Carcinoid Crisis

Carcinoid Crisis

Definition:

-Carcinoid crisis is the most serious and life-threatening complication of carcinoid syndrome and is generally found in people who already have carcinoid syndrome.

-Carcinoid crisis occurs when all of the symptoms of carcinoid syndrome come at the same time. 

Causes:

➧ Spontaneous 

➧ Precipitating factors: 

-Stress, Sympathetic stimulation 

-Hypotension 

-Histamine releasing drugs 

-Tumour manipulation 

-Regional anesthesia due to hypotension 

-Infection 

-Chemotherapy 

Clinical picture:

-Tachycardia, Arrhythmia 

-Hypotension, Shock 

-Flushing, Hyperthermia 

-Bronchospasm 

-Abdominal pain, Diarrhea 

Management:

Inhibit growth h. & vasoactive peptides release:

-Somatostatin analogs (Octreotide, Lanreotide) 

Anti-serotonin:

-Methesergide, Ketanserin, Cyproheptadine, Ondansetron, Alpha-methyl dopa 

Anti-kallikrein:

-Corticosteroids, Aprotinin

Anti-histamine:

-H1 blockers (Diphenhydramine) & H2 blockers (Ranitidine) 

R of Bronchospasm:

-Salbutamol, Aminophylline 

R of Diarrhea:

-Loperamide 

R of Hypotension:

-Vasopressin, Phenylephrine 

R of Hypertension:

-Alpha-blockers, Beta-blockers 

R of Rt. Heart failure:

-Digitalis, Diuretics

Read More

Acute Hypercalcemia

Most Common Causes:

1-Endocrine:

➧ Hyperparathyroidism

➧ MEN

➧ PTH-related peptide (PTHrP) by solid tumors

2-Neoplastic:

➧ Ca with bone metastases

➧ Myeloma

3-Granulomatous:

➧ Sarcoidosis 

➧ Tuberculosis

Clinical picture:

➧ History of polyuria and polydipsia 

➧ Dehydration

➧ Bone pain

➧ Confusion

➧ Anorexia 

➧ Constipation

ECG Changes: (Figure 1)

Figure 1: ECG changes in Acute Hypercalcemia

Workup:

S – Ca (High) ➔ PTH (High) ➜ Primary Hyperparathyroidism

➔ PTH (Low) ➜ Malignancy or other cause

S – Ca > 3.0 is 90% of the time of malignant origin

Management of Hypercalcemia:

Volume repletion and diuresis:

➧ NaCl 0.9%: 4 L in first 24 h.

➧ Loop diuretics: Furosemide: 40-80 mg/2 h. IV

-Natriuresis promotes calcium excretion.

Bisphosphonates IV: (Pamidronate /Zoledronate)

-Potent inhibitors of bone resorption.

Corticosteroids:

➧ Prednisone: 30-60 mg/d.

➧ Hydrocortisone: 200mg/d. IV

-Impeding growth of lymphoid neoplastic tissue & enhance vit. D actions.

Calcitonin:

-4 units/kg/12 h. IM/SC

-Inhibits bone resorption.

Plicamycin-antineoplastic:

-Inhibits resorption.

Dialysis:

-Patients with renal failure.

Urgent Parathyroidectomy

Read more ☛ Acute Hypocalcemia

Read More

Acute Hypocalcemia

Causes:

1-Hypoparathyroidism

➧ Destruction of parathyroids (most commonly surgical – parathyroid resection or accidental).

➧ Acute hypomagnesemia

2-Reduced 1,25 (OH) vit D

3-Chronic renal insufficiency

➧ Acute systemic illness

➧ Drugs: ketoconazole, doxorubicin, cytarabine

➧ Increased uptake of Ca in bone

➧ Osteoblastic metastases

➧ Hungry bone syndrome

4-Complexing of Ca from the circulation

➧ ↑ albumin binding in alkalosis

➧ Acute pancreatitis with the formation of Ca soaps

➧ Transfusion-related citrate complexing

Clinical Picture:

Symptoms:

➧ Perioral numbness

➧ Tingling paresthesias

➧ Muscle cramps

➧ Carpopedal spasm

➧ Seizures

Signs:

➧ Hyperreflexia

➧ Chvostek's sign: (Figure 1, Figure 2)

(Tap on facial n. anterior to the earlobe or between the zygomatic arch and angle of the mouth → Unilateral spasm of facial muscles)

Figure 1: Chvostek's sign

Figure 2: Chvostek's sign

➧ Trousseau's sign: (Figure 3) 

(Inflate BP cuff 20 mmHg > SBP → Carpopedal spasm)

