Bilateral pheochromocytomas: clinical presentation and morbidity rate related to surgery technique and genetic status.

Background: Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60-90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients. Results: Fourteen patients (12.5%, nine women, five men) had synchronous or metachronous bilateral PHEOs (out of 112 PHEO patients who underwent surgery between 1976 and 2021). The median age at diagnosis was 32 years (9-76) (three were children). Nine patients (64.2%) presented synchronous bilateral tumors, five (35.7%) contralateral metachronous tumors, 2-12 years after the first surgical intervention; three (21.4%) were metastatic. Median follow-up: 5 years (1-41), IQR 19 months. A total of 78.5% had a germline mutation (eight RET gene with MEN2A syndrome, three VHL syndrome, three not tested). Post-surgery recurrence was noted in 16.6% of patients (one with MEN2A syndrome and metastatic PHEOs, one with VHL syndrome), with similar rates after total adrenalectomy or cortical-sparing adrenal surgery. AI was avoided in 40% after cortical-sparing surgery. Conclusion: Bilateral PHEOs are usually associated with genetic syndromes. The surgical technique for patients with hereditary bilateral PHEOs should be chosen based on a personalized approach, as they are at higher risk for developing new adrenal tumors requiring additional surgeries.

Effects of block-replace regimen in patients with autoimmune hypothyroidism converted to Graves' disease.

PURPOSE: We present two cases of autoimmune hypothyroidism converted to Graves' disease (GD) and their medical management. METHODS: We tested thyroid function and thyroid antibodies and performed an ophthalmologic examination and neck ultrasound in two patients with autoimmune hypothyroidism converted to GD during a follow-up of several years. CASE REPORTS: The first case is a 33 year-old woman with hypothyroidism due to Hashimoto's thyroiditis (HT). She developed signs and symptoms of hyperthyroidism after 7 years of treatment with the same dose of levothyroxine (LT4). Even when LT4 therapy was discontinued, she remained thyrotoxic, with mild Graves' ophthalmopathy (GO) and very high thyroid-stimulating hormone receptor antibodies (TRAb > 40 IU/L, reference range: <1.75 IU/L). Antithyroid medication was started on a titration regimen, without achievement of euthyroidism. She was switched to a block and replace regimen, using 20 mg of methimazole (MMI) and 75 mcg of LT4 daily, with normalization of thyroid hormones and improvement of GO without steroids. The second case is a 57 year-old man with a 2-year positive medical history of HT and 6 months of LT4 treatment. He developed hyperthyroidism and moderate-severe GO. Despite stopping LT4 and initiating antithyroid medication in a titration regimen, he did not achieve euthyroidism and had active GO. Pulse glucocorticoid therapy and switching to a block-replace regimen was required to achieve euthyroidism and reduce ocular proptosis and diplopia. CONCLUSION: Spontaneous autoimmune conversion of hypothyroidism to hyperthyroidism can occur at any time: it is important to promptly identify these cases so as to manage them effectively.

Clinical presentation of sporadic and hereditary pheochromocytoma/paraganglioma.

Pheochromocytomas (PHEO) and paragangliomas (PGL) can occur sporadic or within genetic predisposition syndromes. Despite shared embryology, there are important differences between PHEO and PGL. The aim of this study was to describe the clinical presentation and disease characteristics of PHEO/PGL. A retrospective analysis of consecutively registered patients diagnosed with or treated for PHEO/PGL in a tertiary care centre was performed. Patients were compared according to anatomic location (PHEO vs PGL) and genetic status (sporadic vs hereditary). In total, we identified 38 women and 29 men, aged 50 ± 19 years. Of these, 42 (63%) had PHEO, and 25 (37%) had PGL. Patients with PHEO presented more frequently with sporadic than hereditary disease (45 years vs 27 (77%) vs 8 (23%)) than patients with PGL (9 (36%) vs 16 (64%), respectively) and were older at diagnosis (55 ± 17 vs 40 ± 18 years, P = 0.001), respectively). About half of the cases in both PHEO and PGL were diagnosed due to disease-related symptoms. In patients with PHEO, tumour diameter was larger (P = 0.001), metanephrine levels higher (P = 0.02), and there was more frequently a history of cardiovascular events than in patients with PGL. In conclusion, we found that patients with PGL more frequently have a hereditary predisposition than those with PHEO, contributing to the fact that diagnosis is generally made earlier in PGL. Although diagnosis in both PHEO and PGL was mostly due to related symptoms, patients with PHEO more often presented with cardiovascular comorbidities than those with PGL which might relate to a higher number of functionally active tumours in the former.

