Question | Answer |
Most common etiology of anterior hypopituitarism | mass lesion |
HA, vomiting, opthalmoplegia (eye in down and out position), ptosis, mydriasis | Pituitary Apoplexy: Acute intrapituitary hemorrhagic vascular events can cause substantial damage to the pituitary and surrounding sellar structures |
T/F: Most patients have normal pituitary function with Empty Sella Syndrome | True, were you even listening to my presentation? |
Most common cause of hyper and hyposecretion of pituitary hormone syndromes in adults | Pituitary adenomas, which recall, are benign |
Most common presenting feature of adult hypopituitarism | Hypogonadism |
What blood tests would you do for anterior hypopituitarism? | TSH, T4, ACTH |
Along with low ACTH and cortisol levels, what differentiates anterior hypopituitarism from primary adrenal insufficiency? | Normal potassium, lack of hyperpigmentation |
Progressive loss of several or all pituitary hormones with a rapid onset post pituitary apoplexy | Panhypopituitarism |
Very low IGF-1 is indicative of | Growth hormone deficiency. |
What are some Tx for anterior hypopituitarism? | Removal of pituitary tumors and replacement of hormones |
4 endocrine active pituitary adenomas (tumors producing hormones) | Prolactinoma, Somatotropinoma, Corticotropinoma, Thyrotropinoma |
3 possibilities on secretions of hormones with pituitary adenomas? | 1) Excess of 1 hormone 2) Deficiency of 1 hormone 3) Deficiency of all hormones |
Preferred imaging study for pituitary? What can you use when that is CONTRA? | MRI; CT (pacemaker/metallic implants around brain or eyes |
What sight problem can a pituitary tumor cause? What does that impair? | Bitemporal hemianopsia...compression of optic nerve medial fibers by tumor impairing peripheral vision on each side |
What is diagnostic for Acromegaly? What might you think would be but isn't, and why? | IGF-1; Might think GH would be as there is an abundance, but it is pulsated randomly and doesn't correlate with disease severity. |
Indolent and often not clinically Dx for 10+ years with acral bony overgrowth; often have MEN 1 genetic abnormalities | Acromegaly |
Leading cause of death in acromegaly? | Cardiovascular |
Txs of acromegaly | Pituitary microsurgery is TOC |
Most common etiology of iatrogenic hypercortisolism | Long term steroid use |
Difference btwn Cushing's syndrome and Cushing's disease? | Syndrome: Excess cortisol from pituitary, adrenal or other sources. Disease: excess pituitary secretion of ACTH |
Sx of what? Thin skin, central obesity, moon facies, purple striae, HTN, DM, hyperpigmentation, buffalo hump, hirsutism | Chronic cortisol excess |
Hematopoietic features of hypercortisolism | Leukocytosis, lymphopenia, eosinopenia |
Will ACTH be high or low in ACTH independent Cushing's Syndrome? | Low (usually from ectopic source or cancer and the high cortisol levels will negatively feedback to pituitary, therefore lowering ACTH) |
What happens to 1) Normal 2) Cushing's Disease and 3) Ectopic ACTH Syndrome (ACTH independent Cushing's Syndrome) during a Dexamethasone Supression test? | 1) Almost completely suppressed 2) Partially suppressed 3) No response to supression |
What is the imaging technique of the most common functional pituitary adenoma? Common Sx include visual-field defects (especially in men), or HA. 90% of women also get microadenomas. | MRI is preferred imaging for Prolactinomas. |
TOC for prolactinomas | Dopamine agonists (Bromocriptine, cabergoline) |
T/F: all pituitary microadenomas are of clinical concern and require evaluation of hormonal status | GOSH I hate these kind of T/F: FALSE, not all microadenomas are of clinical concern but they DO all require evaluation of hormonal status |
Decreased vasopressin, increased dilute urine, hyperosmolality, increased thirst, elevated sodium if water loss | Diabetes Insipidus |
Increased vasopressin, abnormal concentration of urine, reduced osmolality, hyponatremic | Inappropriate ADH |
