Long-term cardiometabolic outcome in patients with pituitary adenoma diagnosed in chilhood and adolescence.

PURPOSE: Pituitary adenomas (PAs) rarely occur in childhood and adolescence. Management of PAs in this critical age can be particularly challenging considering the auxological sequelae and potential long-term cardiometabolic consequences. We aimed to describe the clinical characteristics of patients with PA aged < 18years at diagnosis and during long-term follow-up, focusing on the prevalence of cardio-metabolic comorbidities and the impact of different therapeutic strategies. METHODS: Clinical data at diagnosis and at last follow-up visit (mean 10.3 ± 9.2 years) of 101 patients aged < 18 years with PA, referred to our University Hospital from 1990 to 2017, were retrospectively evaluated. RESULTS: At diagnosis, 11.9% of patients presented with pituitary hormone deficiencies, whose number was positively correlated with pituitary tumor diameter (p < 0.001). At diagnosis, 26.7% of patients were overweight and 15.8% were obese. In patients with hypercortisolism or GH excess the prevalence of obesity was more than 2-fold greater than in general population. No correlation was found between pituitary tumor size and BMI. At baseline, the greater the number of pituitary hormone deficits, the higher BMI (p = 0.039). In prolactinoma patients still on medical therapy at last visit, BMI was higher than at baseline. CONCLUSION: We found an increased prevalence of overweight/obesity only in pediatric and adolescent patients with GH- or ACTH-secreting PA. Regarding cardio-metabolic comorbidities other than obesity/overweight, we have not found anything worth of mention. The remission of hypercortisolism positively impacted on BMI, while medical therapy in patients with prolactinoma seemed unable to avoid weight gain, suggesting a careful metabolic management of these patients.

Serenoa repens as an Endocrine Disruptor in a 10-Year-Old Young Girl: A New Case Report.

Serenoa repens, commonly known as saw palmetto, is the sole species currently classified in the genus Serenoa. The plant is a low shrubby palm that is native of West Indies, and it grows in the coastal lands of North America and other European mediterranean countries. Its fruits contain high concentrations of fatty acids and phytosterols. S. repens extracts have been studied for the symptomatic treatment of benign prostatic hyperplasia. Recently, they have been proposed to treat androgenic alopecia and other hair disorders. We report a new case of hot flashes in a 10-year-old girl using a food supplement containing the extract of S. repens for the treatment of hirsutism. When the girl discontinued the treatment, the hot flashes stopped. A 'rechallenge' of the supplement was tried and symptoms reappeared. About 4 months after starting therapy, the girl experienced menarche. Exposure to the plant-derived product could be responsible for the appearance of menarche. In our opinion, use of phytotherapeutic agents in pediatric patients should be associated to a better evaluation of benefit/risk profile taking in account the physiological changes that occurs at different ages in this subgroup of population.

Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population.

BACKGROUND: Mutations of the thyrotropin receptor (TSHR) and/or Gαs gene have been found in a number of, but not all, autonomously functioning thyroid nodules (AFTNs). Recently, in a 15-year-old girl with a hyperfunctioning papillary thyroid carcinoma, we found two somatic and germline single nucleotide polymorphisms (SNPs): a SNP of the TSHR gene (exon 7, codon 187) and a SNP of Gαs gene (exon 8, codon 185). The same silent SNP of the TSHR gene had been reported in patients with AFTN or familial non-autoimmune hyperthyroidism. No further data about the prevalence of the two SNPs in AFTNs as well as in the general population are available in the literature. AIM: To clarify the possible role of these SNPs in predisposing to AFTN. METHODS: Germline DNA was extracted from blood leukocytes of 115 patients with AFTNs (43 males and 72 females, aged 31-85 years, mean ± SD = 64 ± 13) and 100 sex-matched healthy individuals from the same geographic area, which is marginally iodine deficient. The genotype distribution of the two SNPs was investigated by restriction fragment length polymorphism-polymerase chain reaction. RESULTS: The prevalence of the two SNPs in our study population was low and not different to that found in healthy individuals: 8 % of patients vs. 9 % of controls were heterozygous for the TSHR SNP and 4 % patients vs. 6 % controls were heterozygous for the Gαs SNP. One patient harbored both SNPs. CONCLUSIONS: These results suggest that these two SNPs do not confer susceptibility for the development of AFTN.

