Introduction to Endocrine

1. Introduction to Endocrine Megan Conner, CRNA, MSN

2. Acromegaly Diabetes Insipidus SIADH Addison’s Disease Cushing’s Disease Hyperaldosteronism Hypoaldosteronism Diabetes Mellitus Hyperparathyroidism Hypoparathyroidism Hyperthyroidism Hypothyroidsim Pheochromocytoma Outline

3. Acromegaly • The excessive secretion of growth hormone in an adult. • Often from an adenoma in the anterior pituitary gland resulting in enlargement of sella turcica. • If hypersecretion occurs before puberty, this is gigantism, and the individual grows tall, because it occurs before growth plate closure.

4. Pathophysiology • Excessive production of growth hormone • Does not induce bone lengthening, but rather enhances the growth of periosteal bone. • Bones become massive in size and thickness leading to large hands and feet and overgrowth of vertebrae (arthritis and kyphoscoliosis)

5. Soft tissue changes: • Coarsened facial features: large bulbous nose, supraorbital ridge overgrowth, dental malocclusion, and prominent prognathic mandible • Overgrowth of internal organs: liver, heart, spleen, and kidneys • Lung volume increases and may lead to V/Q mismatch • Symptomatic cardiac disease due to cardiomyopathy, hypertension (28%), and accelerated atherosclerosis leading to CHF, arrhythmias, LVH, abnormal EKG • Insulin antagonist effect of GH produce glucose intolerance (50%) and DM (10-25%)

6. Clinical Manifestations • From expanding tumor include: headaches (55%), papilledema, visual field defects(19%) • Compression or destruction of normal pituitary tissue may lead to panhypopituitarisms

7. Common Features • Skeletal overgrowth • Soft tissue overgrowth • Visceromegaly • Osteoarthritis • Glucose intolerance • Peripheral neuropathy • Skeletal muscle weakness • Extrasellar tumor extension

9. Treatment • Aimed at restoring normal GH levels • Preferred initial: microsurgical removal of tumor with gland preservation via transsphenoidal route • Surgical ablation usually rapidly successful at reducing tumor size, and inhibiting GH secretion, and alleviating some symptoms • Administration of octreotide (a long acting somatostatin) or bromocriptine and gland irradiation are treatment option for patients who aren’t surgical candidates

10. Anesthetic Considerations • Preanesthetic cardiac evaluation: assess EKG, exercise tolerance, recent chest pain or SOB • Due to increase risk of DM, check blood glucose and electrolyte levels • If impairment of adrenal or thyroid axis, then stress-level glucocorticoid therapy and thyroid replacement implemented preoperatively • Entrapment neuropathies are common (CTS) • Perform Allen’s test before placing radial a-line to ensure adequate ulnar artery flow

11. Anesthetic Considerations • May present with challenging airway so careful examination of airway • Prognathic mandible • Facial deformities and large nose • Large thick tongue (macroglossia) • Enlargement of thyroid tissue • Obstructive teeth • Hypertrophy epiglottis • Soft tissue overgrowth in upper airway • Subglottic narrowing • Vocal cord enlargement • Possible turbinate enlargement • Perioperative dyspnea, stridor, or hoarseness indicates airway involvement

12. Transsphenoidal hypophysectomy • Pituitary lies in sella turcica of the sphenoid bone • Cavernous sinus is lateral and contains CN III, IV, V, & VI and cavernous portion of carotid artery • Tumors under 10mm - if larger, will need bifrontal craniotomy • Transsphenoidal has lower morbidity and mortality • Incision in the gingival mucosa beneath the upper lip, enters nasal cavity, dissects through septum, and penetrates roof of sphenoid sinus to sella turcica

13. Transsphenoidal hypophysectomy • Preoperative Preparation: replace the hormones and ameliorate symptoms • Problems with transsphenoidal • Need for mucosal injections of epinephrine or use of coccaine to reduce bleeding • Accumulation of blood and tissue debris in pharynx and stomach • Risks of hemorrhage (Internal carotid art) • Cranial nerve damage • Pituitary hypofunction • Venous air embolism - positioned slightly head up • Diabetes insipidus develops postoperatively in 40% but usually transient • Monitoring as for craniotomies, precordial doppler for detecting VAE, adequate venous access in event of massive hemorrhage

