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Amiodarone iodine induced thyrotoxicosis occurs frequently in patients residing in areas of mild iodine deficiency and in patients with preexisting goiter. Drug therapy of the hyperthyroidism is often unsuccessful. Twenty-three patients with amiodarone induced thyrotoxicosis were either not treated, treated with 40 mg methimazole daily or with methimazole and 1 gm potassium perchlorate daily for up to 40 days and then with methimazole alone. Thyrotoxicosis was more likely to spontaneously remit in patients without goiter. Therapy with methimazole alone was unsuccessful in inducing euthyroidism in 5 patients with goiter. However, combined therapy with methimazole and potassium perchlorate rapidly alleviated hyperthyroidism in almost all patients with goiter. This drug combination is successful because perchlorate inhibits the active transport of iodine into the thyroid and methimazole blocks the intrathyroidal synthesis of thyroid hormones.

Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of l-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month l-thyroxine course (0.1–0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ)=89.1 ± 2.9; P=0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P=0.03), anxiety (P=0.05), somatic complaints (P=0.0005), and depressive features (P=0.002) scales; the total score was also significantly higher (42.0±3.8; P=0.005). After l-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9±4.0; P=0.002 (treated versus untreated)]; somatic complaints (P=0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P=0.04) significantly decreased with respect to untreated patients. The remarkable effects of l-thyroxine treatment observed in the present study indicate that patients with subclinical hypothyroidism may require early therapy to provide specific treatment for their neuropsychological alterations and to avoid progression toward frank hypothyroidism.

Measurements of serum thyroglobulin (hTg) were performed using a specific radioimmunoassay. Sera with detectable anti-thyroglobulin (anti-Tg) antibody titers (>1∶10) as assessed by passive hemagglutination were discarded. Assays were carried out under conditions in which anti-Tg titers less than 1:10 produced no interference. The assay sensitivity was 1.25 ng/ml and the mean ± SE concentration of serum hTg in 58 control subjects was 9.5 ± 0.9 ng/ml (range< 1.25–27 ng/ml). A slight but significant (p<0.025) increase in the mean hTg level was observed in 12 pregnaint women at delivery (25.7 ± 5.2 ng/ml). Moderate to marked elevations of serum hTg were observed in patients with nontoxic goiter (61.4 ± 15 ng/ml; n = 23), subacute thyroiditis (138 ± 67 ng/ml; n =5), toxic adenoma (129 ±47 ng/ml; n =13), untreated (424 ± 101 ng/ml; n = 35) or treated (328 + 222 ng/ml; n =14) toxic diffuse goiter. 88 patients with thyroid carcinoma and 10 with nonthyroidal malignancies were studied. The mean level of serum hTg was increased in untreated differentiated thyroid carcinoma (89.5 ± 19 ng/ml; n = 13) but not in undifferentiated (10 ±2.9 ng/ml; n =6) or medullary (0.8 ±0.2 ng/ml; =3) carcinoma. In treated differentiated thyroid carcinoma the mean hTg levels were normal (8.2 ± 2.2 ng/ml) in patients (n = 24) with no evidence of either a thyroid residue or metastatic disease, moderately increased (56.6 ± 16 ng/ml) in patients (n =27) with residual thyroid tissue, markedly elevated in patients with lymph node metastases (199 ± 50 ng/ml; n = 15) and extremely elevated in those with bone (4004 ± 982 ng/ml; n = 8) or lung (2520 ± 620 ng/ml; n = 5) metastases. There was no significant difference in serum hTg between functioning (n =23) and nonfunctioning (n =5) metastases as assessed by 131| whole body scan. A slight but significant (p< 0.0005) increase in the mean concentration of hTg was observed in nonthyroidal malignancies (21.7 ±4.5 ng/ml; n = 10). Serial measurements showed a transient increase of serum hTg after131| therapy of differentiated thyroid carcinoma, toxic diffuse goiter or toxic adenoma, with peak values usually occurring within the first three days. A fall of serum hTg after administration of suppressive doses of thyroid hormone to patients with nontoxic goiter and a rise after discontinuation of thyroid suppressive therapy in patients with metastatic differentiated thyroid carcinoma was observed. The present data confirm and extend previous data indicating that serum hTg is frequently elevated in thyroid disease, and that the release of hTg from malignant and nonmalignant thyroid tissue is at least in part thyrotropin (TSH) dependent and it is enhanced by radioiodine therapy. Measurements of serum hTg do not differentiate from benign and malignant thyroid disease, but may be usefullly employed in the follow up of differentiated thyroid carcinoma. Of particular interest was the finding that nonfunctioning metastases may be detected by measurement of serum hTg and that bone or lung metastases are associated with much higher levels of serum hTg than lymph node metastases.