Figure 3: Trousseau's sign

➧ Hypotension

➧ Bradycardia

➧ Arrhythmias

➧ Prolonged QT interval (Figure 4)

Figure 4: Prolonged QT interval

ECG Changes: (Figure 5)

Figure 5: ECG changes in Acute Hypocalcemia

Biochemical Workup:

➧ S total Ca⁺², Albumin and Ionized Ca⁺² 

➧ S PO4⁺² 

➧ S Mg⁺² 

➧ Plasma PTH

- Low in hypoparathyroidism

- High in hungry bones syndrome

➧ 25 (OH)D3 and 1,25 (OH)D3 

➧ S. Amylase and Lipase

Management of Hypocalcemia:

1- First correct low Mg⁺²

2- Control of Tetany:

➧ Calcium gluconate: 10 ml of 10% solution IV over 5-10 min. and repeat as necessary in cases with frank generalized tetany.

➧ Slower continuous infusion of Calcium in less acute cases:

- 10% calcium chloride, 8 ml or 10% calcium gluconate, 22 ml in 100 ml isotonic saline over 10 min.-then continuous infusions of 1-2 mg/kg/h elemental calcium, lasting 6-12 h.; Oral daily maintenance 2-4 g.

- Vitamin D: 1-3 mg/d. oral.

3- Correction of alkalosis:

➧ Isotonic saline.

➧ Ammonium chloride: 2 g/4 h. oral to stop tetany.

Read more ☛ Acute Hypercalcemia

Read More

Hypoglycemic Coma

Hypoglycemia in Type I DM:

➧ Common in patients intensively controlled with insulin.

➧ Asymptomatic blood glucose levels of < 50 mg/dL occur daily in up to 56% of patients.

➧ Symptomatic hypoglycemia occurs 2X/week on average.

Severe Hypoglycemia:

➧ An episode requires intervention by another person for the patient to recover function.

Causes of Hypoglycemia in Diabetes:

➧ Delayed, reduced, or missed CHO intake.

➧ Increased glucose utilization (exercise).

➧ Decreased insulin clearance (renal failure).

➧ Alcohol -inhibits hepatic gluconeogenesis.

➧ Adrenal insufficiency or glucocorticoid dosage reduction.

Clinical picture:

Adrenergic:

➧ Tremor, anxiety, palpitations, hunger.

Neuroglycopenic:

➧ Dizziness, decreased concentration, blurred vision, tingling, lethargy.

Severe Hypoglycemia in Intensively Controlled Type I DM:

➧ Up to 25% yearly incidence.

➧ Disabling cognitive effects may take hours to fully resolve.

➧ May lead to seizures, and rarely, permanent neurological deficits.

➧ Estimated to be a causative factor in 4% of deaths.

Hypoglycemia Unawareness:

➧ Loss of autonomic warning symptoms of hypoglycemia.

➧ Occurs in 25-50% of patients with type I DM.

➧ Patients are no longer prompted to eat.

➧ Results in a 7X increased frequency of severe hypoglycemia.

Defective Glucose Counter-regulation in Type I DM:

➧ Reduced or absent glucagon response is common after 2-4 years.

➧ Deficient epinephrine response is common after 5-10 years.

➧ Results in a 25X increased frequency of severe hypoglycemia.

Hypoglycemia Unawareness and Defective Glucose Counter-regulation:

➧ Reversible by short-term avoidance of hypoglycemia.

Reduction of Hypoglycemia in Type I DM:

➧ Identify patients at increased risk:

- History of severe hypoglycemia.

- History of hypoglycemia unawareness.

- Normal or near-normal glycohemoglobin levels.

➧ Raise glycemic targets in the short-term to regain symptom recognition.

➧ Education patients and family members to recognize and treat hypoglycemia.

➧ Have unaware patients test blood glucose before performing a critical task (driving).

➧ Patients should have rapid-acting carbohydrates available at all times.

➧ Apply principles of intensive insulin therapy:

- Frequent home glucose monitoring.

- Flexible insulin regimens with dosage adjustments based on meal size, monitored blood glucose levels and anticipated exercise.

➧ Replace insulin more physiologically:

- Multiple insulin injections.

- New ultra-short acting insulin analogs: lispro, aspart, glulisine.

- Long-acting insulin analogs: glargine, detemir.

- Insulin pumps.

Subcutaneous, Continuous Glucose Monitors:

➧ Now available with alarms for high and low glucose readings.

➧ Useful for catching periods of hypoglycemia (especially overnight) of which patients are unaware.

➧ Shown to reduce the incidence of hypoglycemia in type I DM patients with prior severe hypoglycemia.

