Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.

PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION: Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

Low thyroglobulin concentrations after thyroidectomy increase the prognostic value of undetectable thyroglobulin levels on levo-thyroxine suppressive treatment in low-risk differentiated thyroid cancer.

DESIGN: Recombinant human TSH-stimulated thyroglobulin (Tg) levels (rhTSH-Tg) are sufficient for early follow-up of low-risk differentiated thyroid cancer (DTC) patients after thyroidectomy and radioiodine (131I) remnant ablation (RAI). Serum Tg levels at the time of remnant ablation (ablation-Tg) is thought to be related with rhTSH-Tg and may be predictive of recurrent disease. During long-term follow-up, Tg levels on levo-T4 (L-T4) suppressive treatment (suppressive-Tg) is sufficiently sensitive to avoid further evaluations in patients with undetectable rhTSH-Tg. The aim of our study was to verify whether, in a subgroup of low-risk DTC patients, the association of low ablation-Tg levels (<10 microg/l) with undetectable suppressive-Tg concentrations has a sufficient negative predictive value (NPV) for recurrence of disease, leading to avoid rhTSH testing. METHODS: We enrolled 169 low-risk DTC patients treated by thyroidectomy + RAI and undetectable suppressive-Tg at 12-month followup. In all patients, we retrospectively evaluated ablation-Tg and rhTSH-Tg. For all patients, 2-yr follow-up was available. RESULTS: Based on rhTSH-Tg>2 microg/l, relapsing disease was histologically proven in 2 patients. rhTSH-Tg levels between 0.6-2.0 microg/l, with no evidence of disease, was observed in 10 patients (6%). One hundred and fifty-seven patients showed undetectable rhTSH-Tg. The NPV of undetectable suppressive- Tg was 92.8%. The ablation-Tg level was <10 microg/l in 140 patients. In this group, the NPV of undetectable suppressive- Tg was 100%. CONCLUSION: Our data indicate that undetectable suppressive-Tg value, combined with ablation- Tg levels <10 microg/l, may avoid a significant number of high-cost rhTSH-Tg test.

TSH-secreting adenomas: rare pituitary tumors with multifaceted clinical and biological features.

TSH-secreting pituitary adenomas (TSH-omas) are a rare cause of hyperthyroidism in clinical practice. As their diagnosis is often delayed, these tumors are mostly diagnosed as macroadenomas, preventing an effective and radical cure and leading to serious local and systemic comorbidities. In addition to neurosurgery, medical therapy with the effective and tolerable SS analogs is a fundamental tool for the treatment of TSHomas. We report 3 cases of TSH-macroadenomas which displayed different clinical presentations. All patients showed increased free-thyroid hormone levels with inappropriately normal (2 patients) or high (1 patient) TSH levels. Magnetic resonance imaging (MRI)/computed tomography (CT) evidenced a pituitary macroadenoma and octreoscan was positive in all patients. In the 2 patients who underwent neurosurgery, hormonal hypersecretion by the tumor normalized. Histology showed nuclear pleomorphism and fibrosis, whereas immunohistochemistry showed positivity for TSH and, in a lesser amount, for FSH. In one of these patient (case 1), however, the presence of a tumor remnant inside the left cavernous sinus prompted us, in accordance with the patient, to start therapy with octreotide- long-acting release. As the third patient had a cardiac comorbidity which contraindicated neurosurgery, he underwent satisfactory treatment with long-acting SS analogs alone which normalized thyroid hormone levels. In this case, previous treatment with amiodarone confused and delayed the correct diagnosis of TSH-oma. As a result of improved laboratory and morphological techniques, TSH-omas should currently be diagnosed in early stages, thus enabling most patients to be managed satisfactorily through a combined approach.

Thyroid nodules with indeterminate cytology: prospective comparison between 18F-FDG-PET/CT, multiparametric neck ultrasonography, 99mTc-MIBI scintigraphy and histology.

