Adrenal Gland: Anatomy, Hormones

Importance Of Adrenal Glands

Adrenal glands are called the ‘life-saving glands’ or ‘the essential endocrine glands’. It is because the absence of adrenocortical hormones causes death within 3-15 days and the absence of adrenomedullary hormones drastically decreases the resistance to mental and physical stress.

Functional Anatomy Of Adrenal Glands

• There are two adrenal glands. Each gland is situated on the upper pole of each kidney. Because of this situation, adrenal glands are otherwise called suprarenal glands. Each gland weighs about 4 gm.

Read And Learn More: Medical Physiology Notes

• The adrenal gland is made of two distinct parts, the adrenal cortex and adrenal medulla. The adrenal medulla is the central portion of the gland constituting 20%. The adrenal cortex is the outer portion constituting 80% of the gland. These two parts are different from each other in development, structure, and functions.
• Adrenal medulla develops from the neural crest, which gives origin to the sympathetic nervous system. So, its secretions and functions resemble that of the sympathetic nervous system. Adrenal cortex develops from the mesonephros, which give rise to the renal tissues. It secretes entirely a different group of hormones known as corticosteroids.

 

Histology Of Adrenal Cortex

Adrenal cortex is formed by three layers of structures. Each layer is distinct from one another.

1. Zona glomerulosa – outer layer
2. Zona fasciculata – middle layer
3. Zona reticularis – inner layer

Hormones Of Adrenal Cortex

The hormones secreted by adrenal cortex are collectives known as adrenocortical hormones or corticosteroids. Based on their functions the corticosteroids are classified into three groups:

1. Mineralocorticoids
2. Glucocorticoids
3. Sex hormones.

Synthesis, Transport And Fate Of Adrenocortical Hormones

Synthesis: All adrenocortical hormones are steroid in nature and are synthesized mainly from cholesterol that is absorbed directly from the circulating blood. Small quantity of cholesterol is also synthesized within the cortical cells from acetyl coenzyme A (acetyl-CoA). The synthesis of these hormones is given.

Transport

• Mineralocorticoids: Mineralocorticoids are transported in blood by binding with plasma proteins, especially globulins. The binding is loose and 50% of these hormones are present in free form.
• Glucocorticoids: Glucocorticoids are transported by a special plasma protein known as glucocorticoids-binding globulin or transcortin. Ninety-four percent of glucocorticoids are transported by this protein whereas, about 6% of them are found free in plasma. Albumin plays very little role in glucocorticoid transport.
• Sex Hormones: Adrenal sex hormones are transported by another special plasma protein known as sex hormone-binding globulin.

Fate Of Corticosteroids: Corticosteroids are degraded mainly in the liver and conjugated to form glucuronides and to a lesser extent, form sulfates. About 25% of corticosteroids are excreted in bile and feces and the remaining 75%, in the urine.

Adrenal Sex Hormones

Adrenal sex hormones are secreted mainly by zona reticularis. Zona fasciculata secretes small quantities of sex hormones. Most of the hormones are male sex hormones (androgens). But small quantities of estrogen and progesterone are also secreted by adrenal cortex. Male sex hormones are called androgens. The androgens secreted by adrenal cortex are:

1. Dehydroepiandrosterone
2. Androstenedione
3. Testosterone.

• Dehydroepiandrosterone is the most active adrenal androgen.
• The androgens, in general, are responsible for masculine features of the body. But in normal conditions, the adrenal androgens have insignificant physiological effects, because of the low amount of secretion both in males and females.
• In congenital hyperplasia of the adrenal cortex or tumor of zona reticularis, an excess quantity of androgens is secreted. In males, it does not produce any specie because large quantities of androgens are procure testes also. But in females, the androgens produce masculine features. Some of the androgens are converted into testosterone. Testosterone is responsible for the androgenic activity in adrenogenital syndrome or congenital adrenal hyperplasia

Exogenous Steroids

• Corticosteroids are used as drugs for long. The exogenous steroids are extracted from adrenal cortex of animals or synthesized.
  Commercially available synthetic drugs with corticosteroid effects are widely used.
• These drugs are either used as replacement of natural hormones (replacement therapy) in patients with deficiency disorders such as Addison’s disease or to treat a variety of other conditions such as arthritis, allergic conditions, asthma, skin disorders, etc.

