Endocrine Flashcards

Question

What Is the Significance of a Long QT Interval in a Patient with Hyperthyroidism?

Answer 1

○ Hyperthyroidism is associated with cardiac complications. - Atrial fibrillation is the most common cardiac abnormality occurring in approximately 10–25% of hyperthyroid patients [2]. - The QT interval represents the time for ventricular depolarization and repolarization. It is dependent on heart rate, i.e., a faster heart rate leads to a shorter QT interval. - Therefore, QTc estimates the QT interval corrected for a heart rate of 60 bpm. A prolonged QT interval places the patient at increased risk for tachyarrhythmias, e.g., torsades de pointes and ventricular fibrillation. - The correlation between hyperthyroidism and prolonged QT interval has been previously noted [3]. - Indeed, there is an association between levels of T4 and QTc [3]. - The etiology is not precisely known but may be related to the effect of thyroid hormone on the cardiac myocyte. - The QTc frequently reverts to a normal range once the patient becomes biochemically euthyroid [4].

Answer 2

Hyperthyroidism is associated with changes in cardiac out- put, blood pressure, and systemic and pulmonary vascular resistance. Most patients with pulmonary hypertension and thyroid disease are older with toxic multinodular goiter. Again, the etiology is not entirely known (see relationship between thyroid and cardiovascular disease in the following question). There may be a direct effect of thyroid hormone on pulmonary vasculature. Patients with hyperthyroidism should be considered at risk for pulmonary hypertension. Patients with newly diagnosed pulmonary hypertension should be investigated for thyroid disease, as it may be a reversible cause of pulmonary hypertension.

Answer 3

1. Thyroid Storm This is a rare and life-threatening exacerbation of hyperthyroidism brought on by acute illness, trauma, and thyroid or non-thyroid surgery. Discontinuation of, or poor compliance with, antithyroid medication is a risk factor. Thyroid storm can be diagnosed clinically by severe tachycardia, hypotension, cardiac failure, and hyperpyrexia in the patient under anesthesia. Delirium, extreme anxiety, and altered consciousness progressing to coma can be seen in the awake patient. 2. Cardiovascular Changes Arrhythmias, most frequently sinus tachycardia or atrial fibrillation, systemic and pulmonary hypertension, coronary ischemia, and heart failure can be seen with suboptimal disease control. The extent of involvement of the adrenergic system versus that of direct thyroid hormone stimulation and the interaction between these two systems is unknown. For instance, many of the adrenergic-like effects are mediated via T3 stimulation of cardiac myocytes. In addition, many components of the cardiac beta-adrenergic system are regulated by thyroid hormone. Treatment with beta-blockade improves most of the cardiovascular concerns associated with hyper- thyroidism. Of note, treatment of tachyarrhythmia in the thyrotoxic cardiac patient with beta-blockade is the first- line therapy. In the patient with overt cardiac failure, a cautious trial of short-acting beta-blockade (e.g., esmolol) may be used [5]. 3. Airway Complications In addition to concerns regarding intubation at induc- tion of anesthesia as outlined below, the thyroidectomy patient can develop a number of postoperative airway complications. Airway obstruction may occur secondary to hematoma, tracheomalacia, recurrent laryngeal nerve damage, or hypocalcemic laryngeal tetany [6]. Unilateral recurrent laryngeal nerve damage may result in hoarseness or may be asymptomatic. Bilateral recurrent laryngeal nerve damage can result in aspiration pneumonia or com- plete airway occlusion requiring immediate intubation [7].

Answer 4

A wide spectrum of symptoms is seen, depending on circu- lating levels of T3 and T4. These are outlined by system in Table 18.2. Of particular relevance to the anesthesiologist are symptoms that may indicate a difficult intubation. A goiter causing tracheal compression, retrosternal goiter, or cancer- ous goiter may indicate tracheal obstruction and warrant CT investigation of the size of the mass, its precise location, and the degree of tracheal compression. Positional dyspnea has been reported by 75% of patients with a retrosternal goiter [8]. Dysphagia has been reported as the second most com- mon symptom (43% patients with retrosternal goiter) [9]