Serum interleukin-23 (IL-23) is increased in Hashimoto's thyroiditis.

Recent studies have demonstrated that T-helper 17 lymphocytes (Th17), which produce mostly IL-17, play a major role in several autoimmune diseases commonly thought to be Th1-related, including Hashimoto's thyroiditis (HT). IL-23, a member of the IL-12 cytokine family, is known to guide T cells toward the Th17 phenotype and its serum levels are increased in several autoimmune disease. Few data are available in the literature on IL-23 in HT. Using IL-23 Quantikine ELISA Kit (lower limit of detection 2.7 pg/mL) we analyzed the serum levels of IL-23 in 81 HT patients (75 females and 6 males, aged 14-70; mean age 39±17 years), and an age- and sex-matched group of 80 healthy persons. Both patients and controls did not receive any treatment. The positive detection rates of serum IL-23 were significantly higher in patients with HT: 56% of HT patients had detectable IL-23 in serum compared to 36% of healthy subjects (Chi χ² test, p=0.014). Moreover, HT patients had significantly higher serum concentrations of IL-23 (157.38 ± 17.92 pg/mL) in comparison with healthy controls (21.46 ± 5.4 pg/mL; p <0.0001). No significant correlation was found between serum levels of IL-23 and Tg-Ab or TPO-Ab levels, as well as with TSH values, in HT patients. In conclusion, serum IL-23 is increased in euthyroid and untreated HT patients, as compared to healthy subjects. Our data suggest that IL-23 would play a role in the pathogenesis of HT.

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome.

OBJECTIVE: Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. DESIGN: Cross-sectional. METHODS: Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25-71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. RESULTS: Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or "low BMD for age". In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07-40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99-1.08; P = 0.152). CONCLUSIONS: TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. SIGNIFICANCE STATEMENT: Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

Persistent severe visual field impairment is associated with obesity and tumour invasiveness, but not with pituitary dysfunction, in patients with craniopharyngioma.

PURPOSE: Craniopharyngiomas (CP) are benign tumours of the sellar region. Hypopituitarism, visual deficits, hypothalamic damage with consequent obesity and related increased cardiovascular risk, are complications due to the tumour itself or secondary to treatment strategy. We retrospectively correlated visual field status with clinical, neuroradiological, histopathological features and management strategy, in a single-centre cohort of patients with CP. METHODS: Thirty-four patients (16 M; median age 27.2 ± 21.8 yrs) with CP were included. We evaluated visual field status, assessed by means of standard automated perimetry and expressed as mean deviation (MD), at last follow-up visit (median 14 ± 11.7 yrs). MD has been correlated with clinical, radiological, histological data and treatment modalities. RESULTS: In univariate analysis worst eye MD was significantly associated with panhypopituitarism (p 0.010). In multivariable linear regression, panhypopituitarism (p 0.008), CP recurrence (p 0.020) and DI (p 0.004) were found to be the main independent predictors of a worse visual field outcome. When stratifying patients according to the degree of visual field impairment (MD < -12 dB Vs MD > -12 dB), the main independent predictors of worse visual field outcome were older age at diagnosis (p 0.010), CP histological subtype (p 0.004), invasiveness (p 0.04), CP recurrence (p 0.035), DI (p 0.002) and weight at last follow-up (p 0.012). CONCLUSION: In CP patients the long-term ophthalmological impairment is frequent, especially at older age, and strictly related to tumour invasiveness and recurrence, and associated to pituitary disfunction and obesity.

Parathyroid carcinoma presenting as normocalcemic hyperparathyroidism.

Parathyroid carcinoma (PC) is a rare malignancy, with an indolent but progressive course. Long-term survival is largely dependent on the extent of the primary surgical resection. Hence, pre- or intraoperative suspicion of malignancy is of great importance. We describe the case of a 62-year-old woman with a 2-year history of asthenia and mental depression. Her past medical history was significant for osteoporosis. A diagnosis of primary normocalcemic hyperparathyroidism was established and the patient underwent surgery. PC was suspected intraoperatively because of the size and appearance of the parathyroid mass (a grayish, lobulated 3.5 cm mass). Thus, aggressive surgery (en bloc resection) was performed, along with bilateral neck exploration. Pathological examination of the specimens confirmed the suspicion of PC, demonstrating vascular invasion and extracapsular infiltration into adjacent soft tissue. Immunohistochemical staining revealed an elevated Ki-67 score (8.43%; cut-off value 5%). The mean area of silver-stained nucleolar organizer regions (AgNOR) was high (4.972 µm(2)), indicating an elevated proliferation rate. Serum calcium and parathyroid hormone levels normalized postoperatively, and the patient's 5-year outcome was good. The present case provides evidence that parathyroid malignancy cannot be excluded a priori based on normocalcemic hyperparathyroidism, emphasizing the variability in clinical presentation. Moreover, Ki-67 expression and AgNOR analysis confirmed their additional value in complementing the histological evaluation of a parathyroid malignant mass.