The value of serum thyroglobulin (Tg) determination in the differential diagnosis of congenital hypothyroidism was assessed by serum Tg measurements in 14 patients with proven congenital hypothyroidism, in 3 subjects with transient perinatal hypothyroidism, in 3 newborns with congenital thyroxine binding globulin (TBG) deficiency and in 34 normal controls. Serum Tg was undetectable in all 6 cases with thyroid agenesis, normal or moderately elevated in the 4 cases with ectopic thyroid, markedly increased in the 4 cases with dyshormonogenic goiter and normal in the 3 cases with transient hypothyroidism and in the 3 with TBG deficiency. The present data indicate that serum Tg measurements may be useful in the differentiation of athyreotic hypothyroidism from other conditions of congenital hypothyroidism.

Serum tissue polypeptide antigen, (TPA), carcinoembryonic antigen (CEA), calcitonin (CT) and thyroglobulin (Tg) have been measured by specific radioimmunoassays in 174 patients with various types of thyroid cancer previously submitted to thyroidectomy. Elevated serum TPA concentrations were found in 12 of 13 patients with local invasion or distant metastases from undifferentiated thyroid cancer or thyroid lymphosarcoma, while serum Tg and CEA values were normal or undetectable. In 123 patients with well differentiated thyroid cancer serum TPA was usually normal regardless of the presence or absence of functioning metastases. On the contrary, 14 of 15 patients with “dedifferentiated” metastases from previously differentiated thyroid cancer had elevated serum TPA values, while serum CEA was normal and serum Tg variable. Serum CT was confirmed as the most sensitive marker of metastatic medullary thyroid carcinoma, but elevated serum TPA values were also found in most of these cases. The present data indicate that serum TPA provides a new humoral marker in the follow-up of undifferentiated and “dedifferentiated” thyroid carcinoma and may also be usefully employed as an additional marker for medullary thyroid carcinoma.

Immunoglobulins (IgG) in sera of patients with autoimmune thyroid diseases have been characterized by their ability to bind to thyroid TSH receptor sites. Thyroid membranes were prepared in hypotonic medium and discontinuous sucrose gradient flotation. 125l labelled-bovineTSH bound to the membranes at 0C for 120 min. Binding was linear with membrane concentration. Specific binding was maximum at pH 6.5, but binding studies with IgG were conducted at pH 7.5 in order to keep IgG soluble. Progressive inhibition of binding of label occurred at TSH concentration of 20 ng–50μg/ml, with half displacement at 7–70μg/ml. Unfractionated sera caused nonspecific depression of response. IgG was purified by DEAE-Sephadex absorption and used in concentration of 1.2 mg/ml or 175 μg/tube. Compared to the effect of a normal control pooled IgG on binding (“100%”), IgG from 17 normal subjects averaged 99±9% (range: 120–82%), and from 12 patients with thyroid cancer, 96±11%, both showing no inhibition of 125I-TSH binding. IgG from 15 patients with untreated Graves’ disease significantly (p<0.05) inhibited binding (81±17% of control) with up to 60% displacement of TSH. 53% of the patients were more than 2 SD below the mean normal value. Binding with IgG from sera of 8 patients with Hashimoto’s disease ranged from 61% to 120% of control. IgG from most patients with Graves’ disease compete with TSH for binding to thyroid cell membranes, and thus behave as antibodies to TSH receptors. Some patients with clinical thyroiditis have similar responses, confirming the hypothesis of a common immunologic background in these two diseases.

