combination from MTB,Kaplan,step up ,usmle step 2 secrets and medbullets.including q&A.

1. Endocrinology-Parathyroid gland

2. Parathyroid function
Plasma calcium (Ca) regulation
a. Parathyroid hormone (PTH): secreted in response to
low serum Ca; induces osteoclasts to reabsorb bone and
increases plasma Ca; induces kidneys to increase conversion
of 25-(OH) vitamin D to 1,25-(OH)2 vitamin D, decreases
phosphate reabsorption, and increases distal tubule Ca
reabsorption for net increase in plasma Ca
b. 1,25-(OH)2 vitamin D: metabolite of dietary vitamin D;
production in kidneys increases with PTH secretion; increases
intestinal Ca21 absorption; increases renal proximal tubule
phosphate reabsorption (in opposition to PTH-induced
phosphate wasting)
c. Calcitonin: secreted by thyroid parafollicular cells; inhibits
bone reabsorption

4. • Nephrotic syndrome hypoalbuminuria total
calcium decrease ionized calcium
normal.albumin decrease 1 unit lead to decrease
calcium by 0.8.
• Hypocalcemia need to adjust albumin!!
• ESRD phosphate cant excrete increase
phosphate level acc by decrease calcium level.
(secondary hyperPTH)

5. Hypercalcemia-etiology
• MCC primary hyperPTH
• Malignancy#2
-PTH like peptide(squamous cell lung/esophagus)
cancer
-Bone metastasis (multiple myeloma,breast cancer)
• Sarcoidosis (activate vit d through the
macrophage/granuloma,esp during summer when
they exposed to sun)RX: prednisone(different from
other etiolgy)

6. Etiology hypercalcemina
• Prolong immobilization (MC seen in geriatic
patient)(hypercalcemia of immobilization)
• Hyperthyroidism(activate osteoclast increase serum
calcium )
• Familial hypocalciuric hypercalcemia(DX:look for
calcium in urine)
• Drugs (HCTZ,lithium)
• Paget disease
• Acidosis(increase free calcium due to albumin buffer
acidosis,increase binding of Hydrogen and albumin
which displace calcium from albumin.)

7. Clinical symptoms
• Acute, symptomatic hypercalcemia presents with
confusion, stupor, lethargy,and constipation.
• Cardiovascular
-Short QT syndrome and hypertension
• Bone lesions
- Osteoporosis
• Renal
- Nephrolithiasis
- Diabetes insipidus
- Renal insufficiency

8. Management of hypercalcemia
• IV fluid normal saline (#1) if develop edema or
fluid overload add furosemide(only used after
hydration are severe case!!)
• Calcitonin
• Biphosphanides(pamidronate)(long acting) keep
calcium low ,it takes 24-48h to start working.

9. • A patient with severe hypercalcemia. First line
treatment IVF.If still hypercalcemia add
calcitonin which will wear off after two days)
biphosphanides (takes 2 days to maximally
working)
• If pt is mild hypercalcemia treat with
biphosphanides.

10. A 75-year-old man with a history of malignancy is
admitted with lethargy, confusion,and abdominal
pain. He is found to have a markedly elevated
calcium level.After 3 liters of normal saline and
pamidronate, his calcium level is still markedly
elevated the following day. What is the most
appropriate next step in management?
a. Calcitonin
b. Zolendronic acid
c. Plicamycin
d. Gallium
e. Dialysis
f. Cinacalcet

11. • Answer: A. Calcitonin inhibits osteoclasts. The onset of
action of calcitonin is very rapid, and it wears off
rapidly. Bisphosphonates take several days to work.
• Plicamycin and gallium are older therapies for
hypercalcemia that no longer have any place in
management. When they are given as choices for
therapy, plicamycin and gallium are always wrong.
• Zolendronic acid is a bisphosphonate and does not
add anything to the use of Pamidronate.
• Cinacalcet is an inhibitor of PTH release. If the
hypercalcemia isfrom malignancy, PTH should already
be maximally suppressed.
• Dialysis would be used only for those in renal failure.

