Endocrine 4-6 Flashcards
Which body systems utilize calcium?
Nervous, muscular and skeletal system (99% found in bone)
What is calcium regulated by?
PTH, calcitonin and active vitamin D
The 1% of calcium circulating in the blood is in what 3 forms?
- Free ionized form 45%
- Bound to proteins 45%
- Complex anions 10%
What is the total serum calcium?
8.5-10.5mg/dL
What is the net effect of parathyroid hormone?
Increase in serum calcium and decrease in serum phosphate
What is calcitriol the active form of?
Vitamin D
What is the function of calcitriol?
Enhances intestinal cells to absorb calcium and phosphate into the serum
What are the net effects of calcitriol?
Increase serum calcium
Increase serum phosphate
Where is calcitriol derived from?
Diet or UV light, required enzymatic steps in liver and kidney to become active vitamin D
PTH is synthesized and secreted by what?
Chief cells of the parathyroid gland
In response to low serum Ca++ bone does what?
Bone: PTH stimulates resorption (osteoclastic) which leads to INCREASE in serum Ca++
In response to low serum Ca+++ kidney does what?
PTH promotes Ca++ resorption and stimulates hydroxylation of 25-hydroxyvitamin D (calcidiol) via an enzyme
In response to high serum Ca+++
PTH decreases its production
Increased serum calcium leads to what?
Decreased PTH
Decreased serum calcium leads to what?
Increased PTH
When PTH stimulates the bone what does it do?
Increases osteoclastic activity and decreases osteoblastic activity
When PTH stimulates GI tract what does it do?
Vitamin D: increased absorption of calcium and phosphate
When PTH stimulates the kidneys what does it do?
Activates 1alpha D hydroxylase, increases reabsorption of calcium and increases phosphate excretion
What effect does calcitonin have on the GI tract?
None
What effect does calcitonin have on the kidney?
Decreases absorption of calcium and phosphate
What effect does calcitonin have on the bone?
Increases osteoblastic activity and decreases osteoclastic activity
Hypocalcemia etiologies from the parathyroid
Thyroidectomy, iodine therapy, autoimmune, infiltrative disease, PTH resistance
Hypocalcemia etiologies from Vitamin D deficiency
CKD: #1 cause, malabsorption syndromes, decrease exposure to sunlight, vitD resistant rickets, hyperphosphatemia, drugs accelerate CP450: Phenytoin
Miscellaneous etiologies for hypocalcemia
Hungry bone syndromes, osteoblastic bone metastases, pancreatitis, multiple transfusion, acute respiratory alkalosis, bisphosphonate OD, alcoholics
Hypocalcemia from hypoparathyroidism
Requires all 4 parathyroid glands to be affected, therefore uncommon
What are some symptoms of hypocalcemia + hypoparathyroidism?
Emotional lability, paresthesia (perioral, hands, feet), SOB (diaphragmatic spasms), voice changes (cataract formation) chronic, personality changes (chronic)
What are some PE findings of hypocalcemia + hypoparathyroidism
Tetany, Chvostek’s sign, Trousseau’s sign, muscle stiffness, spasms and cramps, seizures, hypotension, wheezing, voice changes, psychosis, hyperreflexia
What is tetany?
Repetitive discharge of peripheral nerves after single stimulus
What can be used to diagnose hypocalcemia + hypoparathyroidism
EKG, total calcium (correct calcium for low albumin, ionized calcium), PTH, BUN/creatinine, phosphate, mg, albumin, LFTs, PT/INR
Which VitD labs can be tested for hypocalcemia + hypoparathyroidism
Vitamin D levels- 25(OH) cholecalciferol (calcidiol)
1, 25 (OH)2 Cholecalciferol (Calcitriol)- concern for renal dysfunction
How do you treat hypocalcemia + hypoparathyroidism?
Oral calcium, IV calcium, Vitamin D, Mg prn, Diet
What are the oral calcium options to treat hypocalcemia + hypoparathyroidism
Calcium carbonate 1500mg-2000mg daily
Calcium citrate 1gm/day
What are the IV calcium options to treat hypocalcemia + hypoparathyroidism
Calcium Gluconate (preferred) (1-2gms) Calcium Chloride
When is IV calcium administered to patients with hypocalcemia + hypoparathyroidism
Sever symptoms (tetany, seizures) Prolonged QT interval or arrhythmia Suspected abrupt decrease from normal
What are the indications for using Vitamin D for patients with hypocalcemia + hypoparathyroidism
Hypocalcemia secondary to Hypoparathyroidism, hungry bone syndrome, vitamin D deficiency
What forms of vitamin D can be used for hypocalcemia + hypoparathyroidism
Calcitriol and Vitamin D2 (Ergocalciferol)
What should be avoided with hypocalcemia + hypoparathyroidism
Diuretics
What is the most common electrolyte abnormality in adults with malignancies?
