eMedicine Specialties > Neurology > Neuromuscular Diseases

Thyroid Disease

Gabriel Bucurescu, MD, MS, Staff Neurologist, Neurology Service, Philadelphia Veterans Affairs Medical Center

Updated: Jan 29, 2009

Introduction

Background

The thyroid gland plays an important role in tissue metabolism and development. It secretes thyroxine (3,5,3'5'-tetraiodothyronine), which is abbreviated as T4, and small amounts of 3,5,3'-triiodothyronine, abbreviated T3. Both have systemic effects. Abnormal thyroid hormone levels lead to hypothyroid and hyperthyroid states. Inadequate thyroid hormone during development leads to congenital hypothyroidism (also known as cretinism) with associated irreversible brain damage.

Pathophysiology

Thyroid hormones regulate protein synthesis by affecting gene transcription and mRNA stabilization.

Hyperthyroidism

In hyperthyroidism (ie, thyrotoxicosis) increased thyroid function leads to increased cardiac output at rest and after exercise but to decreased muscle bulk and function.

Muscle activity shows altered electrical responses, altered energy metabolism, and increased sensitivity to beta-adrenergic stimuli. In a clinical study of experimental thyrotoxicosis, the activity of oxidative and glycolytic enzymes in skeletal muscle decreased by 21-37%. Lean body mass decreases and rate of whole body protein breakdown is enhanced. Thyroid hormones have profound effects on mitochondrial oxidative activity, synthesis and degradation of proteins, sensitivity of tissues to catecholamines, differentiation of muscle fibers, capillary growth, and levels of antioxidant enzymes and compounds. Muscles show contraction weakness and lack of normal contraction potentiation. Patients have lower levels of carnitine.

The central effects of hyperthyroidism are most pronounced in development. Cerebral circulation and oxygen consumption elevate. Studies on rat brain mitochondria show minimal effects. Measurements from rats suggest well-preserved brain iodothyronine homeostasis despite high thyroid hormone levels. Brain T4 and T3 concentrations and brain T3 production and turnover rates do not change significantly. Levels of glutamate dehydrogenase and pyruvate dehydrogenase activity in the brain are reduced. Beta-adrenergic binding sites in the cerebral cortex are increased and gamma-aminobutyric acid (GABA) binding sites are decreased. Brain levels of serotonin, 5-hydroxyindoleacetic acid, and substance P are altered. Native pain sensitivity and number of opiate receptors are increased. Thyroid hormones affect myelination, therefore increased levels lead to oxidative damage to the myelin membrane and/or the oligodendroglial cells.

Hypothyroidism

In hypothyroidism, muscle contraction and relaxation are slowed while duration is prolonged.

The amount of myosin ATPase decreases. Slowing of release and reaccumulation of calcium in the endoplasmic reticulum may decrease relaxation. In peripheral nerves, segmental demyelination has been observed with decreased nerve conduction velocities. Patients develop polyneuropathy with loss of reflexes and weakness. Decreases in vibration, joint-position, and touch-pressure sensations also are seen.

Frequency

United States

Thyroid disease is common in adults.

• One survey found the prevalence of hypothyroidism to be 1.4% in adult females and 0.1% in adult males. The prevalence of Graves disease, a hyperthyroid condition, is 1.9% in females and about 0.19% in males. Peak age incidence is in the range of 30-50 years.
• Congenital disease occurs in 1 per 4000 neonates in North America and Western Europe. This is seen more frequently in areas of iodine deficiency.

International

About 1 billion people are at risk for iodine deficiency disorders.

• Endemic goiter is most the common manifestation and has a varying prevalence.
• In communities with severe iodine deficiency, prevalence is 5-15% but can reach 100%. This situation occurs in developing countries.

Mortality/Morbidity

• Neurologic complications are seldom fatal.
• Congenital complications of iodine deficiency lead to cretinism and neonatal myxedema.
• Untreated myxedema may lead to myxedema coma and eventually to death in children and adults.
• Severity of symptoms of thyroid disease varies with the degree and duration of the deficiency.
• Some degree of myopathy is found in about 50% of thyrotoxic patients.
• Thyroid storm is an emergency requiring rapid therapy to prevent death.
• Although now uncommon, postoperative thyroid disease can be seen.

