Severe Hyperthyroidism Research Articles

Long-Term Follow-Up of a Patient with Sporadic Nonautoimmune Hyperthyroidism Due to a Thyrotropin-Receptor Mutation (D619G)

ABSTRACT Objective: Sporadic nonautoimmune hyperthyroidism caused by germline mutations of the thyrotropin receptor (TSHR) gene is a very rare disease that manifests as severe congenital hyperthyroidism. We describe a case presenting with sporadic nonautoimmune hyperthyroidism during adolescence. Methods: Laboratory data, imaging, histopathology, clinical follow-up, and DNA sequencing were evaluated. Results: The patient was born at term with a normal birth weight but showed increased growth velocity at approximately 7 months. He had no medical consultation before tachycardia was detected at a school physical examination at the age of 13 years. Thyroid function tests confirmed hyperthyroidism with negative anti-TSHR antibodies. After maintaining methimazole therapy for 12 years, he underwent total thyroidectomy, and the weight of the resected thyroid tissue was 131 g. The subsequent histopathologic findings showed an encapsulated follicular adenoma, adenomatous goiter, and hyperplastic changes of the foll...

The association between irisin and muscle metabolism in different thyroid disorders.

Irisin is a new adipo-myokine, encoded by the FNDC5 gene. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This prospective study assesses the influence of thyrometabolic changes on serum irisin concentration in association with altered muscle metabolism. This is performed on a large cohort of patients affected by severe hypo- or hyperthyroidism, as well as by the expression of the FNDC5 gene in thyroid tissue affected by different pathologies. The study group comprised 119 patients with newly diagnosed severe hyperthyroidism or hypothyroidism, and a control group of 45 healthy subjects. Body composition, serum irisin concentrations, and thyroid-related hormones, creatine kinase, dystrophin and titin concentrations were evaluated. FNDC5 expression was also analysed in tissue samples from 80 patients with nontoxic multinodular goitre, toxic goitre, Graves' disease and papillary thyroid cancer. Irisin concentration was lower in patients with prolonged hypothyroidism. There was a tendency towards lower dystrophin and titin concentrations in patients with hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with hypothyroidism resulted in a decreased muscle mass with an increase in irisin concentrations, while the hyperthyroid group showed an increase in fat mass. Statistically significant overexpression of FNDC5 gene was found in patients with toxic goitre as compared to Graves' disease, papillary thyroid cancer and controls. The presented data support the theory that irisin concentration changes are associated with prolonged hypothyroidism and might primarily constitute the result of prolonged myopathy. These changes are most likely not related to the expression of the FNDC5 gene in the thyroid gland.

Cytomegalovirus-mononucleosis-induced thyroiditis in an immunocompetent patient.

Enteroviruses, including coxsackieviruses and Echovirus, are well known pathogens responsible for the development of thyroiditis. We describe the case of a 49-year-old woman with no personal or family history of thyroid disease who presented to the emergency room with a two-week history of daily fevers up to 39°C, a sore throat, occasional palpitations and diaphoresis, decreased appetite and an unintentional 10 kg weight loss over the same time course Physical examination revealed mild tachycardia, an intention tremor and a normal-sized, nontender thyroid gland without palpable nodules. The remainder of the physical examination was unremarkable and without stigmata of Graves’ disease. Her initial blood tests revealed overt thyrotoxicosis, elevated liver enzymes, an elevated C-reactive protein, a negative monospot and a positive CMV IgM antibody. Thyroid sonography revealed areas of hypoechogenicity and relatively low vascularity. Fine-needle biopsy showed a lymphocytic infiltrate. The patient was treated symptomatically with propranolol. On follow-up, the patient became euthyroid, and her liver enzymes normalised. Previous cases of CMV-induced thyroiditis occurred in immunosuppressed patients. This is the first reported case of a CMV-mononucleosis-induced thyroiditis in an immunocompetent adult patient and serves as a reminder that viral illnesses are a common cause of thyroiditis with abnormal liver enzymes.Learning points:The differential diagnosis of thyrotoxicosis with abnormal liver enzymes includes severe hyperthyroidism and thyroid storm caused by Graves’ disease as well as the thyrotoxic phase of a thyroiditis, usually caused by a virus such as coxsackievirus or, in this case, cytomegalovirus.Cytomegalovirus appears to be a recently recognized causal agent for thyroiditis, both in immunosuppressed and immunocompetent patients.Careful follow-up of thyroid function tests in patients with thyroiditis allows clinicians to determine if patients’ thyroid hormone secretion normalizes or if they remain hypothyroid.

