Late post-partum hemorrhage after cesarean section due to rupture of a false aneurysm of the uterine pedicle

We report a 14 year-old girl with a huge adenomatous goiter in the left lobe in the thyroid gland reaching the aortic arch with elevated thyroglobulin. The tumor grew rapidly for two years since the initial diagnosis as an euthyroid hemilateral goiter. Ultrasonography revealed multinodular tumors and magnetic resonance imaging made clear the lower expanding site of the tumor. We recommend careful follow up of hemilateral diffuse goiters by ultrasonography for earlier detection of nodular changes as seen in our case.     

The basilic vein as an in situ bypass for occlusion of the brachial artery

For 30 years we have followed the case of a euthyroid patient who had a goiter diagnosed at age 15. It was originally diffuse and did not shrink during treatment, first with desiccated thyroid extract and then with triiodothyronine. After treatment was stopped, the goiter gradually became nodular and calcified when the patient was in her late teens or early 20s; it then shrank. She remains clinically and chemically euthyroid, with a calcified, multinodular goiter and persistent elevation of the serum PBI concentration which, early in the course of the disease was shown to include a substantial fraction of butanol-insoluble iodine. In a euthyroid patient, the association of an elevated serum PBI concentration (with an abnormally large butanol-insoluble iodine fraction) with a diffuse goiter that became nodular and calcified may be unique.     

Hyperthyroidism and carcinoma of the thyroid gland

The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a few tumors are suspected preoperatively with ultrasonography or fine needle aspiration or 131 I scan. In 408 patients who underwent surgery for hyperthyroidism in our Surgery Department from January 1967 through December 1994 the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.     

Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors

The majority of familial medullary thyroid neoplasms are associated with germ-line mutations of the RET proto-oncogene, yet very little is known about the mechanisms involved in the pathogenesis of familial and sporadic nonmedullary thyroid tumors. A subset of thyroid tumors have loss of heterozygosity of chromosome 10q22-23, a region harboring the gene responsible for Cowden disease, an autosomal dominant hamartoma syndrome associated with thyroid and breast tumors. PTEN/MMAC1/TEP1 codes for a dual-specificity phosphatase and is likely a tumor suppressor gene. We sought to determine the PTEN status in a series of epithelial thyroid neoplasms. We studied 95 sporadic thyroid tumors, of which 39 were papillary thyroid carcinomas (PTCs), 12 were follicular carcinomas, 9 were anaplastic carcinomas, 5 were Hürthle cell carcinomas, 21 were nonfunctioning follicular adenomas, and 9 were Hürthle cell adenomas. Direct sequencing of PCR-amplified products was performed for all nine exons of PTEN. Two polymorphic markers, one located in intron 8 and another, a dinucleotide repeat marker, AFMa086wg9, located within intron 2, were analyzed in paired blood-tumor DNA samples to assess hemizygous deletions of PTEN. We found a somatic frameshift mutation in one PTC, which was expected to generate a premature stop codon 2 amino acids downstream. Twenty-six % of informative benign tumors (four follicular adenomas and three Hürthle cell adenomas) and only 3 of 49 (6.1%) informative malignant tumors (one PTC, one follicular carcinoma, and one anaplastic carcinoma) showed evidence of hemizygous deletion of PTEN (P = 0.046). We conclude that a subset of thyroid tumors have somatic deletions of the PTEN gene, predominantly the benign forms, and that small intragenic mutations of PTEN are infrequent in thyroid tumors. We speculate that other mechanisms of PTEN inactivation, rather than small intragenic mutations, might occur in the hemizygously deleted samples and act as the "Knudson second hit." Alternatively, other tumor suppressor genes mapping to chromosome 10q22-23 could be the actual targets for such deletions and thus represent the various hits in the pathway of multistep carcinogenesis.     

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.     

Extinction coefficient of thyroglobulin

The extinction coefficient at 280 nm of the solution (pH 7,2-7,4) of thyroglobulin from normal thyroid and nodular euthyroid goiter was measured with the values of 0,6-0,7 to 0,9 ml.mg-1.cm-1. The value of E1%280 as function of the iodoamino acid content depends on the morphological state of the thyroid gland. A simple method for determination of the E1%280 value by measuring of the protein absorption spectrum is proposed.     

