Introduction to Endocrine Megan Conner, CRNA, MSN

Introduction to

EndocrineMegan Conner, CRNA,

MSN

Outline• Acromegaly• Diabetes Insipidus• SIADH • Addison’s Disease• Cushing’s Disease• Hyperaldosteronism• Hypoaldosteronism

• Diabetes Mellitus• Hyperparathyroidism• Hypoparathyroidism• Hyperthyroidism• Hypothyroidsim• Pheochromocytoma

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.

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)

– 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%)

Clinical Manifestations

• From expanding tumor include: headaches (55%), papilledema, visual field defects(19%)

• Compression or destruction of normal pituitary tissue may lead to panhypopituitarisms

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

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

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


• 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

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

• 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

Transsphenoidal hypophysectomy

Diabetes Insipidus (DI)• Reflexes the absence of antidiuretic hormone

(ADH) from one of two pathologies:

1) Destruction of posterior pituitary (neurogenic DI)

• Intracranial trauma• Hypophysectomy• Neoplastic invasion• Sarcoidosis

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


• 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

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.


• Monitoring of urine output and plasma electrolyte concentrations

• In emergency surgery, CVP monitoring may aid in evaluation of volume status

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

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)


• 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

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.

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.


• 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

Cushing’s

Disease

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

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

• 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

• 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

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

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)

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


• Mineralocorticoid effects include:

• Fluid retention

• Hypokalemic alkalosis

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.


• 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


• 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.

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


• 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

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)

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


• 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

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.


• Heart block due to hyperkalemia

• Postural hypotension with or without hyponateremia

• Hyperchloremic metabolic acidosis

Treatment• Liberal sodium intake

• Daily administration of hydrocortisone


• 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

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

• 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%)

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

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)

Treatment• Diet

• Oral hypoglycemic drugs

• Exogenous insulin

• For NIDDM: treatment or avoidance of obesity

• Transplantation of pancreatic tissue


• DM patients have a higher morbidity and mortality in perioperative period due to organ damage a/w with long-term disease

• Ischemic heart disease is the most common cause of perioperative mortality

• Schedule DM patients early in the day

• Careful pre-op assessment:– HTN, CAD, ANS dysfunction result in a labile

cardiovascular course– Assess cardiovascular and volume status– EKG

• Autonomic dysfunction – Delayed gastric emptying (gastroparesis) 20-30%– Prone to N/V, aspiration, abdominal distension– Consider treatment with H2 blockers, reglan,

preinduction antacids, ETT over LMA for GA– May have impaired respiratory response to hypoxia– Sensitive to respiratory depressant effects of

sedatives and anesthetic and require vigilance in perioperative period

• Restrict joint mobility: limited motion of atlanto-occipital joint difficult intubation– Prayer sign: inability to approximate palms of hands

and fingers

Prayer sign

• Check for kidney disease (urinalysis, serum creatinine, BUN) and results may affect anesthetic drug selection

• Pre-op blood glucose, and possible A1C• Check electrolytes• Sustain hyperglycemia with osmotic diuresis

may indicated fluid deficits and electrolyte depletion

• Adequate hydration and good urine output maintained

• Avoided lactate-containing solution d/t lactate conversion to glucose and contribute to hyperglycemia

• Assess oral hypoglycemia and insulin regimens

Oral hypoglycemic agents1. Sulfonylureas:

• Increase secretion of insulin from the pancreas and improve tissue sensitivity to insulin

• Require functioning beta cells so not for IDDM patients• SE: hypoglycemia, cholestatic jaundice, rashes, GI symptoms• Chlorpropamide SE include: SIADH and hyponatremia

2. Alpha glycosidase inhibitors (Acarbose and Miglitol):• Blocks intestinal enzymes that digest starches into absorbable

monosaccharides resulting in slower and lower rise in plasma glucose3. Thiazolidinediones (Rosiglitazone and Pioglitazone):

• Decrease hepatic glucose output and reduce insulin resistance in the patient with NIDDM by sensitizing the insulin receptor for glucose uptake