Answer 5

○ A thorough airway examination is imperative. Most patients with a large goiter, whether retrosternal or causing tracheal deviation, can be intubated with direct laryngoscopy. ○ An observational study of over 300 patients having thyroid surgery reported that the classic predictive criteria for difficult intubation – small mouth opening, short neck, Mallampati class 3 or 4, reduced neck mobility, and short thyromental distance – were reliable predictors of difficult intubation in patients having thyroid surgery. - A large palpable goiter, mediastinal extension, tracheal compression or deviation, and malignancy were not associated with difficult intubation [10]. - Regardless, for the authors there are two principal causes for concern that reduce our threshold for awake fiber-optic intubation: (1) malignancy leading to fibrosis and associated immobile larynx and (2) severe tracheal compression. Retrosternal goiter may be diagnosed clinically by detection of caudal extension of the goiter below the sternal notch. - Superior vena cava syndrome has been reported in 5–9% of patients with retrosternal goiter [11]. Pemberton’s sign will confirm this diagnosis, i.e., with arms raised for 1–2 minutes, a large goiter will inhibit venous return, causing venous engorge-ment, facial edema, cyanosis, and respiratory distress.

Answer 6

• Free T3 and T4 (free hormone is the best indicator of thyroid status) • TSH • TSH receptor antibody • Radioactive iodine uptake • Ultrasound • CT

Answer 7

Two categories of drug are used: (1) those that inhibit thyroid hormone synthesis and (2) those that inhibit the adrenergic-like effects of excess thyroid hormone. ○ Thyroid hormone synthesis is reviewed in Fig. 18.4. ○ Dietary iodide compounds are trapped in the thyroid epithelial follicular cells and oxidized to iodinium ions (I+) by thyroid peroxidase. TSH from the anterior pituitary stimulates synthesis of the Na/I transporter, thyroid peroxidase, and thyroglobulin. Thyroglobulin (specifically its tyrosine amino acid) stored in thyroid colloid is iodinated in a process known as organification to monoiodotyrosine (MIT) and diiodotyrosine (DIT). These molecules are then conjugated (again by thyroid peroxidase) to form triiodothyronine (T3) and tetraiodothyronine (T4). The final steps in the process are proteolysis of thyroglobulin and release of T3 and T4. The ratio of T4:T3 release to plasma is approximately 3:1. T4 is subsequently metabolized to T3 by deiodination in the liver and kidney. T3 is 3–5 times more active than T4 and is responsible for most activity attributed to thyroid hormone. ○ Thionamides Methimazole and propylthiouracil inhibit thyroid hormone synthesis at the organification and conjugation steps. As stores of thyroid hormone can last for months, clinical effects of propylthiouracil and methimazole may not be seen for up to 2 months. Methimazole is the first line of therapy. It is faster acting (though still expected to take between 3 and 8 weeks to be effective), has less potential for hepatotoxicity, and has a longer half-life that facilitates once-daily dosing [12]. Adverse effects associ- ated with thionamide use include rash, hepatotoxicity, and agranulocytosis [13]. Iodine (e.g., Lugol’s solution/potassium iodide) inhibits thyroid hormone secretion within hours of administration. It also inhibits thyroid hormone synthesis at the stage of organification/iodination of thyroglobulin tyrosine. Its effect is maximal at 10–20 days but can be short lived. Its use is recommended as an adjunct in the preoperative preparation of the patient with Graves’ disease or for the treatment of thyroid storm. Glucocorticoids inhibit the conversion of T4 to T3 and reduce thyroid hormone secretion. Beta-blockade is used for control of hyper-adrenergic symptoms. It is frequently started with methimazole to achieve a euthyroid state. The target is a heart rate of 90 bpm.

Answer 8

○ Whenever possible, the patient should be rendered clinically and biochemically euthyroid prior to surgery. This can take several months. TSH levels may remain suppressed, and this is not considered a contraindication to elective surgery. If a euthyroid state cannot be realized, heart rate is the most important factor to control with beta-blockade. There are three principal treatment options for hyperthyroidism – antithyroid drugs, radioactive iodine, and thyroidectomy [13]. Indications for surgery are local compressive symptoms, risk of malignancy, and hyper- thyroidism. Our patient had significant clinical and biochemical hyperthyroidism. She could not takemethimazole due to a hypersensitivity reaction – an urticarial rash with pruritis. Radioactive iodine ablation would have been a reasonable alternative for management of this patient’s hyperthyroidism, but when presented with treatment options, she decided to undergo thyroidectomy. The patient was informed of the risks associated with thyroid storm, and subsequent to this conversation, in consultation with an endocrinologist and the patient’s general surgeon, she was started on propylthiouracil. She tolerated this well, even though there is a risk of developing an adverse reaction with one thionamide if intolerant of the other. Surgery was deferred for 2 months until a state of biochemical and clinical euthyroidism was achieved.

