Endocrinology: Thyroid, Pancreas & Adrenal

Front 1

Describe the embryology of the thyroid.

Back 1

The thyroid develops as a downgrowth from the floor of the pharynx.
It's highly vascularised and bilobed with one lobe on either side of the trachea

Front 2

Describe the histology of the thyroid.

Back 2

The thyroid is made of a system of follicles each enclosing a fluid filled space.
Each follicle is lined with simple cuboidal epithelium which secretes thyroglobulin.
Surounding the follicles is a highly vascularized connective tussue with parafollicular cells

Front 3

What are parafollicular cells?

Back 3

These cells secrete calcitonin and reside in the connective tissue of the thyroid

Front 4

What is thyroglobulin?

Back 4

This is a colloid, jelly-like glycoprotein secreted by the cuboidal epithelial cells which line the thyroid follicles.
Its function is to produce the thyroid hormones thyroxine and triiodothyronine.
Each thyroglobulin molecule has 140 tyrosine amino acids which are used to bind with iodine.

Front 5

What is the main function of the thyroid?

Back 5

The accumulation of iodine

Front 6

How does the thyroid store iodine?
Describe the production of tri-iodothyronine [T3] and thyroxine [T4]

Back 6

An active iodine pump on the outside membrane of follicular cells takes in ingested iodide.
The iodide is then oxidized to iodine by peroxidase.
Iiodine binds with thyroglobulin through tyrosine to form mono- or diiodotyrosine.
Combining these forms either T3 or T4 (tri- and tetra-iodotyronine/thyroxine)

Front 7

Which hormone controls the uptake of iodine?

Back 7

Thyroid stimulating hormone. TSH also promotes release of the thyroid hormones (thyroxine).
The mechanism is dependent on a lysosomal protease released into the pinocytotic vesicles containing thyroglobulin

Front 8

How much iodine is needed daily? How much is stored in the thyroid?

Back 8

150ug of iodine per day is sufficient
The thyroid stores 4000ug in different forms

Front 9

How many thyroxine molecules can complex to one thyroglobulin?
What is the ratio of T3 to T4?

Back 9

5-6 thyroxine molecules for every one thyroglobulin.
There are 18 T4 for every one T3 molecule.
This implies that 90% of released hormones will be thyroxine T4 and 10% tri-iodothryonin T3

Front 10

Describe the nature of thyroid hormones secreted into the bloodstream

Back 10

The hormones are plasma-protein bound. Some of the T4 thyroxine is de-iodinated to T3.
Plasma half-life of thyroxine = 6 days
Plasma half-life of T3 = 1.3 days
T3 is also 40x more potent than T4 and so the net effect of the two is about equal

Front 11

Describe the nature of the thyroid hormones once inside the target cell

Back 11

Both hormones activate transport proteins on the cell membrane which allow them to enter the cell and activate nuclear thyroid receptors to alter DNA transcription
Thyroxine T4 is deiodinated to T3 (80%) or inactive reverse T3 (20%)
90% of active thyroid hormone is T3.

Front 12

What is the main function of the thyroid hormones? How and where is this achieved?

Back 12

To increase or maintain the basal metabolic rate through increased proteins synthesis.
It can be raised up to 60-100% in almost all body tissues.

Front 13

How do thyroid hormones increase protein synthesis in the body tissues?

Back 13

RNA synthesis increases leading to production of ribosomes & mRNA
Also increase in metabolic enzymes, number of mitochondria and Na/K pump activity

Front 14

How do thyroid hormones generally affect growth & maturation?

