Cases Of Overt Hypothyroidism Research Articles

Reassessment of elicitation of myoedema in evaluation of overt hypothyroidism: A pilot study

Introduction:There is a need to reassess the significance of myoedema in evaluation of overt hypothyroidism in the current day clinical practice. It is commonly checked for by flicking across the biceps belly expecting a transient mound at the points of tactile stimuli with mild pressure.Aim and Objective:To assess elicitation of myoedema in overt hypothyroidism (defined arbitrarily as TSH >50 mIU/L in primary hypothyroidism and fT4 <0.6 ng/dl in secondary hypothyroidism).Results:The 28 primary overt hypothyroid (OH) patients were divided into three groups as mild, moderate, and severe depending on TSH levels as those with 50-100, 100-150, and >150 mIU/L. Myoedema was elicited in 8 of 13 in the severe OH group, in 2 of 7 in moderate OH group and in 1 of 8 in the mild OH group. In the group of secondary hypothyroidism, myoedema was elicitable in one of two patients. The odds ratio for presence of both myoedema and clinical features of myopathy in a group of overt hypothyroid patients with TSH >150 mIU/L as compared to <150 mIU/L was 17.5. Similarly, the odds ratio for the presence of only myoedema was 6.4 while the odds ratio for presence of only clinical features of myopathy was 3.67. While the odds ratios involving presence of myoedema neared statistical significance, that with the presence of clinical features of myopathy alone did not.Conclusion:Examination for eliciting myoedema is useful when evaluating a case of overt hypothyroidism.

Thyroid function and morphology in subjects with microdeletion of chromosome 22q11 (del(22)(q11))

Monoallelic microdeletion of chromosome 22q11 (22q11DS) is considered to be the commonest human microdeletion syndrome. Abnormalities of thyroid function are sporadically reported in this syndrome, but very few studies have specifically assessed this issue, and thyroid morphology has not been systematically studied. To evaluate the prevalence of abnormalities of thyroid function and morphology in a cohort of paediatric and adult patients with 22q11DS. Thirty patients with 22q11DS (median age 9.7, range 1.5-43.9 years) were studied. In all subjects, serum free-T(3), free-T(4), TSH, thyroperoxidase, thyroglobulin, and TSHr auto-antibodies, as well as thyroid ultrasonographic data, were evaluated and compared with age- and sex-matched healthy control groups, for paediatric and adult patients. Fourteen (46.6%) patients showed thyroid hypoplasia involving the entire gland. In all the patients, the volume of the left lobe of the thyroid was significantly reduced (P < 0.01). Among the subjects with thyroid hypoplasia, 10 out of 14 (71%) showed a concomitant heart malformation, a condition that was present in five (31%) of the subjects with a normal thyroid volume (P < 0.05). Seven (23.3%) cases of subclinical hypothyroidism and one (3.3%) case of overt hypothyroidism were identified. Three (10%) patients were positive for thyroid auto-antibodies. Of the patients with overt and subclinical hypothyroidism, five out of eight (62.5%) patients showed thyroid hypoplasia. This study confirms the presence of alterations of thyroid function in 22q11DS, and also suggests a frequent occurrence of abnormalities in thyroid morphology in these subjects. Patients with 22q11DS should be monitored for thyroid function, and thyroid ultrasound screening should be considered, especially in those patients with changes in thyroid function or congenital heart malformations. The possible relationship between developmental abnormalities in the heart and the thyroid gland should be confirmed.

