Family History Of Thyroid Disease Research Articles

Are Possible Risk Factors for Differentiated Thyroid Cancer of Prognostic Importance?

The only established risk factor for differentiated thyroid cancer (DTC) is ionizing radiation. How ionizing radiation and other possible risk factors for DTC influence the prognosis has not extensively been investigated. We studied if factors such as smoking, number of children, previous thyroid disorders, previous radiotherapy toward the neck, family history of thyroid diseases, and malignancies influenced survival for patients with DTC. A nested case-control study was conducted within the cohort of all patients diagnosed with DTC in Sweden between 1958-1987. Cases consisted of patients who died from DTC. One control, matched by age at diagnosis, gender, and calendar period was randomly selected from the risk set for each case. Information of risk factors was collected from the medical records. Associations between these factors and prognosis were assessed using conditional logistic regression. Smokers had a borderline significant increased risk of dying from DTC. Previous radiotherapy towards the neck region had no prognostic implication. A family history of DTC influenced prognosis although not significant due to few cases. The remaining risk factors studied did not influence survival. In conclusion, smokers seemed to have a worsened prognosis compared to nonsmokers and a family history of thyroid cancer had a nonsignificant negative effect on survival.

An Investigation of Epidemiologic Factors Associated With Large Nodular Goiter

Sporadic nodular goiter is a common problem in the United States and significant compressive symptoms may occur with progression to a critical size. Potential epidemiological variables associated with the development of large unilateral (> or = 50 g) and bilateral (> or = 100 g) nodular goiter were investigated including: age, gender, race, body mass index (BMI), family history of thyroid disease, pregnancy at time of diagnosis, insurance status, and tobacco or alcohol use. Data were obtained from an IRB-approved thyroid database and retrospective chart review of consecutive patients operated on for nodular goiter from 1990 through 2005. A univariate and multivariate analysis of epidemiological variables in patients with "large" versus "small" nodular goiter was completed. Of the 488 patients operated on for nodular goiter, 113 (23%) were classified as "large," 43 with unilateral (mean 106 +/- 72 g) and 70 with bilateral enlargement (mean 173 +/- 92 g) and 375 (77%) were classified as "small," 179 with unilateral (18 +/- 10 g) and 196 with bilateral (37 +/- 24 g) enlargement. Based on univariate analysis, African-American race, age > or = 40 years, BMI > or = 30 kg/m2, and lack of insurance were associated with an increased risk of large nodular goiter (P < or = 0.001), whereas alcohol use was protective (P = 0.002). A multivariate analysis revealed that African-American race [adjusted odds ratio (adj. OR) 3.3, 95% CI = 2.0-5.4], age > or = 40 years (adj. OR 2.1, 95% CI = 1.2-3.8), and BMI > or = 30 kg/m2 (adj. OR 2.5, 95% CI = 1.5-4.0) were independently associated with large nodular goiter. No significant differences were observed in gender, family history of thyroid disease, pregnancy, or tobacco use (P > 0.1). African-American race, obesity, and increasing age are independent risk factors for the development of large nodular goiter. These results may be helpful in determining how best to monitor patients with nodular goiter, with earlier intervention to help prevent progressive enlargement and its sequelae.

Is there a need to redefine the upper normal limit of TSH?

Mild forms of hypothyroidism--subclinical hypothyroidism--have recently been discussed as being a risk factor for the development of overt thyroid dysfunction and for a number of clinical disorders. The diagnosis critically depends on the definition of the upper normal limit of serum TSH as, by definition, free thyroxine serum concentrations are normal. Cut-off levels of 4-5 mU TSH/l have been conventionally used to diagnose an elevated TSH serum concentration. Recent data from large population studies have suggested a much lower TSH cut-off with an upper limit of 2-2.5 mU/l but application of strict criteria for inclusion of subjects from the general population studies aiming at assessing TSH reference intervals (no personal or family history of thyroid disease, no thyroid antibodies and a normal thyroid on ultrasonography) did not result in an unequivocal upper limit of normal TSH at 2.0-2.5 mU/l. When summarizing the available evidence for lowered upper TSH cut-off values and their potential therapeutic implications there is presently insufficient justification to lower the upper normal limit of TSH and, for practical purposes, it is still recommended to maintain the TSH reference interval of 0.4-4.0 mU/l. Classifying subjects with a TSH value between 2 and 4 mU/l as abnormal, as well as intervening with thyroxine treatment in such subjects, is probably doing more harm than good.