14. Diabetes Insipidus (DI) • Reflexes the absence of antidiuretic hormone (ADH) from one of two pathologies: • 2) Failure of renal tubules to respond to ADH (nephrogenic DI) • Hypokalemia • Hypocalcaemia • Sickle cell anemia • Obstructive uropathy • Chronic renal insufficiency • Long term use of lithium • Destruction of posterior pituitary (neurogenic DI) • Intracranial trauma • Hypophysectomy • Neoplastic invasion • Sarcoidosis

15. Clinical Manifestations • Polydipsia • Polyuria • Poorly concentrated urine despite increase plasma osmolarity • Neurogenic and nephrogenic DI are differentiated based on response to desmopressin, which caused concentration of urine in neurogenic DI, but not nephrogenic DI

16. Treatment • Careful monitoring of urine output, plasma volume, plasma osmolarity. • Isotonic fluids administered until osmolarity is greater than 290. • Neurogenic DI treated with desmopressin 3 mcg/kg. • Nephrogenic DI treated with chlorpropamide, an oral hypoglycemic drug that potentiates the effect of ADH on renal tubules.

17. Anesthetic Considerations • Monitoring of urine output and plasma electrolyte concentrations • In emergency surgery, CVP monitoring may aid in evaluation of volume status

18. Syndrome of Inappropriate ADH (SIADH) • Excessive secretion of ADH • Causes: head injuries, intracranial tumors, pulmonary infections, small cell carcinoma of the lung, hypothyroidism • Clinical Manifestations: dilutional hyponatremia, decreased serum osmolarity, and reduced urine output with high osmolarity  weight gain, skeletal muscle weakness, mental confusion, convulsions • Diagnosis: is done by exclusion of other causes of hyponatremia • Treatment: • fluid restriction (800 ml/day) • if mental confusion, then more aggressive treatment required: IV hypertonic saline, lasix

19. Addison’s Disease • Is primary adrenal insufficiency • Reflects the absence of cortisol and aldosterone due to destruction of adrenal cortex • Most common cause is adrenal hemorrhage secondary to abnormal coagulation • Other causes include: sepsis, accidental trauma, or surgical trauma • Diagnosis requires measurement of plasma cortisol concentration within 1 hour of administration of adrenocorticotropic hormone (ACTH)

20. Clinical Manifestations • Clinical symptoms reflect glucocorticoid and mineralocorticoid deficiency • Weakness • Fatigue • Reduce appetite with weight loss • Abdominal pain • Vomiting • Diarrhea • Volume depletion leading to orthostatic hypotension • Hypoglycemia • Hyponatremia • Hyperkalemia • Lack of catecholamines • In women, oligomenorrhea or amenorrhea

21. Clinical Manifestations • The adrenal-pituitary axis is intact in primary adrenal insufficiency, and ACTH concentrations are elevated as a result of reduced production of cortisol. • Increase ACTH leads to increased melanin formation in skin and hyperpigmentation of knuckles, knees, elbows, lips, buccal mucosa.

22. Treatment • Normal adults secrete 15-25 mg of cortisol (hydrocortisone) and 50 to 250 mcg of aldosterone per day • Therapeutic replacement of glucocorticoids is typically 50% greater than basal adrenal output so the patient is covered for mild stress • Oral replacement of glucocorticoids (with prednisone or hydrocortisone) and mineralocorticoid (with fludrocortisone) • Treatment entails both glucocorticoid and mineralocorticoid replacement • Acute adrenal insufficiency (Addisonian Crisis) is medical emergency, and treatment includes fluids, steroid replacement, inotropes, electrolyte correction.

