Thyroid, Parathyroid, Adrenal Flashcards

Question

What are general treatment options for thyroid lesions?

Answer 1

Medical: Best for pregnant patients RAI: Cannot be used in pregnant patients because it will cross the placenta and ablate the fetal thyroid tissue. Surgery: Leave 2g of thyroid tissue, best for Graves' disease.

Answer 2

INFLAMMATORY (Thyroiditis) 1) Acute suppurative thyroiditis - Pain, tenderness, fever, dysphagia - Tx: Drainage of abscess (sometimes needing thyroidectomy) + antibiotics 2) Chronic thyroiditis - Most common: Hashimoto's (autoimmune, antibodies against thyroid tissue, diffuse enlargement of gland, risk of developing papillary carcinoma) NONMALIGNANT (adenoma, colloid goiter) MALIGNANT 1) Well-differentiated - Papillary (most common); and Follicular (usually anterior neck mass with scalp mass) - Comes from a single cell (follicular cells) - Confirmed through FNAB; for results coming out as follicular tumors or neoplasm, consider them as non-specific as they could be an adenoma, colloid goiter, or cancer. - Main difference is METASTATIC SPREAD: ---> Papillary mets: Lymphatic ---> Follicular mets: Hematogenous 2) Medullary thyroid CA - Familial, associated with MEN IIA/IIB - Check sx in parathyroid and pancreas - Arise from C cells or parafollicular cells - Calcitonin is used as a tumor marker - May spread through lymphatics. - Tx: Total thyroidectomy, neck dissection 3) Anaplastic thyroid CA (rapid growth, death from asphyxia or compression) 4) Lymphoma (least common, check other nodal basins-- inguinal, axillary, thoracic, abdominal, tx with chemo)

Answer 3

All anaplastic cancers are stage IV lesions (in thyroid CA, stage IV does NOT necessarily mean distant mets, which is Stage IVC). Staging of the neck is just N0 or N1, meaning presence or absence indicating good prognosis. Staging of well-differentiated thyroid CA will depend on the age. For patients <55yo, there is just Stage I and II. For patients >55yo, you have the usual staging (Stage I-IV). ``` After staging the patient, determine if low or high risk for recurrence using the following classification schemes: A - age M - mets E - extent S - size ``` A - age G - grade E - extent S - size Age cut-off: 55 Size cut-off: 4cm Positive for any makes it high risk. Implication would be on prognosis and extent of surgery-- if low risk, do a subtotal thyroidectomy (involving isthmus and pyramidal lobe). If high-risk, do a total thyroidectomy. For the neck: Papillary CA: Neck dissection if N1 Follicular CA: None In general, if there are no clinically palpable nodes (N0), no neck dissection is warranted. However, if a total thyroidectomy is warranted, you should do a central node compartment dissection. For distant mets of follicular CA: - Surgery (if possible, rarely done) - RAI (after doing RAI scan to check if there is uptake of RAI in distant mets) - Radiotherapy (if there is no RAI uptake during scanning)

Answer 4

RAI Scan Diagnostic, NOT therapeutic, used just to check for presence or absence of distant mets and if it is responsive to it (3 mci dosage used). RAI Ablation Done to kill remaining thyroid tissue in high-risk patients wherein only a subtotal thyroidectomy is performed (30 mci). RAI Treatment/Therapy For distant metastases (100-200 mci). Timing of giving RAI is 6 weeks, time when TSH is at its highest level. After treating distant mets, start Hormonal Suppressive Therapy, thyroid hormone dosage should be at levels that would bring TSH level below the minimal normal requirement. Thyroglobulin can be used as a hormone marker, because they are produced by the thyroid follicles.

Answer 5

1) Hyperplasia 2) Adenoma 3) Carcinoma

Answer 6

1) Hyperplasia Total parathyroidectomy with autotransplantation, or removal of the 3 1/2 of the glands. 2) Adenoma Removal of diseased gland and biopsy of the rest. 3) Carcinoma Total parathyroidectomy most of the time, including thyroid lobe.

Answer 7

Secondary is due to renal or bone problems; address cause.

Answer 8

b. Bilateral neck dissection and adenoma removal

Answer 9

The medial thyroid comes from the first and second pharyngeal pouches. Lateral portions of the thyroid and parafollicular C cells arise from the fourth and fifth pharyngeal pouches.

Answer 10

Superior thyroid artery (from external carotid artery) Inferior thyroid artery (from thyrocervical trunk)

Answer 11

Superior and middle thyroid veins (drain into internal jugular vein) Inferior thyroid veins (drain into innominate and brachiocephalic veins)

Answer 12

Cricothyroid muscle, which is innervated by the external branch of the superior laryngeal nerve

Answer 13

Subclavian artery on the right | Arch of the aorta on the left

Answer 14

Superior laryngeal nerve

Answer 15

Both drugs block peroxidase oxidation of iodide to iodine, thereby inhibiting incorporation of iodine into T4 and T3. PTU also inhibits peripheral conversion of T4 to T3.

Answer 16

Methimazole | PTU is the safer choice in pregnancy.

Answer 17

Steroids inhibit peripheral conversion of T4 to T3 and lower serum TSH by suppressing the pituitary-thyroid axis.

Answer 18

Large doses of iodine given after an antithyroid medication can inhibit thyroid hormone release by disrupting the coupling of iodide. This is a transient effect.

Answer 19

Graves disease, toxic multinodular goiter, and toxic adenoma

Answer 20

Autoantibodies to TSH receptors (also called thyroid-stimulating antibodies or TSAb) bind and stimulate thyroid hormone production. This leads to thyrotoxicosis, diffuse goiter, pretibial myxedema, and proptosis.

Answer 21

Antithyroid medication Thyroid ablation With/without thyroidectomy

Answer 22

Hashimoto thyroiditis

Answer 23

Hashimoto thyroiditis

Answer 24

Thyroid hormone replacement

Answer 25

Lymphocytic infiltrate

Answer 26

Acute suppurative thyroiditis

Answer 27

Antibiotics | Occasionally, abscess drainage

Answer 28

Subacute (de Quervain) thyroiditis

Answer 29

NSAIDs, steroids

Answer 30

Riedel fibrous struma Painless, progressive goiter Usually euthyroid but may become hypothyroid

Answer 31

Thyroid hormone replacement and steroids | Surgery may be necessary to relieve obstructive symptoms

Answer 32

PTU or methimazole every 4 to 6 hours and inorganic iodide to block synthesis and release of thyroid hormones Dexamethasone to inhibit peripheral conversion of T4 to T3 Propranolol Fever reduction General resuscitation

Answer 33

Multinodular goiter

Answer 34

Presence of or inability to rule out malignancy Compressive symptoms Cosmetic deformity

Answer 35

FNA It has a sensitivity of 86% and a specificity of 91%

Answer 36

Medullary thyroid carcinoma (MTC)

Answer 37

Amyloid among neoplastic cells Immunohistochemistry positive for calcitonin Positive staining for carcinoembryonic antigen (CEA) or calcitonin gene-related peptide Heterogeneity with polygonal or spindle-shaped cells

Answer 38

75% to 80% Unable to differentiate familial versus sporadic at presentation-- all should be tested for RET mutation, pheochromocytoma, and hyperparathyroidism

Answer 39

Total thyroidectomy | High incidence of multicentric disease

Answer 40

MEN2a: Age 6 | MEN 2b: Age 1 to 2

Answer 41

Calcitonin and CEA

Answer 42

Pheochromocytoma

Answer 43

Grossly firm and white | Marked heterogeneity with spindle, polygonal, or multinucleated cells

Answer 44

Poor: only few survive more than 6 months

Answer 45

Elderly patients with a long-standing goiter

Answer 46

Total thyroidectomy with or without external beam radiation | Has small improvement in survival, especially for younger patients

Answer 47

Debulking surgery with tracheostomy

Answer 48

Solid thyroid lesion

Answer 49

Solitary thyroid lesion

Answer 50

Cold thyroid lesion

Answer 51

Papillary thyroid cancer, about 70% to 80% of all thyroid cancers

Answer 52

Insular Columnar Tall cell

Answer 53

Psammoma bodies | Orphan Annie nuclei

Answer 54

High-risk, large (>2 cm), or bilateral tumors: Total thyroidectomy Low-risk, small (<1 cm), or unilateral tumors: Thyroid lobectomy and isthmusectomy

Answer 55

Neck ultrasound

Answer 56

Thyroglobulin

Answer 57

True. Lymph node involvement indicates more aggressive disease.

Answer 58

Vascular or capsular invasion

Answer 59

Bone Next most common is lung Spread is hematogenous

Answer 60

Hurthle cell carcinoma | Higher recurrence rate usually to regional lymph nodes

Answer 61

All lymph nodes were free of disease, and there was no extrathyroidal disease. This patient has T2NOMO disease. Because the patient is older than 45 years, this is stage II papillary thyroid cancer.

Answer 62

1 to 4 cm with aggressive histology, >4 cm | Extrathyroid extension, vascular invasion, multifocal disease, lymph node involvement, distant metastasis

Answer 63

Increased mortality and disease recurrence

Answer 64

Fourth branchial pouch

Answer 65

Third branchial pouch

Answer 66

Third branchial pouch

Answer 67

Inferior thyroid artery (occasionally by branches ofthe superior thyroid artery)

Answer 68

Inferior thyroid artery

Answer 69

Inferior parathyroid glands are medial to the recurrent laryngeal nerves and located below the inferior thyroid artery

Answer 70

Superior parathyroid glands are lateral to the recurrent laryngeal nerves and located above the inferior thyroid artery

Answer 71

Bone: enhances resorption of bone matrix by osteoclasts Kidney: increases tubular reabsorption of filtered calcium and decreases tubular reabsorption of fIltered phosphate Intestine: stimulates renal vitamin D complex synthesis, which increases intestinal absorption of calcium (indirect effect)

Answer 72

Intact parathyroid hormone level (elevated in >95% of patients with primary hyperparathyroidism)

Answer 73

2 to 4 minutes

Answer 74

50% decrease from baseline PTH or a drop of the PTH to the normal range

Answer 75

7-dehydrocholesterol undergoes ultraviolet activation to form vitamin D (cholecalciferol) --> hydroxylated in the liver to form 25-hydroxycholecalciferol--> undergoes a second hydroxylation in the kidneys to its most active form 1,25-dihydroxycholecalciferol

Answer 76

Parafollicular (C cells) of the thyroid

Answer 77

Primary and tertiary hyperparathyroidism

Answer 78

Secondary hyperparathyroidism

Answer 79

Secondary hyperparathyroidism

Answer 80

Tertiary hyperparathyroidism

Answer 81

Hyperchloremic metabolic acidosis

Answer 82

Chloride:phosphate ratio > 33 is highly suggestive of primary hyperparathyroidism

Answer 83

``` Single adenoma (80%) Diffuse hyperplasia and multiple adenomas can also occur ```

Answer 84

Single enlarged gland with 3 normal or small remaining glands associated with the histologic finding of hyperplastic tissue

Answer 85

Symptomatic: Typical bone, renal, gastrointestinal, neuromuscular symptoms Asymptomatic: Significant or life-threatening hypercalcemia Presence of kidney stones detected by abdominal imaging Medical surveillance not desirable/possible Serum calcium level > 1 mg/dL above upper limit of normal Age <50 years Osteoporosis (bone density T-score < -2.5 at any site) Creatinine clearance decreased by >30% Elevated 24-hour urinary calcium excretion (>400 mg/d)

Answer 86

Persistent refers to hypercalcemia that remains within 6 months of initial surgery Recurrent refers to hypercalcemia that returns after 6 months of initial surgery

Answer 87

Missed adenoma

Answer 88

New adenoma formation or recurrent parathyroid cancer

Answer 89

``` Ongoing nephrolithiasis Worsening renal function Worsening bone disease as evidenced by bone mineral density scores Associated neuromuscular symptoms Associated psychiatric symptoms Worrisome progressive hypercalcemia ```

Answer 90

Development of open ulcerative skin lesions from calcinosis or calciphylaxis Persistent bone pain or pathologic fractures (renal osteodystrophy) Ectopic calcifications Intractable pruritus Worsening disease with failure of medical management

Answer 91

Open and inspect the thyroid capsule, palpate gland. Consider intraoperative ultrasound. Dissect superior thymic/paratracheal tissue and complete a cervical thymectomy for missing inferior parathyroid glands Mobilize the pharynx and esophagus to look in the parapharyngeal/retropharyngeal/esophageal spaces for missing superior glands. Open the carotid sheath and expose the common carotid and inspect for potential parathyroid glands. Ligate the ipsilateral inferior thyroid artery and/or perform a thyroid lobectomy (record the location ofall confirmed glands identified). End the procedure and follow the patient for any evidence ofpersistent hypercalcemia. Can reimage the patient for evidence of ectopic parathyroid adenoma.

Answer 92

Normal anatomic position.

Answer 93

Within the first 2 years after freezing

Answer 94

The resected parathyroid tissue is minced into 1-mm fragments. A pocket is then made in the desired muscle. Ten to 20 1-mm fragments of minced parathyroid tissue are inserted into the muscle pocket, which is closed and tagged with hemoclips/suture (for future identification}

Answer 95

Easier to re-explore if patient develops persistent or recurrent disease from autotransplanted tissue. Easier to identify PTH gradients with peripheral blood draws in forearm versus neck (can place BP cuff).

