Endocrine System: thyroid and Adrenal Control

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Major function of the Thyroid Hormone

Growth and Development: T3 is required for secretion of growth hormone from the anterior pituitary. If there is no T3 then a childs growth is decreased. T3 is important for the normal development of the nervous system in fetues and infants. If there is no T3 in fetal life then it results in Congenital hypothyroidism, often caused by dietary iodine deficiency in the mother. T3 is also required for normal alertness and reflexes of all ages.

Metabolic Actions: Major determinant of the rate at which the body produces heat during the basal metabolic state. T3 stimulates carbohydrate absorbtion from the small intestine and increase fatty acid release from adipocytes to provide the energy to help maintain high metabolic rates

Permissive actions: Facilitates the activity of sympathetic nervous system by T3 upregulating beta-adrenergic receptors of many tissues for epinephrine and norepinephrine

Hypothyroidism

When T3 plasma concentration are chronically below normal. Primary defect of the thyroid gland are caused by damage to/loss of functional thyroid tissue or from iodine deficiency.

In iodine deficiency less T3 is produced decreasing plasma concentration of the hormone this decreases negative feedback on the hypothalamus and anterior pituitary so that TRH concentrations become chronically increased in the portal circulation that leads to the anterior pitutiary therefore plasms concentration of TSH is increased. This over stimulation can cause goiters, but if iodine is added to the diet this can be reversed.

Disruption to normal function of the thyroid gland is when cells of the immune system attach and destroy thyroid tissue. Thyroid hormone begins to decrease but TSH concentrations increase because of decreased negative feedback. Overstimulation of the thyroid gland results in hypertrophy. The usual treatment is a pill that contains T4.

The symptoms can be mild or severe depending on the scale of the deficiency include: feeling cold, weight gain, lethargy and Cardiac effects.

Endocrine Response to stress

Stresses such as trauma, pain, infection, sleep deprivation, fright and other emotional stresses cause an increase in the release of cortisol from the adrenal cortex and epinephrine from the adrenal medulla. This is caused by stress inducing CRH secretion from the hypothalamus which stimulates ACTH release from the anterior pituitary, this circulates through the blood reaching the adrenal cortex. Vasopressin also stimulates ACTH to an extend

Cortisol Physiological functions

Although it has an important role for responding to stress it also has other functions:

Permits the action of epinephrine and noreprinephrine on muscles and blood vessels therefore helps to maintain normal blood pressure

Maintains cellular concentrations of metabolic enzymes required to produce glucose between meals.

Anti-inflammatory and anti-immune function by inhibiting the production of prostaglandins, reducing capillary permeability in injured areas and supressing the growth of lymphocytes

Important during fetal and neonatal life for development and helps the lungs to inflate

Funtion of Cortisol in Stress

Effect on organic metabolism:

Stimulation of protein catabolism in bone, lymph, muscle and elsewhere

Stimulate liver uptake of amino acids and their conversion to glucose

Maintenance of plasma glucose concentration

Stimulation of triglyceride catabolism in adipose tissue with release of glycerol and fatty acids into the blood

Increases the ability of smooth musle to contact in response to noreinephrine

Unidentified protective effects against the damaging influences of stress

Inhibition of inflammation and specific immune responses

Inhibition of nonessential function

Chronic stress can result in sustained increases in plasma cortisol this can decrease the activity of the immune system reducing resistance to infection and possibly cancer, worsen diabetes symptoms and decrease fertility

Adrenal Insufficiency

When plasma levels of cortisol are chronically lower than normal. Patients with this suffer from a range of symptoms depending on severity and cause incuding weakness, lethargy and loss of appetite.

Primary adrenal insufficiency/Addison's disease

This is due to a loss of adrenal cortical function. This is rarely caused by a tumor but most commonly is caused by autoimmune attach causing the destruction of many cells in the adrenal glands. This effects all zones of the adrenal cortex so level of aldosterone are also decreases this creates an imbalance of Na+, K+ and water in the blood as alsosterone is a key regulator of these. The loss of salt and water can lead to hypotension. It is diagnosed by measuring plasma concentrations of cortisol. ACTH concentration are increased due to lack of negative feedback. The treatment requires oral administration of glucocorticords and mineralocorticords.