Race

No race predilection is known.

Sex

Thyroid disease is more common in women, but men also are affected.

Age

Thyroid disease is most common in adults aged 30-50 years, but all age groups are affected. Cretinism and neonatal myxedema manifest in the intrauterine/perinatal period.

Clinical

History

Presenting symptoms depend on whether thyroid hormone levels are increased or decreased. Symptoms are generalized initially. Neurologic signs appear after months to years. The brain, peripheral nerves, and muscular systems can be affected.

• Hypothyroidism
  • Hypothyroidism occurs when T4 and T3 levels fall below physiologically required levels.
  • Severe hypothyroidism results in myxedema, which results from accumulation of hydrophilic mucopolysaccharides in subcutaneous tissues.
  • The term myxedema can be synonymous with hypothyroidism. However some reserve myxedema for severe hypothyroidism only.
  • Common symptoms include the following:
    • Weakness, fatigue, lethargy, and somnolence
    • Cold intolerance, decreased sweating
    • Dry, coarse skin
    • Headache
    • Swelling of the face and extremities
    • Impaired memory and cognition, poor concentration
    • Mild weight gain (with anorexia)
    • Coarseness of voice and impaired hearing
    • Paresthesias and arthralgias
    • Muscle cramps
    • Constipation
• Hyperthyroidism
  • Hyperthyroidism results from excessive levels of T4 and T3.
  • Symptoms include the following:
    • Confusion
    • Seizures
    • Nervousness and tremor, emotional lability
    • Muscle weakness
    • Heat intolerance
    • Weight loss (with increased appetite)
    • Palpitations