12. Hyperparathyroidism
• 55-year-old woman has hypercalcemia
discovered as an incidental finding during
normal routine physicial examination. A hand
radiograph is shown

13. HyperPTH - Introduction
• Increased parathyroid hormone (PTH) production that
may be of primary, secondary or tertiary causes
Pathophysiology
• PTH indirectly stimulates osteoclasts by binding to its
receptor on osteoblasts, inducing RANK-L and M-CSF
synthesis
Epidemiology
• occurs in 0.1% of the population
• 90% result form a single adenoma
• remaining 10% from parathyroid hyperplasia
• parathyroid carcinoma accounts for less than 1% of
all cases

14. Classification
Primary
• typically the result of hypersecretion of PTH by a parathyroid
adenoma/hyperplasia may result in osteitis fibrosa cystica
breakdown of bone common involves the jaw
Secondary
• secondary parathyroid hyperplasia as compensation from
hypocalcemia or hyperphosphatemia,↓ gut Ca2+ absorption, ↑
phosphorous
associated conditions
1. chronic renal disease
renal disease causes hypovitaminosis leads to ↓ Ca2+
absorption
2. renal osteodystrophy
bone leisons due to secondary hyperparathyroidism
Tertiary
parathyroid glands become dysregulated after secondary
hyperparathyroidism secrete PTH regardless of Ca2+ level

15. Serum Ca Serum Phos Serum PTH
Primary ↑ ↓ ↑
Secondary normal or ↓ ↑ ↑
Tertiary ↑ ↑ ↑

16. Presentation
• often asymptomatic
• hypercalcemia
• weakness
• kidney stones ("stones")
• bone pain ("bones")
• GIT:constipations ("groans")
• uncommon cause of secondary hypertension
• CNS:Mental status change(psychiatric
overtones)

17. slower manifestations such as:
• • Osteoporosis
• • Nephrolithiasis and renal insufficiency
• • Muscle weakness, anorexia, nausea, vomiting,
and abdominal pain
• • Peptic ulcer disease (calcium stimulates
gastrin)

18. Evaluation
Serology
• primary hypercalcemia, ↑ PTH
• secondary hypocalcemia/normocalcemia , ↑ PTH
• malignancy ↓ PTH
• ↑ alkaline phosphatase
• normal anion gap metabolic acidosis
• ↓ renal reclamation of bicarbonate
Urinalysis
• primary hypercalciuria (renal stones), ↑ cAMP
Radiograph
• cystic bone spaces ("salt and pepper"),often in the skull
• loss of phalange bone mass, ↑ concavity (see key image
of this topic)
EKG
• shortened QT

19. • Bone x-ray is not a good test for bone effects of
high PTH. DEXA densitometry is better.
• Preoperative imaging of the neck with
sonography or nuclear scanning may be helpful
in determining the surgical approach.

20. Treatment
• Surgical removal of the involved parathyroid
glands is the standard of care.
• When surgery is not possible, give cinacalcet
• Acute hypercalcemia IV fluids,Loop diuretics
• Symptomatic hypercalcemia is treated surgically
treat with parathyroidectoy
• complications include post-op hypocalcemia
manifests as numbness, tingling, and muscle cramps
should be treated with IV calcium gluconate

21. In primary hyperPTH,surgery is
indicated if any of the following are
present:
• Symptomatic hypercalcemia
• Calcium>11.5
• Renal insufficiency
• Age<50
• Nephrolithiasis
• Osteoporosis

23. A 45-year-old male undergoes a parathyroidectomy
following the passage of two renal stones in a 12-
month period. A single parathyroid adenoma is
removed. Two days following surgery, the patient
reports numbness and tingling around his mouth and
lips and muscle cramps. What is the most appropriate
next step in the management of this patient?
1. IV calcium gluconate
2. Vitamin D supplementation
3. IV potassium phosphate
4. Surgical neck re-exploration
5. Observation

24. • PREFERRED RESPONSE ▼ 1
• This patient's presentation is consistent with postoperative
hypocalcemia. Treatment with IV calcium gluconate is
appropriate.
• Postoperative hypocalcemia is common following successful
parathyroidectomy. If hypocalcemia is asymptomatic, no
treatment is necessary. Symptoms of hypocalcemia generally
appear 2 to 4 days following surgery and are initially treated with
IV calcium gluconate, or, if symptoms are mild, oral calcium such
as calcium lactate, calcium carbonate, or calcium gluconate. For
symptoms that occur earlier than two days or are asymmetric,
one should be suspicious of other causes.
• French et al. describe the clinical manifestations of hypocalcemia.
“Clinical manifestations of hypocalcemia correlate with both the
magnitude and acuity of fall in serum levels. In general,
symptoms occur at an ionized calcium concentration of 2.8
mg/dL (0.7 mmol/L) and include circumoral paresthesias,
muscle cramps, muscle weakness, myalgias, dysphagia,
irritability, depression, and confusion.”

25. • Incorrect answers:
• Answer 2: Vitamin D supplementation is indicated
in cases where symptoms persist despite IV calcium
gluconate therapy.
• Answer 3: Potassium phosphate is used to treat
hypophosphatemia.
• Answer 4: Surgical neck re-exploration is not
indicated in this patient.
• Answer 5: Observation is indicated in asymptomatic
hypocalcemia. It would not be appropriate in this
situation.