PURPOSE: To evaluate the role of (18)F-flurodeoxiglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in predicting malignancy of thyroid nodules with indeterminate cytology. PATIENTS AND METHODS: We analysed 87 patients who have been scheduled to undergo surgery for thyroid nodule with indeterminate cytology. All patients underwent (18)F-FDG-PET/CT, multiparametric neck ultrasonography (MPUS), and (99m)Tc-methoxyisobutylisonitrile scintigraphy ((99m)Tc-MIBI-scan). Histopathology was the standard of reference. We compared the sensitivity (SE), specificity (SP), accuracy (AC), positive (PPV) and negative predictive (NPV) values of (18)F-FDG-PET/CT with those of (99m)Tc-MIBI-scan and MPUS in detecting cancer. Univariate and multivariate analyses evaluated the association between each diagnostic tool and histopathology. RESULTS: On histopathology, 69 out of 87 nodules were found to be benign and 18 to be malignant. The SE, SP, AC, PPV and NPV of (18)F-FDG-PET/CT were 94, 58, 66, 37 and 98% respectively. The SE, AC and NPV of (18)F-FDG-PET/CT were significantly higher than those of MPUS and (99m)Tc-MIBI-scan. The association of both positive (18)F-FDG-PET/CT and MPUS (FDG+/MPUS+) showed significantly lower SE (61% vs 94%) and NPV (88% vs 98%) than (18)F-FDG-PET/CT alone, but significantly higher SP (77% vs 58%). On univariate analysis, (18)F-FDG-PET/CT and the combination of FDG+/MPUS+ and of FDG+/MIBI- were all significantly associated with histopathology. On multivariate analysis, only FDG+/MIBI- was significantly associated with histopathology. CONCLUSION: The AC of (18)F-FDG-PET /CT in detecting thyroid malignancy is higher than that of (99m)Tc-MIBI-scan and MPUS. A negative (18)F-FDG-PET/CT correctly predicts benign findings on histopathology. The association of FDG+/MPS+ is significantly more specific than (18)F-FDG-PET/CT alone in identifying differentiated thyroid cancer. A positive (18)F-FDG-PET/CT is significantly associated with malignancy when qualitative (99m)Tc-MIBI-scan is rated as negative.

Inhibin B is a more sensitive marker of spermatogenetic damage than FSH in the irradiated non-human primate model.

This study evaluated the effect of bilateral testicular irradiation (2 Gy) on reproductive hormones, testicular volume (TV) and sperm parameters in six adult cynomolgus monkeys. Hormone levels (FSH, inhibin B and testosterone (T)) were determined to find the most valuable endocrine marker of irradiation-induced damage. All parameters were analysed at weekly intervals for 14 weeks. Histological evaluation of both testes was performed at week 14 after irradiation when one monkey was castrated and at week 27 when the remaining five monkeys were bilaterally biopsied. A decrease in body weight, TV (30% of the pre-treatment size) and sperm count was observed after irradiation. Severe oligozoospermia was achieved throughout the study but azoospermia was recorded only occasionally. Histological evaluation revealed a heterogeneous picture with patchy arrangement of seminiferous tubules containing advanced germ cell types. An increase (P<0.05) in FSH levels and, to a lesser degree also in T levels, occurred several weeks after irradiation. Inhibin B levels showed a sharp decline (P<0.001) as soon as 1 week after irradiation. FSH and inhibin B did not return to baseline levels during the observation period. A negative correlation was found between FSH and inhibin B values (r=-0.35, P<0.001). Inhibin B correlated positively with testis volume (r=0.73, P<0.001) and sperm counts (r=0.55, P<0.01). In conclusion, this study shows that inhibin B represents an early and more sensitive marker of testicular damage than FSH. Furthermore, the rapid fall of inhibin B after irradiation suggests that this hormone is a direct parameter of premeiotic germ cell proliferation.

Desmopressin and low-dose ACTH test in rheumatoid arthritis.