Physical

• Hypothyroidism
  • In infants this results in cretinism, which manifests as delayed physical and mental development. Affected infants have enlarged tongues, a coarse cry, thickened subcutaneous tissues, potbelly, umbilical hernia, hearing defects, and speech defects.
  • Other findings are slowness and masking or disinhibition of facial expression.
  • Strabismus may be noted.
  • Some develop thalamic posturing, with severe motor deficits and a characteristic posture.
  • When the patient is laid on one side, the undermost limb extends and the uppermost limb flexes.
  • Other signs include microcephaly; inability to sit, stand, or walk; prominent primitive facial reflexes (especially the visual suck reflex); blepharospasm; and a prominent glabellar reflex.
  • Patients appear autistic (ie, total disregard of surroundings and absence of purposeful activity).
  • Other signs include the following:
    • Hypotonia
    • Cerebellar signs manifesting with ataxia, tremor, and dysmetria
    • Polyneuropathy
    • Cranial nerve deficits
    • Entrapment neuropathy (eg, carpal tunnel syndrome)
    • Slowing of voluntary movements
    • Myopathic weakness, which can be subdivided into 4 subtypes: Kocher-Debre-Semelaigne syndrome, Hoffmann syndrome, atrophic form, and myasthenic form. Muscle hypertrophy is very rare in hypothyroid patients.
    • Neuropsychiatric signs - Dementia, apathy, mental dullness, irritability, sleepiness.
    • Hashimoto encephalopathy (HE), a rare, sometimes controversial classification of neurologic syndromes occurring in patients with steroid-responsive autoimmune thyroid disease. It was first described in 1966 and was associated with serum anti-thyroid antibodies. A single case report linked Hashimoto encephalopathy with painful legs and moving toes syndrome.¹ Other case reports of miscarriages, focal seizures, and palatal tremor associated with Hashimoto encephalopathy have also been made. 
• Hyperthyroidism
  • Hyperthyroidism manifests systemically, affecting primarily muscle function and the central nervous system.
  • It is associated with neuropsychiatric and neurologic syndromes and myopathy (eg, chronic thyrotoxic myopathy, exophthalmic ophthalmoplegia/infiltrative ophthalmopathy/Graves ophthalmopathy), thyrotoxic periodic paralysis, and myasthenia gravis.
  • Neuropsychiatric syndromes include the following:
    • Patients may manifest irritability, nervousness, tremulousness, apprehension, emotional lability, and agitation.
    • Major depression, anxiety, hypomania or mania, schizophreniform disorder, and delirium also may occur. Milder deficits in memory, complex problem solving, and attention may be present.
    • Psychosis (visual and auditory hallucinations) is infrequent.
    • The clinical picture is seldom clear. The onset of symptoms is insidious, and often patients are referred to psychiatrists before the diagnosis is made.
    • This is especially true for older patients, in whom dementia or depression is suspected.
    • The presence of such symptoms may be related to the premorbid personality, but no definitive studies exist to support this theory.
    • One of the difficulties in establishing the contribution of a premorbid personality is the inability of precisely determining the onset of thyroid dysfunction.
    • Psychiatric symptoms have no direct relationship to the severity of the hyperthyroidism; once thyroid hormone levels are back to normal, the symptoms may resolve over months.
  • Neurologic syndromes include chorea, ballism, embolic stroke secondary to tachycardia-induced atrial fibrillation, status epilepticus, and coma (which may occur in thyrotoxic crises). A case report describes a triad of acute ataxia, Graves disease, and stiff person syndrome.²
  • Chronic thyrotoxic myopathy is a common complication.
    • This myopathy is characterized by progressive weakness and wasting of skeletal musculature.
    • Goiter of the nodular type is often present (and sometimes exophthalmos).
    • More than 50% of thyrotoxic patients have some degree of myopathy.
    • The myopathy is slowly progressive; the pelvic girdle and thigh muscles are affected preferentially.
  • Exophthalmic ophthalmoplegia also is known as Graves ophthalmopathy and infiltrative ophthalmopathy.
    • This refers to weakness of external ocular muscles and exophthalmos from Graves disease.
    • Strabismus and diplopia may be present, as well as pain and lid retraction.
    • The term infiltrative ophthalmopathy refers to ocular muscle histology that suggests an autoimmune process: prominent fibroblastic tissue, degenerated fibers, and infiltration of lymphocytes, mononuclear leukocytes, and lipocytes.
  • Thyrotoxic periodic paralysis resembles familial periodic paralysis and manifests with attacks of mild to severe weakness, during which serum potassium levels are generally low.
  • Thyrotoxic neuropathy was also reported. Both the clinical and electrophysiological abnormalities resolved with treatment of the thyrotoxicosis.
  • Myasthenia gravis may be associated with hyperthyroidism.
    • Hyperthyroidism is seen in 5% of patients with myasthenia gravis.
    • Conversely, incidence of myasthenia gravis is 20-30 times higher in hyperthyroid patients than in the general population.
    • Weakness and muscle atrophy from hyperthyroid myopathy can coexist with other abnormalities secondary to myasthenia gravis.

Causes

Clinicians must be able to identify characteristic neurologic deficits of thyroid disease so as to predict and possibly prevent neurologic complications. These include drug effects, which can suppress thyroid-stimulating hormone (TSH) secretion, inhibit thyroid hormone release or synthesis, decrease hormone-protein binding, or inhibit conversion of T4 to T3.

• Drugs affecting the thyroid
  • Dopamine, L-dopa
  • Glucocorticoid excess
  • Iodide
  • Lithium carbonate
  • Sulfonylureas
  • Phenylbutazone
  • Phenytoin
  • Salicylates
  • Fenclofenac
  • Furosemide
  • Propylthiouracil
  • Propranolol
  • Amiodarone
  • Iopanoic acid (Telepaque), iopodate (Oragrafin)
• Causes of hyperthyroidism
  • Graves disease
  • Toxic multinodular goiter
  • Toxic adenoma
  • Iodide-induced hyperthyroidism
  • Subacute thyroiditis
  • Factitious (exogenous) thyroiditis
  • Neonatal thyrotoxicosis (eg, pregnant mother with Graves disease)
  • TSH-secreting pituitary tumor
  • Nontumorigenic pituitary-induced hyperthyroidism
  • Choriocarcinoma (uterine or testicular origin) or hydatidiform mole
  • Struma ovarii
  • Hyperfunctioning thyroid carcinoma (usually metastatic)
• Causes of hypothyroidism: Hypothyroidism can be primary, secondary, or due to tissue resistance to thyroid hormone.
  • Primary causes
    • Destructive lesions such as Hashimoto thyroiditis
    • Idiopathic myxedema
    • Radioactive iodine therapy for hyperthyroidism
    • Subtotal thyroidectomy (eg, surgery for Graves disease)
    • Neck irradiation for other diseases
    • Following acute thyroiditis (can be transient)
    • Cystinosis
    • Defects in enzymes that are necessary for thyroid hormone synthesis (congenital goiter)
    • Endemic goiter (iodine deficiency)
    • Iodine excess (>6 mg/d)
    • Drug-induced thyroid agenesis
    • Thyroid dysgenesis or ectopy
    • Maternal iodide
    • Antithyroid drugs
  • Secondary causes
    • Hypothalamic dysfunction due to neoplasm
    • Eosinophilic granuloma or therapeutic irradiation
    • Pituitary dysfunction due to neoplasm
    • Pituitary surgery or irradiation
    • Idiopathic hypopituitarism
    • Sheehan syndrome (ie, postpartum pituitary necrosis)
    • Dopamine infusion
    • Severe illness
    • Heatstroke
    • Traumatic brain injury