Hypercalcemia
What is the most common cause of hypercalcemia?
Hyperparathyroidism
Hyperparathyroidism is also seen in what?
MEN 1, 2a, and 2b*
SHAMPOO
Sarcoidosis Hyperparathyroidism Alkali milk syndrome Metastastis, multiple myeloma Paget disease OSteogenesis imperfecta Osteoporosis
SHAMPOO is for what?
Hypercalcemia etiologies
DIRT
D vitamin intoxication
Immobility
RTA (renal tubular acidosis)
Thiazides
DIRT is for what?
Hypercalcemia etiologies
The most common cause of primary hyperparathyroidism is what?
Single parathyroid adenoma (80%)
Other causes of hyperparathyroidism
Hyperplasia, carcinoma, famililar hypocalciuric hypercalcemia
What is secondary hyperparathyroidism?
Due to overproduction of PTH due to chronic abnormal stimulus
What can cause secondary hyperparathyroidism
Chronic renal failure and VitD deficiency
What is tertiary hyperparathyroidism?
Due to a state of excessive secretion of PTH after longstanding secondary
What can cause tertiary hyperparathyroidism?
Renal transplant patient
What are the si/sx of hypercalcemia and hyperparathyroidism
“bones stones groans and moans”
What happens to the bones with hypercalcemia and hyperparathyroidism
Joint pain, bone pain
What is the “stones” when referring to hypercalcemia and hyperparathyroidism
Polyuria, kidney stones, hypercalcuria
What is the “groans” when referring to hypercalcemia and hyperparathyroidism
Anorexia, N/V/abd pain, constipation, PUD
What are the “moans” when referring to hypercalcemia and hyperparathyroidism
Weakness, fatigue, depression, inability to concentrate, anxiety and confusin
PE findings of hypercalcemia and hyperparathyroidism
Most of the time PE is non-contributory
Skin: pruritis, skin tenting
Cardiac: HTN, LVH
GI: anorexia, N/V, constipation, pain
Renal: renal colic (kidney stones)
MSK: bone fractures (wrist and vertebrae)
Neuro/Psyc: paresthesias, diminished DTR, muscle weakness, depression
Hypercalcemia diagnostics
Calcium level, PTH, 24hour urinary calcium excretion, chloride phosphate, PTHrP, BUN/Creatinine, Calcitriol or Calcidiol, EKG
If the 24hour urinary calcium excretion is high..
Primary hyperparathyroidism
If the 24hours urinary calcium excretion is low..
Familial hypocalciuric hypercalcemia
PTHrP elevation means what
Malignancy
Elevated calcidiol means what
Excessive dietary intake of calcium or VitD
Elevated calcitriol with normal calcidiol means what
Ectopic production of calcitriol
If PTHrP, calcidiol, and calcitriol are all normal
Bone mets, consider rare causes of hypercalcemia and hyperparathyroidism
T or F Imaging studies are not used to make the diagnosis of primary hyperparathyroidism, but may be used to guide the surgeon
True!
What diagnostic imaging can be used for hyperparathyroidism?
Sestamibi scan, ultrasound of the neck, CT or MRI, bone density measurement by DXA to assess amnt of bone loss, X-ray
DXA
Dual XRay absorptiometry: assess the amount of bone loss
Focus on lumbar spine, hip, and distal radius
What can be some XRay findings for hyperparathyroidism?
Osteitis fibrosa cystica, “salt and pepper” appearance of skull, brown tumor of long bones
What are the treatment options for hyperparathyroidism?
Surveillance, surgical, pharmacological, supportive
Asymptomatic hyperparathyroidism patient treatment
STay active, avoid immobilization, drink fluids, modest dietary calcium, VitD recommendation based on age, bisphosphonates, D/C thiazides, VitA, calcium containing antacids
What do asymptomatic hyperparathyroidism patients require annually?
Serum calcium and creatinine; bone density scan done 1-2 years
Surgery is recommended for which type of patients with hyperparathyroidism?