Management of Hypoglycemic Coma:

-If delayed, can cause permanent neurologic damage.

➧ 50% Dextrose in water: 50 ml IV over 3-5 min. followed by 5% dextrose in a water infusion.

➧ Glucagon: 0.5-1 mg IM/SC.

- Mobilizes hepatic glycogen stores.

➧ Hydrocortisone: for adrenal insufficiency.

➧ Hospitalize: those on sulfonylureas for 24 h.

Read more ☛ Diabetic Ketoacidosis (DKA)

Read More

Diabetic Ketoacidosis (DKA)

Physiology:

Hyperglycemia:

➧ Increased hepatic production of glucose.

➧ Diminished glucose uptake by peripheral tissues.

➧ Insulinopenia / Hyperglucagonemia.

Ketoacidemia:

➧ The ketoacid is acetoacetic acid. The byproduct is acetone. The non-keto- acid is beta-hydroxybutyric acid.

➧ Increased lipolysis and hepatic ketogenesis

➧ Reduced ketolysis by insulin-deficient peripheral tissues.

Fluid and Electrolyte Depletion:

➧ Osmotic diuresis and dehydration due to hyperglycemia.

➧ On average, water deficit is about 5L, sodium 500 mmol, potassium 400 mmol, and chloride 400 mmol.

General Considerations:

➤ Initial presentation of Type I DM (Can also occur in Type II DM).

➤ Increased insulin requirements in Type I DM (Infection, Trauma, Myocardial infarction, Surgery).

➤ Mortality is 5% in patients under 40 y. Up to 20% in elderly.

➤ Estimates of 5-8 episodes per 1000 at-risk diabetics annually.

➤ One of the more common serious complications of insulin pump users – occurs 1 per 80 months of treatment. Typically due to unrecognized pump failure.

➤ Essentials of Diagnosis:

➧ Acidosis with pH < 7.3.

➧ Serum bicarbonate < 15 .mEq/L.

➧ The serum is positive for ketones.

➧ Elevated anion gap (variable, may occur without gap).

➧ Hyperglycemia > 250 mg/dL (no correlation between the severity of hyperglycemia and severity of ketoacidosis).

Clinical picture:

Symptoms:

➧ Early: Polyuria, Polydipsia, Fatigue, N/V.

➧ Late: Stupor – Coma.

Signs:

➧ Rapid, Deep Breathing.

➧ Fruity breath odor of acetone.

➧ Tachycardia, Hypotension, mild Hypothermia.

➧ Abdominal Pain and Tenderness.

Laboratory Findings:

➧ Glycosuria 4+, Ketonuria.

➧ Hyperglycemia, Ketonemia, Low arterial blood pH, and Low plasma bicarbonate.

➧ Elevated serum potassium (despite total body potassium depletion).

➧ Elevated serum amylase (not specific for pancreatitis in this setting, use lipase).

➧ Leukocytosis.

➧ If hyperthermic, likely due to infection since pts with DKA are hypothermic if uninfected.

Management of DKA:

Insulin Replacement:

➧ Regular Insulin IV bolus 0.1-0.2 units/kg to ‘prime’ insulin receptors.

➧ Regular Insulin infusion at 0.1 units/kg/h.

➧ Then replaced with SC regular insulin when hyperglycemia and ketoacidosis are controlled.

➧ Then oral intake + SC intermediate-acting insulin.

Fluid Replacement:

➧ The typical deficit is 4-5 L.

➧ Initially, NS 1 L/h. x 2 h., then 0.5 L/h. x 1-2 h., then 200-300 mL/h. till correction.

➧ Switch to ½ NS if serum Na > 150 mEq/L. 

➧ Add D5W if the glucose falls below 250 mg/dL, to maintain serum glucose 250-300 mg/dL to prevent hypoglycemia and cerebral edema.

Sodium Bicarbonate:

➧ 50 mmol

➧ Clinical benefit has not been demonstrated.

➧ Use to correct pH < 7, target pH of 7-7.2.

Potassium:

➧ 10-30 mEq/h. replacement to be started during the second or third hour of treatment.

Phosphate:

➧ Replete hypophosphatemia of < 1 mg/dL.

➧ 15 mmol K or Na phosphate in 100 mL saline.

➧ Replete slowly (3-4 mmol/h.) to avoid hypocalcemic tetany.

Treatment of Associated Infection:

➧ Antibiotics: as indicated.

➧ Cholecystitis and pyelonephritis may be particularly severe in these patients.

