Thyroid Failure Research Articles

A 2013 Survey of Clinical Practice Patterns in the Management of Primary Hypothyroidism

In 2012, comprehensive clinical practice guidelines (CPGs) were published regarding the management of hypothyroidism. We sought to document current practices in the management of primary hypothyroidism and compare these results with recommendations made in the 2012 American Thyroid Association (ATA)/American Association of Clinical Endocrinologists (AACE) hypothyroidism CPGs. In addition, we sought to examine differences in management among international members of U.S.-based endocrine societies and to compare survey results with those obtained from a survey of ATA members performed 12 years earlier. Clinical members of The Endocrine Society (TES), the ATA, and the AACE were asked to take a web-based survey consisting of 30 questions dealing with testing, treatment, and modulating factors in the management of primary hypothyroidism. In total, 880 respondents completed the survey, including 618 members of TES, 582 AACE members, and 208 ATA members. North American respondents accounted for 67.6%, Latin American 9.7%, European 9.2%, Asia and Oceania 8.1%, and Africa and Middle East 5.5%. Overt hypothyroidism would be treated using l-T4 alone by 99.2% of respondents; 0.8% would use combination l-T4 and liothyronine (l-T3) therapy. Generic l-T4 would be used by 49.3% and a brand name by 49.9%. The rate of replacement would be gradual (38.5%); an empiric dose, adjusted to achieve target (33.6%); or a calculated full replacement dose (27.8%). A target TSH of 1.0 to 1.9 mU/L was favored in the index case, but 3.0 to 3.9 mU/L was the most commonly selected TSH target for an octogenarian. Persistent hypothyroid symptoms despite achieving a target TSH would prompt testing for other causes by 84.3% of respondents, a referral to primary care by 11.3%, and a change to l-T4 plus l-T3 therapy by 3.6%. Evaluation of persistent symptoms would include measurement of T3 levels by 21.9% of respondents. Subclinical disease with a TSH 5.0 to 10.0 mU/L would be treated without further justification by 21.3% of respondents, or in the presence of positive thyroid peroxidase antibodies (62.3%), hypothyroid symptoms (60.9%), high low-density lipoprotein (52.9%), or goiter (46.6%). The TSH target for a newly pregnant patient was <2.5 mU/L for 96.1% of respondents, with 63.5% preferring a TSH target <1.5 mU/L. Thyroid hormone levels would be checked every 4 weeks during pregnancy by 67.7% and every 8 weeks by an additional 21.4%. A hypothyroid patient with TSH of 0.5 mU/L who becomes pregnant would receive an immediate l-T4 dose increase by only 36.9% of respondents. The current survey of clinical endocrinologists catalogs current practice patterns in the management of hypothyroidism and demonstrates 1) a nearly exclusive preference for l-T4 alone as initial therapy, 2) the widespread use of age-specific TSH targets for replacement therapy, 3) a low threshold for treating mild thyroid failure, 4) meticulous attention to TSH targets in the pregnant and prepregnant woman, and 5) a highly variable approach to both the rate and means of restoring euthyroidism for overt disease. Both alignment and focal divergence from recent CPGs are demonstrated.

Autoimmune thyroiditis with minimal change disease presenting acute kidney injury

Autoimmune thyroiditis is the most common cause of hypothyroidism in the world. It is characterized clinically by gradual thyroid failure, goiter formation, or both, because of the autoimmune-mediated destruction of the thyroid gland. Renal involvement presenting proteinuria in autoimmune thyroiditis is not uncommon, occurring in 10% to 30% of the cases. Glomerulonephropathy associated with autoimmune thyroiditis, however, is a rare disease. Most reports of autoimmune thyroiditis with glomerulonephropathy have demonstrated a mixed pathological morphology and have been predominantly associated with membranous glomerulopathy. The case of minimal-change disease associated with thyroiditis presenting acute kidney injury is a rare disease that has not been reported in South Korea. Reported herein is the case of a 16-year-old man diagnosed with Hashimoto’s thyroiditis, with minimal-change disease presenting acute kidney injury. He revealed hypothyroidism, proteinuria, and impaired renal function. Renal biopsy showed minimal-change disease and minimal tubular atrophy. The patient was treated with thyroid hormone, and his renal function and proteinuria improved. Therefore, for patients with autoimmune thyroiditis presenting unexplained proteinuria, glomerulonephropathy should be ruled out. Conversely, for patients with glomerulonephropathy and persistent proteinuria despite proper treatment, thyroid function and antibody tests should be performed.