Influence of Dietary Habits on Oxidative Stress Markers in Hashimoto's Thyroiditis.

Background: There is a growing awareness that nutritional habits may influence risk of several inflammatory and immune-mediated disorders, including autoimmune diseases, through various mechanisms. The aim of the present study was to investigate dietary habits and their relationship with redox homeostasis in the setting of thyroid autoimmunity. Materials and Methods: Two hundred subjects (173 females and 27 males; median age, 37 years) were enrolled. None were under any pharmacological treatment. Exclusion criteria were any infectious/inflammatory/autoimmune comorbidity, kidney failure, diabetes, and cancer. In each subject, serum thyrotropin (TSH), free thyroxine, antithyroid antibodies, and circulating oxidative stress markers were measured. A questionnaire on dietary habits, evaluating the intake frequencies of food groups and adherence to the Mediterranean diet, was submitted to each participant. Results: Among the 200 recruited subjects, 81 (71 females and 10 males) were diagnosed with euthyroid Hashimoto's thyroiditis (HT); the remaining 119 (102 females and 17 males) served as controls. In questionnaires, HT subjects reported higher intake frequencies of animal foods (meat, p = 0.0001; fish, p = 0.0001; dairy products, p = 0.004) compared with controls, who reported higher intake frequencies of plant foods (legumes, p = 0.001; fruits and vegetables, p = 0.030; nuts, p = 0.0005). The number of subjects who preferentially consumed poultry instead of red/processed meat was lower in HT subjects than in controls (p = 0.0141). In logistic regression analysis, meat consumption was associated with increased odds ratio of developing thyroid autoimmunity, while the Mediterranean diet traits were protective. In HT subjects, serum advanced glycation end products (markers of oxidative stress) were significantly higher (p = 0.0001) than in controls, while the activity of glutathione peroxidase and thioredoxin reductase, as well as total plasma antioxidant activity, were lower (p = 0.020, p = 0.023, and p = 0.002, respectively), indicating a condition of oxidative stress. Stepwise regression models demonstrated a significant dependence of oxidative stress parameters on consumption of animal foods, mainly meat. Conclusions: The present study suggests a protective effect of low intake of animal foods toward thyroid autoimmunity and a positive influence of such nutritional patterns on redox balance and potentially on oxidative stress-related disorders.

High bone marrow fat in patients with Cushing's syndrome and vertebral fractures.

PURPOSE: The evaluation of skeletal fragility in Cushing's syndrome (CS) is a clinical challenge, since dual-energy X-ray absorptiometry (DXA) does not capture abnormalities in bone microstructure induced by glucocorticoid excess. Hypercortisolism was shown to increase bone marrow adiposity, but it is still unknown whether high bone marrow fat (BMF) as measured by vertebral magnetic resonance spectroscopy may predict fracture risk in this clinical setting. In this cross-sectional study, we evaluated the association between BMF and vertebral fractures (VFs) in patients with CS. METHODS: Twenty patients (5 M, age 44 ± 13 years) with active CS were evaluated for morphometric VFs, lumbar spine BMF, and bone mineral density (BMD). Fifteen healthy volunteers (4 M, age 43 ± 12 years) acted as control group for BMF evaluation. RESULTS: BMF was significantly higher in CS patients vs. controls (52.0% vs. 27.0%, p < 0.01), and was directly correlated with patients' age (p = 0.03), 24-hours urine-free cortisol (p = 0.03), midnight serum cortisol (p = 0.02), and serum CTX (p = 0.01). Patients with VFs (13 cases) showed significantly higher BMF vs. patients without VFs (65.0% vs. 24.0%, p = 0.03). Fractured patients with either normal BMD or osteopenia showed comparable BMF to fractured patients with either osteoporosis or low BMD for age (p = 0.71). When the analysis was restricted to patients with normal BMD or osteopenia, VFs were still significantly associated with higher BMF (p = 0.05). CONCLUSIONS: This study provides a first evidence that vertebral adiposity may be a marker of hypercortisolism-induced skeletal fragility and measurement of spine BMF could have a role in the diagnostic work-up for the assessment of fracture risk in CS.

