Abstract: Neuropsychological assessment was carried out in schoolchildren from a montane area of Eastern Tuscany (Tiberina Valley). This area was found to be moderately iodine deficient (mean urinary iodine excretion: 39 ώg/g creatinine), with a cumulative goiter prevalence of 51.9% in schoolchildren aged 6-14 yr (goiter prevalence in the control iodine-sufficient area: 5.6%). No significant differences in serum TT4, TT3, FT4I, TSH levels between the endemic and control areas were found, whereas serum thyroglobulin values were significantly higher in the iodine-deficient area (61±8 vs 17±1 ng/ml, p < 0.01). No differences were found as to the height, body weight and pubertal development in the two areas. Neuropsychological assessment, performed in a representative sample of 50 schoolchildren from the endemic area and 50 schoolchildren from the control area, matched for age, sex and socioeconomical conditions, failed to show major differences between the two groups in the global neuropsychological performance and cognitive levels. However, minor but significant differences were noted in the information vocabulary and coding subtests, at least in children aged 8. Although familial cultural influences might play a role, it would appear that some marginal impairment, with particular regard to motor-perceptual functions, be present in areas of moderate iodine deficiency.

Abstract: Although somatostatin inhibits a variety of pituitary and non-pituitary hormones, not univocal data on its effects on ACTH release have been reported so far. In this study we investigated the effects of somatostatin or octreotide on ACTH levels of patients with corticotropin hypersecretion: 7 patients with Addison’s disease, 2 patients previously adrenalectomized for Cushing’s disease, 4 patients with Cushing’s disease and 3 patients with ectopic ACTH syndrome. Plasma ACTH and Cortisol levels were determined after somatostatin (500μg over 60 min) infusion or octreotide (100μg sc) injection. In 5 other patients with Cushing’s disease ACTH and Cortisol responses to CRH (1 μ/kg iv) were evaluated in basal conditions and after octreotide acute administration. In no patients with Addison’s disease any inhibitory influence of somatostatin (Δ % = −21, −25) or octreotide (Δ % = −38 ± 12 vs −39 ± 12 after saline) on plasma ACTH was found. Somatostatin did not significantly inhibit plasma ACTH in the two patients previously adrenalectomized for Cushing’s disease and in 3 patients with Cushing’s syndrome; in other 4 patients with Cushing’s syndrome octreotide did not affect plasma ACTH levels. In 5 patients with Cushing’s disease the plasma ACTH and Cortisol responses to CRH were similar both before (ACTH from 9.9 ± 1.7 pmol/L to 19.4 ± 6.1 pmol/L; Cortisol from 496 ± 43.9 nmol/L to 923 ± 355 nmol/L) and after octreotide injection (ACTH from 8.8 ± 2.4 pmol/L to 19.1 ± 8.2 pmol/L; Cortisol from 510 ± 54.6 nmol/L to 735 ± 220 nmol/L). In conclusion, the acute administration of somatostatin or octreotide is not able to modify ACTH levels in patients with corticotropin hypersecretion either due to hypo-cortisolemic state or consequent to ACTH-secret-ing pituitary or ectopic tumors; moreover, octreotide does not affect the pituitary-adrenal responsiveness to CRH in patients with Cushing’s disease.

