DISORDERS OF THE ADRENAL GLANDS

are paired organs located retroperitoneally at the upper part of each kidney. usually weigh about 3 to 6 g each
consist of two distinct endocrine organs, the cortex and the medulla The adrenal cortex consists of three zones: a. Outer zona glomerulosa b. Inner zona fasciculata c. reticularis

Zona Glomerulosa secretes the mineralocorticoids (aldosterone) Zona fasciculata and reticularies secrete glucocorticoids, androgens, and small quantities of estrogens. The major glucocorticoids are a. cortisol (also known as hydrocortisone) b. corticosterone c. cortisone ninety-five percent (95%) of the glucocorticoids activity results from cortisol.

Adrenal Cortex
The three types of steroid hormones produced

a.Glucocorticoids (hydrocortisone) b.Mineralocorticoids (aldosterone) c. Androgens (male sex hormomes)

Glucocorticoids
Blood sugar
The major function of glucocorticoids is to stimulate gluconeogenesis by the liver. Gluconeogenesis refers to the production of glucose from pyruvate, lactate, glycerol, or amino acids. Glucocorticoids also decrease glucose utilization by cells of the body. these effects cause blood levels of glucose to rise.

Protein
The major effect of glucocorticoids on protein is a reduction of protein stores in all body cells, except liver cells. The glucocorticoids depress amino acid transport into muscle cells, thereby decreasing the synthesis of protein. Amino acids from tissues are also mobilized and used by the liver for gluconeogenesis.

Fat
Glucocorticoids promote mobilization of fatty acids from adipose tissue.

Inflammation
Glucocorticoids prevent the development of inflammation through various processes, including: stabilization of lysosomes, decreased capillary permeability depressed leukocyte activity reduction of fever depression of the immune system.

Pigmentation
when ACTH is secreted, another pituitary hormone, melanocyte-stimulating hormone (MSH), is secreted simultaneously. this hormone stimulates melanocytes, located in the skin, to form the pigment melanin, which causes the skin to darken. ACTH is chemically similar to MSH and, therefore, has a similar darkening effect on the skin.

Mineralocorticoid Hormones
Aldosterone the major mineralocorticoid this hormone causes the reabsorption of sodium and the excretion of potassium in the tubules of the kidneys.

The extracellular fluid volume changes in proportion to the secretion of aldosterone: as aldosterone is released, the kidneys reabsorb sodium, which also causes the kidneys to reabsorb water. therefore aldosterone plays a critical role in maintaining extracellular fluid volume and sodium and potassium balance.

There are four factors responsible for regulating aldosterone levels in the body 1. Potassium
an increase in potassium concentration within the extracellular fluid directly stimulates the zona glomerulosa cells to release aldosterone.

2. ACTH
small amounts of ACTH are required for aldosterone secretion.

3. Sodium
a decrease in sodium stimulates the release of aldosterone. the stimulus for hormone release is likely related to the fact that a reduction in sodium is followed by a reduction in extracellular fluid volume, reducing renal perfusion.

A reduction in sodium causes potassium retention. The increased level of potassium stimulates the release of aldosterone, which, in turn, enhances the excretion of potassium by the kidney.

4. Renin-angiotensin
decrease renal perfusion or decrease in effective circulating volume, renin is released from the juxtaglomerular cells of the kidney. Renin splits angiotensin, a large plasma protein produced by the liver, into angiotensin I a converting enzyme in the lung converts angiotensin I into angiotensin II as blood flows through the lung.

 Angiotensin II causes peripheral vasoconstriction and stimulates the release of aldosterone from the adrenal cortex. The peripheral vasoconstriction helps maintain blood pressure and perfusion. The release of aldosterone causes reabsorption of sodium and subsequently, the release of ADH. Angiotensin, aldosterone, and ADH work in harmony to restore and maintain blood volume.

Adrenal Sex Hormones

(Androgens)
exerts effects similar to those of male sex hormones. ACTH controls the secretion of adrenal androgens

when secreted in normal amounts, the adrenal androgens probably have little effect, but when secreted in excess, in certain inborn enzyme deficiencies, masculinization may result. This is termed as the adrenogenital syndrome.