Answer 96

Bone hunger, hypomagnesemia, failure of parathyroid remnant or graft

Answer 97

Technetium-sestamibi scan, ultrasound, CT-sestamibi fusion, or 4D CT

Answer 98

Surgical trauma to parathyroid glands during thyroid or parathyroid exploration

Answer 99

En bloc tumor resection that includes ipsilateral thyroid lobectomy and resection of adjacent soft tissues

Answer 100

False; capsular rupture may occur with the potential of spreading tumor cells in the neck

Answer 101

Parathyroid hyperplasia (90%)

Answer 102

Hyperparathyroidism; need to correct calcium first.

Answer 103

Pheochromocytoma

Answer 104

ADH and oxytocin

Answer 105

ACTH, FSH, LH, GH, TSH, and prolactin

Answer 106

Octreotide {decreases serum levels of GH and the downstream growth factor somatomedin C)

Answer 107

Microadenoma <1 cm | Macroadenoma >1 cm

Answer 108

MRI with gadolinium

Answer 109

Prolactinoma

Answer 110

Bromocriptine | Transsphenoidal resection for failure of medical management

Answer 111

Waterhouse-Friderichsen syndrome

Answer 112

Empty sella syndrome (primary)

Answer 113

Sheehan syndrome

Answer 114

Nelson syndrome

Answer 115

Craniopharyngioma

Answer 116

Acne, buffalo hump, depression, diabetes, easy bruising, hirsutism, hypertension, moon fades, myopathy, purple striae, truncal obesity, weakness

Answer 117

Phenylethanolamine-N-methyltransferase (PNMT) | Converts norepinephrine to epinephrine via methylation

Answer 118

Tyrosine hydroxylase (hydroxylates tyrosine to dihydroxyphenylalanine [DOPA])

Answer 119

``` Tyrosine ----> DOPA ----> Dopamine ----> Norepinephrine ----> Epinephrine ```

Answer 120

Inferior phrenic artery

Answer 121

Renal artery

Answer 122

Left renal vein

Answer 123

Inferior vena cava

Answer 124

Aldosterone

Answer 125

Glucocorticoids

Answer 126

Androgens/estrogens

Answer 127

21-hydroxylase deficiency (90%)

Answer 128

``` 4 cm or larger enlarging {0.5cm over 6 months), functioning, ominous characteristics (nonhomogeneous, poor washout) on imaging ```

Answer 129

``` Plasma metanephrines, cortisol, BMP, aldosterone, renin, catecholamines ```

Answer 130

HTN, hypokalemia, polyuria

Answer 131

Plasma renin level (suppressed with primary and not suppressed with secondary)

Answer 132

Adrenal adenoma

Answer 133

Greater than 30 is diagnostic for primary hyperaldosteronism

Answer 134

Give a saline infusion; if the urinary aldosterone level is elevated (>12μg/d), the diagnosis of primary hyperaldosteronism is confirmed.

Answer 135

CT scan of the abdomen with thin cuts (3-5 mm) through the adrenal glands

Answer 136

Hypochloremic metabolic alkalosis

Answer 137

Adrenal venous sampling (AVS)

Answer 138

Patients with diagnosed hyperaldosteronism greater than 40 years old

Answer 139

At least 5 times higher on the affected side; if ratios from both sides are similar, then suspect bilateral hyperplasia.

Answer 140

No change. If the patient has bilateral adrenal hyperplasia, a captopril test will cause decreased aldosterone levels.

Answer 141

Spironolactone

Answer 142

Laparoscopic adrenalectomy

Answer 143

Medical therapy with calcium channel blockers, potassium, and spironolactone. If refractory hypokalemia, then bilateral adrenalectomy, steroids, and fludrocortisone.

Answer 144

24-hour urinary free cortisol

Answer 145

``` #1 - Small cell lung carcinoma #2 - Carcinoid ```

Answer 146

<5 pg/mL (low)

Answer 147

15 pg/mL (high)

Answer 148

Administer dexamethasone 1 mg PO at 11 P.M.; check plasma cortisol at 8 A.M. the next day. Cortisol level will be markedly suppressed (<1.8 μ.g/dL) in normal individuals. If cortisol level is not suppressed, the patient has Cushing syndrome.

Answer 149

Obtain baseline plasma cortisol; administer dexamethasone 8 mg PO at 11 P.M.; check 8 A.M. plasma cortisol. Suppression occurs if there is >50% reduction in plasma cortisol, which indicates Cushing syndrome from a pituitary source (if not suppressed, then from an adrenal or ectopic cause).

Answer 150

ACTH level is suppressed

Answer 151

ACTH level is not suppressed

Answer 152

Check baseline serum ACTH and cortisol. Give 1 mcg/kg CRH IV. Draw serum ACTH and cortisol 15 minutes after administering CRH.

Answer 153

ACTH increases at a minimum of 35% above baseline with pituitary lesions only (others do not).

Answer 154

Increased levels of serum dehydroepiandrostenedione (DHEA-S), serum testosterone, and 24-hour urine 7-hydroxysteroids and 17-ketosteroids

Answer 155

24-hour ketosteroids and serum androgens will be suppressed with ovarian tumors but not adrenal tumors

Answer 156

Gadolinium persists in a malignant tumor (poor washout); gadolinium washes out rapidly from an adenoma (rapid washout)

Answer 157

Withdrawal of exogenous steroids

Answer 158

Hyponatremia, hyperkalemia

Answer 159

ACTH stimulation test

Answer 160

Loss of diurnal variation of cortisol levels

Answer 161

Open adrenalectomy

Answer 162

Mitotane, a synthetic derivative of the insecticide dichlorodiphenyltrichloroethane (DDT) that directly suppresses the adrenal cortex and modifies the peripheral metabolism of steroids.

Answer 163

Repeat abdominal imaging every 6 months to a year and annual screening for cortisol and catecholamines/metanephrines for 5 years.

Answer 164

Adrenalectomy; most likely malignant

Answer 165

Pheochromocytoma; inadvertent biopsy can be potentially lethal

Answer 166

Plasma metanephrines (96%)