Symptomatic or pregnant
What is the medical treatment for hyperparathyroidism?
Fluids, Furosemide, IV bisphosphonates, calcitonin, cinacalcet, propranolol can help reduce cardiac symptoms
Who is medical treatment for?
Indicated for poor surgical candidates, those declining surgery, awaiting surgery with severe symptoms
Hypercalcemia treatment medications
Normal saline, loop diuretics, bisphosphonates, calcitonin, Gallium nitrate, dialysis, steorids, magnesium
How does normal saline help hypercalcemia?
Decreased calcium levels through dilution, allows for expansino of ECF volume
How do loop diuretics help hypercalcemia?
Used with hydration will increase calcium excretion
How do bisphosphonates help hypercalcemia?
Inhibit osteoclastic activity
How does calcitonin help hypercalcemia?
Inhibits bone removal by osteoclasts, and promotes bone formation by osteoblasts
How does gallium nitrate help with hypercalcemia
Inhibits bone resorption directly and may inhibit PTH secretion
When primary hyperparathyroidism is symptomatic, the most common presentation in those over the age of 61 involves what?
Nephrolithiasis, fatigue, and bone disease
Surgical treatment for hyperparathyroidism could be considered for who?
If patient is symptomatic and/or there are signs of end-organ damage
Medical treatment for hyperparathyroidism with what is an option for nonsurgical candidates?
Bisphosphonate and/or cinacalcet
Parathyroid cancer lab results
Ca levels >14, PTH levels 5X normal, palpable parathyroid gland
What does treatment of parathyroid cancer consist of?
Below the neck exploration with excision of tumor and ipsilateral thyroid lobe
Parathyroid cancer post op care
Check Ca levels 2 weeks post op, 6 mos, and annually after
Recurrence of parathyroid cancer has been found in who?
15% at 2 years and 67% at 8 years have been reported for MEN1 patients
What is a localized disorder or bone remodeling with excessive bone resorption followed by disorganized bone formation?
Paget disease
The bone turnover rate is 20x higher in what?
Paget disease
Common bones affected in paget disease
Pelvis, lumbar spine, femur, thoracid spine, sacrum, skull, and tinia
What are the 3 phases of paget disease?
- Lytic: osteoclasts are more numerous and larger, bone turnover rate 20x higher
- Mixed phase: Rapid increase in bone formation from numerous osteoblasts
- Final phase: bone formed in woven pattern, weak and causes hypervascular bone state
What is the most common symptom for paget disease?
Pain, 70-90% are asymptomatic
Si/sx of Pagets disease
Osteoarthritis, nerve impingement, hearing loss, bones become soft -> bowed tibias, kyphosis, if skull is involved -> HAs, increased hat size
Diagnosis of Paget disease
Alkaline phosphatase will be elevated
Blood levels to asses for bone turnover rate:
Serum N-terminal propeptide of type 1 collagen (NTx)
Serum BetaC-terminal propeptide of type 1 collagen (betaCTx)
Serum calcium, VitD and serum phosphate
Imaging for Paget disease
Stage 1: Areas of bone loss
Stage 2: “cotton-wool or picture frame” look for skull and vertebrae
Stage 3: “burn out” phase bone appears enlarged and dense
Bone Scintigraphy: radionuclide bone scans
What are some complications of pagets disease?
Pain arthritis, disability, vertebral collapse/fracture, cranial nerve palsies, hearing loss, paralysis
Treament of paget disease involves what?
Surveillance for asymptomatic pts, certain criteria for symptomatic pts
Symptomatic paget disease treatment
Nitrogen containing bisphosphonates
Extensive disease/elderly: IV Zolendronic Acid (preferred)
Less extensive/young: Risendronate or Alendronate PO
Calcitonin, Calcium, VitD, analgesics, rehab, surgical if needed
What is the treatment of choice of Paget disease?
IV infusion of Zolendronate 5mg over 15 minutes
Targeted to achieve a serum alkaline phosphatase in lower half of normal reference range
Paget Disease key points
Its a focal disorder of osteoclasts resulting in increased bone turnover and lytic skeletal lesions that primarily affects older individuals
What are some causes of hyperpituitarism?
Hyperprolactinemia, acromegaly, gigantism, SIADH
What are some causes of hypopituitarism?
Diabetes insipidus, sheehan syndrome, dwarfism
What hormones does the anterior pituitary secrete?
