Pituitary Disorders Flashcards
What is released to the posterior pituitary from the hypothalamus?
ADH and Oxytocin
What is produced in anterior pituitary?
The 6 anterior pituitary hormones:
- ACTH
- TSH
- LH
- FSH
- PRL
- GH
What dz is indicated by increase GH?
Acromegaly/gigantism
What dz is indicated by decreased GH?
Dwarfism
What dz is indicated by increased Prolactin?
Galactorrhea
Endocrine glands secrete ___________.
Hormones directly into the blood stream (Diffuse effects)
Examples of endocrine glands include?
Pituitary, pancreas, ovaries, testes, thyroid
Exocrine glands secrete__________.
Substances into the ducts (more direct effects)
Examples of exocrine glands include?
Sweat glands, mammary glands, salivary glands
What causes Gigantism?
High linear growth during childhood due to excess of IGF-1
What causes Acromegaly?
Excess of IGF-1 in adulthood.
Most common cause of gigantism or acromegaly?
Growth Hormone secreting pituitary adenomas or hyperplasia
Gigantism is typically isolated but can be a feature of other conditions. What are the other conditions?
- Multiple endocrine neoplasia (MEN) type I
- McCune-Albright syndrome
- Neurofibromatosis
- Tuberous Sclerosis
- Carney Complex
What are you more likely to see as a PA in the United States, Gigantism or Acromegaly?
Gigantism is EXTREMELY RARE.
ACROMEGALY is more common than gigantism.
What is the hallmark of Acromegaly?
Insidious onset, delayed detection for about 10 years.
Signs and symptoms of Gigantism due to intracranial mass effect or excess GH/IGF-1?
Tall stature macrocephaly visual changes hypopituitarism HA Frontal bossing Hyperhidrosis Osteoarthritis
Signs and symptoms of acromegaly due to intracranial mass effect or excess GH/IGF-1?
Symptoms due to Intracranial tumor: Visual field defect (bitemporal hemianopsia), hyperprolactinemia.
Symptoms due to excess of GH/IGF-1
Increase ring/shoe size, Hyperhidrosis, Coarsening of facial features, Prognathism, arthritis, doughy-feeling skin over face and extremities. Enlargement of lower lip and nose. Hypertrichosifs, oily skin, Hyperpigmentation (acanthosis nigricans).
What is the DDX for gigantism?
Familial tall stature Exogenous obesity Cerebral gigantis Weaver syndrome Carney complex McCune-Albright syndrome
Define McCune-Albright syndrome
fibrous dysplasia of bone
hyper pigmented skin macules,
precocious sexual development in children.
Goiter, hyperthyroidism, acromegaly, Cushing Syndrome
Diagnosis and W/u for Gigantism?
Dramatic linear growth, macrocephaly, weight gain
MRI-pituitary adenoma (producing GH)
Screening test increased GH and IGF-I
Tx for Gigantism?
Transsphenoidal surgery-1st line
Bromocriptine, octretide
Radiation therapy
Diagnosis and w/u for acromegaly?
Clinical suspicion: enlarged hat/shoe size.
GH levels are UNRELIABLE.
OGTT: GH levels obtained at 0, 30, 60, 90, 120 min. Lack of suppression of GH is diagnostic.
IGF-1: If elevated diagnostic (unless pregnant/puberty)
MRI: Wit hand without GAD confirms pituitary adenoma
First line TX for Acromegaly?
Surgical removal of pituitary gland tumor-Primary tx.
f/u imaging study 12wks post surg-determines residual tumor.
Eval post sure for damage secondary to tumor
For pt’s with postoperative disease only meds are necessary
-somatastatin
-Dopamine-receptor agonist
-GH receptor antagonist
What follow up is necessary for pt’s with Acromegaly?
IGF-I levels monitored
Eval for severe GH deficiency.
Follow up cardiac eval for regurgitant valvular heart disease.
What is the major characteristic of Diabetes Insipidus (DI)
Large volumes of dilute urine
What are the two types of Diabetes Insipidus?
Central
Nephrogenic
Define Central Diabetes Insipidus
Neurogenic, pituitary, or neurohypophyseal: Decreased secretin of ADH.
Define Nephrogenic DI
Decreased ability to concentrate urine because of resistance to ADH action in the kidney
Etiology of Central DI
Most commonly: Idiopathic (inflammatory/autoimmune) Malignant or benign tumors of brain or pituitary (25%) Cranial surgery (20%) Head trauma (16%)
Etiology of Nephrogenic DI
Most common-lithium toxicity (20% of pt's on lithium) or hypercalcemia hypokalemia renal disease pregnancy (transient) Hyperglycemia other drugs - amphotericin B. Cidofovir
What hormone is the primary driver of free water excretion in the body?
