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: 100General: Caucasian male, intubatedHEENT: 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 soundsLymph 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: 100General: Caucasian male, intubatedHEENT: 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 soundsLymph Node Exam: No lymphadenopathy appreciated.Extremities: No cyanosis, clubbing, or edema.

Clinical history

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

Clinical history

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

Clinical history

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

Clinical history

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

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

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

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

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

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

Why relatively normal compared to corrected total calcium?

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

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

Why relatively normal compared to corrected total calcium?

Metabolic acidosis

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

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

Why relatively normal compared to corrected total calcium?

Metabolic acidosis

Laboratory ValuesNa 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 867pH, arterial 7.29; pCO2, arterial 37; pO2, arterial 103

Radiologic StudiesInitial 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.

Radiologic StudiesInitial 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.

Clinical CourseThe 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 OH-Vitamin 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 OH-Vitamin 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 OH-Vitamin 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 OH-Vitamin 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 OH-Vitamin D 27 pg/mL, 25 OH-Vitamin D 10 ng/mL, TSH 3.62.

Corrected calcium = 11.9-13.3

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: 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

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

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 hyperparathyroidismhave rebound hypercalcemia and PTH in recovery

phase?

Do patients without underlying hyperparathyroidismhave 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-sporadicSecondary Hyperparathyroidism

vitamin D deficiencyrenal or GI calcium lossesparathyroid hormone resistance

Tertiary – Chronic End stage renal diseaseFHH- Familial Hypocalciuric hypocalcemiaMen1Men2AFHPT-JT –Familial hyperparathyroidism jaw tumor syndrome

DDx of Hyperparathyroidism

Primary Hyperparathyroidism-sporadicSecondary Hyperparathyroidism

vitamin D deficiencyrenal or GI calcium lossesparathyroid hormone resistance

Tertiary – Chronic End stage renal diseaseFHH- Familial Hypocalciuric hypocalcemiaMen1Men2AFHPT-JT –Familial hyperparathyroidism jaw tumor syndrome

DDx of Hyperparathyroidism

Primary Hyperparathyroidism-sporadicSecondary Hyperparathyroidism

vitamin D deficiencyrenal or GI calcium lossesparathyroid hormone resistance

Tertiary – Chronic End stage renal diseaseFHH- Familial Hypocalciuric hypercalcemiaMen1Men2AFHPT-JT –Familial hyperparathyroidism jaw tumor syndrome

DDx of Hyperparathyroidism

Primary Hyperparathyroidism-sporadicSecondary Hyperparathyroidism

vitamin D deficiencyrenal or GI calcium lossesparathyroid hormone resistance

Tertiary – Chronic End stage renal diseaseFHH- Familial Hypocalciuric hypercalcemiaMen1Men2AFHPT-JT –Familial hyperparathyroidism jaw tumor syndrome

DDx of Hyperparathyroidism

Primary Hyperparathyroidism-sporadicSecondary Hyperparathyroidism

vitamin D deficiencyrenal or GI calcium lossesparathyroid hormone resistance

Tertiary – Chronic End stage renal diseaseFHH- Familial Hypocalciuric hypercalcemiaMen1Men2AFHPT-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

•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 casesof recurrent HPT (non-renal)Jaskowiak Ann Surg 1996

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 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

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

Discussion Questions

4) What additional endocrine evaluation?

Discussion Questions

4) What additional endocrine evaluation?To rule in MEN 1:

Careful family historyGastrinProlactinInsulin24h U cortisol, ACTHpossible: Menin gene testing

Discussion Questions

4) What additional endocrine evaluation?

To rule in MEN 2A: Careful family history CalcitoninPlasma or 24h urine

metanephrinesRet gene testing