1. ENDOCRINE DISEASES BY CYNTHIA L. DIETRICH, D.O. November 23, 2004

2. DIABETES MELLITUS Problem in glucose metabolism, accompanied by predictable long-term vascular and neurologic complications Problem in glucose metabolism, accompanied by predictable long-term vascular and neurologic complications Chronic disease Chronic disease Significant morbidity and mortality Significant morbidity and mortality

3. COMPLICATIONS Hyperglycemia +/- ketoacidosis Hyperglycemia +/- ketoacidosis Hypoglycemia: activation of the sympathetic nervous system (diaphoresis, tremulousness and tachycardia) and insufficient delivery of oxygen to the brain (confusion, seizures and unconsciousness Hypoglycemia: activation of the sympathetic nervous system (diaphoresis, tremulousness and tachycardia) and insufficient delivery of oxygen to the brain (confusion, seizures and unconsciousness

4. Retinopathy- microaneurysms cluster at macula- >terminal vessels obstructed->ischemia->new vessel proliferation Retinopathy- microaneurysms cluster at macula- >terminal vessels obstructed->ischemia->new vessel proliferation Nephropathy-leads to hypertension. Assoc with the highest mortality. Nephropathy-leads to hypertension. Assoc with the highest mortality. Cardiovascular disease- “silent ischemia” Cardiovascular disease- “silent ischemia” Peripheral neuropathy- numbness and tingling progressing to total insensitivity Peripheral neuropathy- numbness and tingling progressing to total insensitivity Stiff joint syndrome- “prayer sign” and atlanto- occipital joint involvement Stiff joint syndrome- “prayer sign” and atlanto- occipital joint involvement

5. Autonomic nervous system dysfunction Autonomic nervous system dysfunction -orthostatic hypotension, resting tachycardia, absent beat-to-beat variation -orthostatic hypotension, resting tachycardia, absent beat-to-beat variation -hypogylcemic unawareness -hypogylcemic unawareness -gastroparesis occurs in 20-30% -gastroparesis occurs in 20-30%

6. IDDM Prevalence 0.4% Prevalence 0.4% Onset most often prior to age 20 Onset most often prior to age 20 Environmental influences are superimposed on a genetic component located on chromosome 6 Environmental influences are superimposed on a genetic component located on chromosome 6 Absolute insulin deficiency Absolute insulin deficiency Pancreatic beta islet cells are destroyed and anti-islet cell antibodies appear Pancreatic beta islet cells are destroyed and anti-islet cell antibodies appear Clinical symptoms when 90% of the beta cells destroyed Clinical symptoms when 90% of the beta cells destroyed Associated with other autoimmune diseases: rhuematoid arthritis and thyroid disease Associated with other autoimmune diseases: rhuematoid arthritis and thyroid disease

7. Clinical presentation is unmistakable: hypergylcemia, polyuria, polydipsia, weight loss, blurred vision and ketoacidosis Clinical presentation is unmistakable: hypergylcemia, polyuria, polydipsia, weight loss, blurred vision and ketoacidosis Long term management requires exogenous insulin, self monitoring, lifestyle adaptations including diet and exercise Long term management requires exogenous insulin, self monitoring, lifestyle adaptations including diet and exercise Insulin formulations rapid (regular), intermediate (Lente, NPH) or long-acting (Ultralente) Insulin formulations rapid (regular), intermediate (Lente, NPH) or long-acting (Ultralente) Goal- HbA1c less than 7.5% Goal- HbA1c less than 7.5%

8. DKA Insulin transfers glucose and amino acids into the cells. Insulin transfers glucose and amino acids into the cells. Hyperglycemia->osmotic diuresis->dehydration- >acidosis. Also, a build up of amino acids in the blood->lipolysis->free fatty acids->converted to ketone bodies in the liver Hyperglycemia->osmotic diuresis->dehydration- >acidosis. Also, a build up of amino acids in the blood->lipolysis->free fatty acids->converted to ketone bodies in the liver Results in a intravascular fluid volume deficit of 5-8 liters, potassium deficit of 200-400 mEq, and NaCl deficit of 350-600 mEq Results in a intravascular fluid volume deficit of 5-8 liters, potassium deficit of 200-400 mEq, and NaCl deficit of 350-600 mEq