• Liver enzymes must be monitored closely4. Biguanides (Metformin):

• Decreases hepatic glucose production and increases peripheral insulin sensitivity

• Lactic acidosis is a potentially fatal problem, it is precipitated by drug accumulation so mild renal impairment is a contraindication

5. Nonsulfonylurea secretagogues (meglitinides and D-phenylalanine):• Increase insulin production by pancreatic beta cells similar to sulfonylureas• Must be taken before each meal, and if a meal is missed the drug should be

omitted

Insulin Preparations• Differ in onset and duration after SQ administration, can

use implantable pumps or syringes• Greatest risk is hypoglycemia• Three classes: short-acting, intermediate-acting, and

long-acting• Imperative know the patient’s normal insulin dosage

regimen and treatment compliance• Most diabetics are on a regimen that consists of both

rapid and intermediate acting insulin taken before breakfast and at evening meal

• Long-acting is discouraged in the perioperative period• Lantus:

– a recombinant DNA analogue of human insulin, and taken once a day

– Forms micro-precipitates in SQ tissue that delays its absorption and prolongs its effect

– Has no peak effect, but behaves like an insulin infusion

Characteristics of Insulin Preparations

Type of Insulin Onset of Action

Peak Action

Duration Route

Short-actingRegular

Rapid-acting

Aspart (Novolog)

Lispro (Humalog)

30-60 min

10-30 min

10-30 min

1-2 hr

30-60 min

30-60 min

5-12 hr

3-5 hr

3-5 hr

IV, SC, IM

SC

SC

Intermediate-actingNPH/ Lente 1-2 hr 4-8 hr 10-20 hr SC

Long-actingUltralente

Glargine

2-4 hr

1-2 hr

8-20 hr

No peak

16-24 hr

24 hr

SC

SC

Time course is based on SC administration.

Intraoperative Management

• Surgery produces a catabolic stress response and elevates stress-induced counter-regulatory hormones.

• Hyperglycemic, ketogenic, lipolytic effects of counter-regulatory hormones in the diabetic patient compound the state of insulin deficiency.

• Therefore, hyperglycemia is common in the surgical period.

• Regional and general anesthesia have been used safely. However, general anesthesia has been shown to induce hormonal changes that accentuate glycogenolysis and gluconeogenesis hyperglycemia.

Anesthetic Considerations• Careful positioning and padding in the diabetic patient d/t

decreased tissue perfusion and peripheral sympathetic neuropathy skin breakdown and ulceration

• Checking glucose is central to safe practice: pre-op, post-op, and intra-op for long procedures

• Hyperglycemia: impair wound healing, impair wound strength, increased with risk of infection, worsens neurologic outcome after ischemic brain injury

• Goal to avoid hypoglycemia and metabolic derangements

• Patients under GA usually maintain with mild transient hyperglycemia to avoid catastrophic effects of hypoglycemia

• There is a debate over tight versus non-tight blood glucose control

Non-Tight Control• Less intensive control, but avoids marked

hyperglycemia and dangerous hypoglycemia• This is the traditional approach for stable

diabetic patient undergoing elective operations• Technique:

– DOS fasting blood glucose level measured– IV infusion 5% Dextrose at 125ml/ 70 kg body weight– After infusion started, 30-50% of patient’s normal

intermediate insulin (NPH or Lente) is administered– Glucose containing infusion continued throughout

surgery. Additional fluid requirement with administration of second glucose-free solution

– Glucose checked every 1-2 hours during surgery– If glucose >200, treated with a IV bolus of regular

insulin

• On average, 1 unit of regular insulin can be expected to decrease blood glucose level 50 mg/dL

• Advantages: easy to implement, successful in preventing significant hypoglycemia and other metabolic extremes, diabetic ketoacidosis, and hyperosmolar states

• Absorption of SQ insulin is unpredictable and erratic d/t BP, blood flow, and temperature variations that occur with anesthesia

• Onset and peak of pre-op intermediate-acting insulin may not correspond with time of surgical stress, especially if there is a delay in surgery

