Effects of thyroid status on clonidine-induced hypo-activity responses in the developing rat

Summary Clonidine-induced hypoactivity was studied in rats made neonatally hypo- and hyperthyroid (PTU or T₄ administered between 1–27 days postnatally) as an indication of central presynaptic ₂-adrenoceptor function. Paradoxically, at 28 days postnatally both treatments caused an increase in clonidine-hypoactivity compared with untreated control animals, which was not due to sex differences amongst littermates in the various groups. It is proposed that whereas the hyperthyroid neonate data perhaps reflect an enhancement of presynaptic ₂ function similar to that seen in the adult rat brain, the result obtained for the hypothyroid neonates could perhaps be due to a retardation of the ontogeny of central noradrenergic neurones.     

Thyroid hormones,Sertoli cell proliferation and differentiation in progenies from carbamazepine-treated rat dams during pregnancy and lactation

Carbamazepine (CBZ) is used in the control of seizure and affective disorders, causing hypothyroidism. Thyroid hormones regulate the Sertoli cell proliferation and differentiation. Clinical aspects must be considered since epileptic fertile women need to continuously use CBZ during pregnancy and lactation. This study aimed to evaluate the effects of CBZ on testis development of rat offspring from dams treated during pregnancy/lactation. Rat dams received CBZ (20 mg kg⁻¹ day⁻¹) or vehicle by intra-peritoneal route during gestation and lactation. Progenies were euthanised at 4, 14, 41, 63 and 93-days post-partum (dpp) for the evaluation of T3, T4 and TSH plasma total levels. Testicular cross sections were submitted to anti-Ki67, anti-PCNA, anti-p27^kip1 and anti-transferrin immunolabelling for the evaluation of Sertoli cells. There was a significant reduction in p27^kip1-positive Sertoli cell numerical densities and an increase in TSH level at 14 dpp. CBZ exposure affected the volume density of transferrin-positive immunolabelling at 63 dpp. These results suggest that CBZ may cause a dysregulation of the controller system of thyroid hormones homeostasis leading to an increase in the proliferation rate at the neonatal phase and a differentiation delay of the Sertoli cell, culminating in an altered function at late puberty. The occurrence of hypothyroidism cannot be completely discarded.     

Investigation and management of the neck lump

A neck lump is a common presenting sign in both the paediatric and adult population and may represent a broad range of benign or malignant diagnoses. The appropriate initial assessment, investigation and management is key to delivering appropriate treatments and to avoid missing potentially serious diagnoses. There is a range of imaging modalities available to the treating clinician and huge variability in the appropriate surgical or non-surgical management of disease. In this article we discuss the approach to the assessment of patients with a neck lump, including the history and examinations which should take place. We discuss the imaging modalities which are most appropriate for each condition and the range of management options available. Both common and rarer diagnoses are discussed through the course of the review.     

Macrofollicular Variant of Follicular Thyroid Carcinoma (MV-FTC) with a Somatic DICER1 Gene Mutation: Case Report and Review of the Literature

Benign thyroid lesions such as multinodular goiter and adenomatoid nodules are well-circumscribed lesions displaying a macrofollicular growth pattern and lack of nuclear atypia. The highly unusual macrofollicular variant of follicular thyroid carcinoma (MV-FTC) mirrors these attributes and is thereby misclassified by cytological examination of fine-needle aspiration biopsies. The MV-FTC diagnosis is instead suggested following histological investigation, in which malignant attributes, most commonly capsular invasion, are noted. The bulk of MV-FTCs described in the literature arise in younger female patients and carry an excellent prognosis. A recent coupling to mutations in the DICER1 tumor suppressor gene has been proposed, possibly indicating aberrancies in micro-RNA (miRNA) patterns as responsible of the tumorigenic process. We describe the cytological, histological and molecular phenotype of a 35 mm large MV-FTC arising in the right thyroid lobe of a 33-year-old female with a family history of multinodular goiter. The tumor was encapsulated and strikingly inconspicuous in terms of cellularity and atypia, but nevertheless displayed multiple foci with capsular invasion. A next-generation molecular screening of tumor DNA revealed missense variants in DICER1 (p. D1709N) and MET (p. T1010I), but no established fusion gene events. After sequencing of germline DNA, the DICER1 mutation was confirmed as somatic, while the MET variant was constitutional. The patient is alive and well, currently awaiting radioiodine treatment. This MV-FTC mirrors previous publications, suggesting that these tumors carry a favorable prognosis and predominantly arise in younger females. Moreover, DICER1 mutations should be considered a common driver event in the development of MV-FTCs.     