OBJECTIVE: To ascertain whether a different regulation and sensitivity of the hypothalamic-pituitary-adrenal axis exists and whether a type of cortisol resistance is present in rheumatoid arthritis (RA) patients, a chronic disease in whose pathogenesis modifications of the steroid milieu are involved. DESIGN: We studied the basal and dynamic response of ACTH and adrenal steroids to various stimuli acting on the hypophysis or directly on the adrenal gland. METHODS: We studied ten RA patients (39.8 +/- 7.4 (S.D.) years), defined according to the American Rheumatism Association, and seven healthy control patients (34.1 +/- 9.6 (S.D.) years). All subjects underwent testing, in random order, with placebo, desmopressin (DDAVP) (10 microg i.v.), ovine corticotropin-releasing hormone (oCRH) (1 microg/kg body weight) and low-dose ACTH (5 microg i.v.), during the follicular phase of two different menstrual cycles. Blood samples were collected at different times for ACTH and adrenal steroids assay. Baseline estradiol (E2), testosterone and IGF-I levels were also evaluated. All subjects collected urine specimens for 24 h urine free cortisol (UFC). RESULTS: No difference in E2, testosterone or UFC was found between RA patients and controls. IGF-I levels were significantly (P < 0.01) lower in RA patients (110.6 +/- 6.4 microg/l) than in controls (207.0 +/- 37.9 microg/l). Mean baseline dehydroepiandrosterone (DHEA) and delta4-androstenedione levels of the four tests were significantly (P < 0.05) lower in RA patients than in controls. In RA, a negative correlation was found between mean DHEA levels, class of disease (r = -0.67, P < 0.05) and erythrocyte sedimentation rate (r = -0.63, P < 0.05). After placebo no difference in ACTH and cortisol area under curves (AUCs) was found between RA patients and controls. After DDAVP no cortisol or ACTH response was found in RA patients, while a significant (P < 0.05) ACTH release was found in controls. Only in RA patients was DDAVP able to induce a significant (P < 0.01) DHEA increase. After oCRH a similar significant response in ACTH (P < 0.05), cortisol (P < 0.01), and DHEA (P < 0.01) was found in both groups. After low-dose ACTH, a similar significant (P < 0.01) cortisol response was found in both RA patients and controls; indeed in RA patients DHEA AUC (2196.0 +/- 321.8 nmol/l per 90 min) was significantly lower (P < 0.01) than DHEA AUC (4280.8 +/- 749.0 nmol/l per 90 min) in controls. A similar significant (P < 0.01), though not abnormal, 17-hydroxyprogesterone response to ACTH was found in both groups. CONCLUSIONS: Our study underlines reduced adrenal steroid and IGF-I levels, but not the previously described cortisol resistance in RA patients; it shows that baseline and dynamic cortisol levels are 'normal' but inadequate in the setting of a sustained inflammatory disease like RA. The reduced basal and low-dose ACTH-induced DHEA levels could reflect both a reduced sensitivity of the adrenal gland to exogenous corticotropin and a decreased steroid synthesis due to a partial adrenal enzymatic defect (P450 17,20 lyase).

The hypothalamic-pituitary-adrenal and gonadal axes in rheumatoid arthritis.

The hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes involvement or response to immune activation seems crucial for the control of excessive inflammatory and immune conditions such as autoimmune rheumatic diseases, including rheumatoid arthritis (RA). However, female patients seem to depend more on the HPA axis, whereas male patients seem to depend more on the HPG axis. In particular, hypoandrogenism may play a pathogenetic role in male RA patients because adrenal and gonadal androgens, both products of the HPA and HPG axes, are considered natural immunosuppressors. A significantly altered steroidogenesis of adrenal androgens (i.e., dehydroepiandrosterone sulfate, DHEAS and DHEA) in nonglucocorticoid-treated premenopausal RA patients has been described. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). A range of physical and psychosocial stressors are also implicated in the activation of the HPA axis and related HPG changes. Chronic and acute stressors appear to have different actions on immune mechanisms with experimental and human studies indicating that acute severe stressors may be even immunosuppressive, while chronic stress may enhance immune responses. The interactions between the immunological and neuroendocrine circuits is the subject of active and extensive ongoing research and might in the near future offer highly promising strategies for hormone-replacement therapies in RA.

