Endo/repro Li Notes

Front 1

What is acquired hypogonadotropic hypogonadism? What is it characterized by? (features in men vs. women?)

Back 1

Hypogonadism caused by decreased gonadotropins from the pituitary.

Characterized by the gradual loss of facial, axillary, pubic, and body hair (more prominent in patients who are also hypoadrenal). Men may note diminished libido, erectile dysfunction, muscle atrophy, infertility, and osteopenia. (See Male Hypogonadism.) Women have amenorrhea, infertility, and predisposition to osteoporosis. Like men, women with hypogonadism have androgen deficiency and may note muscle atrophy.

Front 2

Define sexual precocity.

Back 2

the onset of sexual maturation at any age that is 2.5 standard deviations earlier than the normal age for that population, being usually before the age of 8 years. May be classified as central, or GnRH-dependent, precocious puberty (true); or peripheral, or GnRH-independent, precocious puberty (pseudoprecocious puberty).

Front 3

What is the pathophysiology of central precocious puberty?

Back 3

Cause unclear.

Premature activation of the hypothalamic-pituitary axis is followed by gonadotropin secretion, which in turn stimulates the gonads to produce steroid hormones and, subsequently, pubertal changes.

Front 4

Central precocious puberty is more common in ________. Most of them are otherwise __________ children whose pubertal maturation begins at the early end of the normal distribution curve. CNS imaging studies of these __-__ year olds usually reveal no structural abnormalities.

Back 4

Girls; healthy; 6-8

Front 5

What are some more rare causes of central precocious puberty?

Back 5

CNS neoplasms: hypothalamic hamartomas, optic gliomas, and neurofibromas etc.

Cranial irradiation and CNS injuries

Prolonged excessive therapy with exogenous sex steroids or endocrine disorders such as hypothyroidism may accellerate hypothalamic-pituitary axis maturation, resulting in precocious puberty.

Front 6

What is peripheral GnRH-independent precocious puberty?

Back 6

appearance of pubertal dvpt but the presence of sex steroids is independent of pituitary gonadotropin release.

Front 7

Causes of peripheral GnRH-independent precocious puberty?

Back 7

congenital adrenal hyperplasia, tumors that secrete hCG, tumors of the adrenal gland or gonads, McCune-Albright syndrome (MAS), and exposure to exogenous sex steroid hormones.

Front 8

Pathophysiology of endogenous estrogen overproduction causing precocious puberty?

Back 8

some large follicular cysts capable of E production occur occasionally and may cause early feminization.

Benign tumors of the ovary (teratoma, cystadenoma) may produce E or may induce surrounding ovarian tissue to produce steroids.

Granulosa cell tumors capable of estrogen production are a rare cause of prepubertal feminization.

Even more rare causes: adrenal adenomas and hepatomas.

Front 9

Can exogenous estrogens cause precocious puberty? Give 2 examples.

Back 9

Yes. Ingestion of estrogens or prolonged use of creams containing estrogens is a possible but uncommon cause of early feminization. A phytoestrogen-enriched diet (mostly soybean extracts) could exert a similar effect.

Front 10

What is Mccune-Albright syndrome?

Back 10

Classic MAS consists of at least 2 features of the triad of polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and autonomous endocrine hyperfunction, the most common form of which is GnRH secretion and subsequent precocious puberty.

Other endocrine/nonendocrine tissues may also be affected. (adrenal, thyroid, pituitary, liver, and heart)

Front 11

What is the first sign of MAS usually?

Back 11

early vaginal bleeding.

Front 12

How do you diagnose MAS? Prognosis?

Back 12

on the basis of skin pigmentation and demonstration of bone lesions or pathologic fractures.

Prognosis is unfavorable... due to endocrinopathies often exist as well...

Front 13

Early development of a __________ organ can also occur and is much more common. May mimic precocious puberty.

Back 13

Single (eg, breast tissue). (AKA thelarche-isolated development of breast tissue prior to age 8, most commonly between ages 1-3)

Front 14

MAS is caused by a ____________ somatic mutation in the gene coding for the subunit of the __________ G protein, which is involved in transmitting hormone signals.

Back 14

POSTZYGOTIC somatic mutation

coding for the subunit of the STIMULATORY G Protein involved in transmitting hormone signals. cascades activated in the absence of hormone stimulation.

