Putr- ACC.med - Thyroid Disorders

8/3/2019 Putr- ACC.med - Thyroid Disorders

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Thyroid Disorders: Hyperthyroidism and Thyroid Storm

Introduction

Thyroid hormone affects all organ systems, and is responsible for increasing

metabolic rate, heart rate, ventricle contractility, as well as muscle and central

nervous system excitability. Two major types of thyroid hormones are thyroxine (T4 )

and triiodothyronine (T3). T4 is the major form of thyroid hormone. The ratio of T 4 to

T3 released in the blood is 20:1. Peripherally, T4 is converted to the active T3, which is

three to four times more potent than T4 .

Hyperthyroidism refers to excess circulating hormone resulting only from thyroid

gland hyperfunction whereas thyrotoxicosis refers to excess circulating thyroidhormone originating from any cause (including thyroid hormone overdose).

Thyroid storm is the extreme manifestation of thyrotoxicosis. This is an acute,

severe, life-threatening state of thyrotoxicosis caused either by adrenergic

hyperactivity or altered peripheral response to thyroid hormone following the

presence of one or more precipitants.

Epidemiology

In the U.S., the overall incidence of hyperthyroidism is estimated to be between

0.05% to 1.3%, with the majority being subclinical in terms of presentation.1

Among

hospitalized thyrotoxicosis patients, the incidence of thyroid storm has been noted

to be


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Causes of Hyperthyroidism or Thyrotoxicosis

Table 224-1 Causes of Hyperthyroidism: Primary and Secondary Hyperthyroidism

Primary Hyperthyroidism

Graves disease (toxic diffuse

goiter) (Figure 224-0.1)

Most common of all hyperthyroidism (85% of all cases)

Associated with diffuse goiter, ophthalmopathy, and local

dermopathy

Toxic multinodular goiter Second most common cause of hyperthyroidism

Toxic nodular (adenoma)

goiter (Figure 224-0.2)

An enlarged thyroid gland that contains a small rounded mass or

masses called nodules with overproduction of thyroid hormone

Secondary Hyperthyroidism

Thyrotropin-secreting pituitary

adenoma

Thyroid gland stimulated to produce hormones

Thyroiditis Inflammation of the thyroid gland.

Hashimoto thyroiditis Initially gland is overactive (hyperthyroidism state) but this is

usually followed by a state of hypothyroidism

Subacute painful thyroiditis

(de Quervain thyroiditis)

Subacute painless thyroiditis

Radiation thyroiditis


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Table 224-2 Other Causes of Hyperthyroidism

Nonthyroidal Disease

Ectopic thyroid tissue

(struma ovarii)/teratoma

A rare form of mature teratoma that contains mostly thyroid

tissue.Metastatic thyroid cancer Stimulates production of thyroid hormones.

Human chorionic

gonadotropin

Secreting hydatidiform mole.

Drug-Induced

Iodine Iodine-induced thyrotoxicosis (calledJod-Basedow disease).

After treatment of endemic goiter patients with iodine or

stimulation of thyroid hormones from use of iodine-

containing agents like radiographic contrast agents.

Amiodarone Contains iodine. May cause either thyrotoxicosis or

hypothyroidism.

-Interferon

During treatment for other diseases, such as viral hepatitis

and human immunodeficiency virus infection.

Interleukin-2

Excessive thyroid

hormone ingestion

Thyrotoxicosis factitia Munchausen-like; thyroid hormone is taken by patient to fake

illness.

Ingestion of meat

containing beef thyroid

tissue

Cow thyroid tissue contains thyroid hormones.

Other causes may include nonthyroidal diseases caused by production of thyroid

hormones at sites away from the thyroid glands. Drug-induced thyrotoxicosis is

caused by the interaction of the thyroid glands with certain drugs, causing

stimulation of thyroid hormone production. Excessive thyroid hormone ingestion

caused either by intentional or accidental intake will bring about thyrotoxicosis.

The most common underlying cause of hyperthyroidism in cases of thyroid storm is

Graves disease (85% of all hyperthyroidism cases in the U.S.). It is caused by the

thyrotropin receptor antibodies that stimulate excess and uncontrolled thyroidal

synthesis and secretion of thyroid hormones. It occurs most frequently in young

women (10 times more common in women compared with men) at any age group.3

Toxic multinodular goiter is the second most common group in which thyroid storm

tend to occur. Rare causes of thyrotoxicosis leading to thyroid storm include


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hypersecretory thyroid carcinoma, thyrotropin-secreting pituitary adenoma, struma

ovarii, and human chorionic gonadotropinsecreting hydatidiform mole.

