Large and medium sized artery abnormalities in untreated and treated hypothyroidism.

BACKGROUND: Hypothyroidism is frequently accompanied by cardiac dysfunction, increased vascular resistance and a greater prevalence of hypertension. Whether this condition is also accompanied by alterations of large artery function and structure is not known, however. PATIENTS AND METHODS: We investigated radial artery compliance and wall thickness as well as carotid artery compliance in 11 normotensive recently diagnosed and never treated hypothyroid patients. Fifteen euthyroid healthy age- and sex-matched subjects served as controls. No subject had evidence of large artery atherosclerotic lesions. Carotid artery diameter was evaluated continuously by a B-M mode device and carotid compliance obtained by the Reneman formula. Radial artery diameter and wall thickness were continuously acquired over the systodiastolic blood pressure range (beat-to-beat finger measurement) by an echo-tracking device, and compliance (Langewouters formula) was expressed as the integral of the area under the compliance/blood pressure curve normalized for pulse pressure. RESULTS: Patients with hypothyroidism showed greater radial wall thickness (+109%, P < 0.01) and compliance (+58%, P < 0.03) than controls. Carotid artery compliance was not different in the two groups. In 10 hypothyroid patients L- tiroxine therapy for 9.0 +/- 2.3 months did not change carotid artery function but markedly reduced radial artery wall thickness (-36%, P < 0.05) and compliance (-20%, P < 0.05). CONCLUSIONS: Hypothyroidism is associated with early arterial structural and functional alterations, which involve more muscular than elastic arteries. These alterations, however, are reversible by hormonal replacement therapy.

Acute endocrine effects of interleukin-12 in cancer patients.

IL-12, which play a fundamental antitumor role, would be also involved in the physiological regulation of neuroendocrine and immune interactions. At present, however, there are no data about the endocrine effects of IL-12. This preliminary study was performed to investigate the acute endocrine effects of IL-12 in metastatic renal cell cancer patients. Each IL-12 injection consisted of 0.5 micrograms/kg/bw subcutaneously in the morning. The study has evaluated the effects of 6 different injection cycles. Serum samples were collected before, and 4, 8 and 12 hours from IL-12 injection. In each sample, we have measured by the RIA method serum levels of GH, PRL, TSH, FSH, LH, T3, T4, cortisol, testoterone, estradiol and the pineal hormone melatonin. No significant change occurred in TSH, FSH, LH, T3, T4, testoterone and melatonin mean serum levels in response to IL-12 administration. In contrast, cortisol, PRL and estradiol significantly increased after Il-12 injection. GH also increased in response to IL-12, without however, significant differences with respect to the baseline values. This preliminary study shows that the acute subcutaneous injection of IL-12 may influence the endocrine secretions in humans. In particular, IL-12 would stimulate the secretions of cortisol, PRL and estradiol. Therefore, this study would further confirm that IL-12 may act as biological response modifier in humans, not only on the immune system, but also on the neuroendocrine functions.

Clinical value of ambulatory blood pressure monitoring.

This report reviews the evidence for and against clinical use of ambulatory blood pressure monitoring (ABPM) on a large scale. Such monitoring is supported by a number of data, among which is that the end-organ damage associated with hypertension correlates more with 24-h average blood pressure than with clinic blood pressure, the correlation becoming even closer with addition of blood pressure variability values. However, the evidence thus far collected is largely cross-sectional. Furthermore, ABPM devices have limited accuracy and the procedure has a high cost. Therefore, while prospective studies on the prognostic value of ambulatory blood pressure are awaited, use of this approach should be restricted to a limited number of clinical circumstances (e.g., identification of white-coat hypertension) and used only in specialized centers.

A clinical study of the pineal hormone melatonin in patients with growth hormone or prolactin secreting pituitary tumours.

OBJECTIVES: Despite the well documented influence of the pineal gland on pituitary function, the evaluation of pineal activity is not generally included in the clinical investigation of patients with pituitary tumours. The present study analyzed the circadian secretion of melatonin, the main pineal hormone, in patients with pituitary adenomas. METHODS: The study included 36 patients with pituitary tumours (acromegaly: 11; prolactinoma: 25), by comparing the results with those seen in 42 healthy controls. Moreover, patients were endocrinologically investigated after oral administration of 10 mg of melatonin. RESULTS: Abnormally high serum levels of melatonin during the period of maximum light and abnormally low increases during the night were seen in 7/36 and 16/36 patients, respectively, without any relation to tumour histotype. Moreover, night serum mean levels of melatonin were significantly lower in patients than in controls. Finally, the exogenous administration of melatonin did not influence growth hormone and prolactin secretions in patients with acromegaly and prolactinomas, respectively. CONCLUSION: This study demonstrates the existence of an altered pineal function in patients with pituitary tumours. Further studies will be required to establish the pathogenetic and prognostic significance of pineal disorders in neoplastic disease of the pituitary gland.

Inhibitory effect of interleukin-3 on interleukin-2-induced cortisol release in the immunotherapy of cancer.

The stimulatory effect of IL-2 on cortisol rise represents an undesirable biological event during IL-2 cancer immunotherapy. At present, no cytokine has been proven to be able to counteract IL-2-induced cortisol increase. This study was carried out to evaluate the influence of IL-3 on IL-2 stimulation of cortisol secretion. Five lung cancer patients were investigated after IL-2 (3 x 10(6) IU s.c.), after IL-3 (1 mcg/kg b.w. i.v.) and after IL-3 plus IL-2, by administering IL-3 two hours before IL-2 injection. IL-2 significantly stimulated cortisol secretion. IL-3 alone had no effect on cortisol levels. The pretreatment with IL-3 completely neutralizes IL-2-induced cortisol release. These preliminary results would suggest that IL-3 may be associated with IL-2 during cancer immunotherapy to modulate the effect of IL-2 on the endocrine system.

Preclinical hypogonadism in genetic hemochromatosis in the early stage of the disease: evidence of hypothalamic dysfunction.

We studied endocrine functions at baseline and after TRH and LHRH stimulation in a group of 7 young male patients with genetic hemochromatosis (HE) without liver damage (i.e. fibrosis and cirrhosis). In five patients endocrine re-evaluations after complete iron depletion was also performed. Mean basal testosterone (T), FSH, LH and PRL were significantly lower than in controls. Serum T increased normally after HCG stimulation. The normal or high increments of LH after LHRH stimulation suggest that secretion capacity of LH was intact and that hypothalamic dysfunction could be responsible for the preclinical gonadal deficiency found in our patients. The response of PRL to TRH indicates that secretion capacity of lactotrophs although present, was decreased and did not improve after phlebotomy therapy. After iron depletion the two patients with the lowest basal T levels showed the highest increments indicating that in the early stages of hypothalamic-pituitary damage gonadal dysfunction is still reversible in HE patients.