Symptoms Of Thyroid Dysfunction Research Articles

Raman Spectroscopy as a Potential Adjunct of Thyroid Nodule Evaluation: A Systematic Review.

The incidence of thyroid nodules (TNs) is estimated at 36.5% and 23% in females and males, respectively. A single thyroid nodule is usually detected during ultrasound assessment in patients with symptoms of thyroid dysfunction or neck mass. TNs are classified as benign tumours (non-malignant hyperplasia), benign neoplasms (e.g., adenoma, a non-invasive follicular tumour with papillary nuclear features) or malignant carcinomas (follicular cell-derived or C-cell derived). The differential diagnosis is based on fine-needle aspiration biopsies and cytological assessment (which is burdened with the bias of subjectivity). Raman spectroscopy (RS) is a laser-based, semiquantitative technique which shows for oscillations of many chemical groups in one label-free measurement. RS, through the assessment of chemical content, gives insight into tissue state which, in turn, allows for the differentiation of disease on the basis of spectral characteristics. The purpose of this study was to report if RS could be useful in the differential diagnosis of TN. The Web of Science, PubMed, and Scopus were searched from the beginning of the databases up to the end of June 2023. Two investigators independently screened key data using the terms "Raman spectroscopy" and "thyroid". From the 4046 records found initially, we identified 19 studies addressing the differential diagnosis of TNs applying the RS technique. The lasers used included 532, 633, 785, 830, and 1064 nm lines. The thyroid RS investigations were performed at the cellular and/or tissue level, as well as in serum samples. The accuracy of papillary thyroid carcinoma detection is approx. 90%. Furthermore, medullary, and follicular thyroid carcinoma can be detected with up to 100% accuracy. These results might be biased with low numbers of cases in some research and overfitting of models as well as the reference method. The main biochemical changes one can observe in malignancies are as follows: increase of protein, amino acids (like phenylalanine, tyrosine, and tryptophan), and nucleic acid content in comparison with non-malignant TNs. Herein, we present a review of the literature on the application of RS in the differential diagnosis of TNs. This technique seems to have powerful application potential in thyroid tumour diagnosis.

Thyroid Hormone Resistance Syndrome in an Adolescent Girl: A Case Report

Introduction: Resistance to Thyroid Hormones (RTH) is a rare, hereditary disease characterized by diminished sensitivity of target tissues to thyroid hormones. Most cases (~85%) are caused by mutations in the thyroid hormone receptor beta (THRβ) gene (RTHβ). The clinical spectrum of RTHβ is quite broad and highly heterogeneous, and the hallmark of the condition is a paucity of signs and symptoms of thyroid dysfunction despite elevated levels of T4 and T3, with a concomitant non-suppressed TSH. Case Report: Here, we describe a rare case of RTHβ in a female adolescent who was initially misdiagnosed and treated for Graves’ disease, but whose unusual evolution motivated her transference to a tertiary center. The patient exhibited mild manifestations, presenting with a goiter without compressive symptoms and some degree of cognitive impairment with learning disability. Misdiagnosis of RTHβ as Graves’ disease can lead to unnecessary treatments such as anti-thyroid medication, thyroidectomy or radioiodine, but treatment is generally not necessary for most patients with RTHβ. Discussion and Conclusion: Establishing the diagnosis of RTHβ can be challenging. It must be considered in patients who present with a goiter and increased thyroid hormone levels with an unsuppressed TSH, to potentially avoid an incorrect diagnosis of primary hyperthyroidism and the implementation of unnecessary and harmful treatments. Most patients with RTHβ are asymptomatic, and in children, particular attention must be paid to growth, bone maturation, and mental development.