Anxiety, Depression, and Impaired Quality of Life in Primary Aldosteronism: Why We Shouldn't Ignore It!

Many endocrinopathies are associated with impaired quality of life and psychiatric comorbidities. Personality changes are characteristic features of endocrine diseases and can even be the dominating symptom. In such circumstances, a patient will be treated for an apparent primary psychiatric condition, whereas the underlying endocrine diagnosis is delayed for month or even years. It is textbook knowledge that mania and psychosis may be found in patients with severe hyperthyroidism, whereas patients with Cushing syndrome frequently have depressive symptoms and cognitive disturbances. In pituitary diseases, the spectrum depends on the underlying hyperfunction or hypofunction: acromegalic patients often have maladaptive personality traits and higher rates of affective disorders, and patients with prolactinoma have changes in sleep pattern and cognition.

Successful treatment of severe thyrotoxicosis with radioiodine therapy in a patient with thyrotoxic cardiomyopathy

Thyrotoxic cardiomyopathy (TCM) is a potential life threatening complication of thyrotoxicosis which is potentially reversible with early achievement of euthyroid state. Management of severe thyrotoxicosis in the presence of TCM is a challenging task, especially when thioamides are contraindicated. A 58 yr old male with poorly controlled Grave’s disease of 10 years presented with worsening symptoms of thyrotoxicosis and leg swelling. On examination he was thyrotoxic with a smooth diffuse goiter and also had inactive Grave’s orbitopathy. He had irregularly irregular pulse rate, grossly elevated jugular venous pulses, enlarged heart with tricuspid regurgitation and pulmonary hypertension. FT4 was >8.34 ng/dl (0.8-1.6 ng/dl), free T3 was 20.39 pg/ml (2.3-4.3 pg/ml) and TSH was 0.01 mU (0.5-5.0 mU/L). Serial ECGs showed slow atrial fibrillation with transient complete hear block and echocardiogram showed dilated TCM. He had pancytopenia, most likely resulting from concurrent carbimazole therapy. Medical management of cardiomyopathy was initiated along with lithium, prednisolone and judicious use of beta blockers to control his thyroid status. Within one week he was subjected to radioactive iodine (RAI) therapy following which he was rendered euthyroid . RAI is a safe mode of definitive therapy in patients with TCM provided carful stabilization of underlying cardiac status. Early definitive therapy is required to achieve euthyroid status to minimize irreversible TCM.

Myopathy and dyshagia cause by Severe Hyperthyroidism

Myopathy and dyshagia cause by Severe Hyperthyroidism

Evaluation of long-term results of surgical treatment of toxic goiter

Purpose – to improve the methodology for assessing the long-term results of surgical treatment of toxic goiter. Materials and methods. Studies conducted in 150 surgically treated patients with moderate (48) and severe (102) toxic goiter. We developed methodology of long-term results assessment with gradations of good, satisfactory, unsatisfactory and ineffective treatment. One year after surgery in comparison with baseline data we studied the changes in general condition, structural and functional disorders of the heart muscle, severity and functional class of heart failure, heart rhythm disorders. Results and discussion. In patients with hyperthyroidism of moderate severity good result was found in 26 (54.2%) cases, satisfactory – in 21 (43.7%) patients and unsatisfactory – in 1 (2.1%). In patients with severe thyrotoxicosis remote outcome was assessed as good in 9 (8.8%), satisfactory – in 36 (35.3%), unsatisfactory – in 33 (32.4%) cases. Ineffective surgical treatment was found in 24 (23.5%) patients. We established that long-term results depend on the severity and duration of hyperthyroidism. Unsatisfactory results and ineffective surgical treatment were found in patients with severe rhythm disorders, structural and functional changes in the heart muscle and II or III functional class of heart failure. Conclusions. Long-term results of surgical treatment of toxic goiter determined by the severity of structural changes in the heart muscle and cardiac functional disorders. Along with the growth of the severity and duration of hyperthyroidism increases the number of cardiac rhythm disorders: from supraventricular beats to persistent / permanent atrial fibrillation. In cases of severe thyrotoxicosis, the need of surgical treatment should be considered as soon as possible, at least before development of severe rhythm disorders and cardiac structural and functional changes in the heart muscle.

Lugol's solution-induced painless thyroiditis.

