Thyrotoxic crisis complicated by cardiogenic shock after laparoscopy for suspected acalculous cholecystitis and its successful medical treatment: a case report

Introduction

Background

Thyrotoxic crisis (TC) (Table 1) may develop in patients with known or previously unknown hyperthyroidism, usually Graves’ disease (1). Patients with TC present with symptoms and signs of hyperthyroidism. TC is frequently triggered by exogenous factors, e.g., surgery, trauma, infection, cardiovascular disease, iodine excess (contrast agents, amiodarone), or discontinuation of antithyroid medication (1). The annual incidence of TC is 0.2–0.7/100 000 (2,3). While TC is a rare disease, its mortality rate is high, reaching 25% (1-3). In TC, multiple organ failure, especially heart failure, is the main cause of death (4). TC should be suspected in a hyperthyroid patient if altered consciousness, circulatory instability (e.g., sinus tachycardia, atrial fibrillation, heart failure including cardiogenic shock), fever, or gastrointestinal symptoms (nausea, vomiting, or abdominal pain) are present (1,2).

Rationale and knowledge gap

The evaluation of patients with abdominal pain is a frequent task for emergency physicians. The distinction between patients requiring surgery and those with a “medical” acute abdomen is not always straightforward, and their treatment differs (5). It is important not to subject patients with untreated TC to unnecessary interventions, since they may aggravate the TC (1). Acalculous cholecystitis is described as a possible cause of the abdominal pain in patients with TC (6). Increased thickness of the gallbladder wall may also be a sign of right heart failure, mimicking acalculous cholecystitis (7,8). This association was described in a patient with TC and heart failure almost 70 years ago, with limited diagnostic tools (9). Modern techniques to assess cardiac function were used in our patient. Guideline-directed and optimal medical therapy for the severe heart failure [including norepinephrine and levosimendan (10)] and the hyperthyroidism were successfully implemented.

Objective

This report aims to present a rare patient with upper abdominal pain mimicking acalculous cholecystitis and a delayed diagnosis of TC with severe, successfully treated heart failure. We present this article in accordance with the CARE reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-25-26/rc).

Case presentation

A previously healthy 45-year-old woman of African descent complaining of severe upper abdominal pain, recurrent vomiting, and fever was admitted to the emergency room in July 2021. The pain began 2 weeks prior but became severe in the past few days. She was anxious, hypertensive [blood pressure 170/90 mmHg (normal value <120/80 mmHg)], tachycardic [maximal heart rate 170/min (normal value at rest 60–100/min)], and febrile [temperature 38.9 °C (normal 36.5–37.5 °C)]. An electrocardiogram revealed atrial fibrillation (AFib). The peripheral capillary oxygen saturation (SpO₂) was 97% (normal 90–100%) while the patient was breathing ambient air. There were no overt clinical signs of heart failure, and there were no signs of hypoperfusion, i.e., her extremities were warm and dry, and the patient did not sweat excessively. The upper abdomen was tender to the touch, and bowel sounds were scant. A cursory neurological exam was normal, but the deep tendon reflexes were not tested. The eye examination revealed no abnormalities. The white cell count was 14.5 G/L (reference range 4–9.8 G/L), and the CRP concentration was 50 mg/L (<1.0 mg/L). The bilirubin level was 28 µmol/L (<21 µmol/L), but the liver transaminase and amylase concentrations were normal. On ultrasound, which was painful for the patient, the gallbladder had a three-layered wall with a thickness of 3 mm. Taken together, acute acalculous cholecystitis was suspected, and immediate surgical cholecystectomy was planned.

During preparation for surgery, 5×1 mg of metoprolol was given intravenously (i.v.) to slow the heart rate. Anesthesia was induced with 60 mg propofol i.v., 200 µg fentanyl i.v. and 6 mg midazolam i.v.. The intubated and ventilated patient then became hypotensive (lowest blood pressure 75/65 mmHg), and norepinephrine was administered [a total of 400 µg as initial i.v. boluses, followed by an i.v. infusion of 80 µg over 5 hours (Figure 1A)]. Laparoscopically, the gallbladder was not inflamed and was left in situ. No other cause for the acute abdomen was found.