Abstract: A total of 1050 patients with differentiated thyroid cancer (DTC) have been followed in the Thyroid Center of Padua by means of serum thyroglobulin (Tg) measured with IRMA method and anti-Tg antibodies (TgAb) assays. Circulating TgAbs were detected in 102 (9.7%) patients. In 32 of these 102, TgAbs were evaluated before and after total thyroidectomy and 131I ablation. In these patients no relationship was found between preoperative serum TgAb levels on the one hand and tumor stage at diagnosis or outcome of the disease on the other. During the follow-up, TgAb serum levels decreased or disappeared in 21 cases considered tumor-free, while they remained unchanged or even increased, in comparison with the preoperative ones, in 11 patients, 5 with proven metastases and 6 considered tumor-free. Evaluating the whole group of 102 TgAb-positive patients, we observed that TgAb serum levels, measured after thyroid ablation, were significantly higher in cases with metastases than in those considered tumor-free (653.0 +/- 196.9 vs 157.7 +/- 116.5 U/ml, m +/- SD, p less than 0.0001). In the group of patients with metastases and circulating TgAbs, Tg serum levels were elevated in 27% of cases on TSH-suppressive therapy and in 44% off therapy when nodal metastases were present, and in 67% of cases on TSH-suppressive therapy and in 83% off therapy when distant metastases were present.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: The efficacy of 131I therapy in achieving euthyroidism has been studied in a group of 264 patients followed for up to 10 yr. One hundred and eighty-six were given a dose adjusted for thyroid size and radioactive iodine uptake (Protocol 1), and a second group received the same dosage followed by antithyroid drug therapy plus potassium iodide for 15 days (Protocol 2). At 10-yr follow-up, 50-60% of patients were euthyroid. 25-29% of patients required 2 doses of 131I, and 4-5% required 3 doses. Fewer patients became hypothyroid when their pretreatment FTI was above the average value. More patients became hypothyroid, if their pretreatment test for antimicrosomal antibodies was positive. Patients who required a second dose of radioactive iodide had a significantly greater chance of having worsening of their ophthalmopathy than those who became hypothyroid after the first dose. Treatment with radioactive iodide under either protocol appears to achieve euthyroidism at 10 yr with an incidence higher than that achieved by antithyroid drugs and comparable to that reported for subtotal thyroidectomy.

Abstract: Hypothalamic-pituitary-testicular function was studied in 70 patients with myotonic dystrophy (MD). The diagnosis was confirmed by electromyography. The mean age of the patients was 36.2 ± 13.2 yr and the duration of the disease was 11.17 ± 8.01 yr. Testicular atrophy (testes ≤ 12 ml on a Prader orchidometer) was present in 65.5% of patients. Fertility among married patients was 66.6%. Mean testosterone plasma levels were 438 ± 298 ng/dl vs 520 ± 185 ng/dl in the control group (P = NS). Basal plasma FSH and LH levels, and their response after the administration of 100 mcg of LH-RH were significantly increased although a wide dispersion was observed. Sperm count was carried out in 27 cases, showing a normal count in 7, oligospermia in 12, and azoospermia in 8 patiens. Testicular biopsy was performed in 45 patients being normal in 2, showing mild testicular damage in 8, moderate in 14, and severe in 18; it was nule in 3 of them. A significant relationship between testicular atrophy and the sperm count (p < 0.01), testicular damage and testicular atrophy (p < 0.025), and sperm count and testicular damage (p = 0.017) was found. Basal plasma FSH and LH level were significantly related to the degree of damage in the testicular biopsy. All these findings indicate a primary testicular pathology, prevailing tubular over interstitial damage. We have not found any association between the duration of the disease and gonadal dysfunction.

Abstract: Thirty-nine patients with progressive systemic sclerosis (PSS) in stable clinical conditions were extensively evaluated for the presence of thyroid disease. Two patients had previously undetected hypothyroidism while 7 additional patients had normal serum thyroid hormone levels but an exaggerated TSH response to thyrotropin -releasing hormone (TRH) administration, consistent with subclinical hypothyroidism. Four of the 9 subjects with abnormal TRH responses had positive antithyroid antibodies and of the remaining 5, 4 had been on chlorambucil or prednisone. Basal TSH and TSH response to TRH were significantly higher in PSS patients as a group when compared to a control group and increased with increasing duration of PSS. Serum antithyroid antibodies (an-tithyroglobulin and/or antimicrosomal antibodies) were positive in 18% and thyroid scans were abnormal in 18% of the patients. The euthyroid sick syndrome was not seen. Our findings indicate an increased frequency of, sometimes previously unsuspected, clinical and subclinical hypothyroidism in stable PSS patients which appears to be autoimmune in nature and becomes more prevalent with increased PSS duration. Careful and regular monitoring of the thyroid function in PSS patients is advisable.

Abstract: Growth hormone (GH) induces lipolysis and an increase of free fatty acids (FFA), and FFA inhibit the GH response to arginine and to GH-releasing hormone (GHRH). The aim of this study was to evaluate the effect of the pharmacologic blockade of lipolysis on the GH response to GHRH. Eleven normal men underwent a saline infusion starting at 09:00 h, after administration of placebo or 500 mg acipimox, an antilipolytic agent; at 13:00 h (0 min) they received GHRH, 50 micrograms iv The GH response to GHRH (0 to 120 min) was significantly higher in subjects pretreated with acipimox than in subjects pretreated with placebo. In subjects receiving placebo, but not in those receiving acipimox, a progressive increase of plasma FFA levels took place, and the GH response to GHRH was inversely related to the plasma FFA levels at 0 min. These data indicate that FFA play an important role in the control of GH release, and that acipimox prevents the FFA rise induced by GH.