26. A 62-year-old female presents to general medical
clinic for health maintenance. She is due for a
colonoscopy but before she schedules it, she would
like to have a full exam. She has no complaints and no
significant past medical history. She has been in good
health for most of her life. Vital signs are stable. Her
physical examination is benign. Routine labs reveal a
calcium of 11.2 mg/dL. What is the next step in
management? Topic Review Topic
1. Order PTH
2. Order PTH related peptide
3. Reorder serum calcium
4. Order ACE
5. Order a chest radiograph

27. • PREFERRED RESPONSE ▼ 3
• In a patient with asymptomatic hypercalcemia the first test should
be to confirm hypercalcemia with a second serum calcium. If this
test returns positive, then a PTH level is the next step in
management. If the hypercalcemia were severe or there were
symptoms in this patient the management would be: 1. IV fluids, 2.
Loop diuretics (furosemide) 3. Calcitonin then 4. Bisphosphonates
(long term management). Often times only IV fluids and a loop
diuretic are needed.
• The clinical features of hypercalcemia include the classic stones
(kidney stones), bones (aches and pains), groans (constipation), and
psychiatric overtones (depression and mood liability). However, this
patient presents without these clinical features, and thus a
reasonable next step would be to confirm the hypercalcemia. Recall
the various causes of hypercalcemia. The broad differential includes
endocrinopathies, malignancies, and pharmacologic causes.
Endocrinopathies include hyperparathyroidism. Malignancies
include any metastatic cancers to the bone, multiple myeloma, and
PTH-like peptide producing cancers such as squamous cell lung
cancer. Pharmacologic causes include Vitamin D, milk-alkali
syndrome, and certain medications such as thiazides, and lithium.
Other less common causes are sarcoidosis and familial
hypocalciuric hypercalcemia.

28. • Incorrect Answers:
• Answer 1: Ordering a parathyroid level would be
reasonable in a patient who presents with
hypercalcemia and the cardinal clinical features.
• Answers 2 and 5: These choices are reasonable in
the workup where hypercalcemia of malignancy is
expected.
• Answer 4: An ACE would be a reasonable step in a
patient with hypercalcemia and some features of
sarcoidosis. Since the ACE is a very sensitive but not
highly specific test for sarcoidosis, other workup
would also be indicated including chest radiograph.

30. Hypocalcemia-etiology
1. Acquired (surgical removal #1)
2. vitamin D deficiency
-renal failure
-intestinal malabsorption(crohn disease,celiac
sprue,pancreatitis)
-not enough sunlight
3.) Hypomagnesium-Magnesium is necessary for
PTH to be released from the gland. Low magnesium
levels also lead to increased urinary loss of calcium.
4.)Hyperphosphatemia
5.)Drug: loop diuretics ,alendronate ,phenytoin ,
foscarnet

31. Other Causes
• Other causes include genetic disorders, fat
malabsorption, and low albumin states. For
every point decrease in albumin, the calcium
level decreases by 0.8.
• Low albumin causes a decrease in total
calcium,but the free calcium level is normal;
hence, no symptoms.

32. Presentation
Signs of neural hyperexcitability in hypocalcemia:
• Chvostek sign (facial nerve hyperexcitability)
• Carpopedal spasm
• Perioral numbness
• Mental irritability
• Seizures
• Tetany (Trousseau sign)

33. Diagnostic Tests
• EKG shows a prolonged QT that may eventually
cause arrhythmia.
• Slit lamp exam shows early cataracts.

34. Treatment
• Replace calcium and vitamin D. This is done
orally if symptoms are mild or absent and
intravenously if symptoms are severe.
• Acute stage of hypocalcemia: calcium gluconate
IV.
• Maintenance therapy: oral calcium 2-4g per
day,vitamin D.
• For ESRD:hyperphosphatemia -diet restriction
and phosphate binders(CaCO3/Al3OH2)

35. Hypoparathyroidism
• A 33-year-old woman with a total thyroidectomy
for papillary carcinoma of the thyroid, is noted
to have carpal spasm when her blood pressure is
taken and facial muscle contractions with
tapping over the facial nerve.

36. Serum Ca Serum Phos PTH Common Cause
Hyperparathyroidism ↑ ↓ ↑ adenoma
Hypoparathyroidism ↓ ↑ ↓ parathyroidectomy
Ectopic PTH ↑ ↓ ↓ malignancy
Vit D malabsorption ↓ ↓ ↑
celiac disease, other GI
isease
hypo vit D with no
phosphate excretion
from the kidney.
↓ ↑ ↑
renal failure, pseudo
hypoparathyroidism

