Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a population incidence ranging from 0.001 to 0.002% (1). Aldosterone-producing ACC, a subtype of ACC, is rarer. Papillary thyroid carcinoma (PTC), a slowly progressive cancer with a high survival rate, represents more than 70–90% of thyroid malignancies (2–4). Graves’ disease (GD) is an autoimmune system disorder that results in the overproduction of thyroid hormone When two or more endocrine malignancies are detected in the same person, genetic disorders should be ruled out. However, there is limited insight detailing the association between ACC and PTC (5). Moreover, there are no published reports on the association between ACC and PTC with GD.

Here, we report a unique case of a patient with aldosterone-producing ACC who, surprisingly, also had a localized PTC and GD. The primary concern was the simultaneous appearance of two endocrine tumors, and the possibility of hereditary cancer syndrome.

ACC is a rare malignancy, with a high progression rate and a five-year survival rate less than 50% if locally advanced (6, 7). Most ACCs (approximately 60%) include functional hormone-secreting tumors, leading to tumor detection. Yet 40% of symptomatic patients with ACCs have CS and 24% have concurrent virilization (8). Very few of these tumors secrete primarily aldosterone, and less than 2.5% of ACCs exclusively produce aldosterone (9). Here, we describe a distinctive case of aldosterone-producing ACC. Her aldostern-renin rate(ARR) was 3.2. The European Society for Hypertension suggests a lower cutoff point (ARR between 1.12 and 2.7) (10). The plasma renin concentration(PRC) in this patient was not completely inhibited due to hyperthyroidism, which can increase renin levels (11). The underlying mechanisms may be that increased beta-adrenergic activity and catecholamine production contribute to the increase in mineralocorticoid function of the adrenal glands during thyrotoxicosis and upregulation of the renin angiotensin-aldosterone system (12).

Simultaneous occurrence of two different endocrine neoplasms is notably infrequent. Few cases have described concurrent ACCs and PTC. Only four cases matched closely with our patient among search results from the PubMed database (13–16). One case alone describes comorbidity of APAC and PTC (17). However, few of these patients underwent genetic testing. The comorbidity of both tumors appears suggestive of a hereditary component, with the most likely hereditary syndromes associated with ACC being MEN-1 (mutation in menin), LFS (TP53), and Beckwith-Wiedemann syndrome (11p15 and CDKN1C) (18). The known syndromes caused by a hereditary predisposition to multiple endocrine tumors do not specifically include the concurrence of PTC with ACC.

Genetic tests were performed to exclude known hereditary conditions that could potentially cause a combination of ACC and PTC. Analysis revealed heterozygous TP53 and MEN-1 mutations; however, neither were morbigenous so far. It remains uncertain whether the identified genes are causative for these two neoplasms; therefore, LFS and MEN-1 cannot be excluded.

GD is the most common cause of spontaneous thyrotoxicosis. Based on our investigation, there are no published cases of GD with ACC and PTC or with aldosterone-producing ACC. There is only one published case of a patient with synchronous GD and primary aldosteronism (19). Their perspective on the underlying mechanism associating the two diseases was unclear, but they suggested the possibility of autoimmune mechanisms, such as the actions of autoantibodies (19). GD and PTC may occur concomitantly. The incidence of PTC in GD has increased over time, and the rate of cancer associated with GD is higher than that in euthyroid controls (20–23). The etiology of the increased risk of PTC in GD is not fully understood; nonetheless, thyroid-stimulating immunoglobulin are thought to potentially contribute to this relationship (21, 22). The association between primary aldosteronism, PTC, and GD may be attributed to autoimmune disorders. However, the underlying mechanisms of aldosterone-producing ACCs and PTC with GD warrant further evaluation and research.

A previous meta-analysis revealed that GD has a significantly higher risk of associated multifocality/multicentricity and distant metastases at the time of cancer diagnosis but is not associated with PTC-related mortality or recurrence (24, 25). In our case, the PTC might also be multifocal since the patient had 3 similar solid nodules in the right thyroid lobe and one was confirmed PTC.

There are few case reports documenting the comorbidity of aldosterone-producing ACC and PTC. When the concurrence of two different endocrine neoplasms occurs, it is imperatave for endocrinologists to consider the possibility of a underlying hereditary predisposition. Our genetic analysis found variants of the TP53 and MEN-1 gene; however, they have not yet been established as pathogenic. Based on our extensive review, there are no published cases of synchronized aldosterone-producing ACC, and PTC alongside with GD, and a link between these three diseases remains undetermined. Our case cannot eliminate the possibility of an as-yet-unidentified syndrome; more cases are needed to further elucidate this hypothesis.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving humans were approved by Hainan General Hospital Medical Ethics Committee. The studies were conducted in accordance with the local legislation and institutional requirements. The human samples used in this study were acquired from primarily isolated as part of your previous study for which ethical approval was obtained. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

YZ: Writing – original draft, Writing – review & editing, Conceptualization. JY: Writing – original draft, Writing – review & editing. CF: Data curation, Formal analysis, Writing – review & editing. FW: Formal analysis, Resources, Writing – review & editing. HL: Conceptualization, Supervision, Writing – review & editing. KC: Conceptualization, Supervision, Writing – review & editing.