Where is the pituitary? What is around it?
The anterior pituitary lies in the third ventricle, inferior to the hypothalamus and the pituitary stalk.
It is surrounded by the Sella turcica
Go Look For The Adenoma Please
GH, LH, FSH, TSH, ACTH, PROLACTIN
(A compressive adenoma in pituitary will impair hormone production in this order (i.e. GH-secreting cells are most sensitive to compression)
Anterior Pituitary Cell Types
Somatotrophs (50%) - GH
Corticotrophs (15%) - ACTH
Lactotrophs (15-20%) - PRL (prolactin)
Gonadotrophs (10%) - LH and FSH
Thyrotrophs (5%) - TSH
What hormones does the ant pituitary produce?
Prolactin - 60%
GH - 20%
ACTH - 10%
TSH, LH, FSH - Rare
What inhibits and causes secretion of each of those hormones?
GnRH secretes FSH and LH
GHRH secretes GH
TRH secretes TSH and Prolactin
VIP PHI-27 secretes Prolactin
CRH, ADH (vasopressin) secretes ACTH, B-lipotrophin and B-endorphin
Somatostatin inhibits GH and TSH
Dopamine inhibits TSH and Prolactin
What are the anatomic and hormonal effects of a pituitary tumor?
1. Space occupying effects (tumor can press on other areas)
2. Excess hormone production and its sequel
3. Loss of function of the remaining gland
4. *Pituitary tumors are rarely malignant and seldom metastasize*
What is the most likely hormone to be produced by a pituitary tumor?
What are symptoms and signs of a prolactinoma in premenopausal women and why?
1. Galactorrhea - lactation in the absence of nursing
2. Amenorrhea - hyperprolactinoma suppresses pulsatile LH secretion)
4. Oligomenorrhea - changes in menstrual cycle
What are symptoms and signs of a prolactinoma in postmenopausal women and men and why?
1. Space occupying effects are more common - headaches and visual field disturbances
2. In men, erectile dysfunction, diminished libido
What are symptoms and signs of a prolactinoma due to space occupying effects and why?
1. CSF rihorrhea - if the floor of the sella tucica is eroded or extended into sphenoid cavity
2. If there is a lateral extension into the cavernous sinuses unilateral defects in CN III (most commonly), IV, V and VI occurs
3. If the adenoma compresses the optic chiasm, bi-temporal hemianopsia (loss of temporal vision) occurs
If a pt presented with all/any of the symptoms/signs, what would be your differential diagnosis?
Renal failure (BUN/Cr)
Cirrhosis (LFTs - liver fxn tests)
How would you narrow down your diff diagnosis?
MRI evaluation of the pituitary
What lab work would you order if you suspected a prolactinoma and why? What results would you expect?
Would check serum prolactin level.
Would expect it to be high; >200 mg/dl
What are the other causes of increased prolactin? (What in the pt's hx should make you suspicious for increased prolactin?) Why do those problems (for ex. Hypothyroidism) have an increased prolactin?
3. Nipple piercing, augmentation
4. Chronic chest wall stimulation
5. Hyperthyroidism (high TSH causes prolaction secretion)
6. Pituitary tumors that secrete prolactin
7. Pituitary stalk lesions
8. Dopamine antagonists
What decreases prolactin levels and why?
Dopamine keeps prolactin secretion "in check" because prolactin is secreted continuously unless otherwise inhibited
What radiology study would you order if worried about a prolactinoma?
An MRI evaluation of the pituitary gland and hypothalamus
Explain macroadenoma vs microadenoma to a patient.
Microadenoma (most common) - a tumor < 1 cm in diameter, treated with transsphenoidal surgery
- pituitary function is preserved in 95% of cases
Macroadenoma - a tumor > 1 cm in diameter, treated with radiation therapy
- risk and complications increase, higher risk of panhypopituitarism
How do you treat a prolactinoma and why?
Treat underlying problems FIRST. If TSH is increased, fix that first, then start working down the list.
Medical treatment of choice:
**Transsphenoidal surgery (best for microadenoma):
- Tumors unresponsive to medical treatment
- Tumors affecting visual fields
- Pt refuses medical therapy
- Reserved for macroadenomas that enlarge despite medical therapy
What side effects/outcomes could be anticipated with treatment?
- Side effects such as nausea, dizziness and orthostatic HoTN can be seen with dopamine agonist (take at night to avoid)
- There is a high risk of panhypopituitarism with radiation therapy (10-15% of all pts)
What are symptoms and signs of a growth-hormone pituitary adenoma and why?
- Increased stature
- Protruding mandible (prognathia)
- big tongue (macroglossia)
- enlarged forehead (frontal bossing)
- spade-like hands with widened fingers
- sweaty palms and large feet
- osteoarthritis from abnormal joint loading
- Dialated cardiomyopathy→cariomegaly→cardiac failure
- Impaired glucose tolerance
- Diabetes mellitus (weight gain) - due to tissue insensitivity to insulin causing increased plasma glucose
- Excessive sweating
5. Temporal hemianopsia (blindness in half the visual field
If a pt presented with all/any of the symptoms/signs, what would be your differential diagnosis of elevated GH and IGF-1?