Abstract: Several subgroups of Cushing's disease were recently described (anterior or intermediate lobe origin, hyper-or hypo-pulsatility of cortisol, presence or absence of response after GRH or TRH, cyclical Cushing's disease). We present here a detailed case report on a patient suffering from Cushing's disease whose endocrine functions were extensively investigated. Treatment with bromocriptine, as well as subsequent transsphenoidal surgery, were followed by rapid but transient reversal of symptoms. When clinical manifestations reoccurred, daily measurements of free urinary cortisol revealed a cyclic pattern of cortisol hyperexcretion. A study of ultradian rhythm revealed hyperpulsatility of cortisol secretion. More interestingly, a treatment with sodium valproate, a drug known to inhibit CRH production, was followed by a rapid and longstanding normalization of clinical and biological data for 2 years. Based on these data, and on information from the literature, the present case of Cushing's disease exhibits characteristics suggesting a possible hypothalamic origin.

Abstract: In this paper we present a study of the diurnal variation of testosterone (T) and estradiol (E2) in women, carried out as part of the design of a prospective study on the hormonal and nutritional etiology of breast cancer. Blood samples were obtained 5 times on the same day, in the morning and early afternoon, from 23 women aged between 25 and 63 yr. Twelve were sampled within the first days following daylight-saving time (SUMTI) introduction. In postmenopause, T mean values decreased from 08:00 h to 15:00 h and the effect of blood drawing time was statistically significant (p < 0.01), with no significant effects of SUMTI. For E2 mean values, no significant effect was found for either blood drawing time or SUMTI. In premeno-pause, T mean values decreased from morning to afternoon (p < 0.01 ), while no effect of SUMTI was found. A significant decrease was observed for E2 during the day (p < 0.01), with no significant influence of SUMTI. These results indicate that diurnal variation of T and E2 are such, that one must not neglect the possible effects of timing procedures on hormonal measurements, when hormonal hypotheses are tested in comparative studies on cancer etiology.

Abstract: A female newborn whose mother was taking propylthiouracil (PTU) for Graves' disease, presented with transient thyrotoxicosis (serum triiodothyronine 1,710 ng/dl) and signs of acute hepatic injury. Jaundice and choluria were evident on her fourth day of life. Serum total bilirubin reached 14 mg/dl, with a direct fraction of 11 mg/dl. Serum alanine aminotransferase and aspartate aminotransferase showed moderate elevations (110 IU/l and 61.5 IU/l, respectively), as well as the alkaline phosphatase which increased to about twice the upper limit of normal. When incubated with PTU, the patient's cultured peripheral lymphocytes underwent transformation to more than twice the values found in 2 controls, with a stimulation index (SI) of 3.19, compared to SI of 1.45 and 1.15 for the controls, suggesting a hypersensitivity mechanism involved in the hepatic injury. Although about 20 cases of PTU induced hepatic damage were reported in the medical literature, this is, as far as we know, the first description of neonatal liver injury probably caused by placental transfer of this drug.

Abstract: Acro-osteolysis with diffuse osteoporosis in the absence of other associated diseases is named Hajdu-Cheney syndrome. Reduced bone formation rather than enhanced bone resorption has been indicated as the mechanism of osteoporosis. On the assumption that in this syndrome the active bone resorption which produces distal osteolysis must also predominate in generalized osteoporosis, we investigated boae histology, calcium kinetics, calciotropic hormones and bone markers in a patient suffering from sporadic Hajdu-Cheney syndrome. A radius bone biopsy taken far from the osteolytic lesions showed severe osteoporosis with a marked increase in osteoclastic bone resorption and reduced bone formation. Total body calcium clearance, performed through an analysis of the kinetics of calcium infusion, was 2.8 times higher than in normal controls, indicating the presence of active osteoclastic bone resorption. Serum parathormone, 1, 25-dihydroxycholecalciferol, alkaline phosphatase and urinary hydroxiproline were in the normal range. These data indicate that in Hajdu-Cheney syndrome trabecular osteoporosis is produced by the same mechanism that induces distal osteolysis, which suggests that it may be sustained by local acting factors stimulating osteoclastic resorption.

