Review

Authors: V D Palumbo, V D Palumbo, G Damiano...

Tertiary hyperparathyroidism (HPT III) occurs when an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary hyperparathyroidism. Some authorities reserve the term for secondary hyperparathyroidism that persists after successful renal transplantation. Long-standing chronic kidney disease (CKD) is associated with several metabolic disturbances that lead to increased secretion of PTH, including hyperphosphatemia, calcit-riol deficiency, and hypocalcaemia. Hyperphosphatemia has a direct stimulatory effect on the parathyroid gland cell resulting in nodular hyperplasia and increased PTH secretion. Prolonged hypocalcaemia also causes parathyroid chief cell hyperplasia and excess PTH. Af-ter correction of the primary disorder CKD by renal transplant, the hypertrophied parathyroid tissue fails to resolute, enlarge over and continues to oversecrete PTH, despite serum calcium levels that are within the reference range or even elevated. They also may become resistant to calcimimetic treatment. The main indication for treatment is persistent hypercalcemia and/or an increased PTH, and the primary treatment is surgery. Three procedures are commonly performed: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy. It is important to remove superior parts of thymus as well. The most appropriate surgical procedure, whether it be total, subtotal, or anything less than subtotal including "limited" or "focused" parathyroidectomies, continues to be unclear and controversial. Surgical complications are rare, and para-thyroidectomy appears to be a safe and feasible treatment option for HPT III.

Topics: Humans; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hyperplasia; Hypocalcemia; Kidney Transplantation; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Renal Insufficiency, Chronic; Transplantation, Autologous

PubMed: 33956045
DOI: 10.7417/CT.2021.2322

Review

Authors: Aneesh K Mishra, Anuj Varma

Myasthenia gravis (MG), a rare disease, is the most common neuromuscular junction problem. It's the quintessential autoimmune disease with ocular, bulbar, respiratory, axial, and limb muscles exhibiting a typical fatigable weakening due to the development of antibodies against the acetylcholine receptor (AChR). Infections, stress, surgeries, thymus gland anomalies, and pharmaceutical side effects can also cause it. Ocular symptoms are initially experienced by most of the sufferers. The majority of the sufferers will go through at least one episode of symptom exacerbation during their illness. The immune system in MG interferes with nerve-muscle communication, causing muscles to become weak and tired quickly. The actual cause is not yet known, but a problem in the thymus gland may be the cause. In a person suffering from this disease, the size of the thymus becomes larger than normal, which is also called thymic hyperplasia. It is more common for women to have early-onset MG (EOMG) than for males to have late-onset MG (LOMG). Merely clinical evidence, encompassing the patients' medical history and physical indications of fluctuating muscle weakness in a specific region, is utilized to diagnose MG. Complementary diagnostic procedures and lab techniques aid in confirming the synaptic dysfunction and characterizing its kind and degree. Early diagnosis and the availability of effective treatments have reduced the burden of severe impairment and high mortality previously associated with MG. Current immunomodulation-based therapies come with side effects brought on by persistent immune suppression. Improved knowledge of this relatively uncommon but curable condition is required among primary carers. The objective of this review is to provide information about MG and to help people recognize its symptoms and start treatment without panic so that the progression of this disease can be stopped and complications can be avoided.

PubMed: 38186498
DOI: 10.7759/cureus.50017

Review

Authors: Momal Tara Chand, Jacob Edens, Tayson Taixin Lin...

Thymomas are a heterogeneous group of tumors arising from the epithelium of the thymus. They are categorized by the proportion of neoplastic epithelia to lymphocytes and by the degree of cytologic atypia. Thymomas constitute 0.2-1.5% of all malignancies and nearly all occur in patients over 20 years. We reviewed the available literature and found less than 50 cases of thymoma reported in children (<18 years of age), the youngest being 4 years old, and no cases in newborns. They represent less than 1% of all mediastinal tumors in children. Due to the limited number of cases in the pediatric population, the diagnosis and treatment in this population is extremely challenging. Thymomas in all age groups may be associated with paraneoplastic syndromes, being myasthenia gravis the most common, which is associated with a worse prognosis in the pediatric population. We present the first case of a newborn infant with congenital thymoma. This case demonstrates a rare tumor in an unusual age group and emphasizes the importance of multidisciplinary teamwork in the decision-making and management of this condition.

PubMed: 37780405
DOI: 10.4322/acr.2021.327

Review

Authors: Ying Zhu, Benqiao Wang, Yuehan Hao...

