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3-Parathyroid Glands

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16 views14 pages

3-Parathyroid Glands

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© © All Rights Reserved
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CLINICAL CHEMISTRY 2 CC2 TOPIC

WEEK
PARATHYROID, THYROID AND ADRENAL HORMONES

LECTURER: SHIRLEY SOLITARIO


BACHELOR OF SCIENCE IN MEDICAL LABORATORY SCIENCE
LECTURE 3
TRANSCRIBED BY: BERNADETTE N. VALDEZ
THIRD YEAR-SECOND SEMESTER
03 03
PARATHYROID GLANDS PARATHYROID FUNCTION

• Parathormone, the protein hormone from the parathyroid glands,


regulates calcium and phosphorus metabolism.

• Increased secretion of parathormone results in increased calcium


absorption from the kidney, intestine, and bones, thereby raising the
blood calcium level.

• Some actions of this hormone are increased by the presence of vitamin


D.
• Parathyroid glands are small glands of the endocrine system
which are located in the neck behind the thyroid. • Parathormone also tends to lower the blood phosphorus level.

• They release parathyroid hormone, which plays a role in regulating • Excess parathormone can result in markedly elevated levels of serum
calcium levels in the blood and bone metabolism. calcium, a potentially life-threatening situation.

• When the product of serum calcium and serum phosphorus (calcium


phosphorus) rises, calcium phosphate may precipitate in various organs
of the body and cause tissue calcification.

• The serum level of ionized calcium regulates the output of


parathormone.

• Increased serum calcium results in decreased parathormone


secretion, creating a negative feedback system.
An Illustration of the Parathyroid Gland • The serum level of ionized calcium regulates the output of
parathormone.
A Picture of Parathyroid Gland
• Increased serum calcium results in decreased parathormone
secretion, creating a negative feedback system.

FUNCTIONS OF PARATHORMONE

Parathyroid Hormone (PTH)

PTH release:

1) stimulates osteoclasts
• Parathyroid glands (4) are normally the size of a grain of rice.
2) enhances reabsorption of Ca++ by kidneys
• Occasionally they can be as large as a pea and still be normal.
3) increases absorption of Ca++ by intestinal mucosal cells
• The four parathyroids behind the thyroid gland. Hyperparathyroidism- too much Ca++ drawn out of bone; could be due
• Four or more small glands embedded on posterior surface of to tumor
thyroid gland.
Hypoparathyroidism- most often follow parathyroid gland trauma or
after removal of thyroid--- tetany, muscle twitches, convulsions; if
• Each gland is about the size of a grain of rice (weighs
untreated→respiratory paralysis and death
approximately 30 milligrams and is 3-4 millimeters in diameter)

• Produces Parathormone (PTH).

• Regulates calcium and phosphate levels in an inverse relationship.

• Calcium levels major controlling factor of PTH secretion.

BERNADETTE N. VALDEZ 1 A.Y. 2022-2023 | BSMLS 3 | CC2


PTH Effects Physiology of Parathryroid Glands

• The ONLY purpose of the parathyroid glands is to regulate the


calcium level in our bodies within a very narrow range so that
the nervous and muscular systems can function properly.

• Parathyroid Glands measure the amount of calcium in the blood


every minute of every day. If the calcium levels go down a little bit,
the parathyroid glands recognize it and they will make parathyroid
hormone (PTH) which goes to the bones and takes some
calcium out (makes a withdrawal from the calcium vault) and puts
it into the blood.

• When the calcium in the blood is high enough, then the


parathyroids shut down and stop making PTH.

Hyperparathyroidism

• The single major disease of parathyroid glands is over-activity of


one or more of the parathyroids which make too much
parathyroid hormone causing a potentially serious calcium
imbalance (too high calcium in the blood).

• This is called hyperparathyroidism

Parathyroid Disease and Hyperparathyroidism

Function of Parathyroid + Hyperparathyroidism occurs when one of the parathyroids


develops a tumor which makes too much hormone leading to
+ Parathyroid glands control the calcium in our bodies high calcium and other bad symptoms.
1. how much calcium is in our bones,
Symptoms of Parathyroid Disease (Hyperparathyroidism)
2. how much calcium is in our blood.
+ Loss of energy. Don't feel like doing much. Tired all the time.
+ Calcium is the most important element in our bodies (we use it Chronic fatigue.
to control many systems), so calcium is regulated very carefully.
+ Feel old. Don't have the interest in things that they are used to.

+ Can't concentrate
The Role of Calcium in the Human Body...
+ Depression.
• To provide the electrical energy for our nervous system.
+ Osteoporosis and Osteopenia.
provides the means for electrical impulses to travel along nerves.
+ Pain in the bones ( Legs and Arms and most bones)
• Calcium is what the nervous system of our body uses to conduct
electricity. + Wake up in middle of night. Trouble getting to sleep.
• To provide the electrical energy for our muscular system. + Fatigability ( Tiredness)
• When the calcium levels are not correct, people can feel weak + More irritable and harder to get along with (cranky, bitchy).
and have muscle cramps.
+ Worsening Memory
• To provide strength to our skeletal system. The bones serve
as the storage system to make sure we will always have a good + Gastric acid reflux; heartburn; GERD.
supply of calcium.
+ Decrease in sex drive.
• The most important role of calcium is to provide for the proper
functioning of our nervous system + Thinning hair (predominately in middle aged females on the front
part of the scalp).
• to provide strength to our bones is only secondary.
+ Kidney Stones (and eventually kidney failure).
• Thus, calcium is the most closely regulated element in our
bodies. + High Blood Pressure (sometimes mild, sometimes quite severe)

• Calcium is the ONLY element / mineral that has its own + Recurrent Headaches (usually patients under the age of 40).
regulatory system (the parathyroid glands). There are no
other glands in our bodies that regulate any other element. + Heart Palpitations (arrhythmias). Typically atrial arrhythmias.