Differential Diagnoses

Other Problems to Be Considered

Late-onset dominant ataxias
Limb-girdle dystrophy
Metabolic neuropathy
Mitochondrial cytopathies

Workup

Laboratory Studies

• Blood levels of thyroid hormone and serum thyrotropin (ie, TSH) are the most important diagnostic tests. Levels of free T4 and free T3 in serum provide a better assessment of the thyroid status than total T4 and T3. The levels of T4 and T3 are decreased in hypothyroidism, and they are increased in hyperthyroidism.
• Serum TSH levels range from 0.5 to 5.0 microunits per milliliter. TSH is increased in hypothyroidism, and as thyroid function becomes autonomous, it decreases. It is a useful marker for the efficacy of therapy. The TSH-immunometric assay (TSH-IMA) can discriminate directly between normal TSH and reduced levels without requiring the use of the thyrotropin-releasing hormone (TRH) infusion test. If TSH levels remain high in cases of treated hypothyroidism, the possibility of a TSH-secreting pituitary adenoma should be considered.
• TRH infusion test can be performed by infusing TRH intravenously and measuring TSH in serum to determine the presence of TSH in the pituitary. TSH is reduced in hyperthyroidism in autonomous thyroid production and hypothalamic pituitary disease. This test has been superseded by the TSH-IMA.
• Thyroid hormone-binding ratio (known previously as T4 and T3 uptake) and transthyretin levels are rarely useful for common clinical purposes.
• Radioactive iodine (RAI) uptake can differentiate causes of hyperthyroidism: subacute thyroiditis (low uptake) versus Graves disease (high uptake).
• Antithyroid antibodies, the most important being thyroid microsomal antibody (TMAb), are seen in 95% of patients with Hashimoto thyroiditis but in only 10% of adults with no disease. In Graves disease, 55% of patients have circulating TMAbs. Recently, in a small study, antithyroid antibodies were found to be the most common abnormality in a group of patients with autoimmune manifestations and atypical neurologic features.
• Antithyroperoxidase antibodies from patients with Hashimoto encephalopathy were found to bind to cerebellar cells expressing glial fibrillary acid protein.³
• Thyroglobulin antibodies (TGAbs) are present in the serum of 60% of patients with Hashimoto disease.
• Antibodies against thyroid TSH receptor (TRAbs) are seen in the serum of patients with Graves disease.
• Serum thyroglobulin is most useful in follow-up of metastatic thyroid carcinoma after thyroidectomy.
• Creatine kinase (CK) levels may be elevated.
• Cerebrospinal fluid (CSF) protein may be increased.

