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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.

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 E2 by 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 E2 production. 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.

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 micrograms 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 FF, 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.

Measurements of serum thyroglobulin (hTg) were performed using a specific radioimmunoassay. Sera with detectable anti-thyroglobulin (anti-Tg) antibody titers (> or = 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 pregnant 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 +/- 0.2 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 = 5) 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 131I 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 after 131I 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.(ABSTRACT TRUNCATED AT 400 WORDS)

We have studied the in vitro TSH 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 vitro a large amount of TSH (148.4 microU/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(-8)M. 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(-7)M. The maximal inhibition was 32% at 10(-5)M. 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.

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.

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.

Serum thyroglobulin (Tg) was measured in the cord blood of 635 newborns and serum thyroxine (T4) reverse triiodothyronine (rT3), TSH and T3 were 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 less than 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 less than 0.05) but not with cord T4 or cord rT3. Gestational age was negatively correlated with cord Tg or cord rT3 (rS = 0.97; p less than 0.01; rS = -0.89; p less than 0.02, respectively) while was positively correlated with cord T4 or cord TSH (rS = 0.85; p less than 0.05; rS = 0.86; p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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, TT4 and TSH. Prevalence of goiter in schoolchildren was 77.9% and 94.8% in their parents. Mean (+/- SD) urinary iodine excretion was 55.0 +/- 2.1 micrograms/24 h. 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 less than 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.

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.

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.

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 idiopathic 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.(ABSTRACT TRUNCATED AT 250 WORDS)