• Calcium provides the electrical system for our nervous + Atrial Fibrillation (rapid heart rate, often requiring blood thinners
system. When our calcium levels get elevated (almost always it and pacemakers).
is due to a bad parathyroid gland)
+ High liver function tests (liver blood tests).
What happens?
+ Abnormal blood protein levels.
• Change in personality
+ Patients with un-treated primary hyperparathyroidism will die an
• Nervous system symptoms (depression, etc). So, parathyroid average of 5-6 years earlier than their peers, due to increased rates
disease is not just about osteoporosis and kidney stones, it is of heart disease, stroke, and several types of cancers.
primarily about us feeling "normal" and enjoying life.
+ Hyperparathyroidism is a more deadly disease than high
cholesterol..

BERNADETTE N. VALDEZ 2 A.Y. 2022-2023 | BSMLS 3 | CC2


Yes (if over
Patient 9 10.2 -10.6 85 Yes
30)
Diagnosis
Patient
+ Blood (Serum) calcium levels: Increased Ionized Serum 9.8 - 10.2 100 Possibly Possibly
10
Calcium (Very expensive)
Patient
+ Parathyroid hormone: Increased 9.5-10.2 40 Nope Nope
11
+ Vitamin D Level- 95% of patients with primary
hyperparathyroidism (a parathyroid tumor) have low vitamin D.

+ Serum Calcium -Normal 8.5 to 10.4 TREATMENT OPTIONS FOR PRIMARY HYPERPARATHYROIDISM

+ Serum PTH -Normal 10 to 65 + Standard parathyroid surgery: a major operation.

+ Scan- Positive + Radioguided parathyroidectomy

+ Clinical Diagnosis
THYROID AND ADRENAL HORMONE
• Significant Osteoporosis

• Kidney Stones

• X-ray

• Urine Calcium

+ Thyrotrophins:

+ Thyroid-stimulating hormone (TSH), released under influence of


hypothalamic Thyrotropin-releasing hormone (TRH)

Sources of Thyroid Hormones

Follicular cells

• T4: L-thyroxine
• T3: L-triiodothyronine
• rT3: reverse T3

Parafollicular cells

• Calcitonin

Who Has Hyperparathyroidism?


Thyroid Gland
Serum
Serum PTH
Calcium Parathyroid Needs an
Normal 10 to
Normal 8.5 to Disease? Operation?
65
10.4

Patient 1 11.4 121 Yes Yes

Patient 2 10.5 97 Yes Yes

Patient 3 11.1 55 Yes Yes Thyroid Follicles

Patient 4 10.3 100 Yes Yes

Patient 5 11.8 158 Yes Yes

Patient 6 12.1 50 Yes Yes

Patient 7 10.9 40 Yes Yes

Patient 8 11.4 30 Yes Yes

BERNADETTE N. VALDEZ 3 A.Y. 2022-2023 | BSMLS 3 | CC2


Functions of Thyroid Hormones Hypothalamic-Pituitary Thyroid Axis

1. Acts on every cell Neuroendocrine system that regulates the production and secretion of
thyroid hormones
2. Regulates Metabolism – Glucose, Protein Synthesis and
Oxygen Consumption

3. Growth and Tissue Differentiation

Thyroid-Stimulating Hormone (TSH)

• Acts on the thyroid gland, stimulating it to release T3 & T4

• These thyroid hormones increase glucose catabolism and


body heat production.

• Negative feedback mechanism involved in regulating levels.

Thyroid Hormones

• Thyroxine (T4)

• Triiodothyronine (T3)

Both control metabolic rate and cellular oxidation

• Calcitonin (from parafolicular cells)- lowers blood CA ++

levels and causes CA++ reabsorption in bone

Thyroid-stimulating hormone (TSH):


Triiodothyronine (T3)
• Stimulates the thyroid gland to produce thyroid hormones (A
lack of thyroid hormones either because of a defect in the • most active thyroid hormonal activity
pituitary or the thyroid itself is called hypothyroidism.)
• Almost 80% is produced from the deiodination of T4

• Used for diagnosing T3 thyrotoxicosis


Thyroid Hormone Regulation
• Good indicator of recovery and/or recurrence from hyperthyroidism

Thyroxine/Tetraidothyronine (T4)

• Most abundant and principal secretory product

• Major fraction of organic iodine in the circulation

• A prohormone for T3 production

• Increase in thyroxine inhibits TSH secretion

• Good indicator of thyroid secretory rate

Thyroid Hormone Binding Proteins


Thyroid Hormone Formation
Thyroxine Binding Globulin (TBG)
1. Iodination of tyrosine residues results in the formation of
monoiodotyrosine (MIT) and diiodotyrosine (DIT) - Transports 70-75% of total T4
- Low affinity for T3
2. Conversion of T4 and T3 takes place in tissues like the kidney
and liver. Thyroxine-Binding Prealbumin (Transthyretin)

- Iodine intake must be above 50ug/day - Transports 15-20% of total T4


- No affinity for T3

Thyroxine-Binding Albumin

- Transports T3
- Transports 10% of T4

HyperThyroidIsm

Above Normal, Excess, High, Increase

Thyroid Gland

Medical Disease

Definition: Condition in which the thyroid gland is overactive and


produces too much thyroid hormone

Hyperthyroidism = High Levels of Thyroid Hormone in the Blood

BERNADETTE N. VALDEZ 4 A.Y. 2022-2023 | BSMLS 3 | CC2


Hypothyroidism

Primary hypothyroidism:

- Low T3 and T4, High TSH Hashimoto's disease: autoimmune


Positive for Thyroidal Peroxidase (TPO) Antibody

- Myxedema: peculiar non pitting swelling of the skin, infiltration


of mucopolysaccharide in the skin.

