Educational disclaimer: This article presents a historical surgical case and a contemporary commentary intended for medical education. It is not a substitute for individualized medical advice. Decisions about the management of Graves’ disease should be made between a patient and a qualified clinician, informed by current evidence and applicable clinical practice guidelines.
Introduction
Graves’ disease is an autoimmune disorder in which thyroid-stimulating immunoglobulins act on the TSH receptor of thyroid follicular cells, producing diffuse goiter and a clinical spectrum that can include thyrotoxicosis, Graves’ orbitopathy (also termed thyroid eye disease), and the dermatologic manifestations of pretibial myxedema and acropachy (Bartalena et al., “The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines”).
Three treatment options remain coequal first-line choices for adult Graves’ hyperthyroidism — antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy — selected through shared decision making based on disease severity, goiter size, the presence and activity of orbitopathy, pregnancy status, available expertise, and patient preference (Ross et al., “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis”). When surgery is selected, near-total or total thyroidectomy is the procedure of choice; subtotal thyroidectomy, which retains a deliberately preserved euthyroid remnant, is no longer recommended as a primary strategy (American Thyroid Association, “Surgical Management of Graves’ Disease”; Smithson et al., “Considerations for Thyroidectomy as Treatment for Graves Disease”).
The case that follows is presented as a historical example of subtotal thyroidectomy performed at a time when the procedure was standard and radioiodine was unavailable locally. The accompanying discussion places that historical practice in the context of current guidance.
Case report
Note: This case description is preserved as a historical record. Several diagnostic and therapeutic details reflect the practice of the late twentieth century and would be handled differently today; current equivalents are discussed in the subsequent sections.
G.A., a 45-year-old woman, had a goitre for five years before seeking medical attention. She presented with increased appetite, increased perspiration, heat intolerance, palpitations, anxiety, tremulousness and swelling of the legs. She had pruritus and leg ulcers and had gradually developed proptosis. She reported losing 20 lb over the previous six months.
She attended the Endocrine Clinic, where she was assessed as having thyrotoxicosis and was treated with propranolol and carbimazole. She was also given prednisone and cyclophosphamide for severe dermopathy, and methyldopa for essential hypertension. She was maintained on antithyroid therapy for five years with incomplete thyrotoxic control, her large goitre did not decrease in size, and she was therefore referred for surgical management.
On physical examination the patient was in no cardiorespiratory distress and had no significant lymphadenopathy. Her temperature was normal, pulse 60/min and regular, blood pressure 190/80 mmHg, and heart sounds normal. She had bilateral proptosis and a smooth, diffusely enlarged thyroid (Fig 1). The trachea was central. The legs showed marked pretibial myxoedema with hyperpigmentation up to the mid-calves (Fig 2).
Investigations: hemoglobin 12.9 g/dL; WBC 4.4 × 10⁹/L; serum urea, electrolytes and glucose normal; calcium 2.4 mmol/L; total protein 73 g/L (albumin 36 g/L, globulin 37 g/L); platelets 135 × 10⁹/L; PT 13.7 s (control 12.2 s).
| Test | Result | Reference range |
|---|---|---|
| T4 | 10.5 µg/dL | 5–12 µg/dL |
| T3 | 320 ng/dL | 85–220 ng/dL |
| T3 uptake | 43.5% | 34–45% |
| Free thyroxine index (FTI) | 4.6 | 1.7–5.4 |
| TSH | < 1 µIU/mL | 0–6.5 |
Chest x-ray showed mild cardiomegaly. The electrocardiogram showed sinus bradycardia and was otherwise unremarkable.
Modern diagnostic equivalent: Contemporary confirmation of Graves’ disease relies on a suppressed (third-generation) TSH with elevated free T4 and/or free T3, together with a positive TSH receptor antibody (TRAb) or thyroid stimulating immunoglobulin (TSI). Thyroid ultrasound with Doppler or radionuclide scintigraphy (¹²³I or ⁹⁹ᵐTc pertechnetate) is used selectively when the autoantibody result is equivocal or unavailable (Bartalena et al., 2021 EUGOGO).