Multiple reports on the co-existence of autoimmune diseases and myasthenia gravis (MG) have raised considerable concern. Therefore, we reviewed autoimmune diseases in MG to explore their clinical presentations and determine whether the presence of autoimmune diseases affects the disease severity and treatment strategies for MG. We reviewed all the major immune-mediated coexisting autoimmune conditions associated with MG. PubMed, Embase and Web of Science were searched for relevant studies from their inception to January 2023. There is a higher frequency of concomitant autoimmune diseases in patients with MG than in the general population with a marked risk in women. Most autoimmune comorbidities are linked to AChR-MG; however, there are few reports of MuSK-MG. Thyroid disorders, systemic lupus erythematosus, and vitiligo are the most common system autoimmune diseases associated with MG. In addition, MG can coexist with neurological autoimmune diseases, such as neuromyelitis optica (NMO), inflammatory myopathy (IM), multiple sclerosis (MS), and autoimmune encephalitis (AE), with NMO being the most common. Autoimmune diseases appear to develop more often in early-onset MG (EOMG). MS coexists more commonly with EOMG, while IM coexists with LOMG. In addition, MG complicated by autoimmune diseases tends to have mild clinical manifestations, and the coexistence of autoimmune diseases does not influence the clinical course of MG. The clinical course of neurological autoimmune diseases is typically severe. Autoimmune diseases occur most often after MG or as a combined abnormality; therefore, timely thymectomy followed by immunotherapy could be effective. In addition, thymoma-associated AChR MG is associated with an increased risk of AE and IM, whereas NMO and MS are associated with thymic hyperplasia. The co-occurrence of MG and autoimmune diseases could be attributed to similar immunological mechanisms with different targets and common genetic factor predisposition. This review provides evidence of the association between MG and several comorbid autoimmune diseases.

Topics: Comorbidity; Disease Progression; Female; Multiple Sclerosis; Humans; Thymus Neoplasms; Hashimoto Disease; Encephalitis; Myositis; Myasthenia Gravis; Neuromyelitis Optica; Thymoma

PubMed: 37781409
DOI: 10.3389/fimmu.2023.1223322

Authors: David Suster, Natali Ronen, Douglas C Pierce...

Thymic hyperplasia is a rare condition generally caused by lymphoid follicular hyperplasia associated with autoimmune disorders. True thymic parenchymal hyperplasia unassociated with lymphoid follicular hyperplasia is extremely rare and may give rise to difficulties in diagnosis. We have studied 44 patients with true thymic hyperplasia (38 females and 6 males) aged 7 months to 64 years (mean, 36 years). Eighteen patients presented with symptoms of chest discomfort or shortness of breath; in 20 patients, the lesions were discovered incidentally. Imaging studies demonstrated enlargement of the mediastinum by a mass lesion suspicious for malignancy. All patients were treated with complete surgical excision. The tumors measured from 3.5 to 24 cm (median, 10 cm; mean, 10.46 cm). Histologic examination showed lobules of thymic tissue displaying well-developed corticomedullary architecture, with scattered Hassall corpuscles separated by mature adipose tissue and bounded by a thin fibrous capsule. No cases showed evidence of lymphoid follicular hyperplasia, cytologic atypia, or confluence of the lobules. Immunohistochemical studies showed a normal pattern of distribution for keratin-positive thymic epithelial cells against a background rich in CD3/TdT/CD1a lymphocytes. Twenty-nine cases had an initial clinical or pathological diagnosis of thymoma or thymoma vs thymic hyperplasia. Clinical follow-up in 26 cases showed that all patients were alive and well between 5 and 15 years after diagnosis (mean, 9 years). Thymic parenchymal hyperplasia causing significant enlargement of the normal thymus that is sufficient to cause symptoms or worrisome imaging findings should be considered in the differential diagnosis of anterior mediastinal masses. The criteria for distinguishing such lesions from lymphocyte-rich thymoma are presented.

Topics: Male; Female; Humans; Thymoma; Thymus Hyperplasia; Hyperplasia; Thymus Neoplasms; Diagnosis, Differential; Lymphadenopathy

PubMed: 37149223
DOI: 10.1016/j.modpat.2023.100207

Authors: Yoshiaki Yasumizu, Makoto Kinoshita, Martin Jinye Zhang...

Myasthenia gravis (MG) is etiologically associated with thymus abnormalities, but its pathology in the thymus remains unclear. In this study, we attempt to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We find that the majority of thymomas are constituted by the cortical region. However, the small medullary region is enlarged in seropositive thymomas and contains polygenic enrichment and MG-specific germinal center structures. Neuromuscular medullary thymic epithelial cells, previously identified as MG-specific autoantigen-producing cells, are enriched in the cortico-medullary junction. The medulla is characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells and effector regulatory T cells. Similar germinal center structures and immune microenvironments are also observed in the thymic hyperplasia medulla. This study shows that the medulla and junction areas are linked to MG pathology and provides insights into future MG research.

Topics: Myasthenia Gravis; Humans; Thymoma; Germinal Center; Transcriptome; Thymus Gland; Thymus Neoplasms; Female; Male; Gene Expression Profiling; Middle Aged

PubMed: 39180749
DOI: 10.1016/j.celrep.2024.114677

Review

Authors: Smita Manchanda, Ashu S Bhalla, Manisha Jana...