Twenty-five patients with solitary autonomous thyroid nodules (15 nontoxic, 10 toxic) received percutaneous ethanol injection treatment (PEIT) under sonographic guidance in 4–7 sessions (1–2 weekly). To test different doses, smaller nodules (volume <15 mL) were given 0.75–2.8 mL ethanol/mL nodular tissue while larger nodules received 0.5–1 mL/mL. Except for 1 patient who developed hyperpyrexia, no relevant adverse effects were observed. A slight, asymptomatic increase in serum thyroid hormone levels was observed in both groups during the treatment. Three months after treatment, a biochemical and clinical remission of hyperthyroidism was observed in 8 of 10 patients with toxic nodules. A significant increase of TSH level was seen in both groups (p<0.01). Significant shrinkage of volume (p<0.001) as well as structural alternations of nodules were consistently recorded at sonography. A linear relationship (r=0.98;p<0.0001) between pretreatment volume and volume reduction was found both for large and small nodules, thus suggesting that even limited ethanol doses may be therapeutically effective. A recovery of extranodular parenchyma activity at scintiscan occurred in 16 (64%) of 25 patients. These data confirm that PEIT is effective in obtaining functional ablation and in inducing remission of hyperthyroidism. Adverse effects are infrequent. In spite of the small patient sample, a 0.5–1 mL ethanol dose per each mL of tissue appears as effective as larger doses and seems appropriate for treatment.

A 14-year-old girl presented with classic McCune-Albright syndrome. She underwent the ablation of several cysts during a laparotomy performed on the basis of persistent and intense pelvic pain and recurrent episodes of menometrorrhagia not responsive to pharmacologic therapy. Granulosa cells obtained from an isolated follicle and a cyst were cultured and estradiol (E2) secreted in the culture medium measured. Granulosa cells, obtained from the follicle, produced much higher levels of estradiol compared to those of cells coming both from follicles of equivalent size and preovulatory follicles of normal patients. Secretion of E2by granulosa cells from the cyst was comparable to that of normal preovulatory follicles. We conclude that in this patient, ovaries are hyperfunctioning in terms of E2production. This high production of estradiol and the fact that several cysts were found in the ovaries can justify the high levels of estradiol found in the serum of this patient at the moment of the operation.

Summary: In order to demonstrate the suggested failure of the serotoninergic system in human obesity and to evaluate the role of central serotoninergic activity in prolactin (PRL) and thyroid stimulating hormone (TSH) release in this condition, 13 euthyroid obese and 9 healthy women of normal weight were studied. A TRH test (200 �g i. v.) was performed before and after administration of fenfluramine (FF) 60 mg b. d. for 14 days. In the controls, FF did not modify the expected significant increase in PRL induced by TRH. In obese patients, however, the PRL levels was significantly increased after TRH, but the increase was less than in the controls. After FK the PRL response to TRH was larger than in the pretreatment phase, with values similar to those observed in normal subjects. In neither group FF did change the TSH-stimulating effect of TRH, but the hormonal response in obese patients was greater than in the controls. The restoration of the responsiveness of PRL to TRH after central serotoninergic stimulation confirms the hypothesis that a failure of the serotoninergic system may occur in human obesity. Since FF does not interfere with the secretory pattern of basal and stimulated TSH in normal or obese subjects, the serotoninergic system does not seem to play a major role in the control of TSH secretion.

Serum thyroglobulin (Tg) was measured in the cord blood of 635 newborns and serum thyroxine (T4) reverse triiodothyronine (rT3), TSH and T3were measured in about 200 of them. Cord Tg was detectable in all newborns with a mean + SE value (50 ± 1.3 ng/ml) higher than that found in the serum of adult subjects (n = 144; Tg = 13 ± 1.1; p< 0.0001). Cord Tg had a log-normal distribution. A low, but positive correlation was found between cord Tg and cord TSH (n = 242; r = 0.17; p< 0.05) but not with cord T4or cord rT3. Gestational age was negatively correlated with cord Tg or cord rT3(rs= − 0.97; p< 0.01; rs= 0.89; p< 0.02, respectively) while was positively correlated with cord T4or cord TSH (rs= 0.85; p< 0.05; rs= 0.86; p< 0.01, respectively). Birth weight, maternal diabetes, induction of labor with Oxitocin, cesarian section and newborns’ illness showed no influence on cord Tg levels when considered alone, but decreased cord Tg levels were found in ill newborns delivered by cesarian section. On the contrary, increased cord Tg levels were present in cord blood of newborns who developed hypoglycemia soon after birth and in small for gestational age newborns. In 24 newborns studied daily for the first 6 days of life, serum Tg was always detectable with mean values not different from those found in the cord blood. A progressive decrease in serum Tg concentrations was found after birth during infancy, childhood and adolescence (rs= − 0.88; p< 0.001). Adolescents’ serum Tg levels were similar to those of the adult population.