• Half life of regular insulin is short and a roller coaster profile may develop

Tight control• Maintains blood glucose within narrow range of 100-180

mg/dL• Require infusion pumps and more frequent blood

glucose checks• Recommended for IDDM patient having major surgery

and for patient with poorly controlled NIDDM• Technique:

– Infusion of 5% dextrose with 0.32 units regular insulin/g of dextrose (16 units/L), with 20 mEq KCL at 100 ml/hr

– Infusion started when glucose >200– Glucose checked every hour, and potassium checked after first

hour– If patient has higher insulin needs, an additional 1-2 units of

insulin can be added to bag– Additional fluid requirement with administration of second

glucose-free solution

• Blood glucose levels less than 80 mg/dL treated with D50W, and rechecked in 30 minutes

• 70 kg patient, 15 ml of D50W expected to raise blood glucose concentration by about 30 mg/dL

• Higher insulin infusion requirement are usually required in renal transplantation, CABG, obese patients, septic patients, and those on steroid therapy

• Advantages of tight control: insulin infusion can be finely regulated on a hourly basis, periods of hyperglycemia are less likely, deleterious effect of hyperglycemia may be prevented, continued until the patient is ready to eat and SQ insulin or oral agent can be restarted

NIDDM and Oral Hypoglycemic

Agents• Note duration of action for oral agents• Discontinuing long-acting agents 2 to 3 days before

surgery and converting to shorter-acting agents or insulin affords better perioperative glucose control

• Metformin should be discontinued 2 days before surgery d/t surgical risks of hypotension and renal hypoperfusion place patients at risk for lactic acidosis

• For well-controlled NIDDM patient in for minor to moderate surgery may continued until the evening of surgery

• Regardless of the technique, glucose measured frequently and hyperglycemia treated

Hyperparathyroidism

• Increased parathormone• Serum calcium may be

increased, decreased, or unchanged

• Classified as primary, secondary, or ectopic

• Can result from parathyroid adenoma, gland hyperplasia, or parathyroid cancer

• Primary hyperparathyroidism– Excessive secretion of parathormone by a benign

parathyroid adenoma– Carcinoma of a parathyroid gland– Hyperplasia of parathyroid glands

• Secondary hyperparathyroidism – Compensatory response of parathyroid glands to

secrete more parathormone to counteract a disease process that produces hypocalcemia

• Ectopic hyperparathyroidism– Secretion of parathormone by tissues other than the

parathyroid glands (occurs with carcinomas of the lung, breast, pancreas, kidney, and lymphoproliferative diseases)


• Overactivity leads to high serum calcium– Usually asymptomatic until level more than 11-12 mg/dL– Greater than 14 mg/dL is life-threatening and demands

immediate treatment– Patients with carcinomas usually have increased levels greater

than 7.5 mEq/L

• Clinical signs and symptoms of hypercalcemia– Early: N/V, skeletal muscle weakness, hypotonia– Inability to concentrate urine, polyuria– Oliguric renal failure can occur in advanced cases– Renal stones, peptic ulcer disease, HTN, bone pain, pathologic

fractures hallucinations, mood disturbances, and acute or chronic pancreatitis

“Stones, Bones, & Groans”

• Stones– Nephrolithiasis, nephrocalcinosis, polyuria

• Bones– Osteoclastic absorption of bone overwhelms osteoblastic

deposition– Weakened bones filled with decalcified cavities painful and

susceptible to fracture– Destructive bone disease a/w hyperparathyroidism is osteitis

fibrosa cystica– Despite increased mobilization of phosphorus from bone, serum

phosphate concentration remains normal to low d/t increased urinary excretion

• Groans– Pancreatitis– Peptic ulcer disease

• HTN

• Heart: shortened ventricular refractory period, bradyarrhythmias, BBB, heart block

• Other features: muscle weakness, anorexia, confusion, N/V, lethargy

• Patients with CRF or gastrointestinal malabsorption, may develop compensatory parathyroid gland hyperplasia or secondary hyperparathyroidism in response to hypocalcemia

• Clinical course still includes skeletal symptoms in primary disorder, but is seldom a/w hypercalcemia

Treatment• Saline infusion (150 ml/hr)• Loop diuretics (lasix 40-80 mg IV Q2-4hrs)• Thiazide diuretics not used, because enhance renal

tubular reabsorption of Ca• Bisphosphonates (disodium etidronate) is the drug of

choice in life-threatening hypercalcemia. These drugs bind to hydroxyapatite in bone and act as potent inhibitors of osteoclastic bone resorption.

