Clinical Approach To Pituitary/endocrine Diseases

Question 1

Hypothyroidism

Answer 1

Low levels of thyroid hormone in blood
- causes lowered metabolic rates, HR/contractility and lowered energy levels

Most commonly is caused by autoimmune destruction of the thyroid itself

• this is primary hypothyroidism
• in this case, TSH/TRH will ALWAYS be elevated since the pituitary knows there is low T3/T4 so its trying to get the thyroid to work (but it cant)
• TSH is most clinically sensitive measure

Can be due to damage to the pituitary or hypothalamus however in which case it is secondary
- most common cause is pituitary mass
- really only tested for if patients have symptoms of cancer, hemochromatosis, sarcoidosis or sheehan syndrome. Also if new onset headache or visual changes (especially bitemporal hemianopsia) with hypothyroid symptoms
- this is noted by LOW or NORMAL TSH in blood. T4 is also ALWAYS LOW
Symptoms:
- fatigue
- weight gain
- cold intolerance
- edema
- dry skin
- menstrual irregularities

Question 2

Pathway of TH release

Answer 2

1) hypothalamus releases Thyroid releasing hormone (TRH) to the anterior pituitary
2) anterior pituitary releases thyroid stimulating hormone (TSG) to the thyroid gland
3) thyroid gland secretes T3/T4 hormones

Question 3

Causes of poor lactation in general

Answer 3

Two sub groups

1) poor milk extraction
- infant can latch properly or feeding techniques are improper

2) poor milk production
- stress/obesity/HTN/DM/ elevated androgens
- medications (primarily estrogen or dopaminergic agonists)
- pituitary infarction (Sheehan syndrome)
- breast reduction or radiation

Question 4

How is prolactin regulated?

Answer 4

Is always tonically produced in the anterior pituitary

• is tonically inhibited however by hypothalamic dopamine. Most commonly seen in the action of the baby suckling the nipple
• *when dopamine is lowered = lactation**

Thyrotopin releasing hormone also plays a small role in increasing secretion as well

Serum estrogen and progesterone both also play a role

• estrogen = increases prolactin secretion
• estrogen + progesterone = inhibit production of breast milk at the mammary gland
• after giving birth, estrogen and progesterone levels drop allowing for breast milk to be produced since now it is not being inhibited

Question 5

Prolactin vs oxytocin

Answer 5

Prolactin:

• from anterior pituitary
• function is to increase production of breast milk

Oxytocin:

• from posterior pituitary
• function is to allow for milk ejection from breast by contracting myoepithelial cells

Question 6

Pituitary infarction (Sheehan syndrome)

Answer 6

Seen after pregnancy or during pregnancy

During pregnancy, the pituitary Hypertrophies but blood supply DOESNT. So there is less blood supply to the pituitary as needed and increases risks of infarction (due to stroke, or hemorrhages there or else where in the body)

Question 7

Ovarian function broadly

Answer 7

Normally cyclically produces estrogen and progesterone while also holding eggs. The levels get higher through ovulation
- the cyclically nature matures and grows the endometrial lining of the uterus to prepare it for child birth

If there is no pregnancy that occurs, then estrogen and progesterone levels drop in the ovaries (but not completely) and causes the endometrial lining to “slough off” as menstrual bleeding (known as the period)

Question 8

Ovarian control broadly

Answer 8

Is controlled by the hypothalamus, anterior pituitary and ovaries

1) hypothalamus releases GnRH which goes to the anterior pituitary
2) GnRH increases secretion of FSH and LH from the anterior pituitary gland which goes to the ovaries
3) the ovaries tonically produce estrogen and progesterone, however FSH/LH increases the rate at which these are produced
4) during menstration (or if it does) the ovaries produce estradiol which goes to the hypothalmus and anterior pituitary and lower the activity of these organs (until period is done)

Question 9

How does intrauterine scarring prevent normal menstration?

