A. P. Tommaselli

Prevalence of Coeliac Disease in Patients with Thyroid Autoimmunity

The occurrence of autoimmune thyroid disorders among patients with coeliac disease (CD) is well documented, but the exact prevalence of CD among patients with autoimmune thyroid diseases (ATD) is as yet unclear. We screened 150 newly diagnosed patients with ATD by serum endomysial antibody detection (EmA). In 5 subjects (3.3%) EmA positivity was found; all underwent jejunal biopsy. On gluten-free diet an excellent clinical and histological response was recorded with an improvement of hypothyroidism and reduction of the thyroxine dosage. Our data suggest a significant high prevalence (3.3%) of CD in patients with ATD, in particular with Hashimoto’s thyroiditis.

Partial deficiency of adrenal 11-hydroxylase. A possible cause of primary hypertension.

Results of supraphysiological adrenocorticotropic hormone (ACTH) stimulation of biosynthetic pathways of adrenal zona fasciculata indicate that a deficiency of 11-hydroxylase exists in patients with essential hypertension. The deficiency is suggested by the much greater stimulus of synthesis of deoxycorticosterone (DOC) and deoxycortisol in hypertensive subjects than in controls (p less than 0.001). No significant difference in the synthesis of cortisol, corticosterone, progesterone, 17-hydroxyprogesterone (17-OHP), and delta-4-androstenedione (D4) was observed between the two groups. The ratios for synthesis of DOC and corticosterone and for deoxycortisol and cortisol found in hypertensive patients were significantly higher than those found in controls (p less than 0.001); no significant difference was observed in the synthesis of 17-OHP and progesterone. The synthesis of DOC and deoxycortisol was not significantly correlated with either blood pressure or plasma renin activity. Plasma renin activity was significantly lower in hypertensive subjects than in normotensive subjects (p less than 0.0001), while no difference was found in aldosterone secretion between the two groups. The 11-hydroxylase deficiency in the adrenal zona fasciculata may be one of the genetic factors causing hypertension together with environmental factors (particularly salt intake and work-related stress). The investigation performed in our study may be useful for the evaluation of adrenal zona fasciculata enzymatic activities during the study of hypertensive patients.

Derangement of the hypothalamic GnRH pulse generator in women with epilepsy

An increased frequency of reproductive endocrine diseases has been described in women with epilepsy and a subclinical reproductive dysfunction has been suggested in normally menstruating epileptic women. We assessed the reproductive endocrine function in 11 normally menstruating, drug-free epileptic women, evaluating the basal hormonal profile and LH pulsatile secretion during continuous EEG monitoring. A significant LH hyperpulsatility was observed in epileptic women compared with controls; moreover, a significant increase of gonadotropin basal secretions was observed when inter-ictal paroxysmal activity increased. The derangement of the hypothalamic GnRH pulse generator may represent a subclinical condition associated with epilepsy, not necessarily affecting the regularity of menstrual function. However, it is possible that the alteration of LH pulsatile pattern might eventually cause reproductive endocrine diseases. Paroxysmal activity seems to be an important additional factor in the derangement of gonadotropin secretion.

Interleukin-Ibeta and Beta-Endorphin Orcadian Rhythms are Inversely Related in Normal and Stress-Altered Sleep

Normal sleep is associated to physiological nocturnal rises in Interleukin 1 beta (IL 1 beta) secretion. The 24 h pattern of IL 1 beta, beta-Endorphin (beta-EPH), ACTH and cortisol (F) production was evaluated in four male healthy volunteers. Two subjects were unable to sleep, due to the stress of the experiment; in these cases, no detectable plasma IL 1 beta secretion, both diurnal and nocturnal, was present, beta-EPH plasma levels were significantly higher (p < 0.01) than in the subjects who slept regularly and, in one case, increased F plasma levels were also reported. A strong negative correlation between IL 1 beta and beta-EPH plasma levels was present in all the cases. In conclusion, stress-induced sleep alterations might deeply affect both diurnal and nocturnal IL 1 beta plasma secretion, probably due to the hypothalamus-pituitary-adrenal axis (HPAA) activation, and beta-EPH might be the reliable marker of the stress-induced HPAA activation level.

Alcohol Inhibits 11-Beta-Hydroxysteroid Dehydrogenase Activity in Rat Kidney and Liver

Male Wistar rats were treated with different ethanol concentrations diluted in drinking water in order to evaluate the effect of acute ethanol intoxication on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity in liver and kidney tissue homogenates. Rats with the highest ethanol consumption (15% ethanol supplementation) showed a significant decrease in both hepatic and renal 11 beta-OHSD activity as compared to the control group (p < 0.005). In the same group, aldosterone plasma levels were significantly lower than in controls (p < 0.01), while corticosterone (B) plasma levels were slightly higher, suggesting that the increase in intrarenal B concentrations, probably related to the acute ethanol consumption, might be responsible for a nonspecific B mineralocorticoid activity.

Evaluation, by Noninvasive Methods, of the Effects of Acute Loss of Thyroid Hormones on the Heart

To evaluate the effects of the acute loss of thyroid hormones on the heart the authors studied 11 women with acute hypothyroidism. The cardiac study was performed by means of electrocardiography (ECG), radionuclide ventriculog raphy (RNV) at rest and under effort, and monodimensional echocardiography (MD-echo) and was repeated with ECG and MD-echo after six months of thyrox ine suppressive therapy. The ECG showed a significant prolongation of QT in terval and flattening and inversion of T wave with normal heart rate. The MD-echo revealed left ventricular function in the normal range and normal left ventricular dimensions. RNV showed the ejection fraction in the lower normal range at rest, which increased to a smaller extent under effort in comparison with a control group. The ECG performed during suppressive therapy with L- thyroxine yielded normal findings with an increase of heart rate and of R wave amplitude, and the MD-echo showed no significant variations of cardiac func tion due to the increase of heart rate.

