Screening a coastal population in Southern Italy: iodine deficiency and prevalence of goitre, nutritional aspects and cardiovascular risk factors.

BACKGROUND AND AIM: To evaluate the prevalence of goitre by means of urinary iodine excretion, palpatory and ultrasonographic thyroid examinations in a heterogeneous population living by the sea. METHODS AND RESULTS: We used a special self-administered questionnaire to evaluate thyroid size, iodine intake, eating habits and cardiovascular risk factors in 600 subjects with a mean age of 45 +/- 17 years: 253 men (42.3%) and 347 women (57.7%). Urinary iodine excretion was low (72.1 +/- 15.7 microg/L; median 71.2) and associated with ultrasonographic evidence of an enlarged thyroid (16%) or structural thyroid abnormalities (30%), thus allowing us to define the Salerno Gulf as a mild-moderate area of endemic goitre. All of the subjects ate a Mediterranean diet, with a mean of two portions of fish/week. The cardiovascular risk factors considered were obesity, cigarette smoking, hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes, the prevalences of which were in line with those reported in other studies of similar age-matched populations. CONCLUSIONS: The moderate intake of fish and the consumption of a Mediterranean diet did not prevent goitre. Iodine deficiency and subsequent goitre endemia are also present at sea level, probably because of a diet based on local products grown on soil with a low iodine content or possible seawater, soil and air environmental pollution that may interfere with the availability of iodine. The assessment of iodine deficiency should therefore involve the entire population and not only subjects living far from the sea.

The influence of intense ballet training on trabecular bone mass, hormone status, and gonadotropin structure in young women.

A cross-sectional study on young dancers and exdancers was performed to evaluate the effects of intense weight-bearing exercise and dietary restriction, started during puberty, on bone mineral density (BMD), menarche age, menstrual function, and gonadotropin structure. Twenty current dancers (group 1) and 9 exdancers (group 2) were compared with a control group of 30 age-matched, regularly cycling women. Body weight, body mass index, total daily caloric intake, and nutritional markers were significantly lower (P < 0.05) in groups 1 and 2 than in controls. Using Quantitative Computed Tomography for the BMD evaluation, 12 dancers and 5 exdancers had Z-scores less than 2.5 SD below the mean of the controls; whereas, in 6 dancers and in 2 exdancers, BMD was between 1 and 2.5 SD. Groups 1 and 2 had a delay of menarche, which correlated positively with years of dance before menarche (r = 0.8; P < 0.001). Dancers had low levels and altered structure of circulating gonadotropins, which improved after GnRH stimulation. In conclusion, ballet training performed by dancers during puberty, dietary restriction, and low body mass index can all be associated with reduction in BMD and altered gonadotropin isoforms, with subsequent delay of menarche, menstrual dysfunctions, and insufficient peak bone mass. A longitudinal study must be conducted to confirm the persistence of low lumbar spine bone density in adult age.

Female pseudohermaphroditism and inefficient peak bone mass in an untreated subject affected by 21-hydroxylase congenital adrenal hyperplasia.

Here we describe a subject with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-CAH), in its classical virilizing form, who presented at birth ambiguous genitalia and subsequently was assigned by the parents as male. At the age of 8 years, he underwent a two-step surgical correction of hypospadia and at 22 years old, uterus and ovaries were removed and a bilateral testicular prothesis was surgically placed in scrotum. He refused any chronic glucocorticoid therapy, that was given only acutely to prevent adrenal crises during stress, trauma surgery or severe illness. The patient is now 38 years old, he is genotypically female but phenotypically male, with high endogenous levels of androgen, all of adrenal origin, and with an apparent male sexual life. He had severe osteopenia, probably due to the lack of estrogen/androgen-induced increase in bone mineral density, although periferal estrogen conversion was normal. His skeletal mass, in fact, normally acquired during adolescence and early adult life, could in this case be inefficient, for the precocious pseudopuberty, that caused an inefficient peak bone mass in adolescence period.

Dysregulation of adrenal 11 beta-hydroxylase activity in hypertensive subjects: usefulness of the ACTH 1-17 stimulation test.