LBODP100 A Rare Case Of Pembrolizumab Induced Graves’ Disease

Abstract Cancer immunotherapies have recently changed the therapeutic armamentarium of anti-cancer treatments, particularly for melanoma and cancers of the kidneys, lungs, and colon. Immune checkpoint inhibitors (ICPis) act on various immune checkpoints. Of them, anti-PD-1 antibodies (such as pembrolizumab) are monoclonal antibodies that act against programmed cell death 1 protein. However, by counteracting the regulators of adaptive immunity, this class of drugs may cause immune-related adverse events that involve multiple organs and endocrine glands, such as the thyroid gland. The symptoms of thyroid dysfunction usually present during the first weeks of ICPis therapy. In the current report, we present a case of a 50-year-old male who presented to the emergency department complaining of fever, chills, nausea, and vomiting for one week. The patient had a history of colon cancer with lymph node metastasis status post tumor resection and colostomy. He began Keytruda® (pembrolizumab) treatment after tumor resection, and the presenting symptoms appeared after receiving the first immunotherapy infusion. His medical history was significant for psoriasis and rheumatoid arthritis. The patient's history was unremarkable for thyroid diseases, and he did not receive thyroid medications with no previous exposure to intravenous contrast media, over-the-counter iodine preparations, or biotin. At the emergency department, the patient had a temperature of 101.4°F, a heart rate of 110 bpm, and blood pressure of 130/70 mm Hg. On examination, tenderness was indicated upon palpating the anterior part of the neck. The patient was treated with intravenous fluids, steroids, beta-blockers, and broad-spectrum antibiotics. A workup for sepsis was requested, and it revealed negative blood culture and urine culture results. His laboratory indices demonstrated a suppressed level of TSH (0. 01 mIU/mL) and elevated Free T4 (3.16 ng/dl). Still, his TSH level reported at the Oncology clinic before Keytruda administration was (0.9 mIU/mL), and Free T4 was (1.7 ng/dl). Thyroid ultrasound revealed a heterogeneous thyroid gland consistent with thyroiditis. Antibody testing showed positive thyroid antithyroglobulin antibodies and elevated thyroid-stimulating antibodies (TSI). A radioactive iodine uptake test was ordered, revealing increased contrast uptake. These findings suggested that the cause of thyroid dysfunction was Graves’ disease. The patient was started on Methimazole 20mg per day and discharged home after scheduling an outpatient follow-up appointment with the endocrinologist. This case is one of the rare cases of thyrotoxicosis attributable to Graves’ disease related to pembrolizumab therapy. To the best of our knowledge, two studies in the literature reported three cases of ICPi-induced thyrotoxicosis with thyroid antibody positivity following anti-PD-1 antibody therapy. Presentation: No date and time listed

Asymptomatic Pyriform Sinus Tract Easily Mistaken for Thyroid Nodule

A pyriform sinus tract/fistula is a rare clinical condition where remnants of the third or fourth pharyngeal pouches extend into the pyriform sinus, forming an internal tract. Common initial presentations of pyriform sinus tract/fistulas are cervical cystic masses in neonates or cervical infections in children but there have been a few reported cases of incidental detection of pyriform sinus tracts in adults. A 62-year-old man was referred from a local clinic for evaluation of a hypoechoic thyroid nodule with calcifications on ultrasonography (US). He had no symptoms of thyroid dysfunction or infection and was euthyroid on laboratory results. Neck US was re-performed in our institution and an air-containing nodule was observed in the posterior aspect of the left thyroid gland. Esophagography was performed to identify this lesion, revealing an obstructed sac structure communicating with the left pyriform sinus. The patient was diagnosed with a pyriform sinus and referred to an otolaryngologist.

Radiofrequency Ablation of Solid Benign Thyroid Nodules

Symptomatic solid benign thyroid nodules may present either as nonfunctioning nodules causing compressive symptoms or as hyperfunctioning nodules causing symptoms of hyperthyroidism. While surgical resection or radioiodine ablation of these nodules can be performed, percutaneous radiofrequency ablation (RFA) of benign solid thyroid nodules has been shown to be a safe and effective alternative in select patients. Preprocedural evaluation should include a history focusing on signs and symptoms of thyroid dysfunction, a physical exam, thyroid ultrasound, thyroid function tests, and discussion of key intraprocedural details with the patient such as the anesthesia plan and risks. Thyroid RFA can be safely performed as an outpatient procedure with less than 2% major and minor complication rates. This report will focus on the basic technique of performing RFA for symptomatic thyroid nodules.

COMPARATIVE EVALUATION OF STRUCTURAL AND FUNCTIONAL CHANGES IN THYROID GLAND AFTER IMPLEMENTATION OF INTEGRATED YOGA MODULE (IYM) AS ADJUNCT THERAPY VERSUS CONVENTIONAL LEVOTHYROXINE THERAPY IN HYPOTHYROID FEMALES