All of the following can throw off IGF-1
1. Recent exercise
2. Eating immediately before IGF-1 assay is drawn
3. Acute illness, agitation
4. Diabetes mellitus
How would you narrow down your diff diagnosis?
1. Obtain random IGF-1
2. If random IGF-1 is normal = not acromegaly
3. If the level is abnormal - order fasting IGF-1 and prolactin
4. If the IGF-1 is still elevated, give glucose (glucose normally suppresses GH
5. If elevated GH level (>2mU/L) after 60 minutes = confirms acromegaly
What lab work would you order if you suspected acromegaly and why? What results would you expect?
IGF-1 and glucose method as mentioned above
MRI with contrast for hypothalamic or pituitary tumor - **imaging study of choice for the diagnosis of acromegaly
If patient does have acromegaly, what tests would you order to screen for other possible problems?
Complications of Acromegaly
- Impaired fasting glucose
- Diabetes mellitus
- Cardiac enlargement / failure
- Carpal tunnel and arthritis
What are the other causes of increased growth hormone? (What in the pt's hx should make you suspicious for increased growth hormone?) Why do those problems have an increased growth hormone?
All of the following INCREASE secretion of GH:
1. GHRH - triggers pathway
2. Sleep - associated with growth hormone peaks
4. Trauma - stress to body
5. Acute illness - stress to body
6. Hypoglycemia - Insulin-induced hypoglycemia stimulates GH release 30-45 minutes after the blood glucose reaches its lowest point.
What decreases growth hormone levels and why?
1. Somatostatin - inhibitory peptide
3. Hypothyroidism - Low thyroid hormone levels are also associated with low GH levels.
4. Glucocorticoids - inhibit somatic growth either by increasing somatostatin release or by causing damage to pituitary somatotrophs.
5. Increased levels of IGF-1
What radiology study would you order if worried about a growth hormone pituitary adenoma?
Imaging - MRI with contrast for hypothalamic or pituitary tumor -** imaging study of choice for the diagnosis of acromegaly
Memory tool for acromegaly symptoms
Remember your alphabet - "ABCDEF"
A: Arthritis / arthralgias
B: BP increased
C: Carpal tunnel
E: enlarged organs
F: Field defects in vision
How do you treat a growth-hormone pituitary adenoma and why?
Pituitary microsurgery (Endoscopic transnasal, transsphenoidal resection):
- Treatment of choice
Medical - usually not sufficient by itself:
**Used in patients who have persistent acromegaly despite surgery
**Dopamine agonists (activates dopamine receptors in the absence of dopamine)
**GH receptor antagonist
1. Pegvisomant - blocks the hepatic IGF-1 production, doesn't shrink tumor
- Reserved for patients who fail surgical or medical therapy
What would you tell a patient that wants to take OTC growth hormone?
The pituitary gland won't have to produce as much GH on it's own anymore and cause it to atrophy. When you want it to produce again it will have problems.
What are symptoms and signs of partial and total pituitary failure (know Sheehan's syndrome (coming up below) and gonadotropin def in children) and why?
Usually there is a gradual loss of normal pituitary function.
The order of loss: GH, gonadotropins, TSH, ACTH
Global failure of pituitary gland = panhypopituitarism
Gonadoropin Deficiency - in children
**failure to enter normal puberty
- Girls: delayed breast development, scant pubic and axillary hair, primary amenorrhea
- Boys: phallus and testes remain small, body hair is sparse
- If GH secretion continues, there will be a failure of closure of epiphyses of long bones
What is the etiology of Sheehan's syndrome? What are "red flags" in patient's history?
Etiology: hypothalamic or pituitary dysfunction
Postpartum necrosis = Sheehan's syndrome
- Vascularity and size of the pituitary increases during pregnancy
- There is a history of massive blood loss and/or hypovolemic shock during delivery
- Patient presents with failure to lactate after delivery as well as amenorrhea
- Patient may have symptoms/signs of hypothyroidism and/or glucocorticoid insufficiency
What lab work would you order if you suspected a pituitary failure and why? What results would you expect?
Order labs on pituitary and target organ hormones
Both should be low (Ex. Free T4 is low and TSH is not elevated in response)
What are the causes of pituitary failure? What in patient's history should make you suspicious?
- Pituitary adenoma
- Hypothalamic or CNS tumor
- Head trauma
- Sheehan's syndrome
- Pituitary apoplexy
- Pituitary surgery
- Cranial radiation
6. Empty-Sella Syndrome
- Fluid suppressed the pituitary
What are symptoms/signs of pituitary apoplexy?
*An acute hemorrhage occurs in a preexisting adenoma
- the pt presents with a severe headache and visual field deficits
**This is acute hypopituitarism - treat with glucocorticoids immediately
- The pt requires immediate surgery for decompression of the pituitary fossa
Why do patients die with pituitary apoplexy?
Apoplexy - acute loss of consciousness followed by paralysis
Lack of cortisol
What is the most life-threatening hormone def?
ACTH deficiency - adrenal glands fail to secrete sufficient amounts of cortisol
- Sudden deficiency: Hypotension - may cause cardiovascular colllapse
What is treatment for pituitary apoplexy?
- Treat with glucocorticoids immediately (some kind of steroid / cortisol)
- Requires immediate surgery for decompression of the pituitary fossa