Answer 9

The endometrial growth gets “stuck” on the scarring and prevent sloughing off during periods (or makes the timeframe irregular)

Question 10

Primary Ovarian disorders and GnRH/FSH/LH production

Answer 10

If the ovaries are damaged or not functioning = decreases progesterone/estrogen/estradiol production

This lowers (but not completely eliminates) the inhibition on the anterior pituitary and hypothalmus as it pertains to FSH/LH and GnRH secretion respectively

Therefore, FSH/LH and GnRH will all be very elevated, but estrogen/progesterone will be low and menstrual cycle will be erratic

Question 11

What are the most common causes of amenorrhea?

Answer 11

Pregnancy is #1

Polycystic ovarian syndrome (PCOS) is #2

Functional hypothalamic amenorrhea is 3rd most

Question 12

Primary hypothalamic dysfunction effect on menstration

Answer 12

Is a cause of secondary ovarian dysfunction

If the hypothalamus is damaged or doesnt work properly = lowers secretion of GnRH, FSH/LH and estradiol/progesterone
- EVERYTHING IS LOWERED

Results in amenorrhea

Causes:

• actual damage to hypothalamus
• excessive exercising
• low body weight/malnutrition
• severe systemic illnesses
• severe emotional stress

will resolve after underlying issue resolves

Question 13

How does prolactin decrease ovary function and amenorrhea

Answer 13

Prolactin levels inhibts GnRH release

This is commonly seen in breast feeding**

Question 14

Pituitary primary dysfunction effects on amenorrhea and ovaries

Answer 14

Decreases anterior pituitary function causes a decrease in FSH/LH function and also decreases estrogen and progesterone secretion

GnRH will be VERY HIGH however**

This is a secondary disorder (secondary hypogonadism)

Causes:

• any direct damage or mass to pituitary
• TBIs and stroke history
• hemochromatosis or sarcoidosis
• systemic infections (especially TB/syphills and toxoplasmosis)
• Sheehan syndrome

Question 15

How does thyroid disease cause amenorrhea?

Answer 15

Primary thyroid diseases results in an increase of TRH naturally
- TRH however, also increase prolactin release of the anterior pituitary

Prolactin inhibits GnRH and FSH/LH levels in the blood
- this ends up decrease progesterone/estradiol

Question 16

Adrenal gland functions

Answer 16

Medulla layer = secretes epinephrine and norepinephrine in times of stress
- NOT controlled by pituitary

Inner Cortex layer = secretes cortisol (outer-inner/fascicular layer) in times of stress and androgens (inner-inner/reticular layer) in puberty and just tonically
- IS controlled by pituitary

Outer cortex layer = secretes aldosterone

• increases renal K+ secretion and reabsorbs Na+/H20
• focus is to keep volume levels high
• IS controlled by pituitary

Question 17

Cortisol functions

Answer 17

Stimulates gluconeogenesis

Inhibits immune system function
- more or less just controls it (doesnt turn it off) and prevents/decreases chronic inflammation

Helps maintain vascular tone and blood pressure

Question 18

Adrenal gland regulation by hypothalmus and pituitary

Answer 18

Mental/physical stress leads to increased hypothalamic secretion of corticotrophs releasing hormone (CRH) to the anterior pituitary

Anterior pituitary then secretes ACTH which goes to the adrenal gland and stimulates all its secretion (not much of medulla however)

• primarily secretes excess cortisol**
• does increase synthesis of aldosterone and epinephrine/NE also (but DOESNT release aldosterone and only minor releases epinephrine/NE. Secretion fo aldosterone is controlled by RAAS)

Question 19

Primary adrenal insufficiency (Addison disease)

Answer 19

Damage to the adrenal cortex leads to decreased aldosterone/cortisol and androgens
- primarily an autoimmune cause

Also INCREASES CRH and ACTH (since the hypothalamus and anterior pituitary aren’t affected)