Reversal of Hypothyroidism in Well Chelated β-Thalassemia Major Patients

Thyroid dysfunction is known to occur frequently in β-Thalassemia major patients (TMps), but its prevalence and severity varies in different cohorts according to chelation regimens. Thyroid hormones are critical determinants of brain and somatic development in infants and of metabolic activity in adults affecting the function of virtually every organ system. Thyroid gland mainly secrets T4, whereas 80% of T3 is produced by de-iodination of T4 (liver, kidney, heart and other tissues) and is influenced by a variety of factors. Furthermore, T4 & T3 secretion is tightly regulated within narrow limits by a mechanism that involves the pituitary-secreted TSH which in turn is stimulated by the hypothalamic TRH. Thus, iron overload-related hypothyroidism may be either central (because of deposition in the pituitary or the hypothalamus) and usually associated with other endocrinopathies, or primary (by deposition in the thyroid gland or even other organs). Existing data suggest that the thyroid gland appears to fail before the central components of the axis. In all cases, symptoms occur slowly over time and may vary from subclinical to overt hypothyroidism which is associated with an increased risk of cardiovascular disease. The aim of this study was to investigate the effect of long-term intensive combined chelation therapy on thyroid function in TMps after they were all in negative iron balance. 51 TMps, 25 males 26 females, mean age 29.8±2.03, who were previously maintained on subcutaneous desferrioxamine monotherapy (DFO:40mg/kg, 3–6 days/week) switched to an intensive combined chelation with DFO (40–60mg/kg/d) and Deferiprone (DFP: 75–100mg/kg/d) adapted to individual needs. Thyroid function was assessed initially and after 6 years by TRH stimulation test and TSH, FT4 & FT3 screening. All patients on hormone replacement therapy stopped treatment at least 30 days before the test. This was approved by the Hospital Scientific Committee. Criteria for the diagnosis of subclinical or compensated hypothyroidism was an increase of the TSH levels during the test of more than 20 μIU/ml from the basal value or an elevated basal TSH concentration (>5 μIU/ml) and for overt hypothyroidism a further decrease in FT4 & FT3 levels. With DFO monotherapy 18 TMps were treated with thyroxin therapy. In these patients after combined chelation and an important decrease in iron overload (p<0.0001) as estimated by ferritin levels (2,737±473 vs 450±225mg/dl), MRI liver and heart iron quantification (T2*L & T2*H) and LIC calculated by Ferriscan (13±3 vs. 1.4±0.5mg/gdw), a significant increase was observed in mean FT4 (1.07±0.03 vs. 0.7±0.02ng/ml, p<0.0001) & mean FT3 (2.6±0.1 vs. 1.3± 0.1pg/ml, p<0.0001) and an additional significant decrease in the mean TSH quantitative secretion, calculated as the area under the curve (AUC=1,332±131 vs. 2,231±241, p<0.0001). These 10/18 (56%) TMps with subclinical or compensated hypothyroidism, who normalized TSH, FT4 & FT3 levels and had a normal TRH stimulation test discontinued thyroxin therapy, while another 4/18 (22%) reduced their thyroxin dose. The remaining 4/18 with overt hypothyroidism, while they all improved their TRH stimulation test, only 2 improved to compensated hypothyroidism with TSH levels 5–10mIU/ml and normal FT4 & FT3 levels. Critically, in the other 33/51 euthyroid TMps, no new cases of hypothyroidism were noted after combined chelation and a significant increase (p<0.0001) was observed in the mean FT4 & FT3 levels with a significant decrease (p<0.0001) in the mean TSH quantitative secretion (AUC). This study showed that intensive combined chelation associated with a significant decrease of iron overload may reverse some cases of primary hypothyroidism, either subclinical or compensated, and may prevent progression to overt hypothyroidism, thus influencing the decision to treat with thyroid hormone. It may also improve some cases of overt hypothyroidism suggesting that even iron-induced damage of the thyroid pituitary axis might be ameliorated.

An Increased Incidence of Overt Hypothyroidism after Iodine Fortification of Salt in Denmark: A Prospective Population Study

Iodine fortification (IF) of salt was introduced in Denmark in 1998. Little is known about the effect of a minor increase in iodine intake on the incidence of hypothyroidism. We prospectively identified all new cases of overt hypothyroidism in two areas of Denmark before and for the first 7 yr after IF had been introduced. A computer-based register was used to identify continuously all new cases of overt hypothyroidism in two subcohorts with previous moderate and mild iodine deficiency (ID), respectively (Aalborg, n = 310,124, urinary iodine = 45 microg/liter; and Copenhagen, n = 225,707, urinary iodine = 61 microg/liter). Data were obtained 1) before IF (1997-1998), 2) during voluntary IF (1999-2000), 3) during early (2001-2002) and 4) during late (2003-2005) period with mandatory IF. The overall incidence rate of hypothyroidism increased during the study period: baseline, 38.3/100,000.yr; voluntary IF, 43.7 (not significant vs. baseline); early mandatory IF, 48.7 [vs. baseline, rate ratio (RR) = 1.27; 95% confidence interval (CI) = 1.10-1.47]; and late mandatory IF, 47.2 (vs. baseline, RR = 1.23; 95% CI = 1.07-1.42). There was a geographic difference because hypothyroidism increased only in the area with previous moderate ID: Aalborg, late mandatory IF vs. baseline, 40.3/29.7 (RR = 1.11; 95% CI = 1.11-1.66); Copenhagen, 56.7/51.6 (RR = 1.10; 95% CI = 0.90-1.34). The increase occurred in young and middle-aged adults. Even a cautious iodization of salt was accompanied by a moderate increase in the incidence rate of overt hypothyroidism. This occurred primarily in young and middle-aged subjects with previous moderate ID.

