Pituitary and Hypothalamic Disorders Flashcards
Anterior pituitary disorders?
6
Adenomas Prolactinoma Acromegaly Gigantism Panhypopituitarism Cushing’s Disease
Posterior pituitary disorders?
2
SIADH
Diabetes Insipidus
6 Regulatory Hormones of the Hypothalamus
- Thyrotropin releasing hormone (TRH)
- Gonadotropin releasing hormone (GnRH)
- Corticotropin releasing hormone (CRH)
- Growth hormone releasing hormone (GHRH)
- Growth hormone inhibitory hormone (somatostatin)
- Prolactin inhibiting hormone (PIH)
Major Hormones of the Anterior Pituitary
6 major
- FSH
- LH
- ACTH
- TSH
- Prolactin
- GH
Mnemonic: FLAT PeG
- Also MSH (melanocyte stimulating hormone) but not a major hormone
Hormones of the Posterior Pituitary
2
Where are these hormones manufactured?
- ADH
- Oxytocin
These hormones are manufactured in the hypothalamus
What do these hormones act on?
- ADH?
- Oxytocin? 2
- GH? 3
- ACTH?
- TSH?
- FSH and LH? 3
- Prolactin?
- kidney
- breasts and uterus
- bones and soft tissue but also acts on liver to produce somatostatin
- adrenal glands
- thyroid
- testes, ovaries, corpus luteum
- breasts
Sella turcica pituitary disorder?
depression of the bone at the base of the skull where the pituitary gland is located
Pituitary Tumors can present a variety of ways. What are they?
3
- Hormonal abnormalities
- Neurologic symptoms
- Incidental finding on MRI obtained for another reason (the “incidentaloma”)
What are the pituitary disorder Neurologic symptoms?
2
Headache
Visual field impairment
Adenomas are what?
What are the types? 2
Which is more common?
Which can be worse?
a benign tumor of glandular tissue
Microadenoma
- tumor less than 10 mm in diameter
- More common than macroadenomas
Macroadenoma
- Larger than 10 mm in diameter
- May cause mass effect
Example of a microedema?
Ex: Prolactinoma
Elevated prolactin levels have multiple etiologies.
What are they? 4
Whats the most common cause of sellar region masses?
Most common type of pituitary adenoma?
What do all these usually cause?
- Adenoma (most common cause of sellar region masses)***
- Prolactinoma – most common type of pituitary adenoma**
- Trauma
- Medications
Hypothyroidism
What medications can cause elevated prolactin levels?
4
- SSRI’s (antidepressants)
- antipsychotics,
- cocaine,
- alpha methyldopa (treats hypertension)
A prolactinoma is a tumor of what?
What does it secrete?
May cause compression of what which leads to what?
anterior pituitary
Secretes prolactin
May cause compression of the optic chiasm and lead to bitemporal hemianopsia
Signals from the hypothalamus may be interrupted with damage to the what?
What signals specifically?
And what will remain unchecked?
Stalk
Prolactin inhibiting hormone (dopamine) from the hypothalamus will not be transmitted to the pituitary if the stalk is damaged
Prolactin levels then increase unchecked
Medications that increase serotonin may lead to increased what?
prolactin levels
What are the medications that increase serotonin thus increasing prolactin?
4
- Antidepressants
- Antipsychotics
- Alpha methyldopa (Aldomet…antihypertensive)
- Serotonin is a prolactin releasing factor
What syndrome may also lead to increased prolaction levels?
What stimulates prolaction levels that is releaased from the hypothalamus?
Why would this affect prolactin levels in hypothyroidism?
Hypothyroidism
TRH
Because there is low thyroid hormones being made so the body is producing more TRH
d
d
Adenomas cause increased levels of what?
What does prolaction block? 2
Prolactin
Prolactin blocks gonadotropins FSH and LH
Symptoms of prolactinoma differ in men and women.
Women? 3
Men? 6
Women
- Amenorrhea,
- galactorrhea
- infertility
Men
- Decreased libido,
- gynecomastia,
- erectile dysfunction
- infertility,
- bitemporal hemianopsia
- headache
Symptoms due to decreased testosterone and mass effect from the tumor
What test should we do for diagnosis of prolactinoma?
