scholarly journals A Case of Rare Autoimmune Pancytopenia Due to Graves’ Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A908-A909
Author(s):  
Ally Wen Wang ◽  
Geeti Mahajan ◽  
Aaron Etra ◽  
Shira R Saul

Abstract Introduction: Graves’ disease has been associated with cytopenias, most commonly anemia. Pancytopenia is a rare complication and is not often encountered. Case Presentation: A 54-year-old woman with history of multiple sclerosis on alemtuzumab was referred for abnormal thyroid function tests. At the initial visit, the patient reported a 20-pound unintentional weight loss, tremors, sweating and heat intolerance. She was 3 years post-menopausal and had no history of recent viral illness, contrast exposure or family history of thyroid disease. Physical exam revealed an anxious appearing woman with fine tremors in both hands, hyperreflexia but no lid lag or exophthalmos. Labs included TSH <0.005 uIU/mL (0.400-4.2), free T4 2.89 ng/dL (0.80-1.50), TSH receptor binding antibody 8.24 IU/L (< 2.00), TSI 7.27 IU/L (<0.56), WBC 2900/uL (4500-11000), ANC 1746/uL (1900 - 8000), hemoglobin 11.4 g/dL (11.7-15.0) and platelet 207,000/uL (150,000-450,000). Thyroid ultrasound noted sub-centimeter hypoechoic/cystic nodules and 24-hour thyroid uptake showed 56.4% symmetric uptake (upper limit of normal 30%). Due to leukopenia, the patient was started on propranolol and underwent radioiodine ablation with 14.8 mCI. Two weeks later, she reported easily bruising and gum bleeding and her blood work was significant for pancytopenia. The patient was referred to hematology and two bone marrow samples were obtained. Though MDS/MPN was initially suspected based on atypia in both specimens, there were no immunophenotypic, cytogenetic or molecular abnormalities suggesting a neoplastic process. Instead the patient was thought to have autoimmune pancytopenia secondary to Graves’ and the atypia was believed to be secondary to peripheral consumption. She was started on prednisone 1 mg/kg/day with resolution of her cytopenias. Discussion: Graves’ disease has been associated with hematological abnormalities including isolated anemia (the most common), thrombocytopenia or leukopenia. Pancytopenia is an uncommon complication and is rarely described in the literature. The exact mechanism remains unclear, but may be related to either reduced production of hematopoietic cells from the bone marrow or increased destruction of mature hematopoietic cells due to autoantibodies. Since thyroid hormones are known to increase erythropoietin, this leads to an exaggerated consumption of iron, folic acid and vitamin B12 and can cause various forms of anemias. Leukopenia may be secondary to immunologic destruction whereas thrombocytopenia may be due to antiplatelet antibodies or increased splenic sequestration. Pancytopenia is rare. Our patient was treated with high dose prednisone with resolution of her pancytopenia, which suggests an autoimmune process as the mechanism. Our case showcases a rare complication of Graves’ disease and highlights that high dose steroid therapy may improve cytopenias associated with this condition.

1992 ◽  
Vol 3 (suppl b) ◽  
pp. 123-127 ◽  
Author(s):  
Hans-Georg Klingemann ◽  
Heather Deal ◽  
Dianne Reid ◽  
Connie J Eaves

Despite the use of high dose chemoradiotherapy for the treatment of acute leukemia. relapse continues to be a major cause of death in patients given an autologous bone marrow transplant. Further augmentation of pretransplant chemotherapy causes life threatening toxicity to nonhematopoietic tissues and the effectiveness of currently available ex vivo purging methods in reducing the relapse rate is unclear. Recently, data from experimental models have suggested that bone marrow-derived lymphokine (IL-2)-activated killer (BM-LAK) cells might be used to eliminate residual leukemic cells both in vivo and in vitro. To evaluate this possibility clinically, a procedure was developed for culturing whole marrow harvests with IL-2 prior to use as autografts, and a number of variables examined that might affect either the generation of BM-LAK cells or the recovery of the primitive hematopoietic cells. The use of Dexter long term culture (LTC) conditions, which expose the cells to horse serum and hydrocortisone. supported LAK cell generation as effectively as fetal calf serum (FCS) -containing medium in seven-day cultures. Maintenance of BM-LAK cell activity after a further seven days of culture in the presence of IL-2 was also tested. As in the clinical setting. patients would receive IL-2 in vivo for an additional week immediately following infusion of the cultured marrow autograft. Generation ofBM-LAK activity was dependent on the presence of IL-2 and could be sustained by further incubation in medium containing IL-2. Primitive hematopoietic cells were quantitated by measuring the number of in vitro colony-forming progenitors produced after five weeks in secondary Dexter-type LTC. Maintenance of these 'LTC-initiating cells' was unaffected by lL-2 in the culture medium. These results suggest that LAK cells can be generated efficien tly in seven-day marrow autograft cultures containing IL-2 under conditions that allow the most primitive human hematopoietic cells currently detectable to be maintained.