Selenium exerts protective effects against oxidative stress and cell damage in human thyrocytes and fibroblasts.

PURPOSE: Selenium, incorporated into specific seleno-enzymes, is essential to proper thyroid function and protect cells from oxidative damage induced by H2O2 during thyroid hormone synthesis. Several studies indicated that low selenium levels are associated with thyroid autoimmunity and related disorders, but real effectiveness of selenium supplementation in such diseases is still controversial. We evaluated the effect of selenium on oxidative damage in human thyrocytes and thyroid fibroblasts in vitro. METHODS: To induce oxidative stress, primary cultures were exposed to H2O2, in the presence or the absence of selenium, as either selenomethionine or selenite. We performed the following assays: cell viability, caspase-3 activity, BCL-2/BAX gene expression, DNA fragmentation, malondialdehyde levels, and glutathione peroxidase (GPx) activity measurements. RESULTS: Thyrocytes and thyroid fibroblasts exposed to H2O2 and preincubated with both selenocompounds displayed a significant dose-dependent increase in cell viability compared to cells incubated with H2O2 alone. Pretreatment with selenomethionine and selenite significantly reduced caspase-3 activity and BAX mRNA levels and increased BCL-2 mRNA levels in a dose-dependent manner. Accordingly, H2O2 induced a diffuse pattern of DNA degradation and an increase in malondialdehyde levels, which was prevented by the pretreatment with both selenomethionine and selenite. Both selenocompounds induced an increase in GPx activity, suggesting that these protective effects may be, almost in part, mediated by these selenoproteins. CONCLUSION: In human thyrocytes and fibroblasts in vitro, selenium exerts protective effects against H2O2 in a dose-dependent manner, being selenite effective at lower doses than selenomethionine.

Undetectable or low (<1 ng/ml) postsurgical thyroglobulin values do not rule out metastases in early stage differentiated thyroid cancer patients.

BACKGROUND: Differentiated thyroid cancer (DTC) work-up is based on (near)total-thyroidectomy plus thyroid remnant ablation (TRA) with 131-radioiodine in many patients, and long-life follow-up. 131I-post therapy whole body scan (pT-WBS) and serum thyroglobulin (Tg) are used in identifying metastatic patients. Some authors have evaluated the possibility of using post-surgical Tg (ps-Tg) values in deciding for or against TRA. The aim of our study was to verify the diagnostic accuracy of 131I-pT-WBS and SPECT/CT imaging (post-therapeutic imaging) compared to serum Tg levels in detecting metastases in early stage of DTC patients. RESULTS: Post-therapeutic imaging revealed metastases in 82 out of 570 (14.4%) patients. Metastases were successively confirmed by other diagnostic tools or by histology (sensitivity and PPV = 100%). Seventy-three out of 82 patients (90.2%) showed ps-Tg levels ≤1 ng/ml. In fifty-four per cent of patients, serum Tg levels at TRA remained ≤1 ng/ml. CONCLUSION: In conclusion, ps-Tg levels cannot be used in deciding for or against TRA. In early stage of DTC, post-therapeutic imaging (131I-pT-WBS and SPECT/CT) is an accurate method of detecting metastases, also in patients with stimulated serum Tg values ≤1 ng/ml. METHODS: We retrospectively reviewed the records of 570 consecutive patients affected by pT1-pT3 DTC (F = 450, M = 120), referred to our Nuclear Medicine Units in the last five years to perform TRA after (near)-total-thyroidectomy.All patients underwent TRA 3-4 months after thyroid surgery either in euthyroid or in hypothyroid state. Serum Tg values evaluated in post-surgical period and at TRA were matched with post-therapeutic imaging results.

Hepatocyte Growth Factor/C-Met Axis in Thyroid Cancer: From Diagnostic Biomarker to Therapeutic Target.