23. Anesthetic Considerations • Provide exogenous corticosteroid supplementation • Avoid etomidate • Sensitive to drug induced myocardial depression • Initial dose of muscle relaxant reduced due to skeletal muscle weakness • Consider monitoring glucose and electrolytes

24. Cushing’s Disease

25. Cushing’s Disease • Adrenocortical hyperfunction; chronic glucocorticoid excess. • Clinical manifestations from excess glucose production caused by hypersecretion of cortisol • Caused by adrenal neoplasms, hypersecretion of ACTH, and ectopic ACTH syndrome

26. Cushing’s Syndrome • Caused by excess glucocorticoid hormone • Most common cause is therapeutic administration of supraphysiologic doses of glucocorticoids (as in treatment of arthritis, asthma, autoimmune disorders, allergies, ect.) • Endogenous Cushing’s syndrome result of one of three pathogenic disorders: • Pituitary tumor (Cushing’s Disease) • Adrenal tumor • Ectopic hormone production

27. Cushing’s Disease: specifically denotes anterior pituitary tumor cause of the syndrome • Pituitary tumor produces excessive amount of adrenocorticotropic hormone (ACTH) • Associated with bilateral adrenal hyperplasia • Excess ACTH results in increase skin pigmentation • Most common cause of endogenous Cushing’s syndrome

28. Adrenal Cushing’s syndrome is caused by autonomous cortisol production (ACTH independent) by an adrenal tumor. • Associated with suppressed plasma ACTH levels • Usually unilateral and can be malignant • This form of hyperadrenalism accounts for 20-25% of patients with Cushing syndrome • Ectopic hormone production

29. Diagnosis • By measuring plasma cortisol concentration the morning after a dose of dexamethasone • Dexamethasone suppresses plasma cortisol in physiologically normal patients, but not in those with hyperadrenocorticism • Also based on elevations of plasma and urinary cortisol level and of urinary 17-hydroxycorticosteroids

30. Clinical Manifestations • Reflects cortisol excess from endogenous or exogenous sources and leads to: • Central obesity • Hypertension • Glucose intolerance • Plethoric facies • Purple striae • Muscle weakness • Bruising • Osteoporosis • Poor wound healing • Susceptibility to infection • Thin skin (atrophic unable to withstand stress of normal activity) • Weigh gain in a yoke-like pattern over clavicles, neck, trunk, abdomen, and cheeks • Women manifest a degree of maculinization (hirsutism, hair thinning, acne, oligomenorrhea, amenorrhea) • Men manifest a degree of feminization (gynecomastia, impotence)

32. Mnemonic • C - Central obesity, Cervical fat pads, Collagen fiber weaknessU - Urinary free cortisol and glucose increaseS - Striae, Suppressed immunityH - Hypercortisolism, Hypertension, Hyperglycemia, HirsutismI - Iatrogenic (Increased administration of corticosteroids)N – Non-iatrogenic (Neoplasms)G - Glucose intolerance, Growth retardation

33. Clinical Manifestations • Mineralocorticoid effects include: • Fluid retention • Hypokalemic alkalosis

34. Treatment • Depends on cause of Cushing’s syndrome • Transsphenoidal hypophysectomy is a primary treatment for Cushing’s syndrome cause by anterior pituitary tumor. • Complications in 5% of patients and include transient DI, CSF rhinorrhea, and hemorrhage. • Adrenal Cushing’s syndrome treated by surgical removal of adrenal adenoma. Because contralateral adrenal gland is preoperatively suppressed, glucocorticoid replacement may be necessary for months until adrenal function returns. Bilateral adrenalectomy is a/w post-op complications and permanent glucocorticoid and mineralocorticoid deficiency results. • For ectopic ACTH-secreting tumor, treatment of choice is surgical removal. If surgical removal is not feasible (ex. metastatic carcinoma), metyrapone and ketoconazole may be used to normalize cortisol levels.

35. Anesthetic Considerations • Perioperative considerations focus on normalizing BP, blood glucose levels, intravascular fluid volume, and electrolyte concentrations • Spironolactone • Osteoporosis • Skin damage • Increased risk of infection • Exaggerated effect of muscle relaxants may be seen

36. Anesthetic Considerations • With unilateral or bilateral adrenal resection, glucocorticoids administered at dose equivalent to adrenal output for maximum stress (hydrocortisone 100 mg IV Q8H) • Glucocorticoids continued post-op • Increased frequency of thromboembolic phenomena (DVT 11%, PE 2-3%) • Anesthetic management should take into account for effects of excess cortisol secretion on BP, blood glucose, and electrolytes.