Study of thyroid function in Egyptian children with β-thalassemia major and β-thalassemia intermedia

Thyroid dysfunction is a known complication of transfusion-dependent β-thalassemia. However, information on its frequency and risk factors among Egyptian Children is still unclear. We aimed to determine the frequency of functional thyroid abnormalities among young patients with β-thalassemia and compare the thyroid function status among patients with β-thalassemia major (TM) and β-thalassemia intermedia (TI). This was a cross-sectional study that included 52 β-thalassemia children [27 boys and 25 girls; 34 (65.4%) with TM and 18 (34.6%) with TI]. Their mean age was 16.0±1.91 (range: 12-18) years. Thyroid function and iron load status were assessed by measurement of free tetraiodothyronine, free triiodothyronine, thyroid stimulating hormone (TSH), and serum ferritin concentrations. Serum TSH of the studied cases ranged from 0.28 to 25 μIU/ml with a mean of 4.5±4.8 μIU/ml. None of the studied cases had overt primary hypothyroidism and the frequency of subclinical hypothyroidism was 19.2%. No risk factors for thyroid dysfunction could be identified among our cases. The thyroid profile was comparable in TM and TI patients (P>0.05) and the frequency of subclinical hypothyroidism among TM cases was 20.6% and it was comparable to the 16.7% found among TI patients (P>0.05). No correlations were found between TSH, serum ferritin, chelation therapy, and frequency of blood transfusion. Both TM and TI patients are at risk for subclinical thyroid failure regardless of their iron overload status. Early evaluation of thyroid function in β-thalassemia children and thyroid replacement therapy for subclinical hypothyroidism should be introduced in the treatment protocols.

A Longitudinal Study of Changes in Thyroid Related Hormones among Pregnant Women Residing in an Iodine Deficient Urban Area

Problem Statement. Thyroid gland in women undergoes functional changes during pregnancy. A few studies have described such changes in pregnant women residing in iodine deficient areas. Objective. To document these changes in pregnant women residing in Lahore, a low iodine intake urban area of Pakistan. Patients and Methods. In 254 pregnant women, data of FT4, FT3, and TSH during the first and subsequent trimesters were obtained and compared with those of 110 nonpregnant women. These hormones were determined in serum by radioimmunoassay (RIA) techniques using commercial kits. Results. Compared to nonpregnant women mean FT4 level was decreased, and FT3 and TSH increased significantly (P < 0.05) in pregnant women. A negative correlation of FT4 with TSH was observed in all three trimesters. Serum FT3 was positively correlated with TSH only during the third trimester. As a function of gestation time, FT4 levels progressively decreased, and FT3 and TSH levels increased significantly (one-way ANOVA F = 108.2, 17.3, and 44.8, resp.; all P < 0.05) exhibiting thyroid gland adaptations. Conclusion. Pregnancy is associated with significant alterations in thyroid function due to low iodine intake in women residing in study area. The compensated thyroid function poses a risk of thyroid failure in a number of pregnant women.

Unexplained Somatic Symptoms due to Depression and / or Subclinical Hypothyroidism