Hyperfunction of the Adrenal Cortex Glucocorticoid Excess: Cushings Syndrome

Etiology and Pathophysiology

1. Primary Cushings Syndrome excessive cortisol secretion caused by an intra-adrenal neoplasm (adenoma or carcinoma) 2. Secondary Cushings Syndrome excessive cortisol secretion from an extra-adrenal abnormality.

a. Pituitary-dependent Cushings Syndrome (Cushings disease): adrenal hyperplasia with increased cortisol secretion of adrenocorticotropic hormone (ACTH) secondary to a pituitary or hypothalamic lesion b. Ectopic Cushings Syndrome excessive autonomous secretion of ACTH or cortisol by a non-pituitary, nonadrenal neoplasm

3. Iatrogenically-induced Cushings Syndrome elevated cortisol levels caused by the overzealous or chronic administration of exogenous glucocorticoids.

Pituitary-dependent Cushings Sydrome

is often a disorder of hypothalamic origin in which there is increased release or corticotropin releasing factor (CRF) from the hypothalamus. The resulting excessive secretion of ACTH by the pituitary causes bilateral adrenal hyperplasia and cortisol overproduction.

ACTH secretion continues despite the high circulating cortisol levels, indicating an abnormality in the feedback mechanism.

Ectopic ACTH-producing tumors remain a rare cause of the clinical manifestations of cortisol excess. The most common tumors associated with non-endocrine ACTH production include carcinomas of the lung, pacreas, gallbladder, and thymus. The resulting elevation in circulating cortisol suppresses ACTH output causes bilateral adrenal atrophy.

Clinical Manifestations
1. Moderate Central Obesity
Central obesity is the common finding which is related to fat deposition. The exact mechanism responsible is not known.

Atypical fat distribution usually involves the trunk, especially the cervicodorsal region (buffalo hump), supraclavicular areas, and abdomen
The abdomen appears large and pendulous.

The extremities are thin due to protein wasting, which occurs in cortisol excess. Patients with nonendocrine, ACTHproducing tumors may not always show signs of obesity, because of the wasting and debilitating nature of the neoplastic process.

2. Muscular Weakness
muscular weakness, predominately in the muscles of the pelvic girdle and extremities, secondary to loss of muscle mass may be experienced and is a result of increased protein catabolism. the patient may complain of difficulty in climbing stairs or getting up from a low sitting position.

3. Skin Changes
the skin becomes thin, fragile, paperlike, and liable to injury. Striae, which are pink and purplish and wider than 1 cm, are usually present on the abdomen, breast, buttocks, and axillae. these skin changes are caused by weakening of the collagenous fibers in and under the skin.

 Capillary fragility leads to an increased tendency toward bruising and hematoma formation. Hyperpigmentation of the skin is usually the result of increased circulating ACTH, either ectopic or pituitary dependent.

4. Impaired Glucose Tolerance

elevated cortisol levels promote exaggerated hepatic gluconeogenesis and decrease glucose uptake by adipose and muscle cells. despite the presence of hyperglycemia, serum insulin levels are also elevated, indicating marked insulin resistance.

5. Peptic Ulcers
Peptic ulcers may form because cortisol excess promotes acidic gastric secretions and pepsin production. because cortisol also inhibits gastric mucus production, susceptibility to ulcer formation is increased.

6. High Blood Pressure

The mineralocorticoid activity of cortisol excess promotes renal retention of sodium and water. this expansion of extracellular volume is one of the causes of observed high blood pressure. another probable cause is the cortisolinduced hypersensitivity of blood vessels to circulating catecholamines, resulting in widespread vasoconstriction.

7. Osteoporosis
a particularly unwelcome feature of Cushings syndrome is osteoporosis, which can result in compression fractures of the spine, pathological fractures of the long bones, and persistent backaches.

Cortisol is thought to increase calcium

resorption from the bone and inhibit collagen synthesis, thus interfering with bone formation and replenishment.

8. Increased Risk of Infection

The anti-inflammatory properties of cortisol can greatly retard the bodys healing mechanisms and increase risk of infection. Early signs of infection, such as fever and inflammation, may not appear, thus delaying early identification and treatment of infection

9. Virilization
Virilization may be seen in women as a result of increased androgen secretion. Among the signs are hirsutism, thinning scalp hair, acne, decreased libido, an enlarge clitoris, and menstrual changes ranging from irregularity to total cessation.

10. Psychological Manifestations

Insomia, depression, anxiety, mood swings, and frank psychosis may be observed. The cause is unknown but appears to relate to increased circulating levels of cortisol and ACTH. Some emotional instability may be the patients response to altered body image and decreased self-esteem

11. Hematologic Changes

Red blood cell and granulocyte count may be elevated. Lymphopenia and a decrease in eosinophils may also be observed. Hypokalemia occurs in 20% of cases, because cortisol promotes potassium excretion in the renal tubules.