Congenital bypothyroidism/ Cretinism: NBS


Hyperthyroidism – Tachycardia and Hypertension
Secondary hypothyroidism

- pituitary destruction or pituitary adenoma Low TSH, T3 and


T4 levels

Tertiary hypothyroidism

- due to hypothalamic disease. Low TRH, TSH. T3 and T4


levels

HYPOTHYROIDISM

Hypometabolic State – Decreased Metabolic Activity


Primary Secondary Tertiary
Hypothyroidism – Bradycardia and Hypertension
Failure of the Pituitary disease Hypothalamic disease
Hyperthyroidism VS Hypothyroidism causing reduced causing reduced TRH
thyroid gland
itself TSH (rare) (rarer)
Hyperthyroidism Hypothyroidism

Weight Loss Weight Gain T3 and T4   


TSH   
Increased Appetite Decreased Appetite TRH N N 
Heat Intolerance Cold Intolerance Increased
Increased Sensitivity to Heat Sensitivity to Cold

Tachycardia, Palpitations, Bradycardia


Arhythmias
Diarrhea Constipation

Anxiety, Nervousness, Fatigue, Depression, Impaired


Irritability, Insomnia, Tremors Memory, Impaired
Concentration, "Mental Fog"

Increased Hair and Nail Growth Hair Loss and Thin Nails Dry
Increased Sweating Skin

Hyperthyroidism

Thyrotoxicosis (3)

- T3 thyrotoxicosis or
- Plummer's disease or
- Toxic Multinodular nodule

Riedel's thyroiditis

- Thyroid becomes a woody or stony mass Fibrous thyroiditis Thyroid Disorders

De Quervain's (Subacute Thyroiditis) - Hyperthyroidism (Grave’s, Goiter)

- Painful upon palpation - Hypothyroidism (Cretinism, Myxedema)

Grave's disease Goiter

- Presence of auto-antibodies against TSH receptor and Lack of iodine in diet hyposecretion of T3 & T4
subsequently increases the production of T3 and T4.

Subclinical hyperthyroidism
Cretinism
- TSH is low and FT3 and FT4 is normal no clinical symptoms
hyposecretion of T3 & T4

BERNADETTE N. VALDEZ 5 A.Y. 2022-2023 | BSMLS 3 | CC2


8. The appetite is often increased.

Myxedema THYROID FUNCTION TESTS

hyposecretion of T3 & T4 Laboratory determinations of thyroid function are useful in distinguishing


patients with euthyroidism (normal thyroid gland function) from those
with hyperthyroidism (increased function) or hypothyroidism (decreased
function)

Methods of Diagnosis

1. A blood test: blood TSH level.

2. Physical” If there is obvious involvement of the eyes, a diagnosis


of Graves' disease is almost certain.

Thyroid hormone profile

1. Levels of unbound free thyroid hormones TSH

Exophthalmos- 2. fT4
hyperthyroidism
3. fT3,

o These reflect a true measure of the body’s metabolic rate.

4. Reverse T3 (rT3) is an inactive form of T3 that is produced in the


body particularly during periods of stress.

A patient with Exopthalmic Goiter Specimen requirement

A blood specimen is required which can be collected at any time of day.

1. Antibody screening (for Graves' disease)

Functioning Adenoma and Toxic Multinodular Goiter 2. thyroid scan using radioactively-labelled iodine (which concentrates
in the thyroid gland) can help diagnose the underlying thyroid disease.
+ The thyroid gland (like many other areas of the body)
becomes lumpier as we get older. In the majority of cases, Clinical relevance
these lumps do not produce thyroid hormones and require no
treatment. + Thyroid function decreases with age and an underactive thyroid is
most common in menopausal and
+ Occasionally, a nodule may become "autonomous," which
means that it does not respond to pituitary regulation via TSH + post-menopausal women. Symptoms of underactive thyroid
and produces thyroid hormones independently. include dry and coarse skin, weakness

+ This becomes more likely if the nodule is larger than 3 cm. + and lethargy, constipation, weight gain, slow pulse, heavy and
irregular periods and depression.
+ When there is a single nodule that is independently producing
thyroid hormones, it is called a functioning nodule. Clinical Relevance of rT3

+ If there is more than one functioning nodule, the term 1. Under normal conditions, T4 will convert to both T3 and rT3
toxic, multinodular goiter is used. continually and the body eliminates rT3 quickly.

+ Functioning nodules may be readily detected with a thyroid 2. Under certain conditions, more rT3 is produced and the desirable
scan. conversion of T4 to T3 decreases.

o Conditions when No. 2 will occur

Ultrasound and Thyroid Scan o Fasting, starvation, illnesses such as liver disease and during
times of increased stress.