Pathophysiology

The pathophysiologic mechanisms underlying the shift from uncomplicated

hyperthyroidism to thyroid storm are not entirely clear. However, they involve

adrenergic hyperactivity either via increased thyroid hormone production or

increased receptor sensitivity. Many of the signs and symptoms are related to

adrenergic hyperactivity.

When there is excess of thyroid hormones, circulating T4 and T3 are taken into the

cytoplasm of cells. T4 is converted to its active form, T3, by 5'-deiodinase enzyme viadeiodination in the outer ring of the T4 molecule. Within the cytoplasm, the T3 then

exerts its effect by passing into the nucleus and binding to thyroid hormone

receptors or thyroid hormoneresponsive elements to induce gene activation and

transcription.4

The receptors receiving the hormone will stimulate changes specific

to the tissue.

Lipogenesis and lipolysis occur as thyroid hormone induces enzymes early in the

lipogenic pathway, including malic enzyme, glucose-6-phosphate dehydrogenase,

and fatty acid synthetase.

Increased cholesterol production occurs via transcription of 3-hydroxy-3-

methylglutaryl coenzyme A reductase. Nevertheless, thyroid hormones also cause

increased excretion of cholesterol in the bile, generally resulting in a decrease in

total cholesterol. In the pituitary gland, T3 exerts negative regulation on the

transcription of the genes for the subunit and the common subunit of TSH, resulting

in a suppressed TSH in the context of thyrotoxicosis.

During thyroid storm, precipitants such as infection, stress, myocardial infarction, or

trauma will multiply the effect of thyroid hormones via freeing of thyroid hormones

from their binding sites or increased sensitivity of the receptors in tissues via


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increase in target cell -adrenergic receptor density or postreceptor modifications in

signaling pathways.

Thyroid Storm Precipitation

The precipitants of thyroid storm are as shown in Table 224-3. The most common

precipitating cause of thyroid storm currently is infection.5

Other causes include

diabetic ketoacidosis, hypoglycemia, hyperosmolar coma, radioactive iodide

treatment, pulmonary embolism, thyroid hormone overdose, withdrawal of

antithyroid medications, iodinated contrast medium ingestion, vascular accidents,

surgery, stress, parturition, eclampsia, trauma, and myocardial infarct. In

approximately 20% to 25% of cases, no acute precipitant is identified.

Table 224-3 Precipitants of Thyroid Storm

Systemic insult Cardiovascular insult

Infection Myocardial infarction

Trauma Cerebrovascular accidents

General surgery Pulmonary embolism

Hyperosmolar coma Obstetrics-related

Endocrinal insult Parturition

Diabetic ketoacidosis Eclampsia

Drug- or hormone-related Unknown etiology in up to 25% of cases

Withdrawal of thyroid medication

Iodine administration

Thyroid gland palpation

Ingestion of thyroid hormone


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Clinical Features

History and Comorbidities

The patient may only complain of constitutional symptoms such as generalized

weakness and fatigue. Heat intolerance, diaphoresis, fever, weight loss, anxiety,

emotional lability, palpitations, diarrhea, and hair loss are common historical

features. Medications that can precipitate thyrotoxicosis include iodine-containing

medications, including radiographic contrast material, amiodarone, or large doses of

topical povidone-iodine (especially if there is skin break). If there is a history of

hyperthyroidism, treatment and compliance with medication should be determined.

Physical Examination

In general, patients often appear toxic and agitated. The signs and symptoms of

hyperthyroidism patients are as shown in Table 224-4.

Table 224-4 Symptoms and Signs of Thyrotoxicosis

Affected System Symptoms Signs

Constitutional Lethargy Diaphoresis

Weakness Fever

Heat intolerance Weight loss

Neuropsychiatric Emotional lability Fine tremor

Anxiety Muscle wasting

Confusion Hyperreflexia

Coma Periodic paralysis

Psychosis

Ophthalmologic Diplopia Lid lag

Eye irritation Dry eyes

Exophthalmos

Ophthalmoplegia

Conjunctival infection

Endocrine: thyroid gland (Figure 224-1) Neck fullness Thyroid enlargement


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Tenderness Bruit

Cardiorespiratory Dyspnea Widened pulse pressure

Palpitations Systolic hypertension

Chest pain Sinus tachycardia

Atrial fibrillation or flutterCongestive heart failure

GI Diarrhea Hyperactive bowel sound

Reproductive Oligomenorrhea Gynecomastia

Decreased libido Telangiectasia

Gynecologic Menorrhagia Sparse pubic hair

Irregularity

Hematologic Pale skin Anemia

Leukocytosis

Dermatologic Hair loss Pretibial myxedema

Warm, moist skin

Palmar erythema

Onycholysis

As for thyroid storm, the additional signs and symptoms apart from those evident in

hyperthyroidism are as shown below:

Presenting Signs and Symptoms of Thyroid Storm:


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Fever is often present in thyroid storm and may be quite high. It may herald the

onset of thyrotoxic crisis in previously uncomplicated disease. Palpitations,

tachycardia, and dyspnea are common. A pleuropericardial rub may be heard. The

direct inotropic and chronotropic effects of thyroid hormone on the heart cause

decreased systemic vascular resistance, increased blood volume, increased

contractility, and increased cardiac output. Enhanced contractility produces

elevations in systolic blood pressure and pulse pressure, leading to a dicrotic or

water-hammer pulse. Atrial fibrillation occurs in 10% to 35% of thyrotoxicosis

cases.6,7

Exophthalmos is present in Graves disease. The severity of ophthalmopathy does not

necessarily parallel the magnitude of thyroid dysfunction but reflects the responsible

autoimmune process.

Not all hyperthyroidism patients present with goiter. A goiter is not present with

exogenous administration of thyroid hormone and apathetic thyrotoxicosis.

Likewise, the presence of a goiter does not necessarily confirm the diagnosis of

thyrotoxicosis. Thyroid gland tenderness can be found in inflammatory conditions

such as subacute thyroiditis.8

Thyroid storm is a clinical diagnosis for patients with preexisting hyperthyroidism.

Fever and tachycardia are cardinal features. The differential diagnosis of thyroid

storm (as shown in Table 224-6) includes infection, sepsis, cocaine use, psychosis,

pheochromocytoma, neuroleptic malignant syndrome, and hyperthermia.


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Table 224-6 Differential Diagnosis for Thyroid Storm

Infection and sepsis

Sympathomimetic ingestion (e.g., cocaine, amphetamine, ketamine drug use)

Heat exhaustion

Heat stroke

Delirium tremens

Malignant hyperthermia

Malignant neuroleptic syndrome

Hypothalamic stroke

Pheochromocytoma

Medication withdrawal (e.g., cocaine, opioids, etc.)

Psychosis

Organophosphate poisoning

Differential Diagnosis

In an effort to standardize and objectify thyroid storm as compared with severe

thyrotoxicosis, Burch and Wartofsky have delineated a point system assessing

degrees of dysfunction in four systems: thermoregulatory, central nervous, GI, and

cardiovascular systems (Table 224-7). The point system assists in determining

whether the patient's presentation is unlikely, suggestive, or highly suggestive of

thyroid storm.


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Table 224-7 Burch and Wartofsky's Diagnostic Parameters and Scoring Points for

Thyroid Storm

Diagnostic Parameters Scoring Points

1. Thermoregulatory dysfunction

Temperature C (F)37.237.7 (9999.9) 5

37.738.3 (100100.9) 10

38.338.8 (101101.9) 15

38.939.4 (102102.9) 20

39.439.9 (103103.9) 25

40 (104.0) 30

2. Central nervous system effects

Absent 0

Mild (agitation) 10

Moderate (delirium, psychosis, extreme lethargy) 20Severe (seizures, coma) 30

3. GI-hepatic dysfunction

Absent 0

Moderate (diarrhea, nausea/vomiting, abdominal pain) 10

Severe (unexplained jaundice) 20

4. Cardiovascular dysfunction

Tachycardia (beats/min)

90109 5

110119 10

120129 15

140 25

5. Congestive heart failure

Absent 0

Mild (pedal edema) 5

Moderate (bibasilar rales) 10

Severe (pulmonary edema) 15

6. Atrial fibrillation

Absent 0

Present 10

Scoring system:

Score of 45 : Highly suggestive of thyroid storm.

Score of 2544 : Suggestive of impending storm.

Score of


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Laboratory Evaluation

Serum Thyroid-Stimulating Hormone Level

In primaryhyperthyroidism, the TSH level is low as a result of the negative feedback

mechanism of a high thyroid hormone level. Nevertheless, a low TSH level by itself is

not diagnostic, as serum TSH may be reduced as a result of chronic liver or renal

disease, or the effect of certain drugs like glucocorticoids, which reduce TSH

secretion.

In secondary hyperthyroidism, TSH is increased because of increased production in

the pituitary.