Cortisol, dehydroepiandrosterone sulfate, and androstenedione levels in patients with polymyalgia rheumatica during twelve months of glucocorticoid therapy.

This paper aims to evaluate adrenal gland hormone levels in patients with polymyalgia rheumatica (PMR) during glucocorticoid (GC) therapy. A lower than expected basal production of cortisol was found in active and glucocorticoid-untreated PMR patients, particularly females. The abrupt onset of PMR with clinical features similar to those of the steroid-withdrawal syndrome or adrenal insufficiency, as well as the clinical response to GC therapy in elderly people already age-disposed to an inadequate adrenal and anti-inflammatory response, might represent the most significant pathophysiological basis of the disease.

Assessment of quality of life in recently post-menopausal women on dopaminergic therapy for pathological hyperprolactinaemia.

BACKGROUND: Psychological distress has been reported in pre-menopausal hyperprolactinaemic women. The aim of this study was to assess quality of life in a group of recently post-menopausal women with a long-term history of hyperprolactinaemia. METHODS: Thirty-one recently post-menopausal hyperprolactinaemic women (age range 46-59 years) and 37 control women matched for age and menopausal status. Hyperprolactinaemia had been diagnosed 2-22 years before the study. All hyperprolactinaemic women were on dopaminergic therapy. The self-rating Kellner Symptom Questionnaire (KSQ) and the Hamilton Depression Scale (HDS) were used to evaluate psychiatric profile. Evaluation of climacteric symptoms was performed with the ad-hoc self-rating 21-item Menopausal Rating Scale (MRS). Serum PRL, E2, LH, FSH, and free-thyroid hormones were evaluated. RESULTS: Hyperprolactinaemic women showed normal PRL on dopaminergic therapy. No difference was noted in PRL, LH, FSH, free-T4, and E2 levels between groups. Free-T3 was significantly (p = 0.001) lower in hyperprolactinaemic than in control women. There was no difference in overall scores on the MRS between the groups. Only the item "rapid and strengthened heart-beat" was significantly (p = 0.04) lower in hyperprolactinaemic than in control women. Control women showed a significant correlation between the score for this item and free-thyroid hormone levels. Overall KSQ scores and subsection analysis of items did not show significant differences between groups. On HDS evaluation, depressive symptoms were similar in hyperprolactinaemic and control women. CONCLUSIONS: Quality of life seems unchanged in recently post-menopausal women with a long-term history of hyperprolactinaemia currently on dopaminergic therapy. The present study does not therefore support the differences in psychological profile reported in literature between untreated hyperprolactinaemic and control women unselected for age.

[Anorexia nervosa: a follow-up of nutritional, hormonal and psychiatric parameters]. / Anoressia nervosa: follow-up di parametri nutrizionali, ormonali e psichiatrici.