2001 ◽  
Vol 125 (6) ◽  
pp. 803-807
Author(s):  
S. David Hudnall ◽  
Jack B. Alperin ◽  
John R. Petersen

Abstract The association of Hodgkin disease with monoclonal gammopathy has rarely been reported. We present a case of a 48-year-old woman with a history of autoimmune hemolytic anemia and Graves disease who presented with hepatosplenomegaly and a γ-heavy-chain paraprotein. Histopathology of lymph node and bone marrow revealed nodular lymphocyte-predominance Hodgkin disease, while examination of the spleen revealed plasmacytosis consistent with γ-heavy-chain disease. Following splenectomy, the patient has remained in complete remission for both conditions with no further treatment. To our knowledge, this is the first report of a patient with both γ-heavy-chain disease and nodular lymphocyte-predominance Hodgkin disease. Given recent data indicating the B-cell nature of this form of Hodgkin disease, the authors propose that in this unique case there may be a clonal relationship between these 2 concurrent B-cell lymphoproliferative processes.


2020 ◽  
Vol 13 (3) ◽  
pp. e231337
Author(s):  
Michael S Lundin ◽  
Ahmad Alratroot ◽  
Fawzi Abu Rous ◽  
Saleh Aldasouqi

A 69-year-old woman with a remote history of Graves’ disease treated with radioactive iodine ablation, who was maintained on a stable dose of levothyroxine for 15 years, presented with abnormal and fluctuating thyroid function tests which were confusing. After extensive evaluation, no diagnosis could be made, and it became difficult to optimise the levothyroxine dose, until we became aware of the recently recognised biotin-induced lab interference. It was then noticed that her medication list included biotin 10 mg two times per day. After holding the biotin and repeating the thyroid function tests, the labs made more sense, and the patient was easily made euthyroid with appropriate dose adjustment. We also investigated our own laboratory, and identified the thyroid labs that are performed with biotin-containing assays and developed strategies to increase the awareness about this lab artefact in our clinics.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4940-4940
Author(s):  
Richard McMasters ◽  
Brian K. Turpin ◽  
Michael J. Absalon ◽  
Christine L. Phillips ◽  
Karen Burns ◽  
...  