Background: Unexplained somatic symptoms are common presentation of many diseases including subclinical hypothyroidism and depression. Subclinical hypothyroidism (mild thyroid failure) represents an early stage of thyroid disease that will commonly progress to overt hypothyroidism. Objectives: To assess the presence of depression and subclinical hypothyroidism (mild thyroid failure) in patients presenting with unexplained somatic symptoms aiming for better care provided to those patients. Special care should be provided to females as they are more likely to be affected by both conditions. Method: Patients were collected conveniently from those attended internal medicine clinic during the period from January to August 2013 complaining from multiple unexplained somatic symptoms. Patients with clinical hypothyroidism or anemia or other cause of their presenting somatic complaints were excluded from the study. Remaining 48 patients were having only unexplained somatic symptoms which proved after investigation to have subclinical hypothyroidism with high TSH while their T4 were normal. Then they were screened for depression byPatient Health Questionnaire 9 (PHQ-9), fatigue severity scale (FSS), Somatic Symptom Inventory (SSI), and Sheehan Disability Scale (SDS) for measurement of functional impairment. Results: Females (n=36) represent 75% of cases while males (n=12) represent only 25% of cases. FSS was significantly higher in females than males (t=2.373, p=0.023). Fatigue is the most common presenting symptom among all patients (n=21, 43.7%) followed by weight gain (n=16, 33.3%) and lastly generalized aches (n=11, 22.9%). More females presented with fatigue (n=15, 72.7%) than males (n=6, 28.6%). Females are earlier than males to seek medical advice. Only 19 patients (39.6%) were presented early and females were majority of them (n=17, 89.5%). There were positive correlations between severity of depression and (physical symptoms severity, fatigue, and degree of functional disability). There were significant negative correlations between T4 serum level and (depression severity and degree of functional disability). Conclusion: Mild thyroid failure frequently progresses to overt hypothyroidism. It may clearly be associated with somatic symptoms, depression, memory and cognitive impairment. It is common more in females than males regardless their age. Early detection & treatment of mild thyroid failure and depression has been reported to be cost-effective and can prevent further functional impairment.

Subclinical thyroid disease

Subclinical thyroid disease is a common finding on testing of thyroid function and its management remains controversial. Epidemiological data from large population studies from USA and Europe. There is an increased risk of progression to overt hypothyroidism or hyperthyroidism. The treatment of mild thyroid failure is of importance in optimizing pregnancy outcome. Diagnostic criteria differ and there is variation between management guidelines. The difference was found in long-term clinical outcomes between endogenous and exogenous subclinical hyperthyroidism. Meta-analyses have provided epidemiological data in cardiovascular mortality and morbidity in subclinical thyroid disease. Increased use of echocardiography and bone markers in identifying those who benefit from intervention. A randomized controlled trial to identify those subjects identified from screening programmes that benefit from intervention in terms of morbidity and mortality.

Diagnosis of Hashimoto’s thyroiditis in ultrasound using tissue characterization and pixel classification

Hashimoto's thyroiditis is the most common type of inflammation of the thyroid gland, and accurate diagnosis of Hashimoto's thyroiditis would be helpful to better manage the disease process and predict thyroid failure. Most of the published computer-based techniques that use ultrasound thyroid images for Hashimoto's thyroiditis diagnosis are limited by lack of procedure standardization because individual investigators use various initial ultrasound settings. This article presents a computer-aided diagnostic technique that uses grayscale features and classifiers to provide a more objective and reproducible classification of normal and Hashimoto's thyroiditis-affected cases. In this paradigm, we extracted grayscale features based on entropy, Gabor wavelet, moments, image texture, and higher order spectra from the 100 normal and 100 Hashimoto's thyroiditis-affected ultrasound thyroid images. Significant features were selected using t-test. The resulting feature vectors were used to build the following three classifiers using tenfold stratified cross validation technique: support vector machine, k-nearest neighbor, and radial basis probabilistic neural network. Our results show that a combination of 12 features coupled with support vector machine classifier with the polynomial kernel of order 1 and linear kernel gives the highest accuracy of 80%, sensitivity of 76%, specificity of 84%, and positive predictive value of 83.3% for the detection of Hashimoto's thyroiditis. The proposed computer-aided diagnostic system uses novel features that have not yet been explored for Hashimoto's thyroiditis diagnosis. Even though the accuracy is only 80%, the presented preliminary results are encouraging to warrant analysis of more such powerful features on larger databases.

Is Subclinical Hypothyroidism a Cardiovascular Risk Factor in the Elderly?