9. Treatment of DKA Intubate for CNS depression Intubate for CNS depression Regular insulin 10 units IVP followed by 5-10 units/hr IV Regular insulin 10 units IVP followed by 5-10 units/hr IV Normal saline 5-10 ml/kg/hr IV Normal saline 5-10 ml/kg/hr IV Add 5% glucose when serum blood sugar<250 mg/dl Add 5% glucose when serum blood sugar<250 mg/dl Potassium 0.3-0.5 mEq/kg/hr IV Potassium 0.3-0.5 mEq/kg/hr IV Monitor blood sugar, potassium, arterial pH and urine ketones hourly Monitor blood sugar, potassium, arterial pH and urine ketones hourly Identify cause (sepsis, MI, compliance) Identify cause (sepsis, MI, compliance)

10. ANESTHETIC MANAGEMENT Goal- blood sugar between 120-180 mg/dl Goal- blood sugar between 120-180 mg/dl Surgery scheduled early in the day Surgery scheduled early in the day ¼ to ½ usual daily dose of intermediate acting insulin on the morning of surgery ¼ to ½ usual daily dose of intermediate acting insulin on the morning of surgery Frequent blood sugar analysis, q 1-2 hours intraop Frequent blood sugar analysis, q 1-2 hours intraop Treat blood sugar values above 250 mg/dl Treat blood sugar values above 250 mg/dl

11. Tracheal intubation in patients with autonomic nervous system neuropathy (pre-treat with metoclopramide) Tracheal intubation in patients with autonomic nervous system neuropathy (pre-treat with metoclopramide) Choice of drugs for induction and maintenance less important than monitoring of serum blood sugar Choice of drugs for induction and maintenance less important than monitoring of serum blood sugar +/- regional anesthesia due to peripheral neuropathies +/- regional anesthesia due to peripheral neuropathies Risk of peripheral nerve injury with positioning Risk of peripheral nerve injury with positioning Bradycardia and hypotension may require epi Bradycardia and hypotension may require epi

12. NIDDM Obese, sedentary lifestyle, and advancing age Obese, sedentary lifestyle, and advancing age Prevalence 6.6% Prevalence 6.6% Insulin resistance and a decrease in insulin secretion Insulin resistance and a decrease in insulin secretion Usual onset after age 40 Usual onset after age 40 Insulin resistance is inherited Insulin resistance is inherited Ketosis-resistant Ketosis-resistant

13. Insulin-mediated stimulation of tyrosine kinase is impaired. This is necessary for normal function of insulin receptors. Insulin-mediated stimulation of tyrosine kinase is impaired. This is necessary for normal function of insulin receptors. Effect is reversible with improved control of serum blood sugar Effect is reversible with improved control of serum blood sugar When dietary management fails hypoglcemic drugs stimulate endogenenous insulin secretion, or inhibit gluconeogenesis in the liver and kidneys, and increase glucose uptake in skeletal muscles When dietary management fails hypoglcemic drugs stimulate endogenenous insulin secretion, or inhibit gluconeogenesis in the liver and kidneys, and increase glucose uptake in skeletal muscles Duration can be up to 36 hours Duration can be up to 36 hours

14. HYPEROSMOLAR, HYPERGLYCEMIC NONKETOTIC COMA -elderly, insulin deficiency, renal insufficiency, thirst deficiency -sepsis, hyperalimentation or drugs (corticosteriods) -glucose >600 mg/dl -osmotic diuresis->hypokalemia and dehydration -serum osmolarity >350 mOsm/L -pH >7.3 -hypovolemia (severe, up to 25% total body water) -patients are insulin deficient but liver insulin levels sufficient for metabolism of free fatty acids->no ketosis -coma due to shrinkage of brain cells

