No considerable changes in papillary thyroid microcarcinoma characteristics over a 30-year time period.

BACKGROUND: The prevalence of papillary thyroid microcarcinoma (PTMC) is continuously increasing but its clinical significance and management is still debatable. The aim of this study was to investigate possible changes in the clinical presentation, tumor characteristics, treatment modalities and long-term outcome during the last three decades in patients with PTMC. METHODS: We studied 335 patients with PTMC who were followed up for at least 5 years, from 1982 to 2015, and treated in accordance with the current literature or guidelines at each time-period. Patients were classified according to year of diagnosis into two time periods, TP1 from 1982-2000 and TP2 from 2001-2010. RESULTS: The mean follow-up of the whole cohort was 10.6 ± 5.3 (median 9) years. No change was noted in the mean age at diagnosis or the female to male ratio during the two time periods. In regard to tumor characteristics, multifocality and non-encapsulated follicular variant of PTMC was more often present while classic PTMC was less common in patients in the TP2, compared to patients in the TP1 (p = 0.007, p < 0.001 and p = 0.043 respectively). The prevalence of incidental PTMC was high but similar in both time periods (84.6 vs 80 %, p = 0.286). The majority of patients in TP2 underwent a total or near total thyroidectomy compared to patients in TP1 (91.7 vs 80 %, p = 0.001). However, more patients underwent thyroidectomy for toxic multinodular disease and less for Graves' disease during TP1 compared to patients in the TP2 (p = 0.02 and 0.043 respectively). A significant percentage of patients underwent adjuvant radioiodine ablation, yet no difference was found between the two time periods (73.8 vs 79.5 %, p = 0.228). The rate of persistence was very low and not significant (3.1 vs 6.6 %, p = 0.165), while disease recurrence was observed in only 2 (0.6 %) patients, one from each time period. CONCLUSIONS: We did not observe any important changes regarding the clinical presentation or tumor characteristics of PTMCs during a 30-year period. With applied interventions a favorable course was confirmed in the majority of patients without differences in recurrence or persistence during the last three decades.

Birth weight and polycystic ovary syndrome in adult life: is there a causal link?

OBJECTIVES: Several studies have demonstrated associations of birth weight with metabolic and reproductive abnormalities in adults. The aim of this study was to investigate the birth weight in women with PCOS and its correlation with clinical and biochemical characteristics of the syndrome. MATERIALS AND METHODS: We studied 288 women with PCOS according to the NIH criteria and 166 women with normal cycle and without clinical hyperandrogenism. Birth weight and anthropometric characteristics were recorded, and levels of serum androgens, SHBG, insulin and fasting glucose were measured. RESULTS: Birth weight data were available for 243/288 women with PCOS and age- and BMI-matched 101/166 controls. No differences were found (p> 0.05) in birth weight among women with PCOS and normal controls. Birth weight of PCOS women was negatively correlated with DHEAS levels (p = 0.031, r = -0.143) and positively correlated with waist circumference (p <0.001, r = 0.297) and body mass index (BMI) (p = 0.040, r = 0.132). Birth weight of controls was negatively correlated with SHBG levels (p = 0.021, r = -0.234). Women from both groups were further divided in 6 categories according to birth weight (A. <2.500 gr, B. 2.501-3.000 gr, C. 3.001-3.500 gr, D. 3.501-4.000 gr, E. 4.001-4.500 gr, F. > 4.500 gr). No statistically significant differences were observed in the distribution percentages between PCOS women and controls. (A. 7% vs 7.9%, B. 26.8% vs 20.8%, C. 39.1% vs 48.5%, D. 21.4% vs 20.8%, E. 4.9% vs 2%, F. 0.8% vs 0%), (in all comparisons, p> 0.05). CONCLUSIONS: Women with PCOS do not differ from controls in birth weight distribution. However, birth weight may contribute to subtypes of the syndrome that are characterized by adrenal hyperandrogenism and central obesity.

Volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in women with differentiated thyroid cancer under TSH suppression.

OBJECTIVE: TSH suppression therapy in patients with differentiated thyroid cancer (DTC) has been associated with adverse effects on areal bone mineral density (aBMD) only in postmenopausal women. The purpose of study was to examine the effect of TSH suppression therapy on skeletal integrity using peripheral quantitative computed tomography (pQCT) at the radius and tibia in pre- and postmenopausal women with DTC and controls. STUDY DESIGN AND PATIENTS: Subjects included 80 women with DTC (40 pre- and 40 postmenopausal) and 89 (29 and 60, respectively) controls. pQCT was performed at the radius and tibia, Dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine, while samples were taken for calciotropic hormones and bone markers. RESULTS: No differences were observed concerning aBMD by DXA. In premenopausal women, there were no significant differences concerning vBMD, while cortical thickness was higher at the radius in patients with DTC (P < 0·01) compared with controls. In postmenopausal women with DTC trabecular bone mineral content (BMC), area and vBMD were lower at the radius (all P < 0·05), while at the tibia trabecular BMC and vBMD were lower at the mixed transition zone (14% from the distal end, P < 0·05) compared with controls. Cortical thickness was lower at the radius (P < 0·01) in postmenopausal patients compared with controls. Serum CTX was higher in postmenopausal women with DCT (P < 0·01), while in premenopausal patients, parathyroid hormone (PTH) was lower (P = 0·01) compared with controls. CONCLUSIONS: TSH suppression therapy is associated with higher bone resorption only in postmenopausal women; this adversely affects trabecular and cortical bone properties especially at nonweight-bearing sites such as the radius.