BACKGROUND AND AIM: The aim of this study was to determine the validity of our previous hypothesis of adrenal 11 beta-hydroxylase (11-OH) dysregulation in "essential" low-renin hypertension. METHODS AND RESULTS: A comparison was made between 30 hypertensive patients and 30 age-matched controls (NC) in basal conditions and after ACTH stimulation (ACTH 1-17) test. The 11-deoxycortisol (S) and deoxycorticosterone (DOC) integrated areas under the curve (AUCs) of stimulus were significantly higher in the hypertensives (p < 0.001) and pointed to adrenal 11-OH dysregulation. CONCLUSIONS: The ACTH 1-17 test detects impairment of 11-OH activity of probable genetic origin. The relative mineralocorticoid excess thus provoked could be an additional cause of "essential" low-renin hypertension.

AlphaANP, AVP, and pituitary-thyroid axis in patients with congestive heart failure and acute respiratory failure.

The pituitary-thyroid axis and neurohumoral activation indexes were simultaneously investigated in 16 in-patients hospitalized for cardiac heart failure (CHF), New York Heart Association (NYHA), class II-IV, and Killip clinical scale, class II-III, to evaluate their relationship with CHF morbidity and the relative prognostic value. At entry the patients were divided into two subgroups (A and B), according to the severity of CHF. Patients were further classified into two subgroups, according to the subsequent clinical course (C, poor outcome and D, improved clinical course). Blood samples were obtained every day for the radioimmunoassay measurement of plasma alpha-atrial natriuretic peptide (alphaANP), arginine vasopressin (AVP), and thyroid hormones, and the results were compared with those of 12 control subjects. At admission, alphaANP and 3,3',5'-triiodothyronine (rT3) values were higher, while 3,3',5-triiodothyronine (T3) to rT3 (T3/rT3) ratio was lower in subgroups A and B than in controls (p<0.001), respectively, and in C than in D (p<0.001), respectively, according to the prognosis. Conversely, no differences in other thyroid indexes, nor a significant correlation between alphaANP and either rT3 or T3/rT3 ratio were present in any of the subgroups. AVP plasma levels in subgroup A were not statistically different from those of controls, whereas they were significantly decreased in subgroups B and C (p<0.05) and D (p<0.001). In conclusion, these results indicate that in CHF the pituitary-thyroid axis is not altered, that alphaANP and T3/rT3 ratio are non-invasive and reliable predictors of severity and prognosis, while AVP might be affected by the different pathological processes leading to CHF or by the concomitant use of drugs.

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.

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. lymphoma) 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.

Changes in the glycosylation pattern of circulating gonadotropins after acute administration of gonadotropin-releasing hormone in patients with anorexia nervosa.

To study the involvement of gonadotropin-releasing hormone (GnRH) in glycosylation of circulating gonadotropin isoforms in anorexia nervosa (AN), 14 amenorrhoic patients with AN, 14 age-matched volunteers in early follicular phase, and five normal-weight re-fed patients with AN were investigated under baseline conditions and after acute administration of GnRH. Plasma gonadotropins were assayed using IRMA before and after concanavalin A affinity chromatography. Baseline plasma gonadotropin levels were lower for both AN and re-fed AN patients than in controls (P<0.005). The increase in FSH and LH after GnRH administration was lower than in controls for AN (P<0.005) and re-fed AN (P<0.005 and P<0.05 respectively) patients. Percentages of total gonadotropin not bound to concanavalin A (complex carbohydrate chains) under baseline conditions were higher in patients with AN than in controls (P<0.005) but decreased after GnRH administration (P<0.001). In re-fed AN patients, the percentage of unbound FSH was higher than in controls (P<0.05), and decreased after GnRH administration (P<0.001), whereas the percentages of unbound LH were not significantly different from controls either before or after GnRH administration. These data suggest that: (a) the acute administration of GnRH induces quantitative and qualitative changes in circulating gonadotropin isoforms in both normal controls and AN patients; (b) during recovery the LH response in re-fed AN patients is associated with a glycosylation pattern that is the same as that for controls.

Different dysregulations in adrenal steroid biosynthesis as a prevalent cause of hyperandrogenism in women from southern Italy.