Cystic thyroid lesions in children

BACKGROUND/PURPOSE: Cystic lesions of the thyroid encompass a wide and heterogeneous group of disease states in children, ranging from benign purely cystic entities to malignant tumors. The purpose of this study was to study both the presentation and management of cystic thyroid lesions in the pediatric population. METHODS: A retrospective review of all thyroid masses presenting between 1978 and 1996 and found to be purely or partially cystic on ultrasound examination was conducted, looking at presentation, family history, laboratory values, ultrasound scan and radionuclide imaging, and pathological and cytological evaluation. RESULTS: Twenty-four patients (19 girls, 5 boys) aged 6 to 18 years received the diagnosis of cystic lesions of the thyroid. Of these, 23 presented with painless neck masses, 21 were clinically euthyroid, only one had a single abnormal thyroid function test, only two had mildly positive antithyroid antibody test results, and nearly 30% had a positive family history of thyroid disease. Ultrasonography showed pure cysts in five patients and mixed solid cystic lesions in 19 patients. On scintiscan, six lesions were hot, 13 were cold, three showed normal uptake, and two were mixed. Treatment included either observation, aspiration, cyst sclerosis, surgery, or combinations thereof. Pathological and cytological results included follicular adenoma (n = 9), cystic degeneration (n = 6), multinodular goiter (n = 4), carcinoma (n = 2), branchial cleft cyst (n = 1), and undetermined (n = 2). CONCLUSIONS: Thyroid cysts are often thought to represent benign degenerative disease. Our study, which is the first in the literature to specifically address thyroid cysts in children, shows that ultrasound scan is useful in evaluating thyroid masses, whereas laboratory and radionuclide are of less value, and that single lesions of mixed echogeneity are likely to represent neoplasms, a significant percentage of which are malignant.     

Iodine induced thyroid disease

Although iodine prevents goiter, enlarged thyroid glands continue to be detected in subjects, especially children, in spite of adequate iodine ingestion. Iodine may cause goiter in susceptible individuals by inhibiting the organic binding of iodine as is seen in adult asthmatics, neonates born of iodine ingesting mothers and in subjects residing along the littoral of Japan. Myxedema, especially in treated Graves' disease and Hashimoto's disease, may also be precipitated by iodine. On the other hand, iodine given to euthyroid subjects in areas of endemic goiter and to subjects with nontoxic nodular goiter may induce thyrotoxicosis by disclosing diffuse autonomously functioning thyroid tissue. An indirect adverse effect of iodine upon the thyroid gland may be manifested by lymphocyte glandular infiltrates and chronic thyroiditis which were sparse or absent in thyroid glands removed from subjects living in iodine deficient areas before iodine prophylaxis and therapy. Not only has the incidence of thyroiditis increased, but the histologic and clinical distinctions between treated Graves' disease and chronic thyroiditis have become indistinct. Experimentally, chronic thyroiditis has been produced in animals following large doses of iodine. Accumulated evidence supports the concept that iodine contributes to the genesis of chronic thyroiditis.     

Thyroid surgery in children and teenagers

From 1961 to 1976 62 patients under age 20 underwent thyroidectomy for various thyroid disorders. Twenty-four thyroid lobectomies and eight subtotal or near-total thyroidectomies were performed for benign nodular goiter. Eight near-total thyroidectomies and two thyroid lobectomies were performed for carcinoma. Two patients also had a radical neck dissection. Twenty patients with hyperthyroidism underwent near-total thyroidectomy. Postoperative complications occurred in six patients-all with hyperthyroidism. Operative mortality was zero. Two indications for thyroidectomy in our series were nodular goiter (to rule out carcinoma), and hyperthyroidism (that was not well-controlled medically or where surgery was chosen as primary therapy). In patients with nodular goiters that required surgery, a minimal complication rate occurred. By contrast, surgery for hyperthyroidism was associated with a high postoperative complication rate, six of 20 patients or 30%, which must be anticipated by the surgeon.     

Management of hyperparathyroidism in an endemic goiter area

In an endemic goiter area patients with hyperparathyroidism (HPTH) frequently also have thyroid abnormalities. In a retrospective study of 95 patients with HPTH we assessed the diagnostic accuracy of imaging techniques (ultrasonography or radionuclide scanning) for preoperative localization of parathyroid adenomas. Altogether 86% of our patients had goiter, requiring thyroid resections in 37%. For 19 patients the parathyroid exploration was the second or third cervical operation, most of them due to goiter. We found that the overall rate of transient and permanent recurrent nerve paralysis is considerably increased in patients with previous neck surgery (26% vs. 7%). The combination of ultrasonography and radionuclide scanning can lead surgeons to the site of parathyroid lesions responsible for HPTH in 85% of cases, although frequent nodular goiters can produce pitfalls for correct imaging in iodine-deficient countries. In endemic goiter areas preoperative localization studies can be recommended in patients with primary HPTH--for evaluation of thyroid pathology possibly leading to resection or its accuracy in localizing parathyroid adenomas. These studies also seem justified in patients with previously unsuccessful neck explorations for HPTH.     