Read more ☛ Hypoglycemic Coma

Read More

Pheochromocytoma Crisis

Causes:

➧ The action of unopposed high circulating levels of catecholamines

- α - receptors: Pressor response

- β - receptors: positive ino- and chrono-topic

Precipitating factors:

➧ Spontaneous

➧ Hemorrhage into pheochromocytoma

➧ Exercise

➧ Pressure on abdomen

➧ Urination

➧ Drugs: glucagon, naloxone, metoclopramide, ACTH, cytotoxics, tricyclic antidepressants

Clinical picture:

➧ History of poorly controlled Hypertension or accelerated Hypertension.

➧ Hypertension, palpitations, sweating, pallor, pounding headache, anxiety, tremulousness, pulmonary edema, feeling of impending death, hyperhidrosis, nausea and vomiting, abdominal pain, paralytic ileus, hyperglycemia, hypertensive encephalopathy, myocardial infarction, and stroke.

➧ Attacks build up over a few minutes and fade gradually over 15 min or can be more sustained (60 min).

➧ Signs of end-organ damage (Figure 1)

Figure 1: Hypertensive Retinopathy - Grade IV

Biochemical Diagnosis:

➧ 24 h. urine collection for free catecholamines and metanephrines.

Management of Pheochromocytoma Crisis:

-Do not wait for biochemical confirmation of the diagnosis.

-Be aware of postural hypotension.

-Avoid histamine-releasing drugs.

-Surgical resection treatment of choice.

α-adrenergic blockers:

-Treatment with a-antagonists should precede β-antagonist treatment with 48 h. to avoid exacerbation of the crisis.

➧ Phentolamine: (short-acting) 2-5 mg IV repeated/5 min.

➧ Phenoxybenzamine: 1st choice because it’s irreversible and long-acting

10 mg/12h., then 20-40 mg/8 h.

➧ Prazosin, Terazosin & Doxazosin: are selective α1-blockers. Preferable for long term Rx due to favorable S/E

β-blockers:

-Control tachycardia.

-After adequate α-adrenergic blockage to prevent unopposed hypertension.

➧ Non selective b- antagonist: Propranolol: 1-2 mg/5-10 min. 30-60 mg/d. oral.

➧ Esmolol: 500 µg/kg/min. for 1 min., then 100-300 µg/kg/min.

➧ Metoprolol

➧ Labetalol: α and β blocker.

Catecholamine synthesis inhibitors:

➧ Metyrosine

-Inhibit catecholamine synthesis.

-Used when alpha &beta blockers are ineffective or poorly tolerated.

-Combined for difficult resections.

Calcium channel blockers:

-Inhibit norepinephrine mediated calcium transport.

Acute hypertensive crisis (pre/intra-op):

➧ Nitroprusside

➧ Phentolamine

➧ Nicardipine

Surgery and Post-operative care:

➧ Experienced surgeon/anesthetist team.

➧ Last α & β doses on the day of surgery.

➧ Avoid fentanyl, ketamine, morphine, atropine, halothane, and desflurane during surgery.

➧ Treat hypotension post resection with fluids and intermittent doses of vasopressors.

➧ 24 h. urine metanephrine & catecholamine level 1-2 wks post-surgery and annually for life.

➧ Lifelong glucocorticoid and mineralocorticoid therapy for bilateral adrenalectomy.

➧ Radiotherapy, cryoablation, and combination chemotherapy should be considered for malignant pheochromocytoma.

Read More

Pituitary Apoplexy

Clinical Setting:

➧ Hemorrhagic infarction of a pituitary adenoma/tumor.

➧ Sudden crisis in a patient with a known or previously unknown pituitary tumor.

➧ It may occur in a normal gland during and after childbirth, with head trauma, or in patient on anticoagulation therapy. 

➧ Sheehan’s Syndrome:

-Refers to pituitary apoplexy of the non-tumorous gland. It is due to the postpartum arterial spasm of arterioles supplying the anterior pituitary and its stalk.

Clinical Picture:

➧ Severe headache and visual disturbance

➧ Bitemporal hemianopia (Figure 1)

➧ CN III palsy

➧ Meningeal symptoms with neck stiffness

➧ Symptoms of secondary acute adrenal insufficiency:

-Nausea, vomiting, hypotension, and collapse

Figure 1: Bitemporal Hemianopia

Diagnosis:

➧ CT/MRI scan of head and pituitary

➧ Hormonal studies only of academic interest

➧ Assessment of pituitary function after the acute stage has settled

Management:

a) Hormonal:

➧ Dexamethasone: 4 mg/12 h.

-Glucocorticoid support and relief of cerebral edema.

b) Neurosurgical:

➧ Transsphenoidal pituitary decompression

-After the acute episode the patient must be evaluated for multiple pituitary deficiencies.

Read More