#notes 2020

[mariesstudycorner]

The endocrine system physiology

Part 4 (last part)

In this chapter we're going to talk about:

1. Thyroid Hormones.

2. Insulin & Glucagon.

Thyroid Hormones:

T4 or Thyroxine

T3 or Triiodothyronine

Calcitonin.

T4 & T3 :

T4 and T3 are tyrosine based hormones. Produced by the follicular cells (thyrocytes).

Synthesis:

Iodide (I-) is taken from the bloodstream by follicular cells to the colloid where it gets oxidized to iodine (I) then it combines with thyroglobulin to form MIT (monoiodotyrosine) and DIT (diiodotyrosine) .

Two DIT molecules combine to form T4 while MIT & DIT combine to form T3.

Iodinated thyroglobulin is transported back to the follicular cells and is cleaved by lysosomes.

T4 & T3 are then released into the circulation through MCT transporter.

Regulation:

TRH ➡ TSH ➡ THYROID ➡T4 & T3

➡ By:

⏫Iodide pumping

⏫ Iodination

⏫Thyroglobulin synthesis.

⏫ release of thyroid hormone.

T4 & T3 bind in the plasma to plasma proteins such as:

TBG or Thyroxine binding globulin

Albumin

Transthyretin.

The bound form is the inactive form. While free T3 & T4 form the active form that works on cells.

Note that inside the cell T4 is coverted to T3 by 5-Iodinase.

Effects:

⏫ Basal metabolic rate.

⏫Activation of sympathetic nervous system.

⏫long bone growth

⏫Hair follicle growth

Regulation of body temperature & weight.

Brain development.

Insulin:

Is a peptide hormone produced and secreted by Beta cells which are cells in the islets of langerhans

Synthesis:

Single polypeptide (preproinsulin) ➡ proinsulin (which has 3 chains : peptide A, peptide B and peptide C in between.

Proinsulin gets cleaved on two positions leaving the C chain alone (AWW :-( )

Two disulfide bonds connect The B chain and the A chain to form INSULIN

Effects:

⏬⏬ Blood sugar levels.

How :

In the liver:

Activates the formation of glycogen

(glucose ➡ glycogen)

In adipose tissue:

Activates glycolysis

In skeletal muscles :

stimulates amino acids and glucose uptake into muscle cells ➡ protein production and muscle growth.

Inhibites:

▶ Gluconeogenesis

▶ lipolysis.

Glucagon:

A hormone produced by alpha cells which are cells in the islets of langerhans.

Works by ⏫⏫ blood suger ▶ in situations like: fasting.

And it does that by:

▶ activation of gluconeogenesis & glycogenolysis

▶ activation of lipolysis.

Glucagon is a catabolic hormone which means it promotes the breaking down of large storage molecules inside certain tissues into small energy molecules in the blood.

Glucagon stimulators:

▶ low blood suger

▶ adrenaline

▶ cholecystokinin

Glucagon inhibitors:

▶ high blood sugar

▶ somatostatin

▶GH

Part 1

Part 2

Part 3

🌸- 🌸-🌸-🌸-🌸-🌸-🌸-🌸-🌸

Hello 🌸🍃

With this we're done with a good part of endocrine physiology!Next, we're going to start with clinical cases and diseases related to the endocrine system (aka we're gonna get serious SERIOUS xD) I hope you find this helpful in reviewing or studying ☺

Thank you so much🌸🍃

Marie🌸

[mariesstudycorner]

Diseases of the thyroid gland

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Chapter 1 : Hyperthyroidism.

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We're going to discuss:

What is Hyperthyroidism?

Causes of hyperthyroidism?

Clinical manifestation.

Lab works

Other investigations

Treatment

What is a thyroid storm?

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What is hyperthyroidism?

It is a state where there is ⏫ synthesis of the thyroid hormones : T4 & T3 ➡ ⏫ levels of these hormones in the blood.

