Neurological Manifestations of Thyroid Disease Follow-up

 Author: Gabriel Bucurescu, MD, MS; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE

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.

Thyroid deficiency can impair hippocampal neurogenesis, differentiation, and maturation in

developmental and adult rat brains, suggesting a similar mechanism in humans. Hypothyroidism
changes synaptic transmission and plasticity in area CA1 of the hippocampus, which, in turn,
may be the mechanism that leads to impairment in learning and memory.[1]

Epidemiology
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.

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.

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 - In children, subclinical hypothyroidism has been associated with exacerbation of
migraine headaches [2]
 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 - Prognosis is good if patients become euthyroid [3]
 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, [4] 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 [5, 6] : 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. [7] Other
case reports of miscarriages, focal seizures, and palatal tremor associated with Hashimoto
encephalopathy have also been made. Rare cases of primary demyelination and encephalopathy
have also been reported.

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.

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).[8] A case
report describes a triad of acute ataxia, Graves disease, and stiff person syndrome.[9]

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.

Graves disease has been associated with intracranial arterial stenosis/occlusion (moyamoya
syndrome). The exact mechanism is unknown; it is believed that thyroid hormones may augment
vascular sensitivity to the sympathetic nervous system and induce pathological changes in the
arterial walls.[10]

Subclinical hyperthyroidism has been linked to sudden unexpected death in epilepsy (SUDEP).
The mechanism is hypothesized to be facilitation of cardiovascular abnormalities. Subclinical
hyperthyroidism has been reported to increase heart rate, left ventricular mass, and cardiac
contractility, which, in turn, could lead to diastolic dysfunction and impaired ventricular ejection
fraction response to exercise and atrial arrhythmias.[11]

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 are as follows:

 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 are as follows:

 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)

Hypothyroidism can be primary, secondary, or due to tissue resistance to thyroid hormone.

Primary causes of hypothyroidism are as follows:

 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 of hypothyroidism are as follows:

 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 [12]
 Traumatic brain injury

Differential Diagnoses
 Emergent Management of Myasthenia Gravis
 Essential Tremor
 Inherited Metabolic Disorders Overview
  Lambert-Eaton Myasthenic Syndrome (LEMS)
 Marrow Failure Syndromes
 Median Neuropathy
 Metabolic Myopathies
 Myokymia
 Nutritional Neuropathy
 Periodic Paralyses
 Primary Malignant Skull Tumors
 Spinal Muscular Atrophy
 Thyroid Ophthalmopathy
 Ulnar Neuropathy
 Vitamin B-12 Associated Neurological Diseases

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.[13]
Thyroglobulin antibodies (TGAbs) are present in the serum of 60% of patients with Hashimoto
disease.

Interestingly, increased levels of thyroglobulin antibodies and/or antithyroid peroxidase

antibodies have been found in patients with aquaporin-4 (AQP4) antibody–positive CNS
autoimmunity and multiple sclerosis, both in pediatric and adult age groups. AQP4 antibody
plays an important role in the pathophysiology of neuromyelitis optica (NMO) spectrum
disorders, and such patients have a high frequency of autoimmune thyroid disease.[14]

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 [15, 16, 17, 18]

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
The following procedures may be needed:

 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. [19]

Histologic Findings
Hypothyroidism

Sural nerve biopsies reveal axonal degeneration.

Electron microscopy reveals the following:

 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 reveals the following:

 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 reveal the following:

 Excessive axonal branching

  Degenerative changes of preterminal axons
 Edematous protein infiltration of endoneurium and perineurium
 Segmental demyelination in teased fiber preparation

Electron microscopy reveals the following:

 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 reveals the following:

 Few pathologic changes in hyperthyroidism

 Mild atrophy, infiltration of fat cells, nonspecific focal myofibrillar degeneration,
mitochondrial hypertrophy, and focal dilatation of transverse tubular system

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.[20]

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.[21, 22, 23]

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

Consultations
The following consultations may be warranted:
  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 Summary
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
Class Summary

These medications are preferred for suppressing thyroid function.

View full drug information

Propylthiouracil (PTU)

Propylthiouracil is a derivative of thiourea that inhibits organification of iodine by the thyroid

gland. It also inhibits the conversion of T4 to T3, which is advantage over other agents.

View full drug information

Methimazole (Tapazole)
Methimazole suppresses thyroid function and has a mechanism similar to that of PTU; it does
not inhibit peripheral conversion of T4 to T3. Methimazole is fifteen times as potent as PTU.
PTU-equivalent dosing can be used, divided thrice daily.

Beta-adrenergic blocking agents

Class Summary

These agents are used to treat symptomatic hyperthyroidism.

View full drug information

Propranolol (Inderal)

This nonselective, beta-adrenergic blocking agent treats symptomatic tachycardia. Propranolol

has membrane-stabilizing activity and decreases the automaticity of contractions.

Thyroid hormones
Class Summary

These agents are used in thyroid hormone replacement.

View full drug information

Levothyroxine (Synthroid, Levoxyl)

Levothyroxine is synthetic, but it is identical to natural T4; in its active form, levothyroxine
influences the growth and maturation of tissues; it is involved in normal growth, metabolism, and
development.

Electrolytes
Class Summary

These agents replace depleted electrolytes.

View full drug information

Potassium chloride (K-DUR)

Potassium chloride is essential for the transmission of nerve impulses, maintenance of

intracellular tonicity, and maintenance of normal renal function. It is also vital for skeletal and
smooth muscles. Potassium chloride replaces potassium lost in thyrotoxic periodic paralysis.
Corticosteroids
Class Summary

These agents provide immunosuppressive therapy for Graves ophthalmopathy, especially in

cases of severe exophthalmos.

View full drug information

Prednisone (Deltasone, Sterapred, Orasone)

Prednisone is a widely used glucocorticoid that suppresses inflammatory processes by reversing

increased capillary permeability and suppressing PMN activity; it is used to treat allergic,
inflammatory, and autoimmune disorders.

Tricyclic antidepressants
Class Summary

These agents may help relieve painful polyneuropathy.

View full drug information

Amitriptyline (Elavil)

By inhibiting the reuptake of serotonin and/or norepinephrine by presynaptic neuronal

membrane, amitriptyline may increase the synaptic concentration of these neurotransmitters in
the CNS; it is useful as an analgesic for certain chronic and neuropathic pain.

Antiepileptic agents
Class Summary

These agents are useful in treating neuropathic pain.

View full drug information

Gabapentin (Neurontin)

Gabapentin's exact mechanism is unknown. It is structurally related to GABA and is useful in

some pain syndromes.

Further Outpatient Care

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

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.

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

Patient Education
For patient education resources, see the Endocrine System Center, as well as Thyroid Problems.

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