Answer 167

10% bilateral, 10% malignant, 10% extra-adrenal, 10% hereditary, 10% in children

Answer 168

Organ of Zuckerkandl, thorax/mediastinum, bladder, scrotum

Answer 169

``` MEN type 2, Sturge-Weber syndrome, tuberous sclerosis, von Hippel-Lindau disease, neurofibromatosis type I ```

Answer 170

Diaphoresis, headache, palpitations, and paroxysmal HTN

Answer 171

True; paragangliomas and pheochromocytomas in the organ of Zuckerkandl contain PNMT

Answer 172

Phenoxybenzamine 10 mg BID and increase by 20 mg/d until BP and symptoms controlled; add beta-blocker 3 days prior to surgery (Inderal 10 mg tid); IVF hydration starting 2 days prior to surgery (typically patients are volume contracted)

Answer 173

Neosynephrine, nitroprusside, lidocaine, esmolol, phentolamine

Answer 174

Yearly 24-hour urinary metanephrines/catecholamines

Answer 175

CT scan of the abdomen with thin cuts (3-5 mm) through the adrenal glands

Answer 176

Adrenalectomy for the affected side and observe the contralateral side until there is radiographic/biochemical evidence of disease. Bilateral adrenalectomy for bilateral disease.

Answer 177

Breast cancer

Answer 178

Answer: E. For papillary thyroid cancers larger than 2 cm, total thyroidectomy is indicated. Postoperative 1-131 therapy is given for tumors >4 cm or extrathyroidal disease. Neck dissection is unnecessary without evidence of nodal disease.

Answer 179

Answer: E. The size of the tumor necessitates a total thyroidectomy. This patient has a palpable cervical lymph node, and thus preoperative FNA of the lymph node should be done. A lateral neck dissection is indicated if the lymph node is positive for malignancy.

Answer 180

Answer: D. Calcitonin-positive cells indicate a diagnosis of MTC. Elevated calcium suggests hyperparathyroidism. Along with pheochromocytoma, these diagnoses make up MEN 2a. MEN 2b would include MTC, pheochromocytoma, and mucosal neuromas.

Answer 181

Answer: E. This patient has thyroid storm. Beta-blockers are used to control heart rate with inhibition of peripheral conversion of T4 to T3. Steroids and PTU work by decreasing production and release of thyroid hormones. IV fluids and oxygen are part of routine resuscitative care. I-131 has no role in the treatment of thyroid storm.

Answer 182

Answer: E. MTC is seen in patients with MEN 2a and 2b. Parathyroid hyperplasia is the earliest and most common manifestation of MEN 1. It develops in 80% to 100% of patients by age 40. Gastrinomas are the most common pancreatic islet cell tumor in MEN 1, which occurs in about 50% ofpatients, followed by insulinomas, which develop in 10% to 15% of cases. Prolactinomas are the most common pituitary lesion, which occurs in 10% to 50% of MEN 1 cases.

Answer 183

Answer: B. Nonfunctioning cortical adenomas comprise the majority of adrenal incidentalomas in patients without a history of cancer.

Answer 184

Answer: E. The 2002 NIH consensus conference guidelines for parathyroidectomy in patients with asymptomatic primary hyperparathyroidism are: serum calcium > 1 mg/dL above the upper limits ofnormal; life-threatening hypercalcemia episode; creatinine clearance reduced by 30%; kidney stones on abdominal x-ray; markedly elevated 24-hour urinary calcium excretion >400 mg/dL; age <50 years; long-term medical surveillance not desired or possible; and substantially decreased bone mineral density at the lumbar spine, hip, or distal radius (T score

Answer 185

Answer: C. The patient is found to have an incidentaloma that is asymptomatic and nonfunctioning. However, given its size of 6 cm and CT findings that suggest malignancy, the patient should undergo adrenalectomy. Other CT scan features that suggest malignancy include evidence of necrosis, hemorrhage, local invasion, lymph node metastasis, and high attenuation. Needle biopsy of an adrenal mass should only be performed in patients with a history of malignancy to rule out an adrenal metastasis after ruling out pheochromocytoma. Mitotane is an adrenal cytotoxic agent that is used as adjuvant therapy for adrenocortical carcinoma.

Answer 186

Answer: C. When Cushing syndrome is suspected, the first test should be a 24-hour urinary free cortisol. If it is elevated, a low-dose dexamethasone suppression test is performed. Failure to suppress cortisol levels indicates Cushing syndrome. ACTH levels are then measured. Low ACTH levels indicate a cortisol-secreting tumor, such as a primary adrenal source. A CT scan of the abdomen would be helpful in this case. A high ACTH level suggests a pituitary or ectopic source of ACTH. A high-dose dexamethasone suppression test will differentiate this. The pituitary source will be suppressed; thus, pituitary MRI should be performed. Failure to suppress production suggests an ectopic ACTH tumor, which most commonly is small cell lung cancer or bronchial tumors. CT of the chest would be warranted in this case.

Answer 187

Answer: B. The patient is suspected to have primary hyperaldosteronism, which may be due to bilateral adrenal hyperplasia or an aldosteronoma. Selective venous catheterization for aldosterone sampling in adrenal veins can aid in localizing the aldosteronoma, thus determining ifsurgical intervention would be beneficial. If the aldosteronoma is localized to 1 adrenal gland, then the patient should undergo unilateral adrenalectomy. If bilateral adrenal glands are hyperfunctioning or if there is failure to localize the aldosteronoma, then medical management with spironolactone would be the mainstay therapy. There is increased morbidity with bilateral resection, which is reserved for refractory hypokalemia for cases of bilateral hyperplasia.

Answer 188

Answer: B. The patient has Conn syndrome, or primary hyperaldosteronism. CT scan or imaging such as MRI should be done to evaluate for adrenal mass or hyperplasia. At age greater than 40, AVS is also suggested due to the increased risk of incidental adrenal hyperplasia or mass. This is recommended in the American Association of Clinical Endocrinologists and American Association ofEndocrine Surgeon guidelines for adrenal disease.

Answer 189

Answer: B. Intraoperative PTH testing indicates cure when the post-excision PTH decreases by at least 50% and to within normal range. If PTH does not drop by at least 50% or remains elevated, 4-gland exploration should be pursued. If a parathyroid gland cannot be located, first look in the expected anatomic positions, followed by the thymus, thyroid (using ultrasound), and within the carotid sheath.

Answer 190

Answer: C. Labs show no excess hormonal production, and rapid washout on MRI suggests a benign adrenal adenoma. Follow-up imaging should be obtained in 6 to 12 months and annually along with labs for 5 years. There is no indication of adrenalectomy or mitotane.

Answer 191

Answer: B. The patient has mild to moderate symptoms of primary hyperparathyroidism. Localization studies should be obtained in preparation for parathyroidectomy. Biopsy of suspected parathyroid adenoma is not recommended. In general, cinacalcet is indicated in severe primary hyperparathyroidism when the patient has a contraindication for surgery.

Answer 192

Answer: A. Patients with end-stage renal disease and secondary hyperparathyroidism have vitamin D deficiency, hyperphosphatemia, and hypocalcemia. They are treated with vitamin D supplementation and phosphate binders. Calcimimetics such as cinacalcet are used for treatment of secondary hyperparathyroidism. Parathyroidectomy is recommended when PTH is persistently greater than 800.

Answer 193

A. Adrenalectomy

Answer 194

D. Both need four gland parathyroidectomy

Answer 195

C. There is no need for further excision at this point

Answer 196

E. Total parathyroidectomy with autoimplantation

Answer 197

D. Subtotal parathyroidectomy

Answer 198

D. En bloc total parathyroidectomy with ipsilateral thyroidectomy

Answer 199

Answer:B The Nobel Prize in Physiology or Medicine was awarded to Emil Kocher in 1909. In addition to his research on the physiology of the thyroid, Kocher’s operative methods greatly reduced the mortality risk of thyroidectomy. The Kocher clamp was designed to prevent hemorrhage rom the hyper- vascular gland during thyroidectomy. (See Schwartz 10th ed., p. 1521.)

Answer 200

Answer: C The medial thyroid anlage descends rom the base of the tongue through a channel called the thyroglossal duct at week 3 to 4 of gestation. The duct normally closes after its descent, but may remain patent and is susceptible to secondary infection and dilatation, referred to as a thyroglossal duct cyst. Removal is accomplished with the Sistrunk operation which also removes the central portion of the hyoid bone. (See Schwartz 10th ed., p. 1521.)

Answer 201

Answer: D The superior thyroid arteries arise from the external carotid arteries, and the inferior thyroid arteries arise rom the thyrocervical trunk shortly after their origin from the subclavian arteries. A thyroid ima artery arises directly from the aorta or innominate artery in 1 to 4% of cases. (See Schwartz 10th ed., p. 1523.)

Answer 202

Answer: D The RLN courses within the tracheoesophageal groove after emerging from the vagus nerve at the level of the aortic arch. As it ascends in the neck, the recurrent laryngeal nerve (RNL) may branch, and may pass anterior, posterior, or interdigitate with branches of the ITA. The location of the RLN must be confirmed before the ITA is divided. (See Schwartz 10th ed., p. 1524.)

Answer 203

Answer: A The external branch of the superior laryngeal nerve (SLN) lies on the inferior pharyngeal constrictor muscle and descends alongside the superior thyroid vessels before innervating the cricothyroid muscle. Therefore the superior pole vessels should not be ligated en masse, but should be individually divided low on the thyroid gland. Injury to the SLN leads to inability to tense the ipsilateral vocal cord, and impairs the ability to “hit high notes” while singing, or projecting the voice loudly. (See Schwartz 10th ed., p. 1524.)

Answer 204

Answer: D Thyroid hormones are responsible for maintaining the normal hypoxic and hypercapnic drive in the respiratory center of the brain, and regulate gastrointestinal motility which leads to diarrhea in hyperthyroidism and constipation in hypothyroidism. They also regulate bone and protein turnover and the speed of muscle contraction and regulation, hepatic gluconeogenesis, cholesterol synthesis, and intestinal glucose absorption. (See Schwartz 10th ed., p. 1528.)

Answer 205

Answer: B Graves disease, named after Robert Graves, the Irish physician who described the disorder in three patients in 1835, is the most common cause of hyperthyroidism in North America, and accounts or 60 to 80% of cases. (See Schwartz 10th ed., p. 1531.)

Answer 206

Answer: D Subtotal or total thyroidectomy is now preferred over subtotal thyroidectomy due to a lower recurrence rate. Surgery is preferred over medical therapy (radioactive iodine) in childbearing women who desire to have children in the near future, in noncompliant patients, or when airway obstruction appears likely. (See Schwartz 10th ed., p. 1533.)

Answer 207

Answer: B Follicular neoplasms of the thyroid are less aggressive than papillary neoplasms, and a fine needle aspiration biopsy (FNAB) may be unable to differentiate between a follicular adenoma and a follicular carcinoma. For this reason unilateral lobectomy is recommended for this FNAB diagnosis.(See Schwartz 10th ed., p. 1539.)

Answer 208

Answer: D Mutations in the extracellular domain of the RET tyrosine kinase receptor are associated with multiple endocrine neoplasia type 2A (MEN2A), familial medullary thyroid cancer (FMTC), and Hirschsprung disease. Mutations in the intracellular domain are associated with MEN2B, FMTC, and Hirschsprung disease. (See Schwartz 10th ed)

Answer 209

Answer: A Papillary thyroid cancer accounts for 80% of all thyroid malignancies and is the predominant thyroid cancer in children and individuals exposed to external radiation. (See Schwartz 10th ed., p. 1542.)

Answer 210

Answer:C Total thyroidectomy or total lobectomy on the affected side with subtotal lobectomy on the non-affected side is the recommended treatment of choice for unifocal PTC greater than 1 cm in diameter. Defiinitive operation can be performed without rozen section when the diagnosis is unequivocal on FNAB. (See Schwartz 10th ed., p. 1543.)

Answer 211

Answer: D MC can be spontaneous (in 75%) or familial (in 25%) in MEN2. MEN2A is associated with pheochromocytoma and hyperparathyroidism, whereas MEN2B is associated with pheochromocytoma, Marfanoid habitus, and mucocutaneous ganglioneuromas. (See Schwartz 10th ed., p. 1550.)

Answer 212

Answer: C Children with mutations at codon 634 of the RET tyrosine kinase receptor gene (MEN2A) are advised to undergo thyroidectomy before age 5, whereas children with mutations at codon 918 (MEN2B) should undergo thyroidectomy before age 1. If ultrasound of the neck is normal and calcitonin levels are normal, a formal neck dissection can be avoided. (See Schwartz 10th ed., p. 1550.)

Answer 213

Answer: D Inadvertent injury (ischemia) or removal of the parathyroid glands can cause acute neuromuscular excitability due to hypocalcemia. An expanding hematoma in the neck may not cause bleeding from the wound, but can compress the membranous portion of the trachea and cause dyspnea. Nerve injuries can cause vocal cord paralysis or impaired speech. (See Schwartz 10th ed., p. 1556.)

Answer 214

Answer: D Supernumerary parathyroid glands occur in 7 to 13% of people, and may be located in the thymus (most commonly), within the parenchyma of the thyroid gland, or in the tracheoesophageal groove, the mediastinum, or elsewhere in the neck. (See Schwartz 10th ed., p. 1557.)

Answer 215

Answer: B Localization studies such as sestamibi scans have been shown to allow more limited operations, including those utilizing “mini-incisions” under local anesthesia, or patients who are not good risks for general anesthesia. Improved cosmesis, shorter lengths of stay, and reduced complications are benefits from this approach. (See Schwartz 10th ed., p. 1564.)

Answer 216

Answer: A When the PTH level alls by greater than 50% within 10 minutes after removal of parathyroid tissue, the cause of the hyperparathyroidism is likely to have been removed, and the operation can be stopped. (See Schwartz 10th ed., p. 1566.)

Answer 217

Answer: D In patients with MEN1, hyperparathyroidism should be corrected before treatment of the gastrinoma because resolution of hypercalcemia may allow gastrin levels to all to normal. (See Schwartz 10th ed., p. 1567.)

Answer 218

Answer: A Parathyroid carcinoma occurs in about 1% of patients with primary hyperparathyroidism, or in about 1000 patients per year in the United States. Findings include an elevated serum calcium level greater than 14 mg/dL, and elevated PTH level greater than five times normal, and a palpable mass in the neck, but none of these may be present. Complete surgical removal is the most effective therapy with radical neck dissection in lymphadenopathy is present; however, one-third of patients have metastatic disease when first diagnosed.(See Schwartz 10th ed., p. 1570.)

Answer 219

Answer: C Primary aldosteronism, or Conn syndrome, is seen in about 1% o hypertensive patients. It is more common in middle- aged individual and is usually associated with a single adenoma of the adrenal cortex. The hypertension is usually refractory to medical treatment, and is classically associated with hypokalemia, but may be seen in normokalemic individuals. (See Schwartz 10th ed., p. 1578.)

Answer 220

Answer: B Cushing syndrome refers to any cause of hypercortisolism caused by either an adrenal source or exogenous administration of steroids. Cushing disease refers only to an adrenocorticotropic hormone (ACTH)-secreting adenoma of the pituitary gland. Cushing syndrome due to an isolated adrenal adenoma is far less common than hypercortisolism due to a pituitary adenoma, but adrenalectomy is curative for primary adrenal tumors or for adrenal hyperplasia that persists despite efforts to resect a pituitary tumor. (See Schwartz 10th ed., p. 1580.)

Answer 221