• Hemodialysis• Calcitonin (inhibits of osteoclastic bone resorption)• Surgical removal is treatment in symptomatic primary

hyperparathyroidism.


• Done under GA• Cervical plexus block has been used, especially

in elderly and medically compromised patients• Parathyroid tissue can be in ectopic places

(mediastinum, carotid sheath, or thymus gland)• Minimal EBL• Monitor serum Ca, Mg, and Phos post-op• Ca usually returns to normal in 3-4 days


• Treat of hypercalcemia pre-op (saline hydration, lasix, inhibitors of osteoclastic bone resorption)

• Dehydrated d/t anorexia, vomiting, impaired ability of kidneys to concentrate urine– Hydration with non-calcium containing solutions to

dilute serum Ca, maintain adequate GFR and Ca clearance, and to ensure adequate intravascular volume

– Foley, CVP, frequent assessment of serum electrolytes

• Elevated Ca depresses central and peripheral nervous systems.

• Avoid pre-op sedatives if patient appears lethargic or confused.

• May have decrease GA requirements.• EKG changes with hypercalcemia: shortened QT interval and

prolonged PR interval.• Dysrhythmias and HTN may respond to Ca channel blockers

(verapamil 5-10mg IV).• Due to significant bone disease, patients are susceptible to

fractures and requires careful padding and positioning.• Muscle weakness, hypotonia, and muscle atrophy increase

sensitivity to NDMR. Titrate MR with PNS.• Prophylactic antiemetics, because these patients are prone to

N/V.• With secondary hyperparathyroidism, assess renal status,

and associated complication of CRI (volume overload, anemia, abnormal electrolytes).

• Alkalosis protects against hypercalcemia by shifting the ionized calcium to the protein-bound form.

Hypoparathyroidism• The deficient or absent secretion of parathyroid

hormone or a peripheral resistance to its effect• Pseudohypoparathyroidism: a congenital

disorder in which the release of parathormone is intact but kidneys are unable to respond to the hormone

• Causes: inadvertent removal of parathyroid tissue, irradiation, autoimmune destruction, chronic severe Mg deficiency (alcohol abuse, poor nutrition, malabsorption)


• Low serum Ca• Elevated Phos d/t decreased renal excretion of

phosphate• Clinical signs correlate with degree of hypocalcemia and

rate of calcium decline (sudden drop = more severe symptoms)

• Cardinal features: neuromuscular excitability, muscle spasms, hypocalcemic tetany– Muscle cramps, perioral paresthesias, numbness in feet and

toes, hyperactive deep tendon reflexes– Feeling of restlessness or hyperirritable– Life threatening laryngospasm can occur stridor, labored

respirations, asphyxia


• Classic manifestations of hypocalcemic tetany:– Chvostek’s sign: contracture or twitching of ipsilateral

facial muscles when the facial nerve is tapped at the jaw ankle

– Trousseau’s sign: elicited by inflations of BP cuff slightly above systolic level. Ischemia aggravates muscle irritability in presence of decreased Ca and caused flexion of wrist and thumb with extension of fingers (carpopedal spasm)

Treatment• IV infusion of calcium (calcium gluconate)

until signs of neuromuscular irritability disappear

• Correct any coexisting respiratory or metabolic alkalosis

• Asymptomatic hypocalcemia corrected with oral Ca and vitamin D

• Thiazide diuretics

• Causes:– Transient post-op hypocalcemia result from

parathyroid gland suppression (by pre-op hypercalemia)

– Rapid bone uptake of calcium (“hungry bone syndrome”)