15. TREATMENT OF HHNC Regular insulin 10 units IVP then recheck Regular insulin 10 units IVP then recheck Isotonic salt solution 2-3 liters over the first 1-2 hours Isotonic salt solution 2-3 liters over the first 1-2 hours Subsequent half-strength saline Subsequent half-strength saline When plasma glucose level approaches normal start D5W When plasma glucose level approaches normal start D5W When urine output is resumed supplement potassium When urine output is resumed supplement potassium Remember: this can be reversed with fluids alone, go slowly Remember: this can be reversed with fluids alone, go slowly

16. ANESTHETIC MANAGEMENT Same as IDDM except omit oral hypoglycemic the morning of surgery Same as IDDM except omit oral hypoglycemic the morning of surgery Keep in mind long duration of action of oral hypoglycemic drugs Keep in mind long duration of action of oral hypoglycemic drugs Obesity considerations Obesity considerations

17. GESTATIONAL DIABETES Glucose intolerance first detected during pregnancy Glucose intolerance first detected during pregnancy 2-3% of all pregnancies 2-3% of all pregnancies Detected in the last trimester Detected in the last trimester Resembles NIDDM (50% develop NIDDM within 10 years) Resembles NIDDM (50% develop NIDDM within 10 years) Risk factor for fetal morbidity Risk factor for fetal morbidity Neonatal hypoglycemia Neonatal hypoglycemia Increased Respiratory Distress Syndrome, cardiomegaly and congenital abnormalities Increased Respiratory Distress Syndrome, cardiomegaly and congenital abnormalities

18. THYROID GLAND DYSFUNCTION Overproduction or underproduction of T3 and/or T4 Overproduction or underproduction of T3 and/or T4 Negative feedback regulated by the anterior pituitary gland and the hypothalmus Negative feedback regulated by the anterior pituitary gland and the hypothalmus T3 and T4 act on cells through the adenylate cyclase system, producing changes in speed of biochemical reactions, total body oxygen consumption, and heat production T3 and T4 act on cells through the adenylate cyclase system, producing changes in speed of biochemical reactions, total body oxygen consumption, and heat production

19. HYPERTHYROIDISM Prevalence: 2% women, 0.2% men Prevalence: 2% women, 0.2% men Decreased TSH and increased T4 Decreased TSH and increased T4 Causes: Grave’s Disease, iatrogenic, Toxic nodular goiter and Thyroiditis Causes: Grave’s Disease, iatrogenic, Toxic nodular goiter and Thyroiditis Signs and symptoms: goiter, tachycardia, anxiety, tremor, heat intolerance, fatigue, weight loss, eye signs, skeletal muscle weakness and atrial fibrillation Signs and symptoms: goiter, tachycardia, anxiety, tremor, heat intolerance, fatigue, weight loss, eye signs, skeletal muscle weakness and atrial fibrillation Stimulation of the sympathetic nervous system Stimulation of the sympathetic nervous system

20. TREATMENT OF HYPERTHYROIDISM Antithyroid drugs: (methimazole, carbimazole, propylthiouracil) inhibit oxidation/formation of iodothyromines before treatment with radioiodine or surgery Antithyroid drugs: (methimazole, carbimazole, propylthiouracil) inhibit oxidation/formation of iodothyromines before treatment with radioiodine or surgery B-adrenergic antagonists (propranolol, nadolol, atenolol) decrease some of the tachycardia, anxiety and tremor B-adrenergic antagonists (propranolol, nadolol, atenolol) decrease some of the tachycardia, anxiety and tremor Inorganic iodine inhibits the release of T4 and T3 for a limited time to prepare pt’s for surgery or treat thyrotoxic crisis Inorganic iodine inhibits the release of T4 and T3 for a limited time to prepare pt’s for surgery or treat thyrotoxic crisis

