CPC Clinical Discussion Douglas W. Ball, M.D.

1
CPC Clinical DiscussionDouglas W. Ball, M.D.

• Division of Endocrinology and Metabolism
• January 29, 2008

2
Clinical history

• History of Present Illness
• The patient is a 55-year old Caucasian man who
  presented to an outside hospital with a chief
  complaint of abdominal pain and was admitted with
  acute pancreatitis. Abdominal ultrasound on
  admission only showed gallbladder sludge with no
  evidence of cholelithiasis. Serum triglycerides
  were 268.

3
Clinical history

• History of Present Illness
• The patient is a 55-year old Caucasian man who
  presented to an outside hospital with a chief
  complaint of abdominal pain and was admitted with
  acute pancreatitis. Abdominal ultrasound on
  admission only showed gallbladder sludge with no
  evidence of cholelithiasis. Serum triglycerides
  were 268.

4
Clinical history

• Three days later he was transferred to The Johns
  Hopkins Hospital for management of severe
  pancreatitis complicated by systemic inflammatory
  response syndrome, respiratory failure, and acute
  renal failure.

5
Clinical history

• His past medical history is significant for the
  diagnosis of primary hyperparathyroidism, and he
  is status post single-gland parathyroidectomy for
  parathyroid adenoma. He also has a history of
  hypertension, hypertriglyceridemia and
  depression. The patient denies alcohol use.

6
Clinical history

• Family History
• The patient's family history is unremarkable.

7
Clinical history

• Medications
• Wellbutrin, 100 mg q8h

8
Clinical history

• Medications
• Wellbutrin, 100 mg q8h
• No AIDS drugs, diuretics, metronidazole, valproic
  acid, sulindac.. others

9
Clinical history

• Physical Exam
• Weight 143 lbs. Height 69 inches. T 102.2
  BP 110/60 P 100
• General Caucasian male, intubated
• HEENT Sclera anicteric. Extraocular movements
  intact.
• CV Regular rate and rhythm with no murmurs
  appreciated.
• Lungs Clear to auscultation bilaterally. No
  wheezes, rales or rhonchi.
• Abdomen Diffuse tenderness to palpation.
  Hypoactive bowel sounds
• Lymph Node Exam No lymphadenopathy appreciated.
• Extremities No cyanosis, clubbing, or edema.

10
Clinical history

• Physical Exam
• Weight 143 lbs. Height 69 inches. T 102.2
  BP 110/60 P 100
• General Caucasian male, intubated
• HEENT Sclera anicteric. Extraocular movements
  intact.
• CV Regular rate and rhythm with no murmurs
  appreciated.
• Lungs Clear to auscultation bilaterally. No
  wheezes, rales or rhonchi.
• Abdomen Diffuse tenderness to palpation.
  Hypoactive bowel sounds
• Lymph Node Exam No lymphadenopathy appreciated.
• Extremities No cyanosis, clubbing, or edema.

11
Clinical history

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

12
Clinical history

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

13
Clinical history

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

14
Clinical history

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

15
Add 0.8 mg/dl for every 1 g/dl below 4

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

16
Add 0.8 mg/dl for every 1 g/dl below 4
Corrected calcium 7.28

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

17
Add 0.8 mg/dl for every 1 g/dl below 4
Corrected calcium 7.28

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

Why relatively normal compared to corrected total
calcium?
18
Add 0.8 mg/dl for every 1 g/dl below 4
Corrected calcium 7.28

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

Metabolic acidosis
Why relatively normal compared to corrected total
calcium?
19
Add 0.8 mg/dl for every 1 g/dl below 4
Corrected calcium 7.28

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

Metabolic acidosis
Why relatively normal compared to corrected total
calcium?
20

• Laboratory Values
• Na 145 K 3.8 Cl 119 BUN 87 Glucose 167
  Cre 5.7 Ca 6.6 Tot protein 4.0 Albumin 2.4
  TBili 0.6 ALT 78 AST 102 Alk Phos 45 CO2 16
• WBC 13740Hct 34.4 Plt 128,000 PT 10.4
• Ionized calcium 1.09 Lipase 250 Amylase 867
• pH, arterial 7.29 pCO2, arterial 37 pO2,
  arterial 103

21

• Radiologic Studies
• Initial CT studies noted bilateral pleural
  effusions with associated compressive atelectasis
  and/or infiltrates. Marked edema and stranding
  were seen in the pancreatic bed, compatible with
  fulminant pancreatitis. Several indeterminate
  adrenal nodules were present bilaterally, and a
  stable, non-obstructing 1.5 cm stone was
  identified in the left kidney.

