a screening TSH in an asymptomatic patient.

2.Patients with underactive thyroids require lifelong treatment with levothyroxine.

3.In patients with subacute thyroiditis, relatively large doses of nonsteroidal anti-inflammatory drugs (NSAIDs) or prednisone may be prescribed.

4.For patients with enlarged thyroid glands, surgery may be recommended if the gland begins obstructing the airway.

5.The treatment of patients with malignant thyroid nodules depends on the type of cancer.

B.Patient teaching:

1.Teach the patient about the nature and course of the disease, as well as the signs and symptoms. Frequently, patients are relieved that perceived symptoms are real and that there is treatment. This may also improve patient compliance.

2.Teach the patient to report any side effects of the drug:

a.Tachycardia.

b.Palpitations.

c.Chest pain.

3.Emphasize the need for lifelong treatment with levothyroxine and the dangers of noncompliance.

4.Thyroid replacement should be taken on an empty stomach.

5.The beneficial effects of thyroid replacement occur in about 3 days to 1 week; the patient may not feel the clinical effects for several months.

6.When switching brands or using a generic version, the serum TSH should be checked in 6 weeks.

C.Pharmacological therapy:

1.Patients requiring therapy with levothyroxine should be treated with the same brand/generic consistently since potency varies between brand and generics.

a.Levothyroxine (Synthroid, Levoxyl, Levothroid, Unithroid):

i.Adults 1.6 mcg/kg/d by mouth is administered as a single dose in the morning on an empty stomach to achieve optimal absorption.

ii.Elderly with comorbid CAD or severe COPD should be started at 25 to 50 mcg/d.

iii.Maintenance dose is 50 to 200 mcg by mouth every morning.

iv.Do not give with medication/supplements that interfere with absorption: aluminumcontaining antacids, calcium carbonate, ferrous sulfate, phosphate binders, proton-pump inhibitors, and sucralfate.

v.Reassessment of TSH must be implemented during LT-4 levothyroxine therapy when starting/discontinuing the following: estrogen, androgen therapies, anticonvulsants, rifampin, sertraline, and tyrosine kinase inhibitors.

b.Desiccated thyroid (Armor thyroid):

i.Adult initial dosing is 15 to 30 mg/d by mouth and increased by 15 to 30 mg/d every 4 weeks.

ii.Maintenance dose is 60 to 180 mg/d.

2.The medication should be titrated to the lowest dosage needed to maintain euthyroidism and a nonelevated serum TSH and a normal or slightly elevated T4.

3.Elderly patients and those with CVD should be started on very low doses (25 mcg/d) of levothyroxine; doses are increased very gradually over 8 to 12 weeks as tolerated. Close monitoring for the development of cardiac complications such as angina, arrhythmias, and myocardial infarction needs to be undertaken.

4.Thyroid hormones should be taken on an empty stomach in the mornings to avoid insomnia.

5.Other drugs can reduce the effectiveness/affect absorption of thyroid hormone:

a.Cholesterol-reducing drugs.

b.Cholestyramine interferes with absorption in the gut.

c.Calcium carbonate.

d.Aluminum hydroxide.

e.Sucralfate (Carafate).

f.If taking one of these drugs and levothyroxine, they should be taken 4 to 6 hours apart.

6.Dietary fiber can interfere with levothyroxine absorption. Coffee reduces the absorption of levothyroxine.

7.Pharmacologic treatment of the patient with subclinical hypothyroidism is controversial. If a goiter is present, treatment may be considered.

Follow-Up

A.Patients who are not treated with medication should be seen every 6 to 12 months for reevaluation.

B.When medication is instituted, monitor laboratory values and patient well-being in the office every 4 to 6 weeks.

C.After the dosage is stabilized, the patient with an elevated serum TSH level should be seen every 6 to 12 months:

1.Undetectable TSH levels are indicative of overmedication.

2.High TSH levels are indicative of insufficient medication or patient noncompliance.

D.After the TSH is normalized, regular annual follow-up visits are required.

E.Order DEXA scan as indicated for assessment of bone loss.

Consultation/Referral

A.Consultation with an endocrinologist is recommended for the following:

1.Patients unresponsive to therapy.

2.Pregnant patients.

3.Presence of goiter, nodule, or other structural changes in the thyroid.

4.Compression symptoms of dysphagia.

5.Any patient with myxedema, significant cardiac disease, or involvement or hypothyroidism secondary to pituitary or hypothalamic failure should be managed in consultation with a physician or should be referred to an endocrinologist for continued care.

6.Refer to radiologist/physician if fine-needle aspiration biopsy is required.

Individual Considerations

A.Pregnancy:

1.Pregnancy: Monitor TSH levels monthly during the first trimester.