Figure 1 Timeline showing the cardiac and thyrostatic medication in the ICU (A,B) and the entire observation period of 800 days (C,D). The betablocker (shown in blue in panels A and B) was part of both the cardiac and thyrostatic therapy, and is therefore depicted in duplicate. In C, the daily dose of carbamazepine and the concentrations of fT4 and fT3 are depicted over time. Both fT4 and fT3 remained in the normal range from Day 45 on. The guideline-directed cardiac therapy as prescribed at discharge—which corresponded to the treatment the patient received on the ward—and in the outpatient clinic is listed in D. (E,F) M-mode still frames obtained by transthoracic echocardiography on day 2 of the hospital stay and on day 250 are shown. For both exams the patient was in sinus rhythm. The systolic inward movement and thickening of the IVS (white arrow) and the PW (black arrow) were substantially reduced and asynchronous. The LVEF was 25% (normal >55%). Moreover, moderate-to-severe tricuspid regurgitation and signs of right heart failure were noted (not shown). The estimated pulmonary artery systolic pressure was 35 mmHg (normal <35 mmHg). The systolic function of the slightly dilated left ventricle with eccentric hypertrophy was normal at the follow-up exam (B, LVEF 55%), and the degree of tricuspid regurgitation was mild. The signs of right heart failure were no longer present. The NT-proBNP concentration was 25,657 pg/mL in E, and 181 pg/mL in F (normal <125 pg/mL); data not shown. fT3, free triiodothyronine; fT4, free thyroxine; ICU, intensive care unit; IVS, interventricular septum; LVEF, left ventricular ejection fraction; LVID, left ventricular internal diameter; NT-proBNP, N-terminal pro-B-type natriuretic peptide; PW, posterior wall; RV, right ventricle.

Thyroid function tests were not available at the initial evaluation because acalculous cholecystitis was suspected. The tests were backordered and were obtained at the end of the operation, revealing suppressed thyroid-stimulating hormone (TSH) levels and elevated peripheral hormone levels: TSH <0.05 mU/L (0.27–4.20 mU/L), free thyroxine (fT4) 67.7 pmol/L (12–22 pmol/L), and free triiodothyronine (fT3) 15.7 pmol/L (3.1–6.8 pmol/L). The clinical and biochemical findings were consistent with a diagnosis of hyperthyroidism with TC (Tables 2,3). The patient was transferred to the intensive care unit (ICU).

Multimodal thyrostatic therapy with inhibitors of thyroid peroxidase was started immediately (Figure 1B): Thiamazole (40 mg i.v.) was administered, followed by carbimazole [15 mg twice daily (bid) orally]. Iodine uptake by the thyroid was inhibited by sodium perchlorate¹ [500 mg three times daily (tid) orally for 2 days]. Corticosteroids were added to block the conversion of fT4 to the active fT3 and to compensate for a relative adrenal insufficiency (hydrocortisone 150 mg i.v. on day 1 and methylprednisolone 65 mg i.v. on days 2 and 3). After the administration of beta-blockers (5×1 mg metoprolol i.v. followed by 5 mg bisoprolol bid orally), the patient’s heart rhythm shifted from AFib to a sinus rhythm. The norepinephrine infusion was stopped after 5 hours. The patient was extubated shortly afterward.

A sonographic examination of her thyroid revealed that it was diffusely enlarged, and the parenchyma showed a heterogeneous texture with hypervascularization. Elevated anti-TSH receptor antibody levels [9.4 U/mL (<3.3 U/mL)] confirmed the diagnosis of Graves’ disease.

There were no clinical signs of infection, and serial blood and urine cultures remained sterile.

In the ICU, a small blood pressure amplitude [pulse pressure of 30 mmHg (normal 40–60 mmHg)] and low mixed venous oxygen saturation (SvO₂) of 37% (normal 65–75%) suggested a reduced stroke volume and cardiac output. A serum lactate level of 2.4 mmol/L (normal 0.5–1.6 mmol/L) indicated cardiogenic shock with subsequent acute oliguric kidney injury [creatinine 166 µmol/L (44–80 µmol/L)]. The results of the echocardiography and laboratory tests [NT-proBNP 25,657 ng/L (<125 ng/L)] were consistent with these findings.