Answer 9

Also known as Addison’s disease, primary adrenal insufficiency occurs when the adrenal gland cannot produce sufficient quantities of glucocorticoid and mineralocorticoid hormones

Answer 10

Secondary adrenal insufficiency develops from underpro- duction of adrenocorticotrophic hormone (ACTH) second- ary to pituitary disease or suppression of the hypothalamic-pituitary-adrenal axis (HPAA), rather than damage to the adrenal glands themselves. Insufficient pro- duction of corticotropin-releasing hormone (CRH) due to hypothalamic disease is often termed tertiary adrenal insuf- ficiency. Common causes include the use of prolonged ste- roid therapy (tertiary) and surgery or radiotherapy involving the pituitary (secondary). Due to preserved functional capac- ity of the adrenal cortex, specifically the ability to function as part of the renin-angiotensin system, secondary adrenal insufficiency produces an isolated glucocorticoid deficiency in contrast to primary disease where mineralocorticoid defi- ciency is also a feature. Adrenal insufficiency almost exclu- sively refers to adrenocortical insufficiency. Rare congenital absence of the adrenal cortex may cause a developmental absence of the adrenal medulla. This seldom produces a state of catecholamine deficiency as catecholamines are likely produced elsewhere in the autonomic nervous system, e.g., sympathetic neurons [4].

Answer 11

The adrenal gland consists of two distinct components, the outer cortex and the inner medulla. The adrenal cortex is responsible for the production of glucocorticoid, mineralocorticoid, and androgen hormones. CRH produced by the hypothalamus stimulates the anterior pituitary to synthesize ACTH (Fig. 19.2) [5, 6]. ACTH in turn regulates adrenocortical secretion of glucocorticoids. Aldosterone is the main mineralocorticoid secreted by the adrenal cortex in response to regulation by the renin-angiotensin system. The adrenal medulla is a component of the sympathetic nervous system and is responsible for synthesis of catecholamines, e.g., norepinephrine and epinephrine. It is of no significance in the context of adrenal insufficiency, which, as indicated above, may be more appropriately termed adrenocortical insufficiency

Answer 12

Ninety-five percent of the glucocorticoid hormone output of the adrenal gland is comprised of cortisol. Cortisol is admin- istered therapeutically as hydrocortisone. Corticosterone and cortisone account for the remainder

Answer 13

○ Cortisol is essential for carbohydrate, protein, and fatty acid metabolism, e.g., it is responsible for hepatic gluconeogenesis and antagonizes the actions of insulin, maintaining normal blood glucose concentrations during fasting [6]. ○ Through its actions on glomerular filtration and renal plasma flow, it regulates electrolyte and water homeostasis [7]. It also possesses weak mineralocorticoid activity in this regard. ○ Cortisol modulates the immune system—it is frequently used for the treatment of chronic inflammatory conditions such as rheumatoid arthritis. ○ It facilitates the conversion of norepinephrine to epinephrine in the adrenal medulla and maintains endothelial permeability

Answer 14

- Aldosterone causes sodium and water reabsorption and secretion of potassium ions in the distal renal tubule in response to activation of the renin-angiotensin system and to a lesser extent increased potassium concentration [2]. - Aldosterone also plays a significant role in the regulation of vascular tone