What additional tests?
7
Best initial test
Prolactin level
Additional tests to rule out causes of secondary hyperprolactinemia
- TSH,
- Beta-HCG,
- CMP (electrolytes, liver, renal), 4. LH, FSH,
- serum estradiol (women),
- serum free and total testosterone (men)
- MRI to confirm the diagnosis
Medical treatment for prolactin issues is what?
2
Other options for therapy?
3
is with dopamine agonists.
Cabergoline
Best tolerated
Bromocriptine
- Transsphenoidal pituitary surgery for large symptomatic tumors
- Radiation therapy in some
- Chemotherapy with Temozolomide if no response to medications or radiation and if not a surgical candidate
Acromegaly is an Anterior pituitary disorder characterized by:
Enlargement, thickening, and broadening of bones
Particularly extremities
Causes of Acromegaly
2
- Hypersecretion of GH after fusion of epiphysis with shaft of bone
- Adenomatous tumor of anterior pituitary involving the acidophilic cells.
Signs and symptoms
of acromegaly:
9
Striking features are protrusion of?
- Supraorbital ridges
- Broadening of nose
- Thickening of lips
- Thickening and wrinkles formation on forehead
- Lower jaw (prognathism)
Kyphosis: enlargement of hands and feet with bowing spine
Scalp is thickened and thrown into folds
Overgrowth of body hair
Visceral organs are enlarged
headache
Visual disturbance – Bitemporal hemianopia
CHF common later in life
carpel tunnel
Lab and vital signs that will be different in acromegaly?
3
Thyroid, parathyroid and adrenal glands shows hyperactivity
Hyperglycemia and glucosuria
Hypertension
Acromegaly is almost always caused by what?
What do we have excess of?
Common age?
may be associated with what? 2
pituitary tumor
Excess growth hormone (GH)
Most frequently occurs in ages 20-40
May also be associated with tumors of the pancreas or parathyroid glands
Acromegalics suffer end-organ effects from what?
2
- hypertension
2. abnormal glucose metabolism
Acromegalic Gigantism
pathophysiology?
When does this condition occur?
If GH is produced in excess prior to epiphyseal plate closure…..the results if gigantisim
Gigantism occurs during childhood
Acromegaly appears during adulthood
Gigantism Pituitary disorder characterized by:
2
- Excess growth of body
2. Average height is approximately 7 – 8 feet
Causes of Gigantism
2
- Hypersecretion of GH in childhood or in pre – adult years
2. Tumor of acidophilic cells of Anterior pituitary
Signs and Symptoms
of gigantism?
7
- Huge stature : 7 or 8 feet height
- Hyperglycemia
- glycosuria
- pituitary diabetes mellitus
- Headache due to tumor of pituitary
- Visual disturbances
- Gigantism ends in hypopituitarism (burning of cells of anterior pituitary )
Best initial test is rule out/in acromegaly is what?
What are the other tests that are used to diagnose acromegaly? 2
IGF-1 level
IGF-1 level (insulin like growth factor)
- Serum GH not suppressed following oral glucose load (75-100 g glucose)
- MRI
Pituitary tumor in 90%
Treatment of choice for acromegaly/ gigantism is?
Best surgical therapy?
Best medical therapy?
Alternative surgical and medial therapy? 4
surgical.
Transsphenoidal resection
Best medical therapy is cabergoline (oral)
Or
- ocreotide
- lanreotide
- pegvisomant (subcutaneous injections)
- Gamma knife radiosurgery if they fail transsphenoidal surgery
Hypopituitarism etiology
7
- Pituitary apoplexy
- Sheehan’s syndrome
- Infiltration
- Non-functioning adenoma
- Trauma
- Stroke
- Mass effect
Sheehan’s syndrome is what?
What is pituitary apoplexy?
Post partum pituitary ischemic necrosis
Hemorrhage into the pituitary gland
What could cause infiltration that leads to hypopituitarism?
5
- Sarcoid
- hemochromatosis
- TB
- syphilis
- tumors
The first hormone deficiency to develop with lack of a functioning pituitary is what?
What is the 2nd?
