Immunoreactive endothelin in nodular pathology of the thyroid.

OBJECTIVES: Endothelins (ETs) can act as autocrine and/or paracrine regulators of thyroid homeostasis and growth. The aim of this study was to evaluate immunoreactive ET (i-ET) levels in a group of patients with nodular pathology of the thyroid and to correlate them with the cytomorphological features after fine-needle aspiration (FNA) and with hormonal and immunological status and blood pressure levels. DESIGN: Plasma and cystic i-ET were assayed in a group of patients with varying thyroid function, who underwent FNA for solid and cystic nodular pathology. PATIENTS: 47 patients (32-81 years) with nodular pathology of the thyroid and 18 controls (28-70 years) with normal thyroid function and morphology were studied. MEASUREMENTS: Fasting venous blood samples were collected and the plasma for i-ET was frozen at -80 degrees C until assayed. Sera were frozen at -20 degrees C for FT3, FT4, TSH, TPO autoantibodies and thyroglobulin autoantibodies assay. Cystic fluid was obtained by FNA, centrifuged, and the supernatant was stored at -20 degrees C until i-ET assay. FNA cytology was examined by light microscopy. RESULTS: In patients with cystic nodules, plasma i-ET levels were significantly (P = 0.002) higher (5.7 +/- 1.1 ng/l, +/- SEM) than in both patients with solid nodules (2.6 +/- 0.4 ng/l) and (P = 0.02) controls (3.0 +/- 0.3 ng/l). In patients with cystic nodules, cystic i-ET levels (12.6 +/- 1.9 ng/l) were significantly (P = 0.003) higher than plasma levels (5.7 +/- 1.1 ng/l) and did not correlate with the percentage of FNA cellularity. i-ET levels in cystic fluid (12.6 +/- 1.9 ng/l) were significantly (P = 0.0001) higher than plasma i-ET levels in both patients with solid nodules and controls. No difference in either plasma or cystic i-ET levels was found in patients with cystic nodules in relation to differences in thyroid function. No difference in plasma i-ET levels was found between patients with solid nodules and controls. In controls, no significant difference in plasma i-ET levels was found between males and females. A negative correlation (r = -0.55, P = 0.02) was found between cystic i-ET levels and systolic and diastolic blood pressure. No correlation between cystic or plasma i-ET levels and FT3, FT4 or TSH was found in any of the subjects studied. CONCLUSIONS: It seems that endothelins do not possess a primary role in determining thyroid function and that the increased levels in cystic fluid found in our subjects could be secondary to cystic nodule development.

Differing responses of cortisol to oCRF during endonasal and oral treatment with DDAVP.

Arginine vasopressin (AVP) exerts a potentiating effect on the responses of cortisol and ACTH to ovine CRF (oCRF). A stimulation test using AVP plus oCRF to assess ACTH reserve has been proposed. In central diabetes insipidus, long-term substitution therapy is commonly undertaken with desmopressin (DDAVP), an analogue of the natural hormone which has a greater antidiuretic action but whose effects on the ACTH-cortisol axis are still controversial. The aim of our study was to evaluate the variations in the responses of ACTH and cortisol to oCRF in various phases of the treatment of central diabetes insipidus: no treatment, endonasal treatment with DDAVP solution and oral treatment with DDAVP in tablet form. Seven patients suffering from central diabetes insipidus underwent testing with oCRF during the various phases of treatment. In the absence of DDAVP treatment, normal responses were registered for cortisol (basal 164.1 +/- 29.4 ng ml-1, peak 396.1 +/- 37.9 ng ml-1; P < 0.05) and ACTH (basal 20.4 +/- 3.9 pg ml-1, peak 86.3 +/- 20.9 pg ml-1; P < 0.05) in all patients. During oral treatment with DDAVP, no variation in cortisol response to oCRF was seen. By contrast, when DDAVP was administered endonasally, a significant reduction in cortisol responsiveness to oCRF (secretory area: 2429 +/- 548 ng ml-1 120 min) was noted in comparison with that found during the other two tests (no treatment: 3070 +/- 704 ng ml-1 120 min; oral DDAVP: 3419 +/- 650 ng ml-1 120 min; P < 0.05) performed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Behavior of the pituitary-thyroid axis in acromegalic subjects during prolonged intermittent and pulsatile treatment with octreotide]. / Comportamento dell'asse ipofiso-tiroideo in soggetti acromegalici durante prolungato trattamento intermittente e pulsatile con octreotide.

