Graves' Ophthalmopathy on 68Ga-DOTANOC Positron Emission Tomography/Computed Tomography.

Graves' ophthalmopathy (GO) involves autoimmune activation of fibroblasts, resulting in chronic inflammatory reaction. Somatostatin receptors are expressed in the cells associated with chronic inflammation. We hereby present patients with active GO, with delayed response to the standard treatment regimen, in whom 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) was planned to evaluate the orbital inflammation. 68Ga-DOTANOC PET/CT shows no physiological orbital muscle uptake. It can provide information which may possibly of utility in response assessment and also screening patients who fail to respond to conventional treatment, for newer therapies such as long-acting somatostatin analogs. Copyright:

Figure 1a–i shows 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) orbital cross-section in three different patients (control, patient 1, and patient 2) with physiologic pituitary uptake seen in all three patients (yellow arrows). Figure 1a–c shows sections in a 44-year-old male with a history of pheochromocytoma (taken as control for Graves' ophthalmopathy [GO] group). Scan shows normal extraocular muscles (EOM) with no abnormal uptake (c, white arrow). Figure 1d–f shows sections, in a 65-year-old woman with severe GO (left > right), initially managed for her thyroid eye disease with pulse intravenous methyl prednisolone (6 gm) and left orbital decompression but showed delayed response to treatment. Scan shows bulky EOM (left > right) (e and f, white arrow) with somatostatin receptor (SSTR) expression. Neck sections showed enlarged both lobes of thyroid with increased tracer uptake, with a large nodule in the left lobe (d, black arrow) and also retrosternal extension from the right lobe forming a globular mass (d, red arrow). Fine-needle aspiration cytology from the left lobe cold nodule showed benign adenomatous changes (Bethesda 2). Her thyroid profile suggested hyperthyroid status, fT4 – 2.68 ng/dl (0.9–1.7 ng/dl), fT3 – 5.6 pg/ml (2–4.4 pg/ml), and thyroid stimulating hormone (TSH) <0.005 μIU/ml. For thyroid dysfunction, she was started on antithyroid drug (tablet carbimazole 30 mg/day) which was increased to 40 mg/day. Total thyroidectomy is planned after achieving the euthyroid status. Figure 1g–i shows sections in a 38-year-old woman with severe GO initially treated with oral glucocorticoids. Orbital sections show bulky superior rectus muscle (h and i, white arrow) with SSTR expression. Neck sections showed enlarged both lobes of thyroid showing increased tracer uptake with the presence of pyramidal lobe. Her thyroid profile suggested subclinical hyperthyroid profile, total T4–5.64 μg/dl (5.1–14.1 μg/dl), total T3–151 ng/dl (80–200 ng/dl), and TSH 0.028 μIU/ml. For thyroid dysfunction, she was started on antithyroid drug (tablet carbimazole 20 mg/day).

Figure 1

68Ga-DOTANOC positron emission tomography/computed tomography (control, patient 1, and patient 2). (a-c) Control (pheochromocytoma) showing normal extraocular muscles with no abnormal uptake (c, white arrow). (d-f) A 65-year-old woman with severe Graves' ophthalmopathy showing bulky extraocular muscles with somatostatin receptor expression. Neck shows enlarged thyroid with increased tracer uptake and retrosternal extension forming a globular mass (red arrow). (g-i) A 38-year-old woman with severe Graves' ophthalmopathy showing bulky extraocular muscles (white arrow) with somatostatin receptor expression. Neck sections showing enlarged both lobes of thyroid with pyramidal lobe

GO is an extrathyroidal manifestation of Graves' disease.[12] It involves autoimmune activation of fibroblasts, through different autoantigens, commonly involving thyrotropin receptor.[3] Lymphocytes also play a crucial role. Cluster differentiation (CD4+) T-lymphocytes cause activation of fibroblasts by forming CD40–CD154 bridges.[4] Other mononuclear cells including CD8+ T-cells, B-cells, and plasma cell are also involved, resulting in chronic inflammation in orbital tissue.[5] All these factors cause hyperplasia of adipose tissue, accumulation of glycosaminoglycans resulting in expansion of EOMs, and periorbital soft tissue.[6] In a study by García-Rojas et al., they demonstrated, sensitivity of 18F-fluorodeoxyglucose (18F-FDG) PET/CT in detecting inflammation in GO is superior to other anatomical imaging methods.[7] However, one limitation of 18F-FDG PET/CT is the presence of physiological muscle uptake which can create difficulties in interpretation.[8] The molecular basis of using SSTR imaging in assessing GO is the expression of SSTRs in the cells associated with chronic inflammation in active GO.[9] Few previous studies have demonstrated SSTR expression in periorbital tissue using 111In-pentetreotide scan (Octreoscan) and have also shown that intensity of uptake correlates with clinical stage of GO.[1011] SSTR expression in active GO has also been demonstrated using 68Ga-DOTANOC PET/CT.[12] This also forms the basis for using long-acting somatostatin analogs as a treatment option for refractory GO patients because these peptides inhibit lymphocyte activation, proliferation, and cytokine production.[13] 68Ga-DOTANOC PET/CT shows no physiological orbital muscle uptake as shown in the control patient Figure 1a–c. It can also possibly provide information that can be used in response assessment of patients treated with standard therapies and screening patients who fail to respond to conventional treatment, for newer therapies such as long-acting somatostatin analogs.

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Conflicts of interest

There are no conflicts of interest.