3rd?
4th?
GH
1st hormonal deficiency to develop
LH/FSH
2nd
TSH
3rd
ACTH
4th
Deficiencies of the following hormones cause a variety of symptoms.
- LH/FSH? 6
- GH? 9
- TSH? 5
- ACTH? 5
1. Amenorrhea infertility decreased pubic and axillary hair genital atrophy decreased libido erectile dysfunction
2. ↑ abdominal fat anxiety depression fatigue ↓libido ↓muscle mass osteo(porosis/penia) ↑LDL ↑Triglycerides
3. Fatigue weight gain weakness decreased appetite cold intolerance
4. Fatigue decreased appetite decreased pigmentation low blood pressure low glucose
Congenital panhypopituitarism
signs and symtoms?
5
Micropenis Midline defects Optic atrophy Hypoglycemia Poor growth
What is a Pituitary apoplexy?
Usually secondary to what?
Hemorrhage into the pituitary
Usually secondary to existing adenoma
Acute symptoms of Pituitary apoplexy?
5
How would we treat it/diagnosis?
5
- headache
- nausea and vomiting
- altered mental status
- low blood pressure
- low blood glucose
….a rare endocrine emergency - Stabilize,
- assessement of fluid and electrolyte balances
- IV steroids
- “Acutely unwell” patients should have prompt neurological assessement
- Surgery if severe ophthalmic signs or deteriorating mental status
What is post partum ischemic necrosis of the pituitary?
What is it usually secondary to?
Symtpoms?
Sheehan’s Syndrome
Secondary to
- hypotension
- emboli
- HELLP syndrome
Symptoms
- Difficulty breastfeeding
- extended amenorrhea
Best initial test for hypopituitary function is to check what?
Which ones are these? 4
After initial test what should we of?
anterior pituitary hormones
- LH/FSH
- IGF-1 or GH insulin response test
- TSH
- ACTH
MRI
What do we do for the IGF-1 or GH insulin response test?
Administer insulin to lower blood glucose level
GH should increase due to insulin release
How is ACTH measured?
Measured indirectly through cortisol levels
Sheehan’s Syndrome/hypopituitary function treatment?
3
- Address underlying cause
- Replace needed hormones
- Pituitary apoplexy may require surgical decompression
Causes of Cushing’s disease?
2
- Hypersecretion of glucocorticoids
mainly cortisol - Either pituitary origin or adrenal origin
(disease vs syndrome)
In cushings disease if it is pituitry of origin how would it present clinically?
3
- Increased secretion of ACTH leads to
- hyperplasia of adrenal cortex therefore,
- hypersecretion of glucocorticoids takes place
ACTH is increased by what?
3
- Tumor in pituitary cells (basophilic cells)
- Malignant tumor of nonendocrine origin like cancer of lungs or abdominal viscera
- Hypothalamic disorder causing hypersecretion of corticotropin releasing hormone
Signs and Symtpoms of Cushings disease:
Disproportionate distribution of body fat results in?
4
- Moon face : Fat accumulation and retention of water and salt
- Torso : Fat accumulation in chest and abdomen but slim legs and arms
- Buffalo hump : Fat deposit on the back of neck and shoulder
- Pot belly : Fat accumulation in upper abdomen
Signs and Symtpoms of Cushings disease:
Purple striae : Reddish purple stripes on abdomen due to mainly three reasons?
- Stretching of abdominal wall by excess subcutaneous fat
- Rupture of subdermal tissues due to stretching
- Deficiency of collagen fibers due to protein depletion
Other signs and symtpoms of cushings disease?
12
- Thinning of extremities
- Thinning of skin and subcutaneous tissues
- Darkening of skin on neck (aconthosis)
- Pigmentation of skin
- Facial redness (facial plethora)
- Weakening of muscle
- Facial hair growth ( Hirsutism )
- Bone resorption leads to osteoporosis
- Hyperglycemia due to gluconeogeneis leads to adrenal diabetes and glycosuria
- Hypertension
- Immunosuppression resulting in susceptibility for infection
- Poor healing
What does SIADH stand for?
SIADH is characterized by what?
What is this due to?