Abstract Introduction The development of histiocytic lesions after acute lymphoblastic leukemia (ALL) is rare, occurring in 6 of 971 patients enrolled on BFM treatment regimens for T-ALL (Trebo 2005).  Few cases of histiocytosis arising after a history of T-ALL have been characterized at the molecular level for genomic alterations. One case of fatal Langerhans cell histiocytosis (LCH) following treatment of T-ALL revealed activating mutations in NOTCH1; in contrast, no NOTCH1 mutations were identified in 24 other cases of LCH or Rosai-Dorfman disease without a previous history of T-ALL (Rodig 2008). In patients without prior leukemia, BRAF V600 mutations have been identified in a significant proportion of patients with LCH or Erdheim-Chester Disease but not in other histiocytoses (Haroche 2012). Methodology and Principal Findings Next generation focused exomic sequencing of 236 genes and 47 Introns was conducted on samples of histiocytic lesions from two patients with a previous history of T-ALL. Case 1 A 2 year-old male presented with marked adenopathy, mediastinal mass and white blood cell count 67,000 cells/uL with 30% blasts. The blasts expressed CD45, CD2, CD3 (surface/cyto), CD5, CD7, CD38, CD45 (bright), TCR gamma-delta, but were negative for CD4, CD8, and TdT.  Karyotype was 46,XY,t(8;14)(q24;q11.2),der(12)t(12;20)(q11;q13.3),der(20)t(12;20)(q21;q13.3) with rearrangement of MYC (8q24) confirmed by FISH. He was treated for T-ALL per Children’s Oncology Group (COG) protocol AALL0434 and had 5% residual bone marrow blasts at day 29 of induction. MRD-negative remission was ultimately achieved with high-dose cytarabine and methotrexate followed by consolidation with nelarabine.  He underwent matched unrelated cord blood transplant following conditioning with cyclophosphamide and total body irradiation with cranial boost, and engrafted at day +14. Surveillance bone marrow at day +110 revealed systemic juvenile xanthogranuloma (JXG) without T-ALL. PET/CT revealed FDG-uptake in the diffusely enlarged spleen and throughout the skeleton. Due to progressive cytopenias, therapy was initiated with vinblastine and prednisone as per LCHIII. However, refractory cytopenias exacerbated by splenic sequestration developed following induction, and he was then treated with thalidomide and splenectomy. The spleen weighed 404 grams (expected 40 grams) and was diffusely infiltrated with JXG. The cytopenias dramatically improved and he continued thalidomide for 2 months until PET scan demonstrated progression. Genomic analysis of the JXG lesion revealed NRAS G13D mutation, and FISH demonstrated MYC rearrangement identical to the initial T-ALL sample. Case 2 A 12-year-old male presented with WBC 142,700 cells/uL and CNS leukemia. Flow cytometry showed T-ALL with CD2, surface CD3, CD4, CD5, CD7, CD8, CD24 (subset), CD71, HLA-DR (subset) and TdT (partial). There was a clonal TCR gamma gene rearrangement and a biallelic CDKN2A (p16) deletion by FISH. He was enrolled on COG AALL0434 and had a rapid response with remission in both CNS and marrow at induction day 29.  Following completion of high-dose methotrexate interim maintenance he developed hepatosplenomegaly, pancytopenia and elevated serum bilirubin, ferritin, and triglycerides.  Bone marrow aspirate showed rare hemophagocytosis but no evidence of T-ALL.  He was treated with dexamethasone and etoposide with no response. Follow-up bone marrow revealed brisk hemophagocytosis and a diffuse histiocytic neoplasm. Karyotype was 48,XY,+7,+11[2] /49,idem,+18[3] /46,XY[14]. PET/CT showed hepatosplenomegaly with FDG uptake in anterior mediastinum, hepatic nodules, spleen, and bone marrow. He was treated with Campath and then with intensive chemotherapy with fludarabine, cytarabine, and liposomal daunorubicin with no response and ultimately succumbed to disease. Genomic analysis of the clonal histiocytic infiltrate revealed KRAS G12C, BRAF G469V, NOTCH1 Q2440, and CCND2 G268R mutations, and FISH positive for biallelic CDKN2A (p16) deletion similar to original T-ALL. Conclusions Our extensive genomic characterization suggests a unique molecular pathogenesis for histiocytic disorders arising after T-cell ALL and identified RAS signaling pathway and NOTCH1 mutations. Furthermore, these findings strongly indicate a potential derivation or trans differentiation from the malignant leukemic stem cell clone. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4707-4714 ◽  
Author(s):  
Lijian Shao ◽  
Yan Sun ◽  
Zhonghui Zhang ◽  
Wei Feng ◽  
Yongxing Gao ◽  
...  

Abstract Bone marrow injury is a major adverse side effect of radiation and chemotherapy. Attempts to limit such damage are warranted, but their success requires a better understanding of how radiation and anticancer drugs harm the bone marrow. Here, we report one pivotal role of the BH3-only protein Puma in the radiosensitivity of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Puma deficiency in mice confers resistance to high-dose radiation in a hematopoietic cell–autonomous manner. Unexpectedly, loss of one Puma allele is sufficient to confer mice radioresistance. Interestingly, null mutation in Puma protects both primitive and differentiated hematopoietic cells from damage caused by low-dose radiation but selectively protects HSCs and HPCs against high-dose radiation, thereby accelerating hematopoietic regeneration. Consistent with these findings, Puma is required for radiation-induced apoptosis in HSCs and HPCs, and Puma is selectively induced by irradiation in primitive hematopoietic cells, and this induction is impaired in Puma-heterozygous cells. Together, our data indicate that selective targeting of p53 downstream apoptotic targets may represent a novel strategy to protecting HSCs and HPCs in patients undergoing intensive cancer radiotherapy and chemotherapy.


