Unmasking malignancy—thyrotoxic hypokalemic periodic paralysis and papillary thyroid carcinoma in a young male with Graves’ disease: a case report

Introduction

Background

Thyrotoxic hypokalemic periodic paralysis (THPP) is an uncommon but potentially life-threatening manifestation of hyperthyroidism characterized by transient muscle weakness or paralysis in the setting of hypokalemia (1). The underlying mechanism involves thyroid hormone-induced upregulation of Na⁺/K⁺-ATPase activity, which causes potassium influx into cells. It most commonly affects men of Asian or Hispanic descent, though it can occur in all ethnicities (1-3). Hyperthyroidism due to Graves’ disease is the most common cause of THPP (4), and Graves’ disease itself is associated with thyroid nodularity and, in some cases, increased risk of thyroid cancer (5,6).

Rationale and knowledge gap

Although both THPP and papillary thyroid carcinoma (PTC) are known associations of Graves’ disease, the co-occurrence of all three pathologies (THPP, Graves’ disease, and PTC) in a single patient is exceedingly rare. To our knowledge, only one other case report documenting this triad has been published to date (7).

Objective

We present a unique case of a young male with Graves’ disease and THPP whose acute presentation led to imaging that uncovered a multifocal, metastatic PTC. This case highlights the importance of comprehensive thyroid evaluation in patients presenting with THPP and known Graves’ disease. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-212/rc).

Case presentation

A 26-year-old male with a known history of Graves’ disease since childhood and prior gallstone pancreatitis presented to the emergency department with sudden onset of paralysis. He complained of progressive muscle weakness over 3 days and then awoke the next morning unable to move his arms or legs. He had not been taking methimazole for over a year due to a lapse in medical follow-up after losing insurance coverage.

On arrival, his potassium was 1.8 mmol/L and magnesium was also low. Electrocardiogram was unremarkable. Thyroid-stimulating hormone (TSH) was suppressed (<0.01 mU/L), and free T4 (4.87 ng/dL) and total T3 (3.81 ng/mL) were markedly elevated. He was treated with potassium and magnesium repletion, propranolol, and methimazole. His symptoms improved rapidly.

Thyroid ultrasound revealed a diffusely heterogeneous, hypervascular gland with multiple left-sided nodules, the largest measuring 2.3 cm. Fine-needle aspiration (FNA) was concerning for atypical follicular cells with nuclear crowding. Subsequent computed tomography (CT) of the neck with contrast showed a dominant left thyroid nodule with peripheral calcifications and an enlarged left level IV lymph node (Figure 1). Based on these findings, the patient was referred to surgical oncology for evaluation.

Figure 1 CT neck with contrast. (A) Coronal CT image demonstrates diffuse thyroid enlargement, with the arrow indicating a 2.5 cm calcified nodule in the inferior left thyroid lobe. (B) Axial CT image reveals an abnormal left level IV lymph node, with the arrow indicating the node measuring 1.6 cm in short axis. Scale bar =1 cm. CT, computed tomography.

The patient underwent total thyroidectomy with central and left lateral neck dissections. The gross specimen showed multiple nodules in both lobes of the thyroid and enlarged lymph nodes (Figure 2A). Pathology revealed multifocal PTC including a 3.7 cm widely invasive follicular variant in the left lobe and a 3.0 cm classic variant tumor, as well as a 1.5 cm classic variant tumor in the right lobe (Figure 2B-2D). Nine of thirty lymph nodes were positive for metastatic disease (levels II–V and central compartment), with the largest metastatic deposit measuring 1.9 cm. No extranodal extension or extrathyroidal extension was present. Final staging was pT2N1b.

Figure 2 Gross and histopathologic features of multifocal PTC. (A) Gross photograph of the thyroidectomy specimen with bilateral thyroid enlargement and multiple nodules, along with dissected cervical lymph nodes (scale bar =1 cm). (B) Lymph node metastasis showing tumor nests within lymphoid tissue (H&E, ×40; scale bar =200 µm). (C) Classic variant PTC in the left lobe, displaying papillary fronds with characteristic nuclear clearing and crowding (H&E, ×200; scale bar =50 µm). (D) Widely invasive follicular variant PTC in the left lobe, with irregular follicles infiltrating surrounding parenchyma (H&E, ×100; scale bar =100 µm). H&E, hematoxylin and eosin; PTC, papillary thyroid carcinoma.