21. Radioiodine therapy destroys thyroid tissue Radioiodine therapy destroys thyroid tissue Subtotal thyroidectomy when radioiodine is refused or a large goiter is present causing tracheal compression or cosmetic concerns Subtotal thyroidectomy when radioiodine is refused or a large goiter is present causing tracheal compression or cosmetic concerns

22. ANESTHETIC MANAGEMENT OF HYPERTHYROIDISM Elective surgery should be deferred until the patient is rendered euthyroid and hyperdynamic state controlled with B-blockers Elective surgery should be deferred until the patient is rendered euthyroid and hyperdynamic state controlled with B-blockers Preop: anxiolytics and evaluation of upper airway (CT scan of the neck) Preop: anxiolytics and evaluation of upper airway (CT scan of the neck) Induction: Thiopental has antithyroid activity (no ketamine) Induction: Thiopental has antithyroid activity (no ketamine) Maintenance: isoflurane or sevoflurane (no halothane) and fentanyl or remi. Attention to body temp, heart rate and eye protection (exothalmos) Maintenance: isoflurane or sevoflurane (no halothane) and fentanyl or remi. Attention to body temp, heart rate and eye protection (exothalmos) Muscle relaxation: avoid pancuronium and use glycopyrrolate with reversal agent Muscle relaxation: avoid pancuronium and use glycopyrrolate with reversal agent Treat hypotension with phenylephrine Treat hypotension with phenylephrine

23. COMPLICATIONS OF SUBTOTAL THYROIDECTOMY Damage to the recurrent laryngeal nerve when unilateral->hoarseness, when bilateral->total airway obstruction Damage to the recurrent laryngeal nerve when unilateral->hoarseness, when bilateral->total airway obstruction Damage to superior laryngeal nerve can lead to aspiration Damage to superior laryngeal nerve can lead to aspiration Airway obstruction from tracheomalacia (after extubation) or hematoma (early postop period) Airway obstruction from tracheomalacia (after extubation) or hematoma (early postop period) Hypoparathyroidism-> hypocalcemia develops 24-72 hours postop (but sometimes 1-3 hours postop)->laryngeal stridor->laryngospasm Hypoparathyroidism-> hypocalcemia develops 24-72 hours postop (but sometimes 1-3 hours postop)->laryngeal stridor->laryngospasm

24. THYROTOXIC CRISIS (THYROID STORM) Medical emergency Medical emergency Typically presents 6-18 hours after surgery Typically presents 6-18 hours after surgery Abrupt onset of tachycardia, hyperthermia, agitation, skeletal muscle weakness, congestive heart failure, dehydration and shock due to abrupt release of T4 and T3 into the circulation Abrupt onset of tachycardia, hyperthermia, agitation, skeletal muscle weakness, congestive heart failure, dehydration and shock due to abrupt release of T4 and T3 into the circulation Precipitated by surgery, infection, trauma, toxemia, DKA Precipitated by surgery, infection, trauma, toxemia, DKA

25. TREATMENT OF THYROID STORM Intraveneous cooled crystalloid solutions, acetominophen and cooling blankets Intraveneous cooled crystalloid solutions, acetominophen and cooling blankets Esmolol infusion with goal heart rate <100 Esmolol infusion with goal heart rate <100 Potassium iodide to block release of T4 and T3 Potassium iodide to block release of T4 and T3 Propylthiouracil 100 mg po to inhibit conversion of T4 to T3 Propylthiouracil 100 mg po to inhibit conversion of T4 to T3 Cortisol 100-200 mg IV Cortisol 100-200 mg IV

26. HYPOTHYROIDISM Prevalence 0.5-0.8% Prevalence 0.5-0.8% Increased TSH and decreased T4 and T3 Increased TSH and decreased T4 and T3 Cause is primarily treatment of hyperthyroidism, medically or surgically or Hashimoto’s Thyroiditis Cause is primarily treatment of hyperthyroidism, medically or surgically or Hashimoto’s Thyroiditis Signs and symptoms: lethargy, hypotension, bradycardia, CHF, gastroparesis, hypothermia, hypoventilation, hyponatremia, and poor mentation Signs and symptoms: lethargy, hypotension, bradycardia, CHF, gastroparesis, hypothermia, hypoventilation, hyponatremia, and poor mentation Treatment with Synthroid Treatment with Synthroid