Abstract: Several in vivo experimental and clinical studies suggest that the production of thymic hormones, such as thymulin (Zn-FTS), is modulated by thyroid hormones. It was not determined in these studies, however whether such modulation is exerted directly on the thymic epithelial cells which synthesize and secrete thymic hormones. In order to discriminate between direct and indirect modulation, the effect of thyroid hormones on the in vitro production of thymulin by whole thymic organ culture, as detected by the rosette inhibition assay, has been investigated. Donors of thymuses were young 6N-propyl-2 thyouracil (PTU)-treated hypothyroid Balb/c mice and normal littermates. Thymuses from hypothyroid mice were shown to produce concentrations in vitro nearly undetectable of thymic hormone, when compared to thymuses from normal mice. The in vitro addition of triiodothyronine (T3) caused a complete recovery of the thymic hormone production by thymuses from hypothyroid mice and an increased synthesis even by normal thymuses over control values. The complete blockade of in vitro thymic hormone production with cycloheximide, which inhibits mRNA and protein synthesis but not thyroid hormone permissive actions, suggests that the T3 induced increment of thymic hormone level in the supernatant is due to de novo synthesis. Furthermore, the number of thymulin-producing cells, as detected by immunofluorescence using a specific antithymulin monoclonal antibody, which is quite low in thymuses from hypothyroid mice, is completely regained after in vitro incubation with T3. These findings support the idea that the modulation of thyroid hormones on thymic endocrine activity is directly exerted at thymic level.

Abstract: Thyroxine-binding globulin-slow (TBG-S), a variant found in 4-12% of Black and Pacific Island populations, is inherited as an X-chromosome linked trait. This variant is detected on isoelectric focusing by the characteristic cathodal shift of all its isoforms, suggesting that the difference resides in the core protein. In addition, TBG-S is slightly more thermolabile, which explains why subjects expressing TBG-S have on the average lower serum TBG, and thus reduced T4, concentrations. We now report the molecular basis for this TBG variant, deduced from sequencing the TBG-S gene of an American Black man. Sequencing of the four coding regions and all intron/exon junctions revealed a single nucleotide substitution in the codon for amino acid 171 of the mature protein. The resulting change of the codon GAC to AAC results in replacement of the normal aspartic acid by asparagine. Since the negative charge provided by the aspartic acid is lost when replaced by the neutral asparagine, this substitution seems responsible for the cathodal shift on isoelectric focusing and slower electrophoretic mobility of TBG-S. An identical nucleotide substitution was identified in an unrelated American Black man expressing TBG-S. Whether the TBG-S phenotype observed in populations from the Pacific Islands is caused by the same mutation remains to be determined.

Abstract: The diagnosis of growth hormone (GH) deficiency (GHD) is currently based on failure to increase plasma GH levels to an arbitrary cutoff point of 7 or 10 μg/l in response to two provocative stimuli. False negative responses to these tests, however, frequently occur thus reducing their diagnostic reliability. The aim of this study was to assess a combination of pyridostigmine (PD) and GH-releasing hormone (GHRH) (60 mg oral PD 60 min before 1 μg/Kg GHRH iv) as a reliable test probing pituitary somatotropic function. In fact PD, an acetylcholinesterase inhibitor, strikingly potentiates GH response to GHRH likely by inhibiting somatostatin release. The combination PD + GHRH was tested in normal children and adolescents (NS, n = 27) and in a large group of short children classified as having familial short stature (FSS, n = 24), constitutional growth delay (CGD, n = 34) and GH deficiency (organic, oGHD, n = 6; idiopathic, iGHD, n = 10). In all groups results obtained by PD + GHRH were compared with those obtained by testing with GHRH, Clonidine (CLON) and PD alone and by studying spontaneous nocturnal GH secretion over 8 hours. Assuming 7 μg/l as minimum normal GH peak, a positive response occurred in only 18/24, 11/12 and 12/13 NS for GHRH, CLON, and PD, respectively. In contrast even assuming a minimum normal GH peak as high as 20 μg/l, PD + GHRH induced a positive response in 27/27 NS all having a nocturnal GH mean concentration (MC) ≥ 3 ug/l. Therefore PD + GHRH test gave no false negative responses and this was true not only in NS but even in all FSS and CGD having a GH MC ≥ 3 μg/l. On the other hand, PD + GHRH induced a negative GH response in all oGHD and in 8/10 iGHD patients. In the remaining two iGHD patients, PD + GHRH demonstrated a normal pituitary GH reserve in spite of a GH MC < 3 μg/l and low IGF-I level, thus pointing to a hypothalamic pathogenesis for the GHD. Considering FSS and CGD children having a GH MC < 3 μg/l, PD + GHRH showed a primary pituitary GH deficiency in 3/12 CGD with low plasma IGF-I levels. In conclusion, in slowly growing children PD + GHRH test is the most reliable provocative test for the diagnosis of primary pituitary GH deficiency being capable to discriminate between an unequivocally normal and impaired somatotropic function. The study of spontaneous GH secretion is mandatory only for those patients having low height velocity but a normal GH response to PD + GHRH in order to look for the existence of a GHD due to hypothalamic dysfunction.

