35195585

68 Ga-DOTANOC PET/CT in Multiple Endocrine Neoplasia 1 With Associated Adrenocortical Carcinoma

Shyma Basheer, MD, ** Ramkesh Ratheesan, MBBS,¡ Manjit Sarma, DNB, ** Shanmuga Sundaram Palaniswamy, DNB, ** and Anitha Mathews, MD±

Abstract: Multiple endocrine neoplasia 1 (MEN1) syndrome is an autoso- mal dominant syndrome comprising a triad of pancreatic, pituitary, and parathyroid tumors. Adrenal cortical carcinoma occurs rarely in MEN1 syn- drome. Here, we have presented a case of a 62-year-old woman with adrenal mass and elevated serum parathormone levels, who underwent 68Ga- DOTANOC PET/CT. 68Ga-DOTANOC PET/CT showed intense tracer con- centration in the left adrenal mass and lesions in the liver, pancreas, and peri- toneum. Biopsy of the peritoneal deposit revealed metastatic adrenocortical carcinoma, and further genetic testing showed MEN1 mutation.

Key Words: 68Ga-DOTANOC, adrenocortical carcinoma, MEN1 syndrome, PET/CT

(Clin Nucl Med 2022;47: e389-e392)

Received for publication September 4, 2021; revision accepted December 30, 2021.

From the *Department of Nuclear Medicine and Molecular Imaging, ¡Amrita Vishwa Vidyapeetham, Kochi, Kerala, India; and įDepartment of Pathology, Regional Cancer Centre, Trivandrum, Kerala, India.

Conflicts of interest and sources of funding: none declared.

Correspondence to: Shyma Basheer, MD, Department of Nuclear Medicine and Molecular Imaging, Amrita Institute of Medical Sciences and Research Centre, Kochi Kerala 682041, India. E-mail: shyma.b@gmail.com.

Copyright @ 2022 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/22/4705-e389

DOI: 10.1097/RLU.0000000000004102

REFERENCES

1. Kharb S, Pandit A, Gundgurthi A, et al. Hidden diagnosis of multiple endo- crine neoplasia-1 unraveled during workup of virilization caused by adreno- cortical carcinoma. Indian J Endocrinol Metab. 2013;17:514.

2. Tripathy S, Prakash S, Arun Raj ST, et al. 3P’s of Wermer/MEN1 syndrome on 68Ga-DOTANOC PET/CT scan. Clin Nucl Med. 2020;45:e516-e517.

3. Bharwani N, Rockall AG, Sahdev A, et al. Adrenocortical carcinoma: the range of appearances on CT and MRI. AJR Am J Roentgenol. 2011;196: W706-W714.

4. Almarzouq A, Asfar S, Hussain S, et al. Giant nonfunctioning adrenocortical carcinoma: a case report and review of the literature. BMC Res Notes. 2014;7:769.

5. Sharma P, Singh H, Dhull VS, et al. Adrenal masses of varied etiology: an- atomical and molecular imaging features on PET-CT. Clin Nucl Med. 2014;39:251-260.

6. Fareau GG, Vassilopoulou-Sellin R. Diagnostic challenges in adrenocortical carcinoma: recommendations for surveillance after surgical resection of se- lected adrenal nodules. Endocr Pract. 2007;13:636-641.

7. Sharma P, Singh H, Bal C, et al. PET/CT imaging of neuroendocrine tumors with (68)gallium-labeled somatostatin analogues: an overview and single in- stitutional experience from India. Indian J Nucl Med. 2014;29:2-12.

8. Lastoria S, Marciello F, Faggiano A, et al. Role of 68Ga-DOTATATE PET/ CT in patients with multiple endocrine neoplasia type 1 (MEN1). Endocrine. 2016;52:488-494.

9. Leijon H, Remes S, Hagström J, et al. Variable somatostatin receptor subtype expression in 151 primary pheochromocytomas and paragangliomas. Hum Pathol. 2019;86:66-75.

10. Pauwels E, Cleeren F, Bormans G, et al. Somatostatin receptor PET ligands -the next generation for clinical practice. Am J Nucl Med Mol Imaging. 2018;8:311-331.

11. Gezer E, Çetinarslan B, Cantürk Z, et al. Metastatic MEN1 syndrome treated with lutetium-177-a case report. Eur Endocrinol. 2019;15:92-94.

FIGURE 1. A 62-year-old Indian woman with history of right adrenalectomy for adrenal cortical adenoma 7 years back presented with recent-onset abdominal pain. Ultrasonography suggested malignant lesions involving adrenal, hepatic, pancreatic, and peritoneum. Functional adrenal workup with serum aldosterone and adrenocorticotrophic hormone levels, a dexamethasone suppression test, and measurement of 24-hour urinary metanephrine levels were within reference ranges. However, elevated serum calcium levels (12.9 mg/dL) and serum parathormone levels (438 pg/mL) raised a possibility of multiple endocrine neoplasia 1 (MEN1). Patient was referred for whole-body 68Ga-DOTANOC PET/CT imaging. MIP image of the PET/CT scan (A) showed adrenal lesion, hepatic lesion, and lesions in the abdomen region. Axial CT and fused PET/CT images show normal physiological tracer uptake in pituitary gland, with no obvious CT-detected lesion (B, C), increased tracer uptake in left parathyroid mass (D, E), and in pancreatic lesions (F, G).

A

A

A

B

C

R

R

A

A

D

E

R

R

A

A

F

G

R

R

FIGURE 2. Axial CT and fused PET/CT showed increased tracer uptake in the mass lesion involving the adrenal gland (A, B), large heterogeneously enhancing lesions in liver (C, D), and multiple peritoneal deposits (E, F). Biopsy from the peritoneal mass revealed metastatic adrenocortical carcinoma. On genetic testing, MEN1 mutation was identified.

A

B

R

R

A

A

C

D

R

R

E

A

F

A

V

y

1

y

R

R

FIGURE 3. Photomicrographs show tumor comprising large polyhedral cells with abundant eosinophilic granular cytoplasm and dense nuclear chromatin in sheets with intervening thin-walled capillaries (A; hematoxylin-eosin stain, original magnification ×400). Scattered tumor cells expressing melan-A (B; immunohistochemnstry, original magnification ×400). The tumor cells also expressed immunoreactivity to cytokeratin and vimentin, and Ki67 index was approximately 2%. Multiple endocrine neoplasia 1 is an autosomal dominant endocrine syndrome with classic triad of parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary adenomas.1,2 Adrenocortical carcinomas are rarely associated with MEN1 syndrome.3, In 60% to 85% of adults with adrenocortical carcinoma, patients present with a large mass or symptoms related to mass effect. Because of late presentation of nonfunctioning tumors, approximately 30% of cases present with metastatic disease. Only a few studies are available in the literature, emphasizing the utility of 68Ga-DOTANOC PET/CT imaging on MEN1 syndrome. 68Ga-DOTANOC PET/CT gives a panoramic view of lesions within the pituitary, pancreas, and adrenals, thereby eluding the need of different conventional imaging techniques.8 As somatostatin receptors (SSTRs) constitute a basis for tumor imaging and treatment with somatostatin analogs and peptide receptor radionuclide therapy, 68Ga-DOTANOC PET/CT may have an added value in management of patients with SSTR expressing inoperable/metastatic tumors.9-11 Our case highlights the importance of SSTR imaging in a patient with suspected MEN1 syndrome and also the association of adrenocortical malignancy with MEN1 syndrome, which has clinical implication on therapy and prognostication of the patients.

A

B

C