Well known is the need to treat "acute onset" Anorexia Nervosa in care units. Nevertheless even the "successfully treated" patients show a very high percentage of relapse. The aim of our study has been to revalue different clinical, nutritional (hemoglobin, transferrin, IGF1), hormonal (thyroid function, gonadotropins) and psychiatric (EDI: Eating Disorder Inventory Test) parameters in a group of nineteen women aged 20-34 years (median 27 years) admitted to our department 1-11 years (median 6 years) before for anorexia nervosa treatment. On admission their weight loss was -33% +/- 10% according to Ideal Body Weight (IBW); a "low T3 syndrome" was present and all the patients not treated with estro-progestins were amenorrhoic. After a long hospitalization (median 51 days) the patients showed a significant decrease in weight loss (25% +/- 6%; p < 0.01). At follow-up seventeen patients had a weight better than at discharge (13% +/- 12%; p < 0.01) and 9/17 patients non treated with estro-progestins had spontaneous menses. Nutritional (hemoglobin*: 13 +/- 0.2 g%, transferrin*: 313 +/- 57 mg%, IGF-1: 187 +/- 15 ng/ml) and hormonal (LH*: 9.4 +/- 1 mUI/ml, FSH*: 15 +/- 1.3 mUI/ml, T3: 1 +/- 1 ng/ml) parameters were significantly improved (*p < 0.01, p < 0.05) compared to those at admission (hemoglobin: 12 +/- 0.2 g%, transferrin: 218 +/- 58 mg%, IGF-1: 154 +/- 21 ng/ml, LH: 5.6 +/- 0.8 mUI/ml, FSH: 9.5 +/- 1 mUI/ml, T3: 0.8 +/- 1 ng/ml). The EDI test has shown a persistence of anorexic condition ("overt" or latent) in 2/3 of patients. This study confirms the endocrine and nutritional modifications of anorexia nervosa and underlines the persistence of psychiatric ones in a great number of patients including the "clinically cured", justifying long-term follow-up and the high percentage of disease relapse.

[Sudden and unusual onset of penile plastic induration in 2 patients neurosurgically treated for pituitary macroadenoma]. / Inusuale e repentina comparsa di IPP in due soggetti sottoposti ad intervento neurochirurgico per macroadenoma ipofisario.

Induratio penis plastica (IPP) or Peyronie disease is characterized by the developing of fibrotic plaques in the tunica albuginea of penis, that in the latter stages can lead to impotence. The etiology of this disease is still unknown even if various factors such as inflammation, autoimmunity or traumas are involved. Usually it occurs after 40 years of age, even if cases in young patients have been described. The onset of IPP can be acute in about 50% of the patients, while in the others it is characterized by a chronic but progressive progress. In this work, we describe the cases of two patients 52 and 66 years old, who arrived to our department for a decrease of libido and sexual potency in the last months. The patients were not smokers and took no drugs and they had never complain symptoms and signs of IPP. In both subjects an endocrine pattern compatible with partial hypopituitarism was present and in the first patient it was associated with an ACTH-dependent hypercortisolism. Pituitary imaging with MRI showed in both patients the presence of a mass compatible with macroadenoma, that in the first patient showed characteristic of invasiveness. Both subjects underwent transphenoidal neurosurgery with the exeresis of the neoplasia, with resolution of the secondary hypogonadism and reappearance of the sexual potency. With the resume of sexual activity the patients complained the appearance of painful penis bending during erection. Dynamic echographic evaluation of the penis with 7.5 Mhz linear probe, after the intracavernous injection of prostaglandin E1 10 micrograms, showed in both patients the presence of a hyperechogenic plaque in the tunica albuginea compatible with IPP. Both patients underwent successfully surgery for the excision of the plaque and the apposition of a patch of dura mater. The authors want to underlie as the onset of IPP can be sudden, promoted by the resolution of the hypogonadism secondary to pituitary neoplasia, and contemporary to the normalization of testosterone levels.

[Gonadotropin response to GnRH and seminal parameters in low grade varicocele]. / Risposta delle gonadotropine al GnRH e parametri seminali nel varicocele di basso grado.