An investigation of epidemiologic factors associated with large nodular goiter

Background: Despite the widespread consumption of iodide in the United States, large nodular goiter remains a common problemand its pathogenesis is incompletely understood. Methods: Potential factors involved in the pathogenesis of large unilateral (≥ 50g) and bilateral (≥100g) nodular goiter were investigated including: age, gender, race, body mass index (BMI), family history of thyroid disease, insurance status, cigarette smoking, and alcohol use. Data were obtained from an IRB-approved thyroid database and retrospective chart review of consecutive patients operated on for nodular goiter from 1990-2004.

Risk factors for congenital hypothyroidism: results of a population case-control study (1997–2003)

To identify risk factors for permanent and transient congenital hypothyroidism (CH). A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrollment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) = 12.2, 95% confidence interval (CI): 2.4-62.3). A statistically significant association with additional birth defects, female gender and gestational age >40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR = 1.9, 95% CI: 0.7-5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR = 15.7, 95% CI: 0.9-523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease.

New Reference Intervals for Thyrotropin and Thyroid Hormones Based on National Academy of Clinical Biochemistry Criteria and Regular Ultrasonography of the Thyroid

The aim of our present study was to establish new reference intervals for thyrotropin (TSH) and thyroid hormones based on National Academy of Clinical Biochemistry (NACB) criteria and regular thyroid ultrasonography. We also assessed the effect of potentially confounding factors to modulate the limits of these intervals. We investigated 870 apparently healthy persons and excluded, step by step, those with a family history of thyroid disease, pathologic thyroid ultrasonography results, and increased anti-thyroid peroxidase or anti-thyroglobulin antibodies. Accordingly, only 453 of the 870 persons in the entire group were finally included as reference collective. We measured serum concentrations of TSH, total and free thyroxine (T(4) and FT(4)), and total and free triiodothyronine (T(3) and FT(3)) of the whole and the reference collective on the ELECSYS system assays (Roche Diagnostics) and calculated the 2.5th and 97.5th percentiles for comparison. The calculated lower limit for TSH differed significantly between the reference intervals for healthy persons with an assessed normal thyroid gland vs the nonselected group of healthy blood donors. Age was the only independent factor and was significantly inversely associated with TSH (P <0.0001). Use of oral contraceptives was a significant predictor for variation in T(4) concentrations (P <0.001). Age and oral contraceptives were independently associated with T(3) variations (P <0.05). For FT(4) vs FT(3) variation, gender and (inversely) age (P <0.01) were independent modulating factors. The selection of healthy persons according to NACB criteria combined with sonographic confirmation of a normal thyroid gland provide a valid basis for the reference interval for TSH. Factors indicating a preclinical disease state, such as family history, pathologic ultrasonography result, or increased anti-thyroid peroxidase and anti-thyroglobulin antibodies, can be associated with normal hormone concentrations. Additionally, patient age and gender as well as use of contraceptives should be considered in diagnostic evaluation of thyroid diseases.

Age as a predictor of recurrent hypothyroidism in patients with post-partum thyroid dysfunction

The long term effect of post-partum thyroid dysfunction (PPTD) is not well established. This study was conducted to evaluate the outcome of permanent hypothyroidism and factors predictive of thyroid dysfunction in a large cohort of women with PPTD. In 164 women, treated with levothyroxine for moderate and severe post- partum hypothyroidism, the treatment was discontinued and subjects were followed-up for the recurrence of hypothyroidism. Factors such as thyroid function tests, tyroid peroxidase antibodies (TPOAb) titers, multiparity, history of autoimmune disorders, smoking habits, use of oral contraceptives, family history of thyroid disease, goiter size and age at active phase of PPTD were assessed. Seventy-one post-partum women without PPTD were considered as control group. One hundred forty-eight women (90%) returned for follow-up, and 93 subjects (63%) developed hypothyroidism with a median of 2 months after T4 withdrawal. Of factors predicting recurrence of hypothyroidism, only age, and serum TSH and T3 concentrations at the time of occurrence of PPTD entered the model in multiple stepwise regression analysis. Hypothyroidism occurred earlier and more frequently in women aged 30 and over, as compared to younger ones (p < 0.01), hazard ratio 1.69. In 55 euthyroid subjects with history of PPTD, serum TSH was significantly increased as compared to the control group (3.0 +/- 1.6 vs 0.8 +/- 0.5 mU/l, p < 0.001). These data, representing the largest cohort of women with PPTD who have been followed, show that a significant proportion of women with moderate and severe PPTD, in particular those aged 30 yr and over, develop recurrent hypothyroidism. Proper follow-up of all women with PPTD, the older ones in particular, is recommended.