OBJECTIVE: To investigate the presence of a dysregulation in steroid biosynthesis in women from southern Italy. DESIGN: Controlled clinical study. SETTING: Normal and hyperandrogenic women referred to the Endocrinology Unit of Federico II University Medical School of Naples. PATIENT(S): One hundred fifty untreated young hyperandrogenic women and 50 normal age-matched women. INTERVENTION(S): Morning (basal) blood samples obtained in the early follicular phase and after a long (360 minute) ACTH stimulation test. MAIN OUTCOME MEASURE(S): The adrenal maximal response was calculated as stimulus under curve areas (AUCa), and all steroids were assayed using RIA methods. RESULT(S): A dysregulation of 21-hydroxylase was found in 22 patients (14.7%), with a prevalent increase of 17 alpha-hydroxyprogesterone AUC, whereas in 9 hirsute women (6%), there was a prevalent significant increase in 11-deoxycortisol AUC. In 5 women (3.3%), DHEA and DHEAS basal and AUCs plasma levels were increased, suggesting an impaired 3 beta-olo-dehydrogenase activity. The remaining 114 hyperandrogenic women (76%) compose the nonadrenal group, with a probable diagnosis of primitive functional ovarian hyperandrogenism. CONCLUSION(S): Considering the high prevalence of hirsutism and oligomenorrhea in our female hyperandrogenic population, we suggest an adrenal hyperresponsiveness likely due to a dysregulation in enzymes related to androgen adrenal steroidogenesis.

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 i.v. normal saline solution and a daily i.m. 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.

Usefulness of a chromatographic method to detect circulating antithyroid hormone autoantibodies in canine serum.

Antithyroid hormone autoantibodies (THBA), described in both humans and animals, result in variable interference when thyroid hormone plasma levels are measured by immunoassays. We previously described a quick chromatographic method to detect circulating THBA in humans. In the present experience, we applied the method on canine sera (10 normal dogs and 3 dogs affected by hypothyroidism) to detect the THBA presence in a dog (no. 13) with clinical evidence of hypothyroidism, in spite of apparently extremely high values of thyroid hormone. After a short incubation of samples with 125I-T3 and 125I-T4 in presence of 8-anilino-1-naphtalenesulfonic acid, samples were eluted and radioactivity values counted. Eluate radioactivity values > 10% and > 30% were considered positive for THBA presence for antiT3 and antiT4 detection, respectively. High radioactivity values were detected in dog serum no. 13 and, therefore, it was considered positive for THBA presence. The Scatchard plot analysis revealed the presence of a monoclonal autoantibody with the highest affinity for T3 and an additional tenfold lower affinity for T4. In conclusion, our chromatographic method allows the detection and the characterization of THBA in species different from humans, with species specific differences in thyroid hormone metabolism; thus, taking into account the rarely availability of canine serum TSH and anti-thyroglobulin antibody immunoassay detection methods, it was possible to correctly diagnose the hypothyroidism in a dog with apparently extremely high values of thyroid hormones due to THBA interference.

Usefulness of 123I-metaiodobenzylguanidine (MIBG) scintiscan in the diagnosis of juxta-adrenal schwannoma.

The adrenal scintiscan with 123I-metaiodobenzylguanidine (MIBG), a reliable morphofunctional technique to evaluate catecholamine turnover in adrenal tumors, can be a useful method to investigate adrenal incidentalomas with arterial hypertension. A male patient, 44 yr old with diabetes, unstable arterial hypertension, and sudden paroxysms of tachycardia is described. The presence of a disomogeneous right juxta-adrenal neoplasm with calcifications was evidenced with ultrasound tomography and confirmed by computerized tomography (CT) scan. Adrenal 123I-MIBG scintiscan revealed a unilateral uptake at level of the right juxta-adrenal region, sized similarly to the neoplasm previously evidence by CT scan. Histological findings of the surgically removed neoplasm were consistent with an ancient schwannoma. Apart from pheochromocytomas, the MIBG uptake is commonly reported in neuroblastomas. In neuroblastoma, a bidirectional process of transdifferentiation has been previously reported in vitro between two coexistent cells: cells with specific uptake system for norepinephrine, with 123I-MIBG uptake capability, and cells oriented toward schwann/melanocytic line. The evidence of in vivo MIBG uptake in our schwannoma may be caused by the same possible phenotypic interconversion of above mentioned cell types. In conclusion, the presence of adrenal tumors with MIBG uptake capability, apart from pheochromocytomas, neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, must be considered in the diagnosis of adrenal tumors.

Acute and chronic effects of human recombinant GH (hrGH) on adrenal steroidogenesis in children affected with isolated GH deficiency (IGHD).

