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C. Ferrari, A. Paracchi, E. Parisio, F. Codecasa, M. Mucci, M. Boghen, G. Gerevini and P. Rampini

Abstract. Serum total and free T4 and T3, thyroxinebinding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 μg, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism. Nevertheless, the finding that both FT4 and FT3 are in the normal range in some patients with mild and in most with subclinical hypothyroidism indicates that increased TSH secretion remains the most sensitive index of thyroid failure.

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Jorge R. Ferraris, Horacio M. Domene, Maria E. Escobar, Maria G. Caletti, Jose A. Ramirez and Marco A. Rivarola

Abstract. The effects of chronic renal failure on the hypothalamic-pituitary-ovarian axis in 25 girls, aged 9.1 to 20.9 years (mean 13.8) were studied. Twelve patients on conservative treatment (group A) had serum creatinine values between 176.8 and 1502.8 μmol/l; 9 patients were on haemodialysis (group B); and 12 patients had received a renal transplant (group C). Tanner stage of breast development was delayed relative to chronological age in 5 out of 18 patients. Serum oestradiol was normal or low when related to pubertal stages in all groups. Serum LH was elevated in group A and B patients, but normal in group C patients. Serum FSH was elevated in 6 out of the 21 patients in group A plus B, and in 2 out of the 12 patients in group C. Serum PRL was elevated in 12/12, 6/8, and 4/11 patients in group A, B, and C respectively. After GnRH administration to 4 patients in group A, 3 showed delayed or absent gonadotropin response; all 4 patients studied in group C showed normal gonadotropin response. The data indicate a decreased E2 secretion, abnormal gonadotropin and PRL levels and a blunted gonadotropin response to GnRH in girls with chronic renal failure. These results seem to indicate an alteration of the hypothalamic-pituitary unit that can be reversed after successful renal transplantation.

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E Ferrari, L Cravello, B Muzzoni, D Casarotti, M Paltro, SB Solerte, M Fioravanti, G Cuzzoni, B Pontiggia and F Magri

The aim of this review was to examine the evidence for age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as well as of our personal findings. A statistically significant circadian rhythmicity of serum cortisol was maintained in elderly subjects, even if with a reduced amplitude of the 24 h fluctuations and a trend to an increase of the serum levels in the evening and at night-time, in comparison with young controls. Furthermore, an age-related impairment of HPA sensitivity to steroid feedback was present in elderly people. The occurrence of senile dementia amplified the changes already present in physiological aging. While the cortisol secretion was generally well maintained in aging, the adrenal production of dehydroepiandrosterone and of its sulfate (DHEAS) exhibited an age-related decline. Therefore, the cortisol/DHEAS molar ratio was significantly higher in elderly subjects and even more in demented ones, than in young controls. Due to the opposite effects of cortisol and DHEAS on the brain and particularly on the hippocampal region, the imbalance between glucocorticoids and androgens occurring in physiological and even more in pathological aging, may have adverse effects on the function of this region, whose key role in learning and memory is well known.

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C L Ronchi, C Giavoli, E Ferrante, E Verrua, S Bergamaschi, D I Ferrari, S Corbetta, L Montefusco, M Arosio, B Ambrosi, A Spada and P Beck-Peccoz

Objective

Radiotherapy (RT) for pituitary adenomas, including GH-secreting ones, frequently leads to GH deficiency (GHD). Data on the effects of surgery alone (S) on dynamic GH secretion are limited. The aim of the study was to investigate the occurrence of GHD in acromegalic patients treated with different therapeutic options.

Design and methods

Fifty-six patients in remission from acromegaly, (33 F & 23 M, age: 54±13 years, body mass index (BMI): 28.4±4.1 kg/m2, 21 with adequately substituted pituitary deficiencies) treated by S alone (n=33, group 1) or followed by RT (n=23, group 2), were investigated for GHD by GHRH plus arginine testing, using BMI-adjusted cut-offs. Several metabolic and cardiovascular parameters (waist circumference, body fat percentage, blood pressure, fasting and post-oral glucose tolerance test glucose, HbA1c, insulin resistance and lipid profile) were evaluated in all the patients and 28 control subjects with known diagnosis of GHD.

Results

Serum GH peak after challenge was 8.0±9.7 μg/l, without any correlation with post-glucose GH nadir and IGF-1 levels. The GH response indicated severe GHD in 34 patients (61%) and partial GHD in 15 patients (27%). IGF-1 were below the normal range in 14 patients (25%). The frequency of GHD was similar in the two treatment groups (54% in group 1 and 70% in group 2). No significant differences in metabolic parameters were observed between acromegalic patients and controls with GHD.

Conclusions

Severe GHD may occur in about 60% of patients treated for acromegaly, even when cured after S alone. Thus, a stimulation test (i.e. GHRH plus arginine) is recommended in all cured acromegalic patients, independently from previous treatment.