27. ANESTHETIC MANAGEMENT OF HYPOTHYROISM Preop meds titrate and consider supplemental cortisol Preop meds titrate and consider supplemental cortisol Induction: ketamine Induction: ketamine Maintenance: nitrous oxide plus short acting opioids, benzo’s or ketamine Maintenance: nitrous oxide plus short acting opioids, benzo’s or ketamine Low dose muscle relaxants Low dose muscle relaxants Controlled ventilation of the lungs (vulnerable to excessive decrease in PaCO2) Controlled ventilation of the lungs (vulnerable to excessive decrease in PaCO2) Treat hypotension with ephedrine Treat hypotension with ephedrine Watch for CHF, consider arterial line and PA catheter Watch for CHF, consider arterial line and PA catheter

28. ADRENAL GLAND DYSFUNCTION 1. Hypercortisolism= Cushing’s Syndrome 2. Hypocortisolism= Addison’s Disease 3. Pheochromocytoma

29. CUSHING’S SYNDROME Caused by excessive secretion of corticotropin by anterior pituitary corticotroph tumors (microadenomas) Caused by excessive secretion of corticotropin by anterior pituitary corticotroph tumors (microadenomas) Increased aldosterone, cortisol and testosterone in the adrenal cortex Increased aldosterone, cortisol and testosterone in the adrenal cortex Signs and symptoms: hypertension, hypokalemic alkalosis, hyperglycemia, hypernatremia, osteoporosis, easy bruising, polyuria, buffalo hump, moon facies, excessive body hair, menstrual abnormalities, weight gain, skeletal muscle wasting/weakness, depression and insomnia Signs and symptoms: hypertension, hypokalemic alkalosis, hyperglycemia, hypernatremia, osteoporosis, easy bruising, polyuria, buffalo hump, moon facies, excessive body hair, menstrual abnormalities, weight gain, skeletal muscle wasting/weakness, depression and insomnia

30. Diagnosis with 24 hour urinary secretion of cortisol Diagnosis with 24 hour urinary secretion of cortisol Dexamethasone suppression test distinguishes Cushing’s disease from the ectopic corticotropin syndrome Dexamethasone suppression test distinguishes Cushing’s disease from the ectopic corticotropin syndrome Treatment of choice is transsphenoidal microadenomectomy or 85-90% resection of the anterior pituitary gland Treatment of choice is transsphenoidal microadenomectomy or 85-90% resection of the anterior pituitary gland

31. ANESTHETIC MANAGEMENT Preop evaluation of systemic blood pressure, electrolyte balance and the blood glucose Preop evaluation of systemic blood pressure, electrolyte balance and the blood glucose No single anesthetic the best No single anesthetic the best Replacement therapy hydrocortisone 10 mg/ hr for 24 hours Replacement therapy hydrocortisone 10 mg/ hr for 24 hours Treat hypertension and hypervolemia with a potassium sparing diuretic Treat hypertension and hypervolemia with a potassium sparing diuretic Treat hyperglycemia with insulin Treat hyperglycemia with insulin Care when positioning patient due to osteoporosis Care when positioning patient due to osteoporosis

32. CORTISOL THE ONLY ESSENTIAL HORMONE FOR LIFE THE ONLY ESSENTIAL HORMONE FOR LIFE Maintains blood pressure by facilitating the conversion of norepi to epi Maintains blood pressure by facilitating the conversion of norepi to epi Converts amino acids to glucose Converts amino acids to glucose Suppresses inflammation Suppresses inflammation

