Durvalumab-induced thyroiditis in a patient with non-small cell lung carcinoma: a case report and review of pathogenic mechanisms.

BACKGROUND: Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) have become the current standard-of-care for advanced cancers. This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE), including endocrinopathy. CASE PRESENTATION: A 63-year-old woman was diagnosed with a non-small cell lung carcinoma of the right superior lobe, cT3N2M0. She developed thyrotoxicosis followed by hypothyroidism induced by consolidation immunotherapy with durvalumab (anti-PD-L1). Analysis of the human leukocyte antigen (HLA) region showed HLA-DR4 (susceptible) and DR13 (protective). The possible mechanisms are subsequently discussed in detail. CONCLUSIONS: The case of a patient with thyroiditis associated with the PD-L1 inhibitor durvalumab is described, highlighting the need for proactive monitoring of thyroid hormone levels. Identifying biomarkers associated with an increased risk of ICI-induced side effects (such as HLA) is of interest for better patient selection, optimal management and improved understanding of the mechanisms involved.

A rare cause of persistent hyperparathyroidism.

In a case of patient with persistent hypercalcemia after parathyroidectomy, different imaging techniques and particularly 18F-fluorocholine PET/CT are important to localize the adenoma even in a very unusual location.

Multiple Endocrine Neoplasia or Accidental Association?

Pheochromocytoma, papillary thyroid carcinoma and hyperparathyroidism have rarely been reported together. Whether this association is coincidental or results from an unknown genetic predisposition is difficult to ascertain. We present the case of a patient who was diagnosed with pheochromocytoma, bilateral papillary thyroid carcinoma and parathyroid hyperplasia with primary hyperparathyroidism. A genetic mutation was hypothesized as the connection between these lesions. Previously described mutations were explored. LEARNING POINTS: Parathyroid hyperplasia, primary hyperparathyroidism and papillary thyroid carcinoma individually are common conditions, but association with each other, although possibly incidental, should trigger genetic testing.Further research is needed to reliably explain the relationship between primary hyperparathyroidism and non-medullary thyroid cancer.

Can we safely reduce the administration of 131-iodine in patients with differentiated thyroid cancer? - experience of the Brugmann hospital in Brussels.

BACKGROUND: 131-iodine (131I) administration after surgery remains a standard practice in differentiated thyroid cancer (DTC). In 2014, the American Thyroid Association presented new guidelines for the staging and management of DTC, including no systematic 131I in patients at low-risk of recurrence and a reduced 131I activity in intermediate risk.The present study aims at evaluating the rate of response to treatment following this new therapeutic management compared to our previous treatment strategy in patients with DTC of different risks of recurrence. METHODS: Patients treated and followed up for DTC according to the 2014-ATA guidelines (Group 2) were compared to those treated between 2007 and 2014 (Group 1) in terms of general characteristics, risk of recurrence (based on the 2015-ATA recommendations), preparation to 131I administration, cumulative administered 131I activity and response to treatment. RESULTS: In total, 136 patients were included: 78 in Group 1 and 58 in Group 2. The two groups were not statistically different in terms of clinical characteristics nor risk stratification: 42.3% in Group 1 and 31% in Group 2 were classified as low risk, 38.5 and 48.3% as intermediate risk and 19.2 and 20.7% as high risk (P = 0.38). Two patients (one in each group) with distant metastases were excluded from the analysis.Preparation to 131I administration consisted in rhTSH stimulation in 23.4% of the patients in Group 1 and 100% in Group 2 (p < 0.001).131I was administered to 46/77 patients (59.7%) in Group 1 (5 at low risk of recurrence) and 38/57 patients (66.7%) in Group 2 (0 with a low risk). Among the patients treated by 131I, median cumulative activity was significantly higher in Group 1 (3.70GBq [100 mCi] range 1.11-11.1 GBq [30-300 mCi]) than in Group 2 (1.11 GBq [30 mCi], range 1.11-7.4 GBq [30-200 mCi], P < 0.001). Complete response was found in 90.9% in Group 1 vs. 96.5% in Group 2 (P = 0.20). CONCLUSIONS: Using the 2015-ATA evidence-based guidelines for the management of DTC, meaning no 131I administration in low-risk patients, a low activity in intermediate and even high risk patients, and a systematic use of rhTSH stimulation before 131I therapy allowed us to reduce significantly the median administered 131I activity, with a similar rate of complete therapeutic response.

Hypophosphatemia related to paraneoplastic Cushing syndrome in prostate cancer: cure after bilateral adrenalectomy.

We report the case of a 71-year-old man with progressive metastatic prostate cancer in whom simultaneous occurrence of paraneoplastic Cushing syndrome (CS) and tumor-induced osteomalacia (TIO) initially was suspected. However, the evolution of biochemical markers of phosphate metabolism during disease course and after bilateral adrenalectomy argued against the diagnosis of TIO. Despite the persistence of progressive prostate cancer, CS and hypophosphatemia resolved in parallel after bilateral adrenalectomy. Thus, these data suggest that paraneoplastic CS per se was involved in the pathogenesis of hypophosphatemia. Calcitriol and intact fibroblast growth factor 23 (FGF23) levels were within the reference range at onset, which is inappropriate in the setting of severe hypophosphatemia. All parameters of phosphate metabolism normalized after resolution of hypercortisolism. Based on the known suppressive effect of glucocorticoids (GCs) on bone remodeling and the inverse relationship between bone turnover rate and circulating FGF23 levels, we postulate that GCs interfere indirectly with phosphate homeostasis by inducing inappropriate FGF23 production and release. This mechanism could further aggravate the hypophosphatemia resulting from GC-induced inhibition of intestinal phosphate absorption. Studies directed at the identification of the molecular pathways in bone mediating the interference of GCs with phosphate metabolism are warranted.

Anti DNA antibodies are not restricted to a specific pattern of fluorescence on HEp2 cells.

BACKGROUND: Antinuclear autoantibody determination relies on an initial screening step using immunofluorescence on HEp2 cells. This may be followed by anti-deoxyribonucleic acid (DNA) determination, if the fluorescence of nuclei is homogeneous. We assessed the validity of a restricted algorithm and compared this to a more comprehensive algorithm that accepted any nuclear pattern as a positive indicator. METHODS: Our retrospective study analyzed routine results for antinuclear antibodies (ANA) and their anti-DNA identification [double stranded nuclear DNA (ds-DNA), membrane associated DNA (mDNA), nucleosomes] for 58 systemic lupus erythematosus (SLE) patients (690 sera). We included 158 patients with systemic or organ-specific autoimmune diseases (888 sera), 44 with viral disease (88 sera), 34 cancer patients (89 sera) and 111 patients with inflammation that served as controls (122 sera) for a total of 1187 samples. RESULTS: 1) Anti DNA antibodies are not associated only with a homogeneous pattern, but can also be seen with a speckled or nucleolar pattern. 2) The observed pattern is typical for a particular patient rather than for a specific pathology. 3) A homogeneous pattern does not necessarily indicate SLE, nor does the presence of circulating anti DNA antibodies. 4) Determination of various specificities of anti DNA antibodies, whatever the immunofluorescent pattern, increases the sensitivity and specificity for SLE. CONCLUSIONS: If diagnosis is based exclusively on a homogenous pattern, preselection would have missed identification of SLE as high levels of anti DNA antibodies were also associated with speckled or nucleolar pattern.