Endocrine pathophysiology: hypothalamus, pituitary, thyroid and adrenal

Question 1

Which hormones does the anterior pituitary secrete?

Answer 1

Anterior pituitary secretes:
* Growth hormone
* Follicle stimulating hormone
* Luteinizing hormone
* Adrenocorticotrophic hormone
* Thyroid stimulating hormone
* Prolactin

Question 2

Which peptide hormones does the posterior pituitary secrete?

Answer 2

Posterior pituitary secretes:
* Oxytocin
* Vasopressin (antidiuretic hormone)

Question 3

Neurones send axons down from the ______________

Answer 3

Neurones send axons down from the hypothalamus

Question 4

The anterior pituitary is ectodermal in origin, why is this significant?

Answer 4

The anterior pituitary is ectodermal in origin, this is significant because it connects the anterior pituitary’s functions with the nervous and endocrine systems. It highlights the relationship these systems have to regulate processes/

Question 5

How is the hypothalamus connected to the anterior pituitary?

Answer 5

The hypothalamus is connected to the anterior pituitary by the hypothalamic-pituitary portal system (blood vessels)

Question 6

How does the hypothalamus regulate the anterior pituitary?

Answer 6

The hypothalamus regulates the anterior pituitary by releasing trophic hormones into the blood vessels that travel to the infundibulum to the anterior pituitary. These trophic hormones stimulate or inhibit the release of hormones from endocrine cells of the anterior pituitary.

Question 7

Antidiuretic hormone (vasopressin)

Answer 7

Antidiuretic hormone (ADH) (vasopressin):
* synthesised in the paraventricular nucleus (part of hypothalamus) and transported down the nerves in secretory vesicles before being released (exocytosis) under the influence of an appropriate stimulus
* Anti-diuretic hormone acts to maintain blood pressure, blood volume and tissue water content by controlling the amount of water and hence the concentration of urine excreted by the kidney

Question 8

Oxytocin

Answer 8

Oxytocin:
* synthesised in supraoptic nucleus (hypothalamus)
* involved in stimulating the uterus during parturition and ‘milk let-down’ in breasts

Question 9

The thyroid

Answer 9

Thyroid:
* largest endocrine gland in human body, situated in front of neck.
* regulated by the hypothalamus & anterior pituitary
* mandatory for body temperature, regulation, basal metabolic rate, metabolism, growth, reproductive system, etc.
* Secretes three hormones: Calcitonin, important in calcium homeostasis.
Triiodothyronine (T3) and thyroxine (T4), important in growth and metabolic function.

Question 10

What happens if there is an issue with the thyroid or its hormones?

Answer 10

If there is is an issue with the thyroid or its hormones:
* In absence of thyroid, hypothyroidism occurs.
* If hormones are deficient at birth, congenital abnormality occurs. Cretinism appears in children.
* Thyroid hormones, if deficient, are replaced at birth to avoid mental and growth retardation.
* If there is too much thyroid hormone, hyperthyroidisim occurs.

Question 11

What is the thyroid composed of?

Answer 11

The thyroid is composed of large number of follicles filled with coli. Major constituent glycoprotein is thyroglobulin, secreted by the cells into coli.

Question 12

The posterior pituitary has a neuronal developmental origin as a down-growth from diencephalon, why is this significant?

Answer 12

The posterior pituitary has a neuronal developmental origin as a down-growth from diencephalon. This is significant because the origin emphasizes the integration of neural and endocrine signalling.

Question 13

Where is thyroid hormone secreted from?

Answer 13

Thyroid hormone is secreted from the follicular cells

Question 14

How are thyroid hormones synthesized?

Answer 14

Thyroid hormone synthesis:
* Thyroid follicular cells take up iodide
– oxidize iodide to Iodine via hydroperoxidase
– covalently attach the iodine to the tyrosines of thyroglobulin within the lumen of the follicle

Question 15

Thyroid epithelial cells are organized into _________ that secrete thyroglobulin
(large glycoprotein, mw 660Kd) and accumulates in the follicles as “__________________”

Answer 15

Thyroid epithelial cells are organized into follicles that secrete thyroglobulin
(large glycoprotein, mw 660Kd) and accumulates in the follicles as “colloid”

Question 16

What happens when the thyroid is stimulated by TSH?