Answer 15

If adequate preoperative preparation has not been performed, an acute adrenal or Addisonian crisis can occur even in the presence of a minor stressor [2]. Surgery is one of the most potent activators of the HPAA. The degree of HPAA activation depends on the nature of the surgical procedure and the type of anesthesia, e.g., regional anesthesia or deep general anesthesia can blunt the stress response. ○ A standard surgical stress response sees ACTH secretion begin to increase at surgical incision and remain elevated for several days postoperatively [3]. ○ In the presence of primary adrenal insufficiency, the adrenal cortex cannot respond to ACTH stimulation, and cortisol secretion does not occur. ○ Patients may demonstrate the effects of long-term steroid use or overtreatment: • Cushingoid appearance and weight gain • Hypertension • Fluid retention • Premature atherosclerotic disease with associated risks of myocardial infarction, heart failure, and cerebrovascular disease • Hyperlipidemia • Arrhythmias (e.g., atrial fibrillation or flutter) [9] • Hyperglycemia • Immunosuppression and increased risk of infection ○ Other autoimmune conditions are frequently associated with autoimmune primary adrenal insufficiency, including hypothyroidism, hyperthyroidism, hypoparathyroidism, diabetes mellitus type 1, vitiligo, and pernicious anemia [1].

Answer 16

○ Acute adrenal crisis is cardiovascular shock due to acute stress (e.g., infection, trauma, surgery, pregnancy), to which the patient with adrenal insufficiency is incapable of mounting an appropriate response as a result of glucocorticoid or mineralocorticoid deficiency. ○ Acute adrenal crisis can occur in the patient receiving adequate glucocorticoid replacement therapy without adequate mineralocorticoid replacement. ○ Adrenal crisis occurs less frequently in the setting of secondary adrenal insufficiency as mineralocorticoid production is preserved, allowing for volume status to be maintained. ○ Clinical features of adrenal crisis are listed below. - Needless to say, some of these features are absent in the anesthetized patient: • Cardiovascular shock and hypotension that is refractory to vasopressor and fluid therapy • Hyponatremia • Hyperkalemia • Hypoglycemia • Abdominal, back, or flank pain • Nausea and/or vomiting • Confusion

Answer 17

All patients require glucocorticoid replacement therapy, and most will eventually require mineralocorticoid replacement. There is no commonly accepted approach to glucocorticoid replacement. The short-acting hydrocortisone and longer-acting prednisone are used in different scenarios and patients. Physician preference frequently appears to be of an empirical nature. Features common to all approaches to glucocorticoid replacement are recognition of the importance of mimicking the body’s daily fluctuation in cortisol levels and using the lowest possible dose to ameliorate the symptoms of deficiency. Hydrocortisone is typically used in two or three divided daily doses up to a total of 15–25 mg per day. Patients with compliance issues may benefit from once-daily dosing with prednisone 3–5 mg (Table 19.2) [5]. Aldosterone replacement therapy takes the form of fludrocortisone. The usual dose is 0.1 mg daily

Answer 18

○ Monitoring should be conducted for both overtreatment and undertreatment with glucocorticoids. ○ Clinical assessment for features of glucocorticoid deficiency (anorexia, weight loss, lethargy, hyperpigmentation) or the Cushingoid features of glucocorticoid excess are the most useful means of monitor ing treatment. ○ Plasma ACTH can be used as a biochemical index of treatment success; however, its use has been cautioned against, as it often remains elevated in patients treated with glucocorticoids despite adequate therapy, which can lead to overtreatment [10]. ○ Efficacy of mineralocorticoid replacement therapy can be monitored by assessing for salt craving, postural hypotension, edema, and electrolyte balance.

Answer 19

General measures that should be undertaken involve monitoring and treatment of hypovolemia, hyponatremia, and hyperkalemia.

Answer 20

○ Generally, 8–10 mg/day of cortisol is secreted by the adrenal gland. This will increase during periods of physical and psychological stress. ○ Surgical stress, both the physical and psychological components, increases cortisol output in the healthy individual. - The degree of increase varies with the surgical procedure. For minor procedures total cortisol output increases to approximately 50 mg daily. Major procedures are associated with a daily cortisol output of up to 150 mg daily

Answer 21

○ Patients with primary adrenal insufficiency must receive their baseline steroid therapy and supplemental stress dosing. Several approaches have been described. ○ The protocol advised by the Endocrine Society Clinical Practice Guideline meets our needs in most situation

