DHEA and its sulfated form, DHEA-S, and estradiol are predominantly bound to albumin, whereas testosterone and dihydrotestosterone (DHT) are mostly bound to sex hormone-binding globulin (SHBG).
How do we measure 17- hydroxycorticosteroids (17-OHCS)?
Measured by the Porter-Silber reaction
17-hydroxyprogesterone, 11-desoxycortisol are 17-ketogenic steroids.
Cortisol also an 17-ketogenic steroid can be measured by?
Measured by Zimmermann reaction
What is a Adrenocorticotropic Hormone (ACTH) Stimulation (Cosyntropin) Tests?
Designed to document the functional capacity of the adrenal glands to synthesize cortisol.
The test determines whether the adrenal glands are responsive to ACTH.
Cosyntropin is given to a patient with a low baseline cortisol, what if cortisol level increases?
What if cortisol level does not change?
If cortisol level increases the problem lies with the anterior pituitary (secondary adrenal insufficiency)
If cortisol level does not change, problem lies in the adrenal cortex (primary adrenal insufficiency)
A direct and selective test of anterior pituitary gland function.
Corticotropin-Releasing Hormone (CRH) Stimulation Test
Injection of ovine CRH stimulates ACTH secretion in healthy subjects within 60 to 180 minutes; glucocorticoids inhibit this effect (as in cases of Cushing syndrome)
What test is used to test the integrity of the hypothalamic pituitary adrenal axis?
Insulin-Induced Hypoglycemia Stimulation Test
Insulin is given to produce hypoglycemia which is a physiologic stimulus for release of CRH; plasma ACTH and cortisol concentrations are then measured and will be increased if the hypothalamic pituitary adrenal axis is intact
An indirect test of hypothalamic pituitary adrenal axis function
involves the administration of metyrapone causing a decrease in cortisol
The decrease in cortisol is expected to allow an increase in ACTH secretion,What test is this?
Metyrapone Stimulation Test
This type of test involves the administration of potent glucocorticoid dexamethasone, and measuring serum or urine cortisol concentrations to evaluate the hypothalamic response. What test is this?
Patients with Cushing syndrome of any cause will fail to suppress their morning plasma cortisol concentration to less than 2 µg/dL in response to a 1 mg dose of dexamethasone administered at 10:00PM.
Dexamethasone Suppression Test
What is a Mineralocorticoid Stimulation Tests
Used to determine the function of the renin-angiotensin-aldosterone system by stimulating the renin-angiotensin system based on volume depletion maneuvers such as sodium restriction, upright posture or diuretic administration.
A normal response is a two to threefold increase in plasma renin, indicating that the JGA is responding properly to decreased plasma volume
What test makes use of either saline infusion, oral salt loading, or mineralocorticoid administration, each of which should suppress the secretion of aldosterone by the adrenal gland
Mineralocorticoid Stimulation Tests
What is Adrenal insufficiency (Addison disease) ?
Results from progressive destruction or dysfunction of the adrenal glands by an autoimmune process, the systemic disorder, and inborn error of metabolism (endogenous causes), or by an exogenous cause, such as infection.
The most common cause of primary adrenal insufficiency is infectious diseases like tuberculosis, fungal infections and cytomegalovirus infection.
What is Hypoaldosteronism?
Deficient aldosterone production occurring in conditions other than Addison disease.
Hypoaldosteronism is seen in?
Seen in patients with:
inadequate production of renin by the kidney which leads to secondary aldosterone deficiency (hyporeninemic hypoaldosteronism)
inherited enzyme defects in aldosterone biosynthesis
acquired forms of primary aldosterone deficiency (post-surgical or due to heparin therapy)
Glucocorticoid Excess (Cushing syndrome)is a result of what?
Endogenous Cushing syndrome is a result of autonomous excessive production of cortisol.
What are the characteristics of a person with Glucocorticoid Excess (Cushing syndrome)?
Characteristic clinical features include truncal obesity, moon facies, a buffalo hump on the upper back below the neck, supraclavicular fat pads, myopathy, hypertension, hirsutism, hypokalemic alkalosis, carbohydrate intolerance, secondary osteoporosis, disturbed productive function and neuropsychiatric symptoms.
Exogenous Cushing syndrome is a caused of what?