Symptoms vary widely but most common are

• mild hyperkalemia
• major hyponatremia and ECF fluid loss
• low glucose levels
• spontaneous fevers and mild sepsis-like conditions (especially hypotension)
• lowered sex libido in women*
• decreases pubic/axillary hair growth in women*
• increased skin pigmentation especially around palmar/elbow creases**
• in men the testes producer enough testosterone and androgens to mask this usually so these symptoms are not normally seen in men with normal testie function

** in primary adrenal insufficiency, the increased production of ACTH in response by the anterior pituitary leads to a secondary increase in melanocyte stimulating hormone release. This increase pigmentation especially in crease areas**

Question 20

Adrenal crisis

Answer 20

Also known as acute adrenal insufficiency
- usually brought on by acute infection or severe dehydration/physical stress

Induces severe hypotension, shock, fever, coma, death

This is caused by acute severe loss of everything in adrenal gland. Much easier to see than chronic insufficiency and often can be confused with septic shock

Question 21

Secondary adrenal insufficiency

Answer 21

Looks very similar to primary adrenal insufficiency except it is caused by anterior pituitary damage which leads to decreased ACTH production and secretion.
- remember that ACTH primarily controls secretion of cortisol (although does have minor effects on all other zones of the adrenal gland)

DOESNT show hyperpigmentation and LESS symptoms of androgen loss and hypoaldosteronism

**STILL shows symptoms of hypo secretion of cortisol (low blood sugar, hypotension and random fevers)

Question 22

Why is secondary adrenal insufficiency more common than primary?

Answer 22

Because it is seen in rapid cessation of glucocorticoid medications after prolonged use. THIS IS WHY YOU NEED TO TAPER
- especially prednisone

Introducing exogenous prednisone causes the pituitary to think that cortisol levels are very high in the body

• so this lowers ACTH levels in the body and therefore endogenous cortisol levels
• sudden withdrawal doesn’t give the anterior pituitary enough time to “rebound” and start working again so thou will adrenal insufficiency symptoms because there is no-little cortisol in the body

Question 23

How to differentiate primary from secondary adrenal insufficiency with labs

Answer 23

Both require measurement of morning cortisol and ACTH

If both are low OR low cortisol and NORMAL ACTH = secondary adrenal insufficiency

If cortisol is low but ACTH is very high = primary adrenal insufficiency

Question 24

High yield symtpoms and words for adrenal insuffiency

Answer 24

Hypotension, fatigue, hypoglycemia, Hyperkalemia or hyponatremia without having clear cause = 1st adrenal insufficiency
- may also show hyperpigmentation of skin and creases

Recently stopped a corticosteroid without skin hyperpigmentation or hyperkalemia = 2nd adrenal insufficiency
- may also show visual changes and new headache

Question 25

What is the most unusual chief complaint of adrenal insufficiency?

Answer 25

Psychosis

Question 26

Why is growth hormone difficult to measure?

Answer 26

It is released by the anterior pituitary in a pulsitile fashion

Therefore in order to measure levels clinically, often use insulin growth factor-1 (IGF-1) which correlates well growth hormone and is more stable in levels in blood

Question 27

Growth hormone deficiency

Answer 27

Low levels of growth hormone leads to decreased growth velocity and stature in children
- this is why you need to use a charting curve for kids and screen this in kids who have “fallen off the curve”

Gotta rule out normal variant or pathologic dangerous causes (malnutrition, poor immunity, pituitary tumor, etc.)