Answer: D Pheochromocytomas are solid tumors which appear on computed tomography (CT) scan as soft tissue masses. They are detected with 85 to 95% accuracy, but it is important to avoid intravenous-contrast enhancement when a pheochromocytoma is suspected; intravenous contrast can provoke a hyper- tensive crisis due to release of catecholamines. MR is useful to identify pheochromocytomas, both because they identify soft tissue masses, but also because this tumor tends to enhance on 2-weighted images. Radio-labeled metaiodobenzylguanidine (MIBG) is taken up avidly by the pheochromocytoma because its structure is similar to norepinephrine. Therefore the MIBG scan can localize an occult tumor. Octreotide scans are not used or pheochromocytoma as the tumor does not overexpress somatostatin receptors. (See Schwartz 10th ed., p. 1586.)

Answer 222

Answer: A Extra-adrenal pheochromocytomas (also known as paragangliomas) secrete norepinephrine, because these sites lack the enzyme (phenylethanolamine N-methyltrans erase) which converts norepinephrine to epinephrine. Adrenal pheochromocytomas secrete both epinephrine and norepinephrine as well as dopamine. Some pheochromocytomas secrete only dopamine, and patients with these tumors may be normotensive. (See Schwartz 10th ed., p. 1586.)

Answer 223

Answer: D The preoperative preparation of a patient with a catecholamine-secreting tumor includes alpha-hypertension, a beta-adrenergic blocker to prevent tachycardia, and volume replacement to avoid hypotension due to alpha- and beta- blockers. Steroids are not needed to prevent adrenal insufficiency. (See Schwartz 10th ed., p. 1586.)

Answer 224

Answer: A The adrenal “incidentaloma” is an increasingly common finding with the ubiquitous use of CT scanning, with an incidence of 0.4 to 4.4%. A variety of benign and malignant lesions can account for these findings, and a distant history of malignancy elsewhere should raise the possibility of metastatic disease. Primary malignancy of the adrenal gland is rare, and the functioning tumors are excluded by screening tests or cortisol and catecholamine excess. In the absence of symptoms associated with adrenal disease, annual follow-up of these lesions with imaging and chemical tests seems prudent. (See Schwartz 10th ed., p. 1589.)

Answer 225

Answer: C Laparoscopic (videoscopic) approaches to adrenalectomy have been shown to be advantageous or several outcomes including wound complications, analgesic use, and length of hospital stay. These advantages are in balance to adverse considerations including length of operative time and cost. (See Schwartz 10th ed., p. 1591.)

Answer 226

Answer: C Nelson syndrome describes symptoms due to the progressive enlargement of a persistent ACTH-secreting pituitary fossa tumor. These symptoms include hyperpigmentation, visual field loss, headaches, and extraocular muscle palsies. Interference with the olfactory nerve is not part of the syndrome. (See Schwartz 10th ed., p. 1594.)

Answer 227

ANSWER: B COMMENTS: The arterial blood supply of the thyroid gland is provided by two main arterial branches. The superior thyroid artery arises from the external carotid artery and gives off multiple branches that are collectively referred to as the superior pole vessels. The inferior thyroid artery is given off as a branch of the thyrocervical trunk, which originates from the subclavian artery. The ligament of Berry is a condensation of the thyroid capsule located on the posterior surface of the gland. It is a tough band of tissue that passes either anterior or posterior to the course of the RLN as it travels into the cricothyroid membrane. The superior, middle, and inferior thyroid veins drain the thyroid gland. The superior and middle thyroid veins eventually drain into the internal jugular vein, while the inferior thyroid veins drain into the innominate and brachiocephalic veins. The distal end of the thyroglossal duct persists in approximately 50% of people. This remnant is anatomically referred to as the pyramidal lobe.

Answer 228

ANSWER: C COMMENTS: The most likely diagnosis in this patient is a lingual thyroid. This abnormality arises when the thyroid fails to descend normally into the standard cervical position. In some patients, this may be the only thyroid tissue present. It originates from the base of the tongue in the region of the foramen cecum. The diagnosis is best made by a physical examination that demon- strates a midline anterior cervical mass that moves with protrusion of the tongue as opposed to deglutition. Cervical ultrasound dem- onstrating an absence of thyroid tissue is also highly suggestive of a lingual thyroid. A radioactive uptake scan demonstrates the uptake of iodine within the mass. If the gland is enlarged, patients may have obstructive symptoms such as dysphagia, choking, or airway obstruction. Management of these patients is typically excision.

Answer 229

ANSWER: C COMMENTS: The RLN arises from the vagus nerve after passing into the mediastinum. The left RLN encircles the aortic arch at the ductus arteriosus and then ascends medially in the neck within the tracheoesophageal groove. The right RLN encir- cles the right subclavian artery and ascends laterally to medially toward the tracheoesophageal groove. Once in the central aspect of the neck, the RLN nerve can branch into medial and lateral components. The medial branch typically carries the motor fibers and is at risk for injury along its course toward the crico- thyroid membrane if not identified as a separate structure rela- tive to the lateral sensory branch. The laryngeal nerves can be nonrecurring in approximately 0.5%–1% of patients. In this case, the nerve originates from the cervical position of the vagus nerve. The risk for injury during cervical procedures is higher when the nerve is nonrecurrent because it travels perpendicular rather than parallel to the tracheoesophageal groove. It is more common on the right and is most often associated with the presence of aberrant cervical vascular anatomy such as a retroesophageal subclavian artery. On the left, it is rarer as it is associated with situs inversus and a right-sided aortic arch. The RLN innervates all of the intrinsic muscles of the larynx except the cricothyroid muscle, which is innervated by the external branch of the superior laryngeal nerve.

Answer 230

ANSWER: D COMMENTS: The synthesis and uptake of thyroid hormones con- sists of several steps. It begins with iodine trapping via adenosine triphosphate–dependent transport across the basement membrane of the thyrocyte. Thyroglobulin, a glycoprotein synthesized in the rough endoplasmic reticulum, then becomes iodinated by an intracellularly located catalytic enzyme called thyroid peroxidase. Two diiodotyro- sines are coupled to form T4. Peripherally, T4 is converted to the active thyroid hormone T3. In the euthyroid state, T4 is the predominant hormone produced by the thyroid gland. Peripheral deiodination of T4 to the active form T3 occurs in the liver, muscle, kidney, and anterior pituitary. T3 is transported in the serum bound to circulating carrier proteins such as thyroxine-binding globulin (TBG) and albumin.

Answer 231

ANSWER: E COMMENTS: Hypothyroidism has been associated with a number of pharmacologic therapies, the most frequent being lithium. The mechanism involves blockage of the cyclic adenosine monophos- phate–dependent pathway of hormone synthesis. It is also seen with other agents, including amiodarone, cytokines, and antithyroid medications. No relationship has been demonstrated between hypo- thyroidism and cimetidine.

Answer 232

ANSWER: D COMMENTS: The two most commonly prescribed antithyroid medications in the treatment of Graves’ disease are methimazole and PTU. Both agents work by blocking organic binding of iodine and coupling of iodotyrosines. PTU also inhibits peripheral conver- sion of T4 to T3. Both have a side-effect profile that includes hepa- totoxicity and reversible granulocytopenia. Methimazole is favored since it requires once-daily dosing as a result of its longer half-life. Both cross the placenta during pregnancy, but PTU appears to exhibit less transplacental transfer and has a lower toxicity profile. Radioactive iodine therapy, an alternative to surgery or medical therapy, can worsen exophthalmos following treatment, but neither antithyroid medication alters the degree of the eye findings associ- ated with Graves’ disease.

Answer 233

ANSWER: D COMMENTS: Graves’ disease is an example of an organ-specific autoimmune disease. It has been associated with other autoimmune diseases such as pernicious anemia, vitiligo, alopecia, angioedema, and myasthenia gravis. The extrathyroidal manifestations of Graves’ disease include exophthalmos, pretibial myxedema, acro- pachy, and vitiligo. Patients with severe hypothyroidism may present with myxedema coma and can require initial emergency treatment with high doses of IV T4.

Answer 234

ANSWER: D COMMENTS: A common feature of autoimmune thyroid disease is the presence of immunoreactivity toward specific thyroid anti- gens. More than 90% of patients with Graves’ disease will express elevated thyroid-stimulating antibodies (anti-TSH), which is considered diagnostic. Thyroid antibodies also include thyroid peroxidase antibodies (anti-TPO) and thyroglobulin antibodies (anti-Tg), which typically indicate an autoimmune thyroiditis, but not thyroid function. Rarely in Graves’ disease do patients have antinuclear antibodies such as anti-Ro, anti-dsDNA, or anticar- diolipin antibodies

Answer 235

ANSWER: B COMMENTS: A diagnosis of thyrotoxicosis is suspected in this patient. Of the tests listed, the one most likely to yield a diagnosis is a radioactive uptake scan. The initial workup of a thyroid nodule should not include a thyroid uptake scan unless the patient exhibits signs or symptoms of hyperthyroidism. Elevated uptake with a diffusely enlarged gland confirms the diagnosis of Graves’ disease and assists in differentiating it from other forms of hyperthyroidism. In this patient, the palp- able mass on examination could instead be a toxic nodule, and the radioactive uptake scan would illustrate a “hot” nodule in the setting of a suppressed gland. A thyroid uptake scan is useful in determining whether the patient has a toxic nodular goiter as a potential explanation of her hyperthyroid state. Cervi- cal ultrasound depicts thyroid anatomy, but does not indicate thyroid function. The most useful test in the initial screening of patients for hyperthyroidism is TSH since the suppression of TSH below normal is a sensitive indicator of excess circulating thyroid hormone. It would not be appropriate to initiate therapy for hyperthyroidism, however, until the cause of the hyperthy- roidism is established. Thyroid peroxidase antibodies (anti- TPO) are commonly found in Graves’ disease, but are not diagnostic. A biopsy by FNA would be appropriate if the nodules were found to have no uptake on a radioiodine uptake scan. Treatment of hyperthyroidism includes medical therapy, radioactive iodine, and surgical resection. Presently, the major- ity of patients with thyrotoxicosis are treated with pharmaco- logic agents or, alternatively, ablation with radioactive iodine. Surgical treatment is recommended for patients who have (1) a large goiter with a low radioiodine uptake, (2) noncompliance with medical management, (3) suspicion of malignancy, (4) severe exophthalmos, (5) pregnancy, and (6) age younger than 15 years (because of the risks associated with exposure to radiation).

Answer 236

ANSWER: D COMMENTS: Hashimoto’s disease is a type of autoimmune thyroiditis. Histologically, the gland exhibits a dense lymphocytic infiltrate associated with a dense fibrosis. When the disease is active, patients can experience symptoms associated with either hypothyroidism or hyperthyroidism. The natural progression of the disease is the eventual development of a multinodular goiter associ- ated with hypothyroidism. Surgery is rarely indicated except in the setting of (1) debilitating symptoms of thyroid dysfunction, (2) compressive symptoms from multinodular goiter, and (3) suspicion of malignancy. The presence of a nodular disease mandates FNA to rule out lymphoma or papillary thyroid carcinoma. Hashimoto’s thyroiditis is more common in women than in men (4 to 10:1 female preponderance).

Answer 237

ANSWER: A COMMENTS: Hürthle cell carcinoma is considered a subtype of follicular carcinoma and, similarly, is characterized by vascular or capsular invasion. Hürthle cell carcinomas account for approxi- mately 3% of all thyroid malignancies. Different from follicular carcinoma, Hürthle cell carcinomas are more often multifocal and bilateral, have a higher rate of local nodal metastases (25%), and demonstrate a poor radioactive iodine uptake. Hürthle cell carcino- mas have also been associated with higher mortality than follicular carcinomas (approximately 20% at 10 years). Previous radiation exposure has been correlated with an increase in bilateralism and multicentricity of Hürthle cell neoplasms, as well as an increased incidence of contralateral non–Hürthle cell malignant thyroid lesions.

Answer 238

ANSWER: C COMMENTS: Injury to the RLN occurs in less than 1% of patients. The risk is higher with low-volume surgeons, reoperative surgery, irradiated necks, and invasive cancers. Transient neura- praxia can occur as a result of excessive stretch on the nerve, but typically recovers following the procedure. In such cases, there can be a loss of signal with intraoperative nerve monitoring, just as would be seen if the nerves were completely transected. One should repair the nerve primarily or using a nerve graft if necessary, typi- cally from ansa cervicalis, in order to decrease tension on the repair at the same operation. The goal of repairing the nerve is to maintain tone to the false vocal cords, thereby preventing it from atrophying over time. This, however, should be completed after the ipsilateral lobe of the thyroid is removed to prevent the repair from being disturbed. If this problem is encountered in a patient such as this one in whom the intended operation is not yet complete, the best decision is to complete the procedure on the side where the nerve has been injured and not to proceed to the unaffected side since a diagnosis of malignancy has not yet been established. After the recovery period, the patient should undergo a formal vocal cord evaluation and have a lengthy discussion regarding the risks and benefits of proceeding with the subsequent portion of the operation if necessary. Intraoperative laryngoscopy is of no use because the patient is unresponsive, and a functional vocal cord evaluation is very limited while the patient is still intubated. `

Answer 239

ANSWER: E COMMENTS: The pathologic characteristics of papillary thyroid carcinoma include nuclear grooves and inclusions. Psammoma bodies are also pathognomonic of papillary thyroid carcinoma. Papillary thyroid carcinoma spreads via the lymphatics, while fol- licular thyroid carcinoma spreads hematogenously. MTC spreads via the lymphatics initially. Amyloid deposits represent collections of calcitonin within the thyroid specimen. Hürthle cell carcinoma is a subtype of follicular thyroid carcinoma that has a more aggres- sive phenotype.

Answer 240

ANSWER: D COMMENTS: Primary thyroid lymphoma is rare (<1% of all thyroid malignancies). There is an increased association between lymphoma and Hashimoto’s thyroiditis. The initial workup of a newly diagnosed thyroid mass should be completed. FNA can be diagnostic, but flow cytometry is needed to establish the diagnosis. On ultrasound, the thyroid will classically have a pseudocystic pattern. In the current patient, the presence of Hashimoto’s thyroid- itis, a rapidly enlarging mass, and the constitutional symptoms are highly suggestive of primary thyroid lymphoma. If FNA fails to yield a diagnosis on the first attempt, it has been shown that repeated FNA is unlikely to be diagnostic in subsequent attempts. Observation is not an appropriate step in the management of any patient with a rapidly enlarging neck mass. Performing open or core biopsy is a feasible option in these circumstances and would more likely provide an adequate cell yield to complete flow cytometry and establish monoclonality. Treatment varies between chemother- apy and surgical ablation. Resection is typically reserved for patients who fail to respond to chemotherapy or have completed their course of adjuvant therapy and demonstrated incomplete regression of disease. If surgery is planned, total thyroidectomy should be performed, followed by chemotherapy.

Answer 241