GH, PRL, ACTH, TSH, LH, FSH
What hormones are secreted by the posterior pituitary?
ADH, Oxytocin
What is another name for ADH?
Vasopressin, antidiuretic hormone
Diabetes insipidus is caused by what?
A deficiency in vasopressin (ADH) from posterior pituitary
Where is ADH created?
Hypothalamus, secreted by posterior pituitary
ADH promotes preservation of water from where?
The kidneys
ADH alters water permeability where?
In the distal renal tubules
Defined as the passage of large volume (>3L/24hr) of dilute urine (<300 mOsm/kg
Diabetes insipidus
Inadequate ADH in diabetes insipidus causes what?
Polyuria
What are the two main causes of DI (diabetes insipidus)?
Central and nephrogenic
The central cause of DI
Due to decreased secretion of ADH
The nephrogenic cause of DI
The kidneys are not responding to the normal amount of ADH
The central cause of DI can be broken down into what?
Primary and Secondary
Primary central DI is what?
No identifiable lesion on MRI of pituitary or hypothalamus (around 1/3 cases)
Secondary central DI is what?
Some type of damage to hypothalamus or pituitary stalk by trauma, infection, bleed, tumor, infarction (majority of cases)
What is the etiology of central diabetes insipidus?
Cranial surgery (20%) and head trauma (16%) others: idiopathic, malignant or benign tumors of the pituitary (25%)
What is the etiology of nephrogenic diabetes insipidus?
Lithium toxicity, hypercalcemia, Demeclocyline, steroids, Ofloxacin, Methicillin, pregnancy (transient), renal disease, congenital
What are the si/sx for diabetes insipidus?
Polyuria, polydipsia, nocturia, daily urinary output ranges from 3-20L, dehydration, hypotension, hypernatremia
What are the clinical manifestations of DI caused by?
Absence of ADH
Evaluation of DI
24 hour urine collection, urinalysis, Serum electrolytes and glucose, plasma and urine osmolality, ADH, water deprivation test, water deprivation + ADH, urine specific gravity, urine osmolarity, MRI
What will the serum electrolyte results be for DI?
Serum Na will be high, serum glucose normal
What will the plasma and urine osmolality be for DI?
Plasma osmolality: high
Urine osmolality: low
What will the results be for ADH level with DI?
Central: Low ADH
Nephrogenic: High ADH
What is the treatment for DI?
Hypotonic solution D5W targeted at 500-750ml/hr (pts with severe symptoms)
What is the goal of treatment for DI?
Reduce serum sodium and monitor electrolytes every 4-6 hours
How do you treat central DI?
Desmopression (DDAVP) intranasal 10-40mc daily or oral 0.1-1.2
How do you treat nephrogenic DI?
HCTZ 12/5mg-50mg QD- Diuretic that blocks reabsorption of Na into the kidneys
What is SIADH?
Syndrome of Inappropriate Antidiuretic Hormone
What is SIADH characterized by?
Excessive release of ADH from the posterior pituitary gland
What does the excess ADH do in SIADH?
Promotes renal tubule absorption of water and decrease urinary output, causes water retention
What does SIADH and excessive ADH result in?
Dilutional hyponatremia and low serum osmolality. Hyponatremia can be severe
What is the most common cause of hyponatremia in hospitalized patients?
SIADH
Decreased urinary output will increase what?
Urine osmolality
What are some etiologies of SIADH?
Malignancy (small cell lung cancer, pancreatic cancer), drugs, after pituitary surgery
Si/Sx of SIADH?
HA/ N/V, seizures, altered mental status, LOC, asymptomatic (if development is gradual)
What is the cause of the si/sx for SIADH?
Hyponatremia due to water intoxication-severity and onset of hyponatremia determines the extent of symptoms
What can be used for diagnosis of SIADH?
Urinalysis, urine sodium, urine osmolality, BMP, BUN, serum osmolality, ADH, CT/MRI of head, CXR, CT abd/pelvis
What will the result of urinalysis be with SIADH?
Specific gravity is high
What will the urine sodium be with SIADH?
High
What will the urine osmolality be with SIADH?
High
What will the BMP read with SIADH?
Serum sodium low
What will the BUN read with SIADH?
Low
What will the serum osmolality be with SIADH?
