Overview: 

 

Thyroxine (T4) and triiodothyronine (T3) are thyroid hormones secreted by thyroid gland. Disturbance of these hormones causes wide range of health problems in the body. 

 

Thyroid gland is one of the largest of the endocrine glands ,weighing 15 to 20 grams in adults. The gland is located immediately below the larynx on each side of and anterior to the trachea . The gland resembles a butterfly in shape, consisting two lobes one on either side of trachea. 

 

The thyroid gland synthesize hormones that help control many vital functions of the body. It produces two major hormones, thyroxine (T4) and triiodothyronine(T3). Thyroid gland also secretes calcitonin which is important for calcium metabolism. 

 

T3 is about four times as potent as thyroxine,but it is present in the blood in much smaller quantities and persists for a much shorter time compared with thyroxine. 

 

Nearly about 93 % of metabolically active hormones secreted by the thyroid gland is thyroxine and  7 % triiodothyronine forms. 

Both of these two hormones, T4 and T3 increase the metabolic rate of the body. The secretion of thyroid hormones is mostly controlled by the thyroid stimulating hormone (TSH) from pituitary gland. Normally level T4 and T3 remain at certain range keeping basal metabolic rate at normal level. As secretion of thyroid hormone increases or decreases , there occurs bad impacts on entire body. 

 

Thyroxine (T4) and triiodothyronine (T3) are essential for normal growth and development of the body especially of the nervous system and skeletal. T4 and T3 hormones play vital roles byv regulating metabolism of carbohydrates,proteins and fats. So ,T4 and T3 affect most of cells of the body by increasing metabolic rate and heat production. Along with it T4 and T3  have physiological influence on the heart, skeletal muscles, skin, digestive and reproductive system. 

If secretion of thyroid hormone exceed normal level, it is called hyperthyroidism. If secretion decreases and thyroid hormone levels in blood comes below normal level, it is called hypothyroidism. 

 

Regulations of secretion of thyroxine (T4) and triiodothyronine (T3) : 

Regulation of secretion of T4 and T3 is a vital phenomenon to keep balanced stage of basal metabolism and to maintain health. 

Regulation of secretion of T4 and T3 take place as following:

- Thyroid releasing hormone (TRH) produced from hypothalamus stimulates to produce thyroid stimulating hormone (TSH).

- Thyroid stimulating hormone (TSH) produced from pituitary gland stimulates to produce thyroxine (T4) and triiodothyronine (T3).

- As blood level of T4 and T3 raised above the  normal level, it passes an signal to hypothalamus to inhibit(stop) production of thyroid releasing hormone (TRH) and to pituitary gland to inhibit secretion of thyroid stimulating hormone (TSH ).

- During metabolism use of hormones by most of the body cells make lower the level of T4 and T3 in the blood. 

-  As level of T4 and T3 in the blood comes below the normal level, this condition passes signal to hypothalamus to stimulate secretion of thyroid releasing hormone (TRH) which again stimulate the pituitary gland to secret thyroid stimulating hormone (TSH). TSH stimulates to thyroid gland to secrete T4 and T3 . In this way regulation of T4 and T3 takes place as well designed mechanism. 

- Exercise, stress, malnutrition, low level glucose,sleep may stimulates hypothalamus to secrete TRH which stimulates pituitary gland to produce TSH. As mentioned above TSH stimulates thyroid gland to produce T4 and T3. 

 

In case any faults occur in this regulation of secretion mechanism, secretion of T4 and T3 whether more than normal or very lower than normal.  If secretion occurs more than need it is called hyperthyroidism and  if no secretion occurs or less secretion occurs than need it is called hypothyroidism. Commonly people say thyroid occur. 

 

Hypothyroidism:

Thyroid problems are most occurring problems among endocrine problems. Iodine deficiency and neonatal hypothyroidism remain major challenges for public health in developing countries.  And another frequent cause of thyroid dysfunction is autoimmunity, where the follicular gland structure is destroyed by autoreactive T cells.

 

 

Primary hypothyroidism is confirmed by performing biochemical diagnosis . In primary hypothyroidism a high serum TSH and a low free T4  are found . In autoimmune hypothyroidism thyroid peroxidase autoantibodies is found along with high serum TSH and a low free T4 

 

The prevalence of hypothyroidism in white populations is around 2 percent in women and 0.2 percent in man . The rate is lower in Asia and black populations. 

