Thyroiditis: Evaluation and Treatment.

Thyroiditis is a general term for inflammation of the thyroid gland. The most common forms of thyroiditis encountered by family physicians include Hashimoto, postpartum, and subacute. Most forms of thyroiditis result in a triphasic disease pattern of thyroid dysfunction. Patients will have an initial phase of hyperthyroidism (thyrotoxicosis) attributed to the release of preformed thyroid hormone from damaged thyroid cells. This is followed by hypothyroidism, when the thyroid stores are depleted, and then eventual restoration of normal thyroid function. Some patients may develop permanent hypothyroidism. Hashimoto thyroiditis is an autoimmune disorder that presents with or without signs or symptoms of hypothyroidism, often with a painless goiter, and is associated with elevated thyroid peroxidase antibodies. Patients with Hashimoto thyroiditis and overt hypothyroidism are generally treated with lifelong thyroid hormone therapy. Postpartum thyroiditis occurs within one year of delivery, miscarriage, or medical abortion. Subacute thyroiditis is a self-limited inflammatory disease characterized by anterior neck pain. Treatment of subacute thyroiditis should focus on symptoms. In the hyperthyroid phase, beta blockers can treat adrenergic symptoms. In the hypothyroid phase, treatment is generally not necessary but may be used in patients with signs and symptoms of hypothyroidism or permanent hypothyroidism. Nonsteroidal anti-inflammatory drugs and corticosteroids are indicated for the treatment of thyroid pain. Certain drugs may induce thyroiditis, such as amiodarone, immune checkpoint inhibitors, interleukin-2, interferon-alfa, lithium, and tyrosine kinase inhibitors. In all cases of thyroiditis, surveillance and clinical follow-up are recommended to monitor for changes in thyroid function.

Thyroid complications of SARS and coronavirus disease 2019 (COVID-19).

We have reviewed the available literature on thyroid diseases and coronavirus disease 2019 (COVID-19), and data from the previous coronavirus pandemic, the severe acute respiratory syndrome (SARS) epidemic. We learned that both SARS and COVID-19 patients had thyroid abnormalities. In the limited number of SARS cases, where it was examined, decreased serum T3, T4 and TSH levels were detected. In a study of survivors of SARS approximately 7% of the patients had hypothyroidism. In the previous evaluation evidence was found that pituitary function was also affected in SARS. Others suggested a hypothalamic-pituitary-adrenal axis dysfunction. One result published recently indicates that a primary injury to the thyroid gland itself may play a key role in the pathogenesis of thyroid disorders in COVID-19 patients, too. Subacute thyroiditis, autoimmune thyroiditis and an atypical form of thyroiditis are complications of COVID-19. Thyroid hormone dysfunction affects the outcome by increasing mortality in critical illnesses like acute respiratory distress syndrome, which is a leading complication in COVID-19. Angiotensin-converting enzyme 2 is a membrane-bound enzyme, which is also expressed in the thyroid gland and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses it for docking, entering as well as replication. Based on the available results obtained in the SARS-CoV-2 pandemic, beside others, we suggest that it is necessary to monitor thyroid hormones in COVID-19.

Follicle-stimulating Hormone-secreting Pituitary Adenoma Accompanied by Painful Thyroiditis.

A 30-year-old woman with multiple ovarian cysts presented with high serum estradiol levels. She had a pituitary adenoma, but the follicle-stimulating hormone (FSH) concentration was within the normal range. The patient complained of neck pain and palpitations during the disease course, and laboratory results revealed thyrotoxicosis and a systemic inflammatory response with negative findings for anti-thyroid stimulating hormone (TSH) receptor antibody and positive findings for anti-thyroglobulin and anti-thyroid peroxidase antibodies. Prednisolone improved the symptoms and the thyroid function and was discontinued after two months. A histological examination of the pituitary tumor confirmed it to be FSH-producing pituitary adenoma, with subsequent normalization of the serum estradiol concentration.

Differences in the diagnosis and management of pyriform sinus fistula between newborns and children.