Synthetic Steroids: Synthetic steroids that are commonly used are

1. Cortisone and hydrocortisone which are used for replacement therapy have both glucocorticoid and mineralocorticoid effects
2. Prednisolone has more glucocorticoid activity than mineralocorticoid activity
3. Fludrocortisone (9 fludrocortisone) has more mineralocorticoid activity than glucocorticoid activity. It has the most potent mineralocorticoid effect.
4. Dexamethasone has only a glucocorticoid effect.

Adrenal Glands Applied Physiology

Hyperactivity Of Adrenal Cortex

1. Cushing’s syndrome
2. Hyperaldosteronism
3. Adrenogenital syndrome.

 

1. Cushing’S Syndrome: Cushing’s syndrome is a disorder characterized by obesity.
   • Cushing’S Syndrome Causes:
     • Cushing’s syndrome is due to the hypersecretion of glucocorticoids, particularly cortisol. It may be either due to pituitary origin or adrenal origin.
     • If it is due to pituitary origin it is known as Cushing’s disease. If it is due to adrenal origin it is called Cushing’s syndrome. Generally, these two terms are used interchangeably.
   • Pituitary Origin: Increased secretion of ACTH causes hyperplasia of adrenal cortex leading to hypersecretion of glucocorticoid. ACTH secretion is increased by:
     • Tumor in pituitary cells particularly in basophilic cells, which secrete ACTH
     • Malignant tumor of nonendocrine origin like cancer of lungs or abdominal viscera
     • The hypothalamic disorder causes hypersecretion of corticotropin-releasing hormone.
   • Adrenal Origin: Cortisol secretion is increased by
     1. Tumor in zona fasciculate of adrenal cortex
     2. Carcinoma of the adrenal cortex
     3. Prolonged treatment of chronic inflammatory diseases like rheumatoid arthritis with high dose of exogenous glucocorticoids
     4. Prolonged treatment with high dose of ACTH which stimulates the adrenal cortex to secrete excess glucocorticoids.
   • Recently Cushing’s syndrome is classified into two types:
     • ACTH dependant Cushing’s syndrome which is due to hypersecretion of ACTH
     • ACTH-independent Cushing’s syndrome in which the secretion of ACTH is normal. The syndrome develops due to abnormal membrane receptors for some peptides like interleukin-1, gonadotropin-releasing hormone, and gastric inhibitory polypeptide in the cells of zona fasciculate. The binding of these peptides to the abnormal receptors increases the secretion of glucocorticoids resulting in Cushing’s syndrome. Cushing’s syndrome that is developed by treatment with exogenous glucocorticoids also belongs to this type.
   • Signs and Symptoms
     1. A characteristic feature of this disease is the disproportionate distribution of body fat resulting in some abnormal features:
        • Moon face: The edematous facial appearance due to fat accumulation and retention of water and salt
        • Torso: Fat accumulation in chest and abdomen. Arms and legs are very slim in proportion to the torso (torso means the trunk of the body)
        • Buffalo hump: Due to fat deposit on the back of neck and shoulder
        • Potbelly: Due to fat accumulation in upper abdomen.
     2. Purple striae: Reddish purple stripes on abdomen due to three reasons:
        • Stretching of the abdominal wall by excess subcutaneous fat
        • Rupture of subdermal tissues due to stretching
        • Deficiency of collagen fibers due to protein depletion.
     3. Thinning of extremities
     4. Thinning of skin and subcutaneous tissues due to protein depletion caused by increased catabolism of proteins
     5. Darkening of skin on neck (acanthosis)
     6. Pigmentation of skin – especially in ACTH-dependent type due to hypersecretion of ACTH which has got melanocyte stimulating effect
     7. Facial redness (facial plethora)
     8. Facial hair growth (hirsutism)