Marked excessive retention of sodium AND water stimulated by a large "effective" blood volume and low cardiac output. What diseases are these seen in? | Osmotically inappropriate ADH; seen in CHF, cirrhosis, nephrosis |
Hypernatremiuria, hyponatremia, hyperkalemia, increased ADH in response to decreased intravascular volume | Primary adrenal insufficiency |
Secondary deficiency not associated with thirst, yet polydipsia. | Psychogenic DI |
Decreased ADH resulting in abrupt onset of polyuria, polydipsia | Central Diabetes Insipidus (CDI) |
Most common cause of Central Diabetes Insipidus (CDI) | 30-50% of CDI cases caused by an autoimmune destruction of ADH -secreting cells in hypothalamus; Idiopathic DI |
T/F: DI will always respond to Desmopressin (vasopression challenge test). EC: how does it respond? | False, Nephorgenic DI won't respond as it is a kidney disease...Central DI will respond. Responds by reducing thirst and polyuria. |
4 effects Desmopressin has on the body in central DI | 1) increase urine osmolarity 2) Decrease urine volume 3) Increased body wt (water retention) 4) Decrease plasma osmolarity (diluting plasma and concentrating urine) |
Distinguishes primary vs secondary adrenal insufficiency | Primary: adrenals not responding to massive amounts of ACTH produced by pituitary trying to stimulate cortisol and ACTH causes HYPERPIGMENTATION; Secondary: Normal RENIN-ANGIOTENSIN SYSTEM, Low ACTH |
Most common cause of primary adrenal insufficiency? Other causes? | Autoimmune adrenalitis; TB, bilateral adrenal hemorrhage due to anti-coags, HIV, bilateral metastatic infiltration |
Sodium down, potassium up, elevated ACTH, eosinophilia, lymphocytosis, low aldosterone with non-specific Sx | Chronic primary adrenal insufficiency |
What is the difference between regular cortisol/hydrocortisone and florinef? | Also treats hypotension with salt retention |
What causes an adrenal crisis (acute adrenocortical insufficiency)? | Sudden withdrawal from chronic adrenocortical hormone therapy (like for surgery), pituitary apoplexy, injury to both adrenals (trauma, hemorrhage, thrombosis, infx [mengiococcemia]) |
HA, confusion/coma, elevated temp, HypoTN, Hyperkalemia, hyponatremia, elevated BUN...Tx? | Acute adrenocortical insufficiency: IV hydrocortisone |
Catecholamine-secreting tumors with paroxymal Sx: tachycardia, diaphoresis, HA, HTN, Hyperglycemia, wt loss, palpitations, Dx by plasma fractionated free metanephrines, associated with MEN 2, Age of onset usually 30-50. Tx? | Pheochromacytoma/ Paraganglioma; Tx: Surgery TOC |
HTN and hypokalemia, HTN usually due to adrenal incidentaloma. Aldosterone/renin ratio > 67 (<24 excludes Dx). Imaging? Tx? | Primary aldosteronism (hyperaldosteronism) as inappropriate high aldosterone secretion that doesn't not suppress in response to sodium. Imaging: Thin section CT of adrenals. Tx: laproscopic adrenalectomy or spirolactone if bilateral |
What are the main functions of parathyroid hormone? | acts on bones to induce calcium resorption, acts on kidney to enhance calcium resorption and synthesis of 1,25 Vit D; increase in serum ionized calcium and decrease in serum phosphorus |
What happens to bone with hyperparathyroidism, continuous over time? Tx? | increased osteoclast-mediated bone resorption and osteoporosis. PTH(1-34) is a monotherapy caused a highly significant reduction in fracture incidence. |
Primary target organs for most active vitamin D? | 1,25 (OH)2D; intestine and bone |
What rises and falls with serum phosphorus? Plays a central role in regulation of systemic phosphate homeostasis, vitamin D metabolism, bone mineralization | Fibroblast Growth Factor 23 (FGF-23) |
Tumor marker in sporadic and hereditary cases of medullary thyroid carcionoma | Calcitonin |
Physiologically active form of calcium...50% of calcium in plasma | free or ionized calcium |
If there is a low albumin level, what do you need to check for? Why? | Low albumin means low total calcium (but doesn't effect ionized calcium levels. You would want to measure the ionized calcium in this case to get a true calcium level |