Conditions where there is an increased production of rT3


Symptoms of Thyroid Goiter 1. Fibromyalgia

The disease can result in the formation of a toxic goiter as a result of 2. Chronic fatigue syndrome
thyroid growth in response to a lack of negative feedback mechanisms.
3. Wilson’s Thyroid syndrome
What are the symptoms of thyroid goiter
4. Stress.
1. protruding eyes (exopthalmos),
o Euthyroid syndrome where active T3 is within normal range
2. palpitations and rT3 is elevate.

3. excess sweating Disease of Thyroid Gland

4. diarrhea • Hypothyroidism
• Hyperthyroidism
5. weight loss

6. muscle weakness and

7. unusual sensitivity to heat.

BERNADETTE N. VALDEZ 6 A.Y. 2022-2023 | BSMLS 3 | CC2


THYROID FUNCTION TESTS-INDICATIONS FT3: FREE TRIIODOTHYRONINE

• Suspicion of thyroid disease based on clinical signs and symptoms • pmol/uL – picomole/microliter 1 pmol = 1000nmol/L

• Screening for thyroid disease • Normal Adults: 4.0-7.4 pmol/L In nonthyroidal illness, a low FT3
level is a nonspecific finding.
• Evaluation of treatment for thyroid disease.
• FT3, is done to rule out T3 toxicosis
Why do we perform this test?
FREE THYROXINE INDEX (FTI)
-Patients with thyroid problems and medication • The free thyroxine index (FTI) is a mathematical calculation used
to correct the estimated total T 4 for the amount of TBG present.
-To monitor the treatment of prescribed drugs

Why do we perform this test? • Make a calculation based on results of T 3 uptake and T 4 total, as
follows: FTI- Total T4XT3 UPTAKE(%)/100
-Thyroid prblems are genetic
• Normal Adults: 1.5-4.5 index
-To rule out thyroid problems in new born babies

- On doctor's suggestion METHODS USED TO MEASURE THYROID HORMONES

BLOOD TESTS TO EVALUATE THYROID FUNCTION RIA: Radioimmunoassay

TSH: Thyroid-stimulating hormone ELISA: Enzyme-linked immunosorbant assay

T4: Serum total thyroxine CLIA: Chemiluminescent immunoassay

T3: Serum total triodothyronine FIA: Fluorescent immunoassay

FT4: Free thyroxine THYROID ANTIBODIES

FT3: Free 13 Antithyroid peroxidase antibodies

Thyroid antibodies: Antithyroid peroxidase antibodies, o Used to diagnose suspected Hashimoto's thyroiditis in
Antihyroglobulin antibodies hypothyroidism

Thyroid hormones: Antithyroglobulin antibodies

1) Thyroxine (T4) o Used to diagnose autoimmune thyroiditis or Graves' disease


in hyperthyroidism
2) Triiodothyronine (T3)
TRH RESPONSE TEST
3) Calcitonin
o TRH administration stimulate production of TSH
TSH: THYROID-STIMULATING HORMONE
o If hypothalamo-pituitary-thyroid axis is normal, T3 and T4
One of the best thyroid function screening test secretions will be increased
• Elevated TSH (>5 mU/L hypothyroidism) In primary hyperthyroidism

• Low TSH (<0.5 mU/L hyperthyroidism) o little or no change in TSH levels

• Normal range: 0.5-5mU/L In primary hypothyroidism

T4:SERUM TOTAL THYROXINE o Prompt increase in TSH

• Normal range: 65-150nmol/L In secondary hypothyroidism

• Hypothyroidism: Decreased T4 o Does not produce an increase in TSH

RADIOACTIVE IODINE UPTAKE


• Hyperthyroidism: Increased T4
• 131l used to detect functional derangements of thyroid gland.
T3: SERUM TOTAL TRIIODOTHYRONINE

• Normal range: 1.8- 3nmol/L • About 15 mci of 131l given intravenously

• Hypothyroidism: Decreased T3 • After a few hours, the patient is monitored at the neck region by
movable gamma-ray counter, which will pick up the radiation
• Hyperthyroidism: Increased T3 emitted by thyroid gland

FT4: FREE THYROXINE Normal response

• Is the metabolically active thyroid hormone-not bound to protein • About 25% uptake by thyroid within 2 hours

• About 50% uptake by thyroid within 24 hours


• Should be ordered when TSH is abnormal to determine thyroid
hyperfunction or hypofunction Abnormal response

• Normal range: 10-23 pmol/L • Increased uptake in hyperthyroidism

• Decreased uptake in hyporthyroidism

BERNADETTE N. VALDEZ 7 A.Y. 2022-2023 | BSMLS 3 | CC2


Euthyroid Treatment

Refers to normal functioning thyroid gland in the presence of abnormal 1. Beta blockers are used to decrease symptoms of hyperthyroidism
concentration of TBG such as increased heart rate, tremors, anxiety and heart palpitations,
Increase TBG: pregnancy and estrogen therapy 2. Anti-thyroid drugs are used to decrease the production of thyroid
hormones,
Decrease TBG: nephrotic syndrome, ingestion of certain drugs,
decreased protein in the circulation 3. Graves' disease. These medications take several months to take full
effect and have side-effects such as skin rash or a drop in white blood
Reference ranges cell count, which decreases the ability of the body to fight off infections

TSH: 0.3-4.0 mIU/L 4. radioactive iodine-131 treatment. Radioactive iodine is administered


in order to destroy a portion of or the entire thyroid gland, since the
Free T4: 12.0-22.0 pmol/L radioactive iodine is selectively taken up by the gland and gradually
destroys the cells of the gland.
Free T3: 3.0-7.0 pmol/l
5. the gland may be partially or entirely removed surgically, though
iodine treatment is usually preferred since the surgery is invasive and
carries a risk of damage to the parathyroid glands or the nerves
controlling the vocal cords. If the entire thyroid gland is removed,
hypothyroidism results.