The pathogenetic role of varicocele in male infertility is still controversial. Although epidemiological data have clearly shown a higher incidence of varicocele in the population of subfertile and infertile patients, the real effectiveness of the surgical repair of varicocele, expressed as increase in the pregnancy rate, is still debated. The presurgical gonadotropin releasing hormone (GnRH) test is the most reliable predictive index of successful surgical outcome in terms of fertility. Only patients with an increased gonadotropin response (in particular FSH) to GnRH will benefit from the surgery. The aim of the present study was to evaluate the gonadotropin response to GnRH 50 micrograms i.v. in a group of patients with low-medium grade varicocele. At the beginning of the test, a fine needle was inserted into the forearm and kept patent by a saline solution. Blood samples were collected at the following experimental times: 0, +15, +30, +60, +90, +120 min. The stimulus was administered i.v. as bolus at time 0. The gonadotropin response to the stimulus and baseline levels of testosterone, PRL, 17 beta oestradiol and SHBG were compared with those of a control group. Moreover, all the patients underwent semen analysis after 3-7 days' abstinence and to ultrasound-doppler of the testis. Finally, we preliminarily looked for the presence of microdeletions on the Yq chromosome by polymerase chain reaction. No difference in baseline hormonal levels was found between the patients with varicocele and the controls; the LH response to GnRH was also similar in the two groups. The patients with varicocele showed a significantly (p = 0.03) higher FSH response (13.6 +/- 5.9 mUI/ml) to GnRH than controls (3.8 +/- 0.5 mUI/ml). A significant positive correlation (r = 0.6, p = 0.05) was found between LH peaks after GnRH testing and varicocele grade. Nine of 11 patients with varicocele showed significant seminal abnormalities (i.e., oligoasthenospermia): all patients showed a normal karyotype and no microdeletions were detected on the Yq chromosome. The authors underline the importance of presurgical GnRH testing in patients with low grade varicocele, given the close correlation between gonadotropin-stimulated peaks and varicocele grade found in the study. The presence of significant seminal abnormalities, even in patients with low grade varicocele, suggests the use of molecular genetic techniques to detect possible microdeletions on the Yq chromosome, which may be responsible for the infertility.

Dopaminergic modulation of hexarelin-induced GH and PRL secretion in hyperprolactinemia.

Hexarelin (Hex), a synthetic GH-releasing peptide, has recently been found to possess a weak PRL-releasing effect in normals. The aims of this study were to investigate the effect of Hex on GH and PRL secretion in 10 hyperprolactinemic women (HPRL) and 7 controls (C). All subjects underwent stimulus testing with placebo, bromocriptine (Br) (2.5 mg po at time -60), Hex (2 micrograms/kg/bw i.v.), and Br plus Hex. During placebo, HPRL showed a higher (p < 0.01) PRL area under curve (AUC) than C. Br significantly (p < 0.01) reduced PRL AUC both in HPRL and in C. Hex was able to induce a slight but significant (p < 0.05) PRL release in both groups. PRL response to Hex was abolished (p < 0.01 vs Hex) by Br priming in HPRL, while it was only blunted (p < 0.05 vs Hex) in C. Br induced a significant (p < 0.01) GH increase in both groups. However, GH AUC after Br was significantly higher (p < 0.01) in C than HPRL. Hex induced a significant (p < 0.01) GH release both in HPRL and in C. Br priming did not modify GH response to Hex in HPRL while it slightly (p < 0.05) increased GH response to Hex in C, suggesting that neuroendocrine modifications present in HPRL might, per se, be able to impair GH response to Br plus Hex, thus giving rise to receptor competition. Hex had a weak PRL-releasing effect in both groups studied, this was only blunted by Br priming in C but was abolished in HPRL, suggesting that oversensitivity to DA-ergic agents present in HPRL could be able to antagonize completely Hex action.

[An increased prevalence of thyroid echographic and autoimmune changes in hyperprolactinemic women on therapy with dopaminergic drugs]. / Aumentata prevalenza di alterazioni ecografiche e di autoimmunità tiroidea in donne iperprolattinemiche in terapia con farmaci dopaminergici.