37. • A 56-year-old woman is in the ER after a seizure.
Although suffering from some continued confusion, she
keeps pointing at the area around her mouth and saying
that it feels "funny." Her husband states that she has a
history of osteoarthritis and thyroid cancer, for which she
underwent a total thyroidectomy one month ago. As far as
he knows, she has no family history of epilepsy. Her exam
is notable for 3+ reflexes in her upper and lower
extremities. After applying a blood pressure cuff to her
arm for 3 minutes, her hand looks like Figure A. Which
laboratory abnormality is her blood work most likely to
reveal?
• 1. Low phosphorous
• 2. Low ionized calcium
• 3. Low magnesium
• 4. High 25-hydroxyvitamin D
• 5. High PTH

38. • PREFERRED RESPONSE ▼ 2
• A post-thyroidectomy patient presenting with seizure, circumoral
paresthesias, hyperreflexia, and carpopedal spasm (Trousseau's sign)
most likely has hypoparathyroidism, which causes low ionized
calcium.
• Hypoparathyroidism is a rarer endocrine disorder than
hyperparathyroidism. It most commonly occurs after thyroid,
parathyroid, or other neck surgery. Other causes include autoimmune
disease (specifically, autoimmune polyendocrine syndrome type 1),
radiation neck therapy, genetic syndromes (including DiGeorge
syndrome), mitochondrial disorders, and infiltrative disorders (e.g.,
Wilson's disease, hemochromatosis). Post-thyroid surgery, transient
hypoparathyroidism occurs in 7-46% of patients while the condition
is permanent in closer to 1%.
• abnormal calcium levels are the most common presentation. Aside
from re-measuring the calcium level, other important levels include:
intact parathyroid hormone levels, albumin, creatinine, magnesium,
and calcitriol. Management of hypoparathyroidism includes calcium
gluconate, calcitriol supplementation, and close monitoring.

40. • Figure A depicts a positive Trousseau's sign, which
is found in hypocalcemia after applying a blood
pressure cuff to the arm for at least 3 minutes. The
absence of blood flow combined with low calcium
induces spasm of the hand and forearm.
• Illustration A shows the anatomy of the parathyroid
glands in relation to the thyroid gland, illuminating
why hypoparathyroidism is often a result of thyroid
surgery.
• Illustration B shows the normal role of PTH in
calcium regulation in the body.

41. • Incorrect answers:
• Answer 1: Phosphorous levels are high in
hypoparathyroidism.
• Answer 3: Magnesium levels are normal in
hypoparathyroidism.
• Answer 4: 25-hyroxyvitamin D levels are normal in
hypoparathyroidism. Notably, 1,25
dihydroxyvitamin D (calcitriol) levels are usually low
in hypoparathyroidism, since PTH simulates
conversion of 25-hyroxyvitamin D to 1,25
dihydroxyvitamin D.
• Answer 5: PTH levels are low in
hypoparathyroidism.

42. Pseudohypoparathyroidism
• Rare genetic disorder
Mechanism
• PTH resistance
• decreased target cell response to PTH

43. Classification
• Type 1a - Albright hereditary osteodystrophy
• defect in GNAS1 (Gsα protein)
• defective gene from mother
• upstream defect
• proximal to formation of cAMP
• skeletal defects
• short 4th, and 5th metacarpals and metatarsals or short 4th metacarpal only
• "knuckle, knuckle, dimple, dimple" sign on closed fist
• differentials
• Turner syndrome
• short 4th metacarpal only
• "knuckle, knuckle, dimple, knuckle"
• Down syndrome
• short middle phalanx
• brachydactyly
• exostoses
• round facies
• obesity
• short stature
• diminished intelligence
•

44. • Type 1b
• defect in GNAS1 (Gsα protein)
• normal appearance
• Type 2
• unknown gene defect
• downstream defect
• distal to formation of cAMP
• normal appearance

45. Symptom
• symptoms of hypocalcemia
• paresthesia
• fingertip, toes, perioral
• abdominal pain, biliary colic
• muscle cramps, tetany
• dyspnea (laryngospasm, bronchospasm)
• convulsions
• mental status changes
• anxiety, fatigue, mood swings

46. Laboratory
• high PTH
• low calcium
• high phosphate
• low vit D
• Ellsworth-Howard test
• method to differentiate type 1 and type 2 by
administering exogenous PTH
• Type 1 will show no increase in urinary cAMP and
phosphate
• Type 2 will show increased excretion of urinary
cAMP and phosphate

47. Pseudohypoparathyroidism
1. Hypocalcemia resulting from tissue
nonresponsiveness to PTH
2. Associated with developmental and skeletal
abnormalities (e.g., Albright hereditary
osteodystrophy)
3. H/P : symptoms of hypocalcemia, short stature,
seizures, poor mental development
in children
4. Labs : decreased Ca21, increased phosphate,
increased PTH; administration of
PTH causes no change in serum or urine Ca21
5. Treatment : Ca and vitamin D supplementation