Myelinated axon undergoes complete demyelination in the panencephalopathic--but it is merely subjected to the Wallerian degeneration in the polioencephalopathic type of transmissible spongiform encephalopathies

The aim of a cancer registry is to study the incidence of cancer in a well-determined population and to allow epidemiological research to the setting up of diagnosis and therapeutic strategies. The Belgian Thyroid Cancer Study Group (BTCSG) was founded in 1990. In the present study we report data collected from 1988 to 1995 in 397 patients with a differentiated (papillary and follicular) thyroid carcinoma living in the french-speaking area of Belgium. The sex ratio female/male is 3.5 and the median ages at the diagnosis, is similar (45 yrs, 12-82) in both sexes. Seven cases of thyroid cancer were registered in young patients less than 18 yrs old. Thyroid carcinoma were associated with multinodular goiter in more than 50% cases. Cancer was bilateral in 17%. Papillary histological type accounts for 84% in our series while its diagnosis was established in 45% at early clinical stages (TO-T1). These observations could probably be related with 1) broader indications and more aggressive options for the surgical removal of diffuse multinodular goiter, 2) more sophisticated pathologic examinations that might have led to the detection of a greater incidence of occult carcinomas, incidentally discovered. Lymph nodes metastases were present at the time of diagnosis in 20%, especially in young patients. The risk for local and/or lateral recurrence or distant metastases is significantly related to the size of the tumor, histologically verified lymph node metastases and the values of the EORTC prognostic index (> or = 50) that additionally takes into account the differentiation of the tumor. Considering our short median follow-up time of 25 months, it is currently too early to define if the controversial attitude about the extent of surgery (total thyroidectomy plus I131 or individualized surgery) can also negatively influence the risk for recurrence. In our series, eight patients died of thyroid cancer.     

Value of color-coded Doppler sonography in the differential diagnosis of nodular thyroid gland changes

AIM: The incidence of functional autonomous adenomas, detected in every second nodular goiter by scintigraphic methods is very high in an area of iodine deficiency. The color-coded Doppler sonography (CCDS) as a diagnostic tool in differentiating thyroid nodules is discussed controversially. METHODS: In this prospective study we investigated the value of CCDS in 200 patients with nodular thyroid alterations compared with 99m-Technetium (Tc) scintigraphy. RESULTS: Focal maximas of Tc-uptake were detected in 22.5% of all patients, and 44.5% of the thyroid nodules showed increased vascularity. There was no correlation between nodular vascularity and thyroid 99m-Tc uptake (TcTU). In contrast to this we could demonstrate a significant relation between vascularity and the diameter of the nodule (p < 0.0001). The results are discussed in the context of method specific limitations of ultrasound examinations. CONCLUSION: Our results confirm that CCDS has no great importance in the differentiation of thyroid nodules. Scintigraphy remains the diagnostic method of choice to assess the topographic thyroid function.     

Is it hyperthyroidism? You can't always tell from the clinical picture

Hyperthyroidism usually causes a typical clinical syndrome in younger patients, but in some cases it presents with only minimal or atypical symptoms. This is especially true in older patients, who may have none of the typical signs, such as goiter. Differentiation between a euthyroid hyperthyroxinemic state and hyperthyroidism is crucial to avoid unnecessary treatment of persons with a normally functioning thyroid gland. In addition, distinguishing between causes of hyperthyroidism is important, because the treatments may be completely different. For example, in subacute thyroiditis, supportive care and observation are usually the only treatments needed, whereas in Graves' disease or toxic multinodular goiter, more definitive therapy is required.     

Parameters of linear-quadratic radiation dose-effect relationships: dependence on LET and mechanisms of reproductive cell death

Nitric oxide mediates a wide array of cellular functions in many tissues. It is generated by three known isoforms of nitric oxide synthases (NOS). Recently, the endothelial isoform, NOSIII, was shown to be abundantly expressed in the rat thyroid gland and its expression increased in goitrous glands. In this study, we analyzed whether NOSIII is expressed in human thyroid tissue and whether levels of expression vary in different states of thyroid gland function. Semiquantitative RT-PCR was used to assess variations in NOSIII gene expression in seven patients with Graves' disease, one with a TSH-receptor germline mutation and six hypothyroid patients (Hashimoto's thyroiditis). Protein expression and subcellular localization were determined by immunohistochemistry (two normal thyroids, five multinodular goiters, ten hyperthyroid patients and two hypothyroid patients). NOSIII mRNA was detected in all samples: the levels were significantly higher in tissues from hyperthyroid patients compared with euthyroid and hypothyroid patients. NOSIII immunoreactivity was detected in vascular endothelial cells, but was also found in thyroid follicular cells. In patients with Graves' disease, the immunostaining was diffusely enhanced in all follicular cells. A more intense signal was observed in toxic adenomas and in samples obtained from a patient with severe hyperthyroidism due to an activating mutation in the TSH receptor. In multinodular goiters, large follicles displayed a weak signal whereas small proliferative follicles showed intense immunoreactivity near the apical plasma membrane. In hypothyroid patients, NOSIII immunoreactivity was barely detectable. In summary, NOSIII is expressed both in endothelial cells and thyroid follicular cells. The endothelial localization of NOSIII is consistent with a role for nitric oxide in the vascular control of the thyroid. NOSIII expression in thyroid follicular cells and the variations in its immunoreactivity suggest a possible role for nitric oxide in thyrocyte function and/or growth.     