The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives

Denmark was an area of iodine deficiency, and mandatory iodine fortification of table salt and salt in bread (13 p.p.m. iodine) was initiated in 2000/2001. The Danish investigation on iodine intake and thyroid disease (DanThyr) is the monitoring of the iodine fortification program. DanThyr consists of three main parts: a study of population cohorts initialized before (n=4649) and after (n=3570) iodization of salt, a prospective identification of incident cases of overt hyper- and hypothyroidism in a population of around 550,000 people since 1997, and compilation of data from the national registers on the use of thyroid medication, thyroid surgery, and radioiodine therapy. Studies were carried-out in parallel in subcohorts living in areas with differences in iodine content of ground water. The study showed profound effects of even small differences in iodine intake level on the prevalence of goiter, nodules, and thyroid dysfunction. Mild and moderate iodine deficiency was associated with a decrease in serum TSH with age. Other environmental factors were also important for goiter development (increase in risk, smoking and pregnancy; decrease in risk, oral contraception and alcohol consumption), and the individual risk depended on the genetic background. Environmental factors had only a minor influence on the prevalence of thyroid autoantibodies in the population. There were more cases of overt hypothyroidism in mild than in moderate iodine deficiency caused by a 53% higher incidence of spontaneous (presumably autoimmune) hypothyroidism. On the other hand, there were 49% more cases of overt hyperthyroidism in the area with moderate iodine deficiency. The cautious iodine fortification program, aiming at an average increase in iodine intake of 50 mug/day has been associated with a 50% increase in incidence of hyperthyroidism in the area with the most severe iodine deficiency. The incidence is expected to decrease in the future, but there may be more cases of Graves' hyperthyroidism in young people. A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake of a population have profound effects on the occurrence of thyroid abnormalities. Monitoring and adjustment of iodine intake in the population is an important part of preventive medicine.

Epidemiology of subtypes of hypothyroidism in Denmark

Studies of hypothyroidism are often based on referred patients, and limited information is available on the incidence rates of subtypes of hypothyroidism in the general population. We therefore studied incidences of subtypes of primary, overt hypothyroidism in a Danish population cohort and compared incidences in two subcohorts with different levels of iodine intake. A prospective population-based study, monitoring a well-defined cohort representative of the Danish population. The Danish Investigation of Iodine Intake and Thyroid Diseases registry of hyper- and hypothyroidism was established as part of the monitoring of the iodine fortification of salt in Denmark. A computer-based system linked to laboratory databases identified all patients diagnosed with new, biochemically overt hypothyroidism in populations living in Aalborg (moderate iodine deficiency, n = 311,102) and Copenhagen (mild iodine deficiency, n = 227,632). We subsequently evaluated all identified patients to verify incident thyroid disease, and subclassified hypothyroidism into nosological types. During a 4-year period (2,027,208 person-years) 685 new cases of overt hypothyroidism were diagnosed in the cohort; the incidence rate was 32.8 per 100,000 person-years (standardised to the Danish population). Nosological types of hypothyroidism were: spontaneous (presumably autoimmune) 84.4%, post-partum 4.7%, amiodarone-associated 4.0%, subacute thyroiditis 1.8%, previous radiation or surgery 1.8%, congenital 1.6% and lithium-associated 1.6%. Crude incidence rates were 29.0 around Aalborg and 40.6 in an area of Copenhagen. The higher incidence rate of hypothyroidism in the area with higher iodine intake was caused solely by more cases of spontaneous (presumably autoimmune) hypothyroidism, whereas the incidence of non-spontaneous hypothyroidism (all types combined) was significantly lower in the area with higher iodine intake. In a population-based study we observed a higher incidence of hypothyroidism with higher iodine intake. This was due solely to the entity of spontaneous hypothyroidism. The occurrence of overt hypothyroidism was relatively low in Denmark.

