Week 3 - Lipids, Thyroid, Adrenal, & Hypertension Flashcards
List some of the risk factors for atherosclerosis.
- Age: Men > 45; Women > 55
- Elevated LDL-C
- Low HDL -C
- Family history
- Hypertension
- Diabetes
- Smoking
- Obesity
- Others
Grave’s disease presents with increased/decreased thyroid activity?
Increased
Which three conditions result in an increased thyroid scan?
- Grave’s disease
- Toxic adenoma
- Toxic multinodular goiter
Which three conditions result in a decreased thyroid scan?
- Thyroiditis
- Hashimoto’s
- Iodide excess
What are the three types of thyroiditis?
- Subacute (viral) {painful}
- Painless (silent)
- Post-partum
Thyroid peroxidase (TPO) antibodies are present in which conditions?
- Thyroiditis (except for subacute {viral}).
- Hashimoto’s
- Grave’s disease
TSH receptor antibodies are present in which conditions?
Grave’s disease.
What is the commonest cause of hyperthyroidism?
Grave’s disease.
What is the ratio of females:males affected by Grave’s disease?
7:1
What three extra-thyroidal autoimmune manifestations may present with Grave’s disease?
- Orbitopathy (Ophthalmopathy)
- Pretibial myxedema
- Acropchy
What is apathetic thyrotoxicosis?
Atypical presentation found in the elderly population which presents with atrial fibrillation, weight loss, anorexia, and few other typically hyperthyroid signs.
Which thyroid condition predominates the presentation of autoimmune diseases?
Grave’s disease.
What percentage of Graves’ patients have ophthalmopathy? What percentage actually present symptoms of ophthalmopathy?
> 90-95%
1/3 - 2/3 patients have clinical signs.
How does pretibial myxedema (Grave’s dermopathy) present?
A waxy discolouration and thickening of the skin covering the shins. [Painless]
What is acropachy?
Clubbing of the fingers.
What is bruit?
The unusual sound of blood rushing past an obstruction.
How can you tell Grave’s disease from Hashimoto’s?
Both Hashimoto’s and Grave’s disease will have anti-TPO antibodies. However, only Grave’s disease will have TSH-receptor antibodies.
What are two variants of Hashimoto’s thyroiditis?
Silent Thyroiditis, Post-partum thyroiditis.
How can you differentiate between toxic nodules and Grave’s disease?
Toxic nodules present with no autoimmune signs.
What is primary prevention?
The prevention of events (stroke, MI) before they occur.
What is secondary prevention?
The prevention of additional events in someone with known disease.
What is the job of HDL (makes it “good” cholesterol).
HDL removes excess cholesterol from the cells of the body and returns it to the liver in a process called reverse cholesterol transport.
What are apolipoproteins and what do they do?
They are the surface components of all lipoproteins which act:
- To maintain structure; aid in solubilization.
- As ligands to mediate uptake.
- As cofactors for enzymes.
As chylomicrons –> VLDL –> LDL –> HDL what changes in constituting proportions change?
Proportion of protein, phospholipids, and cholesterol increase while triglycerides decrease to zero.
What is the prevalence of genetic lipid disorders?
1/40 people
______ dyslipidemia lipid disorders are primary.
______ dyslipidemia lipid disorder are secondary.
Primary, Secondary
What does HAART stand for?
Highly Active Anti-Retroviral Therapy
What is the most common genetic lipid disorder?
What is its prevalence?
What is the main defect with this disorder?
What does this defect lead to?
Familial Combined Hyperlipidemia
1/50 - 1/100
Overproduction of apoB100 which leads to an increased number of VLDL particles in the circulation. This increases the level of triglycerides and cholesterol in the blood.
What is the main defect in Familial Hypertriglyceridemia?
What is its prevalence?
Overproduction of triglyceride-enriched VLDL causes a high concentration of triglycerides with normal cholesterol levels.
1/5000
What is lipoprotein lipase?
What cofactor is necessary for it to work?
An enzyme which aids the uptake of cholesterol, lipids, and other chylomicron constituents into the cell.
ApoC2 is a required cofactor.
What does lipoprotein lipase deficiency cause?
What is this diseases prevalence?
This deficiency causes decreased triglyceride uptake into tissues.