Exogenous Cushing syndrome is caused by excessive oral or parenteral glucocorticoid therapy.
What are the clinically significant analytes of virilizing adrenal adenomas?
All Of The Above
DHEA in high concentrations can be found in virilizing ovarian tumors in women.
Adenomas can produce Aldosterone?
Conn Syndrome has several symptoms that are clinical in nature. Identify two of them.
B and C
Incidentalomas are functioning and malignant.
Incidentalomas can be found by using two types of technology. Pick Two.
None of The Above
A and B
A laboratory can confirm the incidentaloma with what two hormones?
A and B
Hyperaldosteronism is the oversecretion of what hormone?
Outside stimulus can activate the rennin-angiotensin system in secondary hyperaldosteronism.
Choose two causes of Mineral Corticoid excess.
Bilateral idiopathic hyperplasia
Aldosterone producing adenoma
None of the Above
All of the Above
If the PAC/PRA given range ratio concentration value is from 20-25. Presume:
A and C
Dictate the four analytes for determining Adrenocortical function.
All of the Above
Cortisol can be measured in several analytes. Name three.
heparinized plasma, EDTA Plasma
C. Whole Blood
D. A and B
Cortisol Concentration is lowest in the morning.
Can Cortisol be associated with Stress, Pregnancy, and Hypoglycemia?
Free Cortisol can be detected by the following methods including:
Ultrafiltration, Gel Filtration
All of the above
Should a 24 hour urine specimen be collected with boric acid and refrigerated?
For collection of Aldosterone, the patient should be upright for:
These proteins bind 99.97% of T4 and 99.7% of T3, thus very small fraction is unbound and available for biological activity.
What is the regulation and control of thyroid hormones?
Regulation and control
Controlled by Negative Feedback System
Thyrotropin-releasing hormone (TRH) from hypothalamus
Thyroid stimulating hormone (TSH) from pituitary
Thyroid hormones from follicular cells of thyroid glands
What are the different thyroid disorders?
having normal thyroid function
a condition caused by excessive production of iodinated thyroid hormones
a condition of deficient thyroid gland activity
What are the different thyroid disorders?
a condition characterized by inflammation of the thyroid gland
a life-threatening condition that develops in a minority of cases of untreated thyrotoxicosis (hyperthyroidism, or overactive thyroid)
Toxic multi-nodular goiter
a condition in which the thyroid gland contains multiple lumps (nodules) that are overactive and that produce excess thyroid hormones. Also known as Parry disease and Plummer disease.
What is a goiter?
An enlargement of the thyroid gland that causes a swelling in the front part of the neck
Occur when the thyroid gland produces either too much thyroid hormone (hyperthyroidism or toxic goiter) or not enough (hypothyroidism or non-toxic goiter).
What is sporadic goiter?
Can form if the diet includes too many goiter-promoting foods, such as soybeans, rutabagas, cabbage, peaches, peanuts, and spinach. These foods can suppress the manufacture of thyroid hormone by interfering with the thyroid's ability to process iodide.
Name hypothyroidism disorders?
What are characteristics of Myxedema?
a severe form of hypothyroidism in which there is accumulation of mucopolysaccharides in the skin and other tissue, leading to a thickening of facial features and a doughy induration of the skin.
What is Cretinism?
Is the archaic term used to describe severe hypothyroidism that develops in the newborn period. Appropriate term is congenital hypothyroidism
What are some differences between Dwarfism and Cretinism?
Dwarfism is caused by hypopituitarism and Cretinism is cause by hypothyroidism. Dwarfism has decreased Growth Hormone secretion while cretinism has decreased T4 and T3. Dwarfs are mentally normal while patients with cretinism have a low IQ.
What are the clinical symptoms of hypothyroidism?
Mental dullness, somnolence, increased sleeping, lethargy, easy fatigability, hoarseness, hair loss, weight gain, cold intolerance, menstrual irregularities, infertility, growth failure, delayed puberty in adolescents, constipation, muscle weakness or cramps, and depressed affect or frank clinical depression.
What are the physical signs of hypothyroidism?
Bradycardia, decreased pulse pressure, cool and/or dry skin, puffy eyes, loss of the outer lateral eyebrows, delayed relaxation phase of reflexes, myopathy, carotenemia, occasional galactorrhea, short stature in affected children, radiologic evidence of delayed bone age in children, congestive heart failure, coma may rarely occure (severe hypothyroidism)
What endogenous disorders cause primary hypothyroidism?