22

• Radiologic Studies
• Initial CT studies noted bilateral pleural
  effusions with associated compressive atelectasis
  and/or infiltrates. Marked edema and stranding
  were seen in the pancreatic bed, compatible with
  fulminant pancreatitis. Several indeterminate
  adrenal nodules were present bilaterally, and a
  stable, non-obstructing 1.5 cm stone was
  identified in the left kidney.

23

• Clinical Course
• The patient was in respiratory failure and acute
  renal failure when he arrived and was admitted to
  the MICU. Imaging and laboratory tests were
  consistent with acute pancreatitis. He
  demonstrated a period of initial improvement and
  was eventually extubated, but two weeks after
  admission developed a high fever and acute
  respiratory decompensation. Repeat CT imaging
  revealed a pulmonary embolus in his main right
  pulmonary artery and pancreatic necrosis.
  Cultures of peripancreatic fluid grew Candida
  albicans, and the patient underwent three
  operations for pancreatic debridement. A
  cholecystectomy, gastojejunostomy tube placement,
  and inferior vena cava filter placement were also
  performed. Additional complications during his
  admission included Pseudomonas aeruginosa-positive
  sputum cultures and critical illness
  neuropathy/myopathy.

24

• an endocrine consultation was obtained for
  hypercalcemia. Review of calcium levels revealed
  hypocalcemia in 6.6- 6.8 mg/dL range on
  presentation to JHH. However, as patients
  condition improved, calcium elevation in
  10.7-12.1 mg/dL was noted persistently. Serum
  albumin during that time ranged between 1.8 and
  2.5 g/dl. An initial biochemical evaluation
  included PTH of 255 pg/mL concurrently with
  calcium of 10.2 mg/dL, PTHrp of lt2.5 pmol/L,
  Phosphorus 2.7 mg/dL, 1,25 OH-Vitamin D 27 pg/mL,
  25 OH-Vitamin D 10 ng/mL, TSH 3.62.

25

• an endocrine consultation was obtained for
  hypercalcemia. Review of calcium levels revealed
  hypocalcemia in 6.6- 6.8 mg/dL range on
  presentation to JHH. However, as patients
  condition improved, calcium elevation in
  10.7-12.1 mg/dL was noted persistently. Serum
  albumin during that time ranged between 1.8 and
  2.5 g/dl. An initial biochemical evaluation
  included PTH of 255 pg/mL concurrently with
  calcium of 10.2 mg/dL, PTHrp of lt2.5 pmol/L,
  Phosphorus 2.7 mg/dL, 1,25 OH-Vitamin D 27 pg/mL,
  25 OH-Vitamin D 10 ng/mL, TSH 3.62.

26
Corrected calcium 11.9-13.3

• an endocrine consultation was obtained for
  hypercalcemia. Review of calcium levels revealed
  hypocalcemia in 6.6- 6.8 mg/dL range on
  presentation to JHH. However, as patients
  condition improved, calcium elevation in
  10.7-12.1 mg/dL was noted persistently. Serum
  albumin during that time ranged between 1.8 and
  2.5 g/dl. An initial biochemical evaluation
  included PTH of 255 pg/mL concurrently with
  calcium of 10.2 mg/dL, PTHrp of lt2.5 pmol/L,
  Phosphorus 2.7 mg/dL, 1,25 OH-Vitamin D 27 pg/mL,
  25 OH-Vitamin D 10 ng/mL, TSH 3.62.