1/1 000 000
What is ApoC2?
It is a protein found on VLDL and chylomicrons which activates the enzyme lipoprotein lipase and causes triglyceride uptake into the tissues.
What does ApoC2 deficiency cause?
What is this diseases prevalence?
This deficiency causes decreased triglyceride uptake into tissues.
1/1 000 000
What is palmar xanthomas? What disease presents with it?
Yellowish (from cholesterol) plaque depositions in the palms of the hands seen with Remnant Removal Disease.
What is IDL, LDLR, and LRP?
Intermediate Density Lipoprotein
Low Density Lipoprotein Receptor
Lipoprotein Receptor-related Protein
What is ApoE?
A class of apolipoprotein found in IDLs and chylomicrons which is responsible for the catabolism of triglyceride-rich lipoprotein constituents and cholesterol.
How does Remnant Removal Disease present?
What causes it?
What is its prevalence?
Elevated cholesterol and triglycerides with palmar xanthomas.
It is caused by a defect in ApoE2 recognition by LDLR and LRP as well as overproduction of VLDL by the liver.
1/5000
How does familial hypercholesterolemia present?
What causes it?
What is its prevalence?
Heterozygotes have cholesterol levels twice normal and develop coronary disease if they are not treated.
Homozygotes get coronary disease in their childhood.
1/500
What is the prevalence of: Familial Combined Hyperlipidemia? Familial Hypercholesterolemia? Familial Ligand-Defective ApoB? Familial Hypertriglyceridemia?
1/50
1/500
1/500
1/5000
What is ApoB responsible for?
VLDL and LDL formation, entrance of cholesterol into tissues.
How does Familial Ligand-Defective ApoB present?
What is its prevalence?
This disease is clinically identical to Familial Hypercholesterolemia.
1/500
There is a(n) ______ relationship between the plasma HDL-C level and the risk for coronary heart disease (CHD). LDL-C and coronary events have a(n) ______ relationship.
inverse, linear
How can you raise HDL?
Exercise, weight loss, smoking cessation, statins, niacin, fibrates, estrogen, and ethanol.
______ stimulates the pituitary to release ______ which stimulates the thyroid to release ___ and ___. ___ is converted to ___ by______ ______ in the ______, ______, ______, and brown fat.
TRH, TSH, T3, T4.
T4, T3, peripheral, deiodinases,
liver, kidneys, thyroid
In the hypothalamic-pituitary-thyroid feedback axis which substance causes the negative feedback?
T3
The thyroid is divided into left and right lobes with a ______ separating them. There may also be a ______ ______ superior to the ______.
isthmus
pyramidal, lobe, isthmus
A thyroidectomy may damage these nerves leading to hoarseness.
Recurrent laryngeal nerves (1% of the time is permanent).
Low TSH suggest ______ while high TSH suggest ______. TSH is the first thing to be detected in abnormal levels and ___ is the last.
Hyperthyroidism, Hypothyroidism
T3
Which antibodies are often present in both Hashimoto’s thyroiditis and Grave’s disease?
Anti-TPO {thyroid peroxidase} antibodies.
These antibodies are only present with Grave’s disease.
TSH receptor antibodies.
What is unique about TSH receptor antibodies?
They stimulate the TSH receptor instead of inhibiting or destroying it.
What is the best single screening test for thyroid function?
TSH level measurement.
What is, by itself, diagnostic of hyperthyroidism?
Elevated TSH.
Thyroid hormone is synthesized from?
Thyroglobulin which is iodinated to either T3 or T4.
Iodine is transported into follicular cells via?
Sodium-iodide symporter (NIS).
In the blood most T3 and T4 is?
Bound to TBP (thyroid binding protein) and albumin. 0.3% T3 and 0.03% T4 are in their free/unbound form.
What is the half-life of T3 and T4? Which is better to use for hormone replacement therapy?
T3: 0.75 days.
T4: 7 days.
T4 is the choice for hormone therapy as it will fluctuate less and cause fewer symptoms for the patient.
Which is the biologically active form of thyroid hormone?
What converts one to the other?
What percentage of each is made in the thyroid?
T3
Peripheral deiodinases converts T4 to T3.