The Thyroid Nodule

A 42-year-old woman presents with a palpable mass on the left side of her neck. She has no neck pain and no symptoms of thyroid dysfunction. Physical examination reveals a solitary, mobile thyroid nodule, 2 cm by 3 cm, without lymphadenopathy. The patient has no family history of thyroid disease and no history of external irradiation. Which investigations should be performed? Assuming that the nodule is benign, which, if any, treatment should be recommended?

Severe hypothyroidism after thalidomide treatment

A man aged 49 reported lethargy and back pain and was found to have multiple myeloma. The treatment began with radiotherapy to the spine and repeated courses of vincristine, doxorubicin and dexamethasone. Then, on reaching plateau phase, he underwent autologous stem-cell transplantation following high-dose melphalan. This led to complete remission of the myeloma. As a part of a clinical trial investigating thalidomide as maintenance therapy for multiple myeloma, he was randomized to receive this drug, initially at 50 mg/day. The dose was increased to 100 mg/day after two weeks and to 200 mg/day after eight weeks. Three months after starting thalidomide, he reported increasing lethargy, constipation and cold intolerance. He had slow-relaxing ankle jerks. There was no goitre. Thyroid function tests revealed gross biochemical hypothyroidism, with thyrotropin (TSH) 4100 mu/L (normal range 0.25–5.5) and free T4 (FT4) 1.8 pmol/L (9.7–25.7). Thyroid peroxidase (TPO) antibodies were present. Two days before starting thalidomide his thyroid function had been essentially normal (TSH 0.21 mu/L, FT4 23.4 pmol/L), and there was no family history of thyroid disease. After the diagnosis of hypothyroidism he was taken off thalidomide and started on thyroxine, with resolution of his symptoms. On thyroxine 125 mg daily he remained euthyroid and his multiple myeloma was still in remission eighteen months from diagnosis. The UK Committee on Safety of Medicines say that they received no other reports of thalidomide-induced hypothyroidism between 1966 and 2003.

Establishment of a serum thyroid stimulating hormone (TSH) reference interval in healthy adults. The importance of environmental factors, including thyroid antibodies.

It has previously been shown that thyroid antibodies affect thyroid stimulating hormone (TSH) concentrations in men and women and that TSH levels are predictive of future thyroid disease. We investigated the validity of the National Academy of Clinical Biochemistry (NACB) guidelines regarding the TSH reference interval by studying 1512 individuals. Two hundred and fifty had at least one thyroid antibody, 121 were taking medications other than estrogens and occasional analgesics, and 105 reported a family history of thyroid disease. Serum TSH, thyroid peroxidase antibodies (TPOab) and thyroglobulin antibodies (Tgab) were determined on AutoDELFIA and TSHRab by a radioreceptor assay (RRA) from Brahms Diagnostica. For individuals without thyroid antibodies and other risk factors, no effect of age and gender was seen for serum TSH. Neither medication nor the presence of Tgab alone had any influence on serum TSH. TPOab alone or in combination with Tgab were associated with an increased serum TSH level. The 'cumulative percentage distributions' of subgroups, as well as the combined population, was In-Gaussian distributed. The central 95% of the population was within the 95% CI in rankit-plots. Consequently, a common reference interval for serum TSH of 0.58-4.07 mlU/l for all adults between 17 and 66 years of age was established. This reference interval is much higher than expected from the NACB-guidelines.