Answer 16

• On stimulation by TSH (from the anterior pituitary)
• Iodide is actively transported from the blood by the iodide pump, transport driven by electrochemical gradient.
• Iodide transported into the colloid of the follicular luman by a second transporter.
• Iodide interacts with accessible tyrosine residues of thyroglobulin.
• Intermediates MIT and DIT are formed
• Coupling of MIT and DIT produce T4 (x2 DIT) and T3 (x1 MIT and x1 DIT)
  – follicular cells endocytose the iodinated thyroglobulin
  – break it down in lysosomes
  – release the iodinated tyrosine derivatives as tetra- iodothyronine (thyroxine) (T4) or triiodothyronine (T3)

Question 17

What is total T4 level decreased in?

Answer 17

Total T4 level is decreased in:
* Premature infants
* Hypopituitarism
* Nephrotic syndrome
* Liver cirrhosis
* Starvation & severe protein energy malnutrition (PEM)
* Protein losing entropathy

Question 18

Facts about Thyroid hormones

Answer 18

Thyroid hormones:
* Lipophillic allows them to bind to blood serum proteins
* T4 less active than T3
* 99% of T3 and T4 are bound to plasma proteins (thyroid-binding globulin).
* 0.04% T4 and 0.4% T3 occur in free form (can enter target cells).
* They are excreted in the bile and urine.
* T4 has a half-life of 6-7 days; T3 has a half-life of 1-2 days.
* Oral absorption of T4 is 80% and T3 95%
* Readily absorbed from GIT and excreted in bile and urine.
* Some of the circulating T4 is deiodinated to T3, the more potent and rapidly acting form.
* 5:1 is the ratio of T4:T3 in thyroid.
* Thyroxine needs selenium and iodine> T3
* Iodine is required for synthesis

Question 19

Dietary sources of iodine

Answer 19

Dietary sources of iodine
* Iodized table salt
* dairy products,
* fish

Question 20

Iodine adult requirement?

Answer 20

Iodine adult requirement: 150 mg, increased to 200 mg in pregnancy.

Question 21

Role of Iodine in T4 and T3 formation

Answer 21

• Oxidation in cells by peroxidase enzyme
• Organification –binding of iodide with tyrosine in thyroid leading to formation of monoiodotyrosine and diiodotyrosine.
• Coupling of MIT and DIT to form T4 and T3, which are stored in gland. When required, released in blood by proteolysis.
  *

Question 22

How do thyroid hormones regulate body temperature?
What other effects do they have?

Answer 22

Thermogenesis: thyroid hormones **regulate body temperature in humans
uncouple ATP synthesis from metabolism
by increasing expression of uncoupling protein (UCP) : generates heat
*direct effect on mitochondria in brown adipose tissue and skeletal muscle
*may be most important role of T3/4 in humans
* increase glucose absorption in GI tract
* enhance lipolysis glycogenolysis and gluconeogenesis
* increased metabolism increases temp
* increase adrenoreceptor expression> potentiate adrenaline and noradrenaline response

Central effect: new evidence that T3/4 act at hypothalamus to:
*stimulate sympathetic output to brown fat (thermogenesis) and liver (gluconeogenesis)
*increase food intake
*regulate body weight (including seasonal changes)

Question 23

When stimulated to release ____________ ___________, follicular cells endocytose a portion of the colloid containing the iodinated thyroglobulin. Through the action of proteolytic enzymes within these cells, the thyroid hormones are released from the thyroidglobulin structure and actively transported in the blood.

Answer 23

When stimulated to release thyroid hormones, follicular cells endocytose a portion of the colloid containing the iodinated thyroglobulin. Through the action of proteolytic enzymes within these cells, the thyroid hormones are released from the thyroidglobulin structure and actively transported in the blood.

Question 24

How is thyroid hormone secretion regulated?

Answer 24

Thyroid hormone secretion is regulated by:
Thyroid stimulating hormone
Thyroid stimulating hormone is regulated by thryotrophin releasing hormone
Thyroid stimulating hormone secretion is inhibited by somatostatin.
Iodide consumption

Question 25

What can iodine deficiency cause?

Answer 25

Iodine deficiency can cause brain damage

Question 26

What is exophthalmos?

