Parathyroid Disoders - Exam 3 Flashcards
Where are the parathyroid glands located? How many? Describe their appearance.
posterior thyroid gland
4 glands located on the posterior thyroid gland
Size -grain of rice to pea-sized
Shape - smooth surface, oval or bean-shaped
Normally not visible or palpable on neck exam
Parathyroid Hormone (PTH), which plays a key role in regulating _____ level. ____: synthesize and release PTH. ______ are less abundant, larger, acidophilic, nonfunctional
extracellular calcium
Principal (chief) cells
Oxyphil cells
Amounts of _____ and ____ increases with age
adipocyte deposits
oxyphil cells
Describe the textures of the thyroid and parathyroid glands
thryoid is bumpy
parathyroid is smooth
What is the net effect of PTH? ______ in the serum interacts with _____ on the surface of cells in the parathyroid glands and kidney
increase serum calcium
Ionized Calcium (aka free calcium, NOT bound to albumin)
calcium-sensing receptors (CaSR)
What do high calcium levels stimulate? What about low calcium levels?
stimulates CaSR receptors → PTH suppression
CaSR receptors are not stimulated → PTH release
What is PTH’s response to low calcium? minutes? hours? days?
minutes: release of preformed PTH
hours: PTH mRNA expression → increased PTH synthesis
days: parathyroid cell replication → increased parathyroid gland mass
What are the 4 functions of calcium?
-maintain skeletal strength
-regulates contraction of muscle
-cellular signaling (especially neurons)
-secretion of hormones and enzymes
Where are the 3 areas that calcium is stored?
1: bone as hydroxyapatite
#2: intracellular fluid
#3: Extracellular fluid
Bone: majority (99%) of the calcium in bone is stored as _____
hydroxyapatite
What is the job of calcium that is stored in the intracellular fluid?
Intracellularsignaling (second messengers), enzyme activation, muscle contraction
What is important to note about the calcium that is stored in extracellular fluid?
50% of the calcium is bound to proteins and only has minimal fluctuation
50% is unbound and fluctuates freely
______ is serum calcium that is not bound to proteins. How is serum calcium balance maintained?
Ionized calcium
by release of calcium from intracellular storage or influx from extracellular fluid
What 3 organs are responsible for maintaining the narrow balance of EXTRAcellular calcium and phosphorus? What are the responsibilities of each?
intestines: absorb dietary Ca
kidneys: reabsorb or excrete Ca as needed
skeletal system: reservoir for Ca, releases and reserving as needed
What is the function of phosphorus?
Helps form several major body components: skeleton (its part of hydroxyapatite), cell membranes, DNA/RNA and ATP
balance of several vitamins and minerals
pH regulation and enzyme activation
Most phosphorus in the body is as the ______. Name 3 places phosphorus is stored?
phosphate ion, PO4
Bone - majority (85%) in bone as hydroxyapatite
Intracellular/Soft Tissues - (14%) of overall body phosphorus. Phosphate ion, several parts of cellular structures and enzymes.
Extracellular Fluid - Blood, extracellular matrix
1% of overall body phosphorus, mainly as the ion PO4
_____ enhances the intestines ability to absorb calcium and phosphorus
vitamin D
In a normal healthy person, how are calcium and phosphorus related? What 3 major hormones maintain this balance?
inverse relationship, when calcium increases phosphorus decreases
PTH
Vit D (Calcitriol)
Calcitonin
What are the effects of PTH on bone? on kidney?
Bone:
Stimulates release of Ca2+
Stimulates release of PO4-
Kidney:
Increased Ca2+ reabsorption
Increased PO4- excretion
Stimulates production of calcitriol (1,25 Vitamin D)
How does PTH effect calcitriol?
Converted from inactive 25-OH Vitamin D by kidneys under the influence of PTH to its metabolically active form
What are the effects of calcitriol on the intestines?
Increased calcium absorption
Increased phosphorus absorption
What are the effects of calcitriol on bone?