Bilateral adrenal incidentalomas differ from unilateral adrenal incidentalomas in subclinical cortisol hypersecretion but not in potential clinical implications.

OBJECTIVE: To investigate the possibility of a different prevalence of subclinical Cushing's syndrome (SCS) and potentially related morbidities between patients with unilateral adrenal incidentalomas (UAI) and bilateral adrenal incidentalomas (BAI), as existing data are few and controversial. DESIGN: Prospective observational study. METHODS: Clinical examination, biochemical tests, and hormonal evaluation were performed in 298 consecutive patients with adrenal incidentalomas, unilateral in 224 patients (75.2%), bilateral in 74 patients (24.8%), with apparently benign masses based on imaging characteristics and after exclusion of overt endocrine disease. The diagnosis of SCS was based on a post-dexamethasone suppression test (2 mg dexamethasone/24 h for 48 h), with serum cortisol level ≥1.8 µg/dl combined with at least one abnormal result of the other hormonal measurements. RESULTS: SCS was diagnosed in 66 out of 298 (22.1%) patients, being more frequent in patients with BAI (35.1 vs 17.9%, P=0.003, for BAI and UAI respectively). Hypertension, type 2 diabetes mellitus, impaired glucose tolerance, and dyslipidemia were of a similar frequency in both groups. SCS patients with UAI and BAI did not differ in age, gender, BMI, waist circumference, and mass size. Factors related to SCS were the presence of BAI (OR, 3.24; 95% CI, 2.31-4.54) and mass size (OR, 2.63; 95% CI, 1.31-5.26). CONCLUSION: BAI patients present more often with SCS when compared with UAI patients; however, morbidities potentially related to subtle cortisol hypersecretion were of a similar frequency in both groups. Further studies are needed to clarify whether this difference in hormonal activity may be related to different pathophysiologies.

Papillary thyroid carcinoma producing granulocyte-macrophage colony-stimulating factor is associated with neutrophilia and eosinophilia.

Thyroid tumors producing colony-stimulating factors associated with neutrophilia and/or eosinophilia are very rare and almost all of them concern anaplastic thyroid cancer. Only one case of papillary thyroid carcinoma associated with neutrophilia and one case of medullary thyroid carcinoma associated with eosinophilia have been reported. In this report a 72-year old male patient with metastatic papillary thyroid carcinoma associated with neutrophilia and eosinophilia is described. While investigating the cause of neutrophilia and eosinophilia, a blind bone marrow biopsy of the posterior iliac crest was performed, which showed infiltration by papillary thyroid carcinoma. High blood levels of granulocyte-macrophage colony-stimulating factor (GM-csF) were found using an enzyme-linked immunosorbent assay. As other causes of neutrophilia and eosinophilia were excluded, we assumed that these were paraneoplastic manifestations induced by GM-csF produced by the thyroid tumor. the disease progressed rapidly, despite appropriate treatment which included thyroidectomy and postoperative radioactive (131)I administration. the patient died 11 months after diagnosis because of extensive lung metastasis. Neutrophilia and eosinophilia were stable findings, while serum thyroglobulin levels remained elevated throughout the follow-up period. to our knowledge, this is the first report of a patient with metastatic papillary thyroid carcinoma in whom neutrophilia and eosinophilia associated with high circulating levels of GM-csF were detected.

Macroprolactinemia in a young man and review of the literature.

A 21-year old man, complaining of headaches and fatigue, with a negative past medical history and a normal clinical examination, underwent a hormonal investigation which revealed hyper-prolactinemia and intact pituitary-gonadal axis. Drug-induced hyperprolactinemia was excluded. Pituitary magnetic resonance imaging indicated a microadenoma in the right part of the gland, with a diameter of 1.5mm. No medical treatment was given as the patient had no symptoms relevant to prolactin excess. The PEG precipitation test was carried out and showed 7% recovery, which was diagnostic of the macroprolactinemia. Relatively few cases of macroprolactinemia have been published in the literature, although the condition is regarded as a fairly common cause of hyperprolactinemia. Macroprolactinemic men represent 10% of published cases.