Back 14

In children, thyroid hormones have a synergistic effect with somatomedins (from STH).
Thyroid hormones also influence development of the CNS and sexual maturity

Front 15

What specific effects do thyroid hormones have on the body systems?
Hint: metabolism of which molecules, circulatory system, GIT, CNS

Back 15

Carbohydrate/fat metabolism increased
Increased levels of lipids in the liver/blood
Increased appetite
Increased cardiac output (and systolic pulse pressure) may lead to hypertension
Enhanced GIT secretion (may lead to diarrhoea)
CNS effects = nervousness, irritability and muscle tremor

Front 16

Describe hypothyroidism

Back 16

Underactive thyroid
Cretinism in children = poor growth, mental retardation, easily treated if spotted early
Myxoedema in adults = hair loss, muscle stiffness, lethargy, decreased mental ability, widespread subcutaneous oedema, goitre, hibernatino coma, advanced arteriosclerosis, death

Front 17

Describe Hyperthyroidism

Back 17

An overactive thyroid (5-15x) associated with goitre, hypertension , raised body temperature, weight loss, hyperactivity.
Mostly caused by Graves' disease

Front 18

When can a goitre occur?

Back 18

Hyperthyroidism when there is an overactive thyroid
Hypothyroidism if there is a compensatory TSH increase

Front 19

Describe Graves' disease

Back 19

autoimmune disease where there is an IgG antibody to the TSH receptors on the thyroid gland
Action of the antibody is to stimulate the production and secretion of the thyroid hormones
Symptoms = exophthalmos (protrusion of the eyes) due to retro-orbital oedema & fat deposition

Front 20

What are the two major hormones produced by the pancreas? Which cells secrete these hormones? What is the target of these hormones?

Back 20

Insulin & Glucagon are both secreted by the Islets of Langerhans.
Both hormones target the liver

Front 21

Where are the Islets of Langerhans?

Back 21

these endocrine cells are scattered throughout the exocrine acinar tissue of the pancreas.
there are around 2 million islets

Front 22

Describe the histology of the Islets of Langerhan

Back 22

In the islets, the cells are arranged in irregular chains and cords separated by rich blood supply
Three cell types exist in the Islets.

Front 23

The Islets of Langerhans contain three cell types. Discuss

Back 23

Peripheral alpha cells (20%) secrete glucagon
Beta cells (70%) secrete insulin
Delta cells (10%) secrete somatostatin

Front 24

What is somatostatin?

Back 24

Hormone secreted by the delta cells of the Islet of Langerhans.
It is identical to the growth hormone release inhibiting hormone (GHRIH)

Front 25

Describe how Diabetes mellitus relates to insulin.

Back 25

Symptom of diabetes mellitus =
Hyperglycaemia in which blood glucose rises over the renal threshold --> glucose in the urine
Insulin injection causes a fall in blood glucose levels

Front 26

What is Insulin?
What are the three effects insulin has on carbohydrates?

Back 26

A small protein with a plasma half-life of 10-15 min.
Glucose transport is enhanced particularly in the muscle/liver
Excess glucose is converted to glycogen and fatty acids in the liver
Reduced production of glucose from amino acids/glycerol (gluconeogenesis)

Front 27

What occurs in the absence of insulin?

Back 27

Free fatty acids and glycerol are released into the blood from adipose tissue.
These reach the liver and become triglycerides which are broken down into acetyl coenzyme A

Front 28

Discuss the development of Ketosis.

Back 28

In the absence of glucose to run the Citric Acid Cycle, acetyl coenzyme A is converted into acetone and ketone bodies.
Accumulation of ketone bodies causes ketosis, acidosis and diabetic coma

Front 29

Describe glucagon.
What are its metabolic effects?

Back 29

Glucagon is a protein with a plasma half-life under 10 min.
It is synthesised as proglucagon.
It promotes glycogenolysis in the liver, gluconeogenesis and lipolysis (adipose tissue)

Front 30

At what blood glucose levels does insulin/glucagon start being released

Back 30

At 100 mg/100ml, insulin is released.
At 70 mg/100 glucagon is secreted

Front 31

What are the two cell types of the adrenal glands?

Back 31

90% cortical layer (mesodermal origin)
10 % medullary layer (ectodermal origin)

Front 32

Describe the histology of the adrenal medulla

Back 32

Also known as chromaffin tissue, the cells are modified postganglionic neurons which are neurosecretory.
There are also associated myelinated fibers of the sympathetic nervous system

Front 33

Describe the general function of the adrenal medulla

Back 33

Secretes adrenalin (80%) and noradrenalin (20%) which are connected to the "fight or flight" response

Front 34

What effects does adrenalin have?