Enhances effects of PTH on bone to promote more calcium release
Where does calcitonin originate? When is it released? What is the effect of calcitonin on the body?
calcitonin-secreting cells (C cells) in the thyroid
Calcitonin is released by the thyroid when C-cells become overstimulated by elevated calcium levels
Works in opposition to PTH
Suppresses renal reabsorption of Ca2+ → increased Ca2+ excretion
Inhibits osteoclasts in bone → decreased release and increased storage of Ca2+
What does the total serum calcium measure? What is normal? Which is the metabolically active form?
protein bound Ca plus free Ca
8.5-10.5
40-50% is protein bound to albumin
ionized calcium is free and considered metabolically active 4.4-5.4
What does high serum calcium mean? low serum calcium?
High - bone breakdown (elevated PTH, cancer), supplementation, kidney dz, meds
Low - low PTH, low vitamin D, kidney disease
____ and ___ could cause a serum calcium to look falsely elevated. _____ could cause it to look falsely low.
hemoconcentration and elevated serum proteins
low serum proteins
Abnormal _____ requires a corrected calcium level! Under what conditions is the corrected calcium calculation NOT accurate?
albumin
serum calcium + [0.8 x (4.0 - albumin)]
acid/base disorders
Acidosis - decreased calcium binding to albumin
Alkalosis - increased calcium binding to albumin
_____ is the current standard for dx of hyperparathyroidism. Is it accurate?
Serum Parathyroid Hormone (PTH)
very sensitive and specific test
What is the process of Vit D becoming active in the body? aka what forms of Vit D and what organs are required?
The LIVER converts D2/D3 (which is normally the form pts take PO) to 25-OH Vit D, which is metabolically inactive
The KIDNEY then takes 25-OH Vit D and converts it to active 1,25 Vit D (calcitriol)
_____ form of vit D is the result when you order a “Vit D level”
Serum 25-hydroxy vitamin D
**Which form of Vit D supplement is synthesized in skin, found in animal-derived diet food?
D3 (Cholecalciferol)
**Which form of Vit D supplement is derived from plant sources?
D2 (Ergocalciferol)
______ Metabolically active form of vitamin D. What is the normal range? What does a high level indicate? low level?
_____ is a result that could make it look falsely evelated
1,25 Vitamin D (Calcitriol)
20-76 pg/mL
High: excess supplementation, hyperparathyroidism, extrarenal production (granulomatous disease, lymphoma)
low: CKD, severe vitamin D deficiency, heritable diseases, tumor-induced osteomalacia, HIV protease inhibitors
What does a high serum phosphorus indicate? Low indicate? ______ are reasons why it could be falsely elevated?
High: hypoparathyroidism, kidney disease, supplementation, acidosis, cell lysis, several other conditions
Low: Low - hyperparathyroidism, malabsorption or poor diet, certain medications, low vitamin D, several other conditions
high levels of lipids, protein, or bilirubin
What is important to note about a serum phosphorus?
can bounce all over the place within the normal range
highest: in late morning in May/June
Lowest: in the evening in the winter
Also varies with food, antacids, renal function, menopause, pregnancy, bedrest
______ naturally found in various cells; especially active in tooth eruption and mammary gland development. Pathologically secreted by cancer cells and attaches to _____ receptors. What is the effect? What does a high test indicate?
Parathyroid Hormone Related Protein (PTHrP)
PTH
Results in a PTH-like effect on the bone and kidney
High - Humoral Hypercalcemia of Malignancy
90% of hypercalcemia results from _____ and ______. What are the other potential causes of hypercalcemia?
hyperparathyroidism due to adenoma and lithium
malignancy
vit D related aka too much vit D
What are the parathyroid related causes of hypercalcemia?
**Adenoma- MC-excess secretion of PTH due to increased parathyroid mass
Lithium: decreases parathyroid gland sensitivity to calcium
What cause of hypercalcemia decreases parathyroid gland sensitivity to calcium?
lithium
What cause of hypercalcemia is due to osteolysis, release of PTH-related protein (PTHrP)?
malignancy
What cause of hypercalcemia is due to increased GI calcium absorption and bone calcium release?
increases in Vit D aka they are supplementing too much
What are some causes of high bone turnover that could lead to hypercalcemia? What is the major one?
hyperthyroid: thyroid hormone stimulated bone resorption
immobilization
**thiazides: decreases urinary calcium excretion in addition to bone resorption
______ decreases urinary calcium excretion in addition to bone resorption. What does it lead to?
thiazides
hypercalcemia
What are some causes of renal failure that can lead to hypercalcemia? What is the major one?