 

Common effects of  decreased secretion of T4 and T3 hormones ( Hyperthyroidism):

- Decreased basal metabolic rate. Comlete lack of thyroid secretion usually causes the basal metabolic rate to fall 40 to 50 % below normal. 

- Depression, psychosis, mental slowness, lethargy 

- Dry skin, brittle hair 

- Bradycardia 

- Dry cold skin, prone to hypothermia 

- Costipation 

- Weight gain, anorexia 

 

Causes of Hypothyroidism : 

 

Primary causes:

-Iodine deficiency 

-Autoimmune hypothyroidism

-Hashimoto's thyroiditis

-Primary myxoedema

-latrogenic treatment

-Subtotal or total thyroidectomy

- External irradiation for  treatment of lymphoma or cancer involving the neck

- Drugs like 

[  ] lodine-containing contrast media

[  ] Amiodarone

[  ] Lithium

[  ] Antithyroid drugs

[  ] p-Aminosalicylic acid

[  ] Interferon-a and other cytokines

[  ] Aminoglutethimide

[  ] Tyrosine kinase inhibitors 

-Congenital hypothyroidism

- Absent or ectopic thyroid gland

- Dyshormonogenesis

- TSH receptor mutation

- Destructive thyroiditis

- Postpartum thyroiditis

- Silent thyroiditis

- Subacute thyroiditis

- Infiltrative disorders

- Amyloidosis

- Sarcoidosis

- Haemochromatosis

- Scleroderma

- Cystinosis

- Riedel's thyroiditis

-Consumptive hypothyroidism due to increased type 3 deiodinase expression 

 

Secondary causes 

- Hypopituitarism

- Pituitary tumours

- Trauma (head injury)

- Pituitary surgery or irradiation

- Infiltrative disorders

- Infarction

- Isolated TSH deficiency or inactivity

- Hypothalamic disease 

 

Hyperthyroidism and Thyrotoxicosis 

 

Hypothyroidism occurs when thyroid  gland release excessive amount T4 and T3 that is more than normal level. Hyperthyroidism occurs in Graves' disease, inflammation of the thyroid or in benign tumor of thyroid. 

Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone. Hyperthyroidism exists when thyrotoxicosis is caused by thyroid overactivity.  It should be noted that there are many types of thyrotoxicosis that are not caused by hyperthyroidism. It is obvious that thyrotoxicosis may occur due to administration of excessive T4. 

 

Causes of Thyrotoxicosis 

 

Primary hyperthyroidism

- Graves' disease

-Toxic multinodular goitre

-Toxic adenoma

-Drugs: iodine excess , lithium, amiodarone

(type 1 amiodarone-induced thyrotoxicosis)

-Thyroid carcinoma or functioning metastases

-Activating mutation of the TSH receptor

-Activating mutation of the Gsa protein 

-Struma ovarii (ectopic thyroid tissue) 

 

Thyrotoxicosis without hyperthyroidism 

 

-Ingestion of excess thyroid hormone (factitious -thyrotoxicosis)

-Subacute thyroiditis

-Silent thyroiditis

-Other causes of thyroid destruction: amiodarone (type 2 amiodarone

induced thyrotoxicosis),  or external irradiation (acute effect), in-

farction of an adenoma 

 

Secondary hyperthyroidism

- TSH-secreting pituitary tumour

- Chorionic gonadotropin-secreting tumours

- Gestational thyrotoxicosis

- Thyroid hormone resistance 

 

 

 

Common effects of  decreased secretion of T4 and T3 hormones(Hyperthyroidism 

 

- Increased basal metabolic rate . Extreme excesses of thyroid secretion may increase the basal metabolic rate to 60 to 100% above normal. 

- Anxiety, physical restlessness, mental excitability 

- Hair loss

- Tachycardia, palpitation, atrial fibrillation 

- Warm sweaty skins, heat intolerance 

- Diarrhea 

- Weight loss, good appetite 

- Exophthalmos in Graves' disease . Most people with hyperthyroidism exhibit some degree of protrusion of the eyeballs,

- muscle weakness

- tremor of the hands.

- nervousness