Thyroid disorders have become quite common worldwide over the past few decades. Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population. Hypothyroid is the most prevalent thyroid dysfunction and more so in females. Despite the problem being so common, there is no proper treatment modality to control this condition. Many of the as an as have a powerful effect on one or more of the endocrine glands. Practicing some of the specific as an as stimulates the activity thyroid gland and its functions. Hence this study is proposed to generate evidence for yogic practices as an adjunct modality for patients of hypothyroid. The objective of this study is to evaluate the structural and functional changes occurring in patients with hypothyroid as a result of the practice yogic module. The effectiveness of adjunct therapy and the quality of life of patients will also be assessed. 120 female patients of hypothyroid will be randomly allotted to an experimental and control group with 60 patients in each group. Group A will be made to follow the yogic practice module designed along with the conventional treatment whereas Group B will continue with regular conventional treatment. We anticipate that the Yogic module works as an effective adjunct treatment for patients of hypothyroidism and can be used as the first line of treatment in newly diagnosed cases of hypothyroid. Integrated yoga Module will be the new inclusion in the therapeutic model of hypothyroid and also can be studied in different endocrine disorders.

Thyroid Dysfunction and Dysmetabolic Syndrome: The Need for Enhanced Thyrovigilance Strategies.

Thyroid dysfunction (TD) is common in metabolic disorders such as diabetes mellitus (DM), cardiovascular disease (CVD), obesity, dyslipidemia, hyperuricemia, kidney and liver dysfunctions, and polycystic ovary syndrome (PCOS). Subclinical hypothyroidism (SHypo) worsens glycemic control in patients with DM, and these patients, especially those with Type-1DM, have higher prevalence of TD. Both TD and DM increase CVD risk. Even minor alteration in thyroid hormone (TH) levels can alter cardiovascular function. While hyperthyroidism increases systolic blood pressure and leads to high-output heart failure, hypothyroidism increases diastolic blood pressure and leads to low-output heart failure. Chronic subclinical hyperthyroidism (SHyper) and SHypo both increase the risk of hypertension, coronary artery disease (CAD) events, CAD deaths, and total deaths. SHyper alters cardiac morphology and function. SHypo causes dyslipidemia and endothelial dysfunction and increases the risk for weight gain and obesity. Overweight and obese patients often have hyperleptinemia, which increases the secretion of thyroid stimulating hormone (TSH) and induces TD. Dyslipidemia associated with TD can increase serum uric acid levels. Hyperuricemia promotes inflammation and may increase the risk for dyslipidemia, atherosclerosis, and CVD. TD increases the risk for developing chronic kidney disease. In nephrotic syndrome, proteinuria is associated with urinary loss of TH leading to TD. Some correlation between TD and severity of liver disease is also seen. TD and PCOS have common risk factors and pathophysiological abnormalities. Hypothyroidism must be excluded before diagnosing PCOS. Current guidelines do not strongly recommend thyroid screening in the presence of all metabolic disorders. However, pragmatic thyrovigilance is required. Clinicians must stay alert to signs and symptoms of TD, maintain high clinical suspicion, and investigate thoroughly. Drug-induced TD should be considered when TH levels do not match clinical findings or when patients are on medications that can alter thyroid function.

Thyroid Function in Children with Down Syndrome in the Polish Population: A Case-Control Study.

Patients with subclinical thyroid disease have few or no clinical symptoms of thyroid dysfunction and thus, laboratory diagnosis is needed. In this context, the objective of the current study was to analyze the prevalence rate and pattern of thyroid function in children with Down syndrome in the Polish population. A total of 30 children, aged 6-12 years, with cytogenetically confirmed Down syndrome were studied. The control group included 27 children. Of the 30 patients with Down syndrome, 14 (46.7%) had abnormal thyroid profiles. Mean thyroid-stimulating hormone (TSH) and fT4 concentrations in children with Down syndrome were found to be significantly increased compared with the controls (4.30 ± 1.9 µIU/mL, 95% CI: 3.55-5.04 µIU/mL vs. 3.10 ± 1.47 µIU/mL, 95% CI: 2.52-3.68 µIU/mL, P = 0.013, 95% CI: 0.26-2.14, and 1.33 ± 0.23 ng/dL, 95% CI: 1.25-1.42 vs. 1.19 ± 0.14 ng/dL, 95% CI: 1.13-1.25, P = 0.008, 95% CI: 0.04-0.24, respectively). In Down syndrome, subclinical hypothyroidism was recognized in 10 children (33.3%) (high TSH and normal fT4 and fT3 levels). Two children (6.67%) had evident hypothyroidism (high TSH and low fT4). In the control group, subclinical hypothyroidism was diagnosed in four (14.8%) children. Children with Down syndrome may have increased secretion of TSH, even when thyroid hormone and autoantibodies are normal, suggesting that an isolated increase in TSH does not predispose the patient to the development of thyroid disease. We also recommend that all patients with Down syndrome should be screened for thyroid dysgenesis, since they have thyroid dysfunction more frequently as compared to the general healthy population.

