Calcium/Bones/PTH (Pales) - SRS Flashcards
What is PTH secretion modulated by?
Calcium sensing receptors on membranes of the parathyroid cells.
High ionized Ca++ causes reduced secretion of PTH, obviously. What else, less obviously causes reduced PTH secretion?
Low (or high) magnesium
What is the effect of PTH on phosphate levels?
Decreased serum phosphate levels d/t increased renal dumping.
What role exactly does UV light have in the vitamin D axis?
Converts 7-dehydrocholesterol to cholecalciferol (vitamin D3)
What does vitamin D do to the gut?
How about to the parathyroid?
- Increases calcium and phosphate absorption in gut
- Suppresses parathyroid cell function
What is the most common cause of hypercalcemia?
Primary hyperparathyroidism
What is the root cause of primary hyperparathyroidism in over 80% of cases?
Single parathyroid adenoma
What makes up the remainder of the causes of primary hyperparathyroidism besides single parathyroid adenoma?
–Double adenoma or gland hyperplasia
–Carcinoma <1%
–Multiple Endocrine Neoplasia (10% of cases)
What is the usual presentation of primary hyperparathyroidism?
•Usually presents as asymptomatic hypercalcemia or with renal stones
Primary hyperparathyroidism results in phosphate and bicarbonate wasting, leading to what two main complications?
–Non-anion gap metabolic acidosis
–Cortical bone loss leading to osteoporosis
Neoplasms Associated with Non-Parathyroid Hormone Mediated Hypercalcemia may be classified as either of what two types?
Humoral hypercalcemia of malignancy
Local osteolytic hypercalcemia
What are the three examples of local osteolytic hypercalcemia neoplasms we covered?
Multiple myeloma
Breast cancer
Lymphomas
What causes tertiary hyperparathyroidism?
Give Pales’ answer, then correct him, because he fucked this up.
Pales states that it is d/t reduced activation of Vitamin D in the setting of chronic renal disease leading to elevated PTH. This is wrong, as he describes secondary hyperparathyroidism. (See Dr. Hertz and Robbins)
Tertiary hypoparathyroidism occurs when the parathyroid becomes autonomous and excessive, resulting in hypercalcemia, and is seen typically in renal transplant recipients.
Secondary hyperparathyroidism is caused by any condition that gives rise to chronic hypocalcemia, which in turn leads to compensatory overactivity of the parathyroid glands. Renal failure is by far the most common cause of secondary hyperparathyroidism, although several other diseases, including inadequate dietary intake of calcium, steatorrhea, and vitamin D deficiency, may also cause this disorder.
Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (2014-09-05). Robbins & Cotran Pathologic Basis of Disease (Robbins Pathology) (p. 1103). Elsevier Health Sciences. Kindle Edition.
Familial Benign Hypocalciuric Hypercalcemia can easily be mistaken for mild hyperparathyroidism.
What is the inheritance pattern in this disease?
What is the mutation here?
•Autosomal dominant inherited disorder
–Causes loss-of-function mutation in CaSR
Where are the receptors affected by the loss-of-function mutation in Familial Benign Hypocalciuric Hypercalcemia?
What happens as a result of this at each site?
Parathyroid Glands: reduced sensing of calcium leads to increased PTH
Renal tubules: reduced calcium sensing leads to reduced calcium in urine. (d/t loss of feedback mechanisms which would decrease calcium reabsorption when serum calcium is high)
In addition to the hypercalcemia, you may see normal or mildly elevated PTH and magnesium levels.
How do you diagnose this condition?
What should you do to treat, surgery or pharm?
–Diagnose with low urinary calcium clearance
–Surgery does not help – treat medically
What is the memory device for hypercalcemia? (Pales adds one here)
- Painful bones
- renal stones
- abdominal groans
- psychic moans
- fatigue overtones
Severe hypercalcemia can have what two significant effects?
Coma or arrhythmias
This patient with chronic renal disease shows up to your clinic and wants to know what is going on. You inform him that his lesions are called?
You further inform him that the cause of these lesions is?
calciphylaxis (small vessel thrombosis and skin necrosis)calciphylaxis (small vessel calcification, thrombosis and skin necrosis).
Caused by hypercalcemia
You further examine your patient with calciphylaxis and on examination of the eye identify the attached findings.
What is this called?
Band Keratopathy
You see a patient who has excessive PTH levels, and find that they have the following…
- –Chronic bone resorption
- –Demineralization
- –Pathologic fractures
- –Cystic bone lesions
What does this patient have?
Osteitis Fibrosa Cystica
The combination of increased osteoclast activity, peritrabecular fibrosis and cystic brown tumors is the hallmark of severe hyperparathyroidism and is known as generalized osteitis fibrosa cystica. What is the other name for this?
Von Recklinghausen Disease of bone
What are the seven components of the management of hypercalcemia according to Pales?
- IV fluids
- Loop Diuretics
- IV Bisphosphonates
- Calcitonin
- Glucocorticoids
- Cinacalcet
- hemodialysis or peritoneal dialysis
What are the five groups of causes of acquired hypoparathyroidism?