Responsible for most instances of hypercalcemia in malignancy. No elevated PTH levels. Usually indicative of squamous cell types as well as renal carcinomas (which have massive overproductions of hormone) | Parathyroid-related protein PTHrP |
At what serum calcium levels do heart arrhythmias occur? Which ones occur? | >14 mg/dL; prolonged PR, shortened QT, heart block, asystole, bradyarrhythmias |
T/F: It doesn't make a difference, how fast calcium rises..we look at the absolute value risen. | False, abrupt rises can have stronger Sx at much more modest levels |
80% single adenoma, elevation of PTH and serum calcium in absense of lithium and low urinary calcium excretion, alk phos increase, elevated 1,25 vit D and low 25 vit D. What is the management? | PTH mediated hypercalcemia: hyperparathyroidism [HPT]. Management: surgical excision of abnormal parathyroid tissue definitive. In mild, ASx disease and older, some still prefer medical surveillance, but more evidence -> surgery |
Which ASx hyperparathyroid patients should have surgery? (6) | 1) Estimated GFR <60 2) -2.5 bone density 3) age under 50 4) if surveillance not desirable/possible 5) Calcium >1mg/dL above upper limit 6) Pregnancy |
What does a Preoperative 99mTc sestamibi scans do? What else can be monitored during surgery? | Predicts location of abnormal gland; Introperative sampling of PTH to confirm removal of suspected adenoma (will decrease to normal) |
2 medical alternatives to surgery with primary hyperparathyroidism | Bisphosphonates, Calcimimetics |
Low urinary calcium excretion, only normal to mildly elevated PTH levels, with a rare genetic component | Familial hypocalciuric hypercalcemia |
Pathophys of Lithium induced hypercalcemia | In treated pts, lithium can shift the PTH secretion curve to the right in response to hypercalcemia, and higher levels of calcium are required to lower PTH secretion, self-perpetuating the cycle |
PTH levels reduced, lymphokines/cytokines promote resorption of bone through local destruction | Direct Bone Marrow Invasion (leukemia, lymphoma, multiple myeloma |
How do you Dx Vitamin D mediated hypercalcemia? | First of all, ensure PTH level is low. Obviously they have to have hypercalcemia, but also increased levels of 25(OH)d [not 1,25(OH)2D]. 25D > 100mg/mL |
1,25(OH)2D levels are elevated, as this specific type of tissue converts 25 -> 1,25 at an increased rate. EC: What diseases are included with this type of tissue? | Granulomatous disease (sarcoidosis, tuberculosis, fungal infections) |
2 causes of hypercalcemia related to high bone turnover | 1) Hyperthyroidism 2) Immobilization |
How do thiazide diuretics cause hypercalcemia? | Reduction in urinary calcium excretion and they may "unmask" Dx of hyperparathyroidism |
Excessive ingestion of calcium and absorbable antacids causing hypercalcemia | Milk Alkali Syndrome |
Hypocalcemia initiates development of secondary hyperparathyroidism which stimulates an increase in calcium. What severe disease can cause this hypercalcemia? | Chronic renal failure. |
The next few slides will be a simple review of hypercalcemia | Get it. |
Elevated/inappropriately normal PTH and normal 24 hour urine calcium excretion: | Primary hyperparathyroidism |
Elevated/inappropriately normal PTH and low urine calcium excretion: | Familial hypocalciuric hypercalcemia |
PTH low and no malignancy | Check 1,25 Vit D, other supplements and drugs |
PTH low and malignancy with elevated PTHrP, 1,25 Vit D | Hypercalcemia of malignancy |
PTH low and malignancy with low PTHrP, 1,25 Vit D | local osteolytic hypercalcemia |
First principle treatment of hypercalcemia | normal hydration and loop diuretic |
How can hypomagnesemia cause hypocalcemia | Hypomagnesia can interfere w/ secretion and peripheral responses to PTH (low/undetectable levels). Low levels of PTH don't stimulate calcium. |
What do you need to check in hypocalcemia in acute pancreatitis? | Ionized calcium (low albumin levels in pancreatitis) |
4 specific things that can cause hypocalcemia and have a HIGH PTH | 1) Vit D deficiency 2) PTH resistance syndromes 3) Medications (bisphosphonates, phenytoin) 4) acute pancreatitis (PTH can be high, low, or normal) |