Estimation of Thyroid Stimulating Hormone Level in Normal Female School Children in a Semi Urban Indian Town- Kumbakonam Urban Rural Epidemiological Study-KURES-2

Symptoms of thyroid dysfunction are non-specific, yet common and hence screening for abnormalities becomes a necessity. To identify subclinical thyroid dysfunction and offer them the correct medical treatment especially in adolescent female children is an excellent option as a public health prophylactic measure. Hence in this study, we sampled 264 asymptomatic school female children for TSH and found an incidence of 3.4% of high TSH (>5). On the other side, the lower values were found in six (if TSH <0.5) or only two children (if TSH < 0.4). The mean with standard error of TSH values were 2.99 ± 0.567. The fasting status was not complied with, and all were random blood samples. All children with abnormal results were counselled with parents and necessary medical advice given. This prevalence is the lowest among similar studies done in any Asian country which is a new finding in our study. Only one child showed a value of 150 who was given drugs and followed up. We theorize that this lesser incidence may be partly due to the study being done in a delta area of a semiurban town.

Study of menstrual disorders in thyroid dysfunction

Background: Abnormal uterine bleeding is the most common problem seen in patients attending the gynecology OPD. Incidence of AUB is 9 to 14%. Thyroid dysfunction causes broad spectrum of reproductive disorders and is one of the causes noted for abnormal uterine bleeding. Thyroid disorders are 10 times more common in women. Therefore, this study is to assess the menstrual and endometrial patterns in women with thyroid disorders. Aims and objectives 1. To assess the menstrual patterns in women with thyroid disorders. 2. To assess the endometrial patterns in women with thyroid disorders. Methodology: This is a descriptive study conducted in department of OBG, ESIC-PGIMSR Bengaluru. 100 patients with signs and symptoms of thyroid dysfunction will be taken. Patients will be grouped into 3 categories- hyperthyroid, hypothyroid and Subclinical hypothyroidism. Menstrual pattern in these patients are studied. Selected patients in peri-menopausal age group with thyroid dysfunction will be subjected to endometrial biopsy. Results: Most common thyroid dysfunction is hypothyroidism seen in 60% of the patients. Most common menstrual irregularity is menorrhagia seen in 51% of the patients. In hypothyroidism patients menorrhagia is seen in 48.3%, in hyperthyroidism, menorrhagia is seen in 35.3% and in subclinical hypothyroidism it is seen in 69.6%of patients. Most common endometrial pattern is simple hyperplasia without atypia seen in 50% of the patients. Conclusion: The present study concludes that there is a strong association between thyroid dysfunction and menstrual irregularities. Thyroid profile should be used in the screening of all the women with abnormal uterine bleeding. If thyroid dysfunction is timely detected and corrected, then menstrual irregularities will settle and unnecessary interventions like endometrial curettage and surgery could be avoided.

Periodontal status of hypothyroid patients on thyroxine replacement therapy: A comparative cross-sectional study.

Background:Thyroid hormones play a significant role in bone remodeling. However, there are few studies on the effect of these hormones on periodontium.Aim:The aim of this study was to evaluate the periodontal status of hypothyroid patients on thyroxine replacement therapy.Materials and Methods:Clinical parameters (plaque index, bleeding index, probing pocket depth [PPD], and clinical attachment level [CAL]) and radiographic parameters (Mandibular cortical width and panoramic mandibular index) were recorded in 52 hypothyroid patients on thyroxine replacement therapy (Study group) and 50 individuals without signs and symptoms of thyroid dysfunction (Control group). The effect of dosage and duration of therapy on clinical and radiographical parameters were also assessed in the study group.Results:Statistically significant higher PPD (P = 0.008) and clinical attachment loss (P = 0.032) were observed in the study group in comparison to the control group. However, no significant differences were observed within the hypothyroid group with varying doses and duration of therapy. Furthermore, there was no correlation between the dosage and duration of therapy with periodontal status. Regression analysis showed that hypothyroidism and thyroxine replacement therapy was a significant predictor of PPD and CAL even after controlling for the effect of age in hypothyroid patients.Conclusion:Hypothyroid patients on thyroxine replacement therapy may be at increased risk for periodontal destruction. However, this needs to be validated through longitudinal studies.