Octreotide, as well as endogenous somatostatin, inhibits GH and TSH secretion. The drug is employed in the medical therapy of acromegaly. We studied the effects of a long-term (1-120 months; median 12 months) therapy with octreotide (300 micrograms/day) given in 3-times intermittent s.c. administration or in pulsatile s.c. (25 micrograms/120 min) way, upon the pituitary-thyroid axis. Thirteen patients (11 with normal thyroid function, 1 with secondary hypothyroidism, 1 with toxic goiter) with active acromegaly were studied. In the euthyroid patients no significative variations in both TSH levels and thyroid hormones were found during octreotide therapy. In the non-euthyroid patients octreotide did not induce changes in the dosages of drugs acting to thyroid function. The 24-hour IC-TSH levels did not show any variation during octreotide. TSH response to TRH was reduced (P < 0.05) during octreotide therapy. No correlation among TSH, IGF-I and GH levels was observed. Long-term treatment of acromegaly with octreotide reduces TSH response to TRH but do not interfere with both 24-hour IC-TSH levels and thyroid function.

A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients.

Cabergoline and quinagolide, two new dopamine agonist drugs with long-lasting activity, are currently under investigation for the treatment of hyperprolactinemia. At present, studies comparing these drugs for tolerability and efficacy in the same patients are lacking. It was our aim to make such a comparison in an open randomized cross-over trial. Cabergoline (0.5 mg twice weekly) and quinagolide (75 micrograms once daily) were given orally. Each drug was administered for 12 weeks. Treatment with the second drug was started after the recurrence of hyperprolactinemia. Twelve women with hyperprolactinemia due to idiopathic disease (n = 6), microprolactinoma (n = 5) or postsurgical empty sella (n = 1) were evaluated. Six women were amenorrheic and 6 were oligomenorrheic. Ten had spontaneous or provoked galactorrhea. Baseline characteristics (age, clinical signs and PRL levels) of patients initially allocated to the two treatment groups were similar. Nine patients completed both treatment cycles and PRL levels were lower under cabergoline (10.7 +/- 3.7 micrograms/L) than under quinagolide (25.0 +/- 7.7 micrograms/L; p < 0.05). One patient discontinued cabergoline because of dryness of the eyes after having completed the quinagolide cycle and 2 patients initially treated with cabergoline discontinued quinagolide because of gastrointestinal symptoms. After completion of the first treatment cycle, the time of recurrence of hyperprolactinemia was significantly longer after cabergoline (14 +/- 7 weeks) than after quinagolide (5 +/- 1 weeks; p < 0.05). At week 12, normal PRL levels (< 20 micrograms/L) were observed in 10 and 6 women during cabergoline and quinagolide, respectively. Only one case was resistant to both drugs. The clinical effects of the two treatments were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women.

The aim of this study was to analyze the effects of delta sleep-inducing peptide (DSIP) on growth hormone (GH) and prolactin (PRL) secretion in eight healthy women with normal cycles (aged 17-36 years). GH and PRL secretion was studied in five women after DSIP (25 micrograms/kg bw IV over 30 min), arginine chlorhydrate (0.5 g/kg bw IV over 30 min) and simultaneous DSIP plus arginine chlorhydrate administration. In three other women the circadian rhythm of GH and PRL was studied during DSIP (25 micrograms/kg bw from 2130h to 2230h) and placebo IV infusion. Serum GH and PRL levels were normal under basal conditions and no effects were noted after the infusion of DSIP. The GH and PRL circadian rhythm was not modified by DSIP administration. DSIP did not influence GH and PRL responsiveness to arginine chlorhydrate. We found that at dosages which are known to modify ECG patterns, DSIP is unable to modify spontaneous or arginine chlorhydrate-induced GH and PRL secretion.

[Treatment of central diabetes insipidus using oral DDAVP. Comparison with intranasal treatment]. / Trattamento del diabete insipido centrale con DDAVP per via orale. Confronto con il trattamento per via endonasale.

The Authors have done a clinical study on the efficacy of desmopressin (DDAVP) tablets in the treatment of central diabetes insipidus in 13 patients who were previously treated with intranasal DDAVP. A comparison has been made between peroral and intranasal forms of DDAVP measuring the urinary volume and osmolarity daily. The right dosage of DDAVP tablets was between 150 and 600 micrograms/die. The patients showed very good compliance during the 4 weeks of treatment with DDAVP.

LHRH-induced gonadotropin release before and after short-term therapy with cabergoline in hyperprolactinaemic patients.

Cabergoline is a new ergot derivative with long-lasting PRL lowering effect. Basal and LHRH stimulated (50 micrograms i.v.) gonadotropin secretion was evaluated before and during cabergoline treatment (0.5-2 mg/week) in 28 women with pathological hyperprolactinaemia. After 4 weeks, PRL and E2 were significantly (p less than 0.01) reduced and increased, respectively. Basal LH and FSH levels did not change. Both LH (p less than 0.05) and FSH (p less than 0.02) responsiveness to LHRH was decreased from the former to the latter test. The study underlines drug-induced variations in gonadotropin responsiveness to LHRH which are probably due to variations in the steroid milieu.