Abstract: The aim of the present study was to evaluate the effects of estrogens and androgens on hypothalamic beta-endorphin (beta-EP) concentrations. Intact or castrated female rats were chronically (2 weeks) treated with estrogen (estradiol benzoate) and/or antiestrogens (clomiphene, cyclophenil or epimestrol), and with androgens (dihydrotestosterone or dehydroepiandrosterone sulphate) and/or antiandrogen (cyproterone acetate). A group of rats treated with vehicle were studied as comparison. The beta-EP concentrations were measured by radioimmunoassay on acidic extracts of rat hypothalami. The administration of clomiphene and cyclophenil significantly reduced hypothalamic beta-EP concentrations in intact rats, while both drugs or estradiol benzoate increased the peptide concentration in castrated rats. Both intact and castrated rats treated with epimestrol showed hypothalamic beta-EP concentrations higher than vehicle treated rats. The estradiol-induced increase of beta-EP was not changed by the concomitant administration of antiestrogens. The administration of dihydrotestosterone significantly decreased beta-EP concentrations in both intact and castrated female rats, while the treatment with dehydroepiandrosterone sulphate only slightly decreased beta-EP levels in intact female rats. The cyproterone acetate-chronically treated rats showed higher beta-EP concentrations than vehicle-treated rats and these changes were reversed by the concomitant addition of dihydrotestosterone or dehydroepiandrosterone sulphate. These results showed that estrogens play a positive role while androgens negatively influence the hypothalamic beta-EP concentrations in female rats, supporting the view that central beta-EP might be a target of gonadal steroid feedback signals.

Abstract: Brain β-endorphin (β-EP) plays an important role in regulating the hypothalamus-pituitary-gonadal axis activity. Cerebrospinal fluid (CSF) β-EP levels seem to reflect the central rather than pituitary secretion. With the aim to correlate the changes of plasma estradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone with brain β-EP, CSF levels of β-EP were measured in 15 normally cycling and 15 postmenopausal women. CSF β-EP levels in post-menopausal women were lower than in fertile women. A positive correlation between plasma E2 and CSF β-EP level was found in all women. In fertile women CSF β-EP levels were inversely correlated to plasma gonadotropin levels. These results showed that CSF β-EP levels differ between fertile and postmenopausal women and are correlated with plasma LH and E2, suggesting a strong linkage between central β-EP levels and pituitary-gonadal axis hormones.

Abstract: Ventricular tachycardia in patients with phenochromocytoma is rare. We report a patient with a norepinephrine-secreting extra-adrenal pheochromocytoma who had exercise induced ventricular tachycardia. Prior to diagnosis, the patient was treated with a selective beta 1 blocker, atenolol, which resulted in suppression of the dysrhythmia and amelioration of the hypertension. This is the first reported case of selective beta blockade suppressing ventricular tachycardia in a patient with a pheochromocytoma. Electrocardiographic abnormalities described in patients with pheochromocytoma are reviewed.