Rectal bleeding in a woman with a thyroid mass

CLINICAL PRESENTATION: (Dr. D. Wiley) A 32-yearold Caucasian woman presented with an enlarging right neck mass. The mass had been present for 2 years and was associated with dysphagia. She has had no hoarseness or symptoms of respiratory compression. She had been clinically euthyroid. She had no history of radiation exposure or therapy. Medical history was significant for a newly diagnosed irondeficient anemia. The patient was adopted after the death of her mother in her mid-thirties. The patient’s adoptive mother stated that her natural mother had a colostomy. There was no known family history of thyroid disease. Review of systems was remarkable for oligomenorrhea, dyspareunia, and hematochezia. On physical examination, the patient had a marfanoid body habitus with a height of 6 0 and a weight of 122#. There were multiple nodules consistent with fibromas located primarily on her face. Her thyroid was nodular with a dominant 6-cm mass in the right lobe. No cervical lymphadenopathy was palpable. Her heart was regular, lungs were clear to auscultation, breasts were without masses, and her abdominal examination benign. Rectal examination was significant for guaiac-positive stool, and no masses were palpable. Laboratory findings at this time included a normal thyroidstimulating hormone level of 0.6 uIU/ml and a hemoglobin level of 13.0 g/dl. A fine-needle aspiration of the right thyroid mass was suspicious for papillary thyroid carcinoma. Colonoscopy identified pancolonic polyposis, consistent with familial adenomatous polyposis. Multiple biopsies throughout the colon and rectum identified tubulovillous and adenomatous polyps on histopathology. An upper endoscopic evaluation identified multiple adenomatous duodenal polyps measuring 1 to 2 mm in size. A computed tomography (CT) of the abdomen and pelvis at this time was unremarkable. Bilateral mammography was negative for malignancy. The patient underwent a total thyroidectomy without complication. Final pathology confirmed a bilateral multifocal papillary carcinoma with the largest lesion measuring 6 cm. There were 4 separate foci, 2 in each lobe. Two of these were classic papillary and the other 2, including the 6-cm lesion, had atypical patterns. These lesions were more solid with less differentiation and the presence of “squamous morules” (Fig. 1). There was no evidence of lymph node metastases.

Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience.

To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves' Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves' orbitopathy patients. This form was used in this first multi-center study. To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. Newly referred patients with Graves' orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis > or =21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P<0.02). There were no important differences among the eight centers regarding the severity and the activity of their patients. In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible.

Palmoplantar pustulosis: a clinicoepidemiological study. The relationship between tobacco use and thyroid function.

Palmoplantar pustulosis (PPP) is a skin disease characterized by chronically recurring sterile pustules on the palms and the soles. Although the aetiology of PPP is unknown, it is interesting to note the high prevalence of tobacco use in these patients. It would seem that there may be a relationship between PPP, autoimmune diseases and alterations of thyroid function. We studied a total of 17 patients with ages ranging from 28 to 67 years, diagnosed with PPP. Patients were interviewed about: autoimmune diseases, psoriasis and thyroid disease, tobacco use (classified as: A, non-smoker; B, ex smoker; C, smoker of less than 20 cigarettes/day; D, smoker of more than 20 cigarettes/day). The patients were interviewed regarding the possible existence of a personal or family history of thyroid disease, determined using thyroid-stimulating hormone, thyroxine, antithyroid antibodies (antimicrosomal and antithyroglobulin antibodies). The majority of the patients smoked cigarettes (according to classification). Of the 12 patients for whom a thyroid study was performed three had been diagnosed with thyroid diseases, an increase in thyroid-stimulating hormone in one case and two showed an increase in antimicrosomial antibodies. We have been able to demonstrate a high prevalence of thyroid dysfunction and tobacco use in patients with PPP.

Lifestyle and Other Risk Factors for Thyroid Cancer in Los Angeles County Females

PURPOSE AND METHODS: We conducted a population-based case-control study of thyroid cancer. Cases were 292 women, aged 15–54 when diagnosed between the years 1980 and 1983 (145 diagnosed in 1980–81 and 147 diagnosed in 1982–83). Female neighborhood controls ( n = 292) were matched to each case on birth-year and race. RESULTS: Among women < 35 years, thyroid disease in first-degree relatives increased thyroid cancer risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1–3.7]. Risk was not associated with fish consumption, although high childhood consumption of shellfish decreased thyroid cancer risk (OR = 0.2, 95% CI = 0.05–0.7 for consumption at least a few times weekly). Among papillary thyroid cancers (82% of cases), frequent adult consumption of saltwater fish decreased risk. Cancer risk was reduced with consumption of certain vegetables, wine, and tea. Other dietary variables, including milk, beer and hard liquor, and coffee were not related to thyroid cancer risk. Among the papillary sample, risk increased with longer use of multivitamins (OR = 2.9, 95% CI = 1.2–7.4 for > 10 years of use). Smoking and body mass were not associated with thyroid cancer risk. CONCLUSIONS: These results suggest a role of family history of thyroid disease and certain dietary variables in the etiology of thyroid cancer in adult females.

