Wk 6: Endocrine Flashcards
Posterior Pituitary:
1) What does it do?
2) What does oxytocin do? Is it measured?
1) Stores and releases two hormones synthesized by hypothalamus
2) Oxytocin
-Stimulates uterine smooth muscle contraction during childbirth
-Promotes milk ejection from mammary glands during breast-feeding
-Possibly involved in bonding and romantic attachment
-Not routinely measured
1) Where is ADH (vasopressin) released from?
2) What does it do? What does this do to urine?
3) What 2 things can trigger it?
1) Posterior pituitary
2) Stimulates water reabsorption in the renal tubule (increases free water in bloodstream)
Urine becomes more concentrated (higher specific gravity)
3) Increase in serum osmolarity detected by hypothalamic osmoreceptors
Or decrease in blood volume detected by left atrial volume receptors
Two patients present to your clinic complaining of new onset polyuria, nocturia, and polydipsia. Initial labs show a low urine osmolality.
a) Marcy, a 35-year-old female, is status post transsphenoidal removal of a pituitary adenoma. You suspect neurogenic diabetes insipidus.
b) Tom, a 25-year-old male, is chronically on lithium for bipolar disorder. You suspect nephrogenic diabetes insipidus.
You order an ADH stimulation test to help confirm your diagnoses. In which patient would you expect the urine osmolarity to increase after ADH administration?
a) Marcy
List 3 Disorders Involving Antidiuretic Hormone (ADH)
1) Diabetes insipidus (DI):
2) Primary (psychogenic) polydipsia:
3) Syndrome of inappropriate secretion of ADΗ (SIADH):
Disorders Involving Antidiuretic Hormone (ADH)
1) What are the 2 causes of diabetes insipidus (DI)?
2) What can cause primary (psychogenic) polydipsia?
3) What is SIADH?
1) Inadequate ADH secretion (neurogenic)1 or kidney is unresponsive to ADH (nephrogenic)2
excrete large volumes of free water with dilute urine; hemoconcentrated blood, excessive thirst
2) Excess intake of water (not due to ADH problems) ADH secretion is suppressed
3) Syndrome of inappropriate secretion of ADΗ (SIADH):
inability to suppress the secretion of ADH leads to impaired water excretion
Differentiating ADH Disorders:
1) What is ADH stimulation test (aka “vasopressin challenge test”, water deprivation test) used for?
2) How does it work?
1) Used to differentiate neurogenic (central) diabetes insipidus vs nephrogenic diabetes insipidus
Is the body not making ADH (neurogenic) or are the kidneys not responding to it (nephrogenic)?
2) Water intake is restricted and urine osmolarity is measured before and after ADH administration
Neurogenic DI = urine osmolarity increases
Nephrogenic DI = no increase
Differentiating ADH Disorders:
1) What are ADH levels in neurogenic DI and primary polydipsia?
2) What are ADH levels in nephrogenic DI and SIADH?
1) Low
2) High
Hypothalamic hormones act on anterior pituitary which synthesizes six hormones; most of these act on what?
Target hormones to regulate other hormones
Growth Hormone (GH):
1) What does it regulate?
2) What can the blood testing identify?
1) Regulates overall body growth via Insulin-Like Growth Factor (IGF) and other peptides
2) GH deficiency in teenagers with short height, delayed sexual maturity
-GH excess in patients with gigantism or acromegaly
-Also used to track GH releasing neoplasms
Growth Hormone (GH):
1) When is it secreted? What does this mean?
2) When can it be taken?
3) What gives a more accurate reflection of GH?
1) Secretion in bursts throughout the day, especially night
Random GH is unreliable
Reference levels overlap significantly with deficient levels
2) Can be taken 60-90 minutes after onset of deep sleep (to minimize time variability)
3) Measuring IGF-1
Adrenocorticotropic Hormone (ACTH, Corticotropin) & Cortisol:
1) How are they related?
2) What two things can it evaluate?
1) CRH (hypothalamus) > stimulates ACTH production (anterior pituitary) > stimulates adrenal cortex to secrete cortisol (> negative feedback for CRH/ACTH)
2) Cushing syndrome: Overproduction of cortisol
Adrenal Insufficiency: Underproduction of cortisol
Hypercortisolism: Cushing “syndrome” and “disease”
1) What is cortisol? What does Cushing “syndrome” refer to?
2) What is the most common cause?
3) What does “endogenous” Cushing syndrome refer to?
1) Cortisol is a glucocorticoid (steroid) hormone; manifestations of excessive corticosteroids
2) Most often iatrogenic due to exogenous corticosteroid drugs
3) Increased cortisol production by the adrenal cortex
“Endogenous” Cushing syndrome: what are the two sources of it?
1) ~25% due to autonomous cortisol production by adrenal cortex (ACTH-independent, primary)
E.g., adrenal adenoma or carcinoma
2) ~75% due to excessive ACTH secretion (ACTH-dependent, secondary)
Excessive ACTH secretion (ACTH-dependent, secondary):
1) What are 90% of these due to?