The duration of preoperative preparation was three weeks, with carbimazole, propranolol and Lugol’s iodine. The patient became euthyroid and then underwent subtotal thyroidectomy with a thyroid remnant approximately one-eighth of the gland. The excised gland weighed 235 g. Its surface was lobular and the cut surface showed focal cystic areas. Histology demonstrated dilated, colloid-filled acini lined by flattened epithelium, occasional papillary infoldings, and nodular fibrosis — a colloid goitre.
Postoperatively the patient developed a small wound hematoma that resolved without intervention. She was discharged on the fourth postoperative day. She subsequently presented at three months with a wound abscess that was drained. At five months she had removal of a silk suture in a suture sinus. At follow-up one year and ten months after surgery she had a healed incision and was euthyroid, but her orbitopathy and dermopathy persisted.
Contemporary structured management:
Diagnosis
Current Graves’ disease diagnosis combines clinical features (diffuse goiter, thyrotoxicosis, and signs of orbitopathy or dermopathy) with biochemical and immunologic confirmation: suppressed sensitive TSH, elevated free T4 and free T3, and positive TRAb. TRAb measurement also has prognostic value — high titers predict a higher risk of orbitopathy and a lower probability of remission with ATDs (Bartalena et al., 2021 EUGOGO).
Treatment options and indications for surgery
ATDs, RAI, and thyroidectomy are three coequal first-line options for adult Graves’ disease (Ross et al., 2016 ATA Guidelines). Indications that favor thyroidectomy include large goiter (>50–80 g) with compressive symptoms, suspicion of coexisting thyroid malignancy, moderate-to-severe or active Graves’ orbitopathy, pregnancy with ATD intolerance, women planning pregnancy in the near term, pediatric patients (especially when ATDs cannot be continued), and a patient preference for rapid definitive cure (American Thyroid Association, “Surgical Management of Graves’ Disease”; Smithson et al., 2019).
Although ATDs remain the most common initial choice worldwide, thyroidectomy delivers the most rapid and durable cure: a meta-analytic synthesis reports recurrence of ~10% after thyroidectomy compared with ~15% after RAI and ~52% after ATDs (Smithson et al., 2019).
Preoperative preparation
The goals of preoperative preparation are to render the patient as close to euthyroid as feasible, mitigate sympathetic overactivity, reduce thyroid gland vascularity, and minimize the risk of perioperative thyroid storm.
| Component | Current standard |
|---|---|
| Antithyroid thionamide drug | Methimazole (1-methyl-2-mercaptimidazole, MMI) 5–40 mg/day titrated to free T4 is first-line, continued until the day of surgery. Carbimazole (a methimazole prodrug) is used interchangeably in some regions. Propylthiouracil (PTU) 50–150 mg TID is reserved for the first trimester of pregnancy, methimazole intolerance, and thyroid storm because of the FDA-required boxed warning for severe hepatotoxicity (Uludag et al., “Preoperative Preparation in Hyperthyroidism and Surgery”). |
| Beta-blocker | Propranolol, atenolol, metoprolol, or esmolol, titrated to a resting heart rate <90 bpm. Cardioselective agents (atenolol 25–100 mg/day, metoprolol) are preferred for tolerability and in asthma. Beta-blocker monotherapy is reserved for patients intolerant of thionamides and iodine (Ross et al., 2016 ATA Guidelines; Uludag et al., 2024). |
| Iodine | Lugol’s solution 5–7 drops three times daily, or Saturated Solution of Potassium Iodide (SSKI) 1–2 drops three times daily, for 7–10 days preoperatively, to reduce gland blood flow and intraoperative bleeding (American Thyroid Association, “Surgical Management of Graves’ Disease”; Smithson et al., 2019). |
| Calcium and vitamin D | Baseline measurement and pre-loading with calcium carbonate (e.g., 1 g three times daily) for several weeks before surgery, plus correction of vitamin D deficiency, reduces postoperative hypocalcemia (Smithson et al., 2019). |
| Corticosteroids | Used selectively for severe or refractory thyrotoxicosis, thyroid storm, or rapid preparation. |
| Rapid preparation (urgent surgery or intolerance) | The Panzer regimen (iopanoic acid 500 mg BID, dexamethasone 1 mg BID, beta-blocker, and a thionamide) achieves euthyroidism in ~7 days; the Fischli regimen (5% Lugol’s 13 drops TID, dexamethasone 2 mg BID, plus beta-blocker) is effective within ~10 days (Uludag et al., 2024). |
Pregnancy follows a specific algorithm: PTU is preferred in the first trimester because methimazole and carbimazole have been associated with embryopathy (aplasia cutis, choanal and esophageal atresia, omphalocele). The patient is then switched to methimazole or carbimazole for the second and third trimesters. Beta-blockers can be used short-term when symptom control demands. When surgery is needed during pregnancy, it is preferred during the second trimester (Uludag et al., 2024; Hyperthyroidism in Pregnancy, StatPearls).