2.Small increases in medication dosage may be required.

3.Some women develop postpartum thyroiditis and hypothyroidism after taking hyperthyroid medication during pregnancy or immediately thereafter.

4.Postpartum: Monitor TSH level at 6 weeks postpartum examination.

5.A common cause of congenital hypothyroidism is maternal and infant iodine deficiency.

6.Monitor the TSH to avoid overtreatment in postpartum women because excess thyroid hormone levels increase the risk of osteoporosis.

7.Hypothyroidism in pregnancy is associated with preeclampsia, anemia, postpartum hemorrhage, cardiac ventricular dysfunction, spontaneous abortion, low birth weight, impaired cognitive development, and fetal mortality.

B.Geriatrics:

1.Some elderly patients who are actually hyperthyroid exhibit symptoms of hypothyroidism. Monitor these patients closely, especially when adjusting the medication dosage and/or adding medications that alter the absorption of the thyroid medication.

2.Target is raised for geriatrics: serum TSH is 4 to 7 mIU/L. (nonelderly it remains 0.5–4.5 mIU/L). In adults aged 80 or older, TSH up to 7.5 mlU/L is normal. If the TSH is greater than 7.5 mlU/L, recheck TSH with a free T4 to confirm prior to treatment (Reubin et al., 2016).

3.For older patients starting dose of LT-4 levothyroxine is 25 to 50 mcg/d; recheck every 6 weeks. Increase dose in small increments until serum TSH stabilizes at 4 to 6 mIU/L. Patients without heart disease, stroke, or dementia may start at larger doses.

4.Geriatrics frequently take morning antacids, laxatives, and iron/calcium supplements. Be sure to instruct them/surrogates not to take LT-4 replacement therapy with those medications, and to wait approximately 2 hours after taking levothyroxine.

5.Symptoms of hypothyroidism such as memory loss, decreased cognitive function, constipation, hypersomnia, and dry skin are frequently attributed to advancing age. To further evaluate elderly patients, assess for positive family history of thyroid disease, past history of hyperthyroid treatment, or a history of surgery/radiotherapy to the neck.

6.CAD and heart failure must be treated in conjunction with thyroid replacement therapy.

7.LT-4 levothyroxine hormone replacement needs to begin slowly and not put stress on the heart and central nervous system. Educate patient and surrogates to notify you if possible signs occur: increase of angina, dyspnea, confusion, changes in sleep patterns, or sudden changes in cognition.

8.Do not assess thyroid function in ill older adults as the TSH is often falsely low or high. If thyroid disease is suspected as part of the illness, recheck to verify. If it is a very low TSH (<0.1 mlU/L) or very high (>20 mlU/L) then thyroid disease is likely (Reubin et al., 2016).

9.Beers Criteria: Synthetic form of desiccated thyroid is not recommended because it tends to cause cardiac adverse effects in geriatrics. An alternative to homeopathic desiccated thyroid extract/treatments is levothyroxine

Thyrotoxicosis/Thyroid Storm

Definition

A.Severe thyrotoxicosis of any cause is called thyrotoxic crisis or storm.

Incidence

A.It is rare; the incidence varies, depending on the cause of the thyrotoxicosis.

B.The mortality associated with thyrotoxicosis is estimated at 30% of documented cases.

C.The average age for thyrotoxicosis is 42 to 43 years and the male to female ratio is 1:3.

Pathogenesis

A.Thyrotoxic crisis or storm usually develops in patients either undiagnosed as being hyperthyroid or those who are known to be severely hyperthyroid, are being treated insufficiently, and are subjected to excessive stress from other causes. Oversecretion of T3 and T4 is followed by a release of epinephrine. Metabolism is dramatically increased. The adrenal glands produce excessive corticosteroids, which is a response to stress.

Predisposing Factors

A.Severe, uncontrolled hyperthyroidism.

B.Noncompliance with anti-hyperthyroid medication.

C.Inadequate preparation for thyroid surgery or recent use of iodinated contrast medium.

D.Acute illnesses: Infections, diabetic ketoacidosis, postmyocardial infarction (MI), drug reaction.

E.Parturition.

Common Complaints

A.Sudden onset of the following:

1.Hyperthermia.

2.Tachycardia (usually atrial tachydysrhythmias).

3.High-output cardiac failure.

4.Altered sensorium (usually agitation, restlessness, delirium).

5.Nausea, vomiting, and diarrhea.

Subjective Data

A.Elicit information regarding the onset, duration, and nature of symptoms.

B.Determine the presence of cardiac symptoms.

C.Take a complete drug history, including whether or not patient has been taking antithyroid medication as prescribed.

