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

CPC
Clinical Discussion
Douglas W. Ball, M.D.
Division of Endocrinology and
Metabolism
January 29, 2008
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.
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.
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.
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.
Clinical history
Family History
The patient's family history is unremarkable.
Clinical history
Medications
Wellbutrin, 100 mg q8h
Clinical history
Medications
Wellbutrin, 100 mg q8h
No AIDS drugs, diuretics, metronidazole,
valproic acid, sulindac….. others
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.
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.
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 13740;Hct 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
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 13740;Hct 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
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 13740;Hct 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
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 13740;Hct 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
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 13740;Hct 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
Corrected calcium = 7.28
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 13740;Hct 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
Corrected calcium = 7.28
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 13740;Hct 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?
Corrected calcium = 7.28
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 13740;Hct 34.4 Plt 128,000; PT 10.4 Metabolic acidosis
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?
Corrected calcium = 7.28
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 13740;Hct 34.4 Plt 128,000; PT 10.4 Metabolic acidosis
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?
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 13740;Hct 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
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, nonobstructing 1.5 cm stone was identified in the
left kidney.
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, nonobstructing 1.5 cm stone was identified in the
left kidney.
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.
…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 patient’s 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
<2.5 pmol/L, Phosphorus 2.7 mg/dL, 1,25 OHVitamin D 27 pg/mL, 25 OH-Vitamin D 10 ng/mL,
TSH 3.62.
…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 patient’s 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
<2.5 pmol/L, Phosphorus 2.7 mg/dL, 1,25 OHVitamin D 27 pg/mL, 25 OH-Vitamin D 10 ng/mL,
TSH 3.62.
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 patient’s 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
<2.5 pmol/L, Phosphorus 2.7 mg/dL, 1,25 OHVitamin D 27 pg/mL, 25 OH-Vitamin D 10 ng/mL,
TSH 3.62.
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 patient’s 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
<2.5 pmol/L, Phosphorus 2.7 mg/dL, 1,25 OHVitamin D 27 pg/mL, 25 OH-Vitamin D 10 ng/mL,
TSH 3.62.
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 patient’s 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
<2.5 pmol/L, Phosphorus 2.7 mg/dL, 1,25 OHVitamin D 27 pg/mL, 25 OH-Vitamin D 10 ng/mL,
TSH 3.62.
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
…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.
Discussion Questions
1) Could hypercalcemia explain his
acute pancreatitis?
Discussion Questions
1) Could hypercalcemia explain his
acute pancreatitis?
Yes
Etiologies of Acute Pancreatitis
Mechanical:
Toxic:
Metabolic:
Drugs:
Trauma:
Vascular:
Genetic:
Gallstones, biliary sludge (?), pancreatic cancer, others
Ethanol, others
Hyperlipidemia, hypercalcemia
AIDS drugs, salicylates, metronidazole, diuretics,
calcium, others
Injury, surgery, ERCP
Ischemia, embolic, vasculitis
CFTR, others
Etiologies of Acute Pancreatitis
Mechanical:
Toxic:
Metabolic:
Drugs:
Trauma:
Vascular:
Genetic:
Gallstones, biliary sludge (?), pancreatic cancer, others
Ethanol, others
Hyperlipidemia, hypercalcemia
AIDS drugs, salicylates, metronidazole, diuretics,
calcium, others
Injury, surgery, ERCP
Ischemia, embolic, vasculitis
CFTR, others
Did the patient have hypercalcemia prior
to developing acute pancreatitis?
Did the patient have hypercalcemia prior
to developing acute pancreatitis?
Probably
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
Do patients without underlying hyperparathyroidism
have rebound hypercalcemia and PTH in recovery
phase?
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
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 -> amylase elevations
Discussion Questions
2) What is the most likely cause of his
initial hypocalcemia?
Discussion Questions
2) What is the most likely cause of his
initial hypocalcemia?
Acute pancreatitis causes Ca FFA soaps
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
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
Discussion Questions
3) What is the most likely cause of his
hyperparathyroidism and what additional studies
would help determine the most likely cause?
DDx of Hypercalcemia
Hyperparathyroidism
Hypercalcemia of malignancy
Drugs:
Thiazide diuretics, lithium others
Vitamin D intoxication
Lymphoma
Adrenal insufficency, pheochromocytoma
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
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
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
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
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
Focused DDx in this case
Primary Hyperparathyroidism-sporadic
Men1
Men2A
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
Known complications of hyperparathyroidism
Peptic ulcer disease
Neuropsychiatric symptoms
Pancreatitis
Bone disease
Nephrolithiasis
Known complications of hyperparathyroidism
Peptic ulcer disease ◄
Neuropsychiatric symptoms ◄
Pancreatitis ◄
Bone disease
Nephrolithiasis ◄
MEN1
Clinical Manifestations
3 P’s: Parathyroid, pancreas, pituitary
Cardinal lesion: parathyroid adenomas
>90% 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%)
MEN1
Clinical Manifestations
3 P’s: Parathyroid, pancreas, pituitary
Cardinal lesion: parathyroid adenomas ◄
>90% 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%)
MEN1
Clinical Manifestations
3 P’s: Parathyroid, pancreas, pituitary
Cardinal lesion: parathyroid adenomas ◄
>90% have hyperpara by age 50
Account for ~10% of cases
recurrent HPT (non-renal)
Frequently multiple and recurrent ◄ ofJaskowiak
Ann Surg 1996
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%)
MEN1:
Additional tumors
Adrenocortical adenomas (25%) ◄
Thyroid follicular adenomas (15%)
Lipomas (30%)
Angiofibromas
Thymic carcinoids (2%)
Bronchial carcinoid (2%)
MEN2A:
Clinical manifestations
Medullary thyroid cancer (>80%)
Pheochromocytoma (50%)
Hyperparathyroidism (15%)
Less likely to be recurrent than in MEN1
Sporadic HPTH
Pros
Common
Can account for pancreatitis, kidney
stones
Cons
Can’t account for adrenal adenomas
Men 1
Pros
Can account for recurrent hyperpara,
kidney stones, pancreatitis, peptic ulcer
dz, adrenal adenomas
Cons
Rare
Negative family history
Men 2A
Pros
Can account for hyperpara, kidney
stones, pancreatitis
Could the adrenal adenomas be misdiagnosed 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
Men 2A
Pros
Can account for hyperpara, kidney
stones, pancreatitis
Could the adrenal adenomas be misdiagnosed 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
Discussion Questions
4) What additional endocrine
evaluation?
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
Discussion Questions
4) What additional endocrine
evaluation?
To rule in MEN 2A:
Careful family history
Calcitonin
Plasma or 24h urine
metanephrines
Ret gene testing