Levosimendan was used to increase cardiac inotropy (i.v. infusion of 12.5 mg over 30 hours), which increased the cardiac index from 2.0 to 3.3 L/min/m² (normal range 2.6–4.2 L/min/m²), and the SvO₂ from 37 to 78%. Heart failure therapy consisting of diuretics (furosemide i.v. 3×10 mg, followed by an infusion of 120 mg over 12 hours on days 2 and 3. Torasemide 10 mg orally once daily [qd] was started on day 4) and beta-blockers (see above) was optimized with the angiotensin receptor blocker valsartan (40 mg orally qd started on day 4). A mineralocorticoid receptor antagonist (spironolactone 25 mg orally qd) was added on day 6. Paroxysmal AFib required anticoagulant therapy: In the ICU i.v. heparin was given (initially 10,000 U daily as a continuous infusion, increased to 15,000 U daily on day 3), and on the ward edoxaban was started (60 mg orally qd).

The patient responded well to the treatment provided. She became afebrile, and her abdominal pain was well controlled with analgesics. The nausea and vomiting abated. There were no side effects from the medication or other adverse events reported. On day 4 after admission, the patient was transferred to the regular ward. The disease course was complicated by nosocomial pneumonia, treated with ceftriaxone 2 g qd for 7 days. No pathogen was identified. Inpatient rehabilitation was started two weeks later.

The thyrostatic treatment was effective; peripheral thyroid hormone levels were normal after 6 weeks of therapy (Figure 1C). Stable euthyroidism allowed the carbimazole dose to be gradually reduced and stopped after 2 years, despite a theoretical recurrence risk of 40% (12). Thyroidectomy or radioactive iodine therapy were declined.

Persistent high blood pressure necessitated a more powerful antihypertensive therapy in the outpatient setting [a polypill containing perindopril 10 mg, amlodipine 10 mg and indapamide 2.5 mg orally qd was started instead of candesartan on day 90. Doxazosine 8 mg orally qd was added on day 400 (Figure 1D)]. With this adapted therapy the blood pressure was well controlled and the cardiac function improved (Figure 1E,1F). A cardiac MRI (cMRI) revealed no signs of myocardial ischemia or left ventricular fibrosis.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Key findings

This case describes clear clinical, laboratory, and imaging evidence of severe heart failure in a patient with TC. In the emergency department, the initial work-up suggested acalculous cholecystitis. The increased thickness of the gallbladder wall, however, was a sign of congestion. Laparoscopically, the gallbladder was not inflamed. Subsequently, TC was diagnosed, confirmed by the results of the thyroid panel. Effective multimodal thyrostatic therapy was started immediately. In the ICU, cardiogenic shock developed, which necessitated treatment with norepinephrine and the inotrope levosimendan. Heart failure therapy led to clinical improvement and recovery of the severely reduced cardiac function. There was no recurrence of the hyperthyroidism during follow-up of two years.

Strengths and limitations

The study adds to the literature of abdominal pain as an unspecific symptom of TC (5,6,9,13). In our patient heart failure was an important causative factor. The diagnosis of heart failure including cardiogenic shock was established by ICU monitoring, echocardiography, and laboratory data. The working diagnosis of acalculous cholecystitis was definitely ruled out by laparoscopy. In retrospect, the indication to perform a laparoscopy was made too early, because the differential diagnosis of TC was not considered initially. We do not know how the disease course would have differed had the hyperthyroidism been known preoperatively. It is likely that the laparoscopy would not have been performed. Moreover, without the trigger of operative stress leading to cardiogenic shock, the TC would probably have run a milder course. A strength of the study is the well documented disease course in the hospital and in the outpatient setting, the latter spanning a period of 2 years. The cardiac therapy for acute heart failure followed current guidelines (14). Updated guidelines for the treatment of hypertension in heart failure patients prefer the use a sodium-glucose co-transporter 2 inhibitor over doxazosine (15). Multimodal treatment of TC suggested by current guidelines was implemented (16-18). This approach resulted in a successful outcome (19).

Comparison with similar research

Thyrotoxicosis is known to cause abdominal pain (5). A retrospective analysis over 10 years in a tertiary care hospital revealed that only 25 patients presented with both TC and an acute abdomen, confirming its rarity. Four of them required a surgical intervention (20). The abdominal pain reported by patients with TC may simulate acalculous cholecystitis. In two case reports, the patients were already prepared for cholecystectomy, but were managed conservatively after the diagnosis of TC was established (6,9). Wohl and Shuman reported that right heart failure caused the abdominal pain in patients with TC almost 70 years ago (9). However, the cardiac function was not quantified, and laboratory markers of heart failure were not available. Two recent papers confirmed that right heart failure may masquerade as acalculous cholecystitis (7,21). The use of levosimendan for the treatment of heart failure caused by TC is new. The inotrope has theoretical advantages over the catecholamine dopamine because the effect of the latter is compromised by the concomitant use of betablockers (10). Levosimendan may help to correct right ventricular dysfunction, especially if pulmonary hypertension is present (22).