– Inadvertent removal of all parathyroid gland tissue


• Goal to prevent further decrease in serum calcium concentrations and treat adverse effects of hypocalcemia– Avoid hyperventilation– Watch for musculoskeletal irritability (seen at serum Ca

6-7mg/dL)– May have altered response to MR– Periodic measurement of serum Ca and iCa– Risk of laryngeal muscle spasm that may cause life-threatening

airway compromise– EKG changes: prolonged QT interval reflecting delayed

ventricular repolarization and a predisposition to ventricular dysrhythmias

– Decreased cardiac contractility– Hypotension– Vigorous diuretics can augment Ca loss

• Respiratory stress following parathyroid surgery may be d/t laryngeal muscle spasm, edema, bleeding in the neck or bilateral recurrent laryngeal nerve injury– Unilateral RLN injury produces hoarseness

usually requires observations– Bilateral RLN injury cause aphonia and

requires immediate airway support and intubation

• Circulating levels of ionized calcium can decline in perioperative period:– Increases in circulating anions (bicarb, phos, citrate)

lower iCa and result in tetany, so avoid:• Hyperventilation• Rapid transfusion of citrated blood• Rapid administration of bicarb

• Initial treatment: 100-200 mg of elemental Ca over 10 minutes

• For maintenance: 1-2 mg/kg/hr of elemental Ca diluted in 50-100 ml of saline

• Continue monitoring electrolytes during replacement: Ca, Mg, Phos, K, and creatinine

Hyperthyroidism• Increased in thyroid function d/t and excess

supply of thyroid hormones, and associated with:– Grave’s Disease– TSH overproduction– Pregnancy– Subacute thyroiditis (excess hormone leaks out d/t

inflammation)– Ovarian tumors and metastatic thyroid carcinoma can

produce extrathyroid hormone– Exogenous consumption of thyroid hormone

Etiology• TSH released from anterior pituitary • Iodine taken up into thyroid gland • Iodine incorporate into tyrosine residue • Hormones triiodothyronine (T3) and thyroxine

(T4) are formed and stored– Peripheral tissues convert T4 to T3

• T3 is three times more potent than T4, and has a shorter half life

• Both T3 and T4 are partially bound to plasma protein thyroid-binding globulin (TBG); only unbound forms are pharmacologically active

• TBG levels can increase with:– Acute liver disease– Pregnancy– Acute intermittent porphyria– Medications (oral hyoglycemics, exogenous

estrogens, clofibrate, opiods)• TBG levels can decrease with:

– Chronic liver disease– Nephrotic syndrome– Anabolic steroids– Acromegaly

• TBG has no direct role in cell metabolism, but its concentration can alter diagnostic tests for thyroid disease


• Lab findings:– Elevated T3 and T4– TSH may be normal or decreased

• Nervousness• Tachycardia• Goiter• Tremors• Muscle weakness• Heat Intolerance• Weight loss despite high caloric intake• Exophthalmos • Cardiac: worsening angina, unexpected onset of CHF, or Afib may

indicate hyperthyroidism, especially in elderly d/t increase hormones aggravate underlying heart disease


• Thyroid storm (thyroidtoxicosis): an abrupt exacerbation of hyperthyroidism caused by a sudden excessive release of thyroid gland hormones into circulation

• Hyperthermia, tachycardia, CHF, dehydration, and shock commonly occur

• Precipitated by surgical stress, but usually seen 6-18 hrs post-op

• Mimics MH, sepsis, hemorrhage, or transfusion or drug reaction

Treatment• Treatment of hyperthyroidism: antithyroid drugs,

subtotal thyroidectomy, or radioactive iodine• Treatment of thyroid storm (thyrotoxicosis):

active cooling, hydration, Beta blockade, steroids if indication of adrenal insufficiency, and initiation of long term therapy

• Six weeks are required to become euthyroid


• Premed: consider Beta blockers• Avoid sympathetic stimulation • Eyes protected if exophthalmos• Drug metabolism and anesthetic requirements

increased• Titrate MR with PNS, d/t presence of muscle

weakness• Treat hypotension with direct-acting agents• Regional anesthesia may be beneficial, b/c

blocks sympathetic response• Local anesthetics with epi may lead to

arrhythmias

Hypothyroidism• Primary: destruction of the thyroid gland and

there is an adequate level of TSH– Chronic thyroiditis– Subtotal thyroidectomy– Radioactive iodine therapy– Irradiation of neck