Postoperatively, the patient was prescribed oral calcium carbonate and calcitriol, though they did develop symptomatic hypocalcemia with perioral and extremity paresthesias. This resolved with IV calcium repletion and the patient was discharged on oral calcium carbonate and calcitriol with plans for future clinic follow-up. On postoperative day 3 the patient returned to the emergency department (ED) with recurrent symptoms and a calcium of 6.3 mg/dL, having reportedly forgotten to take his medications. He was managed with intravenous and oral calcium and discharged after symptom resolution and normalization of serum calcium. At subsequent outpatient follow up, his calcium levels had normalized, and supplementation was tapered. He was referred to endocrinology with plans for radioactive iodine ablation.

The patient’s clinical course is summarized in Table 1.

All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki 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 illustrates a rare triad: THPP, Graves’ disease, and multifocal PTC. While the patient’s THPP episode was not the first sign of Graves’ disease as he had been diagnosed in childhood, it served as the sentinel event that prompted thyroid imaging and led to the discovery of nodules and cervical lymphadenopathy, ultimately leading to the resection of an aggressive malignancy.

Strengths and limitations

This case provides a unique opportunity to examine the interplay between Graves’ disease and its uncommon but severe complications, THPP and thyroid carcinoma. A limitation is the absence of long-term follow-up at the time of writing, particularly regarding radioactive iodine therapy and surveillance for carcinoma recurrence or distant metastasis. Further monitoring will also clarify whether thyroidectomy definitively prevented recurrence of THPP in this patient.

Comparison with similar research

The only other published case describing this triad was by Lin et al., who documented a similar presentation in a 33-year-old male patient (7). That case also involved metastatic PTC diagnosed following an episode of THPP, emphasizing the link between these entities, both occurring in young male patients. Additionally, both cases involved surgical treatment with total thyroidectomy. Absence of any future THPP recurrence in our presented case would provide further evidence to support thyroidectomy as a definitive treatment for THPP.

Also of note, the management of Graves’ disease with concurrent PTC, even in the absence of THPP, typically involves surgical resection when malignancy is confirmed or strongly suspected. Prior studies have demonstrated an increased incidence of incidental PTC in Graves’ patients undergoing thyroidectomy, underscoring the role of surgery as the standard therapeutic approach in this setting (4,5).

Explanations of findings

Graves’ disease has been associated with a slightly increased risk of PTC. The exact mechanism remains uncertain, but proposed explanations include chronic stimulation of the thyroid by thyroid-stimulating immunoglobulins and the pro-tumorigenic influence of the autoimmune inflammatory environment (5,6). THPP arises from a rapid intracellular shift of potassium triggered by thyroid hormone excess and is precipitated by carbohydrate or alcohol intake. While THPP typically resolves with appropriate electrolyte repletion and endocrine therapy, its presence in a patient with nodular Graves’ disease may reflect an underlying physiologic environment conducive to the development of more complex pathology.

Implications and actions needed

The presentation of THPP in a patient with known Graves’ disease should prompt clinicians to reassess for potential underlying malignancy, particularly when thyroid nodularity or lymphadenopathy is present. At the present time, it remains uncertain whether THPP itself confers any additional risk of PTC beyond that of Graves’ disease. Rather than representing a causal factor, THPP should be regarded as a clinical marker of uncontrolled thyrotoxicosis, which itself has been associated with increased cancer risk in Graves’ disease as stated previously (5,6). In this context, the occurrence of THPP in a patient with Graves’ disease warrants heightened vigilance for malignancy, even if a direct mechanistic link between THPP and PTC is currently unproven. Future guidelines may benefit from incorporating THPP as a clinical trigger warranting further structural evaluation in select patients with hyperthyroidism. This case also highlights the importance of considering thyroidectomy not just for symptom control in THPP, but as a diagnostic and therapeutic tool in identifying coexistent malignancy.

Conclusions

This case report highlights the rare coexistence of THPP, Graves’ disease, and multifocal PTC, a clinical triad that has only been described once previously in the literature. While each condition is well-characterized individually, their concurrent presentation in a single patient is exceedingly uncommon and may be easily overlooked.

This case underscores the importance of maintaining a high index of suspicion for underlying structural disease in patients with Graves’ disease who present with THPP. In addition to attributing THPP to the metabolic effects of untreated hyperthyroidism, clinicians should recognize it as a possible marker of coexistent thyroid pathology, including malignancy. Early evaluation with neck imaging and FNA of suspicious nodules or lymphadenopathy should be considered in these cases. In patients with nodular Graves’ disease, whether or not THPP is present, thyroidectomy may be appropriate not only to achieve definitive control of hyperthyroidism but also to facilitate timely diagnosis and management of thyroid carcinoma.

Should further instances of this rare triad be reported, THPP may be recognized as a distinct clinical signal that can guide more timely and comprehensive management of at-risk patients.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-212/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-212/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-212/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 case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki 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 reviewby 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/.

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