Thyroid storm is identified using the Burch–Wartofsky Point Scale (>45 supports the diagnosis) or the Japan Thyroid Association criteria, and is managed with combined thionamide (typically PTU), iodine, corticosteroids, beta-blockade, and supportive care; therapeutic plasma exchange is a Category II (Grade 2C) option for refractory cases (Uludag et al., 2024).
The Adlerberth, Caswell, Lee, and de Mul series have shown that thyroid storm can occur in both euthyroid and biochemically hyperthyroid surgical patients, so adequate preoperative preparation reduces — but does not abolish — perioperative risk, and intraoperative vigilance for storm features remains essential (Uludag et al., 2024).
Procedure of choice: near-total or total thyroidectomy
The 2016 ATA (American Thyroid Association) hyperthyroidism guideline recommends near-total or total thyroidectomy when surgery is chosen for Graves’ disease, performed by a high-volume surgeon (typically defined as >25–30 thyroidectomies per year) (Ross et al., 2016 ATA Guidelines; American Thyroid Association, “Surgical Management of Graves’ Disease”). The rationale is a near-zero rate of recurrent hyperthyroidism and comparable permanent-complication rates relative to subtotal procedures, balanced against the accepted trade-off of lifelong levothyroxine replacement.
A 2024 single-institution comparative series of 427 patients (subtotal vs total/near-total thyroidectomy for Graves’ disease) reported:
- Recurrent hyperthyroidism: 8% with subtotal vs 0% with total/near-total (p < 0.001).
- A remnant tissue cut-off of 4 g distinguished risk groups: recurrence was 0% when the remnant was <4 g and 17.8% when the remnant was ≥4 g (p < 0.001).
- Transient hypoparathyroidism was higher with total/near-total (16.9% vs 0.8%; p < 0.001), but persistent hypoparathyroidism and vocal cord paralysis were comparable between groups (Sengun et al., “Subtotal vs. Total Thyroidectomy and Comparison of the Long-term Results”).
A separately published meta-analytic synthesis reports a 0% recurrence rate after total thyroidectomy with permanent hypoparathyroidism of about 0.5% and recurrence of 4.7% after subtotal thyroidectomy (Smithson et al., 2019).
Intraoperative neural monitoring (IONM) of the recurrent laryngeal nerve is now widely used and is associated with a trend toward lower RLN injury rates compared with visual identification alone (Gunn et al., “Recurrent Laryngeal Nerve Injury After Thyroid Surgery: An Analysis of 11,370 Patients”).
Routine postoperative care after near-total or total thyroidectomy includes immediate initiation of levothyroxine (typical weight-based dose ~1.6 µg/kg/day in adults) titrated to TSH, perioperative calcium and parathyroid hormone monitoring, and standard wound and airway surveillance (American Thyroid Association, “Surgical Management of Graves’ Disease”).
Complications: contemporary rates
| Complication | Contemporary rate | Comment |
|---|---|---|
| Any recurrent laryngeal nerve injury (≤30 days) | ~5–7% overall; 6.9% after total thyroidectomy vs 4.3% after lobectomy in a US NSQIP series of 11,370 patients | Higher in malignancy; lower trend with IONM (Gunn et al., 2020) |
| Permanent RLN palsy | <1–2% in experienced hands | High-volume surgeon dependent (American Thyroid Association) |
| Transient hypocalcemia | 12–60%, frequently 30–40% in Graves’ (hungry bone syndrome) | Mitigated by calcium/vitamin D pre-loading (Smithson et al., 2019) |
| Permanent hypoparathyroidism | <2–5% in high-volume centers | (Smithson et al., 2019) |
| Postoperative cervical hematoma requiring reoperation | 0.5–2% (higher in Graves’ than other indications because of gland vascularity) | (American Thyroid Association; Smithson et al., 2019) |
| Perioperative thyroid storm | Rare in adequately prepared patients | (Uludag et al., 2024) |
| Perioperative mortality | Typically <0.1% | (Smithson et al., 2019) |
Graves’ orbitopathy and pretibial myxedema
Graves’ orbitopathy management has advanced substantially in the last decade. The 2021 EUGOGO clinical practice guidelines structure care around control of risk factors — smoking cessation, prompt restoration and maintenance of euthyroidism, control of TRAb, and management of hypercholesterolemia — and an activity- and severity-based treatment algorithm (Bartalena et al., 2021 EUGOGO):
- Mild and active disease: local treatments (artificial tears), risk-factor control, and a 6-month course of selenium 200 µg/day of sodium selenite in selenium-deficient areas. ATDs or thyroidectomy are preferred over RAI; if RAI is selected, steroid prophylaxis is used.