Surgery

+ Surgery partially remove the thyroid gland (partial thyroidectomy)

+ The purpose is to remove the thyroid tissue that was producing


the excessive thyroid hormone.

Disadvantage of Surgery:

+ If too much tissue is removed, an inadequate production of thyroid


hormone (hypothyroidism) may result.

+ In this case, thyroid replacement therapy is begun.

+ The major complication of surgery is disruption of the surrounding


tissue, including the nerves supplying the vocal cords and the four
tiny glands in the neck that regulate calcium levels in the body (the
parathyroid glands).

+ Accidental removal of these glands may result in low calcium


levels and require calcium replacement therapy

Iodine Intake

Thyroid function tests Excessive Iodine Intake

• TRH (Thyrotropin Releasing Hormone) Stimulation Test + The thyroid gland uses iodine to make thyroid hormones.

+ An excess of iodine may cause hyperthyroidism. Iodine-induced


• Thyroglobulin (Tg) Assay: tumor marker for thyroid
hyperthyroidism is usually seen in patients who already have an
underlying abnormal thyroid gland.
• TSH test
+ Certain medications, such as amiodarone (Cordarone), which is
• Reverse T3 (rT3) used in the treatment of heart problems, contain a large amount of
iodine and may be associated with thyroid function abnormalities.
• Radioactive Iodine Uptake (RAIU)
Excessive Hormone Intake
• Free Thyroxine index: is obtained by multiplying the (Total T4)
times (T3 Uptake) Excessive Intake of Thyroid Hormones

• Total T3: + Taking too much thyroid hormone medication is actually quite
common. Excessive doses of thyroid hormones frequently go
o Free T3: most T3 are bound undetected due to the lack of follow-up of patients taking thyroid
medicine.
o Free T4: most accurate assessment of thyroid hormone levels,
because it avoids changes in plasma protein binding capabilities + Other persons may be abusing the drug in an attempt to achieve
other goals such as weight loss. These patients can be identified
• Thyroid ultrasound by having a low uptake of radioactively-labeled iodine (radioiodine)
on a thyroid scan.
• T3 uptake test

• Thyroxine binding globulin test (TBG) test

• Fine needle aspiration

• Thyroid nuclear scan

BERNADETTE N. VALDEZ 8 A.Y. 2022-2023 | BSMLS 3 | CC2


ADRENAL GLAND HORMONES Hormones of the Adrenal Medulla

The Adrenals • Adrenalin (epinephrine): converts glycogen to glucose in liver

+ Adrenal glands are triangle-shaped glands located on top of the • Noradrenalin (norepinephrine): increases blood pressure
kidneys. (sympathetic nervous system)

+ The outer part of the adrenal gland is called the cortex and • Corticosteroids:  glucose levels)
produces steroid hormones such as cortisol, aldosterone, and
Adrenal Medulla
testosterone. These are generally called corticosteroids
Catecholamine: epinephrine, norepinephrine and dopamine
+ The inner part of the adrenal gland is called the medulla and
produces cathecolamines epinephrine and norepinephrine, Synthesis: from tyrosine by chromaffin cells of the adrenal medulla,
which are commonly called adrenaline and noradrenaline. brain and sympathetic neurons

+ Located above the upper pole of the kidney

+ Pyramidal in structure and weighs about 4-6 grams

+ Consist of adrenal cortex and adrenal medulla Medulla

• Epinephrine
• Norepinephrine

Hormones of the Adrenal Cortex

Glucocorticoids- cortisol
The Adrenals, Kidneys etc.
1. Decrease protein synthesis

2. Increase release and use of fatty acids

3. Stimulates the liver to produce glucose from non carb’s

Mineralcorticoids- aldosterone

1. Stimulates cells in kidney to reabsorb Na+ from filtrate

2. Increases water reabsorption in kidneys

3. Increases blood pressure

Sex Steroids- small amts (androgens)

1. Onset of puberty

2. Sex drive

Functions of Corticosteroids (cortisol, aldosterone, testosterone)

1. regulate the body's metabolism

1.1 the balance of salt and water in the body

1.2 the immune system,

1.3 the sexual function.

Function of Cathecolamines (epinephrine and norepinephrine) or


(Adrenaline and noradrenaline)

1. These hormones help the body cope with physical and emotional
stress by increasing the heart rate and blood pressure. (called “Fight
and Flight” response) to stress.

BERNADETTE N. VALDEZ 9 A.Y. 2022-2023 | BSMLS 3 | CC2


Significance + MIBG (metaiodobenzylguanidine) scans help locate and diagnose
certain types of tumors in the body.
• The hormones released from the adrenal glands are so important
to the overall functioning of your body + MIBG is a substance that gathers in some tumors, particularly
neuroblastoma tumors.
• Tumors of the adrenal glands can secrete excess hormones,
causing an increase in blood pressure or heart rate and reducing + When MIBG is combined with radioactive iodine (tracer), it
immune function. provides a way to identify primary and metastatic (spread) disease.