100% of T4 and 20% of T3 is made in the thyroid.
Thyroid hormone increases the production of?
GH and IGF-1.
What is the most common cause of hypothyroidism, goiter, mental retardation, and preventable brain damage?
Iodine deficiency.
Iodine deficiency will result in ______ while iodine excess may cause ______?
Hyperthyroidism, Hypothyroidism (Possibly Hyperthyroidism)
What is the Wolff-Chaikoff Effect?
Excess iodine can inhibit organification (conversion into thyroid hormone) of iodine and thyroid hormone synthesis will be decreased. A healthy thyroid “escapes” this effect.
What is the Jod-Basedow Effect?
Iodine induced hyperthyroidism (less common). It may occur in individuals with autoimmune thyroid disease. In some patients, especially those with hyperthyroidism, excess iodide may be used as a substrate for thyroid hormone metabolism, promoting and worsening the hyperthyroid state.
What does the radioactive iodine uptake thyroid scan test for?
It is a test of thyroid function.
What is a thyroid ultrasound a test of?
It is a test of thyroid size.
What are “hot areas” of a thyroid scan?
Uptake of radioactive iodide or 99m Technetium is increased in areas with increased thyroid hormone synthesis. These are the “hot areas”.
Why is 99m Technetium better than iodine 131 for radioactive uptake tests?
It gives the patient a much lower dose of radiation.
How is hyperthyroidism diagnosed and investigated?
The patient should have: - Depressed levels of TSH. Then test for: - Elevated T3 and T4. - Iodine uptake thyroid scan. - TSH receptor antibodies (Grave's) and TPO antibodies.
How do toxic nodules present?
A single nodule or irregular, lumpy (multiple nodules), goiter with no autoimmune signs.
Subacute (de Quervain’s) Thyroiditis often precedes a(n)?
URTi
Subacute (de Quervain’s) Thyroiditis initially presents with ______ which may be followed by transient ______ and ___ percent of patients recover completely.
Hyperthyroidism, hypothyroidism, 50.
What do the hormone levels look like in subclinical hyperthyroidism? What is the prognoses/
- Suppressed TSH but normal T3 and T4.
- 40-60% resolve spontaneously over 1-2 years, 9-18% progress to hyperthyroidism over 7 years.
- There is a 9% risk (3x) over two years of atrial fibrillation in addition to risk of congestive heart failure and angina.
Galactorrhea is a rare symptom of?
Hypothyridism
What are the presentation of Hashimoto’s thyroiditis in order from most to least common?
Euthyroid goitre with positive TPO antibodies, hypothyroidism, and a hyperthyroid phase.
What does PGAS stand for?
PolyGlandular Autoimmune Syndrome
Goiters occur with?
Grave’s disease, Hashimoto’s thyroiditis, and subacute (de Quervain’s) thyroiditis.
What is Pemberton’s sign?
When a patient with a large goitre raises their arms the pressure from the goitre decrease the blood drainage from their head. This makes blood build up and turns their faces very red.
What is the prevalence of palpable thyroid nodules?
5% in women and 1% in men living in iodine sufficient areas of the world.
What percentage of nodules are clinically apparent?
10%
What is the prevalence of thyroid cancer?
The majority of nodules are benign. Thyroid cancer incidence is 50/1 000 000.
List some elements which increase the likelihood of a thyroid module being malignant.
Male, history of head and neck irradiation, rapid progression of symptoms, family history of thyroid cancer, and local compressive symptoms including hoarseness.
List some elements of the physical exam which increase the likelihood of malignancy.
Hard fixed nodules, central/tracheal deviation, vocal cord paralysis, evidence of local invasion, and palpable ipsilateral lymph nodes.
How are thyroid nodules investigated?
- Determine TSH levels.
- Ultrasound or thyroid scan.
- Fine needle aspirate (FNA) of nodules > 1cm.
What are the different types of thyroid cancer?
Papillary/papillary-follicular (80%), follicular, hurthle cell, and anaplastic medullary cancer.
What are the two followup tests for thyroid cancer?
- Serum thyroglobulin and anti-thyroglobulin antibody tests every 6-12 months.
- Periodic neck ultrasounds.
What is the most significant concern regarding hypothyroidism for pregnant women?
