HYPOTHYROIDISM -Binod timalsina

Hypothyroidism

■ Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormones.

■ There is a generalized slowing down of metabolic processes.

■ In newborn infants – Cretinism■ In adolescents – short stature, mental

retardation, precocious puberty■ In adults – symptoms largely reversible after

therapy

Interpretation for Thyroid Function Test

High T4 Normal T4 Low T4

High TSH

In vivo or in vitro artefact Pituitary hyperthyroidism

Thyroid hormone resistance Subclinical hypothyroidism Primary hypothyroidism

Normal TSH

As aboveSampling within 6 h of

thyroxine dose Normal

Pituitary or hypothalamic hypothyroidism

Severe non-thyroidal illness

Low TSH Hyperthyroidism

Subclinical hyperthyroidism Subtle thyroxine overreplacement

Autonomous functioning thyroid nodule

Non-thyroidal illness

Pituitary or hypothalamic hypothyroidism

Severe non-thyroidal illness

Etiology of Hypothyroidism

■ Primary – thyroid failure

■ Secondary – pituitary TSH deficit (Hypopituitarism due to pituitary adenoma, apoplexy, infiltrative disease-sarcoidosis)

■ Tertiary – hypothalamic deficiency of TRH (rare)

■ Peripheral resistance to the action of thyroid hormone

Hashimoto’s Thyroiditis

■ Chronic lymphocytic thyroiditis■ Probably the most common cause of

hypothyroidism■ With (younger patients) or without goiter (older

patients – atrophy gland after destruction by immunologic process)

■ High titer of autoantibodies to thyroidal antigens (Thyroglobulin Ab, Thyroperoxidase Ab = TPO Ab = Antimicrosomal Ab = AMA)

Pathogenesis of Hypothyroidism■ Characteristic finding: accumulation of

glycosaminoglycans – mostly hyaluronic acid – in interstitial tissues

■ The accumalation is due not to excessive synthesis but to decreased destruction of glycosaminoglycans.

■ Accumulation of this hydrophilic substance and increased capillary permeability to albumin account for this interstitial edema that is particularly evident in the skin, heart muscle, and striated muscle.

Clinical Manifestations of Hypothyroidism

■ Symptoms and signs vary in relation to the magnitude of the thyroid hormone deficiency, and the acuteness with which the deficiency develops. ❖ Less prominent clinically and better tolerated

when gradual loss of thyroid function (as in most cases of primary hypothyroidism)

❖ Symptoms develop acutely after thyroidectomy or abrupt withdrawal of exogenous thyroid hormone

Clinical Manifestations of Hypothyroidism -- Skin

■ Cool and pale skin blood flow ■ Dry roughness of skin the epidermis has an

atrophied cellular layer and hyperkeratosis ■ Decreased sweating calorigenesis and acinar

gland secretion ■ Generalized nonpitting edema (myxedema) in

severe hypothyroidism infiltration of the skin with glycosaminoglycans and associated water retention

Clinical Manifestations of Hypothyroidism -- Eyes

■ Periorbital edema -- as a manifestation of generalized nonpitting edema or Graves' ophthalmopathy.

■ Graves' ophthalmopathy may persist or worsen when hypothyroidism develops after treatment of Graves' hyperthyroidism. Patients will have variable degrees of stare, protrusion of the eyes, and extraocular muscle weakness.

Clinical Manifestations of Hypothyroidism -- Cardiovascular System

■ Bradycardia reductions in heart rate■ Impaired muscular contractility■ Reduced cardiac output ➔ decreased exercise

capacity and shortness of breath during exercise ■ ECG: low voltage of QRS complexes and P and T

waves■ CXR: cardiomegaly interstitial edema,

myofibrillary swelling, LV dilatation, pericardial effusion

Clinical Manifestations of Hypothyroidism -- Cardiovascular System

■ Myxedema induces coronary artery disease ??■ CAD more common in p’ts with hypothyroidism■ Symptoms and signs of congestive heart failure

are usually absent in patients who have no other cardiac disease

■ Congestive heart failure or angina may worsen when hypothyroidism develops in patients with heart disease

Clinical Manifestations of Hypothyroidism -- Cardiovascular System

■ Hypertension peripheral vascular resistance ❖ In normotensive patients, BP increases are

small (<150/100 mmHg). ❖ The BP of patients with established

hypertension may increase further with the development of hypothyroidism.

Clinical Manifestations of Hypothyroidism -- Respiratory System

■ Fatigue, shortness of breath on exertion, and decreased exercise capacity impaired respiratory function + cardiovascular disease

■ Hypoventilation (shallow and slow respirations) respiratory muscle weakness + reduced pulmonary responses to hypoxia and hypercapnia

■ Obstructive sleep apnea macroglossia

Clinical Manifestations of Hypothyroidism -- Gastrointestinal Disorders

■ Constipation, even ileus gut motility ■ Decreased taste sensation■ Gastric atrophy presence of antiparietal cell

antibodies. Pernicious anemia occurs in 10% of patients with hypothyroidism caused by chronic autoimmune thyroiditis.