Answer 22

○ Chronic steroid use is the most common cause of secondary adrenal insufficiency. ○ Low CRH and ACTH levels lead to atrophy of the adrenal cortex and a decrease in cortisol production (see Fig. 19.2). As the renin-angiotensin-aldosterone pathway is intact, there is no concomitant deficiency of aldosterone. ○ Full recovery of adrenal function after cessation of steroid use, i.e., appropriate endogenous production of glucocorticoids in response to stress, can take several days after a short course of steroids, and between 6 and 12 months after long-term steroid use [3]. Therefore, the perioperative physician must give consideration to the benefits of stress dose steroid administration to prevent the manifestation of adrenal crisis in the perioperative period, versus the risks associated with unnecessary steroid use, e.g., impaired wound healing, immunosuppression, hyperglycemia, and postoperative delirium. ○ There is no agreed-upon dose or duration of steroid known to cause HPAA suppression, and the precise recovery time from HPAA suppression varies. A recent review on this subject suggests that the patient taking any dose of glucocorticoid for less than 3 weeks, or those taking prednisone 5 mg daily for any period of time, do not need steroid stress dose administration [11]. Conversely, the Endocrine Society, in its Clinical Practice Guideline, takes the view that as no harm has been shown to occur with perioperative stress dose steroid administration, prevention of adrenal crisis is more important than prevention of the potential adverse risks of short-term stress dosing [10]. There are numerous practical approaches to the patient with potential HPAA suppression in the perioperative period. One such approach calls for maintenance of the usual steroid dose throughout the surgical period and treating refractory hypotension with rescue dose steroid [5] [11]. ○ A more nuanced strategy assesses the risk of HPAA suppression based on the clinical picture and/or the ACTH stimulation test, i.e., patients at high risk of HPAA suppression (e.g., Cushingoid features, prednisone ≥20 mg/day) and those diagnosed with secondary adrenal suppression using the CTH stimulation test require stress dosing (Table 19.5). - Patients at low risk (e.g., prednisone <5 mg/day) do not require stress dosing. An approach to the dosing required according to surgical type is provided in Table 19.3 [5].

Answer 23

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Answer 24

2a.F 2b.T 2c.T 2d.T 2e.F

Answer 25

- Acromegaly is a rare chronic endocrine disorder caused by excessive secretion of growth hormone (GH) and secondary elevation of insulin-like growth factor-1 (IGF-1). - IGF-1, a protein produced primarily by the liver, mediates the effects of GH. The most common cause of acromegaly is pituitary adenoma (>95% of cases) [3]. - Acromegaly has an incidence of up to 11 cases per million per year and a prevalence of 78 cases per million population [4]. - Due to the insidious nature of the disease diagnosis may be delayed by up to 10 years [5]. - Males and females are affected equally. - The usual age of onset is 40–50 years [2

Answer 26

○ Pituitary adenoma, a benign tumor of the anterior pituitary gland, is the most common pituitary tumor. ○ They are classified according to (1) size, (2) functionality, and (3) endocrine cell of origin. • Tumors smaller than 1 cm are termed microadenomas, while those 1 cm or larger are termed macroadenomas. • Microadenomas are more common than macroadenomas (57.4% vs 42.6%) [6]. • Approximately 65–75% of adenomas are functioning, i.e., produce excess hormone [7]. Microadenomas that are non-functioning are likely to be subclinical and may be detected as an incidental finding on radiologic investigation. - However, non-functioning tumors are more likely to be macroadenomas and present with headache, visual field defects secondary to compression of the optic chiasm, and/or hypopituitarism due to a compression effect on surrounding pituitary cells. • Lactotroph adenomas (prolactinomas) secrete prolactin. These are the most common type of pituitary adenoma (25–40% of adenomas) [8] and are the most common pituitary tumor overall. • Somatotroph adenomas secrete GH (10–20% of adenomas) [9] • Corticotroph adenomas produce adrenocorticotropic hormone (ACTH) (5–10% of adenomas) and are associated with Cushing disease [8]. • Thyrotroph adenomas secrete thyroid-stimulating hormone (TSH) and are the least common adenoma (<1%) [8]. • Plurihormonal adenomas make more than one hormone. They account for approximately 10–15% of all pituitary adenomas [1

Answer 27

The anatomical and physiological effects of the tumor must be elucidated, and treatment optimized. These effects are due to the following: • Hormone overproduction from functional tumoursor • Hormone underproduction secondary to a non-functioning compressive tumour