Low
SIADH treatment for asymptomatic
Restrict fluids <1/5L/day, D/C offending medications, Demeclocycline -> potent inhibitor of ADH
SIADH treatment for symptomatic (seizures, altered)
3% NaCl (hypertonic solution)
Do not increase Na >0.5-1mEQ/L/hr
Check hourly serum sodium, neuro critical care consult
To compare SIADH to DI, SIADH has…
Too much ADH ECF volume excess Hyponatremia Decrease urine output (urine is concentrated and dark) Hypertensive
To compare SIADH to DI, DI has…
No ADH
Increase urinary output (>3L/day) urine appears as water
Hypernatremia
Hypotensive
What is psychogenic polydipsia characterized by?
Polyuria and polydipsia, common occurrence in inpatients with psychiatric disorders
What happens in psychogenic polydipsia?
Hyponatremia in pts can progress to acute water intoxication, management includes fluid restriction, behavioral and pharmacologic modalities
A condition of short stature
Dwarfism
Most common causes of Dwarfism
Familial and delayed growth (non-pathologic)
Dwarfism is defined as
Height that is 2 standard deviations below mean for children of that sex and age (below the 2.3rd percentile)
Achondroplasia is what?
Most common bone dysplasia in humans, occurs in all races with equal frequency
What are the two main categories of dwarfism?
Proportionate Dwarfism and Disproportionate Dwarfism
Proportionate Dwarfism
Caused by metabolic/hormonal syndromes
Pituitary Dwarfism: GH deficiency syndromes
Laron Syndrome
Disproportionate Dwarfism
Achondropalsia, sponydyloepiphyseal dysplasia, diastrophic dysplasia
What is achondroplasia?
Autosomal dominant, spontaneous mutation in FGFR3, normal torso and short limbs
What are the si/sx of achondroplasia?
Normal torso, short limbs, enlarged skulls, central apnea, obstructive apnea, and hydrocephalus, difficult airway
Achondroplasia makes up what % of dwarfism?
70%
Achondroplasia is associated with what?
Advanced paternal age, gene mutation affects bone formation
Spondyloepiphyseal dysplasia (SED)
Shortened trunk, barrel chest, club feet, cleft palate, severe osteoarthritis
SED is associated with what?
Variety of medical problems, mainly orthopedic
What is the adult height in SED?
Varies slightly from under 3 feet to slightly over 4 feet
Diastrophic dysplasia
Autosomal recessive, rare, shortened forearms and calves, limited ROM, cleft palate, deformed hands/feet
Disproportionate dwarfism si of the hands and feet
Polydactyly, hitch-hiker thumb, clubfoot
Disproportionate dwarfism si of the nails
Hypoplastic, short and broad
Disproportionate dwarfism si of the thorax and ribs
Long, narrow thorax, pear-shaped chest
Disproportionate dwarfism si of the heart
ASD, single atrium, patent ductus arteriosum, transposition of great vessels
Other signs of Disproportionate dwarfism
Multiple joint dislocations, long bone fractures
How can you diagnose Disproportionate dwarfism?
Clinically, based on PE can do genetic testing and skeletal xrays
Treatment of Disproportionate dwarfism
Symptomatic relief: tracheotomy, cleft palate repair, leg braces, back braces, club foot surgery
What is pituitary dwarfism a deficiency in?
GH or GHRH (growth hormone releasing hormone)
What else can cause pituitary dwarfism?
Sellar and parasellar tumors that destroy the pituitary gland itself
Auxology
Study of human growth
Si/Sx of pituitary dwarfism
Sever postnatal growth failure, delayed bone age, hypoglycemia, prolonged jaundice, micropenis, high pitched voice, increase body fat, short stature
Diagnostic approach to GHD
Evaluate for other causes of growth failure, including chronic systemic disease, hypothyroidism, turner syndrome (F), skeletal disorders
Diagnostic tests for GHD
Insulin-like growth factor 1 (IGF-1)
Insulin0like growth factor binding protein 3 (IGFBP-3)
Bone age
If bone age and height velocity are normal, you cane exclude what diagnosis?
GHD
What provocative tests are used to confirm the diagnosis of GHD?
GH provocative testing: Agent that will normally provoke a pituitary to release a burst of GH, blood drawn @ 15 min intervals over one hour
What agents are used in the provocative GH testing?
Arginine, Levodopa, Clonidine, Glucagon
What are the results of provocative GH test?
If serum concentrations of GH, IGF-1 and IGFBP-3 remain low, diagnosis can be confirmed
MRI should also be obtained
What is Laron Syndrome?