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Causes:

Graves' disease (diffuse toxic goiter)

Plummer disease (multinodular toxic goiter)

Toxic thyroid adenoma (single nodule)

Subacute thyroiditis & Hashimoto thyroiditis. (Transient hyperthyroidism)

Fetal thyrotoxicosis

Other rare causes:

- postpartum thyroiditis (transiet)

- Iodine-induced hyperthyroidism.

- Excessive dose of levothyroxine.

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1. Graves' disease:

Autoimmune disorder.

Thyroid-stimulating immunoglobulin TSI (IgG) binds to the TSH receptors on the thyroid cells ➡ triggers the synthesis of excess thyroid hormones.

Younger women >

Goiter : every thyroid cell is hyperfunctioning so it affects ALL parts of the gland >> diffuse. Non tender

2. Plummer disease:

Starts with chronic lack of dietary Iodine ➡ low levels of T4 ➡ triggers high levels of TSH ➡ Thyroid hypertrophy & hyperplasia.

The growth is uneven >> nodules.

These nodules become toxic when a genetic mutation happens and causes TSH recepters to be constantly ON. >> ⏫⏫⏫ T4/T3.

That elevation acts as a negative feed back to the pituitary gland to secrete less TSH >> the rest of the thyroid is not functioning >> atrophy .

3. Adenoma : 2% of all cases.

4. Thyroiditis:

Inflammation of the thyroid gland >> releasing the previously synthesized thyroid hormones ➡ temporary ⏫⏫ in circulating T4/T3.

A hypothyoid phase may follow.

5. Fetal thyrotoxicosis:

Classically in an infant born to a mother with Graves disease. TSI are IgG and can cross the placenta.

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Clinical manifestations : Symptoms

Nervousness.

Irritability

Insomnia.

Fine tremor

Hyperactivity

Heat intolerance & excessive sweating.

Weight loss despite increased appetite.

Proximal muscle weakness.

Palpitations.

Signs:

On the thyroid glad:

Graves' : diffusely enlarged. symmetric . Nontender gland. Bruit may be present.

Subacute thyroiditis: exquisitely tender. Diffusely enlarged (viral illness)

Plummer: bump. Irregular . Asymmetric gland.

Toxic adenoma: single nodule with atrophic gland.

Extrathyroidal:

Eyes: - Edema of the extraocular muscles ➡ proptosis (hallmark of Graves') - lid lag - lid retraction

- corneal exposure ➡ excessive tearing.

Cardiovascular effects: ⏫ Blood pressure.

- Arrhythmias : Sinus tachycardia - Atrial fibrillation

Skin: Warm & moist - pretibial myxedema (specific to Graves')

Neurologic: Hyperreflexia - fine tremor.

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Lab works:

⏬⏬ TSH

⏫⏫ free T4 & FT3

Other investigations:

1. RAIU:

Radioactive iodine uptake scan.

Useful to differentiate the causes of hyperthyroidisim.

If the uptake is ⏫look for the findings (forms):

Diffuse ( homogeneous) ➡ Graves'

Heterogeneous (multiple nodules of ⏫uptake) ➡ plummer

Focal (one area of ⏫ uptake w/suppression of rest of the gland) ➡ adenoma (hot nodule)

No RAIU findings (⏬⏬uptake) we look at serum thyroglobulin:

⏫ ➡ Thyroiditis /iodine exposure / extraglandular production

⏬ ➡ Exogenous thyroid hormone.

2. Radioactive T3 uptake:

Gives information about the status of TBG

We give resin to the patient + radioactive T3.

Radioactive T3 will bind to resin only when there is no space left on TBG.

SO WHEN THERE IS ⏫T4 ➡ no available seats on TBG ➡ more radioactive T3 will bind to resin ➡ ⏫ radioactive uptake.

The importance of this is to know if there is true hyperthyroidism or increased TBG

High TBG production ➡ low radioactive T3 uptake.

3. Free thyroxine index (FTI) :

Proportional for FREE T4 concentration.

Calculated to correct for the changes in the thyroid binding proteins.

