Issues in Endocrine Surgery

Educational Objectives

The goal of this program is to improve outcomes of thyroid surgery and management of thyroid disease, and review ethical issues raised by innovation in endocrine surgery. After hearing and assimilating this program, the clinician will be better able to:

1.   Identify possible complications of thyroid surgery, including hypoparathyroidism, recurrent laryngeal nerve injury, and hematoma.

2.   Recognize the indications for total thyroidectomy in a patient with thyroid cancer.

3.   Describe the differences between Graves disease and Plummer’s disease and the management of each condi­tion.

4.   Explain the difference between innovation and research in surgery.

5.   Discuss the ethical implications of those differences as they relate to endocrine surgery.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and plan­ning committee reported nothing to disclose.

Acknowledgements

Drs. Clark and Shen were recorded at The Postgraduate Course in General Surgery, held March 19-21, 2009, in San Francisco, CA, and sponsored by the University of California, San Francisco, School of Medicine. Dr. Angelos spoke at Surgery of the Thyroid and Parathyroid Glands, held November 7-9, 2008, in Boston, MA, and sponsored by Har­vard Medical School. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

How to Avoid Complications in Thyroid Surgery

Orlo H. Clark, MD, Professor of Surgery, University of California, San Francisco, School of Medicine, and Chair of Surgery, Mount Zion Medical Center, San Francisco

Diagnosis: ultrasonography (US) important for staging; ask about family history (higher-than-average recurrence rate associated with family history of thyroid cancer or goiter); 40% of patients exposed to low-dose therapeutic radia­tion develop thyroid cancer; physical examination  —  palpate for nodes; US  —  indicates size, number, and complex­ity of nodules, and possibility of malignancy and/or nodal metastases; computed tomography (CT) and magnetic resonance imaging (MRI) usually unnecessary (indicated for fixed lesion, history of hemoptysis, or substernal mass); have patient discontinue aspirin and any other medication with anticoagulant properties £1 wk before sur­gery

Incision: textbooks advise placement 1 to 2 cm above suprasternal notch (may miss gland if patient has long, thin neck); incision should be 1 cm above or below cricoid cartilage, on normal skin line

Possible complications: hypoparathyroidism (1%-2% of patients); permanent hoarseness from recurrent laryngeal nerve damage (nerve branches in 50% of patients; all motor fibers may be in one branch); bleeding requiring reop­eration (can result in death or brain death); hematoma (symptoms include dyspnea, struggling to sit up, and squeaky voice; may develop quickly); infection;  seroma; external laryngeal nerve damage worrisome because nerve may be small and difficult to see

Technique: incision usually 3 to 4 cm long; if nodule benign, divide isthmus early; recurrent nerve may be injured af­ter thyroid veins divided; speaker then proceeds in cephalad direction, mobilizing between thyroid and carotid ar­tery; superior vessels taken low on gland to minimize damage to external laryngeal nerve; nerve identified by finding vaso nervorum running parallel to it; recurrent nerve enters larynx above cricoid cartilage; upper parathy­roid immediately dorsal to nerve, while lower parathyroid more anterior to nerve (more vulnerable to injury be­cause of need to dissect off for longer distance to keep on vascular pedicle); £80% of patients have microscopic metastases noted on prophylactic neck dissection (now recommended for medullary thyroid cancer)

Treatment: total thyroidectomy indicated for tumors >1 cm; speaker advises doing more difficult side first, and al­ways biopsying parathyroid to confirm identity of tissue; transplant parathyroid if necessary, to preserve vascular­ity; lymph node dissection  —  extensive visibility on US indicates thyroiditis; one focal area usually indicates thyroid cancer; always examine pyramidal lobe; dissect through notch in thyroid cartilage and remove thyroid tis­sue (may impede postoperative radioactive iodine uptake); data show that visible or palpable nodes may adversely affect recurrence and possibly survival; postoperative management  —keep patient in low Fowler position to create negative pressure on neck veins; avoid coughing and emesis; if patient coughs during extubation, place immediate counterpressure on neck; monitor neck measurements

Management of Patients with Graves or Plummer’s Disease

Wen T. Shen, MD, Assistant Professor of Surgery, University of California, San Francisco, School of Medicine

Graves disease: accounts for 50% to 80% of all cases of hyperthyroidism

Pathophysiology: caused by circulating IgG antibodies which activate thyrotropin (TSH) receptors on gland; results in gland hypertrophy and consequent hyperthyroidism, with increased secretion of triiodothyronine (T₃) and thy­roxine (T₄); antibodies thought to stimulate receptors in retro-orbital space, resulting in exophthalmos

Epidemiology: affects »0.5% of population; 5 to 10 times more likely in women than men; peak age of onset 40 to 60 yr, although frequently seen in younger adults; 1% to 5% of cases occur in children (peak age 11 to 14 yr); some evidence of genetic basis