Tertiary hyperparathyroidism
**Milk-alkali syndrome
_____ hyperplasia of the parathyroid glands from prolonged CKD persisting in elevated PTH (even if calcium normalizes with CKD treatment). What can it lead to?
Tertiary hyperparathyroidism
hypercalcemia
_____ Calcium carbonate supplementation to treat osteoporosis or dyspepsia - combination of hypercalcemia, metabolic alkalosis, renal impairment. What can it lead to?
**Milk-alkali syndrome: rates are increasing
hypercalcemia
Bone pain
kidney stones
constipation
stomach ulcers
fatigue
confusion
AMS
Shorted QT interval
Diminished reflexes
Bradycardia
Hypertension
What am I?
What is a highlighted symptom?
Hypercalcemia
**Shorted QT interval
In calcium related disorder the _______ the more prominent the symptoms
more rapid the elevation the more prominent the symptoms
What is the tx for hypercalcemia?
identify and treat the underlying cause
rehydration: IV NS 500-1000 mL/h x 2-4 hrs, as tolerated
Loop Diuretics: IV furosemide
Corticosteroids
Bisphophonates and/or Calcitonin
Tx of hypercalcemia, what do we need to monitor for when using loop diuretics?
Monitor for SE of hypokalemia, hypomagnesemia
Risk of paradoxical increase in Ca2+ due to bone resorption
Tx of hypercalcemia, why are we using corticosteroids?
Decreases conversion of inactive to active vitamin D
Especially beneficial when excess calcitriol is a contributing factor
Tx of hypercalcemia, why are we using Bisphosphonates, Calcitonin?
Decreases release of calcium from bone
Especially beneficial in chronic cases where PTH is elevated
What are the two MC causes of hypocalcemia?
MC causes of hypocalcemia are impaired production of PTH and/or vitamin D
What are some causes of hypocalcemia with a low PTH? Is this considered primary or secondary hypoparathyroidism? What does this cause?
Parathyroid agenesis
Parathyroid destruction: surgical, radiation, cancer, autoimmune
Reduced parathyroid function: Low magnesium - required for PTH production and release
primary
hypocalcemia
What are some causes of hypocalcemia with a high PTH? Is this considered primary or secondary hypoparathyroidism? What does this cause?
**Vitamin D deficiency: Nutritional, poor UV exposure, kidney disease, liver disease
**tissue injury
PTH resistance (PTH receptor mutations)
Malabsorption
Medications: calcium chelators, bisphosphonates
secondary: aka the parathyroid gland is fine, something else is the source of the error
hypocalcemia
anxiety
irritability
seizures
hyperactive reflexes
cramps
Chvostek sign
Trousseau sign
dysrhythmias
prolonged QT interval
What am I?
hypocalcemia
_____ Facial twitching, especially perioral, induced by gently tapping the ipsilateral facial nerve just anterior to the ear
Chvostek’s sign
____ Carpal spasm induced by inflating BP cuff around the arm (must achieve pressure 20 mmHg above obliteration point for 3-5 min)
Trousseau’s sign
What labs would you want to evaluate on pt with hypocalcemia?
Parathyroid hormone (PTH)
Vitamin D (both 25-OH Vitamin D and 1,25 Vitamin D/calcitriol)
Albumin
Creatinine
Calcium (correct if necessary)
Phosphorus
Magnesium
What is the treatment for hypocalcemia? Severe?
identify and treat underlying cause
Calcium replacement (give Vit D if needed)
______________
IV Calcium - 10% calcium gluconate 10-30 mL IV over 10-20 min
IV Magnesium if also low
Vit D if needed
**What can IV calcium cause that you need to be mindful of?
IV calcium can cause vasoconstriction and possible ischemia
_____ excessive PTH secretion leading to hypercalcemia, hypophosphatemia. It is the MC cause of ______. What is the MC pt demographic?
Primary Hyperparathyroidism
hypercalcemia
black then white women over 50-65 years old
Primary Hyperparathyroidism is usually caused by a ______
parathyroid adenoma
often asymptomatic
discovered incidentally
secondary to hypercalcemia: Bone pain, constipation, fatigue, altered mental status, bradycardia, kidney stones/nephrocalcinosis
What am I?