2008 ◽  
Vol 1 ◽  
pp. CMENT.S746 ◽  
Author(s):  
NA Khan ◽  
G Watson ◽  
E Sivayoham ◽  
DJ Willatt

We present a case of 82 years old female with two-week history of neck swelling, odynophagia, hoarseness and cough. There was a tender, fluctuant swelling below the mandible on right side. An urgent C.T scan showed it to be a pyolaryngocele. High dose intra venous antibiotic, analgesia and nasogastric feeding resolved the acute infective episode. The residual laryngocele was treated by an excision via an external approach. A pyolaryngocele is a rare complication of laryngocele that becomes secondarily infected. It can cause feeding and respiratory compromise because of its compression symptoms. A CT is helpful for prompt diagnosis and for planning definitive surgical management. The aim of this paper is to highlight the need to recognise and then treat these cases aggressively. The best treatment option is to remove the laryngocele in-toto to prevent recurrence.


2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Sarah A. Morrow ◽  
Robina Rana ◽  
Donald Lee ◽  
Terri Paul ◽  
Jeffrey L. Mahon

Increased blood pressure is a known adverse effect associated with corticosteroids but little is published regarding the risk with the high doses used in multiple sclerosis (MS). A 53-year-old female with known relapsing remitting MS presented with a new brainstem relapse. Standard of care treatment for an acute MS relapse, 1250 mg of oral prednisone for 5 days, was initiated. She developed an occipital headache and dizziness and felt generally unwell. These symptoms persisted after treatment was complete. On presentation to medical attention, her blood pressure was 199/110 mmHg, although she had no history of hypertension. MRI changes were consistent with posterior reversible encephalopathy syndrome (PRES), demonstrating abnormal T2 signal in both thalami, the posterior occipital and posterior parietal white matter with mild sulcal effacement. As her pressure normalized with medication, her symptoms resolved and the MRI changes improved. No secondary cause of hypertension was found. This is the first reported case of PRES secondary to high dose corticosteroid use for an MS relapse without a history of hypertension and with no other secondary cause of hypertension identified. This rare complication should be considered in MS patients presenting with a headache or other neurological symptoms during treatment for a relapse.


2018 ◽  
Vol 11 ◽  
pp. 117954761878109 ◽  
Author(s):  
Laurence Pincet ◽  
François Gorostidi

Background: Graves disease or other causes of thyrotoxicosis are frequently associated with cytopenia. Although anemia is the most common, other cell lineage can be affected. Pancytopenia is a rare complication of thyrotoxicosis. Case presentation: We report a case of a 33-year-old Chinese man who presented a nonsevere pancytopenia in the context of a newly diagnosed Graves disease. Restauration of euthyroid state led to progressive correction of pancytopenia. Conclusions: Literature review shows other rare cases of pancytopenia. It is usually nonsevere with just extremely rare cases of transfusion reported. Evolution was always favorable after achievement of euthyroid state. Its mechanism remains poorly understood, especially because those patients have no vitamin or iron deficiency. The exact physiopathological process remains unclear but 2 causes seem to overlap: reduced production of hematopoietic cells from the bone marrow and increased destruction or sequestration of mature hematopoietic cells. Despite unclear mechanism, the presence of hematologic abnormalities including pancytopenia must not be considered as a contraindication to antithyroid drug therapy.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A954-A955
Author(s):  
Arwa Albashaireh ◽  
Spyridoula Maraka