Imaging Studies

• Imaging studies such as MRI or CT scan are of limited use in thyroid disease. Pituitary or hypothalamic tumors can be seen, as can metastatic lesions of thyroid carcinoma, which are usually solitary. In cases of severe exophthalmic ophthalmoplegia, extraocular muscle swelling can be observed on both MRI and CT scans (sometimes impinging on the optic nerve). Brains of adults with congenital hypothyroidism may show atrophy, especially of the brain stem and perisylvian regions (with cerebellum sparing). Patients with antibodies against thyroid antigens may show nonspecific MRI changes, probably due to demyelination.
• Thyroid scan (which involves either radioactive iodine 123 or iodine 131) correlates thyroid function and structure. It can diagnose the functional state of a thyroid nodule or search for thyroid tissue in neck masses.
• Thyroid ultrasound can assess whether a thyroid mass is solid or cystic. It is used usually to help in diagnosing a single thyroid nodule; cystic lesions may be simple cysts or benign follicular tumors, which could be managed medically, sparing the patient the need for surgery. However, follicular carcinoma also can become cystic, in which case tissue biopsy would be required. Solid masses suggest a possible tumor, in which case the treating physician would be inclined to proceed to surgery.

Other Tests

• Electroencephalography in hyperthyroidism
  • EEG may support the suspicion of CNS involvement.
  • Alpha rhythm is accelerated, and rolandic mu rhythm may be augmented.
  • Some have reported paroxysmal bursts and clinical seizures (eg, grand mal).
  • Patients with epilepsy and thyroid dysfunction may respond poorly to anticonvulsants until the underlying endocrine problem is treated.
  • Thyroxine can produce epileptic activity.
  • In thyrotoxic crises with encephalopathy, EEG abnormalities are characterized by marked slowing with superimposed fast activity.
  • Triphasic waves are reported rarely.
• Electroencephalography in hypothyroidism
  • EEG is characterized by an excess of low-voltage activity with a poor or absent alpha-blocking response.
  • In myxedematous coma, slow, low-voltage activity predominates.
  • Generalized periodic sharp wave discharges, mimicking Jakob-Creutzfeldt encephalopathy, have been reported in one case.
  • EEG abnormalities tend to resolve as thyroid abnormalities are treated.
  • In myxedematous infants, delay in EEG development (especially of sleep spindle) can occur.
  • Generally, EEG shows excessive low-voltage slowing.
• Electromyography
  • EMG generally provides limited information.
  • Proximal muscles are more likely to show an abnormal pattern than distal muscles.
  • In hyperthyroid patients, abnormalities include reduced duration of mean action potentials and increased mean percentage of polyphasic potentials.
  • Large action potentials may be seen in thyrotoxic myopathy but are not associated histologically with neuropathic change and are not believed to indicate denervation.
  • In hypothyroidism, EMG changes include polyphasic action potentials, hyperirritability, repetitive discharges after reflex motion, and low-voltage, short-duration motor unit potentials. Changes usually resolve as thyroid function normalizes.
• Nerve conduction studies
  • Nerve conduction velocities (NCV) are decreased in hypothyroid patients with polyneuropathy
    • Patients show diffuse sensory neuropathy due to axonal degeneration and not, as previously thought, to segmental demyelination.
    • Amplitude of sensory compound nerve action potentials (CNAP) is reduced and NCVs are slowed.
    • In carpal tunnel syndrome, typical nerve conduction abnormalities are seen.
  • One case was reported of severe hyperthyroidism with motor-sensory neuropathy, moderately slow NCVs, absent sural CNAP, and low sural sensory NCV.
  • Thyrotoxic neuropathy (also known as Basedow paraplegia) is very rare.
• Evoked potential studies
  • Generally these are not useful in thyroid disease.
  • Visual evoked potentials show increased latencies in hyperthyroidism with no change after patients become euthyroid.
  • In hypothyroid patients, amplitudes are decreased and latencies are prolonged.
  • Latencies and amplitudes improved inconsistently among some patients as thyroid function normalized.
  • Brainstem evoked responses are marginally useful, with some studies showing abnormalities.
  • Patients who had been hyperthyroid for longer than 6 months showed increased N19-P23 amplitudes in median somatosensory evoked potentials with the latency unaffected.