ADH
What does ADH function to do?
Alters the water permeability of the cortical and medullary collecting tubes in the kidney.
What response does a decrease in extracellular fluid volume cause in the body?
ADH secretion - to increase water retention
Thirst - to raise water intake
Aldosterone - to preserve sodium
Is DI common in the US?
No. It is relatively uncommon in the US.
What are the symptoms of DI?
Polyuria, Polydipsia, and notcuria
What type of DI is most common?
Central DI following trauma or surgery to the region of the pituitary and hypothalamus
What are signs of DI?
PE is usually normal.
There may be pelvic fullness, flank pain, tenderness if hydronephrosis,
Bladder enlargement
DDX for DI
DMtype1 Histiocytosis Hypercalcemia Hypokalemia Medullary Cystic Disease Sickle Cell Anemia
Testing for DI
24 hr Urine-volume, specific gravity
Serum lytes and glucose
simultaneous plasma and urinary osmolarity
Plasma ADH level
Water deprivation test - aka Vasopressin challenge test
Define Water Deprivation test
- Water deprivation followed by administration of vasopressin differentiates between central and nephrogenic DI.
- caution with this because partial nephrogenic DI or primary polydipsia may have similar results to nephrogenic DI.
Central, and nephrogenic urinary osmolality will be <300mOsm/kg after water deprivation. After admin of ADH osmolality will raise to more than 750mOsm/kg in CENTRAL DI but will not rise at all in nephrogenic DI
Treatment for DI
Fluid replacement-most patients can just drink enough fluid to replace losses.
- in presence of hypernatremia IV fluid with dextrose that is hyperosmolar with respect to serum will rehydrate pt.
- instruct pts when traveling to avoid dehydration, vomitting, and diarrhea must be addressed quickly
What medications can be prescribed for pt with central DI
- Desmopressin; available subQ, IV, Intranasal, and oral.
- Vasopressin: if response to desmopressin to not complete or pt can’t afford desmopressin
What is the difference between desmopressin and Pitressin (vasopressin)
Desmopressin has NO vasopressor activity. Pitressin (vasopressin) HAS vasopressor activity. Desmopressin has more potent antidiuretic activity.
t/f Desmopressin’s primary role is in nephrogenic DI
F: Desmopressin has NO ROLE in tx of nephrogenic DI. Non hormonal drugs are usually more effective in tx of nephrogenic.
What are the second line meds that can be used in tx of DI?
Antidiabetics-sulfonylureas, Anticonvulsants-Carbamazepine, Diuretics-thiazide, Diretics Potassium-sparing, NSAIDs(usually used in nephrogenic)
What is the definition of SIADH
Syndrome of inappropriate antidiuretic hormone secretion (EXCESS ADH). Excess ADH interferes with water intake. Increase in ADH results in increased water reabsorption by kidneys, decreased aldosterone secretion.
Etiology of SIADH?
Neoplasia
Nervous system disorder
Pulmonary disease
Drug induced
What is the cardinal feature of SIADH?
Too much ADH.=water load enhanced
ADH increases the water permeabiltiy of the renal collection ducts, thereby increasing renal water reabsorption.
What is the most common electrolyte derangement occurring in hospitalized patients?
Hyponatremia
Signs and symptoms of SIADH?
anorexia
nausea
vomiting
Neuro symptoms: HA, dulled sensorium, confusion, convulsions, Death
Progressivly more severe psych, neuro, resp as time goes on.
What is diagnostically significant to SIADH?
Thyroid and adrenal function will be normal Serum hypo-osmolarity hyponatremia Urine hyperosmolarity Normal renal function absence of CHF, hypovolemia
What labs should be drawn if SIADH is suspect?
Serum Na+, potassium, chloride, bicarb Plasma osmolality Blood urea nitrogen Serum creatinine Blood glucose Urine osmolality Serum uric acid serum cortisol TSH
Tx of SIADH
- important to remember that if you are correcting hyponatremia this needs to be done very carefully and slowly.
- Rapidity of tx depends on
- degree of hyponatremia
- symptoms
- acuity (<48h)
Review of cause of SIADH
too much ADH-serum dilute-urine concentrated
Review of cause of DI central
not enough ADH-serum concentrated-urine dilute
Review of cause of DI Nephrogenic
Kidney does not respond to ADH-Serum concentrated-urine dilute with normal/high serum ADH level
Review of cause of psychogenic water intoxication
Serum dilute urine dilute
Definition of dwarfism
Person of short stature - under 4’10” in adulthood
Achondroplasia is MC cause (70%)
other causes - genetic, kidney dz, and problems with metabolism or hormones
What are the 2 categories of dwarfism?