Abstract: We studied bone mineralization and calcium homeostasis in two children with hyperthyroidism before and during 3 yr of methimazole therapy in order to evaluate the effects of thyrotoxicosis and its therapy on mineral metabolism. Case 1, female, 4.1 year old with hyperthyroidism from 6 months. Biochemical data: increased thyroid function, phosphate and osteocalcin, decreased 1,25(OH)2 D levels. X-ray: severe osteoporosis; bone mineral content (BMC) −23.0%, BMC/BW −25.1%. Case 2, female, 7.4 year old with hyperthyroidism from 9 months. Biochemical data: thyroid function, ionized calcium and osteocalcin were increased, 1,25(OH)2 D and intact PTH were decreased. X-ray: severe osteoporosis: BMC −32.8%, BMC/BW −36.0, After the patients were euthyroid, they showed an increase of 1,25(OH)2 D and intact PTH into normal values and a fall in calcium and phosphate. Osteocalcin levels returned in normal range one yr after first evaluation. Bone mineral analysis showed no variation of BMC and BMC/BW in the first 6 months of therapy and an increase in the following 6 months. In the following two years BMC and BMC/BW rose to normal range. Our study provides further evidence that in hyperthyroidism an altered mineral homeostasis is present with a reversible disturbance in vitamin D metabolism. We found that the return to euthyroidism was associated with a normalization of mineral homeostasis and with a recovery of bone mineralization. Osteocalcin assay may be an useful index to monitor bone metabolism in hyperthyroidism.

Abstract: To elucidate the role of thyroid ultrasound (TU) in the diagnosis of congenital hypothyroidism (CH), we compared 1) TU and thyroid scintigraphy (TS) in 6 CH newborns and 2) TU results in the 6 CH newborns, in 8 newborns with “false positive” results at screening, in 13 CH children aged 2 mo to 12 yr treated since the neonatal period and in 235 controls aged 0–12 yr. Results: 1) In all 6 CH newborns with no thyroid uptake at TS, TU evidenced small posterior hyperechogenic masses in the thyroid area [Vol: 322 ± 180 (SD) mm3]; 2) In all normal controls and in the 8 “false positive” cases at screening TU showed normal thyroid structures. The thyroid volume was 831 ± 383 mm3 in normal newborns and progressively increased with age. In the older CH children, TU also demonstrated the hyperechogenic masses, but their volume barely increased with age: as a consequence, the difference between the volume of the masses in CH patients and the thyroid tissue in controls, already significant in newborns (p < 0.01), markedly increased with age. The exact nature of these masses is unknown; they could represent poorly vascularized ultimobranchial remnants containing the calcitonin — secreting cells: this hypothesis is supported by our finding that serum concentrations of calcitonin (measured by a sensitive extraction method) (mean ± SD, pg/ml) were lower in the CH patients (2.9 ± 1.5) than in controls (13.0 ± 6.9; p < 0.001) at birth. In conclusion, in all cases of CH, TU showed abnormal structures in the thyroid area. TU and TS provide complementary information in the diagnosis of CH, and TU should be routinely performed in all newborns suspected of CH to avoid unnecessary use of TS in unaffected infants.

Abstract: A case of extremely severe hyperthyroidism due to bone metastasis of papillary thyroid cancer is described. Hyperthyroidism began in this patient soon after the discovery of pelvic metastasis and worsened after total thyroidectomy and after the first dose of radioiodine. The administration of methimazole, prednisone and multiple, fractioned and small doses of radioiodine cured the hyperthyroidism and stabilized the neoplastic growth. Hyperthyroidism lasted for at least six months and hypothyroidism appeared only after seven months. Thus, the fractionation of the doses of radioiodine together with antithyroid drugs appears to be an effective treatment in patients with hyperthyroidism due to metastatic thyroid cancer.

Abstract: The content of epidermal-growth-factor receptor (EGFr) and its relation to TSH-response were examined in 27 malignant thyroid tumors (5 follicular, 6 papillary, 5 medullary, 11 anaplastic carcinomas) and in 30 tumor-like lesions (21 hyperplastic goiters and 9 toxic adenomatous goiters). Normal 12 thyroid tissues adjacent to benign tumors with no evidence of macroscopic or microscopic abnormalities were used as control. All thyroid plasma membranes tested showed specific EGF binding. In membranes from toxic adenomas (2.18 +/- 0.73 fmoles/mg protein) and papillary carcinomas (2.80 +/- 0.80) the EGF binding was similar to that of normal thyroid membranes (2.32 +/- 0.73). Hyperplastic goiters showed an EGF binding (4.4 +/- 0.82) slightly higher than normal tissue. The highest and the lowest EGF binding values were found in anaplastic (11.8 +/- 2.78) and medullary (0.50 +/- 0.39) carcinomas, respectively. An inverse correlation between EGFr content and TSH-response was found when anaplastic thyroid tumors were compared to tumor-like lesions. However no correlation was observed in medullary carcinomas which also failed to respond to TSH and in papillary carcinomas which partially respond to thyrotropin.