■ Weight gain decreased metabolic rate + accumulation of fluid (nonpitting edema) that is rich in glycosaminoglycans

■ Ascites, rare

Clinical Manifestations of Hypothyroidism -- Renal Function

■ Decreased glomerular filtration rate (GFR ) ■ Impaired ability to excrete a water load■ The drug clearance (ex, antiepileptic,

anticoagulant, hypnotic and opioid drugs), is decreased. ➔ Drug toxicity may occur if drug dosage is not reduced.

■ During T4 replacement, drugs that are administered at effective doses in patients who are hypothyroid may become less effective.

Clinical Manifestations of Hypothyroidism -- Anemia

■ Impaired hemoglobin synthesis thyroxine deficiency

■ Iron deficiency increased iron loss with menorrhagia + impaired intestinal absorption of iron

■ Folate deficiency impaired intestinal absorption of folic acid

■ Pernicious anemia vitamin B12 -deficient megaloblastic anemia

Clinical Manifestations of Hypothyroidism -- Reproductive Abnormalities

■ Women with hypothyroidism may have either oligo- or amenorrhea or hypermenorrhea-menorrhagia.

■ Decreased fertility ■ Increased likelihood for early abortion ■ Hyperprolactinemia may occur, and is occasionally

sufficiently severe to cause amenorrhea or galactorrhea

■ The serum sex hormone-binding globulin concentration may be low in hypothyroidism. This will lower serum total but not free sex hormone concentrations.

Clinical Manifestations of Hypothyroidism -- Neurological Dysfunction

■ General depression of central nervous system function

■ Sleepiness, inability to concentrate■ Sluggish thought processes

❖ Respond slowly to questions❖ Less able to retrieve information from memory

■ Agitated psychosis, rare (“myxedema madness”)■ PET: 23% reduction in cerebral blood flow and a

12% reduction in cerebral glucose metabolism

Clinical Manifestations of Hypothyroidism -- Neuromuscular Abnormalities

■ A delay in the relaxation phase of deep tendon reflexes

■ Carpal tunnel syndrome■ Paresthesia ■ Asymptomatic elevation in serum CPK level to

muscle hypertrophy (which may be accompanied by muscle cramps) to proximal muscle weakness to, in rare cases, rhabdomyolysis.

Clinical Manifestations of Hypothyroidism -- Metabolic Abnormalities

■ Hyponatremia may result from a reduction in free water clearance

■ Reversible increases in serum creatinine occur in 20 ~ 90% of hypothyroid patients

■ lipid clearance may be decreased, resulting in an elevation in the serum concentrations of free fatty acids and total and low-density lipoprotein cholesterol

■ Plasma homocysteine concentrations are increased in some hypothyroid patients,

Common Signs and Symptoms of Hypothyroidism

Sign or symptomWeakness

Skin changes (dry or coarse skin)Lethargy

Slow speechEyelid edema

Cold sensationDecreased sweating

Cold skinThick tongueFacial edemaCoarse hairSkin pallor

ForgetfulnessConstipation

Affected patients (%)9997919190898983827976676661

Serum FT4, TSH

Normal FT4, TSHTSH , FT4 FT4 , TSH normal or

Primary hypothyroidism

Euthyroid

Secondary hypothyroidism

TRH test

Excessive response

Normal type response No response

Pituitary lesion

Hypothalamic lesion

Primary hypothyroidism

Treatment of Hypothyroidism

■ Replacement of Triiodothyroxine (T3): unsatisfactory due to rapid absorption, short half-life, and transient effect

■ Levothyroxine (T4):❖ Converted to T3 intracellularly❖ Once daily, half-life: 7 days❖ Well-absorbed❖ Easily monitored by following serum TSH and

T4 levels

Treatment of Hypothyroidism

■ Replacement does of levothyroxine in adults range from 0.05 to 0.2 mg/d. It varies according to the patient’s age and body weight.

■ In young children: 4-5 ug/kg/d■ In adults: average 1.7 ug/kg/d■ In elders, start with lower dose, ex. 0.025mg daily,

increase the dose at 4- to 6-week intervals based on serum FT4 and TSH levels

■ Dose should be increased about 25% during pregnancy

Drugs Potentially Altering Thyroid Hormone Replacement Requirements

Increase replacement requirements Drugs that reduce thyroid hormone production

Lithium Iodine-containing medications

Amiodarone (Cordarone) Drugs that reduce thyroid hormone absorption

Sucralfate (Carafate) Ferrous sulfate (Slow Fe)

Cholestyramine (Questran) Colestipol (Colestid)

Aluminum-containing antacids Calcium products

Drugs that increase metabolism of thyroxine Rifampin (Rifadin)

Phenobarbital Carbamazepine (Tegretol)

Warfarin (Coumadin) Oral hypoglycemic agents

Increase thyroxine availability and may decrease replacement requirements Drugs that displace thyroid hormone from protein binding

Furosemide (Lasix) Mefenamic acid (Ponstel)

Salicylates