Familial insensitivity of the pituitary and periphery to thyroid hormone: a case report in two generations and a review of the literature

A clinically euthyroid 2-yr-old girl was found to have diffuse goiter that measured 3 X 5.5 cm with a prominent systolic bruit. Serum free T4 (3.4 ng/dl) and serum T3 (360 ng/dl) remained elevated for the next 10 months even though she remained clinically euthyroid. Elevation of serum free T4 (3.0 ng/dl) and serum T3 (265 ng/dl) was also present in the 24-yr-old nongoitrous mother who had symptoms and signs of hypothyroidism. Following intravenous injection of TRH, basal TSH levels of 2.7 and 2.8 microunits/ml increased to peak values of 17 and 21 microunits/ml at 30 min in the daughter and mother, respectively. Administration of exogenous T3 followed by sequential testing with boluses of TRH revealed retention of TSH responsiveness in both daughter and mother during pretreatment with dosage regimens of T3 below 125 micrograms daily. Maintenance of TSH responsiveness to TRH in the presence of elevated levels of serum free T4 and serum T3 indicates relative pituitary insensitivity to thyroid hormone which could be overridden by increasing the circulating levels of serum T3 three to fivefold over the already elevated basal levels. The absence of clinical signs of thyrotoxicosis indicates peripheral insensitivity to thyroid hormone with elevated circulating concentrations presumptively compensating for the defect. Resistance to thyroid hormone in two generations of the same family suggests genetic inheritance, and is concordant with four earlier reports of familial aggregation in this syndrome.     

Value of immunoperoxidase staining of thyroglobulin in fine needle aspiration cytology of thyroid diseases

To elucidate the value of thyroglobulin staining by the immunoperoxidase method in fine needle aspiration cytology of thyroid diseases, it was performed on fine needle aspiration smears of 57 cases of various thyroid diseases. Thirteen of 22 cases (59%) with benign nodular goiter were positive. Eight of 14 cases (57%) with papillary thyroid carcinoma were positive. Among these eight cases with positive staining, seven were at clinical stage II or less. Among the other six cases with negative staining, five cases were in clinical stage III or more. There was a significant relationship between clinical stage and thyroglobulin staining (P < .05). One of 10 cases with thyroid cysts was positive. One of four cases with anaplastic carcinoma was positive. One of two cases with follicular thyroid carcinoma was positive. Two cases of subacute thyroiditis were positive. One case of Hashimoto's thyroiditis was positive. Two cases of metastatic thyroid cancer from the ovary were negative. These results reveal that positive thyroglobulin staining was helpful in defining the source of tissue from the thyroid. However, negative staining could not definitively exclude a thyroid origin. Positive thyroglobulin staining in papillary thyroid carcinoma correlated with less advanced clinical stages.     

Primary and secondary carcinomata with focal nodular hyperplasia in a multinodular thyroid: case report

A patient is described whose multinodular thyroid gland was found to have a primary papillary adenocarcinoma, a metastatic renal-cell carcinoma, and focal nodular hyperplasia. To our knowledge, this is the first case report of such an unusual combination. In a patient with known malignancy elsewhere, the possibility that a recent thyroid mass may be a metastasis should be considered.     

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.     

Lateralization of repeated filtered transients

The catabolic phase of thyroid secretion --thyroglubulin (Tg) uptake and hydrolysis, release of hormones--has been investigated in vitro, by incubating thyroid slices with 0.1% labelled Tg, in cases of isolated adenomas. Twenty-two specimens were examined: 11 cold follicular adenomas, 5 hot nodules from euthyroid patients, 2 untreated toxic adenomas, and 4 pretreated toxic adenomas. The results were compared with those obtained in 11 specimens of normal tissue. Tg pinocytosis (the amount of Tg taken up by the slices per mg of tissue) was severely impaired in all the non-toxic nodules, cold or hot, i.e., whatever the in vivo activity of the thyroid iodide pump. In toxic adenomas, every step of the catabolic hormonogenesis was activated: high pinocytotic activity, increased Tg hydrolysis, and the discharge of hormonal products; in pretreated cases, the whole process was slowed down. Enzymic activity of the acid hydrolases, beta-galactosidase and cathepsin, was elevated in all the nodules so far investigated, particularly in the toxic adenomas.