In a previous study we demonstrated that, in children affected with isolated GH deficiency, an acute high-dose human recombinant GH (hrGH) treatment increases the 11-deoxycortisol and induces an IGF-I responsiveness to ACTH. The aim of the present study was to reevaluate, in the same children, the adrenal and IGF-I responsiveness to ACTH after a chronic replacement-dose GH therapy. Ten children (seven males and three females, mean age 7 years) affected with isolated GH deficiency underwent a synthetic ACTH 1-17 test before and after sc administration of human recombinant GH at a dose of 0.6 UI/kg/week for 3 months. After therapy, the 11-deoxycortisol responsiveness to ACTH significantly decreased compared with that observed after acute treatment (P < 0.001), and so it returned to baseline. No differences were detected in the responsiveness to ACTH of cortisol, dehydroepiandrosterone-sulphate, D4-androstenedione, and 17-hydroxyprogesterone. On the other hand, the chronic treatment induced an IGF-I responsiveness to ACTH (P < 0.001). In conclusion, our study demonstrates that, in isolated GH deficiency, replacement doses of hrGH do not modify the adrenal steroid basal levels or its responsiveness to ACTH, whereas both replacement and high doses of hrGH induce an IGF-I responsiveness to ACTH.

Altered glycosylation of pituitary gonadotropins in anorexia nervosa: an alternative explanation for amenorrhea.

To investigate the relevance of glycoprotein polymorphism to gonadotropin bioactivity in vivo, plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH), 17 beta-estradiol (E2), testosterone and sex hormone binding globulin (SHBG) levels in 17 amenorrheic women affected with anorexia nervosa (14-29 years) and 10 age-matched normally cycling women were evaluated. Plasma FSH and LH levels were assayed using radioimmunoassay (RIA) and immunoradiometric assay (IRMA) methods, before and after concanavalin A-Sepharose (Con A) affinity chromatography. Significant RIA-IRMA differences in FSH and LH plasma values were present only in women with anorexia nervosa (p < 0.005). Moreover, in these patients both FSH and LH showed a reduced binding to the Con A, expressed as a percentage of unbound, suggesting altered glycosylation of these moieties. In conclusion, these findings hypothesize the involvement of glycosylation polymorphism in RIA-IRMA differences; support the usefulness of both RIA and IRMA methods in FSH and LH evaluation, before and after Con A chromatography; and suggest a new pathogenetic pathway to explain amenorrhea in anorexia nervosa.

Percutaneous computed tomography-guided ethanol injection in aldosterone-producing adrenocortical adenoma.

The feasibility, safety and effectiveness of percutaneous computed tomography-guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [75Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hours after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasma levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized 1 month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels even on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were still present. Thus, we suggest PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA.

A quick method to detect circulating anti-thyroid hormone autoantibodies.

The aim of this study was to evaluate the feasibility of a chromatographic method to easily detect circulating anti-thyroid hormone autoantibodies (THBA), to calculate their affinity constant and the total thyroid hormone (TH) levels in presence of THBA. This method was applied to sera from 4 subject with suspected THBA and 20 controls (10 normal subjects and 10 patients with thyroid dysfunctions). After a short incubation with 125I-T3 or T4 tracer solution containing 8-anilino-1-naphthalenesulfonic acid as inhibitor of the binding of TH to plasma proteins without affecting THBA binding, the samples were chromatographied on prepacked Sephadex LH 20 columns and eluted with TRIS buffer to separate free TH from THBA-bound TH. Samples were considered THBA positive when radioactivity values in TRIS eluates were higher than in controls. THBA-bound TH were subsequently eluted with methanol and used to calculate the total TH present in patients with THBA. After a validation test using two standardized methods, we propose this method to quickly detect TH-BA in samples with suspected spuriously high values of free and total TH.

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.

Hypothalamic-pituitary-adrenal axis and immune system.

Complex and bidirectional relationships operate between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system (IS) and either in vivo or in vitro evidence supports a physiological role of the HPA axis-IS network. A part of the well-known pharmacological effects of glucocorticoid hormones (GC) as immunodepressive agents, the direct effects of many HPA axis hormones on IS functions are actually documented also in physiologic conditions. Conversely, numerous IS soluble mediators are reported to affect the HPA axis functions at various steps of HPA axis regulation, in both physiologic and pathologic conditions. Stress and aging may represent two paradigmatic conditions to show the relevance of the bidirectional network between HPA axis and IS, as in both HPA activation and IS impairment are frequently coexistent. Finally, in the context of the wide spectrum of HIV-related HPA axis abnormalities, a case of a Cushing's syndrome associated to an acquired immunodeficiency syndrome (AIDS-related complex) in a 24-year-old homosexual drug abuser is reported.