Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study.

BACKGROUND: The routine measurement of serum calcitonin (CT) has been proposed for patients with nodular thyroid disease (NTD), to detect unsuspected medullary thyroid carcinoma (MTC) before surgery. OBJECTIVE: To assess the prevalence of hypercalcitoninemia and MTC in NTD patients; to compare the ability of CT measurement and fine needle aspiration cytology (FNAC) to predict MTC; to identify age groups of NTD patients who should be better candidates than others to undergo routine measurement of CT. PATIENTS AND METHODS: 1425 consecutive patients, referred from April 1, 2003, through March 31, 2004, to four Italian endocrine centers due to NTD, were grouped depending on age, and underwent basal and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when indicated, surgery. Serum CT concentrations were measured by an immunoluminometric assay (ILMA). RESULTS: Hypercalcitoninemia was found in 23 out of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before surgery was 100% for both tests, whereas specificity was 95 and 93%, respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were considered, FNAC sensitivity approached 100%. On the contrary, a correct cytological diagnosis was obtained in only one out of five patients with <10 mm MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia was found in 57% of hypercalcitoninemic patients without MTC. CONCLUSIONS: Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients.

[Exacerbation of autoimmune hypothyroidism after hemi-hypophysectomy in a patient with Cushing's disease]. / Esacerbazione di ipotiroidismo autoimmune dopo emi-ipofisectomia in una paziente con morbo di Cushing.

A 41 year old woman affected by Cushing's disease underwent hemi-hypophysectomy with removal of an ACTH secreting microadenoma. Forty days later, when normal ACTH, cortisol plasma levels and urinary cortisol levels were restored, features of primary autoimmune hypothyroidism developed. While cortisol levels were elevated serum thyroid hormone levels were normal, serum hormone TSH was at the upper limit of the normal range and serum antimicrosomal antibodies were slightly elevated. It is likely that hypothyroidism already present before surgery was not clinically evident due to the immunosuppressive effect of high cortisol levels. The need to assess thyroid function in patient with hypercortisolism is emphasized with the aim to identify the possible onset of autoimmune thyroid disease when cortisol levels are normalized.

Circadian rhythm of plasma testosterone in men with idiopathic hypogonadotrophic hypogonadism before and during pulsatile administration of gonadotrophin-releasing hormone.

OBJECTIVE: The aim was to investigate whether a pulsatile discharge of LH from the pituitary is necessary to achieve the circadian secretion of testosterone. DESIGN: The daily rhythm of the androgen has been studied in patients with idiopathic hypogonadotrophic hypogonadism (IHH) both in the absence of therapy and during pulsatile administration of gonadotrophin releasing hormone (GnRH). PATIENTS: Six patients with IHH and ten normal subjects were analysed. Blood sampling was performed at 2-hourly intervals, for 24 hours. The IHH patients then received synthetic GnRH i.v. at the rate of one pulse every 2 hours (10 micrograms/pulse). On day 11 of treatment, blood samples were taken for the rhythm analysis every 2 hours, for 24 hours. MEASUREMENTS: Plasma testosterone and LH were measured in the individual samples by radioimmunoassay. Evaluation of the rhythm was performed by cosinor analysis. RESULTS: A significant circadian rhythm of plasma testosterone was statistically validated in the normal subjects, whereas no rhythm was detected in the IHH patients in the absence of therapy. On day 11 of GnRH pulsatile administration the IHH patients showed normal testosterone levels and a statistically significant circadian rhythm of the androgen was evident, with acrophase between 0700 and 0800 h. Moreover, the amplitude, acrophase and mesor of testosterone rhythm in IHH patients in the course of treatment were statistically indistinguishable from the corresponding values in the normal subjects. Plasma LH did not show statistically significant circadian variations, either in the control group or in the IHH patients before or during therapy. CONCLUSIONS: We conclude that a physiological circadian rhythm of plasma testosterone can be obtained, in IHH men, by treatment with GnRH. Since the pulsatile administration of exogenous GnRH at constant doses induced a circadian rhythm in testosterone and no daily variations in LH were evident, we suggest that, although a pulsatile secretion of LH is probably necessary for the synchronization of the circadian rhythm with acrophase in the morning, the testosterone variations might be the results of a local testicular modulation of LH action.