Most common known cause of genetically mediated growth hormone insensitivity
Laron Syndrome is caused by mutations in what gene?
GH receptor gene, unable to bind to receptor
What are the mutations associated with Laron Syndrome?
Autosomal recessive mutations, causes severe postnatal growth failure, GH levels are normal or high
Clinical features of Laron Syndrome
Small head circumference, characteristic facies with saddle nose and prominent forehead
Delayed skeletal maturation, small genitalia and testes, short limb length compared with trunk, osteopenia and obesity
What are the signs of Turner Syndrome
Square “shield” chest, webbed neck, cubitus valgus, genu valgum, shortened 4th metacarpals and Madelung deformity of the forearm
What is cubitus valgus?
Abnormal angle of forearm when it hangs
What is genu valgum?
Knees go in and touch
What is the treatment of pituitary dwarfism?
If its a pituitary/GH problem: GH administer SQ
Laron Syndrome: IGF-1
If the childs height is above the 2.3rd percentile?
No referral needed
If the childs height is below the 2.3rd percentile?
Concern, may need referral
If childs height if less than the 1st percentile
Evaluate the rate of growth, if declines or low, refer to Endocrinologist
How is bone age determined?
from a radiograph of the left hand and wrist, and requires expert interpretation
Delayed bone age with <2SD
Refer to endocrinologist
Sheehand syndrome is a disease of what?
Pituitary
Infarction of the pituitary after postpartum hemorrhage, or infarction immediately postpartum
Sheehan syndrome
Si/sx of Sheehan syndrome
History of severe postpartum hemorrhage, severe hypopituitarism: lethargy, anorexia, weight loss, inability to lactate during first days/weeks after delivery
SI/sx of Sheehan syndrome with less severe hypopituitarism
Failure of postpartum lactation, failure to resume menses in weeks/months after delivery, loss of sexual hair, milder fatigue, weight loss, anorexia
Diagnostic studies for Sheehan syndrome
MRI, Hormone evaluation
Hypopituitarism hormone evaluation
Corticotrophin (ACTH), Thyrotropin (TSH), Prolactin, ADH, GH, Gonadotropin
Postpartum hypopituitary lab profile
Must evaluate for adrenal insufficiency immediately, other hormonal deficiencies can be evaluated 4-6 weeks later
MRI results for Sheehan Syndrome
Early abnormalities may be seen- enlargement/ischemia
late changes of small pituitary with normal size sella and eventually an empty sella
Treatment for Sheehan syndrome
Must treat for adrenal insufficiency immediately, other deficiencies can be related 4-6 weeks later
No treatment available for prolactin deficiency
ACTH deficiency hypopituitarism treatment
Hydrocortisone or glucocorticoid
TSH deficiency hypopituitarism treatment
Levothyroxine
Gonadotropin deficiency hypopituitarism treatment
Men: testosterone
Women: Depends on txt goals, estradiol and progestin if pursuing fertility, gonadoptropin or pulsatile GnRH when ovulation induction and fertility
GH deficiency hypopituitarism treatment
Adults replacement not generally recommended
Pituitary in very close to what important structures
Optic chiasm, cranial nerves 3, 4, 6, trigeminal ganglion, ophthalmic division of CN V, carotid artery, cerebral circulation
What hormones are produced by the anterior pituitary?
GH, PRL, ACTH, TSH, LH, FSH
What hormones are released by the posterior pituitary?
ADH, oxytocin
Which pituitary hormones are involved in positive feedback loop?
CRH, TRH, GnRH GHRH
Which pituitary hormones are involved in negative feedback loop?
SST- somatostatin (GHIH growth hormone inhibiting hormone), dopamine
What are the two types of pituitary sellar masses?
Benign and malignant
What type of pituitary sellar mass is benign?
Pituitary adenoma, there is a functional and on-functional form
The functional pituitary adenoma does what?
Produces hormones, about 65-70% of all adenomas
What types of pituitary sellar masses are malignant?
Germ cell tumor (ectopic pinealoma), sarcoma, chordoma, pituitary carcinoma
Pituitary adenoma classifications
Micro/macro < or >1cm, by cell type: gonadotroph, thyrotroph, corticotroph, lactotroph, somatotroph, lactrotroph/somatotroph adenomas
What type of pituitary adenoma is most common?
Lactotroph 40-50% hyperprolactinemia
What type of pituitary adenoma is least common?