Explanation of findings

The pathogenesis of abdominal pain in patients with TC is poorly understood and includes gastroparesis, intestinal hypermotility and bowel ischemia (20). In addition, it may be a sign of liver and gallbladder congestion (8,23). The patient’s heart failure was multifactorial: (I) she had unknown arterial hypertension with hypertensive heart disease; (II) her left ventricular function was substantially reduced by tachycardic AFib; and (III) she had as yet unrecognized hyperthyroidism with TC, which was amplified by surgical intervention (1).

Thyroid hormones have multiple effects on the structure and function of cardiomyocytes, including genomic and rapid nongenomic effects. Both of these types of effects lead to tachycardia, increased stroke volume and heart minute volume (HMV), and vasodilation (4). As counterregulatory measures, the renal renin-angiotensin-aldosterone system is activated and erythropoietin secretion is elevated, increasing the plasma volume (4).

The reduced contractile reserve, together with the tachycardia-related shortened diastolic filling time and volume overload, can lead to high-output heart failure with increased HMV and low peripheral resistance (24-26).

Patients with coronary heart disease or hypertensive cardiopathy often have preexisting impaired left ventricular function. In these most vulnerable patients, TC-induced tachycardia (AFib in up to 20% of patients) may cause overt heart failure with a profoundly reduced ejection fraction (HFrEF), as well as postcapillary pulmonary hypertension (4). After establishment of euthyroidism and guideline-directed therapy, left ventricular function may improve (14,27). AFib converts spontaneously to sinus rhythm in approximately 50% of patients.

Graves’ disease, the florid hyperthyroidism and TC were not recognized initially, possibly due to premature closure of the diagnostic process. A trigger factor for the TC was not present, the most frequent, i.e. an infective disease, which was ruled out by multiple cultures of blood and urine. The laparoscopy was performed to rule out acalculous cholecystitis as well as other surgically amenable pathologies (e.g., perforated viscus or appendicitis). However, the surgical intervention worsened the heart failure resulting in cardiogenic shock.

Implications and actions needed

The evaluation of patients with an acute abdomen remains challenging. A thorough history and careful clinical examination remain important. Focused physical examinations and abdominal ultrasound scans have inherent drawbacks. Since not every patient with TC has typical symptoms and signs, a high index of suspicion is required. The use of the Burch-Wartofsky Score and Akamizu criteria (Tables 2,3) may be of help. The preoperative measurement of TSH levels is important, especially in equivocal cases. To achieve a good outcome, a close interdisciplinary collaboration is essential. Patients with TC must be closely monitored in an ICU.

Conclusions

Patients with TC may present with a “medical” acute abdomen, masquerading as acalculous cholecystitis. The pathogenesis of abdominal pain in TC patients is multifactorial and includes liver (and gallbladder) congestion due to right heart failure. In a patient with hypertensive heart disease, TC can lead to heart failure with substantially reduced left ventricular function in the context of a high-output state and tachycardic AFib. Unnecessary surgical interventions must be avoided in patients with TC, as heart failure severity may increase perioperatively, and result in cardiogenic shock. Guideline-directed optimal medical therapy for TC and heart failure is key to a successful outcome. A thyroid panel is recommended in patients presenting with an equivocal acute abdomen.

Acknowledgments

We thank Prof. Peter Kopp, MD, Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland, for his critical review of the manuscript.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-25-26/rc

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-25-26/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-25-26/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

¹Owing to the risk of aplastic anemia and nephrotic syndrome after prolonged use, sodium perchlorate is rarely used today. In many countries it is not available. Iodide, which inhibits the release of hormones by the thyroid gland (Plummer effect), is used preferentially.