The Effect of Electromagnetic Radiation due to Mobile Phone Use on Thyroid Function in Medical Students Studying in a Medical College in South India.

Background:Enormous increase in mobile phone use throughout the world raises widespread concerns about its possible detrimental effect on human health. Radiofrequency waves are emitted by cell phones. They are non-ionising and the effect on the thyroid gland is part of their non thermal effects. The thyroid gland may be particularly vulnerable to this effect because of its normal anatomical position.Materials and Methods:The study was done to explore the association between radiation exposure and thyroid dysfunction among mobile phone users. It had an exploratory design and unit survey method to collect information from all medical students in a medical college in South India. Inclusion criteria included active use of mobile phone prior to and during the study period. Criteria for exclusion was presence of pre-existsting thyroid disease,thyroid nodule,thyroid goitre/nodule and altered thyroid function.Results:The sample size was 83 undergraduate students. 71% of respondents had no family history of thyroid illness. Among the remainder,20.5% had a first degree relative with thyroid dysfunction,8.4% had a second degree relative affected. Clinical examination revealed that 79.5% of the respondents were normal,13.6% had thyroid swelling,3.6% had symptoms of thyroid dysfunction and 3.6% had both thyroid swelling and symptoms of thyroid dysfunction. 53% of the respondents spent 0.5 hrs on an average talking on the phone daily,28.9% spent 1.5 hrs daily and 10.8% of respondents spent over 3.5 hours. We found there was a significant correlation between total radiation exposure and an increase in TSH among both groups –in those with and without family history of thyroid illness.Conclusion:In our study there was a significant correlation between total radiation exposure and increasing TSH values among both all respondents.

Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed - A Review for Primary Care.

Disorders of thyroid function are common, and screening, diagnosis, and management are often performed by primary care providers. While management of significant biochemical abnormalities is reasonably straight forward, laboratory tests only slightly outside, or even within, the normal range are becoming more difficult to appropriately manage. A large part of this increasing difficulty in appropriate management is caused by patients requesting, and even demanding, certain tests or treatments that may not be indicated. Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population. This, along with a growing body of information available to patients via the lay press and internet suggesting that traditional thyroid function testing is not reliable, has fostered some degree of patient mistrust. Increasingly, when a physician informs a patient that their thyroid is not the cause of their symptoms, the patient is dissatisfied and even angry. This review aims to clarify the interpretation of normal and mild abnormalities of thyroid function tests by describing pituitary-thyroid physiology and through an in depth review of, arguably, the three most important biochemical tests of thyroid function: TSH, free T4, and anti-TPO antibodies. It is important for primary care providers to have an understanding of the shortcomings and proper interpretation of these tests to be better able to discuss thyroid function with their patients.

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DECOMPENSATED CIRRHOSIS

Objective: The objective of the study is to find out, the levels of thyroid hormonesin serum of the patients having decompensate cirrhosis and to determine the frequency of signsand symptoms of thyroid dysfunctions in such patients. Study design: Prospective descriptivestudy. Setting: All medical wards of Civil Hospital and Ojha campus, Dow University of HealthSciences, Karachi, Pakistan. Period: May 2013 to January 2015. Methodology: 76 patientshaving decompensated liver cirrhosis with various presentations, which were fulfilling theinclusion and exclusion criteria and were admitted in medical wards during the study period,were included in this study. Detailed history and examination of each case was performed.Thyroid hormone levels were performed along with other relative laboratory investigations andthe results were obtained. Results: Out of 76 patients 58 patients had low serum T3 levels,whereas 18 had normal T3 levels. 65 patients had normal T4 levels and 11 had low serum T4levels. The TSH levels were found normal in 74 patients and two patients had raised TSH levels.Conclusion: It is concluded that T3 levels is low in cirrhotic patients but at the same time T4 andTSH levels remains normal in majority of cases and the patients remain euthyroid. As far as theclinical scenario is concern, no significance was found in the frequency of sign and symptomsof thyroid dysfunction. Most of the patients did not show signs and symptoms of hyper andhypothyroids.