27
Corrected calcium 11.9-13.3

• an endocrine consultation was obtained for
  hypercalcemia. Review of calcium levels revealed
  hypocalcemia in 6.6- 6.8 mg/dL range on
  presentation to JHH. However, as patients
  condition improved, calcium elevation in
  10.7-12.1 mg/dL was noted persistently. Serum
  albumin during that time ranged between 1.8 and
  2.5 g/dl. An initial biochemical evaluation
  included PTH of 255 pg/mL concurrently with
  calcium of 10.2 mg/dL, PTHrp of lt2.5 pmol/L,
  Phosphorus 2.7 mg/dL, 1,25 OH-Vitamin D 27 pg/mL,
  25 OH-Vitamin D 10 ng/mL, TSH 3.62.

28
Corrected calcium 11.9-13.3

• an endocrine consultation was obtained for
  hypercalcemia. Review of calcium levels revealed
  hypocalcemia in 6.6- 6.8 mg/dL range on
  presentation to JHH. However, as patients
  condition improved, calcium elevation in
  10.7-12.1 mg/dL was noted persistently. Serum
  albumin during that time ranged between 1.8 and
  2.5 g/dl. An initial biochemical evaluation
  included PTH of 255 pg/mL concurrently with
  calcium of 10.2 mg/dL, PTHrp of lt2.5 pmol/L,
  Phosphorus 2.7 mg/dL, 1,25 OH-Vitamin D 27 pg/mL,
  25 OH-Vitamin D 10 ng/mL, TSH 3.62.

29

• While in rehabilitation, he experienced a
  gastrointestinal bleed, and was admitted to an
  outside hospital. Endoscopy revealed ulceration
  in the duodenum and at the gastroesophageal
  junction

30

• He was re-admitted to The Johns Hopkins Hospital
  for further management. At admission he was
  hemodynamically stable and afebrile, but
  presented with elevated white blood cell count,
  liver enzymes, alkaline phosphatase and amylase.
  He was treated with antibiotics and with
  discussion of further surgical intervention.
  Three days after admission, the patient was found
  in cardiopulmonary arrest and resuscitation
  attempts were unsuccessful.

31
Discussion Questions

• Could hypercalcemia explain his acute
  pancreatitis?

32
Discussion Questions

• 1) Could hypercalcemia explain his acute
  pancreatitis?
• Yes

33
Etiologies of Acute Pancreatitis

• Mechanical Gallstones, biliary sludge (?),
  pancreatic cancer, others
• Toxic Ethanol, others
• Metabolic Hyperlipidemia, hypercalcemia
• Drugs AIDS drugs, salicylates, metronidazole,
  diuretics, calcium, others
• Trauma Injury, surgery, ERCP
• Vascular Ischemia, embolic, vasculitis
• Genetic CFTR, others

34
Etiologies of Acute Pancreatitis

• Mechanical Gallstones, biliary sludge (?),
  pancreatic cancer, others
• Toxic Ethanol, others
• Metabolic Hyperlipidemia, hypercalcemia
• Drugs AIDS drugs, salicylates, metronidazole,
  diuretics, calcium, others
• Trauma Injury, surgery, ERCP
• Vascular Ischemia, embolic, vasculitis
• Genetic CFTR, others

35
Did the patient have hypercalcemia prior to
developing acute pancreatitis?
36
Did the patient have hypercalcemia prior to
developing acute pancreatitis?

• Probably

37
Did the patient have hypercalcemia prior to
developing acute pancreatitis?

• Probably
• 1) Prior history of hyperpara
• 2) Nephrolithiasis
• 3) Hypocalcemia during acute pancreatitis with
  rebound hypercalcemia

38
Do patients without underlying hyperparathyroidism
have rebound hypercalcemia and PTH in recovery
phase?
39
Do patients without underlying hyperparathyroidism
have rebound hypercalcemia and PTH in recovery
phase?

• No, apparently not
• Low ionized calcium common during acute
  pancreatitis
• PTH responses variable, but seldom above normal
• No evidence for rebound hypercalcemia in 41
  patients followed prospectively McKay Br J Surg
  1994

40
Hypercalcemia and acute pancreatitis

• Hypercalcemia a rare cause of pancreatitis
• Hyperparathyroidism accounts for fewer than 1
  of cases of pancreatitis
• Mechanism Calcium deposition in pancreatic ducts
• Calcium activation of trypsinogen
• Animal Models Hypercalcemia -gt amylase
  elevations

41
Discussion Questions

• 2) What is the most likely cause of his initial
  hypocalcemia?