Answer 26

Exophthalmos is protruding eyeballs

Question 27

Hyperthyroidism:
* Cause
* Pathology
* Symptoms
* Treatment
* Treatment examples

Answer 27

Hyperthyroidism:
* Cause: excess production or secretion of thyroid hormones
* Pathology: overactive thyroid: large follicle cells, smaller colloid: increases reabsorption
* Symptoms: weight loss, increased HR, anxiety, insomnia, sweating, fatigue, nervousness, increased metabolism
* Treatment focuses on decreasing thyroid synthesis, thyroid release or reducing their effects.
* Treatment examples: Radioactive iodide, Thioureylenes, Iodide ions, beta-adrenoreceptor antagonists (beta blockers), thioamides

Question 28

Thyroid stimulating hormone secretion is inhibited by?

Answer 28

Thyroid stimulating hormone secretion is inhibited by:
* Dopamine
* Bromocriptine (t2d dopamine receptor aganosit)
* Somatostatin
* Corticosteroids

Question 29

Thyroid stimulating hormone secretion is stimulated by?

Answer 29

Thyroid stimulating hormone secretion is stimulated by:
* α-adrenergic agonists

Question 30

Hypothyroidism
* Cause
* Pathology
* Symptoms
* Treatment
* Treatment examples

Answer 30

Hypothyroidism
* Cause: deficient production or secretion of thyroid hormones
* Pathology: underactive thyroid: distended follicles, increased colloid, thin flat epithelial cells.
* Symptoms: tiredness, forgetfullness, puffy face and eyes, goiter, dry skin, cold intolerance, weight gain, bradycardia, changes to hair, constipation (digestive process slowed).
* Treatment: Focused on suppressing thyroid stimulating hormone secretion. Thyroid hormone replacement therapy: synthetic T3 or T4. Iodide if iodide deficiency is the cause.
* Treatment examples: Lyothryonine, Levothyroxine,
* Treatment side effects: Hyperthyroidism (or symptoms of hyperthyroidism).
Cardiovascular toxicity (tachyarrhythmias, angina, and infarction), diarrhoea
CNS stimulation
Insomnia.

Question 31

What does high TSH signify?

Answer 31

High TSH signifies that the body isn’t producing enough thyroid hormones. High TSH is a compensatory response by the body as an attempt to increase thyroid hormone production.

Question 32

Hypothyroidism treatment:
Levothyroxine

Answer 32

Levothyroxine:
* Synthetic levo isomer of T4.
* Oral and I/V preparations are available.
* Low cost & content uniformity.
* Better standardization & stability and long duration.
* Long half-life of T4(7 days)
* Facilitates maintenance of a steady physiologic replacement.

Question 33

Hypothyroidism treatment:
Liothyronine

Answer 33

Liothryonine:
* Synthetic L-T3.
* More difficult to monitor than T4.
* More expensive.
* Shorter half-life.
* Treatment of choice for Myxedema coma.
* Short term suppression of TSH.
* Greater risk of cardiotoxicity.

Question 34

What do the hyperthyroidism treatments focus on doing?

Answer 34

Hyperthyroidism treatments focus on:
* Inhibiting thyroid hormone synthesis (Thioamides)
* Inhibit iodide trapping [Ionic inhibitors]
* Inhibit hormone release
* Destroy thyroid tissue
* Inhibit peripheral conversion of T4 to T3
* Inhibit the peroxidase enzymes catalyzing the oxidation of iodide, iodination of thyroglubulin.
* Inhibit coupling reaction PTU also inhibits the peripheral deiodination of T4 to T3. Do not block uptake of iodine by gland.
* Delay in absorption
* Delay in onset 3-4 weeks, because formed T4 takes time to deplete, only further formation is stopped.

Question 35

Hyperthyroidism treatment: Radioactive iodide

Answer 35

Hyperthyroidism treatment: Radioactive iodide
* Ablation (removal of the thyroid gland)
* Iodide isotope taken orally> taken up by iodide pump on thyroid follicular cells
* Beta radiation is absorbed by the thyroid tissue and the hormone synthesizing cells are destroyed

Side effects: inflammation of the salivary glands.
dry mouth and changes to your taste.
a swollen or tender neck.
feeling flushed.
feeling sick

Considerations: limit other exposure to radiation. delayed effect 2-3 months