FTI : ( Radioactive T3 uptake × serum total T4) /100

FTI : (patient's radioactive T3 uptake / normal radioactive T3 uptake) × total T4

Normal : 4-11

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Treatment :

1. Pharmacologic:

🎐Immediate control of adrenergic symptoms:

B-blockers (propanolol)

🎐 Anti-thyroid drugs: Thionamides

Methimazole:

1- Inhibits thyroid peroxidase ➡ stops the oxidation of Iodide into Iodine

2- Inhibits the coupling of DIT and MIT to form T3 & T4.

PTU (propylthiouracil) :

Shares the same mechanism with Methimazole except that PTU works on the peripheral tissue by

- Inhibiting the converting of T4 into T3.

⚠ Watch for side effects⚠

⚠Agranulocytosis

⚠Skin rash

⚠Arthralgias

Specific ⚠ for PTU is:

Hepatotoxicity.

During pregnancy:

Both can cross the placenta but it is preferred to give:

PTU at the first trimester

Methimazole at the 2nd and 3rd trimester.

Sodium ipodate or iopanoic:

Lowers serum T3 & T4 levels and causes rapid improvement of hyperthyroidism.

Appropriate for acute management of severe hyperthyroidism that's not responding to conventional therapy.

2. RAI ; Radioactive iodine:

Causes destruction of thyroid follicular cells.

Uses IODINE 131

Most common for: Graves' disease & multi-nodular goiter.

If the first dose doesn't control the hyperthyroidism within 6 to 12 months then administer another dose.

✔ Selected pations ✔

✔ Elderly patients w/Graves disease.

✔ Solitary toxic nodule

✔ Patients w/graves disease in whom therapy w/antithyroid drugs fails.

⚠ Warning ⚠

⚠ Hypothyroidism over time in the majority patients. ⚠

Note :

Ophthalmopathy can worsen after RAI prevent that by prophylactic therapy w/prednisone in high-risk patients.

3. Surgery:

Very effective

Only 1% of patients are treated by it.

Often reserved w/patients that have large goiters ; more common in toxic multinodular goiter.

⚠ Side Effects ⚠

⚠ permanent hypothyroidism 30%

⚠Recurrent laryngeal nerve palsy 1%

⚠Permanent hypoparathyroidism 1%

⚠ watch for hypocalcemia (due to inflammation/removal of the parathyroid glands)

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Treatment plan :

Immediate control of adrenergic symptoms (of any cause) ➡ (beta-blocker) propanolol

Non-pregnant patients w/Graves' disease: beta blocker + Methimazole Taper B-blocker after 4-8 weeks (once methimazole takes effect) give methimazole for 1-2 years then measure TSI at 12 months : ✔ Absent ➡ discontinue therapy. ✔ Relapse ➡ Resume methimazole for 1 more year or radioactive therapy.

Pregnant patients w/Graves' disease : Endocrinology consult is indicated before starting treatment.

Toxic multinodular goiter or Toxic adenoma: RAI or surgery Methimazole pretherapy for surgery and before RAI in selected patients.

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What is a thyroid storm?

Rare, life-threatening complication of thyrotoxicosis.

Characterized by an acute exacerbation of the manifestations of hyperthyroidism.

There's usually a precipitating factor: infection, DKA, stress (Surgery, illness, childbirth)

High mortality rate

Clinical manifestations:

✔ Marked fever

✔ Tachycardia

✔ agitation

✔ Confusion

✔ GI symptoms (nausea , vomiting , diarrhea)

Treatment:

Provide supportive therapy : IV fluids , cooling blankets and glucose

Give antithyroid agents (PTU preferred due to its peripheral effects) followed w/iodine.

B-blockers

Dexamethazone (steroids) to impair peripheral generation of T3 from T4 and to provide adrenal support.

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Wow that was a long one XD

I tried to include all the important stuff :)

Resources:

First-aid

Kaplan lecture notes 2019

Medscape

Pocket medicine

Step-up to medicine.