Recurrent and/or metastatic thyroid cancer: therapeutic options.

Thyroid cancer is relatively rare, accounting for 0.5 - 10 cases per 100,000 individuals per year. Despite their generally favourable prognosis, patients with differentiated thyroid cancer are at risk of tumour recurrence for decades after diagnosis. The optimal management remains controversial even in the low-risk patients because of the high cure rates, long natural history and rarity of these tumours. Therapeutic interventions in recurrent and metastatic differentiated thyroid cancer depend on the type of initial treatment, the site and the extent of disease. Surgical excision of the amenable-to-surgery lesions and radioiodine administration remain the first approach. External radiotherapy may be given to patients with inoperable lesions or those not concentrating radioiodine. Chemotherapy has not provided consistently successful results. Various therapeutic approaches for anaplastic carcinoma give poor results, making the development of novel treatments necessary. Innovative strategies, including recombinant human thyroid stimulating hormone, retinoic acid redifferentiation therapy and gene therapy, may lead to further improvement in the management of thyroid cancer arising from follicular cells.

Long term thyroid function after (131)I treatment for toxic adenoma.

UNLABELLED: Radioactive iodine is a widely used treatment for hyperthyroidism caused by solitary autonomously functioning thyroid nodule (toxic adenoma). The aim of this retrospective analysis is to report the long term effects of this therapy on the thyroid function of patients with toxic adenoma treated in our department. Between 1968 and 1996, 160 patients received a single dose of (131)I (range 25-40 mCi) for hyperthyroidism caused by toxic adenoma. In 126 of these (110 females, 26 males), follow-up was feasible either in our Endocrine Outpatient Clinic or through correspondence. The mean observation period was 5.3 years (range 1-21 years, median 4.0). Post treatment evaluation revealed that: a) 57 patients became euthyroid and remained free of disease up to the last visit (mean observation period 5.76+/-0.52 years, range 1-21 years, median 5 years), b) 69 patients developed hypothyroidism, all within 1 to 12 months (5.9+/-0.49 months), c) persistence or recurrence of the disease (ie. thyrotoxicosis) was not observed, d) the (131)I dose, or the (131)I pretreatment TSH levels were not different between patients who developed hypothyroidism and those who became and remained euthyroid. CONCLUSION: 131I administration in the above-mentioned dose to patients with toxic adenoma: a) was a safe and very effective therapy, and b) led to hypothyroidism which developed within the first year after (131)I administration in 55% of the patients.

Normalization of thyroid hormone levels in patients with either hyper- or hypothyroidism results in a profound change of atrial natriuretic peptide (ANP) levels.

Atrial Natriuretic Peptide (ANP) is a hormone produced by cardiac atrial myocytes. Thyroid hormones may affect its release. The aim of this study was to analyze the effect of hyper and hypothyroidism on the secretion of ANP and its relationship with the changes of the renin-angiotensin-aldosterone system. Plasma ANP concentration as well as plasma renin activity (PRA) and aldosterone (ALDO) were measured in 21 patients with hyperthyroidism, 12 patients with hypothyroidism and 29 normal controls. Moreover, in 5 hyperthyroid and 8 hypothyroid patients hormones measurements were performed at diagnosis and 15, 30, 45 and 60 days after starting the appropriate therapy. Statistical analysis was performed employing the Wilcoxon two sample test to compare the ANP levels in normal and hyper or hypothyroid patients while the pairwise comparisons were evaluated using the Spermans rank correlation. Partial correlation and regression models were used to examine the joint effects of multiple predictors on ANP. ANP levels were significantly higher in hyperthyroid (mean+/-SEM, 17+/-1.7 pmol/L, +/-<0.001) and lower in hypothyroid patients (6.18+/-1.14 pmol/L, p<0.01) compared to normals (10.35+/-0.59 pmol/L). In the hyperthyroid patients following treatment with antithyroid drugs plasma ANP levels reached normal values after 15 days and remained stable thereafter. In the hypothyroid patients, ANP levels increased gradually following initiation of treatment with thyroxine, reaching values comparable to controls at day 45. PRA was significantly higher only in hyperthyroid patients compared to controls. ALDO concentrations were not different in all groups studied. No correlation was found between plasma ANP levels and T3, T4, TSH, PRA and ALDO levels in the individual groups, while a positive correlation for T3 (r=0.610, p<0.01), T4 (r=0.653, p<0.01) and pulse rate (r=0.704, p<0.01) and negative correlation with TSH (r=-0.519, p<0.01) was found when all groups were pooled together. In conclusion, our data indicate that thyroid hormones affect positively ANP secretion from cardiac myocytes. This effect may be, at least in part, indirect via hemodynamic alterations.