D.Rule out any excessive acute stressors such as infection, pulmonary or cardiac problems, dialysis, plasmapheresis, and/or emotional stressors.

E.Definitive diagnosis of thyroid storm in older adults:

1.Elevated FT3 and FT4 plus at least one central nervous system (CNS) manifestation (restlessness, delirium, psychosis, lethargy, somnolence) plus one or more of the following symptoms: fever, tachycardia, (congestive heart failure CHF), N/V/D, total bilirubin 3 mg/dl. or

2.Elevated FT3 and FT4 plus a combination of at least three of the following symptoms: fever, tachycardia, CHF, N/V/D, total bilirubin 3 mg/dl.

Physical Examination

A.Check temperature, pulse, respirations, and BP.

B.Inspect:

1.Inspect the skin.

C.Auscultate:

1.Auscultate the heart and lungs.

D.Palpate the neck carefully for thyroid nodules and enlargement.

Diagnostic Tests

A.Serum T3 and free T4.

B.TSH.

Differential Diagnoses

A.Thyroid storm.

B.Thyrotoxic crisis.

Plan

A.General interventions:

1.Closely monitor temperature, pulse, respirations, and BP.

2.Assess the need to hospitalize the patient for supportive therapy: IV fluids, medication treatment, antipyretics, and/or oxygen.

3.Aggressive cooling with cooling blankets/ice packs. Look for signs of infection triggering thyroid storm and treat appropriately.

4.Monitor for acute disturbances of consciousness, psychosis, and convulsions. If necessary, refer to psychiatrist/neurologist for management.

5.Monitor hydration status if fever has occurred or GI symptoms are severe.

6.Monitor for hepatotoxicity with/without jaundice in thyroid storm secondary to potential hepatocyte damage during a thyroid storm.

B. See Section III: Patient Teaching Guide Hyperthyroidism.

C.Pharmaceutical therapy:

1.See Pharmaceutical therapy in section Hyperthyroidism (for PTU, oral methimazole, beta-blockers, calcium channel blockers, antiarrhythmic and warfarin therapy).

2.IV methimazole recommended for severely ill patients with consciousness disturbances during thyroid storm.

3.Corticosteroids (300 mg/d hydrocortisone or 8 mg/d dexamethasone) recommended for thyroid storm regardless of origin.

4.Aggressive anticoagulation therapy should be used based on CHADS2 for patients ≥75 years old, and for adults with diabetes, CHF, HTN, or stroke history. Thyroid storm patients are vulnerable to disseminated intravascular coagulation (DIC).

Follow-Up

A.Following resolution of the crisis, see the patient in the office every 3 to 4 weeks for evaluation and monitoring of serum TSH and free T4 levels.

B.See Follow-Up in section Hyperthyroidism.

Consultation/Referral

A.Refer the patient to a physician immediately for possible hospitalization.

Individual Considerations

A.Pregnancy: See Individual Considerations in section Hyperthyroidism.

B.Geriatrics:

1.Mortality for geriatric thyrotoxicosis patients is 15% to 20% of documented cases. Confusion, consciousness disturbances, and dysrhythmias are common presentations. Geriatrics respond well to immediate hydration (IV fluids), metoprolol, IV hydrocortisone, and PTU. It is recommended to evaluate for hidden urinary tract infections (UTIs)/pulmonary/skin infections which may be the triggering factor.

2.Beers Criteria:

a.Nifedipine (Norvasc) and clonidine (Catapres) have increased sensitivity with geriatrics for potential orthostatic hypotension, bradycardia, and CNS adverse effects. Consider long-acting calcium channel blocker or angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB).

b.Oral anticoagulants (warfarin, aspirin, dabigatran, apixaban) have bleeding risks. Warfarin is recommended with tight INR lab testing during thyroid storm. Consider unfractionated heparin and keep aspirin doses under 325 mg/d with patients who have a history of ulcers.

c.Antiarrhythmics: Digoxin may increase mortality in AFib and CHF and reduce renal clearance, which will increase the risk of toxicity. Amiodarone is more toxic than other treatments in the geriatric patient. Consider propafenone (Rhythmol). Diltiazem or verapamil may be used if ejection factor is stable and/or CHF is stable.

d.Corticosteroids may worsen delirium in geriatrics. Use lowest effective dose for shortest amount of time and avoid combining with aspirin/NSAID to prevent GI bleeds/ulcer formation.

e.If thyroid storm was triggered by an infection, a common prescribed antibiotic for UTI has been nitrofurantoin (Macrobid®\). Use this medication with caution in the geriatric population because of its risk of pulmonary toxicity, neuropathy, hepatotoxicity, and concerns with creatinine clearance.