     9. Weakening of muscles because of protein depletion
     10. Bone resorption and osteoporosis due to protein depletion. Bone becomes susceptible to easy fracture
     11. Hyperglycemia due to gluconeogenesis (from proteins) and inhibition of peripheral utilization of glucose. Hyperglycemia leads to glucosuria and adrenal diabetes
     12. Hypertension by the mineralocorticoid effects of glucocorticoids – retention of sodium and water results in an increase in ECF volume and blood volume leading to hypertension
     13. immunosuppression resulting in susceptibility for infection
     14. Poor wound healing.
   • Tests for Cushing’s Syndrome
     1. Observation of external features
     2. Determination of blood sugar and cortisol levels
     3. Analysis of urine for 17 hydroxy steroids.
   • Treatment for Cushing’s Syndrome: The treatment depends upon the cause of the disease. Treatment may include cortisol-inhibiting drugs, surgical removal of pituitary or adrenal tumor, radiation or chemotherapy.
     • Nelson’s syndrome: It is a disorder that develops after surgical removal of both adrenal glands. It is because of the growth of the pituitary tumor that secretes excess ACTH. The features include headaches and visual problems. Nelson’s syndrome can be treated with radiation or surgical removal of the pituitary gland.
2. Hyperaldosteronism: Increased secretion of aldosterone is called hyperaldosteronism
   • Hyperaldosteronism Causes: Depending upon the causes, hyperaldosteronism is classified into two types:
     1. Primary hyperaldosteronism
     2. Secondary hyperaldosteronism.
   • Primary Hyperaldosteronism: It is otherwise known as Conn’s syndrome. It develops due to a tumor in zona glomerulosa of adrenal cortex. In primary hyperaldosteronism, edema does not occur because of the escape phenomenon.
   • Secondary Hyperaldosteronism: It occurs due to extra adrenal causes such as:
     1. Congestive cardiac failure
     2. Nephrosis
     3. Toxemia of pregnancy
     4. Cirrhosis of liver.
   • Hyperaldosteronism Signs and Symptoms
     1. Increase in ECF volume and blood volume
     2. Hypertension due to increase in ECF volume and blood volume
     3. Severe depletion of potassium. Prolonged depletion of potassium causes renal damage. The kidneys fail to produce concentrated urine. It leads to polyuria and polydipsia
     4. Muscular weakness due to potassium depletion
     5. Metabolic alkalosis due to secretion of large amounts of hydrogen ions into renal tubules. Metabolic alkalosis reduces blood calcium level causing tetany.
3. Adrenogenital Syndrome: Under normal conditions, adrenal cortex secretes small quantities of androgens which do not have any significant effect on sex organs or sexual function. However, secretion of abnormal quantities of adrenal androgens develops adrenogenital syndrome. Testosterone is responsible for the androgenic activity in adrenogenital syndrome.
   • Adrenogenital Syndrome Causes: It is due to the tumor of 2ona reticularis in the adrenal cortex.
   • Adrenogenital Syndrome Symptoms: Adrenogenital syndrome is characterized by the tendency for the development of secondary sexual character of the opposite sex.
     • Symptoms in females: Increased secretion of androgens causes development of male secondary sexual characteristics. The condition is called adrenal virilism. The symptoms are:
       1. Masculinization due to increased muscular growth
       2. Deepening of voice
       3. Amenorrhea
       4. Enlargement of clitoris
       5. Male type of hair growth.
     • Symptoms in males: Sometimes, the tumor of estrogen-secreting cells produces more than the normal quantity of estrogen in males. It produces some symptoms such as:
       1. Feminization
       2. Gynecomastia (enlargement of breast)
       3. Atrophy of testis
       4. Loss of interest in women.