The hepatocyte growth factor (HGF)/c-met axis plays a crucial role in cancer development by promoting cellular proliferation, motility, and morphogenesis, as well as angiogenesis. Different cellular distributions of both the ligand and the receptor in benign vs malignant lesions indicate this biological system as a candidate for a diagnostic biomarker of malignancy occurring in endocrine glands, such as the thyroid and pituitary. Furthermore, the HGF/c-met expression may help to identify a subset of patients eligible for potential targeted therapies with HGF/c-met inhibitors or antagonists in thyroid tumour, as well as in other malignancies. This may be relevant for iodine-refractory cancers, the treatment of which is still a major challenge. With this in mind, HGF/c-met expression in thyroid cancer tissue may be useful for prognostic and therapeutic stratification of patients.

Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto's thyroiditis.

Vitamin D deficiency and/or reduced function, as per certain polymorphisms of the vitamin D receptor (VDR) gene, have been related to several autoimmune disorders. The present study was aimed to investigate the association of Hashimoto's thyroiditis with vitamin D status and functional polymorphisms (SNPs) of the VDR gene. In this case-control study, 200 euthyroid subjects were enrolled: 100 newly diagnosed HT patients (87 F, 13 M; mean age ± SD 42 ± 15 year) and 100 healthy individuals, matched for age, sex, BMI, and month of blood sampling. Serum 25(OH)D3 was measured by HPLC. The VDR SNPs BsmI, ApaI, and TaqI, in strong linkage disequilibrium with each other, were detected by restriction fragment length polymorphism-PCR. The prevalence of vitamin D deficiency in HT patients was significantly higher than that in the control group (70 vs 18.2 %; p < 0.0001), and median serum 25(OH)D3 level was significantly lower in HT patients than controls (median value: 16.2 vs 37.4 ng/ml; p = 0.026). Moreover, there was a significant inverse correlation between serum 25(OH)D3 and TPOAb concentration (r = -0.669; p = 0.034). Contrarily, the genotype distribution of the studied SNPs was not different in the two groups (BsmI p = 0.783; ApaI p = 0.512; TaqI p = 0.471), as was the allelic frequency [f(B) p = 0.776, f(b) p = 0.887; f(A) p = 0.999, f(a) p = 0.999; f(T) p = 0.617; f(t) p = 0.617]. The present study first investigates newly diagnosed untreated HT and suggests that vitamin D deficiency may contribute to HT development and/or progression, acting as an environmental trigger, while the VDR locus does not appear to be involved in conditioning the genetic susceptibility to the disease, at least in Caucasians.

Association of parathyroid carcinoma and thyroid disorders: A clinical review.

Parathyroid carcinoma is a rare malignancy, which usually occurs as a sporadic disease, and less frequently in the setting of genetic syndromes. Despite the association of parathyroid and thyroid disorders being quite common, the coexistence of parathyroid carcinoma and thyroid disease is rare. We reviewed the pertinent literature. The terms "parathyroid carcinoma" and "thyroid disease, hyperthyroidism, thyrotoxicosis, hypothyroidism, thyroid nodule(s), Graves' disease, autonomously functioning thyroid nodules" were used both separately and in reciprocal conjunction to search MEDLINE for articles published from January 2007 to March 2016. The search was prompted by the observation of a never reported association of autonomously functioning thyroid nodules and parathyroid carcinoma. Two hundred and twenty-one parathyroid carcinoma patients have been described during the last 10 years. Neck ultrasonography and parathyroid scintigraphy are the most common instrumental studies used in detecting parathyroid lesions. Serum parathyroid hormone and calcium levels are high in the majority of parathyroid carcinoma patients. Only 21 patients with parathyroid carcinoma and thyroid disorders were found. Our patient is the first casual association between parathyroid carcinoma and autonomously functioning thyroid nodules reported in literature and diagnosed using parathyroid and thyroid scintigraphies. Parathyroid carcinoma is a very rare endocrine tumor and association with thyroid disease is not frequent. Parathyroid carcinoma pre-operative diagnosis is often difficult also because available literature data are not homogenous and there is not a common operative guideline. Our case confirms the role of parathyroid scintigraphy, encouraging the association with thyroid scintigraphy, especially in the presence of (multi)-nodular goiter in order to address the most appropriate surgical management.

Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis.

