Hypothyroidism MEDSTUDENTS-ENDOCRINOLOGY

ENDOCRINOLOGY
MARCELO SPECTOR

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Hypothyroidism Part 1

Definition

Hypothyroidism is a clinical syndrome that results from a deficiency of thyroid hormone, which in turn
results in a generalized slowing down of metabolic processes. A hydrophilic mucopolysaccharide
(glycosaminoglycan) accumulates in subcutaneous tissue, particularly in the skin and muscle, causing a
nonpitting edema referred as myxedema.

Etiology

Hypothyroidism may be classified as (1) Primary (thyroid failure), (2) secondary (due to pituitary TSH
deficit), tertiary (due to hypothalamic deficiency of TRH) or may be due to (4) peripheral resistance 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 or less are suprathyroid in origin. The most common cause of
primary hypothyroidism is Hashimoto’s thyroiditis, which is associated with circulating antithyroid
antibodies and may coexist with diabetes mellitus and other diseases in which circulating antibodies are
found, such as pernicious anemia, systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s
syndrome and chronic hepatitis. Another important cause is surgical or radioiodine ablation of the gland
in the treatment of Graves’ disease. It may also occur as a primary idiopathic disorder.

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

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the drugs above mentioned.

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

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

Secondary and tertiary hypothyroidism occur as a result of pituitary and hypothalamic dysfunction
respectively and are quite rare and usually associated with other symptoms and signs. Another rare cause
is tissue resistance to thyroid hormones, which is usually due to an abnormality in the nuclear receptor
for these hormones.

Epidemiology

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

Pathogenesis

The pathology of the thyroid gland in hypothyroidism depends on the etiology of the syndrome. Thyroid
deficiency affects every tissue in the body so that symptoms are multiple. Pathologically, the most
characteristic finding is the accumulation of glycosaminoglycans in interstitial tissues. Accumulation of
this hydrophilic substance and increased capillary permeability to albumin account for the interstitial
edema that is particularly evident in the skin, heart muscle and striated muscle. The accumulation is not
due to increased synthesis but to decreased destruction of glycosaminoglycans.

Clinical Manifestations

1 - Newborn Infants (Cretinism)

Cretinism may be manifested at birth but usually becomes evident within the first several months,
depending on the extent of thyroid failure. The symptoms of hypothyroidism in newborns include
respiratory difficulty, cyanosis, persistence of physiologic jaundice, poor feeding, hoarse cry,
constipation, somnolence, umbilical hernia, and marked retardation of bone maturation. In later months,
delay in reaching the normal milestones of development becomes evident: short stature, coarse features
with protruding tongue, broad flat nose, widely set eyes, sparse hair, dry skin, impaired mental

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development, retarded bone age and delayed dentition.

2 - Children
Characterized by retarded growth, with shortness of stature, and evidence of mental retardation. Poor
performance at school may call attention to the diagnosis. Variable manifestation of adult
hypothyroidism 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 slow reflexes. Reduced
conversion of carotene to vitamin A and increased blood levels of circulating carotene may give the skin
a yellowish color.

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

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

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

D - Hemathologic

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

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

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

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

Hypothyroidism impairs the conversion of peripheral metabolism of estrogens precursors to estrogen,

resulting in altered FSH and LH secreti

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