T/F: Most transient hypocalcemia will not have a reduction in ionized calcium | True |
Sx: Tetany including: hypoparathyroidism, acute hyperventilation, hypomagnesemia | Any cause of low ionized calcium. |
Twitching of circumoral muscles in response to gentle tapping of facial nerve just anterior to ear | Chvostek's sign |
Carpal spasm may be induced by inflation of blood pressure cuff to 20 mmHg above pt systolic blood pressure for 3 min | Trousseau's sign |
Tx for hypoparathyroidism | replacement of Vit D or 1,25(OH)2D3 and calcium (can be parental) |
Most abundant cells in bone, function as mechanoreceptors detecting strain on bone and signalling changes for remodeling, born from osteoblasts | Osteocytes |
Multinuclated giant cells specialized for resorption of bone. Requires RANKL for activation. | Osteoclasts |
Cytokine responsible for communication between osteoblasts and osteoclasts | RANK ligand or RANKL |
Decoy receptor that binds to RANKL preventing interaction w/ RANK and halting osteoclast differentiation | Osteoprotegerin (OPG) |
7 things that contribute to Osteoporosis | 1) Cig consumption (directly toxic to osteoblasts) 2) Calcium nutrition 3) Vit D deficiency 4) lack of physical activity 5) Estrogen deficiency 6) Medications (glucocorticoids etc) 7) Chronic diseases |
3 Steps to evaluating Osteoporosis | 1) Bone density measurement 2) Risk analysis using FRAX 3) Exclude secondary causes |
Biggest risk for osteoporosis? | Previous fragility fracture after 40 |
Variables on FRAX (13). He did emphasize we needed to know these. | Age, gender, height, weight, previous fracture, parent fractured hip, current smoker, glucocorticoids, RA, secondary osteoporosis, 3+ alcoholic drinks a day, femoral neck BMD, T score |
What test should you use when assessing for moderate risk (10-20%) of osteoporosis? | XRAY looking for compression fracture on spine |
T/F: Vitamin D supplementation prevents and treats osteoporosis but not osteomalacia | False, treats osteomalacia, but not osteoporosis |
slows remodeling cycle, enhances mineralization of bone matrix | Anti-resorptive agents |
Stimulates bone remodeling by increasing bone formation through the osteoblast | Anabolic agent |
T/F: Estrogens are no long used for osteoporosis or CVD prevention | True, simply used as a symptomatic drug for menopause |
What drug would you use for osteoporosis if there is a strong history of breast Ca in the family? | Raloxifene |
First line therapy for Tx of post-menopausal osteoporosis? How do they work? Do you use it for the rest of pts life? | Bisphosphonates; inhibit attachment of osteoclast to bone matrix and enhance programmed cell death; discontinue w/in 5 years to prevent bone loss |
Weird side effect of bisphosphonates (yes I realize this question is in the eye of the beholder) | Atypical femur fractures |
Nasal spray that increases bone density, reduces vertebral fractures... | Calcitonin |
PTH analog requiring adequate vitamin and calcium intake and dramatically increases bone density except in the distal radius (anabolic) (seriously, it is substantial) | Teriparatide injection (RDNA origin) |
Fully human monoclonal antibody specifically binds to RANKL with high affinity improving bone mineral density. Reserved for pts intolerant/nonresponsive to bisphosphonates | Denosumab |
Decreased bone density from defective mineralization...ex: Rickets in children. Indications: Low 25 vit D, hypocalcemia, hypophophatemia, elevated bone alk phos | Osteomalacia |
Bone lesions of increased turnover with disorganized osteoid formation. Sx: bone pain/deformity, kyphosis, elevated bone alk phos, elevated Ca, classic bone scan/XRay features. Major fall risk w/ gait disturbance | Paget's Disease of Bone: Osteitis Deformans |
T/F: Pathologist cannot distinguish between benign and malignant NETs (neuroendocrine tumors) unless metastases is present | True |
Tumors found 64% in the GI (small intestine and rectum) and 28% pulmonary | Carcinoid |