• Disorders that result in decreased adrenal gland function, such as + MIBG scans are helpful for locating both bone and soft tissue
autoimmune diseases or cancer, can lead to low blood sugar and tumors.
heart failure.
How MIBG is done

+ The test is performed by injecting a small amount of radioactive


dye (tracer) through an IV. Pictures are then taken under a
scanner that is similar to a CT scan.

+ The scans may occur 24, 48, or 72 hours after the tracer is given.

+ Doctors will look for bright spots on the scan, these indicate
cancer cells.

PHEOCHROMACYTOMA

DEFINITION: Pheochromacytoma is a catecholamine secreting tumor


of the cromaffin cells of the sympathetic nervous system it is usually
found in the adrenal medulla. Treatment of Pheochromocytoma
+ Pheochromocytoma is a tumor of special cells that arises inside 1. Surgery. During this process one or two adrenal glands can be
the “adrenal glands’ chromaffin cells. (Occurs between 30-60
removed and this is known as Adrenalectomy.
yrs. Of age)
Lymph nodes and tissues maybe removed if the cancer has started to
+ These chromaffin cells may be found anywhere in the heart and in spread
the area around the bladder, but they are mostly found in the
adrenal glands. 2. Chemotherapy where drugs are used to kill the cancer cells (either
pills or Intravenous)
+ When adrenaline or hormones are released too much from the
adrenal gland, they cause high blood pressure.

SYMPTOMS

• Abdominal pain
• Chest pain
• Irritability
• Nervousness
• Pallor
• Palpitations
• Rapid heart rate
• Severe headache CORTEX
• Sweating
• Weight loss • Zona glomerulosa (G-zone; outermost zone)

Causes of Pheochromocytoma ✓ Mineralocorticoids → aldosterone

+ The main cause for most pheochromocytoma is not yet known. • Zona fasciculata (F-zone; middle zone)

+ Inherited pheochromocytoma is a 10 to 20 percent chance of ✓ Glucocorticoids → cortisol


causing the disease. It is from an inherited autosomal dominant
trait. • Zona reticularis (innermost zone)

DIAGNOSTIC TESTS ✓ Androgens → estrogen, progesterone, testosterone

MEDULLA
• Abdominal CT scan
• Adrenal biopsy
✓ Norepinephrine and epinephrine
• Catecholamines blood test
• Glucose test You sent
• Metanephrine blood test.
• MIBG scintiscan Classes of Steroid Hormones
• MRI of abdomen
• Urine catecholamines 1. Mineralocorticoids

o responsible for fluid and electrolyte balance OBG

2. Glucocorticoids

o regulate glucose production and protein metabolism:

BERNADETTE N. VALDEZ 10 A.Y. 2022-2023 | BSMLS 3 | CC2


3. Sex steroids • Inactivated in the liver, with formation of tetrahydroaldosterone

o regulate sexual development and control many aspects of • Regulated by Renin-Angiotensin System
pregnancy

Adrenal Cortex

o produce steroid hormones

Layers of the Location Hormones Secreted


Adrenal cortex
Zona glomerulosa Outermost Mineralocorticoids

✓Major: Aldosterone
✓Conserves sodium

Zona fasciculata 2nd layer Glucocorticoids


Hyperaldosteronism Hypoaldosteronism
✓ Major: Cortisol Increases 1. Primary Hyperaldosteronism 1. Atrophy of adrenal glands
glucose metabolism
• Problem in the adrenal 2. Addison's disease: atrophy of
Zona reticularis Innermost Androgens gland adrenal glands with depressed
production of Aldosterone and
✓ Required for sexual • Conn Syndrome: glucocorticoids
function (before puberty) Aldosterone-secreting
adrenal adenoma 3. Congenital deficiency of 21-
hydroxylase enzyme
• Aldosterone-secreting
adrenal carcinoma
Renin-Angiotensin System or Renin-Angiotensin-Aldosterone
• Hyperplasia of adrenal
• Juxtaglomerular apparatus of the kidneys detect low serum sodium cortex
or decreased BP
2. Secondary
• Renin will be produced (Converting enzyme) Hyperaldosteronism

• Problem where there is


• Renin will catalyze the reaction Angiotensinogen extra-adrenal stimulation

• Angiotensiogen → Angiotensin I → Angiotensin II • Renin-angiotensin system


disorder due to excess
• Angiotensin II stimulates the secretion of Aldosterone (Promotes production of renin
increase in BP and BV)
• Malignant hypertension

• Renin-secreting renal
tumor

GLUCOCORTICOIDS

1. Cortisol
MINERALOCORTICOIDS o most significant physiologically
• Aldosterone the major mineralocorticoid 2. Cortisone

• Synthesized primarily by the Adrenal cortex Cortisol

• -30% of the total aldosterone in plasma circulates bound to cortisol- → stress hormones “Hydro Cortisme"
binding globulin
• 83% bound to cortisol-binding globulin
• 42% interacting with albumin • 12% bound to albumin
• 5% free
Aldosterone