References

1. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am 2006;35:663-86. vii. [Crossref] [PubMed]
2. Akamizu T, Satoh T, Isozaki O, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid 2012;22:661-79. [Crossref] [PubMed]
3. Galindo RJ, Hurtado CR, Pasquel FJ, et al. National Trends in Incidence, Mortality, and Clinical Outcomes of Patients Hospitalized for Thyrotoxicosis With and Without Thyroid Storm in the United States, 2004-2013. Thyroid 2019;29:36-43. [Crossref] [PubMed]
4. Klein I, Danzi S. Thyroid disease and the heart. Circulation 2007;116:1725-35. [Crossref] [PubMed]
5. Murali N, El Hayek SM. Abdominal Pain Mimics. Emerg Med Clin North Am 2021;39:839-50. [Crossref] [PubMed]
6. Elhaj MF, Magboul H, Ahmed AO, et al. Thyrotoxicosis Presenting With Acute Cholecystitis: A Case Report and Literature Review. Cureus 2021;13:e20840. [Crossref] [PubMed]
7. Habib MB, Albandak M, Osman MH, et al. Acalculous Cholecystitis: The Unexpected Mask of De Novo Heart Failure. Clin Case Rep 2025;13:e70324. [Crossref] [PubMed]
8. van Breda Vriesman AC, Engelbrecht MR, Smithuis RH, et al. Diffuse gallbladder wall thickening: differential diagnosis. AJR Am J Roentgenol 2007;188:495-501. [Crossref] [PubMed]
9. WOHL MG. SHUMAN CR. Atypical syndromes in hyperthyroidism. Ann Intern Med 1957;46:857-67. [Crossref] [PubMed]
10. Voll M, Øystese KA, Høiskar E, et al. Case report: a patient with thyroid storm, refractory cardiogenic shock, and cardiac arrest treated with Lugol's iodine solution and veno-arterial extra corporal membrane oxygenation support. Eur Heart J Case Rep 2021;5:ytab017. [Crossref] [PubMed]
11. Burch HB, Wartofsky L. Life-Threatening Thyrotoxicosis: Thyroid Storm. Endocrinology and Metabolism Clinics of North America 1993;22:263-77.
12. Wiersinga WM, Poppe KG, Effraimidis G. Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis. Lancet Diabetes Endocrinol 2023;11:282-98. [Crossref] [PubMed]
13. Bhattacharyya A, Wiles PG. Thyrotoxic crisis presenting as acute abdomen. J R Soc Med 1997;90:681-2. [Crossref] [PubMed]
14. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-726. [Crossref] [PubMed]
15. Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens 2023;41:1874-2071. [Crossref] [PubMed]
16. Satoh T, Isozaki O, Suzuki A, et al. 2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition). Endocr J 2016;63:1025-64.
17. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016;26:1343-421. [Crossref] [PubMed]
18. Kahaly GJ, Bartalena L, Hegedüs L, et al. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J 2018;7:167-86. [Crossref] [PubMed]
19. Furukawa Y, Tanaka K, Isozaki O, et al. Prospective Multicenter Registry-Based Study on Thyroid Storm: The Guidelines for the Management from Japan are Useful. J Clin Endocrinol Metab 2024;110:e87-e96. [Crossref] [PubMed]
20. Leow MK, Chew DE, Zhu M, et al. Thyrotoxicosis and acute abdomen--still as defying and misunderstood today? Brief observations over the recent decade. QJM 2008;101:943-7. [Crossref] [PubMed]
21. Yu Q, Lai W. Heart failure misdiagnosed as acute cholecystitis: a case report. J Med Case Rep 2024;18:497. [Crossref] [PubMed]
22. Kapoor MC. Levosimendan in Right Ventricular Dysfunction. Ann Card Anaesth 2023;26:1-3. [Crossref] [PubMed]
23. Sundaram V, Fang JC. Gastrointestinal and Liver Issues in Heart Failure. Circulation 2016;133:1696-703. [Crossref] [PubMed]
24. Mehta PA, Dubrey SW. High output heart failure. QJM 2009;102:235-41. [Crossref] [PubMed]
25. Cannata A, McDonagh TA. Heart Failure with Preserved Ejection Fraction. N Engl J Med 2025;392:173-84. [Crossref] [PubMed]
26. Shafi I, Harmouch KM, Prakash P, et al. Unmasking High-Output Heart Failure: Beyond Conventional Paradigms. Cardiol Rev 2025; Epub ahead of print. [Crossref]
27. Siu CW, Yeung CY, Lau CP, et al. Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism. Heart 2007;93:483-7. [Crossref] [PubMed]