The negative impact of subclinical hypothyroidism (sHT) on cardiovascular risk, widely recognized in young adults (aged <55-60 y), is still debated in the elderly (>65 y), especially in the oldest olds (>80 y). We searched Medline for reports published with the following search terms: "hypothyroidism," "subclinical hypothyroidism," "ageing," "elderly," "L-thyroxin," "thyroid," "guidelines," "treatment," "quality of life," "cardiovascular risk," "heart failure," "coronary heart disease" (CHD), "atherosclerosis," and "endothelial dysfunction." We limited our search to reports in English published after 1980, although we incorporated some reports published before 1980. We supplemented the search with records from personal files, textbooks, and relevant articles. Analyzed parameters included the epidemiology of thyroid failure, the effect of thyroid hormone on the aging process, cardiovascular function, and CHD risk factors. We also included the potential benefits of L-T4 therapy on the quality of life, cardiovascular events, and survival. TSH levels increase with age, even in older people without thyroid disease. Most longitudinal studies show an increased risk for CHD events and mortality in sHT participants. This increase is less evident in the elderly, mainly in cases of serum TSH values above 10 mIU/L. Lower mortality rate in a cohort of the oldest olds (>85 y) has been reported. sHT in older people should be not regarded as a unique condition, and moderately old patients (aged <70-75 y) could be considered clinically similar to the adult population, albeit with a higher optimal TSH target value. Conversely, the oldest old subjects should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. The decision to treat elderly people is still an unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment.

Hypothyroidism in dogs: pathophysiology, causes and clinical presentation

Hypothyroidism is the most common endocrine disorder in dogs. Primary hypothyroidism is most common, resulting from primary thyroid gland failure associated with either lymphocytic thyroiditis or idiopathic follicular atrophy, both of which occur at approximately equal frequency. Lymphocytic thyroiditis is considered an immune-mediated disease, whereas the pathogenesis of idiopathic follicular atrophy is unknown. Secondary hypothyroidism results from failure of the pituitary gland, and accounts for less than 5% of cases.

Subclinical Hypothyroidism and Heart Failure Risk in Older People

Although the negative impact of subclinical hypothyroidism (sHT) in terms of cardiovascular risk in young adults is mostly acknowledged it remains to be established in the elderly, especially in the oldest old. We searched Medline for reports published with the following search words: hypothyroidism, sHT, ageing, elderly, L-thyroxin, thyroid, guidelines, treatment, quality of life, cardiovascular risk, heart failure (HF), ischemic heart disease (IHD), endothelial dysfunction. The search was restricted to reports published in English since 1980, but some reports published before 1980 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included epidemiology of sHT and thyroid failure the effect of thyroid hormone on ageing process and cardiovascular function as well as the potential benefits of L-thyroxin therapy on quality of life, HF progression and events. TSH levels increase with age, even in older patients without thyroid disease, in whom higher TSH value might favor longevity; better quality of life and lower IHD mortality in the oldest old population has been reported yet. However, at odds with the relationship between sHT and IHD risk and mortality, which shows a clear age dependent feature, vanishing in the last decades of life, the detrimental effect of sHT on HF progression and events remains evident also in older patients, although no data are available in the oldest old population. The lack of specific randomized trials enrolling either old or very old subjects, aimed at evaluate the efficacy of hormonal replacement on overall survival and cardiovascular risk reduction along with the negative effects of possible over-treatment, makes the decision to treat older people a still unresolved clinical challenge. Moreover, the possibility that restoring euthyroidism may be harmful in the elderly should be always taken into account.

Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers

Subclinical hypothyroidism (SH) is a condition characterized by a mild persistent thyroid failure. The main cause is represented by autoimmune thyroiditis, but mutations in genes encoding proteins involved in TSH pathway are thought to be responsible for SH, particularly in cases arising in familial settings. Patients with the syndrome of TSH unresponsiveness may have compensated or overt hypothyroidism with a wide spectrum of clinical and morphological alterations depending on the degree of impairment of TSH-receptor (TSH-R) function. We describe the case of two brothers with non autoimmune SH carrying the same heterozygous mutation in the extracellular domain of TSH-R and presenting with different clinical, biochemical and morphological features. The first one had only a slight persistent elevation of TSH, a normal thyroid ultrasound and did never require l- thyroxine (L-T4) replacement treatment. The second one had a neonatal persistent moderate TSH levels increase associated with a thyroid gland hypoplasia and was treated with L-T4 since the first months of life.These two cases support the recent association of TSH-R mutations inheritance as an autosomal dominant pattern with variable expressivity and suggest that the decision to start replacement therapy in patients with persistent SH due to TSH resistance should be individualized.