Even mild hypothyroidism may have deleterious effects on a child’s cognitive development. Thyroxine dosage should be increased once pregnancy has been confirmed (subclinical hyperthyroidism in pregnancy has no adverse outcomes).
What is a difference between Grave’s disease and Gestational hyperthyroidism (due to hCG)?
Gestational hyperthyroidism will be negative for TSH receptor antibodies. The opthalmopathy seen with Grave’s disease will also be absent.
What is the reason for post-partum hyperthyroidism?
High estrogen during pregnancy can suppress antibodies in Grave’s disease and the thyrotoxic phase of Hashimoto’s thyroiditis These antibodies rebound post-partum causing hyperthyroidism.
Outline thyroid gland development.
- The thyroid develops during the first trimester.
- It forms from a pharyngeal pouch and migrates from the tongue to below the hyoid and larynx.
- The hypothalamic-pituitary-thyroid axis begins to form in the second trimester.
- Exposure to cold and stress at birth stimulates a surge of TSH.
What can, and what cannot, cross the placenta in regards to thyroid development and action?
- Iodide and small amount of T4 (for brain development) can cross the placenta.
- TSH cannot cross the placenta.
What typically causes congenital hypothyroidism?
Developmental defects: Thyroid agenesis/dysgenesis, an ectopic thyroid, or dyshormonogenesis (rare).
What should be used to treat congenital hypothyroidism?
L-thyroxine (10-15 ug/Kg) given as soon as possible to prevent unnecessary brain damage.
How is congenital hypothyroidism diagnosed?
Venous TSH levels.
What is a physical sign which is strongly indicative of congenital hypothyroidism?
A large posterior fontanelle.
The right adrenal gland is shaped like a ______ while the left is ______.
Triangle, semilunar.
The adrenal glands produce the catecholamines: ______ & ______ as well as the corticosteroids: ______ & ______.
Epinephrine & Norepinephrine
Cortisol & Aldosterone
Name the three arteries and two veins which supply blood flow to the adrenal glands.
Superior/Middle/Inferior Suprarenal Arteries.
Right and Left Suprarenal Veins.
Which vessels supply blood flow to the thyroid gland?
The superior {external carotid} and inferior {thyrocervical trunk} provide blood which drains through the superior (internal jugular} and inferior {left brachiocephalic} thyroid veins.
Which thyroid cells produce T3 and T4?
Follicular cells.
Where is the thyroid found?
Inferior to the thyroid cartilage (adams apple) and wrapped around the larynx and trachea.
What is the “optimal” blood pressure?
120/80
At what blood pressure is mild hypertension?
140/90
At what blood pressure is isolated systolic hypertension?
> 140/<90
What are some endocrine causes of hypertension?
- Hyperaldosteronism
- Cushing Syndrome
- Pheochromocytoma
- Hyperthyroidism
- . . .
Hyperaldosteronism will cause?
- Spontaneous hypokalemia (<3.5mmol/L).
- Hypertension refractory to treatment with 3 or more drugs.
- Incidental adrenal adenomas.
What is the classic “triad” of symptoms suggestive of pheochromocytoma?
Headache, sweating, and palpitations.
Other symptoms include pallor, anxiety, nausea, weight loss, and tremor.
What is the “rule of 10’s” in relation to pheochromocytoma?
10% familial
10% extrarenal
10% bilateral
10% malignant
What is pheochromocytoma?
A condition in which a neuroendocrine tumour secretes high amounts of catecholamines (epinephrine and norepinephrine); most commonly occur in the adrenal medulla.
To what degree should blood pressure be recorded?
2 mmHg
What is Cushing’s syndrome?
What is Cushing’s disease?
The signs and symptoms associated with prolonged exposure to high levels of cortisol.
Cushing’s disease involves an adenoma in the pituitary which releases large amounts of ACTH (secondary hypercortisolism).
What are some symptoms of Cushing’s syndrome?
Centripetal obesity, facial plethora, glucose intolerance, weakness, hypertension, hirsutism, acne, osteopenia, abdominal striae . . .
What are the four diseases which result in Cushing’s syndrome?
- Iatrogenic (most common).
- Pituitary Tumour (Cushing’s Disease).
- Adrenal.