Can you usually feel a mass?
Primary Hyperparathyroidism
Parathyroid adenoma is not typically palpable on exam unless it is a carcinoma then you can in 52% of patients
What will the calcium and PTH lab values look like in primary hyperparathyroidism? What will labs look like if carcinoma is present?
corrected or ionized calcium: will be elevated
PTH: will be elevated
____
corrected or ionized calcium: If carcinoma present - levels often ≥ 14.0 mg/dL
**PTH: If carcinoma present - PTH often >5x ULN
What is the way to confirm your dx of primary hyperparathroidism?
elevated PTH in the presence of elevated ionized/corrected calcium
What do you do if PTH is normal/minimally high compared to Ca?
check 24 hr urine Ca
check for familial hypocalciuric hypercalcemia
**What is familial hypocalciuric hypercalcemia? What condition is it associated with?
are autosomal dominant d/o causing decreased function of calcium-sensing receptors on parathyroid and renal cells , so that higher than normal serum calcium concentrations are needed to suppress PTH release
primary hyperparathyroidism
If the 24 hour urine calcium is above _____ is (includes/excludes) FHH. If it is less than _____, what does it tell you? What medications must be help prior to testing?
200-300
excludes: so probably primary hyperparathryoidism
less than 200: FHH or primary hyperparathyroidism with vit D deficiency
Must stop loop and thiazide diuretics prior to testing
_____ helps differentiate primary from secondary hyperparathyroidism. What does the results indicate?
Serum phosphorus
Normal to Low (< 2.5 mg/dL) - primary hyperparathyroidism
High (>4.5 mg/dL) - secondary hyperparathyroidism
What will Serum 25-OH Vitamin D and eGFR look like in primary hyperparathyroidism?
Serum 25-OH Vitamin D - may be low in hyperparathyrodism due to excessive conversion of 25-OH vitamin D to 1,25 vitamin D (calcitriol)
eGRF: just checks the status of the kidneys aka looking for renal dysfunction
Is imaging needed to dx primary hyperparathyroidism?
NOT needed to dx
only needed if you are thinking sx
_____ is the most used imaging for soft tissues in the neck. When is Nuclear Medicine Parathyroid Scan used? When are CT-4D scans used?
Neck US
to check function of Hyperfunctioning parathyroid glands light up brighter than normal tissue
Uses CT imaging to capture rapid uptake and washout of parathyroid adenomas
Mainly used if US and parathyroid scan are indeterminate or if concern for ectopic parathyroid tissue (adenomas, carcinomas)
aka measured over time and looking for metabolic activity
What is the tx for asymptomatic primary hyperparathryoidism?
Geared at keeping bones healthy and minimizing symptoms
Adequate hydration - 6-8 glasses of water/day
Encourage physical activity: reduces bone resorption
Avoid medications that aggravate hypercalcemia: Thiazides, lithium, high doses of vitamin A
Moderate intake of calcium (1000 mg/d) and vitamin D (400-800 IU/d)
routine monitoring of labs: serum calcium, 25-OH Vit D, PTH
renal function labs
24-hr urine for calcium
DEXA scans
What medications should a pt with primary hyperparathyroidism avoid?
Thiazides, lithium, high doses of vitamin A
What is the DEFINITIVE treatment for asymptomatic primary hyperparathyroidism? What are the requirements? What happens if they are symptomatic?
surgery
only have to meet ONE criteria:
Kidney stones or nephrocalcinosis
Bone disease (osteopenia, osteporosis, pathologic fracture)
Persistent urinary calcium >400 mg/dL
Serum calcium >1 mg/dL above ULN
Age <50 years old
same criteria PLUS symptomatic or anyone who wants a cure and is healthy enough for surgery
What is the management for symptomatic nonsurgical primary hyperpararthyroidism whose bone density is WNL? What are the SE? What does it NOT do?
cinacalcet (Sensipar)
nausea, arthralgia, diarrhea, myalgia, paresthesia
Does not improve bone density or reduce calciuria
_____ binds to CaSRs in parathyroids, thereby decreasing PTH secretion. What lab do you need to monitor? and when?
cinacalcet (Sensipar) aka its calcium receptor blocker
Recheck serum calcium one week after initiating!