2) What are the other 10% caused by?
1) Cushing “disease” (2nd most common form overall after iatrogenic) pituitary hypersecretion of ACTH (e.g., adenoma) (90%)
2) Ectopic ACTH production from nonpituitary neuroendocrine neoplasms (e.g., small cell lung cancer)(10%)
What are the steps of Cushing syndrome lab testing?
1) First, exclude exogenous glucocorticoid intake
2) There are 3 first-line tests for diagnosis of Cushing Syndrome, used in combination:
-Diagnosis is established when at least 2 different first-line tests are unequivocally abnormal and cannot be explained by other conditions
3) If Cushing Syndrome diagnosed, establish the cause
slide 14 chart
List and describe the 3 first line tests for diagnosing Cushing syndrome
1) Overnight low-dose dexamethasone suppression test (DЅТ)
-Dexamethasone (1 mg) administered at 11PM and serum cortisol measured at 8 AM the next morning
-Cushing’s pt: Early morning cortisol level is high (not suppressed)
2) Late-night (10-11 PM) salivary cortisol
-In a normal pt, cortisol levels normally drop to a low point (nadir) in the evening (diurnal variation)
-Cortisol is high
3) 24-hour urinary free cortisol (UFC) excretion: high cortisol level
How do you establish the cause of Cushing Syndrome?
1) Measure plasma ACTH (and DHEAS) to differentiate ACTH-dependent vs. ACTH-independent
2) If ACTH-dependent, differentiate pituitary vs. non-pituitary (ectopic) source of ACTH
(via High-dose (8 mg) DST)
If Cushing Syndrome diagnosed, how do you establish the cause? Define this
Measure plasma ACTH (and DHEAS) to differentiate ACTH-dependent vs. ACTH-independent
DHEAS: adrenal androgen whose production is stimulated by ACTH
If a pt’s Cushing syndrome is ACTH-dependent, how do you differentiate pituitary vs. non-pituitary (ectopic) source of ACTH?
1) High-dose (8 mg) DST – overnight test administered similarly to low-dose DST
-High dose will suppress pituitary tumor secretion of ACTH and subsequent early morning cortisol levels but will not suppress an ectopic source (resistant)
-Cortisol level low (suppressed) = pituitary source
-Cortisol level high (not suppressed) = ectopic source
Primary adrenal insufficiency (Addison disease):
1) What causes it?
2) Give examples
1) Dysfunction or absence of the adrenal cortices
2) Autoimmune disease, adrenal infiltration from cancer or infections (e.g., TB), adrenal hemorrhage, congenital, drugs, infections
Central adrenal insufficiency:
1) What causes it?
2) What are the most common causes?
1) Dysfunction of pituitary gland (secondary adrenal insufficiency; low ACTH secretion) or hypothalamus (tertiary; low CRH secretion)
2) Prolonged exogenous use of glucocorticoids or opiates (suppress secretion of CRH/ACTH)
Hypothalamic or pituitary mass lesions, radiation, infiltrative lesions, infections (e.g., TB), injury/trauma, infarction, autoimmune, genetic…
1) Serum cortisol and ACTH are best measured when?
2) What is the first step to hypercortisolism testing?
2) What is the second step? What would high and low results indicate?
1) In early morning (by 8AM)
2) #1: Verify cortisol deficiency: low early morning serum cortisol
3) #2: Measure early morning plasma ACTH (along with concurrent cortisol) to differentiate primary vs. central etiology
High ACTH (with low cortisol) = primary
Low ACTH (with low cortisol) = central
What should you do if a pt has primary hypercortisolism according to their morning plasma ACTH? Describe the results
Confirm dx with cosyntropin (synthetic ACTH) stimulation test (serum cortisol measured after cosyntropin administration)
1) Healthy pt: cortisol rises significantly
2) Primary Adrenal insufficiency: cortisol does not rise significantly (adrenals unable to respond to stimulus)
Luteinizing Hormone (LH) & Follicle Stimulating Hormone (FSH):
1) What produces these?
2) What is the blood test for both (since often done together) used for? Explain
1) Produced by anterior pituitary and act on ovaries/testes
Blood test often performed together
2) Used to evaluate infertility: LH surge indicates ovulation (day of highest fertility); daily samples of LH around mid-cycle can identify LH surge
-Rapidly excreted into urine. Home kits evaluable for urine tests.
Prolactin (PRL): What does it do in females and males?
1) Females: Enhances breast development and lactation
2) Males: Function unclear, possibly immune related
-Only anterior pituitary (AP) hormone that does not stimulate secretion of another hormone
-Used to monitor PRL-secreting pituitary adenomas
1) Describe how TRH works
2) Define the last part of this chain of events
1) TRH (hypothalamus) > stimulates TSH secretion (pituitary) > stimulates thyroid to secrete thyroid hormone (T4/T3)
2) T3 and T4 are two iodine-containing hormones secreted by the thyroid
T4: thyroxine
T3: triiodothyronine
1) What are T3 and T4 called?