- Ectopic ACTH Syndrome (rare).
What are the important adrenal steroid hormones?
- Glucocorticoids (Cortisol)
- Mineral Corticoids (Aldosterone)
- Adrenal Androgens (DHEAS {Dehydroepiandrosterone})
What are some signs/symptoms of adrenal steroid hormone insufficiencies?
Salt cravings, fatigue, weakness, nausea, sense of “impending doom”, weight loss.
Postural drop in BP; postural increase in pulse; hyperpigmentation of gums, creases, and scars; vitiligo (loss of pigment in skin).
What is the name of the best test for adrenal insufficiency and how does it work?
- ACTH stimulation test (Cosyntropin Test).
- Measure baseline cortisol and ACTH.
- Add 250ug of ACTH via IV bolus.
- Measure cortisol at 1 hour.
- Low response means primary insufficiency while a high response means secondary insufficiency.
Without ______ potassium levels slowly ______.
Aldosterone, rise
How is adrenal insufficiency treated?
- IV hydration and steroids.
- Treat precipitating illness.
- Glucocorticoid treatment {primary and secondary}.
- Mineralcorticoid treatment {primary only}.
What is primary adrenal insufficiency?
ADDISON’S DISEASE: ACTH levels are high, but, there is no response from the adrenal cortex. Cortisol, aldosterone, and DHEAS are missing.
What are some symptoms and signs of primary adrenal insufficiency?
Low Sodium, HIGH ACTH, High Potassium, Salt Craving, Nausea/Vomiting/Diarrhea, Hyperpigmentation.
Elevated levels of ACTH stimulates what type of cells?
Melanocytes.
What is secondary adrenal insufficiency?
The pituitary does not produce sufficient ACTH or the hypothalamus {tertiary} does not produce sufficient CRH. Only cortisol is missing.
What are some symptoms and signs of secondary adrenal insufficiency?
Normal (possibly low) Sodium, LOW ACTH, Normal Potassium, No Salt Craving, Less Nausea/Vomiting/Diarrhea, No Hyperpigmentation.
Name some features which differentiate between primary and secondary adrenal insufficiencies.
Primary –> High ACTH, High Potassium, Salt Craving, Hyperpigmentation.
Secondary –> Low ACTH, other aforementioned not present.
Name the regions of the adrenal gland and what they produce.
Cortex
Zona glomerulosa - aldosterone.
Zona fasciculata - cortisol.
Zona reticularis - androgens {DHEA}.
Medulla
Catecholamines epinephrine and norepinephrine.Name some of the important things that cortisol does.
- Gluconeogenesis, decreased peripheral glucose utilization, and hepatic glycogen storage.
- Increases the blood glucose for insulin INSENSITIVE tissues.
- Proteolysis and lipolysis.
- Immunosuppression.
- Impairs calcium absorption.
Name some of the important things that aldosterone does.
- Increases renal absorption of sodium while increasing excretion of potassium.
- Increases BP.
- Affects the sweat and salivary glands, and the colon.
Name some of the important things that renal androgen (DHEA) does.
- Insignificant in males but major in females.
- Associated with well-being and lack of stress.
- DHEA is the most abundant hormone in the body.
Name some of the important things that the catecholamines do.
- Increase cardiac output.
- Redistributes blood flow from the gut, kidneys, and skin to the heart, brain, and skeletal muscles.
- Pupillary dilation, bronchodilation, decreased gut motility.
- Glycogenolysis, gluconeogenesis, and lipolysis.
Fight & Fright vs. Rest and Digest
What is steroidogenesis?
The conversion of cholesterol to steroid hormones such as progesterone, aldosterone, cortisol, DHEA, testosterone, and estradiol. Steroid synthesis occurs within the inner mitochondrial membrane even though cholesterol is made on the smooth endoplasmic reticulum.
What is the rate limiting step in steroidogenesis?
Passage through pore protein STAR (steroidogenic acute regulatory protein).
What are the effects of aromatase inhibition?
Aromatase is inhibited in obesity leading to decreased conversion of testosterone to estradiol, causing hirsutism in women.
21-Hydroylase deficiency will cause?
Inhibition of the production of cortisol resulting in congenital adrenal hyperplasia.