Inhibition of binding of TSH to thyroid plasma membranes by immunoglobulins G (IgG) from patients with Graves’ disease has been interpreted as evidence of an interaction with the TSH receptor, but other explanations may account for this phenomenon. Displacement of receptor-bound TSH might be a more direct index of such an interaction. The aim of the present study was to assess TSH-displacing activity (TDA) of Graves’ IgG by a newly developed assay and compare TDA to TSH-binding inhibiting activity (TBIA) and thyroid-stimulating antibody (TSAb) activity. TDA was assessed by preincubating 125I-TSH with thyroid plasma membranes and by measuring residual bound 125I-TSH after addition of IgG. TBIA was evaluated by determining binding of 125I-TSH to thyroid plasma membranes preincubated with IgG. Results were expressed as % TSH-displacing or binding inhibition activities of test IgG with respect to normal control IgG. The percent of TDA positive Graves’ IgG preparations (72.7%) was greater than that of TBIA positive (48.5%). There was no correlation between TDA and TBIA results, since 11 Graves’ IgG preparations were TDA positive but TBIA negative, and 6 were TDA negative but TBIA positive. Hashimoto’s or idiopatic myxedema IgG preparations were positive in 2/7 in the TDA and in 1/7 in the TBIA assays, respectively. Neither TDA nor TBIA correlated with TSAb determined by cAMP accumulation in thyroid plasma membrane. The TDA assay developed in this study appeared to be more sensitive than the more widely used TBIA assay. No correlation was found between the two assays, indicating that inhibition of TSH binding and displacement of bound TSH are not equivalent and may be due to different phenomena. TDA as well as TBIA were also unrelated to TSAb activity, suggesting that interaction with the TSH receptor does not necessarily imply stimulation of thyroid function.

We have studied the in vitroTSH secretion and the adenylate cyclase (AC) activity of a human pituitary adenoma surgically removed from a hyperthyroid patient showing high serum TSH levels. The tumor appeared almost homogeneously constituted by cells positive for an anti-TSH-beta antiserum and showing the ultrastructural characteristics of the adenomatous thyrotrophs. Adenoma fragments released in vitroa large amount of TSH (148.4 μU/mg prot/30 min), alpha-subunit(35.5 ng/mg prot/30 min) and TSH-beta (10.1 ng/mg prot/30 min). The effects of somatostatin (GHRIH) and dopamine (DA) on the hormone release have been tested in vitro. Both agents markedly inhibited the release of intact TSH and TSH-beta whereas the release of alpha-subunit was less affected. The two agents were effective at concentrations higher than 10−8M. The ability of GHRIH and DA in modulating the AC activity was investigated in membrane fraction preparations. GHRIH inhibited AC at concentrations higher than 10 −7M. The maximal inhibition was 32% at 10−5M. Conversely, DA slightly stimulated AC activity. This effects was not mimicked by the dopaminergic ergot CH 29–717, which was completely ineffective on the enzyme. These results suggest that: 1) in this TSH-secreting pituitary adenoma a normal secretory response to the inhibiting agents (GHRIH and DA) is present; 2) different mechanisms of transduction of the GHRIH and DA signals (cAMP dependent and cAMP independent) could be operating in this tumor.

Thyrotropin-releasing hormone (TRH)-like material was found in human retina obtained at autopsy from eyes used for corneal grafts. The TRH-like material was extracted with methanol and was found to be indistinguishable from synthetic TRH in its immunoreactivity and bioreactivity and in its proteolytic degradation by fresh human serum. The TRH concentration in human retina was similar to that reported in human cerebral cortex. These data are in keeping with the notion that the retina is an extension of the central nervous system. The physiological function of human retinal TRH in unknown: probably it acts as a neurotransmitter.

The goitrogenic role of autoimmune phenomena in endemic goiter is still uncertain. Scanty and discrepant results have been reported in different areas of the world. This prompted us to evaluate the prevalence of circulating thyroid antibodies in an area of North-Western Tuscany during a survey for endemic goiter. The survey was carried out according to the P.A.H.O. criteria in a stable community. In all schoolchildren (n = 142, age range 7–15 yr) and in most of their parents (n = 159), thyroid size was evaluated and urine was collected for iodine determination. Blood was drawn for determination of circulating thyroid microsomal (MAb) and thyroglobulin antibodies (TgAb), TT3, TT4and TSH. Prevalence of goiter in schoolchildren was 77.9% and 94.8% in their parents. Mean (± S.D) urinary iodine excretion was 55.0 ± 2.1 μg/24h. The overall frequency of TgAb and MAb in the adult population was 14.4%, statistically higher than that of control subjects matched for sex and age. The frequency in schoolchildren was 4.3%. The presence of goiter in children was unrelated to the presence of thyroid antibodies in parents, whether goitrous or nongoitrous. A higher prevalence of goiter was found in children with goitrous parents as compared to children with nongoitrous parents (p< 0.005). In conclusion, the frequency of thyroid autoantibodies in the adult population of the endemic area studied was increased, but showed no relation with the presence of goiter. The prevalence of goiter in children was associated with the presence of goiter but not of thyroid autoantibodies in parents. These data suggest that autoimmune phenomena are of limited importance in the development of endemic goiter.