42
Discussion Questions

• 2) What is the most likely cause of his initial
  hypocalcemia?
• Acute pancreatitis causes Ca FFA soaps

43
Discussion Questions

• 2) What is the most likely cause of his initial
  hypocalcemia?
• Acute pancreatitis causes Ca FFA soaps
• Acute renal failure inhibits PTH secretion and
  action

44
Discussion Questions

• 2) What is the most likely cause of his initial
  hypocalcemia?
• Acute pancreatitis causes Ca FFA soaps
• Acute renal failure inhibits PTH secretion and
  action
• low magnesium
• elevated phosphate impairs renal 1 alpha
  hydroxylase, associated with low 1,25 vitamin D

45
Discussion Questions

• 3) What is the most likely cause of his
  hyperparathyroidism and what additional studies
  would help determine the most likely cause?

46
DDx of Hypercalcemia

• Hyperparathyroidism
• Hypercalcemia of malignancy
• Drugs Thiazide diuretics, lithium others Vitamin
  D intoxication
• Lymphoma
• Adrenal insufficency, pheochromocytoma

47
DDx of Hyperparathyroidism

• Primary Hyperparathyroidism-sporadic
• Secondary Hyperparathyroidism
• vitamin D deficiency
• renal or GI calcium losses
• parathyroid hormone resistance
• Tertiary Chronic End stage renal disease
• FHH- Familial Hypocalciuric hypocalcemia
• Men1
• Men2A
• FHPT-JT Familial hyperparathyroidism jaw tumor
  syndrome

48
DDx of Hyperparathyroidism

• Primary Hyperparathyroidism-sporadic
• Secondary Hyperparathyroidism
• vitamin D deficiency
• renal or GI calcium losses
• parathyroid hormone resistance
• Tertiary Chronic End stage renal disease
• FHH- Familial Hypocalciuric hypocalcemia
• Men1
• Men2A
• FHPT-JT Familial hyperparathyroidism jaw tumor
  syndrome

49
DDx of Hyperparathyroidism

• Primary Hyperparathyroidism-sporadic
• Secondary Hyperparathyroidism
• vitamin D deficiency
• renal or GI calcium losses
• parathyroid hormone resistance
• Tertiary Chronic End stage renal disease
• FHH- Familial Hypocalciuric hypercalcemia
• Men1
• Men2A
• FHPT-JT Familial hyperparathyroidism jaw tumor
  syndrome

50
DDx of Hyperparathyroidism

• Primary Hyperparathyroidism-sporadic
• Secondary Hyperparathyroidism
• vitamin D deficiency
• renal or GI calcium losses
• parathyroid hormone resistance
• Tertiary Chronic End stage renal disease
• FHH- Familial Hypocalciuric hypercalcemia
• Men1
• Men2A
• FHPT-JT Familial hyperparathyroidism jaw tumor
  syndrome

51
DDx of Hyperparathyroidism

• Primary Hyperparathyroidism-sporadic
• Secondary Hyperparathyroidism
• vitamin D deficiency
• renal or GI calcium losses
• parathyroid hormone resistance
• Tertiary Chronic End stage renal disease
• FHH- Familial Hypocalciuric hypercalcemia
• Men1
• Men2A
• FHPT-JT Familial hyperparathyroidism jaw tumor
  syndrome

52
Focused DDx in this case

• Primary Hyperparathyroidism-sporadic
• Men1
• Men2A

53
Sporadic Hyperparathyroidism

• Most common cause of hypercalcemia
• Can be mild (adenoma) or severe (carcinoma)
• Recurrent/persistent hyperpara in 5-10 (Fewer
  currently)
• 77 of surgical failures due to missed single
  gland Jaskowiak Ann Surg 1996

54
Known complications of hyperparathyroidism

• Peptic ulcer disease
• Neuropsychiatric symptoms
• Pancreatitis
• Bone disease
• Nephrolithiasis

55
Known complications of hyperparathyroidism

• Peptic ulcer disease ?
• Neuropsychiatric symptoms ?
• Pancreatitis ?
• Bone disease
• Nephrolithiasis ?