Abstract: A 36-year-old woman is reported with a possible variant of the McCune-Albright syndrome. The triad was incomplete because of the absence of skin pigmentation and since the sexual precocity was not evident. The presence of a pituitary mass and the secretory dynamics of growth hormone and prolactin were suggestive of a mammosomatotroph cell adenoma. A toxic multinodular goiter was also associated, but unique was the spontaneous normalization of the thyroid function. Unusual was the silent evolution of the polyostotic fibrous dysplasia, which was only fortuitously discovered during magnetic resonance imaging of the pituitary region. Treatment of the acromegaly with the long-acting somatostatin analogue octreotide resulted in an important inhibition of the GH secretion and in a reduction of the volume of the pituitary adenoma.

Abstract: The effects of somatostatin-14 (SS-14) and the somatostatin-analog octreotide (SMS 201-995, Sandostatin) on proliferation of GH3 pituitary tumor cells were investigated in vitro. SMS 201-995 exerted a significant, but transient, inhibition on GH3 cell growth which reached a maximum at 24 h and was no longer detectable at 48 h. The concentration that evoked the strongest inhibitory effect was 10 nM SMS 201-995, while lower and higher doses resulted in a less pronounced effect. The inhibitory effect SMS 201-995 exerted on cell proliferation was associated with a dose- and time-related reduction in both c-myc and c-fos mRNA levels. SS-14 had no noteworthy influence on either cell proliferation or c-myc and c-fos protooncogene expression. These data demonstrate that SS-analogs transiently inhibit pituitary tumor cell proliferation in vitro.

Abstract: A unique case report with sequential measurements of the plasma concentrations of glucoregulatory hormones, interleukin-6 and tumor necrosis factor during development of hypoglycemia in fatal meningococcemia is presented. Hormonal explanations for hypoglycemia like hyperinsulinemia or defective hypoglycemic counterregulation were excluded. Plasma concentrations of interleukin-6 and tumor necrosis factor were skyhigh. The putative relation between cytokines and hypoglycemia in sepsis is discussed.

Abstract: Amiodarone-induced thyrotoxicosis (AIT) is generally believed to result from increased hormonal synthesis related to the iodine overload. Thyroid damage has recently been incriminated as a pathophysiological mechanism. We report 3 cases of AIT associated with clinical and/or biochemical features consistent with thyroid damage. This hypothesis was supported by a painful thyroid (case 1), transient high serum Tg (case 2), a transient (case 2) or persistent (case 3) hypothyroid phase and an undetectable technetium thyroid uptake during the hypothyroid period (case 3). These clinical observations support the previous histological data indicating that thyroid follicular disruption might contribute to the pathogenesis of AIT.

Abstract: A 62-year-old woman had thyroid storm 5 h after a CT examination (contrast enhancement with 65% meglumine amidotrizoate, Angiografin). At the time of admission to our hospital, serum T4 and serum free T4 levels were markedly elevated (29 micrograms/dl and 9.6 ng/dl, respectively); serum T3 and serum free T3 levels were within normal limits (144 ng/dl and 5.9 pg/ml, respectively). These findings suggest that thyroid storm can occur with excess T4 only (T4-thyroid storm), and that T4-thyroid storm can be caused by administration of iodinated contrast medium.

Abstract: Estrogen deficiency is thought to be the main factor leading to postmenopausal osteoporosis (PMO). A role for calcitonin (CT) has been proposed as mediator of estrogen action on bone, and therefore, as pathogenetic factor of PMO. However, this hypothesis is still controversial. To further analyze the relationships between estrogens and CT in PMO, we studied the effects of one-year estro/progesterone therapy on CT secretory reserve, evaluated by a calcium infusion test in 12 postmenopausal women, as compared to 12 placebo treated subjects. In the hormone treated group, blood levels of CT showed a progressive increase during the study and a plateau was reached at 9 months, indicating that CT production achieved a new steady state. Hormonal therapy also significantly improved the CT response to calcium stimulation test. A concomitant increase of vertebral bone mass was observed in the hormone treated women, who also maintained initial bone density of femoral dyaphyses. On the contrary, the placebo treated group continued to lose bone mineral at both sites. Our study demonstrates that estrogens regulate CT secretion in postmenopausal women; thus, CT may be considered a mediator of estrogen action on bone.