2) What does each do?
1) Collectively called thyroid hormone (90% is T4.)
2) T3 is 10x more potent.
T3 is the active form of thyroid hormone
T4 is used to regulate TSH feedback loop
1) Thyroid hormone affects almost every tissue in the body for wide variety of effects; give examples
2) Thyroid hormone levels are used to measure thyroid function; what do high and low levels tell us?
1) Basal metabolic rate (BMR), O2 consumption, heat production, responsiveness to epinephrine/norepinephrine, heart rate, cardiac contractile strength, CNS activity, GH, IGF-1
2) ↑ T4/T3 = hyperthyroidism
↓ T4/T3 = hypothyroidism
Thyroid panel usually includes what to differentiate hypothyroidism from hyperthyroidism, and primary vs. secondary causes of each.?
Serum TSH, free T4, and T3 TSH and free T4 (+/- T3)
What are the two types of hypothyroidism? What are some causes of each?
1) Primary: thyroid gland problem > low T4/T3 > high -TRH/TSH (compensatory) thyroid ablation, thyroid agenesis, congenital hypothyroidism
2) Secondary: hypothalamus/pituitary gland problem > low TRH and/or TSH > low T4/T3
-trauma, tumor, infarction
Differentiate between primary and secondary hyperthyroidism
1) Primary: high T4/T3; low TRH/TSH (compensatory) [most common]
2) Secondary: high TRH and/or TSH; high T4/T3 [very rare]
Thyroid tests:
1) When can T3 be used?
2) What is TSH the best initial screening test for?
1) T3 can be used if T4 is borderline or normal in the presence of symptoms
2) (Most sensitive) for evaluation for primary hypo- and hyperthyroidism
-Also the best test for monitoring T4 replacement therapy (e.g., in treatment of hypothyroidism)
Parathyroid Hormone (PTH):
1) What does it do?
2) What would happen without it?
1) Increases plasma calcium
(serum phosphate decreases (renal excretion of phosphate in order to retain calcium))
2) Individual would die after a few days due to hypocalcemia
PTH measured simultaneously with calcium to identify what?
1) Hyper-/hypoparathyroidism
2) Distinguish parathyroid vs. nonparathyroid causes of calcium disorders
1) What are some causes of high PTH levels?
2) What abt low PTH levels?
1) Hyperparathyroidism, hypocalcemia compensation, PTH-producing tumor
2) Hypoparathyroidism, hypercalcemia compensation, parathyroid ablation
Describe how to differentiate ACTH-dependent vs. ACTH-independent based on lab tests
1) High cortisol, low ACTH, low DHEAS = ACTH-independent (i.e., adrenal source)
2) High cortisol, high ACTH, high DHEAS = ACTH-dependent (i.e., pituitary or nonpituitary ACTH-secreting tumor)
HbA1c (Glycosylated hemoglobin)
1) Hemoglobin is used to diagnose and monitor ____________________
2) ____% of the hemoglobin in RBCs is hemoglobin A
3) _____% of hemoglobin A is type 1 (HbA1) which has 3 types (A, B, C)
4) HbA1c combines strongly with _________________
1) diabetes mellitus (DM)
2) 98%
3) 7%
4) glucose (glycosylation)
HbA1c (Glycosylated hemoglobin): What doesn’t affect it? What does?
1) Not effected by short-term variations in blood glucose (feeding/fasting, exercise, stress, etc.)
Also not useful for recent management changes
2) Interfering factors include: hemoglobinopathies; chronic blood loss, hemolytic anemia (decreased A1C)
i.e., diseases affecting RBCs/hemoglobin A
The glycosylated Hb (e.g., A1C) or glycated protein tests are particularly beneficial for the following:
Evaluating patient compliance and success of treatment (in diabetes)
Comparing and contrasting the success of therapy
Determining the duration of hyperglycemia in patients with newly diagnosed diabetes
Providing a sensitive estimate of glucose imbalance in patients with mild diabetes
Individualizing diabetic control regimens
Providing a feeling of reward for many patients when the test shows achievement of good diabetic control
Evaluating the diabetic patient whose glucose levels change significantly day to day (brittle diabetic)
Differentiating short-term hyperglycemia in patients who do not have diabetes (e.g., recent stress or myocardial infarction) from those who have diabetes (where the glucose has been persistently elevated)
What is the two-step approach for screening and diagnosis of GDM (preferred by ACOG)? Define each step
1) Step 1: 1 hour 50-g OGTT (more sensitive, less specific)
2) Step 2 (if Step 1 abnormal): 3 hour 100-g OGTT (more specific)
What are the protocols of step 1 and step 2 of GDM screening?
1) Step 1: 50-g oral glucose load given (without regard to previous meals/time of day) plasma glucose level obtained at 1 hour
2) Step 2: fasting plasma glucose level obtained 100-g oral glucose load given obtain plasma glucose levels at 1, 2, and 3 hours after the glucose load