Highly suspected if delayed bone age on XRays, decreased IGF-1 and IGFBP-3
- confirm by giving a substance that promotes GH secretion and still showing low GH levels even altering trying to force it to produce

Question 28

Adult GH deficiency causes

Answer 28

Much rarer and harder to spot since the plates are fused already

Causes:

• increased fat mass
• decreased lean body mass
• decreased bone mineral density
• chronic fatigue

Question 29

ADH regulation

Answer 29

Osmotreceptors in blood vessels recognize low volume and high osmolarity of blood which triggers a release of ADH front he anterior pituitary

ADH then goes to CD of nephrons and upregulates aquaporins to retain water and increase urine osmolality

Question 30

Difference between nephrogenic and central DI

Answer 30

Nephrogenic

• CDs or nephrons are insensitive to ADH
• high ADH levels in blood

Central

• pituitary cant secrete ADH since its damaged
• low levels of ADH in blood

both cause the same symptoms, except central may also present with other endocrine symptoms also

Both are confirmed via administering desmopressin (synthetic ADH)

• if urine becomes concentrated = central
• if urine is still clear = nephrogenic

Question 31

What do you have to rule out first before diagnosing DI?

Answer 31

UTIs

DM

Excessive fluid drinking (benign variant)

All three can also present with polydipsia, polyuria and clear urine

Question 32

Hyperprolactinemia

Answer 32

Excess prolactin secretion from anterior pituitary

Causes spontaneous bilateral galactorrhea and amenorrhea

Causes:

• pregnancy
• prolactin secreting pituitary adenoma
• non secreting pituitary adenoma (caused by mass disrupting dopamine inhibition)
• medications
• primary hypothyroidism (due to increased TRH and TSH secretion
• renal failure (doesnt eliminate prolactin hormone)

Question 33

Hyperthyroidism

Answer 33

Excessive release of T3/T4 hormones

common symptoms:

• anxiety
• palpitations
• heat intolerance
• tremor
• weight loss
• increased appetite

Causes:

• Graves’ disease (most common and caused by TSH autoantibodies that acts as synthetic TSH and induces excess T3/T4. Is a primary thyroid disorder!)
• hasitoxicosis (early phase of hashimoto thyroiditis can cause transient hyperthyroidism before hypothyroidism. Is a primary thyroid disorder!)
• toxic adenoma or goiter (tumor on thyroid that secretes thyroid hormone. Is a primary disorder!)
• pituitary thyrotroph adenomas (is a secondary disorder!)

Question 34

Cushing syndrome

Answer 34

Excess cortisol secretion front he adrenal glands

Symptoms:

• weight gain (especially in upper back and face “buffalo hump”)
• facial flushing and rounded face appearance (“moon-like face”)
• decreased libido
• menstrual cycle changes
• hirsutism
• HTN
• easy brushing and stretchy skin
• glucose intolerance
• striae (classically on the abdomen, lower back and breasts)
• bone loss

Two subtypes

1) ACTH dependent = excess cortisol driven by excess ACTH levels
- “secondary hypercortisolism”
- most common cause = Cushing disease via ACTH producing pituitary tumors

2) ACTH independent = NOT driven by excess ACTH secretion
- “primary hypercortisolism”
- most common cause = iatrogenic via over prescribed steroids or sudden withdrawal of steroids

Question 35

Gigantism/acromegaly

Answer 35

Botha re caused by excessive GH production and secretion

Gigantism = child or with growth plates still currently open
- VERY tall height and long limbs

Acromegaly = growth plates are fused shut already

• causes enlarged jaw/nose and beefy tongue
• excessive lordosis in lumbar region
• enlarging hands/feet with “sausage fingers”
• NO CHANGES in height
• can also increase risk for HTN, cardiomyopathy, sleep apnea and insulin resistance
• also often presents concurrently with other endocrine disorders

Question 36

Why does precocious puberty cause both abnormally tall child but short adult?

Answer 36

Causes excessive growth when plates are still open = tall child

However, also prematurely closes growth plates = short adult

Question 37

SIADH

Answer 37

Excessive ADH/ vasopressin release

ALWAYS presents with hyponatremia and neurologic dysfunctions but EUVOLEMIC and concentrated urine
- also fatigue and weight loss

Most frequent cause is small cell lung cancer surprisingly although it can be posterior pituitary tumors and CNS disorders

• also medications and sometimes really bad pneumonia
• USUALLY NOT an adenoma