Answer 28

• Cardiovascular complications: Hypertension, coronary artery disease, left ventricular hypertrophy, congestive cardiac failure, cardiomyopathy, arrhythmias, and valvular dysfunction due to the effects of excessive GH on the myocardium. Cardiovascular disease is the most frequent comorbidity, accounting for up to 80% of complications and is one of the most common causes of death in acromegaly [11, 12]. The cardiomyopathy seen in these patients mainly affects the left ventricle with ensuing diastolic dysfunction (44% of patients with acromegaly), arrhythmias (48%), and valvular disease (75%) [12]. Cardiac failure is seen in 10% of patients [12]. The etiological mechanisms responsible for hypertension in acromegaly have not been fully clarified. Long-term renal exposure to IGF-1 and GH excess may result in an antidiuretic and antinatriuretic effect [13]. Alternative pathogenic mechanisms attributable to excessive GH and IGF-1 include plasma volume expansion and increasing responsiveness to angiotensin with a subsequent increase in peripheral vascular resistance [14].

Answer 29

• Transsphenoidal surgery is recommended as the primary mode of therapy in most patients [1]. • Medical therapy is usually reserved for patients with persistent disease after surgery or for patients who have adenomas not amenable to surgical resection. • Patients with disease extending beyond the sellar region who may not be amenable to complete resection may undergo surgical debulking followed by medical therapy. • Patients with significant disease after surgery can be treated with somatostatin receptor ligands or the GH receptor antagonist, pegvisomant. Patients with moderate disease after surgery may be treated with a dopamine agonist, e.g., cabergoline.

Answer 30

As most studies evaluating surgical outcome contain small numbers of patients and are up to 20 years old, it is difficult to say anything more substantial than surgery is not entirely curative for pituitary adenoma resection. Typical rates of success appear to be 50–80%, and surgery appears to be more successful for microadenoma than macroadenoma.

Answer 31

Many of the anatomical and physiological changes of acromegaly are reversible to a greater or lesser degree with medical and/or surgical therapy. Most of the soft tissue changes subside after surgery; however, the bony changes are irreversible. Surgical treatment of acromegaly can lead to significant improvement in glucose metabolism and insulin sensitivity [25]. Medical and surgical control of acromegaly generally improves cardiac structure and function, hypertension, and vascular damage. In addition, medical and surgical treatment has been shown to improve sleep apnea and respiratory insufficiency in up to 75% of patients [

Answer 32

• Complete blood count (CBC) • Electrolyte screen • Blood glucose • Blood type and screen +/− crossmatch – The potential for bleeding, especially in repeat procedures, is significant considering the proximity of the internal carotid arteries within the cavernous sinus, which forms the lateral walls of the sella turcica. • Endocrine biochemical indices – Often these have been measured prior to the anesthesiologist reviewing the patient. The most important ones are outlined in Table 20.1 [1, 2]. • Electrocardiogram and chest radiograph • Echocardiography – When clinical indicators of cardiomyopathy are present • Polysomnography / sleep studies – For confirmation of presence of OSA • Spirometry, arterial blood gases (ABG), pulmonary func-tion testing – If signs of respiratory insufficiency are present • Lateral neck radiograph, CT, MRI – For evaluation of airway abnormalities

Answer 33

1a.F 1b.T 1c.T 1d.F 1e.T

Answer 34

2a.F 2b.T 2c.T 2d.F 2e.F

Answer 35

○ Due to excess of catecholamine secretion such as epinephrine, norepinephrine and dopamine, patients are subject to significant perioperative hemodynamic and circulatory complications. - These include hypertensive and hypotensive crises, arrhythmias—particularly tachycardia— myocardial infarction, cardiomyopathy, cardiac failure, and stroke [1]. - The particular pattern of hemodynamic and biochemical effects seen depends on which catecholamines are secreted by the tumor and in what proportion. Secretion from the tumor can either be continuous, episodic, or both and can be precipitated by physical activity (e.g., postural changes) or surgical manipulation (especially until venous drainage from the tumor is interrupted).