Combination Of Lenalidomide, Dexamethasone and Cyclophosphamide as Treatment For The First Relapse Of Multiple Myeloma: Efficacy, Toxicity and Occurance Of Thyroid Abnormalities

BackgroundLenalidomide is immunomodulatory drug with a range of antineoplastic actions, it is highly effective in multiple myeloma (MM). Lenalidomide has been associated with various adverse side effects including fatigue, constipation, haematological and neurological toxicity. Thyroid dysfunction has been reported as a possible side effect of lenalidomide with incidence 5-10%. Symptoms of thyroid dysfunction can overlap with some side effects of lenalidomide. Thyroid hormone levels are not regularly evaluated in patients (pts) on lenalidomide. AimIn this report we have analysed a cohort of 73 MM pts treated with lenalidomide 25 mg daily (day 1-21, repeating of cycle on day +28) in combination with dexamethasone (160 mg or 320 mg per cycle) and cyclophosphamide 50 mg daily with aims to evaluate efficacy and adverse events of this treatment including of possible occurrance of thyroid impairment. MethodsWe have prospectively evaluated 73 pts with the first relapse of MM who received lenalidomide as a part of the second-line treatment between 2008 and 2012, median follow-up from start of treatment was 24 months (range 2-46), median age was 65 years. Median number of cycles was 6 (range 4-10). Thyroid function tests were checked in regular 2-month intervals from the start to the end of lenalidomide treatment - thyroid stimulating hormone (TSH) and free thyroxine (FT4). ResultsOverall response rate (ORR) was 53% (39/73), 10% (7/73) of pts were in complete remission (CR), very good partial response (VGPR) was achieved in 18% of pts (13/73), partial response (PR) in 25% of pts (19/73), minimal response (MR) or stable disease (SD) in 10% of pts (7/73), progression was observed in 37% of pts (27/73). Median time to progression (TTP) and overall survival (OS) from start of lenalidomide treatment were 18.4 and 29.6 months, respectively. Adverse events (AE) in time of lenalidomide treatment were frequent, but mostly grade 1 or 2. The most frequent AE were as follows: anemia (77%), neutropenia (67%), thrombocytopenia (54%), neuropathy (38%), fatigue (65%), infections (49%) and gastrointestinal toxicity (21%). Grade 3 or 4 adverse events included neuropathy (5%), thrombosis (4%), infections (15%), thrombocytopenia (10%), neutropenia (27%) and fatigue (6%). Previous diagnosis of thyroid dysfunction was presented in four MM pts (5%). New thyroid abnormalities grade 2 were developed on lenalidomide treatment in seven pts (10%). Hypothyreosis was presented in five pts, hyperthyreosis in two pts. Treatment of thyroid dysfunction was necesarry in all seven pts. Median time to occurrance of thyroid dysfunction was 4 months (range 2-8 months). ConclusionLenalidomide is effective treatment for the first relapse of MM with ORR 53%, but lenalidomide can cause various adverse events and significant thyroid abnormalities. Regular routine monitoring of TSH could be recommended in MM patients treated with lenalidomide. Treatment of symptomatic thyroid dysfunction can improve the quality of life for patiens undergoing lenalidomide treatment. Disclosures:No relevant conflicts of interest to declare.

SAT0395 Thyroid Autoimmunity, Not Thyroid Hormone, was Associated with Arterial Stiffness in Euthyroid FM Female Patients.

BackgroundMuscle symptoms are frequent in thyroid diseases, and it has been recognized that there are significant similarities between the clinical findings in FM and symptoms of thyroid dysfunction. Some recent...

Thyroid Dysfunction in Chinese Patients with Chronic Hepatitis C Treated with Interferon Alpha: Incidence, Long-Term Outcome and Predictive Factors

BackgroundThyroid dysfunction (TD) represents an extra-hepatic manifestation of chronic hepatitis C (CHC) and it may also be a side effect of interferon-alpha (IFN-α) based treatment. However, previous studies have shown a wide variation in the incidence of TD in patients with CHC. Furthermore, the long-term outcomes and the predictive factors of TD in patients who receive IFN-α based treatment have still not been fully studied.ObjectivesThe purpose of this study was to describe the incidence and long-term outcomes of TD in Chinese patients with CHC receiving IFN-αbased treatment. We also aimed to identify the predictive factors of TD associated with this type of therapy.Patients and MethodsA retrospective case-series study of 592 consecutive CHC patients with normal baseline thyroid functions, who received IFN-αbased therapy, was performed. Thyroid function was assessed at baseline and every three months during treatment, as well as in the follow-up after cessation of therapy. The incidence and long-term outcomes of TD were observed. The prevalence of pretreatment thyroid peroxidase antibodies (TPOAb) were assayed in a sex- and age-matched nested case-control study. Multivariable stepwise regression analysis was used to explore the independent effects of the baseline factors, on the incidence of TD.ResultsAt the end of the IFN-αbased therapy, 68 patients (11.5%) in the study had developed TD, 58 patients (85.3%) presented with subclinical TD, and only 10 patients (14.7%) developed overt thyroiditis. The thyroid function of 46 patients (67.8%) spontaneously returned to normal in the six months of follow-up and only three patients (4.4%) had persistent overt TD symptoms after the 24 month follow-up period. Multivariate stepwise analysis suggested that gender and pretreatment TPOAb were the independent factors related to the incidence of TD. Both female patients (OR, 4.31; 95%CI, 2.06–7.31; P = 1.26×10-4) and participants with a positive pretreatment TPOAb (OR = 3.9, 95%CI, 1.72–8.54, P = 0.008) had an increased risk for the development of TD.ConclusionsThe incidence of TD in Chinese patients with CHC during IFN-αbased therapy was 11.5%, the majority of which was subclinical, while only a very small group had long-term overt TD requiring ongoing medical therapy. Female gender and pretreatment TPOAb positivity are risk factors for the development of TD during IFN-αbased therapy.