Disproportionate dwarfism
Proportionate dwarfism
Define disproportionate dwarfism
some parts of body are small, others are average size - disorders that cause this inhibit the development of bones -
Define proportionate dwarfism
All parts of the body are small. These conditions present at birth and in early childhood and limit overall growth and development-
MC cause of disproportionate dwarfism
Achondroplasia (avg size trunk, short extremities)
MC cause of proportionate dwarfism
growth hormone deficiency (pituitary fails to produce enough GH)
Signs and symptoms of disproportionate dwarfism
Achondroplasia-recessive genetic d/o. Delay in motor skills Frequent ear infections Bowing of legs sleep apnea hydrocephalus crowded teeth Spinal stenosis* Arthritis*
Signs and symptoms of proportionate dwarfism
complications with poorly developed organs
Heart problems - Turner syndrome
Absence of sexual maturation - physical and social function development
Testing for Dwarfism
Measurements (current percentile) ht, wt, head circumference
Appearance- physical exam reveals distinct facial and skeletal features
Imaging: X-rays (delayed mat of bones), MRI (abnormalities of pituitary/hypothalamus)
Genetic tests
Family hx
Hormone (GH)
Surgical Tx for dwarfism
limb lengthening used to be popular but is more controversial now.
For disproportionate dwarfism:
-can correct bone growth direction
-stabilize and correct the spine
-increase size and shape of spine alleviate pressure
-shunt for hydrocephalus
Hormone tx for dwarfism
If d/t GH deficiency: tx w/ injections of synth version of hormone
if Turner syndrome-estrogen, and related hormone tx for sexual development
***-GH supplementation will not improve final adult height for Achondroplasia!!
What are the 5 classifications for pituitary gland d/o
- Neoplastic (Pit adenoma, tumors, mets)
- Inflammatory (sarcoid)
- Infectious (TB)
- Vascular (aneurysm, carotid/sheehan’s=apoplexy)
- Congenital
Pituitary adenoma epidemiology/pathyphys.
benign/common (10%+) MC cause of pituitary hormone hyper/hyposecretion in adults 15% of all intracranial neoplasms!! 1/3 are clinically nonfunctioning Of the hormonally functioning 10-15%=GH And ACTH 50% secrete PROLACTIN (prolactinoma)
Symptoms/signs of pituitary adenomas
50-60% present with visual symptoms due to compression of optic nerve
Nonspecific HA
Lateral extension ophthalmoplegia, diploipa &/or Ptosis
Extension into sphenoid can cause spontaneous CSF Rhinorrhea
endocrine dysfunction-Prolaticn, GH, ACTH
Visual acuity decreased in one or both eyes
pupillary light reaction can be abnormal
What might a bitemporal hemianopsia indicate?
Large pituitary lesion
What hormonal physical findings might be present with prolactinoma?
Females-galactorrhea
Males-galactorhea is uncommon, decreased size of testicles
What hormonal findings would be present with acromegaly?
large hands and feet, coarse facial features with frontal bossing, women may appear masculinized, Prognothism, carpal tunnel syndrome, voice quality changes
hormonal findings for cushings dz.
Obesity, centripetal fat deposition, proximal myopathy, moon face, buffalo hump, post subspace cataracts, atrial htn, bruises, striae
Hormonal findings for hypopituitarism
Chronic=hypotension, generalized weakness, hypothermia, malaise, depression
Acute=sudden hypopituitarism, shock, coma, death
DDX for pituitary adenomas
Basilar artery thrombosis Brainstem gliomas Cavernous sinus syndrome cerebral venous thrombosis craniopharyngioma Dizziness, vertigo, imbalance Intracranial hemorrhage asytrocytoma meningioma Primary CNS Lymphoma TB
Testing for prolactinoma
Elevated prolactin level
Serum prolactin level should be measured if pt is suspected to have a sellar mass (order imaging if high)
What is the best endocrinologic test for acromegaly?
Serum insulin like growth factor 1 (IGF-1) best endocrinology test for acromegaly. IGF-1 reflects concentration in the last 24 hours.
What is the most definitive test for acromegaly?
OGTT (oral glucose tolerance test). + result is the failure of GH to decrease to <1mcg/L after ingesting 50-100 g of glucose
What is the imaging study suggested for pituitary adenomas?
MRI
Tx of pituitary adenomas
Goal is to improve: mass effect hormonal hypo- or hyper- secretion Prevent recurrence Transsphenoidal surgery tx of choice for all pituitary tumors except prolactinomas. Radiation and med tx are adjunct to surgical approach
Tx for Prolactinomas (medical)
Most respond to dopamine receptor agonists.