Changing trends in surgery for Graves’ disease: A cohort comparison of those having surgery intended to preserve thyroid function with those having ablative surgery

BackgroundSurgery for Graves’ disease may be performed with the intent of preserving thyroid function (subtotal thyroidectomy) or ablating thyroid function (total thyroidectomy). This study examines the evolving practice in a specialist endocrine surgical unit.MethodLongitudinal cohort study of patients undergoing surgery for Graves’ disease between 1986 and 2008. Outcome measures were thyroid failure, recurrent toxicity, recurrent laryngeal nerve (RLN) palsy, early reoperation and hypocalcaemia. Time to thyroid failure was analysed by potential predictors.ResultsOf 149 patients (129 female), 78 (52.3 percent) underwent subtotal thyroidectomy with the intention to preserve function (PF) and 71 (47.6 percent) total thyroidectomy with the intention to ablate thyroid function (AF). Mean duration of follow-up was 11.1 years; 14.8 years and 7.0 years respectively. Of 78 PF procedures: six (7.7 percent) patients suffered recurrent toxicity; 68 (87.2 percent) developed thyroid failure (four after treatment for recurrent toxicity); and eight (10 percent) remained euthyroid without replacement. Male gender and remnant gland weight were significant predictors of failure (P = 0.021 and 0.022 respectively). One patient developed permanent RLN palsy and one permanent hypocalcaemia. Of 71 AF procedures: one developed acute airway obstruction; one permanent RLN palsy; four permanent hypocalcaemia; and none developed recurrent toxicity. There were no deaths within a year of surgery. There was no statistically significant difference in complication rates.ConclusionMost PF resections resulted in eventual thyroid failure. The shift to ablative surgery virtually eliminated the need for lifelong specialist follow-up, albeit with an insignificant rise in permanent hypocalcaemia.

Dyslipidaemic Changes in Women with Subclinical Hypothyroidism

In overt hypothyroidism, many lipid abnormalities have been documented. This study was intended to demonstrate the levels of lipid in women with subclinical hypothyroidism (SH). This was a case control study which was done at referral Centre in Chennai. Women with subclinical hypothyroidism and euthyroid women attending our master health checkup clinic were enrolled in this study.Their lipid profile, fasting blood sugar, T3,T4 and TSH levels were measured. In subclinical hypothyroidism, various parameters were compared. Thirty euthyroid and 30 age matched subclinical hypothyroid women were enrolled in this study. There were significant dyslipidaemic changes is SH women as compared to euthyroid controls. Serum total cholesterol and triglyceride levels were significantly higher as compared to those in controls. LDL levels were higher is SH women, but did not reach statistical significance and lower levels of HDL were noticed in SH subjects as compared to those in euthyroid women. A positive association was also reported between serum TSH and lipid parameters in our study group. SH, the earliest form of thyroid failure, has negative metabolic effects on the affected subjects.SH could be one of the causes of secondary hyperlipidaemia and should be viewed as an independent risk factor for atherosclerosis, along with obesity, hypertension, diabetes, etc.

Peculiarities of myocardial diastolic function in patients with autoimmune thyroiditis divided according to the mild hypothyroidism range

The aim of the present study was to evaluate myocardial diastolic function in patients with autoimmune thyroiditis (AT) against the TSH level within the reference range and subclinical interval as well as to determine whether it is related to the thyroid function or other metabolic and functional indices. METHODS. We studied diastolic function of left and right ventricles by the ratio of mitral and tricuspid annular early and late diastolic velocities (em/am and et/at respectively) using tissue Doppler imaging; structural heart characteristics by echocardiography; lipid profile and peroxidation parameters; serum ferritin and iron concentrations in 132 middle-aged women. 36 of them were euthyroid controls, 96 had AT and were ranged according to their TSH value into 4 groups: women with “low- normal” (0.4–2.5 mU/L) and “upper-normal” (2.5–4.0 mU/L) TSH range; patients with subclinical hypothyroidism and TSH below and above 6 mU/L. RESULTS. The increase of TSH value within reference range and subclinical interval was associated with the parallel tendency to the em/am and et/at ratio decrease suggesting detrimental effect of the mildest thyroid failure on the left and right ventricles diastolic function. Thus, patients with TSH values >6 mU/L had significantly lower em/am and et/at ratio compared to the “low-normal” TSH group ( p < 0.05) and controls ( p < 0.01). Among them, the highest LDL cholesterol, myocardial mass index and oxidative stress rate were detected as well as lower iron and ferritin serum concentrations ( p < 0.05 compared to controls with regard to all the parameters listed above). Abnormalities in heart structure, lipid and iron metabolism correlated with alterations in ventricular relaxation suggesting that they can contribute, at least partly, to the diastolic dysfunction devel- opment CONCLUSION. The increase of TSH value within reference range and subclinical interval can affect diastolic function of the heart. Its detrimental effect may be mediated, at least partly, by ventricular mass changes, lipid profile and iron metabolism alterations.