Isotretinoin Associated Reversible Hypothyroidism

Isotretinoin (13-cis retinoic acid) has been regarded as an effective drug for the treatment of acne. Its wide range of adverse effects limits its use, however (1). Isotretinoin has been reported to disturb thyroid function, causing both reversible hypoand hyperthyroidism (1–3), but this impression is not conclusive. The patient presented here supports an association between use of oral 13-cis retinoic acids and reversible hypothyroidism. A 25-year-old woman presented to the Endocrinology Clinic of Aga Khan University Hospital in February 2010 with complains of a weight gain of 3 kg, along with dull mood and mennorrhagia for the previous 3–4 months. There was no history of cold intolerance, constipation, excessive sleep, lethargy, or hair loss. There was no family history of hypothyroidism. Drug history revealed that for 6 months she had taken isotretinoin, 20 mg once daily, for the treatment of acne. This had been stopped about 6 weeks before her presentation. There was no history of alcohol consumption or any other drug intake during this period. On examination, her pulse was 86 beats per minute, blood pressure was 130/80 mm Hg, and weight was 50.5 kg. A small diffuse goiter was noted; the remainder of her physical examination was unremarkable. Thyroid function tests done 1 month before visit, approximately 2 weeks after stopping the isotretinoin, showed a serum thyroid-stimulating hormone (TSH) of 78.97 mIU/mL (normal range 0.4–4.2), triiodothyronine of 1.51 nM (normal range 1.3–3.1), and thyroxine of 4.42 mg/dL (normal range 5.0–12.0). As she reported progressive improvement in her symptoms over the previous month, thyroid hormone replacement therapy was not instituted and she was asked to repeat her serum TSH. Her TSH done on the day of visit, that is, 6 weeks after stopping isotretinoin, was 15.03 mIU/mL. There was no history of thyrotoxic phase during the preceding several months that could have suggested the hypothyroid phase of thyroiditis. She was advised to follow-up in 6 weeks. When she presented again in March for another visit, she was symptom free. Her lab work-up on that day, 12 weeks after stopping isotretinoin, showed a serum TSH of 3.33 mIU/mL and antithyroid peroxidase enzyme levels of 3.30 IU/mL (<12 IU/mL). She was advised to follow-up in case of recurrence of symptoms and have her serum TSH repeated after 6 months. The effects of vitamin A derivatives on thyroid function have been a topic of interest for a number of years. Bexarotene, a compound closely related to isotretinoin, causes hypothyroidism both by central mechanism and by increasing the peripheral degradation of thyroid hormones by a nondeiodinase mediated pathway (4). In the study conducted by Marsden et al. (2), seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 weeks. Their levels of serum triiodothyronine and thyroxine were significantly lower after treatment, but the response to thyrotropin releasing hormone (TRH) stimulation was retained. These findings were partially attributed to induction of hepatic microsomal enzymes by isotretinoin. Another study conducted by Lyons et al. (1) showed mild decrease in the indices of thyroid function after treatment with 0.8 mg/kg 13-cis retinoic acid for 3 months. It was noticed that these changes reverted to normal 1 month after discontinuation of therapy. Oral isotretinoin therapy is increasingly used as an effective antiacne medication. It needs to be kept in mind that this drug could have antithyroid effects in susceptible patients. Therefore, there should be a low threshold for checking thyroid function tests in patients taking isotretinoin even if they have subtle signs or symptoms of thyroid dysfunction.

High Iodine Content of Korean Seaweed Soup: A Health Risk for Lactating Women and Their Infants?