The thymus is a lymphatic organ that undergoes dynamic changes with age and disease. It is important to be familiar with these physiological changes in the thymus gland to be able to identify pathology and make an accurate diagnosis. The thymus may be involved in multisystem disorders or show focal isolated lesions. The aim of this article is to review the radiological anatomy of the thymus, normal variants, and pathology including hyperplasia and benign/malignant lesions involving the thymus gland in the pediatric age group. We also propose an algorithmic approach for imaging evaluation of a suspected thymic mass on the basis of morphologic features.

PubMed: 28224091
DOI: 10.5409/wjcp.v6.i1.10

Authors: L Scappaticcio, P Caruso, N Di Martino...

PURPOSE

Abnormal liver blood tests (ALBTs), neutropenia (NEU) and thymic hyperplasia (TH) are new features of Graves' disease (GD). Our objectives were: (a) to calculate the accuracy of TH in discriminating between Graves' and non-Graves' thyrotoxicosis, compared to ALBTs, NEU and Graves' orbitopathy (GO); (b) to explore the outcome of GD-associated TH and non-GD-associated TH.

METHODS

We prospectively analyzed consecutive adult patients with newly diagnosed thyrotoxicosis from January 2018 to June 2023. TH was detected via neck ultrasound (nUS) then confirmed and followed by magnetic resonance imaging (MRI). For GD vs non-GD clinical sensitivity (SE) and specificity (SPEC), accuracy, positive predictive value (PPV) and negative predictive value (NPV) of GO, TH, ALBTs and NEU were calculated.

RESULTS

264 thyrotoxic patients were included. TH was found in 16.4% (20/122) of GD vs 1.4% (2/142) in non-GD (p < 0.001). SE, SPEC, accuracy, PPV and NPV of the four extrathyroidal manifestations of GD were as follows, respectively: GO 26%, 100%, 66%, 100%, 61%; ALBTs 41%, 89%, 69%, 76%, 66%; NEU 5%, 100%, 56%, 100%, 55%; TH 16%, 98%, 61%, 91%, 98%. In 18 of them, TH regressed within 12 months after achieving euthyroidism under anti-thyroid drug therapy, while in the remaining 2, TH regressed 6 months after thyroid surgery. In the two non-GD patients with TH, thymus disappeared along with euthyroidism.

CONCLUSIONS

TH in the hyperthyroidism scenario provides a high PPV for GD. A conservative approach for the diagnostic work-up and initial management of thyrotoxicosis-associated TH should be adopted.

Topics: Humans; Female; Male; Graves Disease; Adult; Middle Aged; Prospective Studies; Thymus Hyperplasia; Thyrotoxicosis; Follow-Up Studies; Antithyroid Agents; Hyperthyroidism; Graves Ophthalmopathy; Diagnosis, Differential; Magnetic Resonance Imaging; Aged

PubMed: 38553585
DOI: 10.1007/s40618-024-02355-w

Authors: Tetsuro Araki, Lynette M Sholl, Victor H Gerbaudo...

RATIONALE AND OBJECTIVES

To determine the intraobserver and interobserver variabilities of thymic measurements on computed tomography (CT) in patients with pathologic diagnosis of thymic hyperplasia or normal thymus.

MATERIALS AND METHODS

Thirty-three patients with pathologic diagnosis of thymic hyperplasia (n = 25) or normal thymus (n = 8) who had identifiable thymus gland on CT were retrospectively studied. Two radiologists independently measured thymic size and CT attenuation. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess intraobserver and interobserver agreements.

RESULTS

The intraobserver and interobserver agreements of thymic diameters and the lobe length were moderate, with CCCs ranging from 0.73 to 0.89 and from 0.72 to 0.81, respectively. Higher agreement was noted among patients whose measurements were performed on the same CT image in two independent measurements, with intraobserver CCC ≥ 0.95 for diameters and length. After providing readers with an instruction for consistent selection of CT image for measurements, the intraobserver and interobserver agreements improved, resulting in CCCs ranging from 0.81 to 0.92 and from 0.77 to 0.85 for diameters and length, respectively. Thymic lobe thickness had the least agreement. CT attenuation measurements were highly reproducible, with CCCs ranging from 0.88 to 0.97. In patients with thymic CT attenuation >30 HU (Hounsfield unit), the attenuation measurements were more reproducible with narrower 95% limits of agreement.

CONCLUSIONS

Thymic size measurements had moderate-to-high intraobserver and interobserver agreements, when the instruction for consistent selection of images was provided to the readers. CT attenuation was highly reproducible, with higher reproducibility for thymic glands with >30 HU. Awareness of thymic measurement variability is necessary when interpreting measured values of normal thymus and thymic pathology on CT.

Topics: Adult; Aged; Cohort Studies; Female; Humans; Male; Middle Aged; Observer Variation; Reproducibility of Results; Retrospective Studies; Thymus Gland; Thymus Hyperplasia; Tomography, X-Ray Computed; Young Adult

PubMed: 24809315
DOI: 10.1016/j.acra.2014.02.006