HYPOTHYROIDISM: SYMPTOMS AND CAUSES

HYPOTHYROIDISM

Symptoms: 
Dry skin, slow speech, constipation, decrease GI motility, weight gain despite of reduced appetite, dry hair and fallout, facial puffiness, angina, hyperlipidemia, etc.

Signs: 
Pale, dry skin, goiter, cool peripheries, alopecia, bradycardia, ascites, hydrocele, cretinism in children, etc.

This is the most common disease occurring in 5-15% women after 65 years of age. Myxedema is a severe form of hypothyroidism in which there is accumulation of mucopolysaccharides in the skin and other tissues, leading to a thickening of facial features and a doughy induration of the skin. Cretinism is the term used to describe severe hypothyroidism that develops in the newborn.

Fig. Hypothyroidism examination

CAUSES
Primary hypothyroidism: 
This occurs due to extrinsic factors that affect thyroid gland or due to disease of the thyroid gland. As a compensatory mechanism there is release of TRH and TSH which cause thyroid hyperplasia causing enlargement (goiter). Non goiterous hypothyroidism occurs due to functional loss of thyroid gland despite of increased production of TSH and TRH. Primary hypothyroidism is frequently associated with circulating Antithyroid antibodies (autoantibodies).

1. Hashimoto thyroiditis – This is characterized by autoimmune destruction of thyroid gland. Autoantibodies are directed against TPO, Tg and other tissues. Initially there is hyperthyroidism due to Overactivity of thyrocytes where stored thyroid hormones are released about for 6-8 weeks, gland becomes enlarged, palpable and tender i.e. goiterous.  But further gland damage leads to permanent hypothyroidism and goiter regresses.
2. Riedel’s syndrome – Gland become fibrosed
3. Iodine deficiency – Lowered gland iodine; impaired hormone synthesis. This is the most common cause of goiterous hypothyroidism.
4. Acute iodine excess – Transient inhibition of hormone synthesis may become permanent in the presence of coexisting thyroid destructive autoimmune activity

Fig. Growth retardation : effect of Hypothyroidism (All the men showing are of same age) 

 Congenital hypothyroidism

• Caused by structural abnormalities like absent gland, ectopic site, enzymes defects like iodide transport, Organification, peroxidase, deiodinase, mutation in T3, transporter, maternal antibodies. Screening of this condition is done in almost all countries of the world. Here T4 and TSH are measured.
• Drug induced defect – Lithium, glucocorticoid, propranolol, iodine 

Secondary hypothyroidism: 
Due to extrathyroidal disease. Here TSH is low or normal and T3 and T4 are low due to inadequate tropic hormones.
• Anterior pituitary failure – Loss of TSH stimulation of thyroid
• Hypothalamic dysfunction – Loss of TRH stimulation of anterior pituitary

In hypothyroidism serum TSH is elevated (due to lack of feedback regulation) whereas thyroid hormone level is suppressed in case of primary hypothyroidism. In secondary hypothyroidism due to defect in pituitary or hypothalamus, TSH is undersecreted which causes reduced synthesis of thyroid hormones.
In many patients of primary hyperthyroidism no goiter or history of goiter is found.

Subclinical hypothyroidism
In this condition TSH level is raised (but <10 mU/L) but thyroid hormone level are normal.

ATA Guidelines for hypothyroid screening

Measurement of TSH
• At age 35
• Every 5 years after 35 yrs.
• More frequently with risk factor or symptoms: goiter, family history, lithium use, amiodarone use.

After giving thyroxine as medication to treat hypothyroidism it is important to wait at least five half-lives (7x5 = 35 days, since levothyroxine has half life of 7 days) before rechecking thyroid function tests in order to achieve a new steady state.