Hypoactivity Of the Adrenal Cortex

1. Addison’s disease or chronic adrenal insufficiency
2. Congenital adrenal hyperplasia.

 

1. Addison’S Disease Or Chronic Adrenal Insufficiency: It is the failure of adrenal cortex to secrete all the corticosteroids. It is classified into three types:
   1. Primary Addison’s disease – due to adrenal cause
   2. Secondary Addison’s disease – due to failure of the anterior pituitary to secrete ACTH
   3. Tertiary Addison’s disease – due to failure of the hypothalamus to secrete CRF.
      • Causes for Primary Addison’s Disease
        1. Atrophy of adrenal cortex due to autoimmune diseases
        2. Destruction of the gland because of tuberculosis
        3. Destruction of hormone-secreting cells in the adrenal cortex by malignant tissues
        4. Congenital failure to secrete cortisol
        5. Adrenalectomy and failure to take hormone therapy.
      • Primary Addison’s Disease Signs and Symptoms: The signs and symptoms develop in Addison’s disease because of a deficiency of both cortisol and aldosterone. The common signs and symptom are:
        1. Pigmentation of skin and mucous membrane due to excess ACTH secretion because of cortisol deficiency. ACTH causes pigmentation by its melanocyte-stimulating action
        2. Muscular weakness
        3. Dehydration with loss of sodium
        4. Hypotension
        5. Decreased cardiac output and decreased workload of the heart leading to a decrease in size of the heart
        6. Hypoglycemia
        7. Nausea, vomiting, and diarrhea. Prolonged vomiting and diarrhea cause dehydration and loss of body weight
        8. Susceptibility to any type of infection
        9. Inability to withstand any stress resulting in Addisonian crisis.
      • Tests for Addison’s Disease
        1. Measurement of blood level of cortisol and aldosterone
        2. Measurement of amount of steroids excreted in urine.
      • Addisonian Crisis Adrenal Crisis or Acute Adrenal Insufficiency: It is a common symptom of Addison’s disease characterized by sudden collapse associated with an increase in need for large quantities of glucocorticoids. The condition becomes fatal if not treated in time.
      • Addisonian Crisis Causes
        1. Exposure to even mild stress
        2. Hypoglycemia due to fasting
        3. Trauma
        4. Surgical operation
        5. Sudden withdrawal of glucocorticoid treatment.
2. Congenital Adrenal Hyperplasia: It is a congenital disorder characterized by increase in size of the adrenal cortex. Size increases due to an abnormal increase in the number of steroid-secreting cortical cells.
   • Congenital Adrenal Hyperplasia Causes:
     • Even though the size of the gland increases, cortisol secretion decreases. It is because of the congenital deficiency of the enzymes necessary for the synthesis of cortisol, particularly, 21-hydroxylase.
     • Lack of this enzyme reduces the synthesis of cortisol. It in turn, increases the secretion of ACTH from the pituitary bv feedback mechanism.
     • ACTH stimulates the adrenal cortex causing hyperplasia with the accumulation of lipid droplets. Hence, it is also called congenital lipid nal hyperplasia. Cortisol cannot be synthesized cause of a lack of 21-hydroxylase. Therefore, due to the constant simulation of the adrenal cortex by ACTH, the secretion of androgens increases. It results in sexual abnormalities such as virilism.
   • Congenital Adrenal Hyperplasia Symptoms: The characteristic features of adrenal hyperplasia are virilism and excess body growth.
   • In boys: Adrenal hyperplasia produces a condition known as macrogenitosomia praecox. The features of this condition are:
     1. Precocious body growth, causing stocky appearance called Infant Hercules
     2. Precocious sexual development with enlarged penis even at age of 4 years.
   • In girls: In girls, adrenal hyperplasia produces masculinization. It is otherwise called virilism. In some cases of genetic disorders, the female child is born with external genitalia of the male type. This condition is called pseudohermaphroditism.