Iodine requirements increase during pregnancy and lactation due to increased maternal thyroid hormone production and iodine excretion, fetal iodine requirements, and loss of iodine in breast milk. Seaweed preparations are a source of dietary iodine. Korean and many Korean-American women traditionally consume brown seaweed soup (Undaria pinnatifida) daily during the early postpartum period (Supplementary Data; Supplementary Data are available online at www .liebertonline.com/thy) (1). This tradition is maintained among Korean and Korean-American women such that their breast milk iodine correlates strongly with frequency and quantity of seaweed soup consumption (2,3). As the iodine content of this soup has not been reported, we randomly selected 10 brands of dried brown seaweed from Korea and China available in the United States. Seaweed soup from each brand was prepared utilizing the following ingredients: 1 oz of dried seaweed, 6 cups water, 1⁄4 pound beef, 11⁄2 tablespoons soy sauce, 2 teaspoons sesame oil, 1 teaspoon garlic, and *1⁄2 teaspoon noniodized sea salt (Supplementary Data). Iodine content of the dried seaweeds and the soups were measured spectrophotometrically after digestion with hydrochloric acid and dilution with iodine free deionized water, as described by Benotti et al. (see Supplementary Data). The mean iodine content of the dried seaweed was 359 254 mg/g (mean SD), or 10173 7200mg/oz. The mean iodine content of seaweed broth was 1.9 0.7 mg/mL, with 1 bowl (250 mL) of broth containing an average of 487 178 mg of iodine. The mean iodine content of blended seaweed soup contents (broth, cooked seaweed) was 1705 930 mg/250 mL. Potential sources of variability in soup iodine (see Supplementary Data) include the iodine contents of dry seaweed and other ingredients (e.g., iodized salt, iodine-containing soy sauce, and anchovy soup base), cooking methodologies, and the quantity of seaweed in recipes (4). The iodine content of seaweed varies with harvest location and season, salinity and temperature of water, depth and portion of seaweed harvested, and storage conditions (4). The World Health Organization (WHO) guidelines recommend 250 mg/day of iodine intake during pregnancy and lactation, whereas the Institute of Medicine (IOM) recommends 220mg/day of iodine intake during pregnancy and 290 mg/day during lactation (Supplementary Data). The IOM recommends a tolerable upper limit of iodine intake of 1100mg/day, whereas the WHO suggests an upper limit of 500mg/day for pregnant and lactating women and 180mg/ day for infants. More than 90% of postpartum lactating Korean women consume seaweed soup at least three times daily in the first postpartum week, and up to 75% of these women have seaweed soup at least once daily up to 4 weeks postpartum (3). Our findings indicate that this constitutes an average iodine intake of at least 1400 mg/day in the first postpartum week based solely on 250 mL seaweed soup broth three times daily, and at least 5000mg/day if the entire contents of each serving are consumed (broth and seaweed). High levels of breast milk iodine values in Korean postpartum women have been reported (2,3). Depending on quantity and frequency of intake, postpartum women who consume Korean seaweed soup may have daily iodine intakes and breast milk iodine concentrations that far exceed the WHO and IOM upper limits. Iodine-induced hypothyroidism, iodine-induced thyrotoxicosis, and iodine-induced goiter are potential adverse effects of excess iodine consumption. However, the effects of high iodine intake are dependent on several factors, including iodine status (i.e., degree and duration of iodine deficiency or sufficiency) before excess iodine exposure, as well as any preexisting thyroid autoimmunity, thyroid dysfunction, and/or thyroid nodularity. Chung et al. reported subclinical hypothyroidism in preterm Korean infants exposed to high iodine content in breast milk (2). Additionally, cases of iodine-induced neonatal hypothyroidism due to maternal seaweed consumption were reported in Australia. Increased incidence and/or exacerbation of postpartum thyroiditis are also potential risks of high iodine intake. However, these effects were not observed in the only Korean study to date evaluating this relationship. Further studies should be carried out to evaluate the potential adverse effects of sustained high dietary iodine in postpartum women of Korean descent and their infants. In addition, there should be a raised cultural awareness among endocrinologists and other medical providers regarding this common source of high dietary iodine. A careful dietary history should be part of the evaluation and follow-up of postpartum Korean women and their infants, especially in the setting of signs and/or symptoms of thyroid dysfunction, thyroid autoimmunity, nodular thyroid anatomy, or pre-existing thyroid dysfunction. In addition, Korean women