Answer 36

Pheochromocytomas can be classified as sporadic or familial. - Approximately 70% of tumors are sporadic. Familial predisposition is seen in patients with some hereditary conditions, e.g., neurofibromatosis type 1 (NF-1), von Hippel-Lindau disease, multiple endocrine neoplasia type 2, and familial carotid body tumors. - Pheochromocytoma occurs in 0.1–5.7% of NF-1 patients and in 50% of patients with multiple endocrine neoplasia type 2 (MEN2) syndrome [2].

Answer 37

○ Familial pheochromocytomas are more likely to be bilateral. ○ After unilateral adrenalectomy in MEN2, there is a 30–50% risk of a contralateral tumor developing within 10 years [3]. ○ Surgical management of familial pheochromocytoma is controversial, as the risk of recurrence must be balanced with the risk of development of Addisonian adrenal insufficiency. ○ Options for management include complete bilateral adrenalectomy, unilateral adrenalectomy, and bilateral partial adrenal cortex sparing adrenalectomy

Answer 38

○ General consensus suggests initial assessment should take place when adrenergic blockade is commenced 7–14 days prior to surgery [1]. ○ Follow-up with the patient or surgical team 2–3 days prior to surgery to gauge the success of medical preparation is prudent.

Answer 39

○ End-organ damage secondary to pheochromocytoma-induced hypertension is specifically sought (Table 21.1) [4]. ○ Specific pharmacological agents being used to control blood pressure, heart rate, and subsequent normalization of intravascular volume are ascertained, along with their effects on the goals of treatment.

Answer 40

○ A multidisciplinary approach with contributions from an endocrinologist, surgeon, and anesthesiologist serves to achieve the best possible outcome by seamless implementation of an organized plan of care.

Answer 41

○ The classic triad of symptoms includes headaches, palpitations, and sweating. ○ Other symptoms reported are tachycardia, anxiety, dyspnea, weakness, orthostatic hypotension, blurred vision, and pallor [4]. - Hypertension can be sustained or paroxysmal. Up to 15% of patients are normotensive [5]. - The focal point of preoperative assessment is end-organ damage resulting from excess catecholamine secretion. - Table 21.1 can be used as a guide to clinical evaluation. cardiac failure, and arrhythmia suggestive of an underlying cardiomyopathy are of immediate relevance. Cerebrovascular disease, peripheral ischemia, and acute renal failure indicate more widespread secondary end-organ complications. - A family history of hereditary conditions associated with pheochromocytoma may be evident, e.g., MEN2, von Hippel-Lindau, and neurofibromatosis. ○ Symptoms and signs of ischemic heart disease, congestive

Answer 42

• Baseline laboratory testing includes complete blood count, electrolytes and creatinine, and blood glucose • Type and screen. • Chest radiograph, looking specifically for cardiomegaly and pulmonary edema. • 12-lead ECG; echocardiography is indicated to assess left and right systolic and diastolic function, and to rule out catecholamine induced cardiomyopathy in patients with long-standing disease. • Patients presenting with pheochromocytoma should be further investigated for other neoplasia (e.g., thyroid carcinomas, parathyroid hyperplasia, central and peripheral nervous tumors) [2].

Answer 43

• The primary objectives of preoperative optimization are control of blood pressure, heart rate, arrhythmias, and restoration of intravascular fluid volume [1]. • The Roizen criteria aim to assess the adequacy of preoperative alpha blockade (Table 21.2) [6, 7]. • Patient counselling and education should include information on avoidance of certain drugs and foods that may stimulate catecholamine release or decrease reuptake: – Sympathomimetic drugs, e.g., methamphetamine, pseudoephedrine – Tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin reuptake inhibitors – Dopaminergic agents such as antipsychotics and anti-emetics, e.g., prochlorperazine – Corticosteroids – Tyramine-containing food, e.g., cheese, wine • Lifestyle advice on avoidance of strenuous physical activity, tobacco, and alcohol [5]. • Strict glucose control in diabetics in order to avoid glycemic diuresis induced volume depletion.