• Secondary: d/t CNS dysfunction and results in decreased TSH– Hypothalamic dysfunction (leading to a

thyrotropin-releasing deficiency– Anterior pituitary dysfunction (TSH deficiency)


• Primary: decreased T3 and T4, increased TSH

• Secondary: decreased T3,T4, TSH

• Resin T3 uptake decreased in both

• Lethargy• Constipation• Cold intolerance• Facial edema with enlarged tongue• Reversible cardiomyopathy • Pericardial effusion • Dilutional hyponatremia• Ascites • Anemia• Adynamic ileus with delayed gastric empting• Adrenal atrophy with decrease cortisol production • Decreased water excretion• Decreased cardiac output• Bradycardia• Hypovolemia• Diminished baroreceptors reflexes• Myexdema coma (profound hypothyroidism)


• Treatment requires exogenous supplementation• T4 requires 10 days to have an effect and T3 begins to

have an effect in 6 hours• Treatment of myxedema coma: IV administration of T3,

and if adrenal insufficiency suspected, cortisol• Digitalis should be used sparingly to treat CHF, b/c it is

not well tolerated by patients with hypothyroidism• Careful fluid replacement is important, but these patient

may be vulnerable to water intoxications and hyponatremia

• If emergency surgery is necessary:– Avoidance of pre-op sedation d/t profound

CNS and respiratory sensitivity to depression– Cortisol supplementation considered– Intravascular volume optimized– Anemia corrected– Airway problems r/t to large tongue– Poor gastric empting– Increased sensitivity to all depressants

medications

Pheochromocytoma• Catecholamine-secreting tumors derived most

commonly (90%) form adrenomedullary chromaffin cells

• Extraadrenal pheochromocytomas have been found anywhere from the pelvis to the skull bases

• They are most often extraadrenal and secrete dopamine

• Malignant pheochromocytomas usually spread through venous lymphatic channels to the liver

Etiology• Rare, occur less than 0.5% of

hypertensive patients

• Usually occurs in 3rd to 5th decade

• Maybe associated with neurocutaneous syndromes (von Hippel-Lindau teberous sclerosis, Sturge-Weber syndrome, multiple endocrine neoplasia (MEN) type 2A or 2B)

• Pheochromocytomas produce, store, and secrete catecholamines (mostly Norepi and epi)


• Diagnosis is made by a 24 hour urine test to measure “free” norepinephrine

• Normotension despite increase plasma concentration of catecholamines is thought to reflect a down regulation of alpha receptors

• Clonidine suppresses hypertension from neurogenic release but not from a pheochromocytoma

• CT to localize and diagnosis pheochromocytoma

• Hypertension• Diaphoresis*• Tachycardia*• Headache*• Tremulousness• Palpitations• Weight loss• Sense of doom• Anxiety• Pallor• Orthostatic hypotension• Hct >45

• Paroxysm can be triggered by:– Acute physical stress– Abdominal palpitation– Defecation– Hypotension– Activations of sympathetic NS– Micturition (if in urinary bladder)

• Not usually triggered by mental or psychological stress

• Symptoms usually reflect predominance of alpha adrenergic activity over beta adrenergic effects– Alpha adrenergic inhibition of insulin, mild

hyperglycemia– Increased cardiac output and heart rate– Increased metabolism– Increased oxygen consumption– Hyperthermia– Vasoconstriction in extremities may produce pain,

paresthesias, intermittent claudication or ischemia

• Hypertension is most common symptom (90%), and paroxysmal hypertension (40-50%)

• Sustained HTN resistant to conventional treatment

• If pheochromocytoma are predominately epi secreting, HTN can alternate with periods of hypotension a/w syncope

• Coronary artery spasm can to MI or CHF• EKG changes• Death d/t CHF, MI, or intracerebral hemorrhage