33. ADDISON’S DISEASE Absense of cortisol and aldosterone due to destruction of the adrenal cortex Absense of cortisol and aldosterone due to destruction of the adrenal cortex Causes: hemorrhage in anticoagulated patients, sepsis, surgical or accidental trauma Causes: hemorrhage in anticoagulated patients, sepsis, surgical or accidental trauma Diagnosis by measurement of plasma cortisol before and 1 hour after administration of corticotropin Diagnosis by measurement of plasma cortisol before and 1 hour after administration of corticotropin Signs and symptoms: weight loss, skeletal muscle weakness, hypotension, fluid depletion, hyperkalemia, hyponatremia, hypoglycemia, abdominal/back pain Signs and symptoms: weight loss, skeletal muscle weakness, hypotension, fluid depletion, hyperkalemia, hyponatremia, hypoglycemia, abdominal/back pain

34. MANAGEMENT OF A PATIENT WITH ADDISON’S DISEASE You must give exogenous corticosteriods! You must give exogenous corticosteriods! Intraveneous infusion of sodium containing fluids Intraveneous infusion of sodium containing fluids Invasive monitoring with arterial line and CVP or PA catheter Invasive monitoring with arterial line and CVP or PA catheter Frequent measurements of glucose and electrolytes Frequent measurements of glucose and electrolytes Decrease initial dose of muscle relaxants Decrease initial dose of muscle relaxants

35. PHEOCHROMOCYTOMA Catecholamine-secreting tumor that originates in the adrenal medulla or in the chromaffin tissues along the paravertebral sympathetic chain, extending from the pelvis to the base of the skull Catecholamine-secreting tumor that originates in the adrenal medulla or in the chromaffin tissues along the paravertebral sympathetic chain, extending from the pelvis to the base of the skull Age: 30-50 years Age: 30-50 years 50% deaths occur during unrelated surgery or pregnancy 50% deaths occur during unrelated surgery or pregnancy Diagnosis by 24 hour urine for norepinepherine and CT scan Diagnosis by 24 hour urine for norepinepherine and CT scan Associated with Multiple endocrine neoplasia (MEN) Associated with Multiple endocrine neoplasia (MEN)

36. Signs and symptoms: tachycardia, diaphoresis, headache, hypertension, hyperglycemia, hypovolemia, tremulous, palpitations, weight loss Signs and symptoms: tachycardia, diaphoresis, headache, hypertension, hyperglycemia, hypovolemia, tremulous, palpitations, weight loss Treatment is surgical excision of the tumor(s) Treatment is surgical excision of the tumor(s)

37. ANESTHETIC MANAGEMENT OF PHEOCHROMOCYTOMA Correct hypovolemia (serial hematocrits) Correct hypovolemia (serial hematocrits) Alpha blockade before beta blockade Alpha blockade before beta blockade Alpha blockage: phenoxybenzamine 10-20 mg PO bid for 14 days pre-op Alpha blockage: phenoxybenzamine 10-20 mg PO bid for 14 days pre-op Beta blockade: propranolol 40 mg PO bid pre- op Beta blockade: propranolol 40 mg PO bid pre- op Pre-op: benzo with scopalamine Pre-op: benzo with scopalamine Avoid histamine releasing drugs Avoid histamine releasing drugs Arterial line pre-induction Arterial line pre-induction

38. Induction: etomidate, thiopental or propofol Induction: etomidate, thiopental or propofol Lidocaine 1-2 mg/kg prior to intubation Lidocaine 1-2 mg/kg prior to intubation Consider PA catheter Consider PA catheter Maintenance: sevoflurane due to rapid changes in concentration and fentanyl or remifentanyl Maintenance: sevoflurane due to rapid changes in concentration and fentanyl or remifentanyl Treat hypertension with phentolamine 1-5 mg IV or nitroprusside Treat hypertension with phentolamine 1-5 mg IV or nitroprusside Treat reflex tachycardia with an esmolol infusion Treat reflex tachycardia with an esmolol infusion