Unusual association of thyroiditis, Addison’s disease, ovarian failure and celiac disease in a young woman

The coexistence of autoimmune endocrine diseases, particularly autoimmune thyroid disease and celiac disease (CD), has recently been reported. We here present a 23-year-old woman with a diagnosis of hypothyroidism due to Hashimoto’s thyroiditis, autoimmune Addison’s disease, and kariotypically normal spontaneous premature ovarian failure. Considering the close association between autoimmune diseases and CD, we decided to search for IgA anti-endomysium antibodies (EmA) in the serum. The positivity of EmA and the presence of total villous atrophy at jejunal biopsy allowed the diagnosis of CD. On a gluten-free diet the patient showed a marked clinical improvement accompanied, over a 3-month period, by a progressive decrease in the need for thyroid and adrenal replacement therapies. After 6 months, serum EmA became negative and after 12 months a new jejunal biopsy showed complete mucosal recovery. After 18 months on gluten-free diet, the anti-thyroid antibodies titre decreased significantly, and we could discontinue thyroid substitutive therapy. This case emphasizes the association between autoimmune polyglandular disease and CD; the precocious identification of these cases is clinically relevant not only for the high risk of complications (e.g. Iymphoma) inherent to untreated CD, but also because CD is one of the causes for the failure of substitute hormonal therapy in patients with autoimmune thyroid disease.

Increased Spontaneous Release of Tumor Necrosis Factor-α/Cachectin in Headache Patients. A Possible Correlation with Plasma Endotoxin and Hypothalamic-Pituitary-Adrenal Axis

Tumor Necrosis Factor-alpha/cachectin (TNF-alpha/cachectin), Lipopolysaccharide (LPS), ACTH, beta-Endorphin (beta-EPH), and Cortisol (F) levels were determined in 33 Headache patients: 22 patients were affected with Migraine (M) and 11 patients with Chronic Type Tension Headache (CTTH). TNF-alpha/cachectin serum level was detected in 15 out of 22 migraneous patients and in no CTTH patients. Plasma LPS was observed in 11 out of 15 TNF-alpha/cachectin positive migraneous patients (73%) and in 3 out of 11 CTTH patients (27%). A negative correlation was observed between TNF-alpha/cachectin values and either ACTH or beta-EPH. In the group of migraneous patients the presence of serum TNF-alpha/cachectin showed a sensibility of .6 and a specificity of 1. The endocrine and immunological implications concerning these data are discussed.

Hormonal pattern in women affected by rheumatoid arthritis

Gonadal sex hormones may account for the sexual dimorphism in the immune response and for the greater incidence of autoimmune disease in females. We have previously reported the presence of progesterone (P) deficiency in female patients with thyroid and ovarian autoimmune disease. In this context, the hormonal profile in 9 women with rheumatoid arthritis (RA) and in 9 age-matched ealthy women, were evaluated to verify the presence of a steroid hormone secretion impairment in a systemic autoimmune disease, further supporting our hypothesis of P deficiency involvement. P and androgen plasma levels, in the luteal phase, were significantly lower (p<0.05 and 0.005, respectively) in RA patients than in the control group, with a consequent decrease of the free androgen index. Moreover, despite normal Cortisol values, corticosterone (B) plasma levels were significantly higher in the RA patients (p<0.01 and 0.05 in follicular and luteal phase, respectively). Therefore, our present data confirm the androgen deficiency in patients with a systemic autoimmune disease, such as RA and support the immunomodulator effect of P. Finally, the higher B plasma levels in RA patients may suggest the presence of a slight impairment of the immune hypothalamic-pituitary-adrenal axis (HPAA), supporting its role in certain phases of RA pathogenesis. In conclusion, in addition to androgens, the immunomodulator role of P should also be taken into account in the pathogenesis of the systemic autoimmune disease.

Success of glucocorticoid replacement therapy on fertility in two adult males with 21-CAH homozygote classic form

A normal gonadal maturation with normal fertility are some of the major goals of long-term replacement therapy in adult males with Congenital Adrenal Hyperplasia (CAH). We describe here two young men, G.O. (case A, 23 years old) and S.S.(case B, 24 years old), both with a well defined diagnosis of CAH due to 21-hydroxylase deficiency classic homozygote form (21-CAH). In case A the diagnosis of the 21-CAH classic virilizing form was made at 3 years of age. The patient has undergone glucocorticoid therapy and is now 170 cm tall; all his hormonal findings are within the normal range. The semen analysis has shown a good fertility potential, with a slight modification when the patient decided to discontinue the therapy. In case B the diagnosis of the 21-CAH salt wasting form was performed at 9 days of age. The patient was initially treated with iv normal saline solution and a daily im injection of hydrocortisone and, subsequently, with mineral and glucocorticoid replacement therapy po. A satisfactory adult stature (165 cm) was attained. The patient is still on therapy, with a good hormonal profile. The semen analysis has shown an apparently normal fertility. In conclusion, our experience in adult males with 21-CAH, who have been administered prompt and adequate replacement therapy, shows that these patients can attain normal quality of life, satisfactory growth and development, normal sexual maturation and activity, and adequate sperm fertilizing ability, thereby supporting the usefulness of continuing this therapy during adult age.