Biologically active luteinizing hormone (LH) in Klinefelter's syndrome: response to gonadotropin-releasing hormone (GnRH) and effects of testosterone undecanoate.

Basal and gonadotropin-releasing hormone (GnRH)-stimulated levels of biologically active and immunoreactive LH (bLH and iLH) were measured in six patients with Klinefelter's syndrome (KS) (mean age 24.7 years). In the same patients the diurnal rhythm of serum testosterone (T) was investigated (morning values vs. evening values). The results were compared with those obtained in ten normal young men (mean age 29.3 years). Moreover, in one patient with KS we studied the effects of testosterone undecanoate (TU) administration on bLH and iLH basal levels. A sensitive "in vitro" bioassay, based on T production by mechanically dispersed mouse Leydig cells, was employed to assess LH bioactivity. Levels of iLH and T were determined by a double antibody radio-immunoassay technique. Mean basal levels of bLH and iLH were significantly higher (p less than 0.001) in the Klinefelter patients than in normal men, whereas the mean bioactivity to immunoreactivity (b/i) ratio of LH was similar in the two groups. The mean morning T concentration was significantly higher in normal men (p less than 0.001) than in the Klinefelter group. The diurnal T rhythm was lost in the patients with KS. In the Klinefelter patients the relative maximum response of bLH to GnRH (bLH delta%) was significantly lower (p less than 0.02) than in the control men. In addition, the b/i ratio of GnRH-stimulated Lh decreased significantly (p less than 0.05) from basal values in the Klinefelter patients, whereas it remained unchanged in the control group. In the patient with KS treated with androgen replacement therapy, TU decreased iLH serum levels more than bLH concentrations, thereby increasing the b/i ratio of basally secreted LH.

Decrease in luteinizing hormone biological activity/immunoreactivity ratio in elderly men.

Basal serum concentrations of biologically active luteinizing hormone (BIO-LH), immunoreactive LH (RIA-LH) and testosterone (T), as well as the LH bioactivity/immunoreactivity (B/I) ratios were measured in 57 healthy, elderly male volunteers aged 60-94 yr. As a reference group, 53 healthy young men aged 18-49 yr were also studied. LH biological activity was assessed by an in vitro bioassay method based on testosterone production by mechanically dispersed mouse Leydig cell preparations in response to graded doses of LH. The mean BIO-LH and RIA-LH serum concentrations in the elderly men showed a significant increase (two- and three-fold, respectively, P less than 0.001, as compared with the values in the young men, whereas the mean LH B/I ratio and T values were significantly decreased (-22% and -43%, respectively, P less than 0.001). The decrease in the LH B/I ratio in elderly men led us to hypothesize that the ageing pituitary may secrete molecules of LH possessing a reduced bioactivity in relation to their immunoreactivity.

Age and sex related variations in biologically active and immunoreactive serum luteinizing hormone.

Relatively recent data from the literature show some discrepancies between bioactive LH (Bio-LH) and radioimmunoreactive LH (Ria-LH) in different endocrinological conditions. In 202 subjects of both sexes we have studied biologically active and immunoreactive LH and their ratio (B/l ratio) pattern through life. The results show that in male puberty the in vitro bioassay method gives a more discriminating measurement of serum LH than the radioimmunoassay. The ratio between bioactive and immunoreactive LH is well correlated with the increase of serum testosterone levels from male prepuberty to adulthood. On the contrary, there is no difference of B/l ratio between prepubertal girls and fertile women, in spite of the different gonadotropin levels. Finally LH bioactivity increases less markedly in elderly men than in postmenopausal women. These data suggest that, among several factors which may influence not only the quantity but also the quality of LH secreted, gonadotropin secretion rate and sex steroid milieu play an important role and may partly explain the B/l ratio changes in the situations investigated.