What is the management for symptomatic nonsurgical primary hyperpararthyroidism whose also has osteoporosis? What does it NOT do?
Bisphosphonates:
oral: alendronate (Fosamax), ibandronate (Boniva)
IV: pamidronate (Aredia), zoledronic acid (Reclast)
_____
Oral versions do not significantly impact hypercalcemia or hypercalciuria!
IV: Can temporarily treat hypercalcemia
_____ bind to hydroxyapatite and, when resorbed by osteoclasts, impair ability of osteoclasts to continue to resorb bone
Also decrease numbers of active osteoclasts by inhibiting osteoclast progenitor development and encouraging osteoclast apoptosis.
Oral version, what is the pt education?
When is the IV version used?
Bisphosphonates
oral: Patient must be able to remain upright for 30 minutes after ingestion
IV: Can temporarily treat hypercalcemia
May be used to help prepare patients with severe hypercalcemia for surgery
Which management for primary hyperparathyroidism can cause a slight reduction in serum calcium specifically when given to postmenopausal women? Is it first line?
Estrogen Replacement: aka protective effect on CA in the bones
NOT first line
_____ selective estrogen receptor modulator (SERM). Estrogen agonist in the bone to decrease bone resorption. Estrogen antagonist in the uterus and breast to reduce cancer risk. Is it a first line tx? What condition?
Raloxifene (Evista)
NOT first line to treat primary hyperparathyroidism
What are complications of primary hyperparathyroidism?
Weakened bones → osteopenia, osteoporosis, pathologic fractures (treat with Prolia, DEXA scan q 2 years, vertebrae at highest risk of fracture)
Vit D deficiency
renals effects: nephrolithiasis, nephrocalcinosis, CKD
____ excessive PTH secretion leading to hypercalcemia, hypophosphatemia that is caused by an underlying chronic abnormal stimulus or disease. What is the MC etiology?
Secondary Hyperparathyroidism
chronic kidney disease
Why is chronic kidney disease the MC cause of secondary hyperparathyroidism? What is the 2nd most common cause?
Poor renal reabsorption of calcium (hypocalcemia)
Inhibited excretion of phosphate (hyperphosphatemia)
Inadequate renal conversion of 25-OH Vit D to 1,25 Vit D
______
Vit D deficiency
What is the MC pt demographic for secondary hyperparathyroidism?
Black/Hispanic elderly women
HTN
edema
abnormal laboratory values: Low Vit D
LESS likely to have classic s/s of hyperparathyroidism
s/s of hypocalcemia: hyper- reflexive
What am I?
What will BUN/Creatine/eGFR show?
PTH/Calcium/Phosphorus/1,25 Vit D?
secondary hyperparathyroidism
BUN/Cr: will be elevated
eGFR: will be decreased
PTH - elevated
Calcium - low to normal
Phosphorus - high in CKD; low in vitamin D deficiency
1,25 Vitamin D - low in CKD and vitamin D deficiency
When would you order imaging on a pt with secondary hyperparathyroidism?
to look for complications
aka bone pain to look for pathologic fractures
What is the management of secondary hyperparathyroidism?
refer to nephro if CKD is present
Vit D supplementation specifically 1,25 Vit D (Calcitrol aka the one that you do NOT need good kidneys for because it is already active)
What is the MC cause of hypoparathyroidism? What are other causes?
typically involves some damage to the parathyroids usually some time of neck sx
autoimmune, radiation, infection, infiltration of cancer etc
______ group of disorders characterized by kidney and/or bone resistance to PTH. What will calcium, phosphate and PTH lab values look like? What is the treatment?