Organ systems affected: ocular  —  exophthalmos and lid lag; thyroid  —  hypertrophy and diffuse goiter, sometimes with audible bruit or thrill due to intense hypervascularity; cardiovascular  —  tachycardia and possibly life-threatening arrhythmias; dermatologic  —  pretibial myxedema (swelling along shin); in general, skin moist and warm; gastrointestinal  —  diarrhea and increased stool frequency; neurologic and psychiatric  —nervousness, irri­tability, tremor, proximal weakness, disrupted sleep-wake cycles (including insomnia), and hyperreflexia; miscellaneous  —  involuntary weight loss and heat intolerance

Laboratory evaluation: suppressed TSH, elevated T₄ and T₃, elevated thyroid stimulating immunoglobulin (TSI; negative in 10%-15% of patients), and possible elevation of other thyroid antibodies

Imaging studies: US illuminates extent of gland (consider axial CT or MRI if gland extends substernally); thyroid scanning used less often today, but still helpful in indeterminate cases, or when trying to distinguish functioning nodule

Treatment options: antithyroid medications  —  propylthiouracil (PTU) and methimazole inhibit thyroid hormone synthesis; PTU also inhibits conversion of T₄ to T₃; mainstay of treatment in Europe (not as often in United States); less crossing of placenta with PTU (preferred treatment for pregnant women); agranulocytosis most significant side effect; occurs on 0.5% of patients; can be life-threatening; measure white blood cells in any patient taking PTU or methimazole who complains of sore throat or fever; rash, arthralgias, gastrointestinal (GI) symptoms also possible; hepatotox­icity rare, but use caution when treating patients with liver disease; relapse rate after discontinuation 30% to 60%; hypothyroidism rare; radioactive iodine (¹³¹ I)  —goal of treatment ablation of thyroid gland and induction of hypothyroidism; now first-line therapy for most endocrinologists in United States; effective in 70% to 80% of cases; side effects include radiation thyroiditis (tenderness in thyroid); severe worsening of ophthalmopathy, es­pecially among patients who smoke (treat with steroids pre- and posttreatment with ¹³¹ I); unconfirmed but worri­some risk for extrathyroidal cancers, especially among pediatric patients; absolutely contraindicated in pregnancy or in patients wishing to become pregnant; radiation therapists advise against becoming pregnant for ³6 to 12 mo after treatment; also contraindicated for patients with substernal goiter (precipitates gland necrosis, which may result in bleeding into chest)

Thyroid surgery: indicated for patients who fail therapy with ¹³¹ I, women currently or wishing to become pregnant, patients with large or symptomatic goiter, suspicious nodules or worrisome lymphadenopathy on US, or with severe ophthalmopathy; sometimes recommended in pediatric cases; total thyroidectomy now recommended whenever possible (less extensive surgery associated with recurrence rates £20%); if recurrent laryngeal nerve jeopardized, perform near-total thyroidectomy, leaving »1 g of tissue overlying nerve; parathyroid autotrans­plantation recommended if surgeon concerned about gland’s viability, or if gland seen on pathology specimen; postoperative complication rates high in this patient population because glands enlarged and hypervascular; rate of nerve injury 1% to 5%; temporary hypoparathyroidism in £40% of cases, permanent in 1% to 4%  

Preoperative preparation: Lugol’s solution or saturated solution of potassium iodide (SSKI) recommended to de­crease thyroid size and vascularity; b-blockers such as propranolol recommended for patients with tremor or sympathetic overdrive; metoprolol or atenolol also good choices; patient should be as hemodynamically nor­mal as possible preoperatively; electrosurgical (eg, LigaSure) or ultrasonic (eg, Harmonic scalpel) sealing of vessels recommended for best hemostasis; intraoperative nerve monitor may help reassure surgeon; because of high incidence of postoperative hypocalcemia and preexisting high-turnover bone disease with Graves disease, speaker and colleagues routinely prescribe postoperative oral calcium supplements (with vitamin D when needed); supplements sometimes recommended preoperatively; ophthalmopathy progresses in 10% to 30% of patients, despite total thyroidectomy; subsequent ¹³¹ I ablation may be necessary

Plummer’s disease: multinodular or uninodular goiter; accounts for 15% to 30% of cases of hyperthyroidism; more common in iodine-deficient areas; associated with autonomous function of solitary or multiple nodules arising from various types of somatic mutations; clinical presentation similar to that of Graves disease but without oph­thalmopathy or elevated TSI levels; TSH levels low, and T₃ and T₄ levels high; US often sufficient for preopera­tive planning; fine needle aspiration recommended for suspicious nodules

Treatment: antithyroid medications ineffective in long term; ¹³¹ I used, but multiple doses often needed; indications for surgery include suspicious nodules, local compressive symptoms, failure of nonoperative management, or pregnancy or desired pregnancy; lobectomy recommended if patient has solitary toxic nodule and remainder of gland normal; multiple nodules common, and total thyroidectomy indicated in these cases; complication rates in experienced hands <1%