Bone health in children with long–term idiopathic subclinical hypothyroidism

BackgroundSubclinical hypothyroidism (SH) is a relatively common condition characterized by a mild persistent thyroid failure. The management of children with SH is still a controversial issue and the decision to treat with L-thyroxine represents a clinical dilemma. Thyroid hormone and TSH play an important role in skeletal growth and bone mineral homeostasis.AimTo evaluate whether untreated idiopathic SH may affect bone health in childhood and to compare two different diagnostic tools such as dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS).Patients and MethodsTwenty-five children and adolescents (11 males) aged 9.8 ± 3.5 years (range 4.2-18.7) with untreated idiopathic SH were enrolled in the study. SH was diagnosed on the basis of normal FT4 levels with TSH concentrations between 4.2 and 10 mU/l. Children have been followed for 3.3 ± 0.3 years from the time of SH diagnosis. Twenty-five healthy children, age- and sex-matched, were enrolled as controls. Patients and controls underwent DXA to evaluate lumbar spine bone mineral density (BMD) and QUS at proximal phalanges of the non-dominant hand to assess bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) and bone transmission time (BTT).ResultsMean BMD Z-score was −0.4 ± 1.36 in patients and −0.2 ± 1.2 in controls. Mean Ad-SoS Z-score was 0.01 ± 1.0 in patients and 0.1 ± 1.2 in controls and mean BTT Z-score was −0.03 ± 0.8 and 0.04 ± 1.1 respectively. All values were within the normal range, both in patients and in controls. There were no statistically significant differences between the two groups.ConclusionBone health, evaluated by lumbar spine DXA and phalangeal QUS, is not impaired in our children, despite long-term duration of idiopathic SH. Data about bone status provided by QUS are comparable to those provided by DXA. Therefore, QUS may represent a good, cheaper and safe screening test for bone evaluation in children with SH.

Is there a relationship between premature gray hair and other autoimmune phenomena with diminished ovarian reserve?

Premature hair graying (PHG) has been associated with autoimmune disease (AD) including premature ovarian, thyroid, and adrenal failure and reduced bone mineral density at menopause, suggesting that these latter women have earlier reduced ovarian reserve. This study was designed to determine whether women undergoing treatment for unexplained infertility with PHG and/or AD and normal ovarian reserve at baseline, CD3 FSH < 15 mIU/ml and estradiol < 100 pg/ml, have impaired treatment markers of ovarian reserve.

Age and Gender Substantially Influence the Relationship Between Thyroid Status and the Lipoprotein Profile: Results from a Large Cross-Sectional Study