Preeclampsia-like syndrome that is associated with severe hypothyroidism in a 20-week pregnant woman

We report a case of overt hypothyroidism that was associated with a preeclampsia-like syndrome and fetal death in a 37-year-old woman (gravidity, 7; parity, 6). Rapid and robust correction of hypothyroidism is recommended in this situation.

Familial aggregation of autoimmune thyroiditis in first-degree relatives of patients with juvenile autoimmune thyroid disease.

Several studies have shown aggregation of autoimmune thyroiditis in families by estimation of thyroid antibodies. However, the prevalence by concurrent estimation with fine-needle aspiration cytology (FNAC) and thyroid antibodies has not been previously reported. We therefore studied 222 first-degree relatives (group 1) of 71 index cases diagnosed as lymphocytic thyroiditis on FNAC and 81 family members (group 2) of 23 goitrous children diagnosed as colloid goiter on FNAC for comparison. Successful FNAC conducted in 122 group 1 subjects revealed lymphocytic thyroiditis in 51 (42%), whereas lymphocytic thyroiditis was diagnosed in only 5 goitrous subjects (13%) in group 2. Among group 1 subjects with FNAC-proven lymphocytic thyroiditis, antithyroid peroxidase (TPO) antibodies were found in 35 (67%), while in anti-TPO antibody positive goitrous relatives of group 1, lymphocytic thyroiditis was found in 36 (78%). Eight new cases of overt hypothyroidism and 45 new cases of subclinical hypothyroidism were diagnosed among group 1 subjects. Our study suggests: (1). familial clustering of autoimmune thyroiditis; (2). if only FNAC or thyroid antibodies is used for diagnosis of autoimmune thyroiditis in children, 22%-33% of cases are likely to be missed; and (3). serum thyrotropin (TSH) should be offered to all first-degree relatives of patients with juvenile autoimmune thyroiditis.

Prevalence and relevance of thyroid dysfunction in 1922 cholesterol screening participants

Controversy persists about the role of subclinical hypothyroidism in hypercholesterolemia. This study aimed to assess in a clinically healthy, middle-aged population of employees the prevalence of thyroid function disorders and their relation to demographic variables and cardiovascular risk factors. 1922 (former) employees were screened with follow-up of newly identified cases of undiagnosed (subclinical) hypothyroidism and hyperthyroidism. Thyroid stimulating hormone (TSH), prevalence and course of (subclinical) hypo- and hyperthyroidism and their relation to cardiovascular risk factors (cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, systolic and diastolic blood pressure) were assessed. The prevalence of newly diagnosed subclinical hypothyroidism (cut-off TSH concentration: 4.0 mU/L) was 1.1% (17 women and 5 men) with a mean TSH concentration of 7.37 (95% CI 5.18–9.56) mU/L. No case of overt hypothyroidism could be diagnosed. Elevated levels of antibodies to microsomal or thyroglobulin antigens were detected in six subjects with subclinical hypothyroidism (27.3%). Fifteen subjects (0.8%, 13 women and 2 men) had TSH concentrations below 0.1 mU/L. The cardiovascular risk profile of subjects with mild subclinical hypothyroidism was not different from subjects with normal TSH levels. The prevalence of subclinical hypothyroidism was 0.8% in normocholesterolemic (cholesterol <5.2 mmol/l) and 1.4% in hypercholesterolemic subjects (n.s.). One woman each with the subclinical form of the disease developed hypothyroidism or hyperthyroidism after 21 and 11 months of follow-up, respectively. Subclinical hypothyroidism and subclinical hyperthyroidism were rarely observed in a target group for coronary heart disease prevention. Mild subclinical hypothyroidism was not associated with any adverse cardiovascular risk profile. These results argue against indiscriminate measurements of TSH concentrations in clinically healthy subjects either with normocholesterolemia or hypercholesterolemia.