Thyrotoph 1% hyperthyroidism
Mutations in what genes can play a role in pituitary adenomas?
MEN1, Gs-alpha, PTTG, FGF receptor-4
Pituitary adenoma si/sx
Neurologic symptoms: visual changes, HA, CSF rhinorrhea (rare), hormonal changes too, can also be asymptomatic
Pituitary adenoma visual symptoms
Blurry vision, diplopia, bitemporal hemianopia visual field defect, diminished visual acuity
All varies based on tumor size/location
Visual changes happen with pituitary adenomas when they are how big?
> 2cm
Pituitary apoplexy
Si of pituitary adenoma, infarct or hemorrhage into the adenoma
Si/sx of pituitary apoplexy
Severe acute onset HA, vomiting, visual field deficits-diplopia/BTH, other cranial nerve dysfunction (3, 4, 5, 6), fever beck stiffness, impaired consciousness/AMS
Diagnostic studies for pituitary adenoma
Hormonal evaluation like serum prolactin, insulin-like growth factor 1, 24 hour urinary free cortisol and elevated ACTH, MRI
If a thyrotroph adenoma is suspected which lab tests are done
Alpha subunit, total or free T4, TSH
If a gonadotroph adenoma is suspected, which lab tests are done
LH, FSH
Diagnosis of pituitary adenoma
MRI: consistent with adenoma, hormone hypersecretion (functional vs. non functional), evaluation for visual abnormalities
Pituitary adenoma/ incidentaloma evaluation
Size >10mm typical hormone evaluation
Size <10mm without clinical findings: measure serum prolactin, could consider MRI at 6 mos and 12 mos, no eval for visual defects
Treatment goals of pituitary adenomas
Nonfunctioning: relief of visual impairments and other neurologic symptoms, removal of macroadenomas completely to avoid recurrence, management of hormonal deficiencies
Pituitary adenoma treatment
surgical therapy treatment of choice
Medical therapy: ID hormone deficiency and tx preoperatively
Adjuvant radiation therapy
What are some post-op hormone deficiencies from pituitary adenoma?
Hypocortisolism, diabetes insipidus and SIADH
Outcome of pituitary adenoma surgery
Most have reduced size of adenoma, visual function improvement, hormone deficiencies unlikely to improve, mortality rate 1% serious complications 5%
Follow-up pituitary adenoma surgery
Non-surgical pts: MRI every 6-12 mos, visual field exam every 6-12 mos, monitor and treat hormone deficiencies
Post transsphenoidal resection: 4-6 weeks, residual adenoma monitor with MRI
Hyperprolactinemia physiologic causes
Sleep, physical exertion, food, stress/trauma, coitus, pregnancy, postpartum state, nursing/nipple stimulation, surgery
Pituitary/hypothalamic disorders that cause hyperprolactinemia
Prolactinoma, acromegaly, other pituitary tumors, infiltrative disorders (MS), hypothalamic and pituitary stalk disease or damage
“Other” causes of hyperprolactinemia
Primary hypothyroidism, seizures, PCO, neurogenic causes (chest wall trauma, herpes zoster), renal insufficiency, cirrhosis
What can cause hypothalamic-pituitary disease?
Lactotroph adenoma (prolactinoma), decreased dopaminergic inhibition of prolactin secretion (drugs or damage), disease in or near hypothalamus/pituitary
Drug-induced causes of hyperprolactinemia
Ranitidine, Cocaine/amphetamines, metoclopramide, opioids, risperidone, SSRIs, verapamil, hydroxyzine
30-40% of all pituitary adenomas are what?
Prolactinomas
Prolactinomas are frequently diagnosed in who?
Women age 20-40. Ones in men are usualyl larger
90% of prolactinomas are what?
Microadenomas
10% macroadenomas
Clinical manifestations of hyperprolactinemia?
Galactorrhea, infertility, osteopenia, decrased libido
Clinical manifestations of hyperprolactinemia in women?
Oligo-amenorrhea, acne/hirsutism, estrogen deficiency sxs/dyspareunia
Clinical manifestations of hyperprolactinemia in men?