How is Cushing's syndrome diagnosed?

Diagnosis is based on a review of a person's medical history, a physical examination, and laboratory tests. X rays of the adrenal or pituitary glands can be useful in locating tumors.

 No single lab test is perfect and usually several are needed. The three most common tests used to diagnose Cushing's syndrome a. 24-hour urinary free cortisol test b. measurement of midnight plasma cortisol or late-night salivary cortisol, c. and the low-dose dexamethasone suppression test.

Tests to Diagnose Cushing's Syndrome

24-hour urinary free cortisol level.

In this test, a person's urine is collected several times over a 24-hour period and tested for cortisol. Levels higher than 50 to 100 micrograms a day for an adult suggest Cushing's syndrome. The normal upper limit varies in different laboratories, depending on which measurement technique is used.

Midnight plasma cortisol and late-night salivary cortisol measurements.

The midnight plasma cortisol test measures cortisol concentrations in the blood. Cortisol production is normally suppressed at night, but in Cushing's syndrome, this suppression doesn't occur. If the cortisol level is more than 50 nanomoles per liter (nmol/L), Cushing's syndrome is suspected.

The test generally requires a 48-hour hospital stay to avoid falsely elevated cortisol levels due to stress.

 However, a late-night or bedtime saliva sample can be obtained at home, then tested to determine the cortisol level. Diagnostic ranges vary, depending on the measurement technique used.

Low-dose dexamethasone suppression test (LDDST).

In the LDDST, a person is given a low dose of dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 2 days. Urine is collected before dexamethasone is administered and several times on each day of the test.

 Cortisol and other glucocorticoids signal the pituitary to release less ACTH, so the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. If cortisol levels do not drop, Cushing's syndrome is suspected.

The LDDST may not show a drop in cortisol levels in people with depression, alcoholism, high estrogen levels, acute illness, or stress, falsely indicating Cushing's syndrome.

Radiologic imaging: direct visualization

of the endocrine glands. Imaging tests reveal the size and shape of the pituitary and adrenal glands and help determine if a tumor is present. The most common imaging tests are a. Computerized Tomography (CT) scan b. Magnetic Resonance Imaging (MRI).

 A CT scan produces a series of x-ray pictures giving a cross-sectional image of a body part. MRI also produces images of internal organs but without exposing patients to ionizing radiation.

How is Cushing's syndrome treated? Treatment depends on the specific reason for excess cortisol and may include a.Surgery b. radiation, c. chemotherapy d. cortisol-inhibiting drugs.

Nursing Management
1. Prevent accidental injury from falls or pathologic injuries that may result from osteoporosis. 2. Guard against or detect infection that may result from an impaired immune response brought on by an increase circulating glucocorticoids.

3. Encourage increased activity to overcome the immobility imposed by weakness and fatigue 4. Promote coping strategies to deal with the change in body image.

Mineralocorticoid Excess:

Aldosteronism

Etiology and Pathophysiology

Aldosteronism develops from excessive secretion of aldosterone, the most potent mineralocorticoid, from the adrenal cortex.

The two types of aldosteronism are based on etiology: 1. Primary Aldosteronism (Conns syndrome) is caused by oversecretion of aldosterone either by adrenal adenoma (80% of cases) or by bilateral adrenal hyperplasia (20%).

In primary aldosteronism, the normal feedback control for regulating aldosterone secretion is lacking. Aldosterone is produced and secreted regardless of body needs and in defiance of normal suppressive stimuli.

2. Secondary Aldosteronism
is the term applied when aldosterone secretion from both adrenal cortices is stimulated by sources extreneous to the adrenals. The cause include the following: Chronic renal failure Therapy with diuretics Renin-secreting tumors

Secondary Aldosteronism is usually the result

of a decrease in the effective plasma volume or perfusion pressure detected by the renal strectch receptors in the juxtaglomerular apparatus in the kidney. The resulting release of renin and subsequent activation of angiotensin II stimulate aldosterone release. Aldosterone stimulates the exchange of sodium for petassium in the distal tubule of the kidney, leading to sodium retention, potassium excretion, volume expansion, and an increase in blood pressure.