BACKGROUND: Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)--compounds formed by the transformation of proteins--were evaluated as potential new markers of oxidative stress in this disease. METHODS: This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; M age = 38 ± 13 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. RESULTS: Serum d-ROMs were elevated, and BAP decreased in HT patients compared with controls (p < 0.001), and the two parameters were inversely correlated (r = -0.211; p = 0.027), clearly indicating an enhanced oxidative stress. Furthermore, AGE levels were higher in HT patients (M = 223.18 AU/g prot) than in controls (M = 189.636 AU/g prot; p = 0.020) and inversely correlated with BAP levels (r = -0.196; p = 0.037). In uni- and multivariate analysis, serum antithyroperoxidase antibodies were the main predictors for d-ROMs (p = 0.006), BAP (p < 0.001), and AGEs (p = 0.014), irrespective of thyrotropin and/or free thyroxine values. No differences in AOPPs levels were found between patients and controls (p = 0.923). CONCLUSIONS: Oxidants are increased and antioxidants decreased in euthyroid HT patients. As a result, the oxidative/antioxidative balance is shifted toward the oxidative side. Moreover, this study reports on a possible significant involvement of AGEs in HT, thus contributing to a better definition of the redox homoeostasis dysregulation in HT.

(99m)Tc-Methoxy-Isobutyl-Isonitrile Scintigraphy Is a Useful Tool for Assessing the Risk of Malignancy in Thyroid Nodules with Indeterminate Fine-Needle Cytology.

BACKGROUND: Thyroid nodular disease is a very common clinical problem. The diagnostic algorithm includes laboratory tests, thyroid ultrasound (US), thyroid scintigraphy, and, if necessary, US-guided fine-needle aspiration cytology. However, cytology results are reported as indeterminate in a not negligible number of patients. This is a central problem in the workup of patients, since about 55-85% of those undergoing surgery do not have thyroid cancer at final histology diagnosis. The aim of this study was to evaluate prospectively the role of (99m)Tc-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) thyroid scintigraphy in differentiating malignant from benign thyroid nodules with indeterminate cytology using quantitative analysis. METHOD: One hundred five patients affected by nodular thyroid goiter and with a euthyroid or hypothyroid functional status were prospectively evaluated. All patients had a suspicious nodule ≥15 mm in maximal diameter on US. All nodules were "cold" on (99m)Tc-pertechnetate scintigraphy and had a cytological diagnosis of class III or IV according to the Bethesda system. Planar images of the thyroid were acquired 10 and 60 minutes after (99m)Tc-MIBI administration. All cold nodules were MIBI-positive. Using quantitative analysis, the MIBI washout index (WOind) was calculated as a percentage reduction value of mean MIBI nodular uptake between early (+10 minutes) and late (+60 minutes) scans. RESULTS: Subdividing the patients into positive and negative for malignancy (either including or excluding patients with Hürthle cell adenoma) and performing receiver operating characterist curve analysis, the optimal WOind cutoff in differentiating malignant from benign follicular lesions was set at -19%. The overall sensitivity and specificity of (99m)Tc-MIBI quantitative analysis in identifying patients with malignant lesions was 100% and 90.9%, respectively. However, after excluding patients with Hürthle cell adenomas from the negative patient group, the overall sensitivity and specificity both reached 100%. CONCLUSION: The use of MIBI scintigraphy using quantitative analysis in the workup of cold nodules with indeterminate cytology is suggested in order to stratify patient risk for a malignant lesion better, thus reducing the number of patients referred to surgery. Surgical treatment should be planned in those patients with a WOind up to -19%.

Abnormal radioiodine uptake on post-therapy whole body scan and sodium/iodine symporter expression in a dermoid cyst of the ovary: report of a case and review of the literature.

In patients affected by differentiated thyroid cancer, the whole-body scan (WBS) with 131-radioiodine, especially when performed after a therapeutic activity of 131I, represents a sensitive procedure for detecting thyroid remnant and/or metastatic disease. Nevertheless, a wide spectrum of potentially pitfalls has been reported. Herein we describe a 63-year-old woman affected by follicular thyroid cancer, who was accidentally found to have an abdominal mass at post-dose WBS (pWBS). pWBS showed abnormal radioiodine uptake in the upper mediastinum, consistent with lymph-node metastases, and a slight radioiodine uptake in an abdominal focal area. Computed tomography revealed an inhomogeneous mass in the pelvis, previously unrecognized. The lesion, surgically removed, was found to be a typical dermoid cyst of the ovary, without any evidence of thyroid tissue. By immunohistochemistry, a moderate expression of the sodium-iodine symporter (NIS) was demonstrated in the epithelial cells, suggesting a NIS-dependent uptake of radioiodine by the cyst.