Prolactin (PRL) possesses mitogenic and immunomodulatory properties. We evaluated the prevalence of ultrasonographic thyroid alterations and thyroid autoimmunity in hyperprolactinaemic (HPRL) women and correlated these with PRL levels. Furthermore, we studied the PRL binding in human benign nodular thyroid tissues. 133 HPRL patients (16-63 years) and 103 healthy female controls (16-63 years) with no known history of thyroid disease were studied. Blood samples were collected for PRL, FT3, FT4, TSH, thyroid peroxidase auto-antibodies (TPO Ab) and thyroglobulin auto-antibodies (Tg Ab) assays. All subjects underwent thyroid ultrasonography. PRL binding to thyroid membranes was determined by in-vitro radioreceptor assay in 5 human benign nodular thyroid fragments obtained from female patients. No difference in TSH levels was found, while FT3 (4.5 +/- 0.1 pmol/L) and FT4 (16.2 +/- 0.4 pmol/L) levels were significantly higher in controls than in HPRL (FT3: 3.8 +/- 0.1 pmol/L, p = 0.01, FT4: 15.4 +/- 0.2 pmol/L, p = 0.04). The prevalence of thyroid ultrasonographic alterations (simple goitre, uni-multinodular goitre, chronic thyroiditis) was significantly higher in HPRL (30.8%) than in controls (15.5%, p = 0.01) but did not correlate with mean initial and actual PRL levels or duration of the disease. The prevalence of autoantibodies was significantly higher in HPRL (29.6%) than in controls (14.3%, p = 0.04) but did not correlate with PRL levels. Very low specific PRL binding to thyroid membranes was detected. The high prevalence of thyroid ultrasonographic alterations and autoimmunity in HPRL suggests a possible role of PRL in the development of thyroid diseases. Clinical and instrumental thyroid screening may therefore be advisable in these patients.

PET/CT imaging in neuroblastoma.

123Iodine-metaiodobenzylguanidine (123I-MIBG) scintigraphy is currently the tracer of choice for neuroblastoma (NB). It has high diagnostic accuracy and prognostic value for the assessment of patients after chemotherapy. A positive 123I-MIBG scan is also used for the basis of targeted radionuclide therapy with 131I-MIBG. I-123 MIBG scan however has some limitations which should be taken into account. Moreover the reasons for false negative MIBG results have not been entirely elucidated. Meticulous correlation with radiological examinations and recognition of the normal distribution pattern of 123I-MIBG in children is vital to obtain optimal results. With its technical superiorities, positron emission tomography/computed tomography (PET/CT) can be successfully introduced into the diagnostic workup of NB. Different PET tracers have been offered for imaging in patients with NB, and the efficacy of this modality has been compared with that of 123I-MIBG scan. Our review aims to analyze the present role of PET/CT imaging and radiopharmaceuticals in NB.

Role of low-cost thyroid follow-up in children treated with radiotherapy for primary tumors at high risk of developing a second thyroid tumor.

AIM: Differentiated thyroid cancer (DTC) is uncommon in childhood and data on its prevalence as a second malignant neoplasm (SNM) after radiotherapy (RT) for malignancies are limited. We evaluated: 1) the incidence DTC in pediatric-oncologic patients treated with RT; 2) the relationship between DTC, RT and the features of the first malignancy; 3) the usefulness of thyroid follow-up in irradiated oncological patients. METHODS: We have followed up 252 patients treated with RT out of 966 oncologic pediatric patients. Thyroid follow-up included TSH level evaluation and neck ultrasonography. In the presence of thyroid nodule/s ≥1 cm and/or with ultrasonography suspicious for malignancy, fine needle aspiration biopsy (FNAB) was performed. When papillary/follicular lesions were detected by cytology, thyroidectomy was performed. If DTC was confirmed, patients underwent radioactive iodine (RAI) treatment. RESULTS: At least one thyroid nodule was detected in 106 irradiated patients (42%): 45 patients underwent FNAB and 27 underwent thyroidectomy. Seventeen DTC (6.7%) were found on histology. A higher incidence of DTC was seen in patients with neuroblastoma (38%) or Wilms' tumor (18%). One third of DTC showed capsule invasion, and one fourth node involvement. Eleven patients, treated with a single RAI treatment, showed undetectable thyroglobulin levels after rh-TSH-stimulation. Five patients underwent at least two RAI treatments: four patients showed complete remission and one patient partial remission. CONCLUSION: A high rate of DTC, often with invasive features, was observed in children treated with RT for primary tumors. This finding underlines the usefulness of thorough low-cost thyroid follow-up in this high-risk population.