Impact of nodal metastases on prognosis in patients with well-differentiated thyroid cancer.

To study the clinical and pathological variables predicting lymph node metastases in patients with well-differentiated thyroid carcinoma and to examine the impact of these metastases on recurrence and survival. Cohort study. Median follow-up, 56 months. Tertiary referral university teaching hospital. The study included 522 consecutive patients with well-differentiated thyroid carcinoma treated between 1964 and 1999. Data were collected on age, sex, family history of thyroid disease, prior radiation exposure, stage of disease, pathological diagnosis, size of tumor, multifocality of disease, recurrence, and survival. Total thyroidectomy and postoperative iodine 131 ablation. Disease-free and overall survival. A total of 347 patients with stage I disease and 118 with stage II disease were identified. The median age of patients with neck disease was 3 years younger than those without neck disease and most had papillary carcinoma. Patients with multifocal disease were more likely to have neck disease (P =.02). On univariate analysis, disease-free and overall survival rates were significantly lower in patients who presented with neck node metastases (P<.001 and P =.005); this difference in survival remained highly significant on multivariate analysis for disease-free survival (P =.001), with a relative hazard of 6.27. When treated with total thyroidectomy and routine postoperative iodine 131 ablation, patients with well-differentiated thyroid carcinoma who present with neck node metastases outside the central compartment of the neck have an approximately 6-fold risk of developing recurrences, most of which occur in the neck.

Serum leptin concentrations of patients with sequential thyroid function changes.

Leptin, a recently discovered protein produced in adipocytes, regulates body weight by suppressing food intake and/or increasing energy expenditure. Thyroid hormones, which increase the basal metabolic rate and thermogenesis, have been reported to be one of leptin's regulating factors because alternations in thyroid status might lead to compensatory changes in circulating leptin. The aim of this study was to assess the influence of sequential changes in thyroid function on serum leptin levels. The thyroid function status of 65 patients (55 women and 10 men, aged 40.6 +/- 15.2 years, mean +/- SD) with differentiated thyroid cancer who had received near-total thyroidectomy was studied before I-131 ablation therapy and after 2-4 and 6 months of levo-thyroxine suppressive therapy. Thirty-three (26 women, seven men; aged 41.0 +/- 10.4 years, mean +/- SD) of them were found to have become hypothyroid, then euthyroid and subsequently subclinically hyperthyroid. Their body mass index (BMI), body fat (%BF) by electrical bioimpedance, thyroid function and fasting serum leptin in these states were assessed and compared to those of 38 controls (30 women, eight men, aged 40.2 +/- 11.3 years, mean +/- SD). The controls had no past history or family history of thyroid diseases, and had the same range of BMI, between 20 and 30 kg/m2, as the patients. No difference in serum leptin levels was found between patients and controls with comparable age, sex, and BMI distribution in the euthyroid state. Using a repeated measures anova, tests of TSH, free T4 (FT4), BMI,%BF and leptin were performed on the 33 patients with sex as a grouping factor and thyroid state as a time factor. The sex difference for %BF and leptin proved to be statistically significant (P < 0.0001, and P = 0.0003, respectively). Serum leptin levels increased significantly from the hypothyroid to the subclinical hyperthyroid state (P < 0.0001) with a more pronounced increase found in females than in males (P = 0.03). Change of BMI during sequential thyroid function alterations was significant (P = 0.04) while change in %BF was not significant (P = 0.09). Pearson correlation analysis showed that serum leptin levels significantly correlated with BMI, %BF, FT4, and TSH (all P < 0.05). Using the generalized estimating equations, multivariate regression analysis revealed that FT4 was a statistically independent predictor for serum leptin (P < 0.0001). While other parameters were held constant, the mean serum leptin level increased by 1.47 units when serum FT4 was increased by one unit. In conclusion, our data indicate that circulating thyroid hormone plays a relevant role in regulating leptin metabolism independent of BMI and body fat.