• Promotes renal tubular reabsorption of sodium and secretion of


potassium

• Half-life: 15-20 minutes

BERNADETTE N. VALDEZ 11 A.Y. 2022-2023 | BSMLS 3 | CC2


Effects of Cortisol + Yam is the common name for some plant species in the genus
Dioscorea (family Dioscoreaceae) that form edible tubers.
• Decreased glucose utilization by cells = ↑ blood sugar.
+ These are perennial herbaceous vines cultivated for the
o Enhances gluconeogenesis consumption of their starchy tubers in Africa, Asia, Latin America,
the Caribbean and Oceania.
• It contributes to the maintenance of blood pressure by augmenting
+ There are many cultivars of yam. Although the sweet potato
the constrictive effects of catecholamines on blood vessels.
(Ipomoea batatas) has also been referred to as a yam in parts of
the United States and Canada, it is not part of the family
• activates anti-stress and anti-inflammatory pathways
Dioscoreaceae, rather it is in the Morning glory family
Convolvulaceae
Diurnal rhythm
How to control Stress to Maintain Adrenal Gland Health
-the peak of cortisol production is in the morning, usually around 8-9
am. The trough values are seen at approximately 10-11pm 1. Take a yoga class or learn some meditation techniques to help calm
your mind and take you out of the "fight or flight" response.

Practice slow, deep breathing techniques to slow your heart rate


and ease any tension or anxiety in your body.

+ Use herbs like Eleutherococcus (150 mg daily) or Ashwagandha


(250 mg daily) to support adrenal function and increase your ability
to deal with stress.

+ Ashwagandha is a traditional Indian herb that has been used for


centuries to support feelings of well-being.

Risks of Long-Term Stress on Adrenal Glands + Eleutherococcus is an Asian herb that provides antioxidants and
other nutrients to support immune health and reduce the effects of
1. Cortisol continually released from the adrenal glands in response to stress on the body.
chronic stress can damage body tissues.
Adrenocorticotropin hormone (ACTH):
2. Long-term adrenal stimulation can lead to high blood pressure and
stomach ulcers and deplete white blood cell levels, increasing your + Stimulates the adrenal gland to produce several related steroid
risk of infection. hormones

3. The adrenal glands themselves can become unable to produce • Corticotropins:


sufficient levels of cortisol to deal with the constant stress being
experienced. • Adrenocorticotropic hormone (ACTH), released under influence
of hypothalamic Corticotropin-Releasing Hormone (CRH)
Symptoms of poor adrenal function include fatigue, muscle aches and
low blood sugar. • Beta-endorphin, released under influence of hypothalamic
Corticotropin-Releasing Hormone (CRH)]

1. Primary Hypercortisolism 1. Primary Hypocortisolism

• Adrenal adenoma or • Atrophy of adrenal gland,


carcinoma autoimmune disease, TB,
prolonged high dosage
• Exogenous administration cortisol
of cortisol
2. Secondary Hypocortisolism
• Cushing Syndrome
• Pituitary hypofunction
Symptoms of Cushing:

Increased therapy serum


cortisol, decreased ACTH,
Weight gain in face (moon face)
and abdomen, buffalo hump
back, thinning of skin, easy
bruising, hypertension, muscle
wasting, decreased immune
Meaning of DHEA response
• Dehydroepiandrosterone, a hormone precursor, exists naturally 2. Secondary
in yams. Claimed to enhance immunity, memory, and neural Hypercortisolism
functioning; hamper osteoporosis; combat atherosclerosis,
hyperglycemia, and cancer.

• Being researched as a treatment for depression, arthritis, CUSHING'S SYNDROME


asthma, lupus erythematosus, and fraility ( moral weakness)
in the elderly. described by Harvey Cushing (1930s)
• Not for pregnant or nursing women, children, or patients with 1. Cushing's Disease - increase in cortisol production caused by
breast, uterine, prostate, or ovarian cancers or prostate excessive development and activity of the pituitary gland.
enlargement; can cause irregular heartbeats, insomnia, anxiety,
acne. 2. Cushing's Syndrome -increase in cortisol production as a result of
tumors which produce either excessive ACTH or cortisol

BERNADETTE N. VALDEZ 12 A.Y. 2022-2023 | BSMLS 3 | CC2


• Hypertension Primary Secondary

• Osteoporosis Adrenal Glands Pituitary

• Immune suppression • High ACTH • Low ACTH

o Inhibits phospholipase A2 • High MSH • Low MSH


o Inhibits IL-2
• High K+, high H+ (metab. • K+ok, H+ok
o Inhibits histamine
Acidosis)
• Hypopigmentation
• Muscle weakness with thin extremities • Hyperpigmentation
• hypoglycemia
• Moon face, buffalo humps and truncal obesity • hypoglycemia

• Abdominal striae (due to impaired collagen synthesis "thinning of


skin") Addison’s Disease Hypocortisolism or Primary Adrenal
Insufficiency
Cushing’s Syndrome or Hypercortisolism
Hyposecretion of glucocorticoids and mineral
Hypersecretion of cortisone; may be caused by an corticoids;
ACTH releasing tumor in pituitary
Symptoms- wt loss, fatigue,
Symptoms: trunkal obesity and moon face, dizziness, changes in mood and
emotional instability personality, low levels of plasma
glucose and Na+ levels, high levels
Treatment: removal of adrenal gland and hormone of K+
replacement
Treatment- corticosteroid replacement therapy

President of the US: John F.