Could [18]F-fluorodeoxyglucose PET/CT change the therapeutic management of stage IV thyroid cancer with positive (131)I whole body scan?

AIM: Stage-IV differentiated thyroid cancer (DTC) patients may present elevated serum thyroglobulin (Tg) levels associated with positive [(131)I] whole-body-scan (WBS). Nevertheless some patients in whom WBS does not reveal new sites of disease show increased Tg levels. This finding prompts thorough restaging in order to exclude the presence of metastases unable to concentrate iodine. The aim of our study was to evaluate the impact of [(18)F]FDG-PET/CT in both the assessment of overall extent of the disease and the therapeutic management in a group of stage-IV DTC patients. METHODS: On suspicious of non-iodine concentrating additional metastases, 20 stage-IV DTC patients with increasing Tg levels and stable positive post-therapy WBS were enrolled. Conventional imaging (CI) procedures, including neck ultrasonography, bone-scintigraphy and computed tomography (CT) were performed before [(18)F]FDG-PET/CT. RESULTS: [(18)F]FDG-PET/CT was positive in 16 out of 20 patients (80%). In 9 patients (45%) [(18)F]FDG PET/CT detected a larger number of tumour recurrences/metastatic sites than WBS+CI. [(18)F]FDG PET/CT findings prompted modification of the management of 11 patients (55%), in whom surgery or external radiotherapy were eventually considered more appropriate than radioactive iodine therapy. These further therapies improved the quality of life in several patients but did not change their survival rate. CONCLUSION: Our results showed that [18F]FDG-PET/CT can detect new radioiodine-negative metastases in advanced DTC patients with unchanged positive WBS and increasing Tg levels. [(18)F]FDG-PET/CT may constitute a useful tool in the choice of the best therapeutic strategy in such difficult cases.

Hypopituitarism in the elderly: multifaceted clinical and biochemical presentation.

UNLABELLED: Hypopituitarism (HYPO) is a rare and under-investigated pathology in the elderly. AIM: to review our case records of patients > or =65 yrs with first diagnosis of anterior global hypopituitarism, in order to evaluate presentation symptoms, etiology, biochemical and hormonal pictures, pituitary morphology, and efficacy of therapy. PATIENTS: 15 patients (65-82 yrs) were studied: in 11 (73%) HYPO was secondary to pituitary macroadenoma (non-secreting in 10 and GH-secreting in 1); in 3 it was associated to empty sella, and in 1 to pituitary hypoplasia. RESULTS: major presenting symptoms were visual-field defects and asthenia (40%) but also memory and/or gait impairment and nausea (30%) and depression (20%) were significantly observed. Dyslipidemia (73%), anemia (20%) and severe hyponatremia (13%) were found. After starting substitutive therapy and clinical improvement, 10 patients with macroadenoma underwent uneventful neurosurgery, which improved visual alterations but not pituitary function. Immunohistochemistry showed positivity for FSH in one patient and for GH in one patient. Six out of the eight patients with a post-surgical tumor remnant required treatment (surgery/radiotherapy/somatostatin analogue treatment in the acromegalic patient). CONCLUSIONS: The diagnosis of HYPO is often delayed in the elderly, since symptoms may be ascribed to aging and associated comorbidities. In our series, most of the aspecific symptoms were retrospectively addressed to HYPO since their resolution/improvement with replacement therapy. The prevalent cause of HYPO remains non-functioning pituitary macroadenomas. Hyponatremia can be a life-threatening presenting symptom. Symptoms considered apparently aspecific in the elderly should be investigated in order to possibly diagnose an important treatable disorder as HYPO.