Answer 44

- The currently accepted consensus focuses on α-adrenoreceptor antagonists as the mainstay of management, with β-adrenoreceptor antagonists and calcium channel antagonists as adjuncts, when needed, to achieve additional blood pressure and heart rate control. - Metyrosine, or similar agents, can be indicated in rare cases of wide-spread metastatic or highly active disease [7]. - α-adrenoreceptor antagonists counteract the vasoconstrictive effects of catecholamines and restore intravascular plasma volume [5]. Historically, the non-competitive α1- and α2-adrenoreceptor antagonist, phenoxybenzamine (PBZ), was the most widely used agent. PBZ is nonselective and irreversible (the effect diminishes only after de novo α-adrenoreceptor synthesis) with a long duration of action and may contribute significantly to postoperative hypotension [1]. - Reduction of symptoms (especially sweating) and reduction of blood pressure reflect the efficacy of therapy. Patients should be counselled on side effects: orthostatic hypotension with reflex tachycardia, nasal congestion, possible sedation, and at higher doses, paradoxical hypertension. Titration may be necessary to alleviate these side effects. A high sodium and fluid diet can correct the pre- existing volume contraction in this patient population and counteract hypotensive episodes related to initiation of alpha receptor blockade. - Selective α1-adrenoreceptors such as prazosin and terazosin have shorter half-lives, as they are competitive inhibitors. This results in less reflex tachycardia and a shorter postoperative hypotensive period [1]. Disadvantages of using shorter acting agents include incomplete α-adrenergic blockade that contributes to more episodes of intraoperative hypertension. Conversely, PBZ is associated with hypotension lasting for several hours post-resection and requires ICU admission on occasion for stabilization of intravascular volume.

Answer 45

β-adrenoreceptor antagonists: - The use of these agents is indicated for patients who have persistent tachycardia or tachyarrhythmias [1]. - β-adrenoreceptor antagonists should never be given without prior α-adrenoreceptor blockade due to the potential for unopposed vasoconstrictive effects that can lead to malignant hypertension and end-organ damage. - When adequate α-adrenoreceptor blockade is achieved, β-adrenoreceptor antagonists can be initiated. Suggested regimes include the use of short-acting agents such as propranolol (6 mg every 6 hours) and after a period of 24–48 hours, if tolerated, the patient can be started on a long-acting preparation (e.g., metoprolol, atenolol) titrated to achieve a resting heart rate of 60–80 beats per minute

Answer 46

- These drugs control hypertension, tachyarrhythmias, and coronary vasospasm by the inhibition of norepinephrine-mediated calcium influx into vascular smooth muscle. - Nicardipine, a dihydropyridine, is the most commonly used agent for pheochromocytoma management, used as a sustained release preparation at a starting dose of 30 mg twice daily. - The main role of calcium channel antagonists in this patient population is to supplement α- and β-adrenoreceptor blockade. - They may also be used in normotensive patients with paroxysmal hypertension or intolerance to α-adrenoreceptor antago- nists [1]. -!Calcium channel antagonists are unlikely to cause orthostatic hypotension or hypotension during normotensive periods.

Answer 47

: Metyrosine competitively inhibits tyrosine hydroxylase. This enzyme governs the rate-limiting step in the biosynthesis of catecholamine. - It can be used in conjunction with α-adrenoreceptor antagonists. The consideration of add-on therapy should be guided by intolerance of side effects of escalating doses of monotherapy as well as inadequate control of blood pressure by monotherapy [1]

Answer 48

• Preoperative medical optimization with α-adrenoreceptor antagonists can result in patients experiencing side effects such as postural hypotension with reflex tachycardia, syncope, and nasal congestion. This can be ameliorated with careful dose titration. • Severe refractory hypotension with the acute withdrawal of catecholamine stimulation can occur postoperatively [7].

Answer 49

○ Continuous blood pressure monitoring, judicious fluid balance management, and administration of vasoactive and anti-arrhythmic drugs in the perioperative period contribute to improved patient outcome. - Arterial blood pressure monitoring is a prerequisite. - Central venous pressure monitoring and anticipated vasopressor support is the accepted standard of care. - Pulmonary artery catheter use and intraoperative TEE monitoring may be indicated in certain cases such as severe hemodynamic instability, pulmonary hypertension, or significant myocardial disease

Answer 50

1a.F 1b.F 1c.F 1d.T 1e.T

Answer 51

2a.F 2b.F 2c.T 2d.T 2e.F

Endocrine Flashcards

(84 cards)