5 things that give GI NETs a poor prognosis | 1) Liver/lymph node metastases 2) elevated alk phos 3) primary size/speed of growth 4) Vascular invasion 5) High mitotic counts/necrosis |
Low 5-HT (serotonin) content, occasionally secrete ACTH or 5-HTP, may metastasize to bone; doesn't usually cause "carcinoid syndrome" | Foregut turmors |
High serotonin content, most frequently cause carcinoid syndrome when they mets, release serotonin and tachykinins, no 5-HTP or ACTH, usually multiple, 80% in ileum, less mets to bone | Midgut carcinoids; usually in small intestine or colon |
Rarely contain serotonin, cause carcinoid syndrome, or secrete 5-HTP or ACTH, but do have numerous peptides. Mets to bone | Hindgut tumors; rectum, transverse and descending colon |
Flushing DD: (6) (I included the main ones) | 1) Emotional 2) Food ingestion 3) Meds 4) Rosacea 5) Menopause 6) Carcinoid |
What is the urticarial eruption associated with NETs called? | Mastocytosis |
Carcinoid syndrome Sx | 1) Watery diarrhea 2) Flushing 3) Wheezing 4) Cardiac manifestations (97% have TRICUSPID INSUFFICIENCY [louder w/inspiration, holosystolic, big neck veins], fibrotic plaques on right side) |
Main Dx tool for carcinoid syndrome | Urinary 5-HIAA excretion rate (would be elevated) |
2 Tx for pancreatic endocrine tumors (with hormone excesses) | 1) Correct gastric acid hypersecretion and hypoglycemia 2) Surgical resection if feasible (often isn't) |
60-90% malignant tumor w/ PUD Sx (H. pylori neg, multiple ulcers, refractory to Tx, diarrhea). Dx: Fasting hypergastrinemia (rule out pernicious anemia); gastrin level >1000 and pH <2 when off anti-secretory meds | PET: Gastrinoma (Zollinger-Ellison Syndrome) |
Tx for Gastrinoma (Zollinger-Ellison Syndrome) | Anti-secretory medications, Whipple surgery if negative for MEN1 |
Attacks of hypoglycemia, Sx occur w/ fasting, confusion, disorientation, coma, Dx: simultaneous hypoglycemia w/ elevated insulin level; derived from beta cells w/ ectopic insulin secretion; Tx??? | Insulinoma; Surgery TOC |
Tumor secreting excess vasoactive intestinal polypeptide, 80-90% in pancreas, 37-68% have hepatic metastases at Dx. Sx: large volume diarrhea "pancreatic cholera", hypokalemia, dehydration, flushing, hyperglycemia. Tx? | Vipoma; correct dehydration, replace potassium, surgery indicated only if metastases present |
T/F: Lanreotide DOES reduce progression of disease more than placebo, but doesn't affect mortality or quality of life with neuroendocrine metastatic tumors | True |
Single most important prognostic factor in survival for carcinoids (specifically gastrinomas) | liver metastases |
Manifestations and Genetics of MEN 1 | Primary hypeparathyroidism (95%), enteropancreatic tumors, PRL, non-functional adrenal cortical, fore-gut carcinoid, skin angiofibromas; Genetics: autosomal dominant (screen family members) |
Manifestations of MEN 2A | Genetics: need total thyroidectomy and lymph node dissection as early as first months of life; HYPERTHYROIDISM |
Manifestations of MEN 2B | earlier onset MEDULLARY THYROIDISM (more aggressive), |
Disorders that accompany benign or malignant tumors but are not related directly to mass effects or invasion; atypical manifestations in pt w/cancer should raise suspicion | Paraneoplastic syndromes |
Some endocrine paraneoplastic syndromes (3) | 1) hypercalcemia a) PTHrP b) 1,25 vit D 2) Hyponatremia 3) Cushing's Syndrome |
Hirsuitism vs Virilization; What does virilization suggest? | Virilization: androgen levels high enough to cause findings like deepening of voice, breast atrophy, increased libido, increased muscle bulk; ominous sign suggesting ovarian/adrenal malignancy. Hirsuitism: FH, excessive male pattern hair growth |
Hirsuitism score >8 suggests? | Androgen hair growth should be assessed by hormonal evaluation (total and free testosterone >12 indicates virilizing tumor; DHEA >18.5 suggests adrenal tumor |
Unilateral, firm, fixed enlargement of breast | EXCLUDE Malignancy with mammogram |
Fractionated excretion of sodium with pre-renal? | Low |
Urine osmolality in ATN? | Low, high in pre-renal |