Front 15

Why do GnRH analogues work in treating central precocious puberty?

Back 15

GnRH analogues initially cause an increase in the pituitary release of gonadotropins but not long after this does desensitization occur. GnRH receptors are downregulated and therefore are less active in stimulating release of gonadotropins from the pituitary.

GnRH analogues also competetively bind the receptor, have greater resistance to degradation and increased affinity for the pituitary GnRH receptors.

Front 16

Treatment with GnRH analogues decreases gonadotropins and sex steroids to _________ levels, which is followed by ?

Back 16

prepubertal; regression of secondary sexual features.

Front 17

Treatment of precocious puberty with GnRH analogues also causes deceleration in the __________ ___________ rate, preserving or even improving predicted _________.

Back 17

skeletal maturation rate; height.

Front 18

In girls with central precocious puberty, when does treatment with GnRH analogues end?

Back 18

when puberty is appropriate based on her age and emotional maturity. Resumption of puberty occurs promptly after discontinuation of GnRH analogue therapy.

Front 19

How is GnRH is normally secreted? (quality) How about gonadotropins?

Back 19

episodic bursts (circhoral secretion)

Gonadotropins are also exerted in a pulsatile fashion so the episodic bursts of GnRH are essential for normal secretion of gonadotropins.

Front 20

What happens if GnRH is administered by constant infusion vs episodically? (what is the rate of secretion with best LH response?)

Back 20

Constant infusion: Downregulation of GnRH receptors in the ant pit and LH decreases to low levels.

Episodic (best response at 1 pulse per hour) LH secretion is stimulated.

Front 21

Frequency of GnRH secretions is ________ by and _________ by progesterone and testosterone.

Back 21

increased by estrogens, decreased by progesterone and testosterone.

Front 22

The frequency _________ late in the follicular phase of the cycle, culminating in the LH surge.

Back 22

increases (due to increased estrogen production)

Front 23

the frequency decreases during the _______ phase as a result of the action of __________.

Back 23

secretory; progesterone

Front 24

When estrogen and progesterone secretion decrease at the end of the cycle, frequency __________.

Back 24

increases

Front 25

At the time of the midcycle LH surge, the sensitivity of the gonadotropes to GnRH is greatly _______ because of their exposure to GnRH pulses of the frequency that exist at this time.

Back 25

increased

Front 26

Norepinephrine and possibly epinephrine _______ GnRH pulse frequency.

Back 26

increase.

Front 27

Opioid peptides (enkephalins and Beta-endorphin) ________ the frequency of GnRH pulses.

Back 27

reduce

Front 28

What are the diseases that are commonly treated with GnRH analogues?

Back 28

precocious puberty, endometriosis, leiomyomas, and cancer of the prostate.

Front 29

How does estrogen regulate LH secretion?

Back 29

A moderate, constant amount of circulating estrogen causes negative feedback on LH secretion. An elevated amount of estrogen causes positive feedback on LH secretion (hence the LH surge). It also only causes positive feedback after a minimum of about 36 hours in monkeys... So there must be elevated estrogen for a prolonged period to cause positive feedback.

Front 30

What color is the adrenal cortex?

Back 30

yellow due to cholesterol!

Front 31

Aldosterone is made in which part of the adrenal gland?

Back 31

Zona glomerulosa

Front 32

Cortisol is made in which layer?

Back 32

fasciculata

Front 33

Sex steroids are made in which layer of the adrenal cortex?

Back 33

reticularis

Front 34

What is the mnemonic for remembering layers and their associated hormones?

Back 34

it gets sweeter as it gets deeper/

Front 35

What is Cushing Syndrome?

Back 35

Excess cortisol

Front 36

What are the clinical features of cushing syndrome?

Back 36

muscle weakness with thin extremities, moon facies, buffalo hump, and truncal obesity (excess glucose --> insulin --> fat deposition), abdominal striae (ruptured blood vessels due to impaired repair of collagen), HTN (cortisol upregulates the alpha 1 receptors on arterioles), osteoporosis, immune suppression

Front 37

what are the 3 major mechanisms in which cortisol inhibits immune system?

Back 37

inhibits phospholipase A2

inhibits IL-2

Inhibits histamine release from mast cells

Front 38

How do you diagnose cushing syndrome?