Conflicting data are reported on the association between mild thyroid failure and lipid profile, primarily regarding serum triglyceride values and patients with slightly elevated thyrotropin (TSH, <10 mIU/L). In this study, we assessed the possible influence of gender and age on this relationship. The study included 2308 consecutive patients who were seen for suspected or diagnosed thyroid disease (1874 women, 434 men, mean age 47.5±14.1 and 46.9±14.0 years, respectively) and on whom studies of thyroid status and lipoprotein profile were conducted after an overnight fast. Patients with uncontrolled diabetes mellitus and those taking lipid-lowering drugs were excluded. There were 628 patients receiving L-thyroxine who had a diagnosis of hypothyroidism: 200 were hyperthyroid, and 120 were still hypothyroid. Overall, 648 patients were hypothyroid, and 290 were hyperthyroid. No gender difference in the frequency of TSH values in the ranges studied (i.e., TSH frequency distribution) was observed. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDLc) values (p<0.0003 and p<0.003, respectively) as well as the LDL/high-density lipoprotein cholesterol (HDLc) ratio (p<0.03) were elevated not only in unselected women with TSH values in the 4th TSH group (>10 mIU/L) but also in those of the 3rd group (3.6-10.0 mIU/L) who were older than 50 years (TC and LDLc p=0.01, LDL/HDLc ratio p=0.02 vs. euthyroid women). Among unselected men, only those of the 4th TSH group had elevated triglyceride (p<0.0001) but not cholesterol values. However, men of the 3rd and 4th TSH group who were older than 65 years had significantly higher TC, LDLc, and LDL/HDLc values as well (p=0.03, p=0.02 and p=0.01, respectively vs. euthyroid men). In the final model of stepwise regression for predicting each lipid parameter variation on the basis of age, TSH, free thyroxine (FT4), and body mass index (BMI) analysis, age had the highest standardized coefficient (0.36 and 0.37, respectively), followed by TSH (0.20 and 0.11, respectively) and FT4 (-0.11 and -0.09, respectively) when looking at TC and LDLc; whereas BMI had the highest standardized coefficient (0.28), followed by age (0.15) and TSH (0.11) when looking at triglyceride variation. This study confirms a gender differentiation in the relationship between hypothyroidism and the lipid profile, which is substantially influenced by age, especially in patients with mild thyroid impairment (TSH<10 mIU/L).

Incidence and Prevalence of Hypothyroidism in Patients Affected by Chronic Heart Failure: Role of Amiodarone

It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodine-containing antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17%and, as expected, it was significantly higher in females than males (33% vs 13%; p < 0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.

The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto’s thyroiditis and isolated hyperthyrotropinaemia: a 3‐year follow‐up

The natural history of Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors. This is retrospective cross-sectional study. Three hundred and twenty-three patients with HT (88 boys and 235 girls) and 59 with IH (30 boys and 29 girls), mean age 9·9 ± 3·8 years were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but <100% of the upper limit (G1). All IH subjects had elevated TSH. Potential risk factors for thyroid failure were evaluated after 3 years and included the presence or familiarity for endocrine/autoimmune diseases, premature birth, signs and symptoms of hypothyroidism, TSH levels, antithyroid antibodies and thyroid volume. HT: Of those with HT, 170 G0 patients remained stable, 31 moved to G1 and 35 to G2 (hypothyroidism). Thirty-six G1 children moved to G0, 17 remained stable and 34 moved to G2. Of patients with IH: 23 normalized, 28 remained stable and eight became overtly hypothyroid. In patients with HT, the presence of coeliac disease, elevated TSH and thyroid peroxidase antibodies (TPOAb) increased the risk of developing hypothyroidism by 4·0-, 3·4- and 3·5-fold, respectively. The increase in TSH levels during follow-up was strongly predictive of the development of hypothyroidism. In patients with IH, no predictive factor could be identified. Coeliac disease, elevated TSH and TPOAb at presentation and a progressive increase in TSH are predictive factors for thyroid failure in HT patients.

Autoimmune Thyroid Diseases

Autoimmune thyroid disease is characterized by the presence of autoantibodies against thyroid peroxidase (TPO), thyroglobulin (Tg), and the thyroid simulating hormone recep­ tor (TSHR). The thyroid gland is a site of autoantibody secretion in autoimmune thyroid disease by the B cells infiltrated into the thyroid. Hashimoto’s thyroiditis, a chronic autoim ­ mune thyroid disease, characterized by the occurrence of high levels of serum thyroid an­ tibodies for TPO and Tg and goiter, is the most common type of thyroiditis. A firm, diffuse, painless goiter is the most common initial finding in Hashimoto’s thyroiditis. Some patients have atrophic thyroid glands rather than goiter, which may represent the final stage of thyroid failure in Hashimoto’s thyroiditis. Levothyroxine is the treatment of choice for Ha­ shimoto’s thyroiditis presenting overt hypothyroidism. Patients with Hashimoto’s thyroid­ itis and a thyroid nodule should undergo fine ­needle aspiration biopsy to rule out lym­ phoma and thyroid carcinoma. Graves’ disease is the most common cause of spontaneous hyperthyroidism in patients younger than 40 years of age. Patients with Graves’ disease re­ veal heterogeneous lymphocytic infiltration without follicular destruction and also show various clinical presentations.