Cohort study of thyroid cancer in a San Francisco Bay area population.

Using data from a large health plan, we performed a cohort study of thyroid cancer among 204,964 persons (aged 10--89 at baseline in 1964--1973, 54% female) followed for a median of 20 years. There were 196 incident thyroid cancers (73 in men, 123 in women). Risk was independently and positively related to female gender [relative risk (RR) = 1.56, 95% confidence interval (CI) = 1.12--2.19], Asian race (RR = 2.86, 95% CI = 1.76--4.65), completed college or post-graduate education (RR = 1.76, 95% CI = 1.20--2.59), history of goiter (RR = 3.36, 95% CI = 1.82--6.20), radiation of the neck region (RR = 2.33, 95% CI = 1.28--4.23) and family history of thyroid disease (RR = 2.18, 95% CI = 1.17--4.05). An inverse association was found for black race (RR = 0.55, 95% CI = 0.33--0.91). Cigarette smoking, alcohol consumption, personal history of hyperthyroidism, hypothyroidism, overweight or obesity, weight gain since age 20, height, occupational exposures, reproductive factors, oral contraceptives and hormone use did not show statistically significant relations to thyroid cancer. These results provide further evidence for a role of female gender, radiation, goiter, Asian race, high educational attainment and family history of thyroid disease in the etiology of thyroid cancer.

Thyroïdite chronique auto-immune chez l’enfant

Objective. – The aim of the study was to describe the clinical characteristics and long-term follow-up of a group of children with chronic autoimmune thyroiditis. Patients and methods. – Sixty children (age: 11.9 ± 2.7 years) were studied in a retrospective analysis. Results. – At diagnosis, 34 of the children were hypothyroid (compensated hypothyroidism, n = 15; true hypothyroidism, n = 19) and 26 euthyroid. Thyroid ultrasonography showed characteristic features of heterogenicity and/or hypoechogenicity in all patients. Other autoimmune diseases were found in ten subjects (17%) and 23% had a family history of thyroid disease. At the end of the follow-up, nine of 45 children (20% of the cases) followed up for at least one year (mean follow-up 4.4 ± 3.7 years), demonstrated a change in thyroid function. Hypothyroidism was detected in two initially euthyroid patients. Among initially hypothyroid patients, seven (28%) recovered normal thyroid function, allowing L-thyroxine withdrawal for four weeks, after 1.5 to 8.4 years. No factor was found to be predictive of the course of the disease. All subjects treated with L-thyroxine for hypothyroidism reached normal final height. Conclusion. – The natural course of chronic lymphocytic thyroiditis is variable and unpredictable. Recovery from hypothyroidism does occur and can be aided by the L-thyroxine withdrawal test. The disease requires lifelong thyroid surveillance, especially in women during pregnancy, in order to avoid a potential adverse effect on the future child.

Post-partum thyroiditis in South Brazil presenting as thyrotoxicosis: prevalence and risk factors.

The prevalence of post-partum thyroiditis (PPT) has been reported in several countries (1.9 to 16.7%) but is not known in Brazil. Several factors have been associated to its development, such as a female sex of the newborn, PPT in a previous pregnancy, a family history of thyroid disease and cigarette smoking. To investigate the prevalence of PPT and its risk factors in a southern Brazilian city, a three-cross-sectional observation study was performed. PPT was diagnosed in 14/284 subjects (5.3%) and all cases had thyrotoxicosis (13 sub-clinical and one clinical). Serum total T4 and free T4 were higher and serum TSH was lower in PPT subjects. Anti-thyroid antibodies were positive in 16.7% of PPT subjects and in 4.5% of those with no thyroid dysfunction. Goiter was identified in 14.3% of PPT subjects and in 15% of no PPT subjects. Thyroid was hardened more frequently in PPT subjects (21.4%) than in others (5.2%). Male sex of the newborn was associated to PPT, increasing 11 times the risk of PPT. Cigarette smoking was associated to PPT in group II subjects. There was no clinical sign or symptom able to contribute to this diagnosis, except the presence of hardened thyroid. Based on these findings, PPT, manifesting itself as mild thyrotoxicosis, is a common problem in southern Brazil and is associated to male sex of the newborn.