- Post-operative
- Autoimmune
- Heavy metals
- Magnesium deficiency
- “other causes”
What are the auto-immune conditions that tend to cause hypoparathyroidism?
SLE
PGA type 1 - autoimmune polyendocrinopathy
What are the heavy metals that cause hypoparathyroidism?
- Wilson’s disease - Copper
- Hemochromatosis - Iron
What are some “other” causes of hypoparathyroidism?
- Infection
- Reidel Thyroiditis
- Tumor
- Granulomas
PGA Type 1: Autoimmune polyendocrinopathy typically presents in childhood with two of what three possible conditions?
- Candidiasis
- hypoparathyroidism
- Addison Disease
PGA Type 1: Autoimmune polyendocrinopathy may present with 4 physical findings and autoimmune thyroid disease. What are the four possible physical findings>
- Cataracts
- Uveitis
- Alopecia
- Vitiligo
Congenital hypoparathyroidism comes in what three flavors?
- Abnormal calcium-sensing receptors suppress the parathyroid glands
- Barakat or HDR Syndrome
- DiGeorge’s Syndrome
In congenital hypoparathyroidism with abnormal calcium-sensing receptors, hypocalcemia will be seen without elevation of PTH. What is the inheritance pattern of this disorder?
Autosomal dominant
What are the three components of Barakat Syndrome?
This is an autosomal dominant mutation of what?
AKA HDR syndrome - Hypoparathyroidism, Deafness, Renal dysplasia
Mutation of GATA3
What is the memory device for DiGeorge’s syndrome?
CATCH-22
•Cardiac Abnormalities
–(tetrology of Fallot)
- Abnormal fascies
- Thymic aplasia
- Cleft palate
- Hypocalcemia–Autoimmune hypoparathyroidism
Deletion q-22
Pseudohypoparathyroidism arises d/t what?
What does it present with?
End-organ resistance to PTH.
- Hypocalcemia and hyperphosphatemia d/t renal tubular resistance to PTH
- Increased circulating PTH
What PTH receptors are typically unaffected in pseudohypoparathyroidism? What does this lead to?
Normal PTH receptors still found in the bone = boney changes of hyperparathyroidism
A patient with Albright heredetary osteodystrophy would present with what six phenotypical characteristics?
- Short stature
- obese
- Bradydactyly,
- round faces
- Dermal ossifications
- Mental retardation
What are the main signs of Rickets?
- Delayed closure of fontanelles
- Rachitic rosary
- Curved radius and ulna
- bowed legs
- Large, lumpy joints
Osteomalacia presents with pain in the bones, particularly the hips, fractures and muscle weakness. What is the source of the problem.
D deficiency leads to problems mineralizing the bone.
What are the three phases of Paget’s disease?
- Osteolytic phase
- Mixed phase
- Osteoblastic phase
Where does the osteolytic phase of pagets primarily hit?
See wedge-shaped resorption front at either end of long bones or circumscribed osteolytic lesions in the skull
In the mixed phase of pagets you see less bone remodeling and more?
Sclerosis
Cotton wool appearance of bone is associated with what phase of Pagets disease?
Osetoblastic phase
- “Cotton wool” appearance with patchy increase in bone density
- Bone scan shows osteoblastic uptake and can help identify the extent of the disease
What is the cure for Pagets?
There isn’t one, but we can decrease the rate of osteoclastic bone resorption.
Ha, I got you on the last one. Now that you know Pagets is not cureable, what are the ways we manage the condition?
- Tx of choice is bisphosphonates
- calcitonin
- Symptomatic therapy
What are the downsides of calcitonin for the treatment of pagets?
- Can develop neutralizing antibodies
- Not as potent as the bisphosphonates
- Shorter lived suppression
As we all know, in Pagets, the alkaline phosphatase score is insanely high… What are the levels of the following?
- –Serum C-telopeptide
- –Urinary hydroxyproline
- –Serum calcium
- –Serum C-telopeptide (high)
- –Urinary hydroxyproline (high in active disease)
- –Serum calcium (usually high)
Osteoporosis is a silent skeletal disorder characterized by compromised bone strength and increased predisposition to fracture. Risk factors can be genetic, hormonal, lifestyle/nutrition, medications or medical conditions.
What are the major risk factors for this condition that fall under the “genetic” category?
- Female
- white
- Asian
- FmHx of osteoporosis
- small body size or weight
What are the hormonal risk factors for osteoporosis?
menopause (natural, premature, or surgical)
What are some lifestyle/nutritional risk factors for osteoporosis?
- inadequate calcium intake,
- smoking,
- excessive alcohol consumption,
- eating disorders,
- excessive physical activity causing amenorrhea
What are the medications we discussed that predispose patients to osteoporosis?