Pseudohypoparathyroidism
decreased calcium
increased phosphate
increased PTH
calcium and vitamin D therapy to maintain normal serum calcium levels
akak kidney/bones are not responding to PTH
You can see ____ associated with hemochromatosis, Wilson’s disease and/or Riedel thyroiditis
Hypoparathyroidism
functionally hypoparathyroidism is associated with _____ levels. What will severely low levels do to PTH? low? high?
abnormal magnesium levels
Severe hypomagnesemia (<0.5) - “false block” of CaSR which SUPPRESS PTH
Mildly low magnesium - INCREASE PTH release
High magnesium - SUPPRESS PTH release
_____ causes a “false block” of CaSR which suppresses PTH
Severe hypomagnesemia (<0.5)
______ is directly proportional to how abnormal the calcium level is. What is the hallmark symptom?
Hypoparathyroidism
tetany due to neuromuscular irritability
mild: paresthesias
severe: spasms, seizure
can see Trousseau’s and Chvostek’s signs
neurodegeneration, poor dentition, cataracts are all s/s of _____
chronic hypoparathyroidism
poor dentition (calcium leaving the teeth)
What is the ACUTE management of hypoparathyroidism? What is the goal?
maintain the airway
IV calcium gluconate 10% if there is tetany, seizures, bronchospasm, laryngospasm, prolonged QT interval, refractory heart failure
Goal of serum calcium 8-9 mg/dL
start PO Calcitriol (1, 25 Vit D) and calcium when the pt can tolerate aka swallow the medication
if needed: Magnesium supplementation
What forms are available for Calcitriol?
Cholecalciferol D3? Ergocalciferol D2?
Calcitriol:
capsules
solution
injection
Cholecalciferol:
capsule only
Ergocalciferol:
capsules
solution
What do you give for hypomagnesium in the case of acute hypoparathyroid management?
Dosing for moderate-severe hypomagnesemia:
magnesium sulfate IV 1-2 g every 6 hours
Transition to magnesium oxide 400 mg 1-2 times daily PO
What is the management of chronic hypoparathyroidism? What is the monitoring for each?
Oral calcium: monitor serum calcium q 3-6 months: need to keep calcium on the LOWER end of normal
Vit D and Magnesium supplement PRN
???Pts who are intolerant of, or refractory to calcium/Vit D-> PTH replacement therapy: Teriparatide (Forteo); (administered SQ), Synthetic PTH (1-34), Palopegteriparatide (prodrug)??
____
Urine and serum calcium, serum creatinine, phosphorus, 25-OH vit D
Every 3-6 months initially, then every 6-12 months
consider renal US if persistant hypercalciuria
What is the prevention of hypoparathyroidism?
cryopreserved parathyroid tissue that are then injected into the brachioradialis, pectoralis or SCM
______ Fat soluble vitamin, often from plant sources. What routes does it come in?
ergocalciferol D2
solution
capsule/ tablet
___ and ___ MOA Stimulates calcium and phosphorus absorption in small intestine.
Stimulates calcium reabsorption at renal tubule.
Stimulates secretion of calcium from bone into the blood.
Vit D3 and D2
____ - Peak effect approximately 1 month with daily dosing. Metabolism - liver, kidney. Elimination - urine
Vit D2: Ergocalciferol and Vit D3: cholecalciferol
What are the SE of Vit D2/D3 and Calcitriol? CI?
SE: hypercalcemia - constipation, confusion, fatigue, arrhythmias
CI: Allergy to medication
Hypercalcemia
Hypervitaminosis D
_____ Fat soluble vitamin, often from animal sources. What routes does it come in?
Vit D3: Cholecalciferol
solution
capsule/tablet
____ is the metabolically active form of Vit D. What routes does it come in? What kind of pt is it good for? Who usually prescribes it?
1,25 Vitamin D (calcitriol)
Solution
Capsule
IV
good choice for pt’s who have bad kidneys
nephro rx only due to the higher chance of it causing problems due to its already active form
______ MOA binds to and activates vitamin D receptor in kidney, parathyroid, intestine, bone. Decreases PTH levels, stimulates calcium absorption, can enhance the effects of PTH on bone.
1,25 Vitamin D (calcitriol)
When does 1,25 Vitamin D (calcitriol) start working?
begins working in 2 hours as compared to Vit D2/3 that takes a month to start working
_____ is oral calcium salt and is used in hypocalcemia prevention/treatment. What is a potential SE?
calcium carbonate
hypercalcemia
_____ is IV calcium salt and is given in severe hypocalcemia. What is a potential SE?
Calcium Gluconate
hypercalcemia: aka it works too well
_____ is an antacid and electrolyte. When do you exercise caution when giving to _____ pt. **What is a SE?
Magnesium Oxide
Caution if renal impairment
Diarrhea GI irritation