ANSWER: C COMMENTS: Papillary thyroid carcinoma is the most common type of thyroid malignancy. Patients have an overall predicted 5-year survival rate greater than 95%. Several clinical factors are currently used as prognosticators of a patient’s clinical outcome. B-type RAF (BRAF) is part of the Raf kinase family and plays a fundamental role in the classic intracellular signaling mitogen- activated protein kinase (MAPK) pathway. BRAF mutations occur in papillary and anaplastic tumors, but not in follicular thyroid carcinomas. BRAF mutations are associated with an increased risk for LN metastasis, extrathyroidal invasion, and advanced tumor stages. RET is the gene found to be mutated in patients with MTC. RET can also fuse with other genes, and such fusion products have been implicated in the pathogenesis of papillary thyroid carcinoma. Menin is mutated in patients with multiple endocrine neoplasia type I. Both p53 and RAS have not been identified as genetic prognos- ticators in patients with papillary thyroid carcinoma.

Answer 242

ANSWER: A COMMENTS: Approximately 1% of thyroid malignancies in the United States are discovered to be anaplastic thyroid carcinoma. Elderly women are more commonly affected. The tumors are often large and may be fixed to surrounding structures with areas of necrosis that can be visualized on MRI. Diagnosis is confirmed with the above FNA biopsy result. All patients should undergo a preoperative laryngoscopy to assess the status of the vocal cords. A total thyroidectomy with LN dissection is recommended for intrathyroidal masses. En bloc resection should be considered if an R1 resection can be achieved for tumors with extrathyroidal exten- sion. Cytotoxic chemotherapy is typically given along with adju- vant radiation for patients with a good performance status and no evidence of metastatic disease. Tracheostomy should be avoided for as long as possible unless there is impending airway loss.

Answer 243

ANSWER: A COMMENTS: Metastases to the thyroid are rare. The most common metastases to the thyroid are from renal cell carcinoma, and they can develop several years after the initial diagnosis. Other types of cancer that metastasize to the thyroid include lung and breast cancers. Management depends on the state of the primary disease in other locations and the predicted overall survival.

Answer 244

ANSWER: D COMMENTS: There is an associated increased risk for thyroid malignancy in patients with thyroid nodules and any of the follow- ing features: radiation exposure, rapid growth during observation, family history of thyroid cancer, cold nodule on radioactive uptake scan, male gender, and age older than 45 years. Hot nodules on a thyroid uptake scan generally indicate hyperfunctioning growth associated with such conditions as toxic multinodular goiter or Graves’ disease.

Answer 245

ANSWER: D COMMENTS: The initial workup of a new thyroid nodule involves obtaining a thorough history and physical examination, with particular attention to the sequelae of hyper- and hypothyroid- ism, symptoms of compression, and signs of malignancy. The physical examination focuses on palpation of the thyroid and cervi- cal lymphadenopathy. Ultrasonography should be performed to document whether a nodule is suspicious and warrants further workup before surgery. If a diagnosis of malignancy is made, the extent of surgery (subtotal versus complete versus LN dissection) can be determined preoperatively. Thyroid dysfunction involves measurement of TSH. The thyroid production of T4 is assessed by measuring both free and total T4. Total T4 is the amount of both free and protein-bound hormone. Thyroglobulin is not routinely measured as part of the initial assessment of thyroid function. Obtaining a family history of thyroid dysfunction or malignancy and a history of radiation are other key aspects of the history taking and physical examination.

Answer 246

ANSWER: D COMMENTS: Calcitonin is produced by the parafollicular cells of the thyroid gland. This 32–amino acid polypeptide is the princi- pal hormone responsible for lowering serum calcium levels during states of hypercalcemia. The action of calcitonin takes place on the surface receptors of osteoclasts, which work to inhibit bone resorp- tion and thus reduce serum calcium levels. MTCs are tumors of the parafollicular cells that produce calcitonin. The resulting hyper- calcitoninemia seen in these patients can be a measure of tumor burden. Carcinoembryonic antigen (CEA) may also be elevated in some patients with MTC. Calcitonin doubling times of greater than 2 years are associated with a better long-term prognosis than the doubling times of less than 6 months. The American Thyroid Asso- ciation (ATA) provides a web-based calculator to monitor the levels of calcitonin and CEA to aid in the follow-up and management of patients with MTC.

Answer 247

ANSWER: B COMMENTS: Preoperatively, patients with Graves’ disease should have their thyrotoxic state controlled through the use of antithyroid medications. Without this, induction of anesthesia can induce a thyroid storm. Many endocrine surgeons advocate giving patients a 7- to 10-day preoperative course of either Lugol’s solution or SSKI to help diminish the hypervascularity of the gland and minimize operative blood loss, although some studies have shown that preoperative administration of concentrated iodide preparations can also induce hypertrophy of the gland and should possibly be avoided in patients with diffusely enlarged toxic goiters. When given in concentrated doses, iodine can inhibit the release of thyroid hormone. This process of “thyroid stunning” is referred to as the Wolff–Chaikoff effect. It is sometimes seen in patients who have a diagnostic radioactive iodine scan and then demonstrate minimal uptake of radioactive iodine when the thera- peutic dose is given. In preparing hyperthyroid patients for surgery, administration of potassium iodide solutions has been shown to treat hyperactivity and decrease intraoperative blood loss during thyroidectomy. This stunning effect is transient and is thus not used for the long-term management of hyperthyroid patients. Concentrated potassium iodide (Lugol’s solution) should be used with caution in this setting since it will aggravate the hyperthyroidism after its initial effect wears off. β-Blockers are used to mitigate the symptoms of adrenergic stimulation but are not given to all patients with Graves’ disease preoperatively unless they exhibit signs of thyrotoxic-induced tachycardia. β-Blockers do not directly inhibit synthesis of thyroid hormone, but they do counteract some of the peripheral effects of its action on the car- diovascular system. Corticosteroids not only inhibit peripheral conversion of T4 to T3 but also suppress the production of TSH. In acute severe hyperthyroid states, corticosteroids can help in the initial treatment.

Answer 248

ANSWER: D COMMENTS: Thyrotoxicosis occurs in approximately 0.1%– 0.4% of pregnancies in the United States. If not recognized and treated promptly, severe complications can arise in both the mother and the fetus. The hormonal changes and fluctuating metabolic demands during pregnancy have an important impact on thyroid physiology. These changes can make interpretation of laboratory tests of thyroid function in pregnant patients extremely challeng- ing. During pregnancy, there is a rise in TBG, which in turn causes an increase in the total serum T4 and T3. The degree of change in TBG levels is dependent on the particular trimester. By 16 to 20 weeks, serum TBG levels have in most cases risen to double the nonpregnant values. Additionally, hCG shares structural similarity with TSH and has been shown to have weak thyroid-stimulating activity. This fact may explain why thyroid nodules often increase in size during pregnancy. The mimicked activity of TSH allows hCG to provide negative feedback in such a way that TSH levels during pregnancy are always lower than is reflective of the true thyroid functional state. Thus if normal ranges of TSH that are specific to pregnancy are not used, hyperthyroidism can be inap- propriately diagnosed. Additionally, in pregnancy, renal clearance of iodine is increased, and thus patients will have increased base- line 24-h radioactive iodine uptake when compared with nonpreg- nant patients. The increased renal clearance has no direct effect on the circulating levels of total T3. In fact, pregnant patients have increased T4 and T3 levels because of their increased total plasma volumes.

Answer 249

ANSWER: B COMMENTS: In a clinically euthyroid patient, the initial test of choice should be cervical ultrasound followed by FNA of any suspicious nodules discovered on clinical or radiographic examina- tion. FNA has a false-negative rate of approximately 3% and a false-positive rate of 4%. A TSH level should be ordered to docu- ment thyroid function. Not all calcifications on thyroid ultrasound are associated with a malignant lesion. Typical benign cystic lesions will exhibit a complete halo (intact capsule) and peripheral calcifi- cations. Size is not generally thought to be a consistent predictor of malignancy. However, lesions greater than 1 cm are believed to be amenable to fine-needle biopsy. Table 16.1 lists some of the ultrasonographic features associated with benign and malignant disease.

Answer 250

ANSWER: D COMMENTS: A finding of follicular neoplasm on FNA carries approximately 15%–30% risk of harboring a malignancy. At a minimum, the patient should undergo a right lobectomy with or without a frozen resection. Surgical excision is necessary because follicular neoplasms cannot be diagnosed as malignant or benign without microscopic examination of the nodule’s capsule. In patients who have additional risk factors for thyroid cancer (e.g., family history and exposure to radiation), total thyroidectomy should strongly be considered to avoid the need for reoperative surgery given the higher likelihood of finding a malignant nodule. Only patients with atypia of undetermined significance should be offered the option of observation and repeated imaging in 6 months. Expression arrays, which are being used to investigate microRNAs that have been impli- cated for their role in carcinogenesis, are sometimes used to aid in the determination of the risk of malignancy for inconclusive FNA biopsies although their utility has yet to be definitely established.

Answer 251

ANSWER: C COMMENTS: Papillary thyroid carcinoma carries a very favor- able prognosis with a 10-year survival of greater than 95%. Risk stratification is a fundamental aspect of how treatment and surveil- lance algorithms are developed. For well-differentiated thyroid carcinomas, the TNM staging is divided into those younger than 45 years old and those 45 years or older. For those younger than 45 years, stage I includes any T or N and M0 and stage II includes any T or N and M1. For those 45 years or older, stage I includes T1, N0, and M0; stage II includes T2 or T3, N0, and M0; stage III includes T4, N0, M0, and any T, N1, M0; and stage IV includes any T or N, and M1. All undifferentiated or anaplastic carcinomas are stage IV. In addition to the TNM staging system, other fre- quently used systems include AGES (age, grade, extrathyroidal extension, and size) and AMES (age, metastases, extension, and size). Although each of these staging systems does a reasonable job of predicting cancer-specific survival, none have any prognostic value in assessing the risk of recurrence. Thyroglobulin levels are not a part of any of the current staging systems and are most useful in the surveillance for recurrence of thyroid cancer after thyroidec- tomy and/or radioactive iodine therapy.

Answer 252

ANSWER: D COMMENTS: MTC arises from the parafollicular cells of the thyroid. Its serum tumor marker is calcitonin. Patients with diffuse and advanced disease can have symptoms of calcitonin excess (diarrhea, flushing, and abdominal cramping). More than 80% of cases of MTC are sporadic and thus have no hereditary association. That being said, every patient in whom MTC is newly diagnosed should be referred for genetic counseling and evaluation for a RET protooncogene mutation because there are identifiable genetic mutations that predict the prognosis and aggressiveness of the disease. The overall survival of patients with MTC is determined largely by the completeness of resection and the presence of per- sistent disease. Thus surgical treatment of MTC tends to favor aggressive therapy. All patients with biopsy-confirmed MTC and no evidence of nodal or distant metastases should undergo a minimum total thyroidectomy with bilateral central node dis- section. Whether lateral compartment dissection is performed is dependent on whether there is radiographic or operative evidence of gross disease. Current 2015 ATA guidelines for MTC recom- mend that all patients with findings on FNA or a calcitonin level suggestive of MTC should undergo preoperative neck ultrasonog- raphy for the evaluation of LN metastases. Biochemical screening for associated manifestations (e.g., hyperparathyroidism and pheo- chromocytoma) should also be performed by obtaining a serum calcium level and measurement of either plasma metanephrines or 24-h urine catecholamines. CEA and calcitonin are useful tumor markers in predicting disease burden and recurrence in patients with MTC.

Answer 253

ANSWER: E COMMENTS: According to the 2016 Cancer Facts and Figures published by the American Cancer Society, the incidence of thyroid cancer has not only been rising worldwide over the past few decades but is now the most rapidly increasing cancer in the United States. In the United States, rates have increased by over 5% per year from 2003 to 2012. Current evidence supports the fact that the increase is most likely multifactorial, including radiation exposure, environmental, hormonal, and genetic factors. The rise is also partly attributed to increased detection as a result of both an increased use of imaging and more sensitive diagnostic modalities. The iodine status does appear to influence the subtype of thyroid cancer that populations are at risk for. There is a reported increased risk for thyroid cancer in iodine-replete areas, mainly papillary thyroid carcinoma, whereas iodine-deficient areas show a slightly increased incidence of follicular thyroid carcinoma. The utilization of thyroid function tests is not directly associated with the rise in the incidence of thyroid cancer.

Answer 254

ANSWER: B COMMENTS: There are typically four parathyroid glands. Super- numerary glands have been found in up to 13% of people on autopsy. They are typically light brown in appearance, measure 7 mm in size, and each weighs 50 mg. The superior glands are dorsal and lateral to the RLN, while the inferior glands are ventral and medial to the RLN. Parathyroid glands primarily derive their blood supply from the inferior thyroid artery. Branches of the superior thyroid artery can provide up to 20% of the blood supply of the superior glands. Branches from the thyroidea ima, in addition to vessels to the trachea, esophagus, larynx, and mediastinum, may also be found.

Answer 255

ANSWER: D COMMENTS: Calcium is the most abundant cation in the human body. As much as 99% of calcium is stored in the musculoskeletal system. The remainder is present in serum and exists in three forms: (1) 45% is bound to albumin and is biologically inert, (2) 50% is ionized and metabolically active, and (3) a small percentage is complexed with citrate and is also biologically inactive. Hypoalbuminemia means that more of the total serum calcium will be free and metabolically active. Although total serum calcium may be low, the patient may not be metabolically hypocalcemic. Ionized calcium levels are inversely affected by the pH of blood. A one-unit rise in pH will decrease the ionized calcium level by 0.36 mmol/L. Hypoventilation would cause a drop in pH and thus a subsequent rise in the ionized calcium level.

Answer 256

ANSWER: B COMMENTS: Vitamin D synthesis begins in the keratinocytes of the skin. Subsequently, hydroxylation occurs in the liver to yield 25-hydroxyvitamin D. The final step in the conversion of vitamin D to its active form occurs in the kidney, where a second hydrox- ylation reaction takes place to yield 1,25-dihydroxyvitamin D. Sun- light plays a key role in the initial synthesis step in the skin. Persons who are not exposed to sunlight require supplemental vitamin D through dietary intake.