Pyriform sinus fistula (PSF) is a rare congenital entity. We hypothesized that clinical features, diagnosis and treatment may differ between newborns and children. 190 patients diagnosed with PSF were divided into two groups: neonatal (n = 15) and childhood (n = 175). The medical records including demographic and clinical data were retrospectively analyzed. There were 102 boys and 88 girls in this study. Most patients presented as a left-sided neck lesion. A neck mass, with or without infection and respiratory distress, was the common finding in newborn patients. Prenatal diagnosis was made in three cases. However, in childhood group, initial symptoms were neck abscess (78.8%), acute thyroiditis (11.4%), neck mass (6.9%), and thyroid lesion (2.8%). The presence of a cervical mass with air pocket showed on CT image was thought to be the pathognomonic finding of neonatal PSF. The diagnosis was usually established by barium esophagography in older children. Delayed accurate diagnosis was detected in both groups. The median time from onset to diagnosis was 22 months and 1 year respectively. Endoscopic-assisted open surgery was performed successfully in all patients, with good outcomes in majority cases of both groups (93.3% and 95.4%). Recurrence was developed in 5 patients. PSF should be suspected in newborns with cervical mass and in children with recurrent neck infection, especially on the left side. Early diagnosis and treatment might avoid repeated surgical procedures. Complete resection of the cyst and fistula in non-infected state is essential for good outcomes.

CD8+ tumour-infiltrating lymphocytes and COX2 expression may predict relapse in differentiated thyroid cancer.

BACKGROUND/OBJECTIVE: There is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour-associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients. DESIGN: Retrospective cohort study. PATIENTS: We studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas. MEASUREMENTS: Immune cell markers were evaluated using immunohistochemistry, including tumour-associated macrophages (CD68) and subsets of tumour-infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis. RESULTS: Concurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0·001) and expression of COX2 (P =0·01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional-hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2. CONCLUSION: In conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures.

Ultrasound scoring in combination with ultrasound elastography for differentiating benign and malignant thyroid nodules.

OBJECTIVE: The aim of this study was to evaluate the value of ultrasound scores obtained by conventional ultrasonography and ultrasound elastography in the differentiation of benign and malignant thyroid nodules in Chinese patients. METHODS: This study included 297 patients who were referred for surgery for compressive symptoms or suspicion of malignancy. Five hundred and twelve thyroid nodules were examined by ultrasonography. The final diagnosis was based on histological findings. A seven-point ultrasound scoring system based on conventional ultrasonography and a five-point scoring system based on ultrasound elastography were applied independently or in combination. The receiver operating characteristic (ROC) curves were graphed, and the areas under the curves (AUCs) were compared using the χ(2) -test. RESULTS: Solid composition, hypo-echoic appearance, an irregular or blurred margin, an aspect ratio ≥1, intranodular blood flow and presence of microcalcifications were significant predictors of malignant thyroid nodules. The AUC (95% CI) was 0·9067 (0·8817-0·9318) for the ultrasound scores based on conventional ultrasonography and 0·9080 (0·8842-0·9317) for the elasticity scores. The combination of these two scoring systems provided good accuracy with an AUC (95% CI) of 0·9415 (0·9223-0·9606), which was significantly higher than that obtained with the conventional ultrasound scores (χ(2)  = 36·03, P < 0·001) or the elasticity scores (χ(2)  = 12·80, P < 0·001) individually. When we set the cut-point to ≥5, the sensitivity and specificity were 85·22% and 87·38%, respectively. CONCLUSIONS: Elastography in combination with conventional ultrasonography is a promising imaging-based approach that can assist in the differential diagnosis of thyroid cancer.

Thyroiditis: an integrated approach.