- Moderate-to-severe and active disease: first-line intravenous methylprednisolone (cumulative dose 4.5 g over 12 weeks) plus oral mycophenolate sodium (0.72 g daily for 24 weeks). Early thyroidectomy can improve response to immunosuppression and is preferred over RAI in this group.
- Sight-threatening disease: high-dose IV methylprednisolone (500–1000 mg daily for 3 days or every second day) and urgent orbital decompression if the response is poor.
- Inactive disease: rehabilitative surgery (orbital decompression, strabismus, eyelid).
Teprotumumab, an Insulin-like Growth Factor 1 Receptor (IGF-1R)-blocking monoclonal antibody was approved by the FDA in January 2020 for thyroid eye disease, administered as eight intravenous infusions over 24 weeks. It produces clinically meaningful reductions in proptosis and Clinical Activity Score in pivotal trials and is now incorporated into second-line and selected first-line regimens for moderate-to-severe active Thyroid Eye Disease (TED) (FDA, Teprotumumab Summary Review (NDA 761143), 2020; Tappeiner and Mayet, “Teprotumumab for the Treatment of Thyroid Eye Disease”).
Pretibial myxedema is now managed primarily with potent topical or intralesional corticosteroids and compression therapy, with reports of emerging immunomodulators including Janus Kinase (JAK) inhibitors for refractory disease (Cleveland Clinic, “Pretibial Myxedema (Graves’ Dermopathy)”). Cyclophosphamide is no longer part of standard care for either orbitopathy or pretibial myxedema.
Discussion
The case describes a regimen that, in its day, was reasonable: subtotal thyroidectomy with a deliberately retained euthyroid remnant, after preparation with carbimazole, propranolol and Lugol’s iodine. Three features stand out when the case is viewed through a contemporary lens.
First, the surgical philosophy has reversed. Where the historical goal was to retain a remnant that would maintain euthyroidism and avoid lifelong levothyroxine, current practice aims for definitive hypothyroidism via near-total or total thyroidectomy, treating recurrence as the larger clinical and surgical problem (Ross et al., 2016 ATA Guidelines; Sengun et al., 2024). The 2024 Sengun et al. data — recurrence of 0% with total/near-total versus 8% with subtotal, and 18% recurrence when the remnant is ≥4 g — illustrate the trade-off in concrete numbers.
Second, the medical regimen for orbitopathy and dermopathy has changed completely. The patient in this case received prednisone and cyclophosphamide for severe dermopathy; current practice would substitute risk-factor control, IV methylprednisolone with mycophenolate for active moderate-to-severe orbitopathy, teprotumumab for selected refractory or severe TED, and topical/intralesional steroids with compression for pretibial myxedema (Bartalena et al., 2021 EUGOGO; FDA Teprotumumab Summary Review, 2020). It is also notable that thyroidectomy alone does not reliably halt or reverse orbitopathy, as illustrated by the persistence of eye and skin disease in this case at follow-up; early surgery may, however, improve response to immunosuppressive therapy in moderate-to-severe active disease (Bartalena et al., 2021 EUGOGO).
Third, the diagnostic workup is now driven by sensitive TSH and TRAb rather than the T3-uptake/FTI panel used historically (Bartalena et al., 2021 EUGOGO). For this patient, a TRAb level would today be measured at diagnosis and could inform prognosis for both hyperthyroidism remission and orbitopathy course.