Answer 257

ANSWER: A COMMENTS: Calcitonin is produced by the parafollicular cells (C cells) of the thyroid gland and works to oppose the actions of PTH. It helps lower ionized calcium levels in primarily two ways. First, it inhibits osteoclast-mediated bone resorption. Second, it inhibits resorption of calcium and phosphate by the kidney. Calci- tonin has no direct effects on intestinal absorption or osteoblast- mediated bone formation. It is also used in the treatment of hypercalcemic crisis (4 IU/kg subcutaneously/intramuscularly). It acts quickly (24 to 48 h) and is more effective when used in com- bination with glucocorticoids. Finally, calcitonin is a useful marker with regard to surveillance in medullary thyroid carcinoma.

Answer 258

ANSWER: A COMMENTS: PTH has a variety of actions and targets to help increase serum calcium levels. The parathyroid cells express a G protein–coupled membrane receptor that senses serum calcium levels. When calcium levels fall below appropriate levels, the receptor stimulates the release of PTH into the circulation. PTH has a half-life of about 2 to 4 min in the circulation. Before its rapid clearance, it first targets osteoclasts and stimulates them to resorb calcium and phosphate from bone. In the kidney, PTH blocks calcium excretion at the distal convoluted tubule. It indirectly pro- motes intestinal absorption of calcium by enhancing the renally mediated activation of vitamin D.

Answer 259

ANSWER: E COMMENTS: A number of conditions can cause hypercalcemia, including granulomatous disorders such as sarcoidosis, tuberculo- sis, and histoplasmosis. Medications can falsely elevate the serum calcium level. Examples include thiazide diuretics, lithium, and vitamin A or D. Other conditions include Paget’s disease, immobi- lization, and malignancy. In hospitalized patients, malignancy is the most common cause of hypercalcemia.

Answer 260

ANSWER: B COMMENTS: In a patient with suspected PHPT, it is important to document normal renal function before the interpretation of parathyroid function tests. The minimum testing that should be performed includes intact PTH, serum calcium, blood urea nitrogen (BUN), creatinine, and vitamin D levels. In addition, a 24-h urine calcium excretion should be measured to exclude FHH. Measuring PTH-related protein (PTHrp) is unnecessary unless metastatic cancer is suspected. FHH should be strongly considered in patients who have a family history of hypercalcemia and no previous history of normal calcium levels.

Answer 261

ANSWER: B COMMENTS: The pathophysiology of secondary hyperparathy- roidism is multifactorial and can result from phosphorous retention, altered vitamin D metabolism and resistance, altered metabolism of PTH, impaired calcemic response to PTH, and possible genetic mutations. The condition most commonly occurs in patients with a history of chronic renal failure. Gastric bypass has also been an increasingly recognized cause of altered vitamin D metabolism. Patients will commonly have an elevated PTH level and normal serum calcium. In such a setting, vitamin D levels should be mea- sured and, if low, treated for a minimum of 6 weeks with supple- mental vitamin D.

Answer 262

ANSWER: A COMMENTS: Secondary hyperparathyroidism is most com- monly managed medically with the use of calcimimetic agents (e.g., cinacalcet), phosphate binders, adequate calcium intake, and vitamin D replacement. Cinacalcet works by binding the calcium- sensing receptors on the chief cells of the parathyroid gland and increasing its sensitivity to extracellular calcium. Surgical treat- ment is indicated in patients with (1) renal osteodystrophy, (2) calciphylaxis, (3) calcium phosphate product of ≥70, (4) soft tissue calcium deposition and tumoral calcinosis, and (5) calcium level greater than 11 mg/dL with an inappropriately high level of PTH. Renal osteodystrophy is a major issue in hemodialysis patients. The aluminum present in the dialysate bath accumulates in the bone and contributes to the development of osteomalacia. Osteitis fibrosa cystica, a type of renal osteodystrophy, is characterized by marrow fibrosis and increased bone turnover. Bone cysts, osteopenia, and decreased bone strength develop. To halt the progression of this disease process, these patients with secondary hyperparathyroidism are treated surgically. Calciphylaxis is a rare vascular disorder in which calcium is deposited in the media of small- to medium-sized arteries. As a result, ischemic damage to the dermal and epidermal structures develops. The ulcerated lesions are extremely painful and can become infected with subsequent sepsis, and eventually death. Patients with early signs of calciphylaxis should undergo an urgent parathyroidectomy, although there is some evidence that aggressive management of serum calcium and parathyroid levels with cinacalcet may be beneficial. Care should be taken in wound care management because aggressive debridement can lead to chronic nonhealing wounds since wound healing is very poor in these patients. Uremic pruritus is characterized by severe itching that is thought to result from increased deposition of calcium salt in the dermis without the visible lesions of calciphylaxis. Parathy- roidectomy seems to alleviate these symptoms and halts progres- sion to the more serious skin and vascular complications seen with calciphylaxis.

Answer 263

ANSWER: B COMMENTS: PHPT is a relatively common disorder that affects 0.3% of the human population, most commonly women. The exact cause of PHPT is unknown. In 80% of patients only a single adenoma is present, but multiple adenomas or hyperplasia can be present in up to 15%–20%. Patients with PHPT can have symp- tomatic or “asymptomatic” disease. Some degree of renal dysfunc- tion is present in up to 80% of patients. Nephrolithiasis, however, is far less common, with an incidence of approximately 20%–25%. The clinical manifestations of PHPT vary widely across patients, but if a detailed history is taken, many will complain of polydipsia and polyuria from the calciuresis associated with the disease. Although PHPT occurs sporadically in the majority of patients, in a small percentage it is part of a familial syndrome. Multiple endo- crine neoplasia type I (MEN-I) results from a germline mutation in the menin gene located on chromosome 11q12-13. Patients with MEN-I are susceptible to the development of pancreatic neuroen- docrine tumors, pituitary adenomas, and PHPT. MEN-IIA is an autosomal dominantly inherited condition caused by a germline mutation on chromosome 11 that is associated with PHPT, pheo- chromocytoma, and medullary thyroid cancer. Patients with famil- ial jaw tumor syndrome have a higher risk for the development of parathyroid carcinoma. Familial hypercalcemic hypocalciuria is associated with elevated calcium levels and low urinary excretion of calcium. The primary defect is the abnormal sensing of calcium in blood by the parathyroid gland and the renal tubules, which causes inappropriate secretion of PTH and excessive renal reab- sorption of calcium.

Answer 264

ANSWER: E COMMENTS: Guidelines for surgery in asymptomatic PHPT include age less than 50 years old; a serum calcium measurement 1.0 mg/dL (0.25 mmol/L) above the upper limit of normal; bone mineral density by dual-energy x-ray absorptiometry (DXA) with a T-score < −2.5 at lumbar, spine, total hip, femoral neck, or distal 1/3 radius, vertebral fracture on x-ray, computed tomography (CT), magnetic resonance imaging (MRI), 24-h urine for calcium > 400 mg/day (>10 mmol/day) and increased risk of stone on biochemical stone risk analysis, or the presence of nephrolithiasis or nephrocal- cinosis on x-ray, ultrasound, or CT. For patients with PHPT who do not undergo surgery, monitoring guidelines include at minimum obtaining an annual serum calcium, DXA every 1 to 2 years, and annual estimated glomerular filtration rate (eGFR)/serum creatinine.

Answer 265

ANSWER: A COMMENTS: Although all of these imaging studies have been used to identify the location of a parathyroid adenoma, MRI is the least sensitive of those listed. Routine preoperative localization in patients with PHPT includes neck ultrasound and technetium-99m– labeled sestamibi scan. Sestamibi scan has a reported sensitivity as high as 90%. Ultrasound is slightly less sensitive (75%), but the ease of in-office use makes it a useful tool for the general surgeon. SPECT, when used with planar sestamibi, is very good at locating potential ectopic glands such as those in the mediastinum. 4D-CT incorporates contrast perfusion in hyperfunctioning parathyroid tissue over time. This additional layer provides functional informa- tion in addition to the anatomic information provided by a standard CT scan. In a recent study, 4D-CT has shown improved sensitivity over all other modalities, especially when used in combination with ultrasound.

Answer 266

ANSWER: A COMMENTS: No study has yet identified a reliable predictor for determining which patients with sporadic hyperparathyroidism will have multigland disease. The exception is in familial, secondary, and tertiary hyperparathyroidism. Because of the nearly uniform inci- dence of four-gland hyperplasia, all these patients are managed with bilateral neck exploration and either total parathyroidectomy with autotransplantation or three-and-a-half gland parathyroidectomy. Although some surgeons believe that patients with higher preopera- tive PTH or calcium levels (or both) are more likely to have multi- gland disease, this has not been proved to be true in clinical studies.

Answer 267

ANSWER: B COMMENTS: Focused parathyroidectomy is the preferred approach in patients who have a solitary lesion that is imaged conclusively by ultrasound, sestamibi, or other appropriate imaging modalities. If the surgeon is not attempting to visualize all four glands, the use of IOPTH to determine whether all hyperfunction- ing tissue has been removed and to document an appropriate drop in PTH levels after the removal of the suspected gland is the stan- dard of care. The most common criterion used is a 50% or greater reduction in the PTH level from the baseline 10 min after parathy- roidectomy. The best clinical marker of single-gland disease is concordant preoperative imaging in combination with an appropri- ate correction of IOPTH levels. Previous neck surgery or lack of concordant imaging on two types of studies is not a contraindica- tion to attempting focused parathyroidectomy. Patients suspected of having multigland disease are managed by four-gland explora- tion via a smaller incision.

Answer 268

ANSWER: A COMMENTS: Hyperparathyroidism during pregnancy is often unrecognized and is associated with a 3.5-fold increase in miscar- riage. Loss of the pregnancy most often occurs during the late second trimester. The incidence of hyperparathyroidism in preg- nancy is 0.7%. Maternal complications include hyperemesis, neph- rolithiasis, and pancreatitis. Fetal complications include spontaneous abortion and growth retardation. In those who reach delivery, neo- natal complications include hypocalcemic crisis within the first few days of life. Calcimimetic medications have not been used in the setting of hyperparathyroidism in pregnancy. Calcitonin has no role in the management of hyperparathyroidism.

Answer 269

ANSWER: E COMMENTS: Although this patient did experience a 50% drop from the highest preremoval level, 200 ng/L is still quite elevated. When the surgeon is going to accept a 50% drop, the final level should either approach normal or be following a kinetic trend toward normal. A preexcision level that is within a few-fold eleva- tion of the upper limit of normal should demonstrate normal kinet- ics and rapidly approach normal levels within two to three half-lives of the hormone after the adenoma is removed. The first steps in this situation should be to repeat the PTH level 15 to 20 min following gland removal and send off a frozen section for confirmation of the candidate gland removed. It would then be appropriate to either await the results of these two tests or proceed with the four-gland exploration. The use of intraoperative PTH monitoring has revolu- tionized how parathyroid surgery is performed. It has allowed sur- geons to perform directed operations and, before leaving the operating room, document whether a biochemical cure has been achieved with relative certainty. Many surgeons include determina- tion of a preincision PTH level, a stimulated (pre–pedicle ligation) level, and subsequent postremoval levels at 5-min intervals until a normal level is achieved. In patients with secondary or tertiary hyperparathyroidism and stimulation levels as high as 2000 ng/L, a 90% decrease has been suggested as being indicative of cure.

Answer 270

ANSWER: D COMMENTS: The left inferior parathyroid gland has not been identified in this patient. “Hyperplastic parathyroid tissue” has been confirmed on frozen section in the three identified glands. Failure to find a normal parathyroid gland among those identified should alert the surgeon that the patient probably has four-gland hyperpla- sia. Failure to find the remaining gland places the patient at a high risk for persistent hyperparathyroidism. Most lower parathyroid glands are found in proximity to the lower thyroid pole. If not found at this location, the thyrothymic ligament and thymus should be explored. If the IOPTH level does not normalize after this maneu- ver, intraoperative ultrasound of the left thyroid lobe versus left lobectomy should be performed. Finally, central neck dissection and exploration of the left carotid sheath are performed. The pro- cedure is terminated after these steps, and further imaging and localization studies should be undertaken if the patient has persis- tent hyperparathyroidism.

Answer 271

ANSWER: D COMMENTS: The most common causes for persistent and recur- rent hyperparathyroidism include ectopic parathyroids, unrecognized hyperplasia, or supernumerary glands. The most common ectopic location is paraesophageal (28%), followed by mediastinal (26%), intrathymic (25%), intrathyroidal (11%), carotid sheath (9%), and high cervical or undescended (2%). Less common causes include missed adenoma in a normal position, incomplete resection of an abnormal gland, parathyroid carcinoma, and parathyromatosis.

Answer 272

ANSWER: C COMMENTS: “Hungry bone syndrome” is characterized by post- parathyroidectomy hypocalcemia and hypophosphatemia. Patients most at risk are those with four-gland hyperplasia from secondary or tertiary hyperparathyroidism. The postoperative calcium level in these patients can drop critically low and necessitate intravenous calcium supplementation. During this period both serum calcium and phosphate levels must be monitored closely. In some patients it can take more than 4 to 5 days for serum calcium and phosphate levels to stabilize. Other patients shown to have increased risk for this condition are those who are older or have concomitant thyro- toxicosis or a large single adenoma. The preoperative PTH level has not been found to be an independent predictor of whether “hungry bone syndrome” will develop postoperatively.

Answer 273

ANSWER: B COMMENTS: The first step in the management of this patient with hypercalcemia should be aggressive immediate IV hydration with 0.9% saline solution and a goal urine output above 100 mL/h. After an adequate urine output is established, a loop diuretic should be given to facilitate the renal clearance of calcium. Other adjuncts include the use of bisphosphonates, calcitonin, mithramycin, gallium nitrate, and glucocorticoids. Table 17.1 lists therapies used to treat hypercalcemic crisis, along with the onset of action, advan- tages, and disadvantages of each treatment.

Answer 274

ANSWER: C COMMENTS: Postoperative hypocalcemia following parathy- roidectomy is not unusual. The majority of patients are asymptom- atic and identified only when routine postoperative laboratory tests are obtained. In asymptomatic patients, oral calcium and vitamin D should be initiated promptly. Symptomatic patients will most com- monly complain of circumoral numbness first followed by tingling in their extremities. These two features are early signs of hypocal- cemia. PTH and calcium levels should be drawn. If the patient is hypocalcemic, high doses of calcium should be started. If PTH is undetectable, 1, 25-dihydroxy vitamin D (calcitriol) should be started 0.25 to 0.5 μg twice a day. On examination, these patients may have carpopedal spasm elicited by occlusion of blood flow to the forearm (Trousseau sign) or contraction of the facial muscles elicited by tapping on the facial nerve (Chvostek sign). However, nearly 20% of the general population has a positive Chvostek sign. If the condition is allowed to worsen, tetany, laryngeal stridor, or tonic–clonic seizures can develop, all of which can be fatal. These patients should be treated immediately with intravenous calcium.