Tx for acromegaly (medical)
Somatastatin analogues - tx increased post op levels of GH.
Dopamine agonists are sometimes used
Replacement tx for absent hormones
What type of Pituitary adenomas are candidates for Transsphenoidal surgery?
Acromegaly (decreases GH to less than 5mcg/L in 60%)
Cushing disease: First line of tx. Curative in 80%
What additional consultations should be made for a pt with a pituitary adenoma?
Ophtho., neuro-ophtho neuroradiologist endocrinologist Neurosurgeon gynecologist neuropathologist radiation medicine
What d/o is considered an endocrine emergency and is caused by either a hemorrhage into a pre-existing adenoma, or Sheehan’s syndrome post-partum?
Pituitary apoplexy
What are signs and symptoms of pituitary apoplexy?
Severe H/A, Bilateral vision changes, ophthalmoplegia.
If severe: CV collapse, LOC, hypoglycemia, CNS hemorrhage-death
What is the tx for pituitary apoplexy?
If no visual loss or impaired conciousness- glucocorticoids
If visual/neuro sx-surgical decompression
Define hyperprolactinemia
hyper secretion of the pituitary leading to elevated serum prolactin.
What hormone inhibits the production of prolactin?
Dopamine (from the pituitary)
What hormone mildly increases prolactin?
Mildly increased by TRH/estrogens
What does high prolactin suppress?
GNrH to decrease FSH/LH
What percent of people with amenorrhea and galactorrhea have hyperprolactinemia?
75%
Signs and symptoms of hyperprolactinemia in females
Menstrual changes (amenorrhea),
Galactorrhea
Infertility
MC presentation at a young age always consider in females with nipple d/c
Signs and symptoms of hyperprolactinemia in males
Hypogonadism decreased libido erectile dysfunction infertility sometimes gynecomastia sometimes galactorrhea
testing for hyperprolactinemia
Fasting, morning prolactin level
if elevated exclude non-neoplastic reasons
pregnancy, hypothyroidism, medications
If cause is unknown obtain MRI of pituitary
tx of hyperprolactinemia (medical)
Dopamine agonist (bromocriptine, cabergoline)
- dopamines inhibit PRL
- decreases tumor size
- lower PRL level
- may cause nausea
Tx of hyperprolactinemia (surgical)
Trans-sphenoid resection
for pt’s with drug intolerance, tumors resistant to med tx., persistent visual field defect, and large tumors
Follow up for hyperprolactinemia
Fasting PRL monitored monthly
Visual field testing and MRI
Complications of hyperprolactinemia
Blindness
hemorrhage
osteoporosis
infertility
What is it important to educate your patients about when treating them for hyperprolactinemia?
A decrease in PRL levels may restore ovulation-when returning to normal pregnancy is possible (educate re birth control)
Galactorrhea Definition
Not a disease - a sign
nipple discharge unrelated to normal milk production of breast feeding
MC cause is hyperprolactinemia
Etiology for galactorrhea
Hyperprolactinemia, prolactinoma medications: sedatives, antidepressives, antipsychotics, antihtn, BCP's cocaine/opiods Herbal supp. (fennel, annise, fenugreek) Hypothyroid Chronic renal dz Excessive breast tim Spinal cord surgery Idiopathic
signs and sx of glactorrhea
Pathologic-persistant d/c, unilateral, limited to 1 duct, serous, sanguinous, serosanguinous
What must you do if the d/c dt galactorrhea is bloody?
cancer workup
Testing for galactorrhea
Labs: PRL level, Beta HCG (preg), TSH, LFT, BUN, Creat, FSH, LH
RAD: MRI, US, Mammo,
definition of hypopituitarism
Clinical syndrome of deficiency of pituitary hormone.
Can be Panhypopituitarism: effecting all of pituitary hormones
of
Partial hypopituitarism: effecting only 1 or several pituitary hormones
etiology of hypopituitarism
Neoplastic (MC), genetic, congenital, traumatic, vascular, infectious.
Is hypopituitarism rare or common?
Rare-affects less than 20,000 individuals in the US
Hormonal signs of hypopituitarism
ACTH deficiency TSH deficiency - hypothyroid Gonadotropin deficieny - hypogonadism GH deficiency - Failure to thrive, short stature ADH deficiency - polyuria and polydipsia
Structural signs of hypopituitarism
HA Diplopia Visual field deficit Polydipsia/polyuria -rarely SIADH
tests for hypopituitarism
8am cortisol TSH FT4 IGF-1 TTEST-men PRL level mentrual status - females Provocative tests for GH and ACTH deficiency
TX of hypopituitarism
Directed at etiology
Individualized hormone replacement