Back 34

Direct rapid sympathetic stimulation including increased heart rate, increased blood flow to the brain/muscle (mental alertness), bronchodilation, decreased flow to the skin/GIT, incrased lipolysis/glycogenolysis

Front 35

Recall the three zones of the adrenal cortex

Back 35

Zona glomerulosa = outermost
Zona fasciculata = largest layer with radiating cords of cells
Zona reticularis = inner layer next to the medulla

Front 36

The adrenal cortex is under the control of what hormone?

Back 36

ACTH adrenocorticotrophic hormone

Front 37

What are the three general groups of the steroid hormones of the adrenal cortex?

Back 37

Glucocorticoids (ie cortisol)
Mineralocorticoids (ie aldosterone/corticosterone)
Androgens (ie androstenedione)

Front 38

The major glucocorticoid hormone is _____. Which part of the adneral cortex is it secreted from?

Back 38

95% of secreted glucocorticoids is hydrocortisone AKA cortisol. It's secreted from the zona fasiculata

Front 39

What are the two major and two minor hormones of the adrenal cortex? What group do they belong to and what part of the cortex are they secreted from

Back 39

Cortisol (major glucocorticoid) from the zona fasiculata
Aldosterone (major mineralcorticoid) zona glomerulosa
Corticosterone (minor mineralcorticoid)
Androgen (minor androgen)

Front 40

How does the secretion of cortisol effect blood?

Back 40

Hydrocortisone stimulates liver gluconeogenesis leading to elevated blood glucose levels. It also promotes protein breakdown except in the liver. This leads to increase in blood protein and amino acid levels.

Front 41

The major function of cortisol is related to ______.

Back 41

Any stresses to the body will cause ACTH to be secreted followed by cortisol

Front 42

The major mineralocorticoid is ____. Which part of the adrenal cortex is it secreted from?

Back 42

95% of secreted mineralocorticoid is aldosterone secreted from the zona glomerulosa

Front 43

What is the major function(s) of aldosterone in the kidney?

Back 43

Aldosterone increases sodium reabsorption in the distal convoluted tubule and collecting duct.
It promotes secreted of potassium and hydrogen ions.

Front 44

Describe the mechanism of controlling aldosterone secretion.

Back 44

When blood volume falls, aldosterone is secreted with antidiuretic hormone ADH.
The renin-angiotensin system may play a greater part in aldosterone release than ACTH

Front 45

What is androstenedione?

Back 45

An androgen secreted by both sexes and is a precursor to sex hormones.
Females - mild anabolic effect
Males - masked by testosterone

Front 46

Describe Addison's disease.
Causes, Effect, Symptoms, Treatment

Back 46

Causes = congenital hypoactivity, autoimmune destruction, tuberculosis
Effect = adrenal cortex hypoactivity in the form of glucocorticoid insufficiency
Symptoms = hypotension, sodium/fluid loss, hypoglycaemia, coma
Slower onset = increased ACTH secretion --> MSH release
Treatment = replacement therapy with hydrocortisone

Front 47

Describe Conn's Syndome
Cause, Effect, Symptoms, Treatment

Back 47

Cause = tumor of the zona glomerulosa
Effect = increased secretion of aldosterone (hyperaldosteronism)
Symptoms = sodium/fluid retension, overstimulation of renin-angiotensin system, muscle weakness from potassium deficiency
Treatment = tumor removal & hormone replacement therapy

Front 48

Describe Cushing's Syndrome
Cause, Effect, Symptoms, Treatment

Back 48

Cause = ACTH overproduction/ pituitary tumor, adrenal cortical tumor
Effect = increased secretion of glucocorticoids
Symptoms = hyperglycaemia leading to polyuria/polydipsia, muscle loss and osteoporosis due to protein use for gluconeogenesis
Untreated = death by CVS disease, diabetes mellitus
Treatment = removal of tumor & hormone replacement therapy