Twenty-five patients with solitary autonomous thyroid nodules (15 nontoxic, 10 toxic) received percutaneous ethanol injection treatment (PEIT) under sonographic guidance in 4–7 sessions (1–2 weekly). To test different doses, smaller nodules (volume <15 mL) were given 0.75–2.8 mL ethanol/mL nodular tissue while larger nodules received 0.5–1 mL/mL. Except for 1 patient who developed hyperpyrexia, no relevant adverse effects were observed. A slight, asymptomatic increase in serum thyroid hormone levels was observed in both groups during the treatment. Three months after treatment, a biochemical and clinical remission of hyperthyroidism was observed in 8 of 10 patients with toxic nodules. A significant increase of TSH level was seen in both groups (p<0.01). Significant shrinkage of volume (p<0.001) as well as structural alternations of nodules were consistently recorded at sonography. A linear relationship (r=0.98;p<0.0001) between pretreatment volume and volume reduction was found both for large and small nodules, thus suggesting that even limited ethanol doses may be therapeutically effective. A recovery of extranodular parenchyma activity at scintiscan occurred in 16 (64%) of 25 patients. These data confirm that PEIT is effective in obtaining functional ablation and in inducing remission of hyperthyroidism. Adverse effects are infrequent. In spite of the small patient sample, a 0.5–1 mL ethanol dose per each mL of tissue appears as effective as larger doses and seems appropriate for treatment. On a injecté de l'éthanol par voie percutanée (IEP) et sous échographie chez 25 patients ayant un nodule solitaire autonome de la thyroïde (15 non-toxiques, 10 toxiques), à raison de 4–7 séances (1–2 par semaine). Pour évaluer les doses nécessaires en fonction de la taille, les patients ayant un nodule plus petit (volume <15 mL) ont reçu 0.75–2.8 mL de'éthanol/mL de tissu nodulaire, alors que ceux porteurs de nodules de plus gros volume ont reçu un volume dose de 0.5 mL/mL. Hormis un cas d'hyperpyrexie transitoire, il n'a pas été observé d'effects secondaires notables. On a constaté une augmentation modérée, asymptomatique, des taux hormonaux sériques dans les deux groupes pendant le traitement. Trois mois aprés la fin du traitement, une rémission clinique et biologique a été observée chez 8 des 10 patients ayant un nodule toxique. Une augmentation significative des niveaux de TSH a été notée dans les deux groupes (p<0.01). Une diminution significative du volume (p<0.001), ainsi que des modifications structurales ont toujours été documentées par l'échographie. Une corrélation linéaire hautement significative a été retrouvée (r=0.98;p<0.0001) entre le volume pré-opératoire et la réduction tumorale à la fois pour les grands et les petits nodules, suggèrant que même une injection limitée d'éthanol peut être thérapeutiquement efficace. La récupération d'une activité scintigraphique extranodulaire a été observee chez 16 des 25 patients (64%). Ces données confirment que l'IPE est un moyen efficace pour obtenir une “ablation fonctionnelle” de la thyroïde et induire une rémission d'hyperthyroide. Les effets secondaires apparaissent peu fréquents. Malgré la taille réduite des effectifs dans cette étude, il semble que la dose de 0.5–1 mL d'éthanol par mL de tissu soit aussi efficace qu'une dose plus importante. Veinticinco pacientes con nodulos tiroideos solitarios autónomos (15 no tóxicos, 10 tóxicos) fueron tratados mediante inyección de etanol por vía percutánea (TIEP) bajo guía ultrasonigráfica en 4–7 sesiones (1–2 semanales). Con el objeto de probar diferentes dosis, los nódulos pequeños (volumen<15 mL) fueron tratados con dosis de 0.75–2.8 mL etanol/mL de tejido nodular, en tanto que los nódulos mayores recibieron 0.5–1.0 mL. Aparte de un paciente que exhibió hiperpirexia transitoria, no se observaron efectos adversos. En el curso del tratamiento se registró una leve y asintomática elevación de los niveles séricos de hormona tiroidea en ambos grupos. A los tres meses de efectuado el tratamiento se comprobó remisión bioquímica y clínica del hipertiroidismo en 8 de 10 pacientes tóxicos, y elevación significativa de los niveles de TSH en ambos grupos (p<0.01). En forma consistente la sonografía demostró reducción significativa del volumen (p<0.0001) y alteraciones estructurales de los nódulos. Se encontró una relación linear entre el volumen de la masa anterior al tratamiento y la reducción, tanto para los nódulos grandes como para los pequeños, lo cual sugiere que aún las dosis limitadas de etanol poseen eficacia terapéutica. Se demostró recuperación de la actividad parenquimatosa extranodular en 16 de 25 pacientes (64%). Los datos confirman que el TIEP es efectivo para lograr la ablación funcional y la remisión del hipertiroidismo, cuando éste se encuentra presente; los efectos adversos son muy raros. A pesar de lo pequeno de la muestra de pacientes, parece que una dosis de 0.5–1.0 mL de etanol por cada mL de tejido es tan eficaz como las dosis mayores y que resulta apropiada para el tratamiento de los nódulos solitarios autónomos de la glándula tiroides.