Mucous membrane pemphigoid, thymoma, and myasthenia gravis

In November 1997, approximately 1 year before being evaluated at the Mayo Clinic, Rochester, a 63-year-old woman presented with erosive tongue lesions that were diagnosed by her physician as oral lichen planus. The lesions responded well to 3 months of treatment with systemic and topical corticosteroids and topical antiyeast medication. She stopped taking the medications and had a relapse. A few months after the oral lesions developed, her left eyelid became ptotic. Results of magnetic resonance imaging of her brain were normal, and the ptosis resolved spontaneously after 2 weeks. One year later, her right eyelid began to droop, and the results of edrophonium testing were positive. She was prescribed prednisone, 30 mg daily, and pyridostigmine, as needed. The ptosis improved, but never fully resolved. Radiography revealed a left ‘‘thyroid nodule,’' but computed tomography did not show a mediastinal mass. She was advised to have the ‘‘nodule’' removed surgically and came to the Mayo Clinic, Rochester, for a second opinion. Her medical history was significant for the following: tinnitus, glaucoma, early bilateral cataracts, and long-standing hypertension, for which she took losartan, 50 mg twice daily. Other medications included: prednisone, 30 mg daily; pyridostigmine as needed; famotidine, 40 mg daily; and eyedrops for glaucoma. She denied any history of hyperthyroidism or hypothyroidism, head and neck irradiation, family history of thyroid disease, or diplopia. Hepatitis serologic studies revealed hepatitis B exposure and recovery, hepatitis C immunity, and a previous hepatitis A viral infection. On examination at the Mayo Clinic, Rochester, an erosive hypertrophic plaque was noted on the posterior dorsal half of the tongue, and vesicles and erythematous erosions on the hard and soft palates ( Fig. 1a). A lace-like white pattern was seen on the buccal mucosa bilaterally, and a small erosive patch on the left buccal mucosa ( Fig. 1b). Ocular and nasal mucous membranes were normal in appearance, and there were no pertinent skin findings. Dermatopathologic examination of an excisional biopsy specimen from the left dorsum of the tongue demonstrated an ulcer with epitheliomatous hyperplasia and a granulomatous reaction, presumably due to yeast infection. Silver staining showed hyphae and yeast at the base of the tongue ulcer. The results of the direct immunofluorescence study were negative and revealed no lichenoid changes on hematoxylin and eosin staining. Indirect immunofluorescence testing of the serum revealed a 1 : 80 titer of basement membrane zone antibodies, reflecting pemphigoid. This test was positive on repeat study. Salt-split skin on monkey esophagus revealed an epidermal pattern of basement membrane zone antibodies. Treatment included fluocinonide gel applied to the involved areas four times daily and oral antiyeast therapy (fluconazole, 200 mg once daily by mouth) while the rest of the evaluation was being completed. Figure 1(a)Open in figure viewerPowerPoint Erosive hypertrophic tongue plaque. Figure (b) Open in figure viewerPowerPoint Erosive patch on the buccal mucosa. As part of the evaluation of the ptosis, a myasthenia gravis antibody panel was performed. It revealed the following abnormalities: striated muscle antibody at 1 : 480 (reference range, <1 : 60), acetylcholine receptor binding antibody at 6.33 nmol/L (reference range, ≤ 0.02 nmol/L), acetylcholine receptor blocking antibody at 31% (reference range, 0–25%), and acetylcholine receptor modulating antibody at 100% (reference range, 0–20%), suggesting thymoma. Treatment included pyridostigmine, 30–45 mg 3–4 times daily, to control the myasthenia symptoms, while the ill-defined neck mass was being evaluated. A mildly enlarged thyroid was noted on physical examination. Hematology panel revealed thyroid-stimulating hormone (TSH) levels in the low normal range; the thyroid microsomal antibody was normal. Chest radiography showed minor tracheal deviation, and a previous computed tomogram showed what appeared to be a 3-cm enlarged mass in the thyroid. Ultrasonographically guided thyroid biopsy did not show malignancy, but a benign mesenchymal-type tumor was found and surgical excision was planned. Intraoperatively, a thymoma of the left cervical thymic tongue was found. At 6 months' follow-up, the ptosis and oral mucosal lesions had improved significantly, although she continued topical corticosteroid therapy intermittently for minor erosive oral disease.