Treatment• Surgical excision of tumor after medical

control is optimized– Alpha blockade to normalize BP – Normotension facilitates and increase in

intravascular fluid volume decreased hematocrit

– If cardiac arrhythmias or tachycardia persist after alpha blockade, then beta blockade is indicated in the absence of CHF

• Pre-op aims at reversed effect of excessive adrenergic stimulation. – Antihypertensive therapy

• Alpha adrenergic antagonist or calcium channel blockers

– Volume replacement

• End points for patients awaiting surgery:– BP should not be >165/90– BP on standing should not be lower than 80/45– ECG with no ST segment or T-wave abnormality that

can not be attributed to a permanent defect– No symptoms of catecholamine excess– No more than one PVC every 5 minutes


• Select drugs that do not stimulate catecholamine release

• Avoiding sympathetic nervous system activation

• Implement monitor techniques that facilitate early and appropriate intervention when catecholamine-induced changes in cardiovascular function occur

• Done with an open laparotomy• Avoid:

– Dopamine antagonist– Contrast media– Indirect-acting agents– Drugs that block neuronal catecholamine reuptake– Histamine– Glucagon– Pancuronium – Hypoxia and hypercapnia– Succinycholine d/t increased intra-abdominal

pressure with fasciculation

• Pre-op sedation to decrease anxiety and prevent activation of SNS (Benzos)

• Avoid pre-op atropine or robinul lead to tachydysrhythmias

• Large bore IVs, PAC, CVP, and A-line to help with fluid management, intervention with inotrope or vasodilating drugs, ABGs, frequent labs

• Keep rate of fluid replacement with rate of loss

3 Critical Junctures1- Induction and intubation

– Barbiturates, benzos, or propofol, mask with volatile agent or N2O, lidocaine, fentanyl or sufentanil

– SNP and phentolamine readily available to treat HTN

– Select anesthetic agent based on ability to decrease SNS activity and low likelihood of sensitizing the myocardium to dysrhythmic effects of catecholamines

3 Critical Junctures2 - Manipulation of tumor HTN and

dysrhythmias– SNP*, phentolamine*, increased anesthetic agent,

propranolol, lidocaine, labetalol, esmolol*– Use beta blockers cautiously b/c accentuate left

ventricular dysfunction in patient with cardiomyopathy– Correct hypotension with neo or norepi, avoid indirect-

acting sympathomimetics b/c these are unpredictable– Magnesium Sulfate may be useful: inhibits

catecholamine release from adrenal medulla and peripheral adrenergic nerve terminals, decrease sensitivity of alpha adrenergic receptors to catecholamines, to exert a direct vasodilators effect

3 Critical Junctures3 - After ligation of tumor’s venous drainage

– Decreased catecholamines and the down regulation of adrenergic receptors decrease BP

– Decrease anesthetic level, increase IVF administration, neo or norepi for BP

– Hyperglycemia common before excision, and hypoglycemia after excision

• Beta blockade impairs hepatic glucose production and glucagon secretion mechanism

• Beta blockade may also mask hypoglycemic signs by preventing tachycardia and tremor

• Check glucose frequently

• Pheochromocytoma may present as a hypermetabolic state and mimic light anesthesia, thyroid crisis, MH, or sepsis– HTN, tachycardia, hypertension, respiratory

acidosis

• Post Op– Fluid shifts, pain, hypoxia, hypercapnia,

autonomic instability, urinary retention, and residual tumor are all potential causes of post-op hypertension

– 50% of patients remain hypertensive– Post-op catecholamines levels decrease over

several days– Normal BP returns in about 10 days in 75% of

patients– Post op pain can be accomplished with

neuraxial opiods and help with early tracheal extubation

References• Clinical Anesthesia, 5th Edition by

Barash, Cullen, et al

• Anesthesiologist’s Manual of Surgical Procedures 3rd Edition by Jaffe

• Handbook of Nurse Anesthesia 3rd Edition by Nagelhout & Plaus

Documents

Introduction to Endocrine Megan Conner, CRNA, MSN