Clinical Manifestations
the signs and symptoms of aldosteronism result from an exaggeration of aldosterones effect on the kidney. The hallmark signs are a.high blood pressure b. hypokalemia.

Hypertension
Increased sodium and water retention by the kidney, with subsequent volume expansion, can cause dramatic elevations in blood pressure. Left ventricular enlargement may be noted as a cardiac adaptation to high blood pressure.

Edema is rare in primary aldosteronism

The reason is that glomerular filtration rate and renal tubular damage evoke polyuria. Edema, however is commom in secondary hyperaldosteronism.

Hypokalemia
excessive renal excretion of potassium is a direct effect of aldosterone excess. Potassium wasting often leads to muscular weakness and cardiac arrythmias because of alteration in neuromuscular activity.

when potassium levels fall, hydrogen ions move into the cells, to replace intracellular potassium losses and maintain electroneutrality, and into the urine in the tubules in exchange for sodium ions.

 The result of this hydrogen ion shifting is metabolic alkalosis. Signs of tetany may be seen, because metabolic alkalosis reduces the amount of free ionized calcium in the plasma. Despite a high sodium intake, urine and aldosterone levels remain inappropriately elevated.

Medical Management
Preferred treatment:
Partial or total adrenalectomy, the response to which is often good. It may take up to 1 month or more after surgery for blood pressure and suppressed renin levels to return to normal.

Medications
Before Surgery
High blood pressure and hypokalemia can be treated with an aldosterone antagonist

Spironolactone inhibits aldosterone synthesis

and its effects on the distal tubules.

Sodium intake is restricted

As less sodium is presented to the distal tubules, less potassium is excreted in exchange for sodium.

Androgen Excess
Adrenogenital Syndrome

Etiology and Pathology

the adrenogenital syndrome is a virilization syndrome that results from excessive production of adrenal androgens. These androgens are eventually converted to testosterone, which accounts for the observed virilism.

a. inherited (Congenital Adrenal Hyperplasia)

the most common disorder in infancy and childhood and it has a genetic predisposition. any of the enzymes required for cortisol and possibly aldosterone production may be deficient. the cortisol deficit stimulates increased production of ACTH, which in turn stimulates the the adrenal cortex, resulting in excessive androgen release.

b. Acquired (Adrenal virilism) is relatively rare it is usually secondary to a virilizing tumor of the adrenal cortex.

Clinical Manifestations
For female newborn with CAH
The external genetalia of newborn female are usually ambiguous (female pseudohermaphroditism) Clitoris is enlarged Uretral opening at its base Labial fusion Virilism persists as she grows older.

Acquired Adrenal Virilism

Prepubescent girls
Pubic hair and clitoral enlargement No breast enlargement at puberty Delayed menses

Prepubescent boys
Demonstrate hirsutism Penis and prostate development equal in size to those of adult male Testes fail to mature

Medical Management
Treatment depends on the type of lesion suspected.
In CAH, there is a deficit in cortisol production with a resultant increase in ACTH secretion. Increased circulating levels of ACTH produce the characteristic adrenal hyperplasia and excessive androgen release. The therapy then, consists of administering glucocorticoids to shut off negative feedback loop and suppress pituitary ACTH secretion.

Hypofunction of the Adrenal Cortex:

Adrenocortical Insufficiency

Etiology and Pathology

Adrenocortical insufficiency
includes all conditions in which suppression of the adrenal is accompanied by a marked decreased in production and secretion of adrenocortical hormones.

The various types of adrenal insufficiency fall into two general categories based on etiology: 1. Primary Adrenal Insufficiency (Addisons disease)
results from intrinsic pathological changes in both adrenal glands. can occur at any age, and is found equally in men and women as the level of adrenocortical hormones falls, ACTH secretion is increased by the anterior pituitary by the intrinsic feedback mechanism.

2. Secondary Adrenal Insufficiency is caused by a deficit in ACTH, due either to pathological changes in the anterior pituitary gland or to adrenal suppression by exogenously administered steroids. a decrease in circulating ACTH with a resulting decrease in adrenocortical hormone is found.

In Females:
endogenous secondary adrenal insufficiency is caused by postpartum pituitary infarction (Sheehans syndrome) Pituitary tumor Idiopathic

In Males
approximately half have a pituitary tumor, whereas in the remaining half, no discernable cause can be found.