Back 38

24 hour urine cortisol test.

Front 39

Causes of cushing syndrome?

Back 39

exogenous corticosteroids (only cause that gives you atrophy of both adrenals)

Primary adrenal adenoma, hyperplasia, or carcinoma (adenoma adrenal will be big, but the neg feedback on ACTH will cause opposite adrenal to be atrophic)

ACTH-secreting pituitary adenoma (both adrenals big and producing excess cortisol)

Paraneoplastic ACTH secretion (small cell carcinoma of the lung)

Front 40

Which diseases do you distinguish when you use a high-dose dexamethasone suppression test? What is the mechanism of this test?

Back 40

ACTH producing pituitary adenoma vs ectopic ACTH production by small cell lung carcinoma.

Suppresses ACTH production by the pituitary adenoma but does not suppress ACTH production by the small cell lung carcinoma

follow cortisol levels

Front 41

What is the presentation of hyperaldosteronism?

Back 41

excess aldosterone: hypernatremia, hypokalemia, metabolic alkalosis (dumping Hydrogen ions), HTN

Front 42

What is the most common cause of hyperaldosteronism?

Back 42

Adrenal adenoma

Front 43

What are other causes of hyperaldosteronism?

Back 43

sporadic hyperplasia and carcinoma of the adrenal gland

Front 44

What do labs show you in primary hyperaldosteronism?

Back 44

high aldosterone, low renin/

Front 45

Secondary hyperaldosteronism occurs due to ...?

Back 45

fibromuscular dysplasia (young woman) thickening of the wall of the blood vessel, activating the JGA.

Atherosclerosis (elderly males) decreases blood flow to the kidney, activating the JGA.

Each of these secrete renin which ultimately results in high aldosterone

Front 46

Define congenital adrenal hyperplasia briefly.

Back 46

excess sex steroids with hyperplasia of both adrenal glands. due to a congenital defect in the enzymes necessary for steroidogenesis.

Front 47

What is the first step in the pathway from cholesterol to mineralocorticoids, glucocorticoids, and sex steroids?

Back 47

Cholesterol to pregnenolone catalyzed by cholesterol side chain cleavage enzyme.

Front 48

If patient had clitoral enlargement (female) or precocious puberty (male) with life-threatening hypotension, excess ACTH (big adrenals), and hyponatremia and hyperkalemia, and hypovolemic, which enzyme is deficient?

Back 48

21 hydroxylase. Steroidogenesis is shunted towards sex steroid production. Deficiency of cortisol leads to increased ACTH which results in bilateral adrenal hyperplasia

Front 49

Clinical features of congenital adrenal hyperplasia?

Back 49

salt wasting with hyponatremia, hyperkalemia, and hypovolemia,

Life-threatening hypotension

Clitoral enlargement (females) or precocious puberty (males)

Front 50

Which two enzymes do you need to produce glucocorticoids?

Back 50

21 hydroxylase, and 11 beta hydroxylase

Front 51

Which enzyme do you need to produce weak mineralocorticoids?

Back 51

21 hydroxylase

Front 52

Which enzyme do you need to produce a higher level of mineralocorticoids?

Back 52

11 beta hydroxylase.

Front 53

If a patient presents with clitoral enlargement, hypotension, but non-severe hyponatremia (no salt wasting) which enzyme would be deficient?

Back 53

11 beta hydroxylase. (21 hydroxylase can make a weak mineralocorticoid, deoxycorticosterone)

Front 54

If patient presents with hypertension, and lack of sexual development, which enzyme is deficient?

Back 54

17 hydroxylase

Front 55

in any case of enzyme deficiency of the adrenal gland, you will always have a lack of which hormone? This causes which feature that is shared between all of the enzyme deficiencies?

Back 55

cortisol, adrenal hyperplasia due to increased ACTH.

Front 56

What is the most common congenital cardiac malformation in Turner's Syndrome? Usually occurs in __________ but can occur with ______ _________.

What is the murmur?

What happens to the valve over time?

Back 56

bicuspid aortic valve

Isolation; aortic coarctation

aortic ejection sound, which is an early systolic, high-frequency click heard over the R 2nd interspace.

it calcifies- may result in progressive valvular dysfunction, manifesting with aortic infectious endocarditis due to abnormal leaflet structure and turbulent flow.