3
Syndrome of Inappropriate Antidiuretic Hormone
euvolemic hyponatremia due to elevated ADH levels.
- Reabsorption of excess fluid
- Low sodium
- Low serum osmolality
IF SIADH is chronic how will the patient usually present?
Symptoms of hyponatremia include? 4
asymptomatic.
Asymptomatic
- Headache
- Nausea and vomiting
- Altered mental status
- Seizures
Causes of SIADH?
4
Traumatic brain injury
Malignancy
Meningitis
Medications
Work up and diagnosis
of SIADH?
3
- CMP
- Urine sodium and osmolality
- Urine sodium is inappropriately high (>20 mEg/L) with low serum sodium (less than 130)
What do we have to rule out in the work up for SIADH and how do we do that (2)?
Rule out SIADH producing cancers
- CXR (small cell cancer of the lung)
- CT abdomen (pancreatic cancer)
Treatment for SIADH aims at increasing the what?
How do we do this?
FOr symtpomatic patients how would we treat it?
serum sodium levels.
Fluid restriction 1200-1800 mL per day
- Hypertonic saline (3%) 1-2 ml/kg IV over 3-4 hours
Do not correct sodium too quickly as may cause central pontine myelinolysis
AKA osmotic demyelination syndrome
What does osmotic demyelination syndrome result in?
results in destruction of the myelin sheath covering nerve cells in the pons (middle brainstem)….pretty much irreversible
Diabetes Insipidus a posterior pituitary disorder characterized by what?
excess excretion of water through urine
Diabetes Insipidus occurs due to what?
What are the two kinds?
Which is more common?
lack of appropriate levels of ADH
Central***
Nephrogenic
What is central diabetes insipidus due to? 2
What is nephrogenic diabetes insipidus due to?
- Deficiency of ADH (vasopressin)
- Resistance to ADH
Defect in the kidney tubules that interferes with water reabsorption
What is out of sync in diabetes insipidus?
How so?
Plasma and urine osmolality are out of sync.
Elevated plasma sodium with an inability to concentrate the urine
Symtpoms of diabetes insipidus?
5
- Intense thirst (2-20L per day)
- Polydipsia (intake of excess water)
- Craving for ice water
- Polyuria, nocturia, enuresis
- Hypernatremia
WHy does polyuria occur in diabetes insipidus?
Daily output?
Due to absence of ADH ,the epithelial cells of distal convoluted tubule in the nephron and the collecting duct of the kidney becomes impermeable to water
Daily output is 4 to 12 liters.
Why does polydipsia occur in diabetes insipidus?
Because of polyuria ,thirst center in hypothalamus results in intake of large quantity of water
Causes of diabetes insipidus?
4
Develops due to the deficiency of ADH which occurs in the following conditions:
1. Lesion (injury) or degradation of supraoptic and paraventricular nuclei of hypothalamus
- Lesion in hypothalamo-hypophyseal tract
- Atrophy of posterior pituitary
- Inability of renal tubules to give response to ADH hormone. Called as Nephrogenic diabetic insipidus.
Etiology of central diabetes insipidous? 6
Etiology of nephrogenic diabetes insipidous?
5
1 and 2. Most common…..due to trauma or tumor
- Idiopathic,
- cerebral anoxia,
- meningitis,
- radiation
- Meds: lithium, demeclocycline (tetracycline abx)
- Hypercalcemia,
- hypokalemia
- Infiltrative disease
- Sjogren’s syndrome
Work up for diabetes insipidus includes comparison of what?
What tests would we do? 6
urine and serum sodium levels.
- CMP (includes a serum sodium)
- Plasma osmolality
- Plasma ADH
- Urine sodium and osmolality
- Water deprivation test
Serum sodium will continue to increase and urine sodium will still be low
- DDAVP (desmopressin…..synthetic replacement for vasopressin, the hormone that reduces urine production) test
Urine sodium should increase if central DI
Treatment for diabetes insipidus for central (1) and nephrogenic treatment? 2
Central
1. Best treatment is DDAVP
Nephrogenic
1. Hydrochlorothiazide or
2. amiloride
Block reabsorption of sodium in the kidneys to keep the plasma sodium down some
