Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production.

CONTEXT: The molecular basis for anatomically dispersed clinical manifestations in Graves' disease (GD) eludes our understanding. Bone marrow-derived, pluripotent fibrocytes represent a subset of peripheral blood mononuclear cells and infiltrate the orbital and thyroid tissues in GD. These cells may be involved in the pathogenesis of thyroid-associated ophthalmopathy (TAO). OBJECTIVE: The objective of the study was to quantify fibrocyte display of functional cell surface TSH receptor (TSHR), identify the profile of chemokines they express after TSHR activation, and determine whether circulating TSHR(+) peripheral blood fibrocytes are more frequent in situ in patients with TAO. DESIGN/SETTING/PARTICIPANTS: Using a newly developed technique, fibrocytes were directly identified in peripheral blood from 31 patients with TAO and 19 healthy subjects receiving care at a multidisciplinary academic center. MAIN OUTCOME MEASURES: The frequency in situ of fibrocytes (collagen 1(+), CD45(+), CD34(+), CD14(+), CD86(+) peripheral blood mononuclear cells) was assessed by multiparameter flow cytometry and correlated to clinical disease activity and smoking status. Levels of TSHR-displaying fibrocytes and their response to TSH and TSHR-activating antibody, M22, were measured by flow cytometry, Luminex, and real-time PCR. RESULTS: The levels of TSHR expression by fibrocytes are substantially higher than those found in orbital fibroblasts. Moreover, the frequency of TSHR(+) fibrocytes in patients with TAO was greater than that in healthy subjects in situ. Their abundance is not influenced by disease activity or smoking history. These cells produce high levels of several cytokines and chemokines including IL-8, regulated upon activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 when treated with TSH or M22. TSH induces IL-8 production at the pretranslational level. This induced cytokine can be detected in intact fibrocytes ex vivo. CONCLUSIONS: Frequency of circulating TSHR(+) fibrocytes is markedly increased in patients with TAO, and they express proinflammatory chemokines in response to TSH. Because they infiltrate both orbit and thyroid in GD, they may represent the link between systemic immunoreactivity and organ-specific autoimmunity.

Diagnostic ability of Barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography.

OBJECTIVES: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index), calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. METHODS: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. RESULTS: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy) met the inclusion criteria for the study. The mean Barrett's index values (+/- SD) were 64.47% +/- 6.06% and 49.44% +/- 10.94%in the groups with and without dysthyroid optic neuropathy, respectively (p<0.001). Barrett's index sensitivity ranged from 32% to 100%, and Barrett's index specificity ranged from 24% to 100%. The best combination of sensitivity and specificity was 79%/72% for BI=60% (odds ratio: 9.2). CONCLUSIONS: Barrett's Index is a useful indicator of dysthyroid optic neuropathy and may contribute to early diagnosis and treatment. Patients with a Barrett's index >60% should be carefully examined and followed for the development of dysthyroid optic neuropathy.

Diagnostic ability of barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography

OBJECTIVES: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index), calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. METHODS: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. RESULTS: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy) met the inclusion criteria for the study. The mean Barrett's index values (± SD) were 64.47 percent ± 6.06 percent and 49.44 percent ± 10.94 percentin the groups with and without dysthyroid optic neuropathy, respectively (p<0.001). Barrett's index sensitivity ranged from 32 percent to 100 percent, and Barrett's index specificity ranged from 24 percent to 100 percent. The best combination of sensitivity and specificity was 79 percent/72 percent for BI=60 percent (odds ratio: 9.2). CONCLUSIONS: Barrett's Index is a useful indicator of dysthyroid optic neuropathy and may contribute to early diagnosis and treatment. Patients with a Barrett's index >60 percent should be carefully examined and followed for the development of dysthyroid optic neuropathy.

Bilateral progressive enophthalmos as the presenting sign of metastatic breast carcinoma.

A 51-year-old woman, without systemic symptoms, complained of slowly progressive receding eyes. She had severe bilateral enophthalmos and markedly restricted extraocular movements in all fields of gaze. Computed tomography showed an infiltrative homogenous mass filling both orbits. Gynecologic and systemic investigation revealed bilateral lobular breast carcinoma, without metastasis to other organs. She was started on chemotherapy and 2 years after the diagnosis remains in good general health, despite persistence of severe enophthalmos. This case serves to emphasize that bilateral progressive enophthalmos may be the presenting sign of metastatic breast carcinoma even when local symptoms in the breast are absent. Clinicians should be aware of this sign to establish an early diagnosis and treatment.