Abstract Introduction: Subclinical hypothyroidism (SCH) is diagnosed based on elevated thyrotropin (TSH) and normal thyroxine (FT4) levels. Previous guidelines recommended treatment of SCH with levothyroxine (LT4) when TSH is > 10 uIU/mL or if TSH <10 uIU/mL with symptoms suggestive of hypothyroidism, positive thyroperoxidase antibodies (TPO Ab) or evidence/risk factors of cardiovascular disease. There has been an increasing practice of LT4 prescription for SCH, which contributes to making LT4 the second most prescribed drug in the US. Case: This case reviews the course of a patient with SCH treated with LT4. A 68 year old woman with medical history of hyperlipidemia, osteoporosis, and non-toxic multinodular goiter was diagnosed with SCH due to Hashimoto’s thyroiditis based on TSH 9.59 uIU/mL (0.34 - 5.60), FT4 0.66 ng/dL (0.58 - 1.64), and +TPO Ab. The patient had similar thyroid function tests (TFT) 1 year ago. She reported symptoms of hair loss, dry skin, and fatigue. She decided to undergo a trial of LT4 50 mcg daily. Two months later, her TSH had normalized and she reported slight improvement of fatigue. After one year on LT4, the patient reported symptoms of anxiety and heat intolerance and decided to stop LT4. Laboratory work up revealed TSH 0.22 uIU/mL and FT4 1.03 ng/dL consistent with exogenous hyperthyroidism. At the time of her follow up, the patient had been off LT4 for about 3 weeks. She continued to have ongoing fatigue, but reported resolution of the hyperthyroid symptoms. She was advised to stay off LT4 and to have yearly TFT. Discussion This case illustrates that not only LT4 treatment for SCH did not result in apparent improvement of hypothyroid-related symptoms, but also caused iatrogenic hyperthyroidism. A recent meta-analysis of 21 randomized clinical trials including 2192 patients with SCH found that LT4 therapy is not significantly associated with improvement in general quality of life or thyroid-related symptoms. Additionally, there is evidence of potential harm associated with LT4 and added burden of lifelong management. In 2019, a new guideline panel issued a strong recommendation against thyroid hormones in adults with SCH. Patients who are already on LT4 therapy for SCH may benefit from LT4 deprescribing. Clinicians need to discuss with their patients if LT4 discontinuation is a reasonable consideration. Studies at low risk of bias assessing patient important outcomes after LT4 discontinuation are required imminently.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A945-A945
Author(s):  
Purnima Kabir ◽  
Chantal Lewis ◽  
Joshua Hendrix

Abstract Background: Graves’ Orbitopathy, also known as Thyroid Eye Disease (TED) is a severe ocular manifestation of Graves’ Disease. It manifests as an autoantibody mediated reaction to the thyroid hormone stimulating receptor (TSH-R), these receptors are closely linked with the insulin-like growth factor-1 receptors (IGF-1R). The TSH-R antibodies play a major role in the pathogenesis of TED. The activation of the TSH-R and IGF-1R on orbital fibroblasts and adipocytes lead to IGF-1 expression. This initiates inflammation, fibroblast proliferation and accumulation of glycosaminoglycans in the orbital tissue. Treatment modalities include glucocorticoids, orbital radiation and orbital decompressions. Recent understanding of the molecular basis of TED has resulted in targeted therapy with Teprotumumab, an inhibitory monoclonal antibody against IGF-1R. There is limited literature on the outcomes of Teprotumumab use after orbital decompression surgery. Clinical Case: 43-year-old female presented with symptoms of diplopia, periorbital pain, dry eyes and tremor. Ocular exam: Vision was correctable to 20/20 in each eye, restricted motility, bilateral lid edema, lid retraction with superior scleral show and conjunctival injection. Clinical Activity Score > 4. Diagnostic tests: TSH 0.00 undetectable (N:0.5-5.0mIU/L) FT4 3.19 (N:0.7-1.9ng/dL) TSI thyroid stimulating immunoglobulin 490% of baseline (N: 130% of baseline). Diagnosis of Graves’ disease with associated orbitopathy was made. In addition to medical management for Graves’ thyroid disease she was referred to ophthalmology. She was treated with high dose steroids for 4 weeks with no resolution of symptoms. She was then referred to an oculoplastic surgeon for bilateral orbital decompressions which resulted in mild improvement in diplopia but a residual proptosis. The decision was made to treat with teprotumumab, which had recently been FDA approved. Patient reported improved symptoms without complicating enophthalmos. Review confirmed improved proptosis on Hertel Exophthalmometry. The right eye improved from 22 mm to 16 mm and the left eye from 21 mm to 17 mm (N <20.1 mm Caucasian females) with preserved visual acuity, improved lid retraction, resolved conjunctival chemosis and decreased periorbital pain after 6 doses of Teprotumumab therapy. Conclusion: Graves’ orbitopathy can result in debilitating symptoms affecting quality of life. Targeted molecular therapy such as teprotumumab is an effective treatment even after orbital decompression. Reference: Ting, M., Ezra, D.G. Teprotumumab: a disease modifying treatment for graves’ orbitopathy. Thyroid Res13, 12 (2020). https://doi.org/10.1186/s13044-020-00086-7


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