Autoimmune thyroid diseases such as Hashimoto thyroiditis, atrophic thyroiditis, late-stage graves disease, and postpartum thyroiditis. Inborn errors in thyroid hormone biosynthesis such as Na+/ iodine pump dysfunction, inadequate organification/ iodination-TPO dysfuntion, defective thyroglobulin, deiodinase deficiency, and pendred syndrome-hypothyroidism and deafness. Developmental disorders involving the thyroid gland such as congenital hypothyroidism: aplasia, hypoplasia, and ectopic thyroid: lingual thyroid, thyroglossal duct cyst. Consumptive hypothyroidism (increased metabolism of T4, and T3 by tumors)
What exogenous disorders cause primary hypothyroidism?
Iodine excess/ deficiency, drugs, thionamides, lithium, nitroprusside, amiodarone, biologicals like interferon and interleukin-2, dietary goitrogens, radiation-induced hypothyroidism, surgical removal of the thyroid gland, and viral or bacterial thyroiditis.
For primary hypothyroidism what happens to T3, T4, FT4I, and T3U and TSH.
Concentrations of T3, T4, FT4I, and T3U decrease while TSH concentration increases.
Due to the negative feedback mechanism, the low concentrations of T3, T4 is sensed by the pituitary gland causing it to secrete more TSH in order for the thyroid to secrete more T3 and T4, however since the thyroid is not functioning properly T3 and T4 are not secreted, which causes more secretion of TSH by the pituitary gland.
For secondary hypothyroidism what happens to T3, T4, FT4I, and T3U and TSH?
Concentrations of T3, T4, FT4I, T3U and TSH decreases.
In secondary hypothyroidism, why do the concentrations of T3, T4, FT4I, T3U and TSH decrease?
Because the pituitary gland is not properly functioning causing a decrease in TSH secretion, which in turn causes the decrease in T3 and T4 secretion by the thyroid.
What is Hypothyroidism?
A Condition of deficiency thyroid gland activity leading to lethargy, muscle weakness, and intolerance to cold.
What disease caused by Hypothyroidism?
Hashimoto’s Disease (Hashimoto’s thyroiditis)
What is Hashimoto’s Disease?
Is an autoimmune disease, a disorder in which the immune system turns against the body's own tissues. In people with Hashimoto's, the immune system attacks the thyroid, leading to hypothyroidism.
People who have family members who have thyroid disease or other autoimmune diseases usually develops the disease. (Genetic component)
Hashimoto's affects about seven times as many women as men, suggesting that sex hormones may play a role. Furthermore, some women have thyroid problems during the first year after having a baby.
What is autoimmune disease?
Immune system disorderscause abnormally low activity or over activity of the immune system. In cases of immune system over activity, the body attacks and damages its own tissues. For example, Immune deficiency diseases decrease the body's ability to fight invaders, causing vulnerability to infections.
What is thyroid disease?
Any dysfunction of the butterfly-shaped gland at the base of the neck (thyroid).
What are the other Causes of Hypothyroidism included:
Process, Initially, the gland is usually enlarge for instance,
What is the Etiology of Inborn error in thyroid hormone biosynthesis?
Are rare cause of primary hypothyroidism because of
Biochemical defects of iodine transport from loss-of-function mutations in sodium iodide symporter transporter system.
What is the etiology of Iodine Deficiency or excess?
Worldwide, the most common cause of goiter is iodine deficiency producing endemic goiter with or without nodularity.
Excess iodine can cause a transient state of reduces thyroid function.
What is the etiology of drug-induced?
Various drugs effect thyroid function.
What is the etiology of surgical and radiation-Induced?
Surgical removal of TG will produce hypothyroidism. External irradiation of the TG (treatment of lymphoma or Hodgkin Disease) or ingestive iodine also has been known to cause hypothyroidism.
What is the etiology of Viral or Bacterial Thyroiditis?
Although rarely occurring, some (1) viral infections (such as, sub-acute thyroiditis or giant cell thyroiditis), or 2 bacterial infections (acute thyroiditis or abscesses) of TG will seriously damage the TG and lead to hypothyroidism.
What is the etiology of Subclinical hypothyroidism?