Lugol’s solution is usually employed for a limited period for thyroidectomy preparation in patients with Graves’ disease and for the control of severe thyrotoxicosis and thyroid storm. We describe a rare case of Lugol’s solution-induced painless thyroiditis. In November 2014, a 59-year-old woman was prescribed Lugol’s solution four drops per day for the alleviation of menopausal symptoms. She was referred to our clinic in June 2015 for fatigue, hair loss, and a 20-lb weight loss without thyroid pain or discomfort. Physical examination revealed a normal thyroid gland. On 7 May 2015, laboratory tests revealed a suppressed thyroid-stimulating hormone (TSH) 0.01 U/L with elevated free T4 3.31 ng/dL (42.54 pmol/L). Repeat testing on 25 May 2015 showed spontaneous normalization of the free thyroid hormone levels with persistently low TSH 0.10 U/L. Following these results, a family physician prescribed methimazole 10 mg PO TID and very soon after, the TSH concentration rose to >100 U/L along with subnormal free T4 and T3 levels. Methimazole was promptly discontinued, namely within 18 days of its initiation. Over the course of the next few months, the patient spontaneously achieved clinical and biochemical euthyroidism. To our knowledge, this is a unique case of painless thyroiditis induced by Lugol’s solution, which has not been reported before. Lugol’s solution is a short-term medication given for the preparation of thyroidectomy in patients with Graves’ disease and for the control of severe thyrotoxicosis. Iodine excess can cause both hyperthyroidism and hypothyroidism. Rarely, Lugol’s solution can cause acute painless thyroiditis.Learning points:Lugol’s solution is used for thyroidectomy preparation in patients with Graves’ disease and for the control of severe thyrotoxicosis and thyroid storm.Iodine excess can cause both hypothyroidism and thyrotoxicosis. Thyroid glands with an underlying pathology are particularly susceptible to the adverse effect of iodine.The prolonged off-label use of Lugol’s solution can be harmful. Rarely, Lugol’s solution can cause acute painful thyroiditis.

Therapeutic options in severe thyrotoxicosis with malabsorption

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Severe hyperthyroidism imposes large amounts of antithyroid compounds

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Consistent, but Totally Misleading, Thyroid Function Test Results

A 69-year-old male patient was referred due to biochemical evidence of severe hyperthyroidism (Table 1). His past medical history was notable for multiple sclerosis, for which he was included in a therapeutic protocol. Clinical examination did not reveal symptoms consistent with his biochemical assessment. The thyroid ultrasound showed no anomalies. His …

Persistent Graves\u2019 hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report

BackgroundGraves’ disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves’ disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves’ disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves’ hyperthyroidism.Case presentationA 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves’ hyperthyroidism.ConclusionsThe possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves’ disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves’ disease or indicate the outcome of the disease, and that active Graves’ disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves’ disease and treatment efficacy.

Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan-Herndon-Dudley Syndrome.

Mutations in the thyroid hormone transporter SLC16A2 (MCT8) cause the Allan-Herndon-Dudley Syndrome (AHDS), characterized by severe psychomotor retardation and peripheral thyrotoxicosis. Here, we report three newly identified AHDS patients. Previously documented mutations were identified in probands 1 (p.R271H) and 2 (p.G564R), resulting in a severe clinical phenotype. A novel mutation (p.G564E) was identified in proband 3, affecting the same Gly564 residue, but resulting in a relatively mild clinical phenotype. Functional analysis in transiently transfected COS-1 and JEG-3 cells showed a near-complete inactivation of TH transport for p.G564R, whereas considerable cell-type-dependent residual transport activity was observed for p.G564E. Both mutants showed a strong decrease in protein expression levels, but differentially affected Vmax and Km values of T3 transport. Our findings illustrate that different mutations affecting the same residue may have a differential impact on SLC16A2 transporter function, which translates into differences in severity of the clinical phenotype.

PERIOPERATIVE MANAGEMENT OF MANDIBULAR FRACTURES IN A PATIENT WITH SEVERE HYPERTHYROIDISM: A CASE REPORT

Purpose: In this report, we had managed to perioperative of mandibular fractures in a patient with severe hyperthyroidism. Methods: A 26-year-old man required emergency admission to the hospital after having a fall and losing consciousness. A computed tomography (CT) scan revealed a fracture line in the mental region and both sides of the condyle. He had a previous history of hyperthyroidism and was prescribed thiamazole, propranolol hydrochloride, and potassium iodide, but he did not take medicine by self-judgement. His laboratory findings were as follows: FT3, 7.53[Formula: see text]pg/mL; FT4, 4.26[Formula: see text]ng/mL; and TSH, undetectable. Therefore, we planned for surgery immediately after his condition improved. We also postponed his maxilla-mandibular fixation (MMF) procedure because there was a probability that MMF procedure caused thyroid crisis. Result: Seventeen days after his injury, he had greatly reduced his risk of having thyroid crisis, he underwent open reduction of his mandibular fractures under general anesthesia. As perioperative management, the patient underwent an opening training and oral care before and after surgery in addition to thyroidal treatment. Conclusion: The procedures prevented adhesion of temporomandibular joint and recovered aperture size. Moreover, we diagnosed agranulocytosis from intraoral lesion and obtained good course in response to early.