Thyroid hemiagenesis, Graves' disease and differentiated thyroid cancer: a very rare association: case report and review of literature.

OBJECTIVE: Thyroid hemiagenesis is a rare congenital disorder characterized by the absence of a lobe and/or of isthmus. Studies on the association between thyroid hemiagenesis, Graves' disease and differentiated thyroid cancer are rare. CASE PRESENTATION: We describe the medical and surgical history of a patient in whom a molecular evaluation was performed. A 36-year-old man presented with symptoms and signs of hyperthyroidism of a few months' duration. Hyperthyroidism was confirmed biochemically and anti-TSH-receptor antibodies were positive. Thyroid ultrasonography showed no left lobe and demonstrated a diffused enlargement of the right lobe; an ipoechoic, non-homogenous nodule 15 millimeters in size was identified in the middle part of the lobe. A 99mTc-pertechnetate thyroid scintigraphy (111 MBq) confirmed thyroid hemiagenesis due to the absence of the left lobe. Treatment with methimazole (30 mg/day) was started. As the patient's hyperthyroidism improved, he underwent fine-needle needle aspiration cytology (FNAC) of the right nodule. Cytology was suspicious for malignancy (THY4) and the patient was referred for surgery. Histopathological findings revealed a papillary thyroid carcinoma. The molecular analysis did not show PAX8 or TSHR mutations in the thyroid tissue nor mutations of BRAF, H-RAS, N-RAS or K-RAS genes in the tumor. CONCLUSION: Though thus far studies on the association of thyroid hemiagenesis, Graves' disease and differentiated thyroid cancer are extremely rare, the possibility of the development of thyroid cancer must be taken into account in patients affected by thyroid hemiagenesis and the nodular variant of Graves' disease.

Effects of GH replacement therapy on thyroid volume and nodule development in GH deficient adults: a retrospective cohort study.

OBJECTIVE: Despite the well-known effects of GH/IGF1 signaling on the thyroid, few data are available on the risk of developing nodular goiter in hypopituitary subjects during GH replacement therapy (GHRT). We aimed to define the effects of GH therapy on thyroid volume (TV) and nodular growth. DESIGN: The records of 96 subjects (47 males and 49 females, median age 48 years) with GH deficit (GHD) were investigated. Seventy also had central hypothyroidism (CH). At the time of our retrospective evaluation, median treatment duration was 5 years. RESULTS: Pre-treatment TV was smaller in GHD patients than in healthy subjects (P=0.030). During GH treatment, TV significantly increased (P=0.016 for the entire group and P=0.014 in euthyroid GHD patients). Before starting GH therapy, 17 patients harbored thyroid nodules. During GH therapy, nodule size increased slightly in seven patients, and new thyroid nodules occurred in nine patients. Among the 79 patients without pre-existing thyroid nodules, 17 developed one or more nodules. There was no difference in the prevalence of CH in GHD patients with or without thyroid nodules (P=0.915; P=0.841, when patients with pre-therapy nodular goiter were excluded), the main predictor for nodule development being serum IGF1 (P=0.038). CONCLUSIONS: GHRT is associated with TV's increase in GHD patients. Thyroid nodules developed in 27% of patients, mainly in relation to pre-therapy IGF1 levels, independently of normal or impaired TSH stimulation.

Radioiodine uptake in a renal cyst mimicking a metastasis in a patient affected by differentiated thyroid cancer: case report and review of the literature.

We report a 55-year-old man affected by differentiated thyroid carcinoma with lymph nodes metastases. After conventional levothyroxine withdrawal, the patient underwent thyroid remnant ablation by oral administration of radioiodine-131 ablative activity (3700 MBq). 7 days later, post-therapy whole body scan (pWBS) demonstrated thyroid remnant and showed a large area of abnormal radioiodine uptake located in the posterior left upper abdomen. Ultrasonography of the abdominal region revealed a cyst in left kidney corresponding to the focal radioiodine uptake. On the same day, 131I static images of the posterior upper abdomen obtained before and after administration of furosemide, showed that radioiodine uptake in the lesion was markedly lower after diuretic administration, indicating that radioiodine accumulation in the renal cyst is linked to an active secretory process by the renal tubule. Due to its non-negligible frequency, renal cyst should be taken into account in DTC patients as a potential pitfall at 131I pWBS.