- Glucocorticoids
- anticonvulsants
- heparin
Name as many indications for measuring BMD as you can. (9 listed)
- Women age >65 (regardless of fracture risk)
- Postmenopausal women <65 who have at least one risk factor for osteoporosis other than menopause
- Postmenopausal women who present with fractures
- Women who are considering therapy for osteoporosis and for whom bone mineral densitometry test results would influence this decision
- Women who have been receiving hormone replacement therapy for a prolonged period
- Radiographic findings suggestive of osteoporosis or vertebral deformity
- Corticosteroid therapy for more than 3 months
- Primary hyperparathyroidism
- Treatment for osteoporosis (to monitor therapeutic response)
What is the gold standard for measuring bone mass?
What are four reasons why?
Dual energy X-ray absorbtiometry
- –Best correlation with fracture risk
- –Short scanning time
- –Low exposure to radiation
- –Can measure in all areas of skeleton
What are two other not as good methods for measuring bone density?
–Quantitative CT, single-photon absorbtiometry
–Quantitative ultrasound
What is a T score?
What is it used for?
What would a T score of -1 mean?
–Standard deviation from the mean BMD of a young healthy population
–Primarily used to diagnose osteoporosis
–T-Score of -1 = 10% bone loss
What is a Z score?
What three patient populations is it primarily used for?
–Standard deviation from the BMD of an age and sex matched group
–Used for younger men, children, and premenopausal women
Give the WHO definitions for Bone mass and their associated T scores.
- Normal Bone Mass = T-Score > -1
- Osteopenia = T-Score -1 to -2.5
- Osteoporosis = T-Score <-2.5
- Established Osteoporosis = T-Score <-2.5 and osteoporotic fracture
Exercise and physical activity are important in treating osteoporosis, but there is no consensus on how much or what type. Nonetheless, what did Dr. Pales recommend?
–30 minutes of weight bearing or resistance exercise at least 4 times per week
How do alendronate and risedronate work?
Bisphosphonates • Pyrophosphate derivatives that bind to boney surface and inhibit osteoclastic bone resorption.
Bisphosphonates are poorly absorbed and must be taken during fasting states. They are associated with •Significant anti-fracture efficacy at spine, hip and other sites. At what T score levels is Alendronate more effective at reducing fractures?
•Alendronate more effective in reducing fractures with severe osteoporosis than osteopenia. So T score under -2.5.
Zolendronate is a newer bisphosphonate shown to significantly increase BMD. What is another reason this drug is neato?
Single injected dose suppresses bone turnover for a full year
According to the women’s health initiative, what are the downsides of hormone replacement therapy for osteoporosis?
Increased risk of…
- CV disease
- Breast cancer
- Stroke
- DVT
- PE
What is the major SERM used to tx osteoporosis?
Raloxifene
Raloxifene is a somewhat reasonable HRT option since it has a decreased risk profile. What specifically is different about the risks with this drug?
–Estrogen-like effect on bone but inhibits effects of estrogen on breast and uterus
–Increased BMD, decreases risk of vertebral fractures, (not hip fractures though)
–No increased risk of CV disease and decreases breast cancer risk. (Does Increase risk for DVT/PE though)
Calcitonin is administered as a nasal spray indicated for women who are 5 years post menopause, and increases BMD in the spine which decreases risk of vertebral fractures.
Where does it not decrease fracture risk?\
What other beneficial effect does it have?
- Does not affect incidence of hip fractures
- Analgesic effect on bone pain
Teriparatide is the only anabolic agent for osteoporosis and is administered SQ for no more than 2 yrs duration. What is its MOA (generally speaking)?
Stimulates osteoblastic bone formation
Teriparatide (rPTH) increases BMD and decreases fracture risk and is indicated for patients with high fracture risk and are intolerant of other medications.
In what patients should you not use this drug? 3
- Avoid with Paget’s
- hx of radiation involving bone,
- skeletal cancer – possible osteosarcoma.
Denosumab was approved in 2010, and is a monoclonal antibody that is administered SQ every 6 months. What does it do?
Works as an exogenous osteoprotegrin, binding RANKL inhibiting osteoclast activation.
What are the effects of Pagets disease on the following serum values?
- Calcium
- Phosphate
- Alk Phos
- PTH
What is the general theme of this condition?
- Calcium - Unaffected
- Phosphate - Unaffected
- Alk Phos - Elevated
- PTH - Unaffected
Abnormal bone architecture
What are the effects of Vonrecklinghausens disease of bone on the following serum values?
- Calcium
- Phosphate
- Alk Phos
- PTH
What is the general theme of this condition?
- Calcium - elevated
- Phosphate - decreased
- Alk Phos - Elevated
- PTH - Elevated
Brown tumors (Osteitis fibrosa cystica)
What are the effects of osteomalacia and rickets on the following serum values?
- Calcium
- Phosphate
- Alk Phos
- PTH
What is the general theme of this condition?
- Calcium - decreased
- Phosphate - decreased
- Alk Phos - variable
- PTH - elevated
Soft bones
What are the effects of osteopetrosis on the following serum values?
- Calcium
- Phosphate
- Alk Phos
- PTH
What is the general theme of this condition?
- Calcium - Unaffected
- Phosphate - Unaffected
- Alk Phos - Unaffected
- PTH - Unaffected
Thick dense bones, AKA marble bone