A persistent elevation in TSH (6 to 12 weeks or longer) in the setting of FT4 concentrations that are repeatedly found within reference interval.
What is the other name for hyperthyroidism/thyrotoxicosis disease?
What are the causes of hyperthyroidism/thyrotoxicosis disease?
What are the clinical techniques involved in hyperthyroidism treatment?
T3 toxicosis, graves’ disease, hashimoto’s disease and postpartum thyroiditis, toxic nodular or multinodular goiter, gain-of-function mutations in thyroid-stimulation hormone receptor, central hyperthyroidism, human chorionic gonadotropin, iodine-induced hyperthyroidism, thyroid-storm and apathic hyperthyroidism, subclinical hyperthyroidism, pregnancy and other exogenous causes.
What is Graves’ disease also known as?
Toxic diffuse goiter and Flajani-Basedow-Graves disease.
What is Graves’ disease or hyperthyroidism?
Is an autoimmune disease that affects the thyroid, resulting in hyperthyroidism and an enlarged thyroid.
What are the signs and sympptomes of hyperthyroidism?
Include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea, and weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye problems such as bulging, a condition known as Graves' ophthalmopathy. About 25% to 80% of people with the condition develop eye problems.
What are the hyperthyroidism’s laboratory evaluation?
Laboratory Evaluation of Hyperthyroidism:
↑ THBR (thyroid hormone binding ratio)
Graves disease is an autoimmune disorder that involves ?
Over activity of the throid gland (hyperthyroidism)
What are some of the Grave’s disease symptoms in the human body
Thick red skin usually on the shings or tops of the feet
Thyroid hormone affect a numerous of body funtions includind ?
Heart and nervous system function
The primary treatment goals for graves disease are to ?
Inhibit the production of thyroid hormones
Lessen the severity of symptoms
Some treatment for Graves’s disease are ?
Anti thyroid medication
Disorders associated with thyroid hormone excess or deficiency in absence of thyroid disease
-Significant nutritional deprivation
-Acute severe illness
What happens in primary hypothyroidism?
TSH increased, FT4 decresed.
What happens in primary hyperthyroidism?
TSH decreased, FT4 increased.
What hormone is the American Thyroid Association’s recommended for screening test?
Measurement of Thyroid Stimulating Hormone (TSH)
What is the method for Measurement of Thyroid Stimulating Hormone (TSH)?
Measurements are done using the two-site "sandwich" heterogenous immunoassay involving enzyme, fluorometric substrate or chemiluminescent labels.
Both serum and plasma are used for what type of measurements.
TSH is stable for how many days at 2 to 8°C, and for at least 1 month when stored frozen.
For newborn screening, whole blood may be collected by heel puncture how many hours after birth.
48 to 72
Secretion of TSH is circadian with big concentrations occurring between ______(time of day), and the lowest between _______(time of day).
2:00 to 4:00 AM
5:00 to 6:00 PM
Measurement is done using electron capture gas chromatography, high performance liquid chromatography, and isotope dilution tandem mass spectrometry. This is the Measurement of what?
Total Thyroxine (T4)
What is the preferred specimen (EDTA and heparin plasma can also be used) for Total Thyroxine .
Because total T4 alone provides limited clinical information, FT4 measurements are preferred. True or False?
What does T3 stand for?
What is the techniques of choice to measure T3 in body fluids predominantly serum or plasma?
Give 2 examples.
Serum specimens should be tested within ______ hours of collection.
What temperature must serum specimens be stored at after 24 hours?
2 to 8°C
What does ‘rT3’ stand for?
Measurement are done, using which immunoassay?
True or False: rT3 measurement has limited diagnostic value.
True or False: The diagnosis of non-thyroidal illnesses can usually be established without measuring rT3.
What are the methods of measurement of Free Thyroid Hormones?
•serve as reference methods
–Direct Equilibrium Dialysis
Indirect or estimate assays
•for general laboratory use
–Two-step and One-step immunoassay
What type of measurement are used in Thyroxine Binding Globulin (TBG)?
•competitive, heterogenous method
•measurement of bound conjugate by chemiluminescence
•enhance microparticle turbidimetry
Measurement of Thyroglobulin (Tg) is done by:
Competitive and noncompetitive immunossasys
What are the 4 autoantibodies of clinical interest which are found in thyroid disease?