Ethics and Endocrine Surgery

Peter Angelos, MD, PhD, Professor and Chief of Endocrine Surgery, and Associate Director, MacLean Center for Clinical Medical Ethics, University of Chicago, Chicago, IL

Influence of innovation: produce new technologies or new applications for existing technologies; wide acceptance requires broad dissemination

Other benefits of innovation: aids marketing; valued in medical care in general and particularly in surgery; patients want surgeons to be innovative; most in favor of new technology; relatively little evidence-based medicine in en­docrine surgery; therefore, must be careful how new techniques and procedures “sold” to patients; newness alone not necessarily improvement

Drawbacks: restrictive research oversight prevents access to newest innovations; alternatively, patients may be ex­posed to unnecessary risks because new techniques not yet well understood or effective; tension exists between encouraging more innovations to help patients and protecting patients from “the unbridled enthusiasm of surgi­cal innovators”

Examples of surgical innovations that proved ineffective (or worse): prefrontal lobotomy for treating psychiatric illness; internal mammary artery ligation for treating angina; gastric freezing for treating ulcers

Clarification of terms: minor modifications  —  small changes or tinkering with established procedure (eg, stapled rather than hand-sewn anastomosis); innovative procedure  —  new or modified procedure that differs from cur­rently accepted local practice  (eg, radiofrequency ablation [RFA] of thyroid nodules); research  —systematic in­vestigation designed to develop or contribute to generalizable knowledge (definition given in National Institutes of Health Code of Federal Regulations; eg, comparison of anterior laparoscopic and posterior endoscopic ap­proaches to adrenalectomy)

Disclosure issues: Society for University Surgeons (SUS) position paper suggests patients should understand proce­dure, but minor modifications need not be discussed; planned innovation should be disclosed in informed con­sent, while unplanned innovation should be disclosed afterward; procedure that has not been described in North American surgical text considered innovation and should be discussed with patient

SUS position on research: defined as “systematic investigation to contribute to generalizable knowledge”; research on human subjects requires review by institutional review board (IRB), and has specific and detailed consent re­quirements and documentation

Problems with SUS position: intraoperative innovations may emerge from unforeseen circumstances; if outcome good, surgeon may repeat; however, must be careful to avoid “reckless experimentation”; planned study re­quires IRB approval and informed consent; innovation ethics paradigm  —  informal, with little oversight; regu­latory ethics paradigm  —  rigorous formal review and IRB oversight; effective innovation requires balancing of both

Oversight alternatives to IRBs: informal review with senior surgical colleagues; formal review with department chairs; formal innovative surgery committees (encouraged by SUS); no reports of formation of this type of for­mal review at any institution, suggesting that barriers may exist; also raises question of whether committee would help or hinder innovation

Conclusions: adoption of innovative surgical techniques can be problematic; innovation without formal review po­tentially slippery slope; can be difficult to determine when innovation crosses line into research; wholesale adop­tion of regulatory ethics paradigm will likely slow innovation and create more work for IRBs; oversight should not slow adoption of new technologies; surgeons must be careful how they present new technologies to patients; new mechanism for formal review of surgical innovation may be critical to future of surgery

Suggested Reading

Angelos P et al: Ethical issues in surgical treatment and research. Curr Probl Surg 40:353, 2003; Biffl WL et al: Responsi­ble development and application of surgical innovations: a position statement of the Society of University Surgeons. J Am Coll Surg 206:1204, 2008; Chammas MC et al: Predictive value for malignancy in the finding of microcalcifications on ul­trasonography of thyroid nodules. Head Neck 30:1206, 2008; Desser TS, Kamaya A: Ultrasound of thyroid nodules. Neu­roimaging Clin N Am 18:463, 2008; Efremidou EI et al: The efficacy and safety of total thyroidectomy in the management of benign thyroid disease: a review of 932 cases. Can J Surg 52:39, 2009; Elaraj DM, Clark OH: Changing management in patients with papillary thyroid cancer. Curr Treat Options Oncol 8:305, 2007; Elsayed YA et al: Effect of near-total thy­roidectomy on thyroid orbitopathy due to toxic goiter. World J Surg 33:758, 2009; Erbil Y et al: Risk factors of incidental parathyroidectomy after thyroidectomy for benign thyroid disorders. Int J Surg 7:58, 2009; Gosnell JE, Clark OH: Surgi­cal approaches to thyroid tumors. Endocrinol Metab Clin North Am 37:437, 2008; Hegedüs L: Treatment of Graves’ hyper­thyroidism: evidence-based and emerging modalities. Endocrinol Metab Clin North Am 38:355, 2009; Jones JW et al: The ethics of innovative surgical approaches for well-established procedures. J Vasc Surg 40:199, 2004; McKneally MF, Daar AS: Introducing new technologies: protecting subjects of surgical innovation and research. World J Surg 27:930, 2003.