Prevalence and Correction of Hypothyroidism in a Large Cohort of Patients Referred for Dyslipidemia

Treatment of hypercholesterolemia can reduce the risk of developing premature atherosclerosis. The hypercholesterolemia caused by hypothyroidism is potentially reversible by thyroid hormone replacement therapy. We determined the prevalence of hypothyroidism in patients referred to a university lipid research clinic and studied the changes in lipid and lipoprotein levels on restoration of the euthyroid state. A retrospective follow-up study was performed. In all 1509 consecutive referrals for severe dyslipidemia, thyrotropin levels were measured. Patients with hypothyroidism were identified by means of a computed database, from January 1, 1989, to July 1, 1993, first by levothyroxine sodium medication and second by serum thyrotropin values greater than 5 mU/L. Twenty-one patients were available to evaluate the effect of restoration of the euthyroid state on plasma lipid and lipoprotein levels. The observed prevalence of hypothyroidism proved to be 4.2% (64/1509). The disorder was previously known in 25 patients and newly diagnosed in 39 patients (11 with overt hypothyroidism and 28 with subclinical hypothyroidism). Significant reductions in total cholesterol and low-density lipoprotein cholesterol levels occurred only in patients with pretreatment thyrotropin values of 10 mU/L or more. The prevalence of newly diagnosed cases of overt hypothyroidism in patients referred to a lipid clinic is approximately two times that in the general population. The absence of significant reductions in total cholesterol and low-density lipoprotein cholesterol levels on levothyroxine treatment in patients with minor subclinical hypothyroidism (thyrotropin level, < 10 mU/L) does not support the view that this condition is a risk factor for atherosclerosis mediated by an elevated low-density lipoprotein cholesterol level. All patients referred for diagnosis and treatment of dyslipidemia should be screened for hypothyroidism by measurement of thyrotropin values.

Hypothyroidism in Textile Workers

Four cases of overt hypothyroidism, three of whom were men in their early forties, had occurred over a period of 6 years at a textile factory where thiourea and resorcinol were used in the finishing departments. A follow-up survey of 189 men and 48 women (44 per cent of employees) revealed 12 new cases of varying grades of hypothyroidism, categorized after the system proposed by Evered. These included a case of mild hypothyroidism in a male worker, who subsequently received thyroid hormone replacement therapy as a hospital out-patient. A full occupational hygiene survey was carried out to determine possible sources of exposure to thiourea and resorcinol. Although we were unable to demonstrate a statistically significant occurrence of biochemically and immunologically detectable disturbances in thyroid function among this workforce, we did note that three of the original index cases and several of those workers with varying degrees of minor dysfunction in the follow-up study seemed to cluster in locations where exhausted fumes could accumulate.

ENDEMIC GOITRE IN CENTRAL CHINA CAUSED BY EXCESSIVE IODINE INTAKE

Thyroid status was examined in children from two villages in central China where the iodine concentrations in drinking water were 462.5 and 54 μg/1. Goitres were present in 65% (n = 120) and 15.4% (n=51), respectively. All children in both groups were clinically euthyroid and neurologically normal. Growth measurements and intellectual performance were similar in the two groups. Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of overt hypothyroidism were detected in the high-iodine village.

Thyroid function in women with breast cancer

The thyroid function was evaluated in a study group of 226 breast cancer patients and in control groups, consisting of 125 patients with various other malignancies, 61 women with benign breast disease and 166 healthy blood donors. The mean serum concentrations of total T 3 and T 4 were significantly higher in the breast cancer group than in the controls. The mean TFI (thyroid function index), measured by two indirect techniques (T 3RU, T 4/TBG) or by direct free T 4 measurement, was also significantly higher in this group of patients than in controls. Individual values of TFI exceeding the upper limit of the normal range were related with elevated total T 4 levels and not with abnormal concentrations of total TBG. Eight women with breast cancer (3.5%) and one patient with head and neck cancer were clinically hyperthyroid. No case of overt hypothyroidism was observed. There was no relation between thyroid function and spread of the disease (TNM). The control groups, including patients with other-than-breast cancers, did not show any significant modification of the thyroid function tests. In the present study, breast cancer patients, as a group, show a thyroid dysfunction distinct from the non-specific abnormalities (low T 3 syndrome) frequently observed in patients with a variety of acute or chronic non-thyroidal illnesses.