Serum immunoglobulin G4 levels and Graves' disease phenotype.

We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p < 0.001), had higher antithyroid peroxidase antibody (p = 0.01), and anti-thyroglobulin antibody levels (p = 0.006) and required shorter duration of the first methimazole treatment cycle (p = 0.041) than patients with immunoglobulin G4 below the 75th percentile. At diagnosis, patients with immunoglobulin G4 levels above the 90th percentile (>286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

Antithyroid drugs during breastfeeding.

Antithyroid drugs (ATDs) are widely used for the treatment of Graves' disease (GD) in the general population. Over the past decade, there has been an increasing awareness that several disturbances of thyroid function may occur in mothers after delivery which may be more prevalent than previously appreciated. Exacerbation of immune reactions occurs 3-12 month following delivery. Management of hyperthyroidism during lactation requires special considerations and should be implemented to prevent any adverse outcomes in mother and neonate. Continuation of breastfeeding is safe and should be encouraged in hyperthyroid mothers taking ATDs, whether these are ATDs being continued after gestation or indeed ATD treatment initiated in the postpartum period. Given PTU hepatotoxicity concerns, experts currently recommend using low-to-moderate MMI doses as a first-line therapy in lactating mothers. PTU should be reserved only as a second-line agent for cases of severe hyperthyroidism (thyroid storm) and allergic reactions to previous MMI treatment. ATD should be administered in divided doses immediately following each feeding. Evaluation of thyroid function tests is advisable at least 3-4 weeks after the initiation of breastfeeding.

Thyrotoxic Cardiomyopathy and Heart Failure in Patients with Toxic Goiter. Changes after Surgery

Changes in the severity of heart failure in patients with toxic goiter after surgery are insufficiently studied.The objective of the research was to study changes in cardiac disorders in the remote period after surgical treatment of toxic goiter.Material and methods. The study included 48 patients with toxic goiter and moderate thyrotoxicosis and 102 patients with severe thyrotoxicosis. Cardiac disorders and changes in cardiac function after surgery were studied using the following gradation: good, satisfactory, unsatisfactory results and ineffective treatment.Results. Good and satisfactory results of surgical treatment in patients with moderate thyrotoxicosis were obtained in 47 (98%) cases and in patients with severe thyrotoxicosis they were achieved in 45 (44%) cases. Unsatisfactory outcome was determined by the severity of thyrotoxicosis, its duration, and low exercise tolerance during the 6-min walking test.Conclusions. Persistent severe thyrotoxicosis leads to atrial fibrillation and heart failure, which in most cases (66%) after surgical treatment of toxic goiter do not undergo reversible changes.

Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis.

SummaryType II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy.Learning pointsType II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

Enfermedad tiroidea y gestación

IntroductionThyroid dysfunction is common during pregnancy and it is associated to adverse maternal and foetal outcomes. DiagnosisBecause of the changes in thyroid physiology during normal pregnancy, the use of triméster-specific reference ranges for thyroid stimulating hormone (TSH) and free thyroxin (fT4) is recommended for the diagnosis and monitoring during the follow-up. TreatmentWomen with pre-existing hypothyroidism who become pregnant should increase their levothyroxine dose around 25-30% in early pregnancy. When hypothyroidism is discovered during pregnancy, levothyroxine treatment should be initiated to restore euthyroidism as soon as possible. Subclinical and mild overt asymptomatic hyperthyroidism during pregnancy can be monitored with no treatment. Moderate to severe hyperthyroidism requires treatment with the lowest dose of thionamides able to maintain mother's free T4 in the high level of the normal range.

Severe Iron-deficiency Anemia and Celiac Disease

We report a case of a 37-year-old woman with atypical presentation of celiac disease in relation to severe iron-deficiency and hyperthyroidism. During the investigation for iron-deficiency anemia, after exclusion of hematologic disorders, she was diagnosed with celiac disease by small-bowel biopsy. After starting the gluten free diet, the serum hemoglobin values were corrected and the symptoms of hyperthyroidism improved. Our presentation demonstrates that for patients with severe iron-deficiency anemia, the examination for the celiac disease should be considered. The quality of life and morbidity of patients with hyperthyroidism, iron-deficiency anemia and celiac disease may be improved by gluten withdrawal.