Thyroiditis is a general term that encompasses several clinical disorders characterized by inflammation of the thyroid gland. The most common is Hashimoto thyroiditis; patients typically present with a nontender goiter, hypothyroidism, and an elevated thyroid peroxidase antibody level. Treatment with levothyroxine ameliorates the hypothyroidism and may reduce goiter size. Postpartum thyroiditis is transient or persistent thyroid dysfunction that occurs within one year of childbirth, miscarriage, or medical abortion. Release of preformed thyroid hormone into the bloodstream may result in hyperthyroidism. This may be followed by transient or permanent hypothyroidism as a result of depletion of thyroid hormone stores and destruction of thyroid hormone-producing cells. Patients should be monitored for changes in thyroid function. Beta blockers can treat symptoms in the initial hyperthyroid phase; in the subsequent hypothyroid phase, levothyroxine should be considered in women with a serum thyroid-stimulating hormone level greater than 10 mIU per L, or in women with a thyroid-stimulating hormone level of 4 to 10 mIU per L who are symptomatic or desire fertility. Subacute thyroiditis is a transient thyrotoxic state characterized by anterior neck pain, suppressed thyroid-stimulating hormone, and low radioactive iodine uptake on thyroid scanning. Many cases of subacute thyroiditis follow an upper respiratory viral illness, which is thought to trigger an inflammatory destruction of thyroid follicles. In most cases, the thyroid gland spontaneously resumes normal thyroid hormone production after several months. Treatment with high-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs is directed toward relief of thyroid pain.

Increased lymphangiogenesis in Riedel thyroiditis (Immunoglobulin G4-related thyroid disease).

The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease. We report the clinicopathological, immunohistochemical, and ultrastructural features of a case of RT in a 39-year-old white Spanish woman, admitted with a hard goiter and cold nodule in the left thyroid lobe. This case represents 0.05 % of a series of 1,973 consecutive thyroidectomies performed in our hospital. More than 80 % of the left thyroid lobe was effaced by fibrosis and inflammation (lymphocytes, 57 IgG4+ plasma cells per 1 high-power field, an IgG4/IgG ratio of 0.67, and eosinophils) with extension into the surrounding tissues and occlusive phlebitis. Immunostaining for podoplanin (D2-40) detected signs of increased lymphangiogenesis in the fibroinflammatory areas that were confirmed by electron microscopy. A strong, diffuse stain for podoplanin and transforming growth factor ß1 was also detected in the same areas. The increased number of lymphatic vessels in RT is reported for the first time. Our findings support the inclusion of RT within the spectrum of IgG4-related thyroid disease (IgG4-RTD). Although the etiology and physiopathology of IgG4-RTD still remain elusive, the results obtained in the present case suggest the participation of lymphatic vessels in the pathogenesis of RT.

Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment.

Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multitargeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. Since their introduction as adjunct treatment for renal cell carcinoma and gastrointestinal stromal tumors (GIST), a number of reports have demonstrated that TKI can induce thyroid dysfunction which was especially more common with sunitinib maleate. Many mechanisms with respect to this adverse effect of tyrosine kinase inhibitors have been proposed including their induction of thyroiditis, capillary regression in the thyroid gland, antithyroid peroxidase antibody production, and their ability to decrease iodine uptake by the thyroid gland. Of interest is the observation that TKI-induced thyroid dysfunction may actually be protective as it was shown to improve overall survival, and it was suggested that it may have a prognostic value. Followup on thyroid function tests while patients are maintained on tyrosine kinase inhibitor is strongly recommended. When thyroid dysfunction occurs, appropriate treatment should be individualized depending on patients symptoms and thyroid stimulating hormone level.

Treatment of pretibial myxedema with dexamethazone injected subcutaneously by mesotherapy needles.