Kennedy

Primary Aldosteronism (Conn's Syndrome)

→occurs when there is a small tumor of the zona glomerulosa cells and
secretes large amounts of aldosterone

→in a few instances, hyperplastic adrenal cortices secrete aldosterone


rather than cortisol

• Hypokalemia

Addison's Disease • slight increase in extracellular fluid volume and blood volume

• 1st described by Thomas Edison in 1855 • very slight increase in plasma sodium concentration (usually not
more than a 4 to 6 mEq/L increase)
• A disorder characterized by a decreased in the production of
CORTISOL or other steroids. • hypertension

• May be due to: Other Diseases of the Adrenals

o Defect in the synthesis of hormones in adrenal glands + Congenital adrenal hyperplasia (CAH) refers to any of several
autosomal recessive diseases resulting from mutations of genes
o Low ACTH production due to damage to the hypothalamus or for enzymes mediating the biochemical steps of production of
pituitary cortisol from cholesterol by the adrenal glands (steroidogenesis)

+ A paraganglioma is a rare neuroendocrine neoplasm that may


develop at various body sites (including the head, neck, thorax and
abdomen
BERNADETTE N. VALDEZ 13 A.Y. 2022-2023 | BSMLS 3 | CC2
Hormones Regulated by the Hypothalamic/Pituitary System + In addition, if baseline cortisol is very low, this test should be
avoided, as it could trigger an Addisonian crisis.
Pituitary Stimulating Hypothalamic Releasing
Hormone Procedure : Insulin Tolerance Test
Hormone Hormone
1. The doctor will draw blood to measure the cortisol level.
Thyroid Thyroid-stimulating Thyrotropin-releasing 2. Next, insulin is injected in order to lower your blood glucose.
hormones T4, hormone (TSH) hormone (TRH)
T3 3. Blood will be drawn periodically to measure cortisol as glucose level
drops.

Cortisol Adrenocorticotropin Corticotropin-releasing 4. Low blood glucose is a powerful stimulus to the pituitary to
hormone (ACTH) factor (CRF) produce ACTH, which leads to high cortisol levels.

+ Sweating, rapid heart beat, and hunger are normal responses to


Estrogen or Follicle-stimulating Luteinizing hormone- low glucose.
testosterone hormone (FSH), releasing hormone
luteinizing hormone (LHRH) or gonadotropin- + Once the blood sugar drops sufficiently and blood is collected, the
(LH) releasing hormone test is stopped by feeding you juice and snacks.
(GnRH)

Estrogen or Follicle-stimulating Luteinizing hormone- CRH Stimulation Test


testosterone hormone (FSH), releasing hormone
luteinizing hormone (LHRH) or gonadotropin- + CRH is the acronym for corticotropin-releasing hormone.
(LH) releasing hormone
+ CRH causes the pituitary gland to secrete ACTH, which in turn
(GnRH)
causes the adrenal glands to secrete cortisol.

Insulinlike Growth hormone Growth hormone- + The doctor will draw blood and measure the cortisol level.
growth releasing hormone
+ Next, synthetic CRH is injected into your bloodstream.
factor-I (IGF- (GHRH)
I) + Blood cortisol is measured every 30 minutes for about an hour and
a half after the injection.

CRH stimulation test Interpretation


Diagnosis
1. If CRH injection causes an ACTH response, but no cortisol
Baseline Laboratory Testing
response, the pituitary is functioning but the adrenal glands are
1. Measurement of cortisol and ACTH levels. ACTH is the acronym for not.
adrenocorticotropin hormone.
+ Such results are consistent with the diagnosis of primary
• ACTH is necessary for the adrenal glands to produce cortisol and adrenal insufficiency or Addison’s disease.
other hormones.
2. If CRH injection does not generate ACTH response, the problem
is the pituitary gland (secondary adrenal insufficiency).
• Cortisol levels follow a natural cycle throughout the day- high in
the morning ( 8AM, blood test should be done.) + CRH injection produces a delayed ACTH response, the problem is
the hypothalamus.

Laboratory Diagnosis for Primary Adrenal Insufficiency or


Addison’s Disease
Other Methods of Diagnosis
+ ACTH Stimulation Test
Imaging Tests: CT and MRI Scans
1. Blood is collected and cortisol and ACTH are measured.
+ Shape and size of each gland and determine if their appearance
2. Cosyntropin (a synthetic derivative of ACTH) is injected. is normal or if something may be wrong.

3. Blood is collected again to re-evaluate the cortisol level. + The imaging tests can support a diagnosis of adrenal
insufficiency.
Note: This is done twice: 30 and 60 minutes after the injection.
+ The hormone tests are more reliable diagnosis, imaging tests
A normal response after cosyntropin injection is an increased cortisol can provide further supporting information.
level.
Treatment of Addison’s Disease
Additional Test for Primary Adrenal Insufficiency or Addison’s
Disease + Replacement of cortisol with an oral synthetic glucocorticoid
given 2X a day
Insulin Tolerance Test
+ Generic drug names for glucocorticoids include hydrocortisone,
+ Considered as the “gold standard” test for diagnosing adrenal prednisone, and dexamethasone.
insufficiency.
+ The purpose is to give you the minimum amount of glucocorticoid
+ It is potentially dangerous and only should be performed by needed to replace body’s normal cortisol production—taking too
experienced physicians (usually endocrinologists). much can cause its own problems, such as weight gain and even
diabetes.
+ It is considered unsafe to perform this test on people with ischemic
heart disease or epilepsy. + Aldosterone is replaced with an oral mineralcorticoid.

+ The generic drug name is fludrocortisone. Increase salt intake.

BERNADETTE N. VALDEZ 14 A.Y. 2022-2023 | BSMLS 3 | CC2

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