Secondary adrenal insufficiency

Is caused by deficiency of ACTH which can arise from a pituitary disease. It's symptoms are not usually as server as aldosterone secretion is not affected.

Cushing's Syndrome

There is excess cortisol in the blood which can be caused by a primary or secondary defect. Primary defects could be cortisol secreting tumor where as secondary defects could be due to an ACTH secreting tumor in the pituitary gland. Cushing's disease promotes uncontrolled catabolism of bone, muscle, skin and other organs especailly at night when normal coritsol concentration would be low. Problems caused by this syndrome are: Osteoporosis; muscle weakness; blood sugar increase; Immunosuppression; Redistribution of fat; hypertension. Hypertension is caused by the pharmological effects of cortisol not increased aldosterone production which has a similar effect. The treatment depends on the cause: Surgical removal of the pituitary tumor or Adrenalectomy

Synthesis of Thyroid Hormone

The thyroid produces thyroxine (T4) and triiodothyronine (T3) which both contain iodine. T4 is usually converted into T3 by deiodinases so T3 is therefore considered the major hormone even though levels of T4 are usually higher in the blood. Within the thyroid gland there are lots of follicles which are made of an enclosed sphere of epithelial cells surrounding a core containing colloid.

Synthesis begins when iodide is actively co-transported with sodium ions across the basolateral membrane. The Na+ is then pumped back out by Na+/K+-ATPases

The negatively charge Iodide ions diffuse to the apical membrane of the follicular epithelial cells.

Iodide is transported into the colloid using a mechanism believed to use pendrin an integral membrane protein where it is rapidly oxidised to Iodine which is attached by thyroid peroxidase to the phenolic rings of tyrosine residues within thyroglobin (a protein found in the colloid). If one iodine attaches it is called monoiodotyrosine(MIT) or if two are added then it is called diiodotyrosine (DIT),

The phenolic ring of MIT or DIT is removed from the rest of the tyrosine molecule and added to another DIT. If two DIT molecules are coupled the result it T4 or if one MIT and one DIT molecule are coupled the result is T3

Extensions of the colloid -facing membrane of follicular epithelial cells engulf portions of the colloid with iodinated thyroglobin by endocytosis

It then comes into contact with lysosome in the cell interior. Proteolysis of thyroglobin releases T3 and T4.

T3 and T4 are then able to diffuse out into the intestinal fluid the to the blood.

Control of Thyroid Function

Actions of the follicular epithelial cells are stimulated by TSH which is stimulates by TRH. TSH also increases: protein synthesis in the follicular epithelial cells; DNA replication; cell division and the amount of RER required for protein synthesis. Excess exposure of thyroid glands to TSH causes hypertropy (increase in size) which is known as a goiter.

Hyperthyroidism

This can arise from tumors in the thyroid gland that secret hormones but the most common cause is an autoimmune disease called Graves' disease. Antibodies are produced that bind to and activate TSH receptors leading to chronic overstimulation. The symptoms include: heat intolerance, weight loss, increased appetite and signs of increased sympathetic nervous system activity. It can be very serious because of the effects it has on the cardiovascular system. It can be treated by drugs that inhibit thyroid hormone synthesis, surgical removal of the thyroid gland or by using radioactive iodine to destroy portions of the thyroid gland.

Other hormones released during stress

Aldosterone and vasopressin to retain water and Na+; ,Growth hormone, glucagon beta-endorphin. Insulin production usually decreases. The changes in growth hormone, glucagon and insulin are to mobilise energy storesand increase plasma concentration of glucose. beta-endorphin is thought to have painkilling effects. The activation of the sympathetic nervous system termed 'Fight or flight' secretes epinephrine.