Pretibial myxedema (PTM) is a rare extrathyroidal manifestation of Graves' disease that requires treatment when the clinical picture is markedly evident. In addition to topical treatment with steroid ointments, there have been previous reports of subcutaneous injections of steroids. This procedure may cause nodular degeneration of the skin due to fat atrophy when standard needles are used. In the present study, we have tried a novel modality of treatment of PTM by injecting a solution of dexamethasone in the subcutaneous tissue using needles employed for mesotherapy. These needles are ≤4 mm long and deliver the medication within the dermis or the first layer of the subcutaneous fat. We have treated five patients, four with diffuse and one with elephanthiasic PTM. We utilized multiple injections of a solution of dexamethasone, lidocaine, and saline in the PTM plaque and in the pretibial area, both in the PTM plaque and in the area surrounding the lesions, once a week for three consecutive weeks. Two patients with a more severe form of PTM underwent another two cycles four to six weeks after initial treatment. Patients were studied before and after treatment by clinical assessment and ultrasound of the pretibial skin. The treatment was well-tolerated, with only moderate pain upon injection of the solution. One month after treatment, all patients showed improvement of PTM at clinical assessment and a reduction of the thickness of the lesions at ultrasound of ∼15%, involving mostly the dermis. Moreover, all patients reported amelioration of the leg appearance. The present study, although preliminary, shows that intralesion steroid injection with mesotherapy needles in PTM is effective and well tolerated, and does not cause undesired long-term modifications of the skin. More studies are warranted to standardize such treatment in larger groups of patients.

Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies.

BACKGROUND: Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. OBJECTIVE: To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. METHODS: Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. RESULTS: Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. CONCLUSIONS: PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.

Lithium toxicity precipitated by thyrotoxicosis due to silent thyroiditis: cardiac arrest, quadriplegia, and coma.

BACKGROUND: Lithium is widely used to treat bipolar disorders. Lithium toxicity is generally caused by inappropriately high doses of lithium or impaired lithium excretion. Most lithium is eliminated via the kidneys and, since thyroid hormone increases tubular reabsorption of lithium, thyrotoxicosis could contribute to the development of lithium toxicity. We report a case of severe lithium toxicity that was apparently precipitated by the onset of thyrotoxicosis resulting from silent thyroiditis and dehydration. PATIENT FINDINGS: The patient was a 64-year-old woman who was admitted for muscle weakness in the lower extremities, diarrhea, and palpitations. She had bipolar disorder and was being treated with lithium carbonate, which she discontinued one week before admission. Her circulating lithium levels had been monitored yearly. Early in her admission she was dehydrated and had febrile episodes, paroxysmal atrial fibrillation, and muscle weakness. Initially, fluid therapy was started, but she lost consciousness and had a cardiac arrest for 2 minutes due to prolonged sinus arrest. Chest compression and manual artificial ventilation were performed, and body surface pacing was started. Serum lithium was markedly elevated to 3.81 mEq/L (therapeutic range, 0.4-1.0 mEq/L), and thyroid hormone levels were increased (free triiodothyronine, 8.12 pg/mL; free thyroxine, 4.45 ng/dL), while thyrotropin (TSH) was suppressed (<0.01 µIU/mL). Hemodialysis was performed, and a temporary pacemaker was inserted for severe sinus bradycardia. The serum thyroglobulin was 4680 ng/mL (reference range, <32.7 ng/mL). A TSH receptor antibody test was negative. Glucocorticoid therapy and inorganic iodine (100 mg) were administered and continued until day 11. However, her neurological symptoms deteriorated with floppy quadriplegia and deep coma. She gradually recovered. On day 36, she was discharged without any neurological symptoms or thyrotoxicosis. SUMMARY: A 64-year-old woman taking lithium for bipolar disorder developed lithium toxicity in the setting of what seemed likely to be a recent onset of thyrotoxicosis due to silent thyroiditis. CONCLUSIONS: Thyrotoxicosis may be a contributing cause of lithium toxicity, particularly if it is abrupt in onset and even with cessation of lithium therapy if renal function is compromised. Thyroid function should be assessed immediately in patients with suspected lithium toxicity.

Inappropriate elevation of serum thyrotropin levels in patients treated with axitinib.