The superior laryngeal nerve loop and its surgical implications

Summary Based upon findings from 60 cadavers (120 sides), the incidence of superior laryngeal nerve loop, connecting the cervical sympathetic chain and the superior laryngeal nerve and its branches, the external and internal laryngeal nerve, was 98.3% (118 out of 120 sides). In most cases the loop connected the sympathetic chain and the external laryngeal nerve. The external laryngeal nerve was looped, and not linear as traditionally thought. The loop could be divided into three categories, V-shaped, U-shaped and mixed, and subdivided into 5 types and 17 subtypes according to morphological variation. The loop without exception innervated not only the cricothyroid muscle, but also the thyroid gland. The loop is one of the origins of the thyroid nerve. It seems that for thyroid surgery the loop, when lower in position, should be carefully separated from the superior thyroid vessels before the latter are ligated, in order to preserve a normal nerve supply to the muscle as well as to the part of the gland that remains after surgery.

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L'anse du nerf larynge supérieur, étude anatomique et applications chirurgicales

Résumé La fréquence d'une anse du nerf laryngé supérieur réalisant une anastomose entre la chaine sympathique cervicale et le nerf laryngé supérieur et/ou ses branches (rameau laryngé externe et ingerne), est de 98,3 % (118/120). Ce résultat s'appuie sur l'étude de 60 cadavres. Dans la plupart des cas, l'anastomose se fait entre la chaine sympathique cervicale et le rameau laryngé externe. Ce rameau laryngé externe a un trajet curviligne et non linéaire conformément aux données classiques. Il existe trois catégories d'anses : en "V", en "U" et mixte ; on peut également les subdiviser en 5 types et 17 sous-types en fonction des variations morphologiques. Cette anse innerve constamment non seulement le muscle cricothyroïdien mais aussi la glande thyroïde dont elle fournit une partie de l'innervation. Lors de la chirurgie thyroïdienne, si l'anse est en position basse, les nerfs doivent être soigneusement disséqués et séparés des vaisseaux thyroïdiens supérieurs avant ligature de ces derniers de façon à conserver l'innervation normale du muscle et de la partie restante de la glande.

     

Mitotic counts in rat adenohypophysial thyrotrophs and somatotrophs: Effects of short-term thyroidectomy,thyroxine, and thyrotropin-releasing hormone

The question of whether thyroxine (T₄) and thyrotropin-releasing hormone (TRH) affect mitoses in pituitary thyrotrophs (Tt) and somatotrophs (St) of hypothyroid rats was investigated. Fifteen day thyroidectomized (Tx) rats were used. Groups of Tx animals received T₄ or TRH or both. Except 6 and 24 h TRH groups, the animals were sacrificed 12 h after injections. Unoperated euthyroid rats served as controls. In Tx group adenohypophysial mitoses were significantly increased. T₄ diminished mitoses in Tx rats. Mitotic counts were decreased in 6 and 24 h Tx groups, but increased in 12 h TRH group. TRH plus T₄ in Tx animals had a synergistic effect on adenohypophysial mitoses. In unoperated controls few mitoses were observed in Tt and more mitoses in St. In Tx rats more mitoses were seen in Tt than in St. T₄ alone failed to reduce mitoses in Tt but increased them in St. We concluded that T₄ affects Tt and St replication. In normal rats mitoses occur mainly in St. In Tx rats mitotic activity increased in Tt. TRH plus T₄ have a synergistic motogenic effect on St. T₄ but not TRH affects St replication. It appears that the presence, of T₄ is necessary for St multiplication.     

Neurological prognosis correlated with variations over time in the number of subependymal nodules in tuberous sclerosis

In tuberous sclerosis (TS), brain CT reveals subependymal nodules, cortical tubers and white matter lesions. This study is a retrospective analysis of the relationship between the variations over time in the number of subependymal nodules and the clinical course in cases of tuberous sclerosis. Twenty-four children with tuberous sclerosis, who attended the National Children's Hospital as outpatients, were followed by means of brain CT examinations for 7 years and 1 month on average. Cranial MRI was also performed in 22 cases. Brain CT disclosed subependymal nodules already in early infancy. In almost all cases, the number of subependymal nodules gradually increased with age, especially around the frontal horn of the lateral ventricle. The increase stopped at around age 10. The cases with five or more subependymal nodules at the initial or subsequent CT examination (17 patients; Group A) exhibited a significantly greater number of cortical tubers than those with less than five (five patients; Group B) and had white matter lesions unlike Group B. In addition, the number of cases with either infantile spasms or mental retardation was significantly higher in Group A than Group B (P<0.005). In conclusion, the number of ventricular subependymal nodules may allow prediction of the severity of the cerebral dysfunction in TS. Our results suggest that its variation may reflect the degree of the embryologic disorder when neuronal cells grow in the early gestational period.     