Free Thyroid Hormone Levels: Free Thyroxine and Free Triiodothyronine

A low TSH with an elevated free thyroxine (FT4) confirms thyrotoxicosis. On the other

hand, a low TSH with a normal FT4 but elevated free triiodothyronine (FT3 ) is also

diagnostic of T3 thyrotoxicosis. T3 thyrotoxicosis occurs in


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affected by conditions that affect protein binding. With the improved assays for FT 4

and FT3, there is now little indication to measure total T3 and total T4.

Thyroid Antibody Titers

If Graves disease is suspected, thyroid antibody titers (to thyroid peroxidase or

thyroglobulin) will help determine diagnosis. Thyroid-stimulating antibodies are

detected in Graves disease.

Thyroid hormone studies, complete blood count, electrolytes, glucose, and renal and

liver function tests should be considered to identify comorbid abnormalities, but

treatment has to start upon suspicion of the diagnosis. Hyperglycemia tends to occur

because of a catecholamine-induced inhibition of insulin release, and increasedglycogenolysis and rapid intestinal absorption of glucose.

Mild hypercalcemia and elevated alkaline phosphatase can occur because of

hemoconcentration and enhanced thyroid hormonestimulated bone resorption.9

Hyperthyroidism induces liver enzyme metabolism, causing raised liver enzymes.

A high serum cortisol value is an expected finding in thyrotoxic individuals. This

should be the normal reaction of an adrenal gland to a body under stress. The

finding of an abnormally low cortisol level in a patient with Graves disease should

raise suspicion of coincidental adrenal insufficiency.

Imaging

Chest radiograph (or chest CT without contrast when appropriate) can be done to

rule out an infectious source as a precipitant. A thyroid sonogram with Doppler flow

can be done to assess thyroid gland size, vascularity, and the presence of nodules.

Typically, a thyroid gland secreting excessive hormones would be enlarged and have

enhanced Doppler flow. On the other hand, in the setting of subacute, postpartum

thyroiditis, silent thyroiditis, or exogenous causes of hyperthyroidism, the thyroid

gland would be expected to be small with decreased Doppler flow. Nuclear medicine


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imaging with iodine-131 would reveal a greatly increased uptake of radioiodine as

early as 1 or 2 hours after administration of the agent.

ECG in Thyrotoxicosis

ECG findings in thyrotoxicosis most commonly include sinus tachycardia and atrial

fibrillation. Sinus tachycardia occurs in approximately 40% of cases.7

Atrial fibrillation

occurs in 10% to 35% of thyrotoxicosis patientswith a tendency to occur more

commonly in patients >60 years old who are more likely to have underlying

structural heart disease.7 Premature ventricular contractions and heart blocks may

be present. Atrial premature contractions and atrial flutter may also occur in

thyrotoxicosis.

Standard Treatment for Thyroid Storm

The order of therapy in treating thyroid storm is very important with regard to the

use of thionamide and iodine therapy. Inhibition of thyroid gland synthesis of new

thyroid hormone with a thionamide should be initiated before iodine therapy to

prevent the stimulation of new thyroid hormone synthesis that can occur if iodine is

given too soon.

Treatment aims are as follows:

1. Supportive care

2. Inhibition of thyroid hormone release

3. Inhibition of new hormone production

4. Peripheral -adrenergic receptor blockade

5. Preventing peripheral conversion of T4 to T3


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References

Biro E, Bako G, et al. Association of systemic and thyroid autoimmune diseases. Clin

Rheumatol. 2006;25:240.

Cagliero E, Apruzzese W, Perlmutter GS, Nathan DM. Musculoskeletal disorders of

the hand and shoulder in patients with diabetes mellitus. Am J Med. 2002;112:487.(Study of hand and shoulder complications in diabetic patients and controls).

Kloppenburg M, Dijkmans BA, Rasker JJ. Effect of therapy for thyroid dysfunction on

musculoskeletal symptoms. Clin Rheumatol. 1993;12:341.

Lacks S, Jacobs RP. Acromegalic arthropathy: a reversible rheumatic disease.J

Rheumatol. 1986;13:634. (Case report and general review.

Lockshin M. Endocrine origins of rheumatic disease. Diagnostic clues to interrelated

syndromes. Postgrad Med. 2002;111:87. (Overview for primary care clinicians).

McGuire JL. The endocrine system and connective tissue disorders. BullRheum Dis.

1990;39:1. (A somewhat dated, but more detailed review of the subject published by

the Arthritis Foundation).

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