ENDOCRINOLOGY

MARCELO SPECTOR, MD

Medstudents' Homepage


Hypothyroidism Part 1





Definition

Hypothyroidism is a clinical syndrome that results from a deficiencyof thyroid hormone, which in turn results in a generalized slowing downof metabolic processes. A hydrophilicmucopolysaccharide(glycosaminoglycan) accumulates in subcutaneoustissue, particularly in the skin and muscle, causing a nonpitting edemareferred as myxedema.

Etiology

Hypothyroidism may be classified as (1) Primary (thyroid failure),(2) secondary (due to pituitary TSH deficit), tertiary (due tohypothalamic deficiency of TRH) or may be due to (4) peripheralresistance to the action of thyroid hormones.

Primary hypothyroidism, that caused by thyroid gland malfunction,accounts for 95 per cent of hypothyroidism cases, and only 5 per cent orless are suprathyroid in origin. The most common cause of primaryhypothyroidism is Hashimoto’s thyroiditis, which is associated withcirculating antithyroid antibodies and may coexist with diabetesmellitus and other diseases in which circulating antibodies are found,such as pernicious anemia, systemic lupus erythematosus, rheumatoidarthritis, Sjogren’s syndrome and chronic hepatitis. Another importantcause is surgical or radioiodine ablation of the gland in the treatmentof Graves’ disease. It may also occur as a primary idiopathicdisorder.

Hypothyroidism can also occur with normal or nearly normal thyroidtissue, that can be caused by severe iodine deficiency. Some drugs mayinhibit organification of thyroidal Iodo, but in most cases thehypothyroidism associated with these drugs is mild. The most importantdrugs causing hypothyroidism are: lithium carbonate,para-aminosalicyclic acid, amiodarone, sulfonamides and phenylbutazona.Chronic therapy with the antithyroid drugs propilthiouracil andmetimazole will have the same result of the drugs above mentioned.

It may occur during the late phase of subacute thyroiditis, this isusually transient, but it is permanent in about 10 per cent ofpatients.

Screening of newborns for hypothyroidism is now widely practiced, andthe incidence of this condition is about 1 in 4000 births. About 65 percent of infants with congenital hypothyroidism in North America havethyroid agenesis or hypoplasia, 25 per cent have ectopic thyroid glands,and about 10 per cent have defects in one of the steps required forthyroid hormone synthesis. Placental transfer of TSH-Ab (block) from amother with Hashimoto’s thyroiditis, may result in agenesis of thethyroid gland. Rare causes of neonatal hypothyroidism includeadministration during pregnancy of iodides, antithyroid drugs, orradioactive iodine for thyrotoxicosis.

Secondary and tertiary hypothyroidism occur as a result of pituitaryand hypothalamic dysfunction respectively and are quite rare and usuallyassociated with other symptoms and signs. Another rare cause is tissueresistance to thyroid hormones, which is usually due to an abnormalityin the nuclear receptor for these hormones.

Epidemiology

It is a common disorder in adults. In one epidemiologic survey, 1.4per cent of adult females and about 0.1 per cent of adult males wereaffected.

Pathogenesis

The pathology of the thyroid gland in hypothyroidism depends on theetiology of the syndrome. Thyroid deficiency affects every tissue in thebody so that symptoms are multiple. Pathologically, the mostcharacteristic finding is the accumulation of glycosaminoglycans ininterstitial tissues. Accumulation of this hydrophilic substance andincreased capillary permeability to albumin account for the interstitialedema that is particularly evident in the skin, heart muscle andstriated muscle. The accumulation is not due to increased synthesis butto decreased destruction of glycosaminoglycans.

Clinical Manifestations

1 - Newborn Infants (Cretinism)
Cretinism may be manifested at birth but usually becomes evidentwithin the first several months, depending on the extent of thyroidfailure. The symptoms of hypothyroidism in newborns include respiratorydifficulty, cyanosis, persistence of physiologic jaundice, poor feeding,hoarse cry, constipation, somnolence, umbilical hernia, and markedretardation of bone maturation. In later months, delay in reaching thenormal milestones of development becomes evident: short stature, coarsefeatures with protruding tongue, broad flat nose, widely set eyes,sparse hair, dry skin, impaired mental development, retarded bone ageand delayed dentition.

2 - Children
Characterized by retarded growth, with shortness of stature, andevidence of mental retardation. Poor performance at school may callattention to the diagnosis. Variable manifestation of adulthypothyroidism is present.

3 - Adults
Comon features of hypothyroidism include easy fatigability, coldness,weight gain, constipation, menstrual irregularities, and muscle cramps.Physical findings include a cool, rough, dry skin, puffy face and hands,hair becomes dry and tends to fall, a hoarse, husky voice, and slowreflexes. Reduced conversion of carotene to vitamin A and increasedblood levels of circulating carotene may give the skin a yellowishcolor.

A - Cardiovascular Signs
Impaired muscular contraction, bradycardia, and diminished cardiacoutput. Cardiac enlargement may occur, due in part to interstitialedema, nonspecific myofibrillary swelling, and left ventriculardilatation but often to pericardial effusion. Although cardiac output isreduced, congestive heart failure and pulmonary edema are rarely noted.If the heart is small, pituitary hypothyroidism or coincident primaryadrenal insufficiency (Schimidt’s syndrome) should be considered. Thereis controversy about whether myxedema induces coronary artery disease,but coronary artery disease is more common in patients withhypothyroidism. Particularly in older patients. In patients with anginapectoris, hypothyroidism may protect the heart from ischemic stress, andreplacement therapy may aggravate the angina.

B - Pulmonary Function
Shallow, slow respiration and impaired respiratory response tohypercapnia or hypoxia. Respiratory failure is a major problem inpatients with myxedema coma.

C - Gastrointestinal Tract
Peristalsis is markedly slowed, resulting in chronic constipation andoccasionally severe fecal impaction or ileus.

D - Hemathologic

Anemia is the major manifestation. There are at least four mechanismsthat may contribute to the anemia: impaired hemoglobin synthesis, irondeficiency from increased iron loss with menorrhagia, as well asimpaired intestinal absorption or iron, folate deficiency due toimpaired intestinal absorption of folic acid, and pernicious anemia,with vitamin B12 deficiency.

E - Renal Function
Decreased glomerular filtration rate and impaired ability to excretewater load.

F - Neuromuscular System
Severe muscle cramps, paresthesias, and muscle weakness.

G - Nervous System
Symptoms may include chronic fatigue, lethargy, and inability toconcentrate. In the elderly CNS symptoms may be erroneously attributedto aging or other disorders such as Parkinson’s disease, depression, orAlzheimer’s disease. Carpal tunnel syndrome may occur. If untreated,hypothyroidism may pass into a hypothermic, stuporous state (myxedemacoma) that may be fatal.

Hypothyroidism impairs the conversion of peripheral metabolism ofestrogens precursors to estrogen, resulting in altered FSH and LHsecreti