Answer 275

ANSWER: C COMMENTS: This scenario is a classic description of a patient with parathyromatosis. This rare condition is manifested clinically as recur- rent or persistent hyperparathyroidism following multiple attempts at resection. On exploration, patients will have several small nodules of hyperfunctioning parathyroid tissue throughout the neck and possibly the mediastinum. It can be difficult to distinguish this condition from parathyroid carcinoma or an “atypical adenoma.” Parathyromatosis is believed to result from either a low-grade parathyroid malignancy, fracture of the parathyroid adenoma capsule at the original procedure, or overgrowth of embryologic rests of parathyroid tissue Management of these patients involves either serial debulking of the disease when it can be radiographically identified or pharmacologic treatment. Patients are rarely cured with surgery.

Answer 276

ANSWER: C COMMENTS: A preoperative serum calcium level greater than 14 mg/dL, a palpable nodule, and adherence to surrounding tissues have all been found to be useful predictors of parathyroid carci- noma. Additionally, patients with familial hyperparathyroidism with jaw tumor syndrome, which is associated with tumor suppres- sor locus HRPT2 (parafibromin or CDC73) on chromosome 1, have an increased risk for parathyroid cancer. Parathyroid carcinoma is rare and represents just 1% of all cases of PHPT. The prognosis is extremely poor, and most patients have advanced disease when initially seen. Parathyroid carcinoma should be suspected in a patient with a preoperative calcium level greater than 14 mg/dL or a serum PTH level two to three times the upper limit of normal. Intraoperatively, parathyroid cancers are typically large and less brown than a benign parathyroid adenoma. Invasion or adherence to the surrounding tissues should also raise suspicion for parathy- roid carcinoma. Appropriate surgical management of this condition entails en bloc resection of the tumor with ipsilateral thyroid lobec- tomy. It is not necessary to perform a total thyroidectomy. A com- partment-oriented lymph node dissection is necessary only if there is gross evidence of lymph node involvement.

Answer 277

ANSWER: E COMMENTS: Persistent hypercalcemia is characterized by hypercalcemia that fails to correct after parathyroidectomy. Recur- rent hyperparathyroidism occurs less frequently and is defined by the development of postoperative hypercalcemia at least 6 months after having achieved normocalcemia. Preoperative localization is the mainstay of treatment algorithms for patients with persistent or recurrent hyperparathyroidism. The tests available can be divided into those that are noninvasive versus invasive. The noninvasive tests include ultrasound, sestamibi scanning, SPECT, MRI, stan- dard CT, and 4D-CT. Invasive testing includes selective venous sampling and intraoperative radioprobe guidance. Patients receive intravenous technetium-99m in the morning of the surgery, and then the radioprobe is used intraoperatively to identify the parathy- roid gland. One limitation of this technology is a high background level, which can prevent the identification of an intrathyroidal para- thyroid gland. PET has yet to have any defined role in parathyroid localization.

Answer 278

ANSWER: B COMMENTS: The adrenal glands are retroperitoneal organs located superior and medial to the kidneys. The right gland is pyramidal in shape (resembling a Witch’s hat), and the left gland is semilunar in shape. The adrenal gland is divided into two parts, a cortex and a medulla, which account for approximately 80%–90% and 10%–20% of the gland’s volume, respectively. Histologically, the cortex is divided into the outer zona glomerulosa, the middle zona fasciculata, and the inner zona reticularis. The adrenal medulla is composed of chromaffin cells derived from the neural crest tissue.

Answer 279

ANSWER: D COMMENTS: The arterial supply of the adrenal gland arises from three sources. Superiorly, branches arise from the inferior phrenic artery, whereas the middle branches originate from the aorta. Along the medial and inferior aspect of the gland are contributory branches given off by the ipsilateral renal artery. The anatomy of the venous drainage of the left and right adrenal gland differ. The inferior phrenic vein joins the left adrenal vein before it drains into the left renal vein and can measure 2 cm in length. Variably, the left inferior phrenic vein will drain separately into the left renal vein. On the right, the adrenal vein enters directly into the IVC posteriorly and is shorter and broader than the left one. This shorter configuration can make ligation technically more challenging.

Answer 280

ANSWER: A COMMENTS: Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis. The first step in catecholamine synthe- sis involves the conversion of l-tyrosine into dihydroxyphenylala- nine (l-dopa) by the enzyme tyrosine hydroxylase. Dopa decarboxylase then converts l-dopa into dopamine. Dopamine is subsequently converted to norepinephrine by the enzyme dopamine α-hydroxylase. PNMT is the enzyme located exclusively in the adrenal gland and is responsible for the conversion of norepineph- rine into epinephrine.

Answer 281

ANSWER: D COMMENTS: Histologically, the adrenal gland is divided into two components: the centrally located medulla and the peripherally located cortex. The adrenal cortex arises from the mesoderm and accounts for approximately 90% of the total adrenal mass. Histo- logically, the cortex is made up of three zones: the glomerulosa, fasciculata, and reticularis. Each zone corresponds to the synthesis of mineralocorticosteroids, corticosteroids, and sex steroids, respectively. The medulla is composed of chromaffin cells derived from ectodermal neural crest cells. The chromaffin cells are inner- vated by sympathetic fibers traveling from the sympathetic chain. They secrete the vasoactive catecholamines, epinephrine and nor- epinephrine. Norepinephrine is converted to epinephrine by the enzyme PNMT. This enzyme is exclusively located within the adrenal medulla and is not found in ectopic adrenal medullary tissue. Thus ectopic pheochromocytomas are incapable of produc- ing epinephrine since they lack this enzyme.

Answer 282

ANSWER: E COMMENTS: Aldosterone synthesis is under the control of angio- tensin II, potassium, and, to a lesser extent, ACTH. Its synthesis is inhibited by somatostatin, dopamine, atrial natriuretic factor, and heparin. Aldosterone synthase (CYP11B2) is restricted to the zona glomerulosa, where aldosterone is primarily synthesized. Angioten- sin II and potassium stimulate aldosterone secretion by increasing the transcription of CYP11B2. ACTH increases aldosterone secre- tion by no more than 10%–20% over baseline values and does so by stimulating the earlier pathways of adrenal steroidogenesis. Epi- nephrine plays no direct regulatory role in aldosterone synthesis.

Answer 283

ANSWER: A COMMENTS: The most common cause of CAH is mutations or deletions of CYP21A2, the gene that encodes for 21-hydroxylase. This enzyme defect accounts for more than 90% of the cases of CAH. In most patients, it is manifested as a salt-wasting form in which lack of the 21-hydroxylase enzyme impedes the downstream synthesis of aldosterone. Clinically, this becomes apparent within the first few months of life with the development of hypovolemia and hyperkalemia. There is excess production of ACTH because of the lack of negative feedback on steroid synthesis. Upstream pre- cursors accumulate as a result of lack of the 21-hydroxylase enzyme and are then shunted into the sex steroidogenesis pathway. This leads to the presence of ambiguous genitalia in females. The diag- nosis is made by finding elevated levels of 17-hydroxyprogeste- rone, the 21-hydroxylase substrate, and by genetic testing. Re

Answer 284

ANSWER: C COMMENTS: Acute adrenal insufficiency is a life-threatening emergency. In the critically ill patient population it can develop in either the acute or chronic phase of the illness. In the intensive care setting, if acute hypotension that is not cardiogenic in origin and is refractory to pressor support develops suddenly, acute adrenal insufficiency should be excluded. The cosyntropin stimulation test is the definitive means of diagnosing adrenal insufficiency. This test, however, can take up to 24 h to return. In the acute setting, evidence of hyperkalemia, hyperglycemia, and refractory hypoten- sion is sufficient to begin empirically treating these patients with steroids until the diagnosis can be confirmed. Morning salivary cortisol concentration higher than 5.8 ng/mL or morning serum cortisol concentration higher than 15 ug/dL rule out adrenal insuf- ficiency as the cause.

Answer 285

ANSWER: B COMMENTS: The first step in the management of a hypotensive patient suspected of having adrenal insufficiency is volume resus- citation followed by empirical steroid replacement. Corticosteroid replacement in patients with acute adrenal insufficiency should include the IV administration of either hydrocortisone 100 mg every 6 to 8 h or dexamethasone 4 mg every 24 h. Dexamethasone is long acting and does not interfere with the administration of a cosyntropin stimulation test. Blood transfusion will not reverse this patient’s condition and is not generally recommended for patients with a hemoglobin level greater than 7 g/dL.

Answer 286

ANSWER: C COMMENTS: In 1855, Thomas Addison described a clinical con- dition that involved salt wasting, skin hyperpigmentation, and his- topathologic destruction of the adrenal gland. Additional clinical symptoms of the disorder can include nausea and vague abdominal pain, musculoskeletal complaints, and postural dizziness. The most characteristic feature of Addison disease is hyperpigmentation of the skin and mucous membranes. When Addison disease was first described, tuberculous adrenalitis was the most common cause of primary adrenal insufficiency. As a result of the decreased inci- dence of advanced tuberculosis, the current most common cause is an autoimmune reaction known as Addison disease. Autoimmune Addison disease is typically associated with other autoimmune disorders such as type 1 diabetes mellitus. In patients with chronic adrenal insufficiency, maintenance therapy can be achieved with short-acting glucocorticoids (e.g., hydrocortisone—multiple recommended regimens), which are pre- ferred as they better mimic the normal diurnal rhythm, longer-acting glucocorticoids (e.g., prednisone), which may be useful in noncom- pliant patients, and the mineralocorticoid fludrocortisone, usual dose 0.1 mg/day. Treatment regimens should be tailored to each individual patient and monitored on a regular basis. Supplemental corticoste- roids are required during physiologic stress such as illness, trauma, anesthesia, and surgical procedures. One standard dose should not be applied to all patients with adrenal insufficiency, but should rather be individualized to account for the amount of glucocorticoids the patient is taking and the procedure or stress they are undergoing.

Answer 287

ANSWER: B COMMENTS: Overall, the most common cause of Cushing syn- drome is the exogenous use of corticosteroids. Among the endog- enous types of Cushing syndrome, an ACTH-hypersecreting pituitary adenoma is the most common (70%). Adrenal adenomas and ectopic ACTH-producing tumors each account for 10% of the endogenous causes of Cushing syndrome.

Answer 288

ANSWER: E COMMENTS: Etomidate, a commonly used induction agent for general anesthesia, is a potent inhibitor of the 11-hydroxylase enzyme. It is the only inhibitor of steroid synthesis that can be given parenterally and can lead to the development of adrenal insuffi- ciency. It is the treatment of choice in critically ill patients with hypercortisolism who are unable to take oral medications. Its onset of action is very rapid (<1 min), and its half-life is only 3 to 5 h. The medication is administered as a continuous infusion, with nonhypnotic doses ranging between 0.2 and 0.6 mg/kg per h. The infusion is titrated according to the decline in serum cortisol levels. Once the cortisol levels are brought within a physiologic range, some patients may require hydrocortisone supplementation to avoid the development of adrenal insufficiency.

Answer 289

ANSWER: D COMMENTS: Failure to suppress the cortisol production after the administration of high-dose dexamethasone concomitant with ele- vated plasma ACTH levels suggests that the hypothalamic-pitu- itary-adrenal axis is not intact. This scenario suggests the presence of an ectopic source of ACTH. Ectopic ACTH-producing tumors account for 10%–15% of cases of Cushing syndrome. Thoracic tumors are more common than abdominal tumors as a cause of ectopic ACTH syndrome. Of those arising in the mediastinum, primary lung carcinoids are the most common. Following in fre- quency are small cell lung cancer and thymic tumors. In approxi- mately 20% of patients, the site of ACTH production is never found.

Answer 290

ANSWER: C COMMENTS: Patients with Cushing syndrome can have a wide variety of symptoms. Classically, patients will have newly diag- nosed or poorly controlled hypertension, glucose intolerance, and truncal obesity. Additional signs and symptoms include easy bruising, proximal muscle weakness, decreased libido, nephroli- thiasis, and a flushed facial appearance (facial plethora). Nephro- lithiasis occurs in up to 50% of patients with Cushing syndrome. The underlying pathogenesis is not yet clearly defined. There is evidence that patients with Cushing syndrome have elevated urinary uric acid secretion, which could contribute to increased stone formation. Additionally, there is a documented increased risk of 1.9% for deep venous thrombosis in patients with Cushing syndrome in the nonoperative setting. In postoperative Cushing patients, the risk for venous thromboembolism ranges between 0% and 5.6%. Chronic glucocorticoid excess produces a metabolic syndrome that is associated with increased morbidity and mortal- ity. The elevated risk for venous thromboembolic disease is thought, in part, to be due to the increased prevalence of cardio- vascular disease, glucose intolerance, and obesity. Some research- ers have postulated that hypercortisolism is associated with a hypercoagulable state independent of these associated risk factors. Hyperkalemia is not a feature of Cushing syndrome; in fact, hypo- kalemia is more likely to occur given the weak mineralocorticoid effect of cortisol.

Answer 291

ANSWER: E COMMENTS: Adrenal cortical carcinomas are rare with a worldwide incidence of 2 per 1 million. Size is the most impor- tant criteria to help diagnose malignancy. The majority are spo- radic, but they are also associated with Li-Fraumeni syndrome and multiple endocrine neoplasia type 1. Approximately half are nonfunctioning, while the other half secretes cortisol (30%), androgens (20%), estrogens (10%), aldosterone (2%), and mul- tiple hormones (35%). Adequacy of resection is the most impor- tant predictor of survival. Those who undergo complete en bloc resection with involved lymph nodes and other surrounding organs (e.g., diaphragm, kidney, pancreas, liver, or IVC) have 5-year survival rates ranging from 32% to 48%. Mitotane has adrenolytic activity and can be used for the treatment of meta- static or unresectable disease. Systemic chemotherapeutic agents can also be used but provide inconsistent responses. There is a role for neoadjuvant therapy in those with borderline resectable cases.

Answer 292