Procedures

• Thyroidectomy
• Fine-needle biopsy
• Muscle or peripheral nerve biopsy: This can confirm diagnosis or differentiate diagnoses. Both hyperthyroid and hypothyroid patients may have disturbed levels of carnitine but by separate mechanisms.⁴

Histologic Findings

• Hypothyroidism
  • Sural nerve biopsies - Axonal degeneration
  • Electron microscopy
    • Focal microfibrillar disorganization, sometimes with nemaline rods
    • Mitochondrial accumulation
    • Occasional basophilic degeneration: In cardiac and skeletal muscle, basophilic degeneration is due to deposits of polysaccharide material.
    • No definite abnormalities in muscle from individuals with congenital hypothyroidism
  • Muscle histology
    • Type I fiber excess
    • Atrophy of type I and II fibers
    • Altered oxidative enzyme activity, abnormal collection of glycogen, peripheral crescents, and distention of cytoplasmic reticulum
    • Vacuolar myopathy
    • Increased central nuclear counts
    • Central cores with oxidative activity in type I fibers
    • Impaired myelin formation
• Hyperthyroidism
  • Sural nerve biopsies
    • Excessive axonal branching
    • Degenerative changes of preterminal axons
    • Edematous protein infiltration of endoneurium and perineurium
    • Segmental demyelination in teased fiber preparation
  • Electron microscopy
    • Increased glycogen, acid mucopolysaccharides, and aggregates of glycogen and cytoplasmic laminar bodies in Schwann cells
    • In brain, small neuronal cell bodies with increased cell packing density, decreased neurophil, decreased myelin, and gliosis (especially in the substantia nigra and globus pallidus)
  • Muscle histology
    • Few pathologic changes in hyperthyroidism
    • Mild atrophy, infiltration of fat cells, nonspecific focal myofibrillar degeneration, mitochondrial hypertrophy, and focal dilatation of transverse tubular system

Treatment

Medical Care

Neurologic manifestations in thyroid disease generally develop slowly. They are diagnosed months or years after initial endocrine problems.

• Patients seek care after developing characteristic systemic signs and symptoms.
• Polyneuropathy is rarely the initial manifestation of undetected hypothyroidism. Metastatic thyroid carcinoma rarely presents as an initial brain metastatic lesion.
• Chorea-ballism has been reported sporadically. Chorea has been associated with elevated levels of antithyroid antibodies, with the symptoms responding to oral steroid treatment.
• Interestingly, one study reports that mild hypothyroidism is associated with better survival of ambulatory elderly patients after acute stroke.⁵
• Several reports of intracranial vascular disease (arterial occlusion, superior sagittal sinus thrombosis, cerebral vein thrombosis) have been reported associated with both hypothyroidism and hyperthyroidism. However, the patients had multiple pathologies, and a clear correlation with thyroid disease is difficult to establish.^6,7,8

Surgical Care

Surgery is indicated in the treatment of thyroid masses and large goiters.

Consultations

• Internal medicine/endocrinologist
• Head and neck surgeon
• Nuclear medicine specialist
• Radiation oncologist
• Pathologist

Diet

Iodine deficiency is not widespread in the United States, although immigrants from areas of endemic deficiency may require dietary consultation. Pregnant women may require more careful screening.

Activity

No restrictions are recommended typically.

Medication

The goal is to establish a euthyroid state. In hypothyroidism, this involves thyroid replacement, which is attained readily. In hyperthyroidism, elevated thyroid hormone is treated with surgery, which causes hypothyroidism and requires thyroid replacement, or with drugs and radioactive iodine.

Symptoms that are associated with abnormal thyroid states are treatable.

Thiourea derivatives

These medications are preferred for suppressing thyroid function.

Propylthiouracil (PTU)

Derivative of thiourea that inhibits organification of iodine by thyroid gland. Also inhibits conversion of T4 to T3, which is advantage over other agents.

Dosing

Adult

300-450 mg/d PO divided tid; rarely, as much as 1600 mg/d may be required

Pediatric

Adjust dosage according to severity of disease and patient weight

Interactions

Has anti-vitamin K activity and may potentiate activity of oral anticoagulants

Contraindications

Documented hypersensitivity; breastfeeding mothers

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause rash, vasculitis, and rarely, hepatocellular damage and agranulocytosis; use sparingly in pregnant patients, because drug crosses placenta

Methimazole (Tapazole)

Suppresses thyroid function and has mechanism similar to that of PTU; does not inhibit peripheral conversion of T4 to T3.
Fifteen times as potent as PTU. PTU equivalent dosing can be used, divided tid.