 Idiopathic atrophy of the adrenal glands, probably the result of some autoimmune process in which the circulating adrenal antibodies slowly destroy the glands. Patients often have a family history of adrenal insufficiency. They may also have concurrent autoimmune disorders involving the thyroid gland and gonads.

Most common cause of Addisons Disease

Clinical Manifestations
Whatever the etiology, hypofunction of the adrenal cortex interferes with the bodys ability to handle internal and external stress. The signs ans symptoms observed are related to deficiencies in both aldosterone and cortisol.

1. Fluid and Electrolyte Imbalances

Aldosterone deficiency renders the distal tubules of the nephron incapable of conserving sodium. As a result, sodium is lost through the kidneys The volume of extracellular fluid is depleted; blood volume decreases, and blood pressure falls. Postural hypotension and syncope are common

an impaired ability to conserve sodium in the nephron and appropriately excrete the water load leads to hyponatremia.

Potassium levels rise as the cation exchange in the distal tubule can no longer take place at a normal rate. marked elevated potassium levels may also result in ascending paralysis with flaccid quadriplegia and mixed sensory defects.

2. Hypoglycemia
The absence of cortisol results in a fall in hepatic gluconeogenesis and a rise in tissue glucose uptake. Hypoglycemia is the result. this problem is even more common in patients with secondary adrenal insufficiency because other pituirary hormones that play a role in glucose metabolism are suppressed.

3. Fatigue
weakness may progress to the point that fatigue is continuous, and the patient is bedridden. Often the voice becomes weak because of cortisol deficit with altered carbohydrate metabolism and potassium wasting.

4. Hyperpigmentation
Hyperpigmentation is a striking, although inconsistent, feature of adrenal insufficiency in Addisons disease caused by high circulating levels of ACTH. Commonly appears as a diffuse brown, bronze, or tan darkening over exposed and unexposed areas Common sites include the areolae, creases of the hand, scars.

 Bluish black splotches in the mucous membranes, such as the gums and vaginal surfaces. Vitiligo, a condition of patchy depigmentation surrounded by areas of increased pigmentation, is also common.

5. Gastrointestinal Signs
Anorexia, nausea, vomiting, diarrhea and abdominal pain are frequent findings in uncontrolled adrenal insufficiency. The primary result from a cortisol and volume deficit. The symptoms tend to cause weight loss and augment the problem of dehydration, which, in turn, contributes to hypotension.

6. Stress
Irritability, restlessness, and confusions are frequently observed.
Extreme incapacitating prostration can occur in the presence of even mild emotional or physical stress.

7. Sexual Effects
in the male
Adrenal androgen deficiency is usually of little consequence because testicular androgen production is sufficient.

in the female
axillary and pubic hair becomes scanty. Amenorrhea and decreased libido may also be experienced.

Laboratory Values
Plasma ACTH values are elevated Failure of cortisol to rise Hypofunction of the adrenal cortex, if undiagnosed and untrated, carries a poor and fatal prognosis.

Medical Management
Acute Adrenal Crisis Increasing levels of cortisol (hydrocortisone, Solu-Cortef) Replacing the extracellular volume deficit (5% dextrose in normal saline)

Nursing Management
1. Maintain normal fluid and electrolyte balance to offset potential extracellular volume deficit and hyperkalemia 2. Minimize physical and emotional stress 3. Promote optimal activity in self-care to overcome muscle weakness and fatigue. 4. Provide good nutrition to prevent hypoglycemia 5. Encourage adherence to the treatment plan in the face of long term management.

Hyperfunction of the Adrenal Medulla

Pheochromocytoma

The adrenal medulla is, in reality, an extension of the sympathetic nervous system.
the medullary production of cathecholamines (epinephrine and norepinephrine) is important in regulating a mutlitude of diverse meatabolic processes that ensure greater physiologic reserve, and adaptability in times of preconceived danger.

Secretion of epinephrine causes

decreased blood flow to tissues that are not needed in emergency situations, such as gastrointestinal tract. increased flood flow to tissues that are important for effective fight or flight, such as cardiac and skeletal muscles.

Cathecolamines also induce the release of free fatty acids, increase the basal metabolic rate, elevate the blood glucose level.

Etiology and Pathology

Pheochromocytoma is a rare, often benign tumor that originates from the chromaffin cells and secretes catecholamines in excess. 85% of the tumor reside within the medulla of one or both adrenal glands. The right gland is affected more often than the left.

 overproduction of epinephrine occurs only in adrenal pheochromocytoma

whereas
excessive norepinephrine production can be found in both adrenal and extre-adrenal tumors.
Pheochromocytoma often occurs in association with hyperparathyroidism and thyroid medullary carcinoma in multiple endocrine neoplasia (MEN) syndromes.