ANSWER: B COMMENTS: The rich vascular supply of the adrenal glands predisposes them to metastases. Approximately 25% of patients with carcinomas will eventually develop adrenal involvement. The primary cancers are those of the gastrointestinal tract, lung, breast, pancreas, kidney, and skin (melanoma). It remains essential to complete a functional workup for adrenal incidentalomas even in a patient with a prior history of malignancies. If, however, the functional workup is negative and clinical suspicion is high for a metastatic adrenal lesion, in contrast to primary adrenal lesions, biopsy of the adrenal gland may be warranted to aid in establishing a diagnosis.

Answer 293

ANSWER: B COMMENTS: This patient has Von Hippel-Lindau disease with an associated pheochromocytoma. Pallor, headache, and a sense of impending doom are all relatively common symptoms of patients with pheochromocytoma. Hyperglycemia is also a relatively common feature in such patients. The insulin-producing islet cells of the pancreas are under inhibitory control by α2-receptors. Thus with catecholamine excess, a relative hypoinsulinemia can develop and lead to hyperglycemia. Flushing, nausea, and fever can occur rarely. Elevated plasma-free metanephrine and normetanephrine levels are the most sensitive biochemical tests to diagnose a pheochromocytoma. However, its specificity (risk for false-posi- tive results) is lower than that of urinary epinephrine, urinary norepinephrine, urinary vanillylmandelic acid, and urinary total metanephrines. The specificity of plasma-free metanephrines can be improved by using a cutoff value of at least four times the upper limit of normal. Table 18.1 illustrates the specificity of other biochemical tests performed for the evaluation of pheochromocytoma.

Answer 294

ANSWER: A COMMENTS: The workup of an incidental adrenal mass includes screening and secondary confirmatory testing. Screening tests include (1) a low-dose dexamethasone test or a 24-h urine cortisol (or both), (2) a morning PAC and PRA, (3) plasma-free metaneph- rine and normetanephrine or 24-h total and fractionated urinary metanephrines (or both), and (4) a late-night salivary cortisol test. Confirmatory tests are done when the results of initial testing are equivocal and include, but are not limited to, a high-dose dexa- methasone test and a salt-loading aldosterone suppression test. Measurement of the serum ACTH level is performed once a diag- nosis of hypercortisolism is established. Cortisol levels follow a circadian rhythm, which explains why random cortisol levels are not useful in the screening of these patients. When there is normal diurnal variation, cortisol should be at its lowest at late night. In patients suspected of having Cushing syndrome, an elevated serum cortisol level at 11 pm can be an early, albeit not definitive, factor in the diagnosis of the condition. For its simplicity, measurement of late-night salivary cortisol levels has increased in popularity and has a sensitivity and specificity approaching 90%–95%. A low or suppressed level of ACTH or dehydroepiandrosterone sulfate (DHEAS) concentration further supports the diagnosis of subclini- cal Cushing syndrome. In recent years, DHEAS has been obtained when there is a suspicion for ACC as well, as this can be elevated.

Answer 295

ANSWER: C COMMENTS: The most likely diagnosis in this patient is primary hyperaldosteronism. There is a general consensus that all patients with young age, poorly controlled hypertension, and a history of hypokalemia should undergo evaluation for an aldoste- rone-secreting adenoma. Hypokalemia can be associated with myalgias, constipation, and fatigue. The initial step is measuring the aldosterone-to-renin ratio. This test should be performed after discontinuing such interfering medications as spironolactone. An aldosterone-to-renin ratio of greater than 20 (e.g., a serum aldo- sterone level of ≥10 ng/dL with a renin level of <0.5 ng/mL) is suggestive of the diagnosis. The diagnosis is then confirmed by doing a 24-h urine aldosterone, sodium, and potassium test with the patient ingesting a high-salt diet. A 24-h urinary aldosterone level greater than 12 μg in 24 h is considered positive. After establishing the biochemical diagnosis, the next step is to deter- mine whether there is laterality of the disease. Only at this time should diagnostic imaging be ordered.

Answer 296

ANSWER: D COMMENTS: After establishing the biochemical diagnosis, the next step is to determine whether there is laterality of the disease. Selective venous sampling is indicated when patients are >40 years old, have bilateral adrenal lesions, or no visible adrenal lesion on imaging. Adrenal vein sampling (AVS) is done by performing simultaneous measurements of serum cortisol and aldosterone in the cannulated adrenal veins and the peripheral circulation. Confir- mation of successful cannulation is established by documenting a greater than five-fold elevation in cortisol concentration relative to the peripheral circulation. Lateralization is confirmed by an unbal- anced ratio of aldosterone to cortisol when comparing one side with the other. Corrected aldosterone/cortisol ratios (i.e., aldosterone/ cortisol ratio of one side to aldosterone/cortisol ratio of the other side) of greater than 4:1 are indicative of a unilateral source of aldosterone excess.

Answer 297

ANSWER: A COMMENTS: The most common cause of primary hyperaldos- teronism is bilateral idiopathic hyperplasia (60%–70%). The second most common cause is an aldosterone-producing adenoma (35%), also known as Conn’s syndrome. The remaining subtypes include unilateral adrenal hyperplasia (2%), carcinoma (<1%), and familial hyperaldosteronism types I and II (<1%). It is important to distin- guish which subtype of hyperaldosteronism a patient has because some types, including bilateral idiopathic hyperplasia, are managed nonoperatively. Secondary hyperaldosteronism is the result of increased renin production by the kidney. This condition can be the consequence of reduced intravascular volume as is seen in congestive heart failure, cirrhosis, nephrosis, renovascular hypertension, Bartter syndrome, and pregnancy. Adrenal function is normal, and treat- ment is directed at the underlying condition.

Answer 298

ANSWER: C COMMENTS: Despite no previous history suggesting an underly- ing biochemical syndrome, the first step in the management of an incidental adrenal lesion is to complete a functional evaluation. If the lesion is nonfunctional, the next step in the management is to distinguish benign from malignant disease. MRI can be useful in this regard, but most times an index of suspicion for a malignant process can be garnered from CT alone. An image-guided biopsy is not believed to be useful in helping differentiate benign from malignant adrenal lesions. According to the National Institutes of Health State-of-the-Science Conference on the workup of adrenal incidentalomas, FNA is recommended in patients with a history of malignancy and no other signs of metastases. Before percutaneous biopsy, it is imperative that the presence of a pheochromocytoma be excluded since a life-threatening pheochromocytoma crisis can occur with this intervention. Metastatic lung cancer should be con- sidered in the differential diagnosis, but CT of the lung should not be the initial step in this patient.

Answer 299

ANSWER: E COMMENTS: In the evaluation of nonfunctional tumors, there are a number of radiographic findings that can assist the clinician in determining whether a lesion is likely to be benign or malignant (Table 18.2). Measurement of HU on CT is a commonly used parameter and is associated with acceptable rates of specificity and sensitivity when other features such as size, shape, or growth are considered. Less than 10 HU on noncontrast CT is indicative of a benign lesion. When IV contrast material is administered and delayed imaging is performed, the rapidity of washout of the con- trast agent can be measured. Benign lesions typically demonstrate rapid washout, with a greater than 50% loss of initial attenuation on delayed imaging at 10 to 15 min. Less than 50% washout sug- gests malignancy or pheochromocytoma. Lipid-poor adenomas may have values of 20 to 40 HU on noncontrast CT but will dem- onstrate >50% washout at 10 to 15 min.

Answer 300

ANSWER: D COMMENTS: The imaging characteristics described are typical of myelolipoma. These lesions are composed of erythroid, myeloid, and an abundant amount of adipose tissue. On noncontrast CT, they are of low attenuation and consist of nearly pure fat. On MRI, they are hyperintense on T1-weighted images. On T2-weighted images, malignant lesions are typically hyperintense, as are pheochromo- cytomas, while benign lesions are isointense relative to the liver. In comparison, aldosteronomas rarely get this large and are slower growing. Myelolipomas are not indicated for surgical removal unless they are causing symptoms of compression or pain.

Answer 301

ANSWER: C COMMENTS: The American Association of Clinical Endocri- nologists (AACE)/American Association of Endocrine Surgeons (AAES) medical guidelines for the management of adrenal inci- dentalomas recommend that surgical resection be considered for any nonfunctional adrenal incidentaloma 4 cm or larger. Observa- tion is appropriate for lesions smaller than 4 cm. In distinguishing between a malignant tumor and a benign lesion, size alone was associated with a 93% sensitivity and 24% specificity using the cutoff of 4 cm. With improved imaging and the use of laparoscopy in adrenal surgery, more benign tumors are being removed.

Answer 302

ANSWER: A COMMENTS: Considerable controversy exists around the appro- priate surgical management of pheochromocytomas in patients with MEN. If at initial evaluation only one side shows evidence of a mass and a unilateral adrenalectomy is performed, the chance of a contralateral pheochromocytoma developing over an interval of 12 years is 52%. Patients with MEN type II should not undergo pro- phylactic removal of the contralateral side if no mass or presence of pheochromocytoma is confirmed. When the laterality of the pheochromocytoma is at question and the patient’s disease is rela- tively asymptomatic, some surgeons favor observation in young patients as nearly a fourth of patients will experience at least one episode of acute adrenal insufficiency requiring hospitalization. This is a special concern in young patients, in whom the reliability of taking medications regularly or adjusting for physiologic stress- ors is highly variable. Alternatively, surgeons have begun perform- ing laparoscopic cortical-sparing procedures in these patients, in whom the success rate of avoiding exogenous steroid dependence is reported to be between 65% and 100%. Thus in the patient described here, it would be appropriate to perform a left cortical- sparing adrenalectomy, a left adrenalectomy, a left adrenalectomy with the cortical-sparing removal of the right, or a bilateral cortical- sparing adrenalectomy. AVS in these patients preoperatively can be a useful adjunct to assess the prevalence of bilateral pheochromo- cytomas when imaging is not able to lateralize the side of an active disease.

Answer 303

ANSWER: D COMMENTS: Preoperative catecholamine receptor blockade is done to reduce the incidence and magnitude of intraoperative fluctuations in blood pressure and the development of arrhyth- mias. A α-blocker such as atenolol should never be administered before the use of an α-blocker because α-blockade can cause severe vasoconstriction and hypertension from inhibition of the vasodilator action of epinephrine. Prazosin and phenoxybenza- mine are both α-blockers and have been used routinely for pre- operative α-blockade in patients with pheochromocytoma. The use of calcium channel blockers has become more popular as they are better tolerated by patients, readily available, and less costly, and can be used as a substitute or as an adjunct to an α-blocker. Intraoperative magnesium sulfate infusion is used for its cardiovascular-stabilizing properties. The benefit of these agents is that coronary vasospasm is reduced and, when given in conjunction with an α-blocker, they can reduce the dosage of the α-blocker needed.

Answer 304

ANSWER: C COMMENTS: In the postoperative setting, patients with pheo- chromocytoma should be monitored closely for signs or symp- toms associated with hypoglycemia. Profound hypoglycemia can develop in these patients as a result of the rebound hyper- insulinemia that occurs with the removal of the inhibitory cat- echolamine effect. Liver glycogen stores may be severely depleted in these patients because catecholamines promote gly- cogen breakdown. Thus the patient’s ability to respond acutely to the hypoglycemia is impaired. It is unpredictable in which patient the hypoglycemia will develop, so those with pheochro- mocytoma are usually administered a prophylactic dextrose infusion postoperatively.

Answer 305

Patients with hyperparathyroidism develop demineralization, and 1.5% shows osteitis fibrosa cystica. The presence of subperiosteal resorption of bone of the phalanges and lamina dura of the teeth are fairly diagnostic radiological findings of hyperparathyroidism. Chondromas account for 20% of benign tumors of the rib and occur at the costochondral junction. Osteochondromas arise from the cortex and usually occur in men. Eosinophilic granuloma results in a destructive lesion apparent on x-ray.

Answer 306

Low vitamin D levels Familial hypocalciuric hypercalcemia Primary hyperparathyroidism (PHPT) is the result of inappropriate parathyroid hormone production by one or more intrinsically abnormal parathyroid glands and is the most common cause of hypercalcemia. Parathyroid carcinoma is responsible for approximately 1% of PHPT and generally is characterized by very high blood calcium and parathyroid hormone levels (total serum calcium >14 mg/dL, with blood parathyroid hormone levels >300 pg/mL). The diagnosis of PHPT is entirely biochemical and depends on the presence of both inappropriate blood calcium and parathyroid hormone level elevations, in the context of normal blood vitamin D levels. Vitamin D plays an important role in normal blood calcium homeostasis, and low vitamin D levels may result in an appropriate compensatory elevation in blood parathyroid hormone, leading to an incorrect diagnosis of PHPT. In addition, biochemical testing for familial hypocalciuric hypercalcemia (FHH), an autosomal dominant syndrome resulting from loss-of-function mutation(s) in the calcium sensing receptor gene, is necessary before diagnosing PHPT. This condition is characterized by mild elevations in blood-intact parathyroid hormone level, with associated relative hypercalcemia, and is diagnosed by 24-hour urine calcium level testing. A value of less than 100 mg in 24 hours is diagnostic of FHH and rules out PHPT.

Answer 307

1) Annual reassessment for the development of symptoms 2) Annual blood testing to reassess whether the magnitude of their hypercalcemia has reached levels meriting parathyroidectomy 3) Bone mineral density scanning every 1 to 2 years to evaluate for the development of osteoporosis

Answer 308

Age: <50 years Serum calcium: 1.0 mg/dL (0.25 mmol/L) above upper limit of normal 24-hour urinary calcium: >400 mg/day (10 mmol/day) Renal involvement: Creatinine clearance <60 mL/min or nephrolithiasis/nephrocalcinosis Bone mineral density: T-score

Answer 309

1) SHPT refractory to medical therapy: • Parathyroid hormone >600-800 pg/mL • Calcium × Phosphorus product >55 2) Renal osteodystrophy 3) Calciphylaxis 4) Other retractable symptoms, including uremic pruritus, persistent anemia, bone pain, muscle pain, abdominal pain, fatigue, and weakness

Answer 310

Severe hypercalcemia (calcium >12.5 mg/dL) Persistent hypercalcemia ≥2 years after renal transplantation, associated with: * Decline in renal function, without graft rejection * Nephrolithiasis * Progressive bone disease * Pancreatitis

Answer 311

I Nondiagnostic or unsatisfactory (1-4% risk of malignancy) II Benign (0-3% risk of malignancy) III Atypia of undetermined significance or follicular lesion of undetermined significance (5-15% risk of malignancy) IV Follicular neoplasm or suspicious for a follicular neoplasm (15-30% risk of malignancy) V Suspicious for malignancy (60-75% risk of malignancy) VI Malignant (97-99% risk of malignancy)

Answer 312

Widened palpebral fissure

Answer 313

Infrequent blinking

Answer 314

Global lag during elevation

Answer 315

Tremor of the closed eyelids

Answer 316

Lag of the lower lids during elevation of the globes

Answer 317

Jerking of the lagging lid

Answer 318

Absence of forehead wrinkling with upward gaze