Dosing

Adult

Mild hyperthyroidism: 15 mg/d PO; adjust to effect
Moderately severe hyperthyroidism: 20-30 mg/d PO; adjust to effect
Severe hyperthyroidism: 60 mg/d PO; adjust to effect
Maintenance dose: 5-15 mg PO qd

Pediatric

Initial dose: 0.4 mg/kg PO divided tid
Maintenance dose: Half initial dose

Interactions

Has anti-vitamin K activity and may potentiate activity of oral anticoagulants

Contraindications

Documented hypersensitivity; breastfeeding mothers

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause agranulocytosis; closely monitor patients for adverse effects; may cause hypoprothrombinemia and bleeding

Beta-adrenergic blocking agents

These agents are used to treat symptomatic hyperthyroidism.

Propranolol (Inderal)

This nonselective, beta-adrenergic blocking agent treats symptomatic tachycardia. Has membrane-stabilizing activity and decreases automaticity of contractions.

Dosing

Adult

20-40 mg PO q4-6h

Pediatric

2-4 mg/kg/d PO divided bid

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability, possibly reducing effects
Conversely, calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase levels, and thus toxicity or effects
May increase toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure (CHF); bronchial asthma; bradycardia; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with renal or hepatic dysfunction (may reduce intraocular pressure); beta-adrenergic blockade may decrease signs and symptoms of acute hypoglycemia
Abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor patient closely

Thyroid hormones

These agents are used in thyroid hormone replacement.

Levothyroxine (Synthroid, Levoxyl)

Synthetic, but identical to natural T4; in its active form, influences growth and maturation of tissues; is involved in normal growth, metabolism, and development.

Dosing

Adult

25 mcg PO initially; increase to effect prn

Pediatric

10-15 mcg/kg/d PO initially; adjust to effect prn

Interactions

Cholestyramine may decrease levothyroxine absorption; estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid gland; levothyroxine increases effect of anticoagulants; conversion of hypothyroid patient to euthyroid state may decrease activity of some beta-blockers

Contraindications

Documented hypersensitivity; uncorrected adrenal insufficiency; untreated thyrotoxicosis

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Treatment of myxedema coma may require simultaneous administration of glucocorticoids; caution in patients with angina pectoris or cardiovascular disorders; monitor thyroid status periodically

Electrolytes

These agents replace depleted electrolytes.

Potassium chloride (K-DUR)

Essential for transmission of nerve impulses, maintenance of intracellular tonicity, and maintenance of normal renal function. Also vital for skeletal and smooth muscles. Replaces potassium lost in thyrotoxic periodic paralysis.

Dosing

Adult

100-200 mEq PO during an attack

Pediatric

Administer as in adults

Interactions

ACE inhibitors may elevate serum potassium concentrations; potassium-sparing diuretics and potassium-containing salt substitutes can produce severe hyperkalemia; hypokalemia may result in digoxin toxicity, use caution if discontinuing potassium preparation for patients who are maintained on digoxin

Contraindications

Hyperkalemia; renal failure and conditions in which potassium retention is present; oliguria or azotemia; crush syndrome; severe hemolytic reactions; anuria; adrenocortical insufficiency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

High plasma concentrations of potassium may cause death due to cardiac depression, arrhythmias, or arrest; plasma levels do not necessarily reflect tissue levels
Monitor potassium replacement therapy whenever possible by continuous or serial ECG

Corticosteroids

These agents provide immunosuppressive therapy for Graves ophthalmopathy, especially in cases of severe exophthalmos.

Prednisone (Deltasone, Sterapred, Orasone)

Widely used glucocorticoid that suppresses inflammatory processes by reversing increased capillary permeability and suppressing PMN activity; used to treat allergic, inflammatory, and autoimmune disorders.