A new high-pressure liquid chromatography (HPLC) method for simultaneous quantitative determination of the urinary metabolites of toluene, m-xylene, and styrene (hippuric acid, m-methylhippuric acid, phenylglyoxylic acid, mandelic acid) is described. The extraction procedure was performed on acidified urines, after addition of 4-hydroxybenzoic acid as internal standard, using a butylchloride/isopropanol mixture and drying 0.5 ml of the organic layer under nitrogen flow. The residue obtained was dissolved in 0.1 ml water/acetonitrile and 5 µl were injected into an HPLC apparatus equipped with a 0.26 × 25 cm HC ODS SIL X column.

A 72-year-old woman was referred to our hospital for diarrhea, abdominal and back pain, weight loss, low serum potassium level. Pathological findings and high circulating Vasoactive Intestinal Peptide (VIP) levels allowed us to diagnose “VIPoma syndrome”. The patient underwent a treatment with SMS 201–995 with improvement of symptomatology and reduction of circulating VIP levels. After a wash-out period the patient was treated with salmon calcitonin with a net improvement of diarrhea, normalization of potassium serum level and reduction of VIP level. The symptomatology recurred after calcitonin withdrawal. These data confirm the effectiveness of SMS 201–995 in the VIPoma syndrome and suggest that calcitonin may ameliorate symptomatology and reduce circulating VIP level in patients with VIPoma tumor.

The three-dimensional architecture of the human isthmic myosalpinx is directly visualized by means of scanning electron microscopy after removal of interstitial connective tissue through NaOH maceration and ultrasound microdissection. These investigations show that the myosalpinx is composed of irregularly running bundles of smooth muscle cells, changing their orientation within the myosalpinx and displaying longitudinal, oblique and circular directions. The muscular bundles anastomose and intermingle with other bundles running at different levels in the oviduct wall, and actually give rise to a wide and complex muscular network in which no distinct layers are readily discernible. These morphological data are consistent with the physiological findings that the transport of gametes and embryo in very early stages in the isthmic portion of the oviduct tube is the result of a discontinuous pattern of forward and backward movements.

The thyrotropin-releasing hormone (TRH) content in whole hypothalamus was measured by specific radioimmunoassay in rats exposed to a daily light-dark cycle (06:00–18:00 light, 18:00–06:00 dark) and in animals exposed to constant light or constant darkness for 12 days. A nyctohemeral variation of hypothalamic TRH was observed in light-dark exposed animals, while this variation was abolished by exposure either to constant light or constant darkness. These data indicate that any study involving hypothalamic TRH determination should be carried out taking into account the diurnal variation and the effect of environmental light exposure.

Measurements of serum thyroxine binding globulin (TBG) by a ligand partitioning sandwich assay were performed in 173 healthy subjects between three months and 92 yr of age. Significant sex-related differences were observed in subjects aged 21 to 50 yr. In males, serum TBG declined progressively reaching a nadir in the fourth decade and then increased with advancing age. In contrast, no significant age-related variation was observed in females.