Blutgruppenantigenexpression in papillären karzinomen der schilddrüse Eine immunhistochemische und klinische studie über das Vorkommen von Lewis-, AB0- und verwandten antigenen

Zusammenfassung In einer immunhistochemischen Arbeit wurden 104 papilläre Schilddrüsenkarzinome auf das Vorkommen von Blutgruppenantigenen des AB0- und Lewis-Systems sowie verwandter, tumorassoziierter Antigene mit Typ-1- und Typ-2-Grundstruktur untersucht. Folgende Strukturen wurden im Gewebe nachgewiesen: CA-50 (sialinierter Typ-1-Vorläufer), CA-19-9 (Sialyl-Le^a), Le^a, Le^b, A, B, H, Le^x, Sialyl-Le^x und Le^y. Während gesundes, adultes Schilddrüsengewebe keine Blutgruppenantigene exprimierte, waren die papillären Karzinome durch die progressive Expression dieser Strukturen gekennzeichnet. Die meisten Tumoren reagierten mit dem C-50-Antikörper (84%), während deutlich weniger Gewebe das CA-19-9-Antigen aufwiesen (38%). Die Typ-2-Strukturen Le^x (47%) und Le^y (13%) wurden deutlich seltener gefunden als die korrespondierenden Typ-1-Antigene Le^a (71%) und Le^b (62%). Die Vorbehandlung mit Neuraminidase verstärkte die Le^a- und Le^x-Färbeergebnisse in 27 bzw. 44 Fällen. Von den A-, B-, und H-Antigenen wurden die A-Determinanten am häufigsten nachgewiesen (24%). In vergleichenden Untersuchungen von Serienschnitten der gleichen Tumoren wurde eine Koexpression mehrerer Typ-1-Antigene im denselben Tumorarealen festgestellt. Karzinome mit Expression von Typ-1- und Typ-2-Strukturen wiesen häufig eine komplementäre Antigenexpression in verschiedenen Bereichen der Gewebe auf. Einige Tumoren exprimierten Typ-1- und Typ-2-Strukturen auch in den gleichen Zellen, jedoch in verschiedenen Bereichen der jeweiligen Zellen.In 68 Fällen wurde eine Follow-up-Untersuchung durchgeführt. Die Beobachtungszeiträume lagen zwischen 12 und 217 Monaten. In 13 Fällen rezidivierte der Tumor, 7 dieser Patienten verstarben an dem Tumorleiden. Die meisten Rezidive traten bei Patienten auf, deren Tumoren die Grenzen des Organs überschritten hatten (pT4, n=19), während keines der pT1-Karzinome (n=20) zu einem Rezidiv geführt hatte. Während Lymphknotenmetastasen in 39 Fällen auftraten, wiesen 6 Patienten Fernmetastasen auf. Die klinischen Ergebnisse wurden mit den Färbeergebnissen korreliert. Es bestand kein Zusammenhang zwischen Antigenexpression und Tumordifferenzierung. Die pT4-Tumoren zeigten eine signifikant stärkere Expression der CA-50-, CA-19-9-, Le^a und Sialyl-Le^x-Strukturen. Karzinome mit Le^y-Expression wiesen signifikant häufiger Metastasen auf. Le^y, H-Typ-1 und H-Typ-2 traten häufiger in rezidivierenden Tumoren auf. Im Gegensatz dazu waren alle Patienten, deren Karzinom das A-Antigen exprimierte, fernmetastasen- und rezidivfrei (n=14). In der multiplen Regressionsanalyse wies der Faktor Fernmetastasierung die größte prognostische Relevanz auf, während im Vergleich dazu die Färbeergebnisse statistisch von untergeordneter Bedeutung waren.

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Blood group antigen expression in papillary carcinoma of the thyroid — An immunohistochemical and clinical study on the occurrence of Lewis-, AB0, and derived antigens