Erectile dysfunction, gynecomastia
Hyperprolactinemia labs to evaluate
Diluted fasting prolactin, TFTS, LFTs, Ca, Cre/BUN, HCG, IFG-1 (if clinccally indicated)
Evaluation of hyperprolactinemia
PE, MRI with and without gadolinium
If suprasellar extension: obtain visual fields
If macroadenoma: perform ant pit testing for GH, thyroid and adrenal insufficiency
Hyperprolactinemia diagnosis
Serum prolactin level will be significantly elevated
MRI with pituitary lesion/adenoma
Prolactinoma treatment indications
Tumor growth, oligo or amenorrhea/hypogonadism, bothersome galactorrhea, infertility
Hyperprolactinemic patients with a microadenoma may be followed without treatment if they are
Asymptomatic, eugonadal, have stable MRI scans
Prolactinoma therapy
Dopamine agonists: first choice in most pts
Cabergoline: first choice
Bromocriptine: first choice for women wanting pregnancy
Can also do surgery and radiation
Prolactinoma indications for surgery
Visual field defects unresponsive to meds, macroadenomas unresponsive to meds, tumor growth while on meds, intolerance to dopamine agonists, pituitary apoplexy (rare), CS rhinorrhea or >50% shrinkage of tumor with meds
Hyperprolactinemia: Goals for dopamine agonist therapy
Normalize prolactin levels and achieve remission of associated symptoms, reduce/stabilize tumor size, preserving ant pit function, prevent disease progression
What is the presentation of acromegaly?
Prognathism, HA, vision defect, skin tags, enlarged tongue/macroglossia, front bossing*, course features, enlarged hands and feet, osteoarthritis, carpal tunnel
Which clinical features are most commonly seen in acromegaly?
Acral enlargement and or coarse features, sweating, menstrual disorder, HA, arthritis, carpal tunnel syndrome, Diabetes, HTN
Why is the diagnosis of acromegaly delayed?
Due to gradual development
What are some co-morbidities associated with acromegaly?
HTN and heart disease, cerebrovascular events and HA, arthritis, insulin-resistant diabetes, sleep apnea
Baseline evaluation of acromegaly involves what?
IFG-1, pituitary function testing (if macroadenoma), PRL, glucose, LFTs, Cr/BUN, MRI of pituitary, visual fields, CH suppression with oral glucose
What is the surgical therapy for acromegaly?
Transsphednoial pituitary microsurgery
What is the medical therapy for acromegaly?
Dopamine agonists, somatostatin analogs, Pegvisomant
What is the radiation therapy for acromegaly?
Stereotactic radiosurgery
What are the goals of therapy for acromegaly?
Control tumor size, IGF-1 normal an dOGTT suppression of GH <1mcg/L
What somatostatin analogs can be used for acromegaly?
Octreotide and Lanreotide
Which Dopamine agonists can be used for acromegaly?
Bromocriptine and Cabergoline
Which GH receptor antagonists can be used for acromegaly?
Pegvisomant
What are examples of primary neoplastic pituitary tumors?
Pituicytoma, Germ cell tumors, sarcomas, chordomas, lymphomas, carcinomas
What types of pituitary neoplastic malignant tumors are metastatic?
Breast cancer in women, lung cancer in mean
Pituicytoma
Low-grade indolent glioma. Arises from post pituitary
How does Pituicytoma present?
Sellar mass; usually mistaken for pituitary adenoma. No known hormonal secretory function
Germ cell tumors
3rd decade of life, imaging will show mass in 3rd ventricle
Si/sx of germ cell tumors
HA, N/V, lethargy, diplopia, hypopituitarism, diabetes insipidus, paralysis of upward conjugate gaze (Parinaud’s syndrome)
What is Parinaud’s Syndrome
Occurs in germ cell tumors. Its the paralysis of upward conjugate gaze
Lab studies for germ cell tumors
Serum concentrations of B-hCG or AFP may be increased, highly malignant and metastasize readily
Chordomas
Local aggressive tumors, metastasize
Si/sx of chordomas
HA, visual impairment, ant pituitary hormonal deficiencies
Primary lymphoma
HA, visual and oculomotor impairment, ant pituitary hormonal deficiencies, ADH deficiency
What will MRI show of a primary lymphoma?
Sellar mass with variable extrasellar extension
Metastatic Disease
Metastases to the pituitary and hypothalamus, accounts for 1-2% of sellar masses
Who is metastatic disease commonly seen in?
Breast cancer in women and lung cancer in men (and many other cancers)
Symptoms of metastatic disease
Diabetes insipidus, visual field defects, ant pituitary hormonal deficiencies, retroorbital pain and ophthalmoplegia, poor prognosis