37. Hyperaldosteronism • Primary hyperaldosteronism (Conn’s syndrome) is excess secretion of aldosterone from a functional tumor independent of physiologic stimulus • Secondary hyperaldosteronism is when increased renin secretion is responsible for excess secretion of aldosterone

38. Clinical Manifestations • Hyperaldosteronism should be suspected if diastolic hypertension (100-125 mmHg) and plasma potassium < 3.5 mEq/L • HTN due to aldosterone-induced sodium retention and leads to increased extracellular fluid volume • Hypokalemic metabolic alkalosis due to aldosterone-induced renal excretion of potassium and hydrogen • Skeletal muscle weakness (due to hypokalemia) • Hypokalemic nephropathy polyuria and inability to optimally concentrate urine

39. Diagnosis • Confirmed by increased plasma concentration of aldosterone and increased urinary potassium excretion (greater than 30 mEq/L) despite coexisting hypokalemia • Measurement of plasma renin activity permits classification of the disease as primary (low renin activity) or secondary (increase renin activity)

40. Treatment • Supplemental potassium • Administration of aldosterone antagonist (spironolactone) • Antihypertensives • Diuresis with potassium-sparing diuretic (triamterene) to minimize drug induced hypokalemia • Surgical excision is definitive treatment for aldosterone-secreting tumor

41. Anesthetic Considerations • Pre-op correction of hypokalemia and treatment of hypertension • Assess for hypovolemia as evidence by orthostatic hypotension • Consider invasive monitoring (CVP, PAC) • Consider supplementation with exogenous cortisol

42. Hypoaldosteronism • Is suggested by hyperkalemia in the absence of renal insufficiency • Can be caused by: • a congenital deficiency of aldosterone synthetase or hyporeninemia from a defect in juxtaglomerular apparatus • Treatment with ACE inhibitor leading to a loss of angiotensin stimulation • Hyporeninemic hypoaldosteronism typically occurs in patients >45 with chronic renal disease, DM, or both. • Indomethacin-induced prostaglandin deficiency is a reversible cause of this syndrome.

43. Clinical Manifestations • Heart block due to hyperkalemia • Postural hypotension with or without hyponateremia • Hyperchloremic metabolic acidosis

44. Treatment • Liberal sodium intake • Daily administration of hydrocortisone

45. Anesthetic Considerations • Pre-op check of serum potassium level (should be less than 5.5 mEq/L for elective surgery) • EKG to check for effects of hyperkalemia (tall T waves, heart block) • Avoid hypoventilation to prevent further increase in serum potassium • Avoid succinylcholine • IVF without potassium • Hypovolemia corrected with fluid replacement possibly with help of CVP

46. Diabetes Mellitus • A complex metabolic derangement caused by relative or absolute insulin deficiency • Affect 17 million in US (6% of population) • Rise attributed to overweight population, sedentary life-styles, and rise in number of elderly people

47. Insulin-dependent DM (IDDM or type 1 DM) • Typically develops before age 16 • From autoimmune destruction of pancreatic beta cells, may be precipitated by a viral infection • 15% have other autoimmune diseases • Depend on exogenous insulin to prevent ketoacidosis • Non-insulin-dependent DM (NIDDM, adult onset DM, or type 2 DM) • Often develops after age 35 • Prevalence increase with age among black women • Many may require insulin therapy, but not prone to ketoacidosis • Patients are typically overweight (90%)

48. Complications of DM • Ketoacidosis: a serious acute metabolic complications defined as hyperglycemia in the presence of metabolic acidosis: • Nausea, vomiting, lethargy, signs of hypovolemia with dehydration d/t osmotic effect of glucose • Causes: • Poor compliance with insulin therapy, insulin resistance d/t infection, silent MI, beta 2 agonist to inhibit labor

49. Complication of DM • NIDDM: macroangiopathies such as CAD, cerebrovascular disease, PVD with sequelae of premature MI, angina pectoris or peripheral vascular insufficiency • IDDM: microvascular complications and disorders of the nervous system such as retinopathy, nephropathy, autonomic and peripheral nervous system dysfunction • May also have: • Arterial disease • Cataracts • Peripheral neuropathies • Arterial thrombotic lesions • Delayed wound healing • Stiff joint syndrome (affecting laryngoscopy)