BACKGROUND: Although anticancer treatment with the tyrosine kinase inhibitor (TKI) axitinib frequently causes thyroid dysfunction, the associated mechanism and clinical features have not been elucidated. METHODS: Six patients were treated with axitinib for metastatic renal cell carcinoma at the Hamamatsu University School of Medicine between 2008 and 2010. We reviewed their thyroid function results and compared them to those of patients treated with two other TKIs, sunitinib or sorafenib, and to those of subjects with normal hypothalamic-pituitary-thyroid (HPT) function. RESULTS: Axitinib-induced thyroid dysfunction was observed in all patients, and two patterns were observed: increased serum thyrotropin (TSH) levels within one month after administration occurred in five patients and transient thyrotoxicosis due to destructive thyroiditis occurred in five patients within 7 months of treatment. Four patients exhibited both. When the relationship between the serum TSH and thyroid hormones was evaluated using plots of TSH versus both free thyroxine and free triiodothyronine, four patients showed an inappropriate elevation of serum TSH during administration of axitinib. Their values apparently shifted against the regression line compared to data from patients with a normal HPT function. A similar tendency, though weaker, was observed in some patients treated with sunitinib or sorafenib. CONCLUSION: This is the first study to report an inappropriate elevation of serum TSH levels in patients treated with axitinib.

[Advances in study of vascular endothelial growth factor and thyroid disease].

The basic function of vascular endothelial growth factor (VEGF) is to promote vascular growth. Recent studies show that VEGF plays a vital role in various thyroid diseases through prompting angiogenesis. But the function of VEGF and specific change condition in different thyroid disease still needs further explorations. This review mainly focuses on the molecular characteristics and clinical application of VEGF.

Vocal characteristics in patients with thyroiditis.

OBJECTIVE: The aim of the present study was to describe the vocal characteristics of patients with thyroiditis in a clinical setting. MATERIALS AND METHODS: A total of 17 consecutive patients with the diagnosis of thyroiditis presenting to the endocrinology clinic were invited to participate in the study. A group of 29 healthy subjects were used as controls. They underwent acoustic analysis and a perceptual evaluation using the GRABS classification. The mean score of each parameter was computed, and the distribution of severity of each perceptual parameter were listed. RESULTS: There was no significant difference in any of the acoustic parameters between the patients and the controls, and there was no significant difference in the mean score of all the perceptual parameters between the patients and the controls. Even when examining the distribution of the severity of evaluation, there was no significant difference between the patients and the controls, as well. CONCLUSION: Patients with thyroiditis do not have abnormal perceptual vocal evaluation or acoustic findings compared with controls.

Study on cutoff value setting for differential diagnosis between Graves' disease and painless thyroiditis using the TRAb (Elecsys TRAb) measurement via the fully automated electrochemiluminescence immunoassay system.

The purposes of this study are to set the Elecsys TRAb cutoff value by which GD and PT can be accurately diagnosed simply; and to investigate the usefulness of the vascularity index (VI) obtained from power Doppler sonography (PDS). Using 109 normal controls, 186 GD patients, and 109 PT patients who were diagnosed through Tc-99m uptake, we set the cutoff value by conducting ROC analysis on the Elecsys TRAb values. The cutoff value as a result of the ROC analysis on the Elecsys TRAb values of the normal controls and GD patients was 0.8 IU/L with 100% of sensitivity and specificity. Because all 89 cases (81.6% of the entire PT cases) with Elecsys TRAb =<0.8 IU/L are PT, the cutoff =<0.8IU/L can thus be diagnosed as PT. In contrast, because all 166 cases (88.7% of the entire GD) with Elecsys TRAb >=3.0 IU/L except for one case of PT are GD, the cutoff >=3.0 IU/L can be diagnosed as GD. So Elecsys TRAb between 0.8-3.0 IU/L was dubbed gray zone (GZ). Finally, the cutoff value of 1.5 IU/L from the ROC on the PT and GD cases was chosen as the cutoff with 96.2% of sensitivity and 94.6 of specificity. All PDS VI >=80% were GD including 4 of 6 cases with GZ and all PDS VI <50% plus Elecsys TRAb-negative cases were PT including 4 of 5 cases with GZ. In conclusion, Elecsys TRAb cutoff and VI value for differential diagnosis between GD and PT has been set successfully.