Conclusion
Near-total or total thyroidectomy is the contemporary surgical procedure of choice for Graves’ disease, performed by a high-volume surgeon after structured preoperative preparation with a thionamide (methimazole or its prodrug carbimazole — propylthiouracil in the first trimester of pregnancy), a beta-blocker, and Lugol’s solution or SSKI for 7–10 days. Lifelong levothyroxine replacement, titrated to TSH, is the planned and accepted outcome. Graves’ orbitopathy is managed alongside surgery using the EUGOGO algorithm, with teprotumumab as a major recent addition. Subtotal thyroidectomy, as performed in the historical case described above, retains educational value as an example of an earlier paradigm but is no longer recommended as a first-choice operation for Graves’ disease (Ross et al., 2016 ATA Guidelines; American Thyroid Association, “Surgical Management of Graves’ Disease”; Smithson et al., 2019; Sengun et al., 2024; Bartalena et al., 2021 EUGOGO).
References
American Thyroid Association. “Surgical Management of Graves’ Disease.” American Thyroid Association, July 25, 2018. Accessed May 15, 2026. Link: https://www.thyroid.org/surgical-management-graves-disease/.
Bartalena, Luigi, George J. Kahaly, Lelio Baldeschi, Colin M. Dayan, Anja Eckstein, Claudio Marcocci, Michele Marinò, et al. “The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves’ Orbitopathy.” European Journal of Endocrinology 185, no. 4 (2021): G43–G67. https://doi.org/10.1530/EJE-21-0479. Link: https://academic.oup.com/ejendo/article/185/4/G43/6654384.
Cleveland Clinic. “Pretibial Myxedema (Graves’ Dermopathy).” Cleveland Clinic, December 9, 2022. Accessed May 15, 2026. Link: https://my.clevelandclinic.org/health/diseases/24514-pretibial-myxedema.
Gunn, Alexander, Taofik Oyekunle, Michael Stang, Hadiza Kazaure, and Randall Scheri. “Recurrent Laryngeal Nerve Injury After Thyroid Surgery: An Analysis of 11,370 Patients.” Journal of Surgical Research 255 (2020): 42–49. Link: https://pubmed.ncbi.nlm.nih.gov/32540579/.
Ross, Douglas S., Henry B. Burch, David S. Cooper, M. Carol Greenlee, Peter Laurberg, Ana Luiza Maia, Scott A. Rivkees, Mary Samuels, Julie Ann Sosa, Marius N. Stan, and Martin A. Walter. “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.” Thyroid 26, no. 10 (2016): 1343–1421. https://doi.org/10.1089/thy.2016.0229. Link: https://www.liebertpub.com/doi/10.1089/thy.2016.0229.
Sengun, Berke, Yalin Iscan, Ismail Cem Sormaz, Nihat Aksakal, Gulcin Yegen, Hulya Hacisahinogullari, Emine Goknur Isik, Fatih Tunca, and Yasemin Giles Senyurek. “Subtotal vs. Total Thyroidectomy and Comparison of the Long-term Results in Patients with Graves’ Disease.” Journal of Investigative Surgery (published online December 2024). Link: https://pubmed.ncbi.nlm.nih.gov/39816432/.
Smithson, Mary, Ammar Asban, Jason Miller, and Herbert Chen. “Considerations for Thyroidectomy as Treatment for Graves Disease.” Gland Surgery 8, Suppl. 2 (2019): S106–S114. Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC6482648/.
Tappeiner, Christoph, and Anne-Lise Mayet. “Teprotumumab for the Treatment of Thyroid Eye Disease.” Frontiers in Endocrinology 15 (2024): article 11508897. Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC11508897/.
U.S. Food and Drug Administration. “Teprotumumab-trbw (Tepezza) Summary Review, BLA 761143.” FDA Center for Drug Evaluation and Research, 2020. Accessed May 15, 2026. Link: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/761143Orig1s000SumR.pdf.
Uludag, Mehmet, Isik Cetinoglu, Mehmet Taner Unlu, Ozan Caliskan, and Nurcihan Aygun. “Preoperative Preparation in Hyperthyroidism and Surgery in Special Situations.” Sisli Etfal Hastanesi Tip Bulteni 58, no. 3 (2024): 261–276. Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC11472198/.
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