56

• MEN1
• Clinical Manifestations
• 3 Ps Parathyroid, pancreas, pituitary
• Cardinal lesion parathyroid adenomas
• gt90 have hyperpara by age 50
• Frequently multiple and recurrent
• GI tumors (50)
• gastrinoma (40)associated with severe peptic
  ulcers
• carcinoid (10), insulinoma (10),
• glucagon , VIP, somatostatin, non-secretory
• Pituitary tumors (30)
• prolactinoma (20), non-secretory, GH (5),
  ACTH (2)

57

• MEN1
• Clinical Manifestations
• 3 Ps Parathyroid, pancreas, pituitary
• Cardinal lesion parathyroid adenomas ?
• gt90 have hyperpara by age 50
• Frequently multiple and recurrent ?
• GI tumors (50)
• gastrinoma (40)associated with severe peptic
  ulcers ??
• carcinoid (10), insulinoma (10),
• glucagon , VIP, somatostatin, non-secretory
• Pituitary tumors (30)
• prolactinoma (20), non-secretory, GH (5),
  ACTH (2)

58

• MEN1
• Clinical Manifestations
• 3 Ps Parathyroid, pancreas, pituitary
• Cardinal lesion parathyroid adenomas ?
• gt90 have hyperpara by age 50
• Frequently multiple and recurrent ?
• GI tumors (50)
• gastrinoma (40)associated with severe peptic
  ulcers ??
• carcinoid (10), insulinoma (10),
• glucagon , VIP, somatostatin, non-secretory
• Pituitary tumors (30)
• prolactinoma (20), non-secretory, GH (5),
  ACTH (2)

Account for 10 of cases of recurrent HPT
(non-renal) Jaskowiak Ann Surg 1996
59

• MEN1
• Additional tumors
• Adrenocortical adenomas (25) ?
• Thyroid follicular adenomas (15)
• Lipomas (30)
• Angiofibromas
• Thymic carcinoids (2)
• Bronchial carcinoid (2)

60

• MEN2A
• Clinical manifestations
• Medullary thyroid cancer (gt80)
• Pheochromocytoma (50)
• Hyperparathyroidism (15)
• Less likely to be recurrent than in MEN1

61

• Sporadic HPTH
• Pros
• Common
• Can account for pancreatitis, kidney stones
• Cons
• Cant account for adrenal adenomas

62

• Men 1
• Pros
• Can account for recurrent hyperpara, kidney
  stones, pancreatitis, peptic ulcer dz, adrenal
  adenomas
• Cons
• Rare
• Negative family history

63

• Men 2A
• Pros
• Can account for hyperpara, kidney stones,
  pancreatitis
• Could the adrenal adenomas be mis-diagnosed
  bilateral pheochromocytomas?
• Patient had pre-existing hypertension and died
  sudden cardiac death
• Cons
• No history to suggest thyroid tumor
• No mention of in-patient hypertension
• Negative family history

64

• Men 2A
• Pros
• Can account for hyperpara, kidney stones,
  pancreatitis
• Could the adrenal adenomas be mis-diagnosed
  bilateral pheochromocytomas?
• Patient had pre-existing hypertension and died
  sudden cardiac death
• Cons
• No history to suggest thyroid tumor
• No mention of in-patient hypertension
• Negative family history

65
Discussion Questions

• 4) What additional endocrine evaluation?

66
Discussion Questions

• 4) What additional endocrine evaluation?
• To rule in MEN 1
• Careful family history
• Gastrin
• Prolactin
• Insulin
• 24h U cortisol, ACTH
• possible Menin gene testing

67
Discussion Questions

• 4) What additional endocrine evaluation?
• To rule in MEN 2A
• Careful family history Calcitonin
• Plasma or 24h urine metanephrines
• Ret gene testing