Dosing

Adult

15-20 mg/d PO, although as much as 100 mg may be necessary; after obtaining satisfactory response, can be tapered slowly

Pediatric

Adjust dosage according to severity of symptoms (as in adult dosing)

Interactions

Drugs that induce hepatic enzymes may increase clearance; estrogens may decrease clearance; may increase digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids—in such cases, consider increasing maintenance glucocorticoid dose; diuretics may cause hypokalemia, monitor patients

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections; peptic ulcer disease; hepatic dysfunction; connective tissue infections

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Patients are at risk for multiple complications, such as severe infections; abruptly discontinuing glucocorticoids may cause adrenal crisis; complications of glucocorticoid use include hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, infections

Tricyclic antidepressants

These agents may help relieve painful polyneuropathy.

Amitriptyline (Elavil)

By inhibiting reuptake of serotonin and/or norepinephrine by presynaptic neuronal membrane, may increase synaptic concentration of these neurotransmitters in CNS; useful as analgesic for certain chronic and neuropathic pain.

Dosing

Adult

10-100 mg PO qhs

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Metabolized by P-450 2D6 system, so drugs that inhibit this enzyme system (eg, cimetidine, quinidine) may increase levels
Phenobarbital may decrease effects by increasing its metabolism; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Contraindications

Documented hypersensitivity; MAOIs within past 14 d; caution in patients who have seizures, cardiac arrhythmias, glaucoma, or history of urinary retention

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Schizophrenic patients may develop increased symptoms of psychosis; caution in patients with impaired liver function; lowers seizure threshold
Common adverse effects include antimuscarinic effects such as dry mouth, sedation, and blurred vision; others include orthostatic hypotension, increased appetite, and constipation; caution in patients who have seizures, cardiac arrhythmias, glaucoma, or history of urinary retention

Antiepileptic agents

These agents are useful in treating neuropathic pain.

Gabapentin (Neurontin)

Exact mechanism unknown. Structurally related to GABA; useful in some pain syndromes.

Dosing

Adult

300-1200 mg PO tid

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Antacids may reduce bioavailability significantly, so administer gabapentin at least 2 h following antacid; may increase norethindrone levels significantly

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not administer to patients with renal failure, since it is excreted by kidneys

Follow-up

Further Inpatient Care

• Neurologic manifestations in thyroid diseases are manageable on an outpatient basis. Therapy is maintained for months (if not years). In most cases, neurologic abnormalities slowly resolve.
• Thyroid storm and myxedema coma are exceptions. Both are emergencies that require aggressive treatment in the ICU. The mortality rate of thyroid storm can be as high as 20-40%. The symptoms usually are exaggerated manifestations of the symptoms seen in hyperthyroidism; a superimposed infection and the stress associated with it would exacerbate the symptoms. Fever, abdominal pain, delirium, and psychosis can occur. The patient may become obtunded. Thyroid storm should be suspected in any patient with severe hyperpyrexia, tachycardia, and a goiter.

Further Outpatient Care

Pregnant patients require follow-up at least monthly. Closely observe these newborns for thyroid disease.

Prognosis

Prognosis is generally good, since most symptoms are reversible with correction of the underlying problem.

Patient Education

For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

Miscellaneous

Medicolegal Pitfalls

Generally, no specific problem is anticipated unless the diagnosis is missed for months or years, which then results in permanent sequelae. However, such delays can occur because the early symptoms can be nonspecific.

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Keywords

thyroid neuropathy, thyroid myopathy, hyperthyroidism, hypothyroidism, Graves disease, myxedema, cretinism, thyrotoxicosis, Graves ophthalmopathy, thyroid eye disease, thyroid ophthalmopathy, thyroid orbitopathy, infiltrative ophthalmopathy, thyroid disease, T3, T4, thyroxine, thyroid hormones, regulation of thyroid hormones, myasthenia gravis, chronic thyrotoxic myopathy

Contributor Information and Disclosures

Author

Gabriel Bucurescu, MD, MS, Staff Neurologist, Neurology Service, Philadelphia Veterans Affairs Medical Center
Gabriel Bucurescu, MD, MS is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, and American Epilepsy Society
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
Thomas A Kent, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences, Royal Society of Medicine, Sigma Xi, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Agapito S Lorenzo, MD, Laboratory Director, Associate Professor, Departments of Neurology, Creighton University and University of Nebraska Medical Center
Agapito S Lorenzo, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

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