AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 recent 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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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
    • Neuropsychiatric signs - Dementia, apathy, mental dullness, irritability, sleepiness
• 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).
  • 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.
  • 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

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

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

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab 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.
• 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).
• 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 - Can confirm diagnosis or differentiate diagnoses. Both hyperthyroid and hypothyroid patients may have disturbed levels of carnitine but by separate mechanisms (Sinclair, 2005).

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

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Neurologic manifestations 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.

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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

Drug Category: Thiourea derivatives

These medications are preferred for suppressing thyroid function.

Drug Name	Methimazole (Tapazole)
Description	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.
Adult Dose	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 Dose	Initial dose: 0.4 mg/kg PO divided tid Maintenance dose: Half initial dose
Contraindications	Documented hypersensitivity; breastfeeding mothers
Interactions	Has anti-vitamin K activity and may potentiate activity of oral anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	May cause agranulocytosis; closely monitor patients for adverse effects; may cause hypoprothrombinemia and bleeding

Drug Category: Beta-adrenergic blocking agents

These agents are used to treat symptomatic hyperthyroidism.

Drug Category: Thyroid hormones

These agents are used in thyroid hormone replacement.

Drug Category: Electrolytes

These agents replace depleted electrolytes.

Drug Category: Corticosteroids

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

Drug Category: Tricyclic antidepressants

These agents may help relieve painful polyneuropathy.

Drug Category: Antiepileptic agents

These agents are useful in treating neuropathic pain.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Neurologic manifestations 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

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal 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.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Adams RD, Victor M, Ropper AH. The endocrine myopathies. In: Principles of Neurology. 6th ed. New York: McGraw-Hill;. 1997:1440-2.
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• Boyages SC, Halpern J-P. Endemic cretinism: toward a unifying hypothesis. Thyroid. 1993;3(1):59-69. [Medline].
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• Jagannathan NR, Tandon N, Raghunathan P, Kochupillai N. Reversal of abnormalities of myelination by thyroxine therapy in congenital hypothyroidism: localized in vivo proton magnetic resonance spectroscopy (MRS) study. Brain Res Dev Brain Res. Aug 8 1998;109(2):179-86. [Medline].
• Lai CL, Liu CK, Tai CT, et al. A study of central and peripheral nerve conduction in patients with primary hypothyroidism: the effects of thyroxine replacement. Kaohsiung J Med Sci. May 1998;14(5):294-302. [Medline].
• Larsen PR. The Thyroid. In: Wyngaarden JB, Smith LH Jr, Bennett JC, et al, eds. Cecil Textbook of Medicine. 19th ed. Philadelphia: Saunders;. 1992:1248-71.
• Losa M, Mortini P, Minelli R, Giovanelli M. Coexistence of TSH-secreting pituitary adenoma and autoimmune hypothyroidism. J Endocrinol Invest. 2006;29:555-559. [Medline].
• Madeira MD, Cadete-Leite A, Andrade JP, et al. Effects of hypothyroidism upon the granular layer of the dentate gyrus in male and female adult rats: a morphometric study. J Comp Neurol. Dec 1 1991;314(1):171-86. [Medline].
• Marta CB, Adamo AM, Soto EF, Pasquini JM. Sustained neonatal hyperthyroidism in the rat affects myelination in the central nervous system. J Neurosci Res. Jul 15 1998;53(2):251-9. [Medline].
• Muthipeedika JM, Moosa A, Kumar A, Suchowersky O. Bilateral chorea--ballism associated with hyperthyroidism. Mov Disord. Apr 2005;20(4):512; author reply 512. [Medline].
• Ozata M, Ozkardes A, Dolu H, et al. Evaluation of central motor conduction in hypothyroid and hyperthyroid patients. J Endocrinol Invest. 1996;19:670-677. [Medline].
• Ozata M, Ozkardes A, Corakci A, Gundogan MA. Subclinical hypothyroidism does not lead to alterations either in peripheral nerves or in brainstem auditory evoked potentials (BAEPs). Thyroid. 1995;5(3):201-205. [Medline].
• Ozkan Y, Colak R. Sheehan syndrome: clinical and laboratory evaluation of 20 cases. Neuro Endocrinol Lett. Jun 2005;26(3):257-60. [Medline].
• Ozkardes A, Ozata M, Beyhan Z, et al. Acute hypothyroidism leads to reversible alterations in central nervous system as revealed by somatosensory evoked potentials. Electroencephalography and clinical neurophysiology. 1996;100:500-504. [Medline].
• Parker RJ, Davidson AC. Hypothyroidism--an unexpected diagnosis following emergency treatment for heatstroke. Int J Clin Pract Suppl. Apr 2005;31-3. [Medline].
• Perelman AH, Clemons RD. The fetus in maternal hyperthyroidism. Thyroid. 1992;2(3):225-228. [Medline].
• Quattrini A, Nemni R, Marchettini P, et al. Effect of hypothyroidism on rat peripheral nervous system. Neuroreport. 1993;4:499-502. [Medline].
• Sinclair C, Gilchrist JM, Hennessey JV, Kandula M. Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve. Sep 2005;32(3):357-9. [Medline].
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Article Last Updated: Nov 14, 2006