Clinical Manifestations
High blood pressure is the hallmark
manifestation of these tumors. Blood pressure elevation of 200-300 mmHg systolic and 150-175 mmHg diastolic this is in response to spontaneous and paroxysmal release of catecholamines.

Other symptoms associated with catecholamine excess: Nausea Vomiting Constipation Abdominal pain Penile pain dysuria These symptoms are probably provoked by sphincter spasm and decreased peristalsis

The insulin-inhibitive and hepatic glycogenolytic effects of catecholamines often produce hyperglycemia with glucosuria, polyuria and polydipsia.

Diagnosis
Pheochromocytoma can be diagnosed in about 90% of patients on the basis of laboratory data. Screening 24 hour urine collections for catecholamines and their metabolites is the most common diagnostic tool.

Treatment
Surgical removal of the tumor is the treatment of choice and is successful in 90% of cases.

Ovaries
are nodular glands located on each side of the uterus Estrogens are secreted primarily by the graafian follicles of the ovaries, with small amounts secreted by the adrenal cortex During pregnancy, large amounts of estrogens are secreted by the placenta.

Estrogens
Primary functions of estrogens is to stimulate the growth of the female sex organs such as: Fallopian tubes Uterus Vagina Labia majora Labia minora

Under the influence of estrogens there is fat deposition of the breasts capability of milk production increase in bone growth closing of the epiphysis important in ovulation These hormones cause calcium and phosphate retention a slight increase in body protein increase in metabolism increase in fat deposition in the subcutaneous tissues.

Progesterone
is produced primarily by the corpus luteum of the ovaries in the nonpregnant female and by the placenta during pregnancy The most important function: prepares the uterus for the implantation of a fertilized ovum.

The hormone enhances the development of the lobules and alveoli of the breasts, necessary for the production of milk; however, prolactin stimulation is necessary for milk secretion. During pregnancy, progesterone from the corpus luteum, and later from the placenta, inhibits contractions of the muscular wall of the uterus until the onset of labor.

Testes
the hormones secreted by the testes are called Androgesns and they include: a. Testosterone b. Dihydrotestosterone c. Androstenedione Testosterone is the most potent and plentiful of the androgens and is, therefore, considered the primary hormone responsible for masculinization.

 the hormone is formed by the interstitial cells of Leydig of the testes The cells are numerous in the male newborn and male adult. Androgens are also secreted by the adrenal gland in both men and women; however, the concentration is generally so small as to contribute little to the hormones masculinizing effects. Testosterone is metabolized in the liver and excreted in the urine.

Androgens
Testosterone is secreted in the beginning at about the 7th week of gestation. The hormone causes the development of male sex characteristics including Growth of penis Prostate gland Scrotum Seminal vesicles is also responsible for descent of the testes into the scrotum.

At Puberty
The hormone causes development of secondary sex characteristics such as: Growth of hair in the pubic area, chest, axillae, and face. Deepening of the voice Skin increases in thickness There is an increased secretion from the sebaceous glands, which may contribute to acne.

 increased muscular development and increased size and strength of bones. the epiphyses of the bones to close; hence, an early puberty may prevent the male from growing as tall as he would have with the later puberty. Some of the other effects include: increased protein anabolism increased metabolism increased libido increased sodium and water retention

 The hypothalamus secretes a hormone luteinizing hormone-releasing hormone (LHRH). This hormone, in turn, stimulates the anterior pituitary to secrete luteinizing hormone, which stimulates the testes to mature and secrete testosterone.

There is a negative feedback to the hypothalamus: As circulating levels of testosterone rise, LHRH is inhibited. Conversely, as the level of testosterone decreases, LHRH and LH are released, stimulating the testes to produce testosterone.

Pineal Gland
The pineal gland is a small pineconeshaped mass of glandular tissue found just posterior to the thalamus of the brain. The pineal gland produces the hormone melatonin that helps to regulate the human sleep-wake cycle known as the circadian rhythm.

 The activity of the pineal gland is inhibited by stimulation from the photoreceptors of the retina.

This light sensitivity causes melatonin to be produced only in low light or darkness. Increased melatonin production causes humans to feel drowsy at nighttime when the pineal gland is active.