Nine monoclonal antibodies, lectin from Ulex europaeus and neuraminidase enzyme were employed to demonstrate the occurrence of type 1 and type 2 blood group antigens in 104 cases of papillary carcinoma of the thyroid. The reagents applied, recognize the following blood group related antigens: CA-50 (sialylated type 1 precursor), CA-19-9 (sialylated Le^a), Le^a, Le^b, A, B, H, Le^x, sialylated Le^x, and Le^y.Immunohistochemical studies revealed that papillary carcinoma of the thyroid, in contrast to histologically normal thyroid tissue, is characterised by a progressive expression of blood group antigens. Most tumours (84%) reacted with C-50 antibody, whereas only a minority of the tissues demonstrated the CA-19-9 antigen (38%). Type 2 structures Le^x (47%) and Le^y (13%) were found less often than their corresponding type 1 isomers Le^a (71%) and Le^b (62%). Desialylation with neuraminidase increased the Le^a and Le^x staining intensity in 27 and 44 cases, respectively. of the A, B, H antigens the A determinants encountered most frequently (24%).Comparative examinations of sequential sections of the same tumour revealed coexpression of type 1 antigens in the same areas. In carcinomas showing type 1 and type 2 antigen reactivity, a complementary distribution of the structures in different tumour areas was often demonstrated. Some tumours presented combined type 1 and type 2 antigen expression in the same cells, however, in distinct areas within the cell.A follow-up examination was carried out in 68 of the 104 cases. The observation time ranged from 12 to 217 months. Thirteen patients suffered from recurrence, of which 7 died. While lymphatic metastases occurred in 39 tumours, distant metastases were detected in 6 patients. Most of the recurrences were found in patients with tumour classification pT4 (n=19), whereas none of the pT1 carcinomas (n=20) showed recurrence.The clinical results were compared to the blood group antigen expression results. There was no correlation between antigen expression and differentiation degree of the tumour. The pT4 tumours showed a significant higher expression of the CA-50, CA-19-9, Le^a and Sialyl Le^x structures. Carcinomas expressing the Le^y antigen were associated with a significant higher level of metastasizing capacity. The Le^y, H type 1 and H type 2 antigens occurred more frequently in recurrent tumours (n=14). In contrast, none of the patients whose carcinomas expressed the Aantigens (n=14) suffered from a recurrence or hematogenous metastasis.Multiple stepwise regression analysis was carried out to check the importance of each staining and clinical factor. In this analysis, distant metastasis was the most important parameter, whereas the staining results were of minor statistical importance.

     

Das Tumorrezidiv am Hals nach papillarem Schilddrüsenkarzinom Eine statistische Analyse zur Rezidivwahrscheinlichkeit nach Radikaloperation

Zusammenfassung 308 Patienten mit papillärem Schilddrüsenkarzinom (82,6% des Gesamtkrankengutes, Operation 19522–1987), die postoperativ als tumorfrei eingestuft worden waren, wurden retrospektiv analysiert. Die Beobachtungszeit reicht von 1 Monat bis zu 29,4 Jahren (mediane Beobachtungszeit 4,58 Jahre). Bei 32 Patienten (10,4%) wurde ein Tumorrezidiv am Hals diagnostiziert (lokal und/oder regionär). 8 davon sind am Ende der Beobachtungszeit nicht tumorfrei, 6 sind am Tumor verstorben (tumorbedingte Todesrate 18,8%, relative Mortalität 66,7%, im Gesamtmaterial 2,9% bzw. 29,0%). Die kumulative Rezidivwahrscheinlichkeit beträgt 9,98% nach 5 und 16,98% nach 10 Jahren. Die statistische Analyse der Rezidivwahrscheinlichkeit erfolgte nur an Patienten, die mindestens 5 Jahre beobachtet wurden oder innerhalb dieses Zeitraumes verstarben. Als Einflußgrößen wurden neben Alter and Geschlecht, tumorstadium und histologische Kriterien des Tumors berücksichtigt. Als bestimmend für das Auftreten eines Rezidivs nach 5 Jahren Beobachtungszeit erweisen sich der Status der regiondren Lymphknoten, der Differenzierungsgrad des Tumors und das Geschlecht der Patienten. Zur Verbesserung der Rezidivrate wird eine abgestufte therapeutische Radikalität in Abhängigkeit von den Einflußgrößen empfohlen.

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Cervical tumour recurrence after papillary thyroid carcinoma. A statistical analysis on the recurrence after potentially curative surgery

Summary 308 cases of papillary thyroid carcinoma (82.6% of our patients operated on between 1952 and 1987) who had undergone potentially curative surgery were analysed postoperatively. The follow-up ranges from 1 month to 29.4 years (median 4.58 years). In 32 cases (10.4%) a cervical tumour recurrence (local recurrence and/or cervical lymph nodes) was found. 8 of these are not free of tumour at the end of the follow-up, 6 had died of thyroid carcinoma (case fatality rate 18.8%, mortality rate 66.7%, in the entire material 2.9% and 29.0% respectively). The cumulative recurrence rate is 9.98% after 5 years and 16.98% after 10 years. A statistical analysis of the probability of recurrence was carried out only for patients who could be followed at least 5 years or those who died within 5 years. Age, sex, stage of tumour and histological criteria were taken into account as statistical variables. The state of cervical lymph nodes, the differentiation of the tumour and the patients' sex turned out to be determining factors for tumour recurrence after 5 years. In order to improve the recurrence rate a differentiated surgical radicality, depending on the above mentioned variables, is recommended.