Challenges and Limitations of Endocrine Toxicity Evaluation in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy-Retrospective Study from a Tertiary-Level Hospital in Romania.

(1) Background: The endocrine system has become a prominent target to autoimmune damage during treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Real-world data regarding endocrine immune-related adverse events (irAEs) are needed to explore their impact in cancer patients. An analysis was conducted to evaluate endocrine irAEs caused by ICIs, besides the challenges and limitations of daily medical practice in oncology in Romania. (2) Methods: This was a retrospective cohort study of lung cancer patients treated with ICIs at Coltea Clinical Hospital, Bucharest, Romania, from 1 November 2017 to 30 November 2022. Endocrine irAEs were identified through endocrinological assessment and were distinguished as any occurring endocrinopathy during treatment with ICIs and related to immunotherapy. Descriptive analyses were performed. (3) Results: Of 310 cancer patients treated with ICIs, we identified 151 with lung cancer. From this cohort, 109 NSCLC patients qualified for baseline endocrine estimation and 13 patients (11.9%) developed endocrine irAEs, such as hypophysitis (4.5%), thyroid disorder (5.5%) and primary adrenal insufficiency (1.8%), with one or more endocrine glands being affected. There might be a correlation between endocrine irAEs and duration of ICI treatment. (4) Conclusions: Early diagnosis and adequate management of endocrine irAEs may be challenging in lung cancer patients. A high incidence of endocrine irAEs is expected with the growing use of ICIs, and because not all endocrine events are immune-related, cooperation between oncologists and endocrinologists is crucial in the management of these patients. More data are needed to confirm the correlation between endocrine irAEs and the efficacy of ICIs.

A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer.

Background: Cabozantinib inhibits pathways involved in medullary thyroid cancer (MTC). Cabozantinib is approved as 140 mg/day in capsules for MTC and 60 mg/day in tablets for other solid tumors. This study compared the two doses in progressive metastatic MTC. Methods: In this Phase 4, randomized, double-blind noninferiority (NI) trial (NCT01896479), patients with progressive metastatic MTC were randomized 1:1 to cabozantinib 60 mg/day tablet or 140 mg/day capsules. The primary end point was progression-free survival (PFS) by blinded independent radiology committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. NI would be concluded if the upper 95% confidence interval [CI] for the PFS hazard ratio (HR) was less than the NI margin, 1.58. The secondary end point was objective response rate (ORR) by BIRC per RECIST v1.1; additional end points included safety and pharmacokinetics. Results: At data cutoff (July 15, 2020), 247 patients were randomized to the 60 mg/day tablet arm (n = 123) and the 140 mg/day capsules arm (n = 124). NI was not met (median PFS 11.0 months vs. 13.9 months in the 60 and 140 mg/day arms [HR 1.24; CI 0.90-1.70; p = 0.19]). The ORR was 33% in both arms. Generally, adverse event (AE) incidence was lower in the 60 mg/day arm (Grade 3/4, 63% vs. 72%), as were dose reductions (69% vs. 81%) and treatment discontinuations due to AEs (23% vs. 36%). Initially, cabozantinib plasma concentrations were higher in the 140 mg/day arm but became similar between arms at later time points. Conclusions: PFS NI of the cabozantinib 60 mg/day tablet vs. 140 mg/day capsules was not met. The 60 mg/day tablet had the same ORR and lower rates of AEs. Clinical Trial Registry: ClinicalTrials.gov NCT01896479.

Matrix metalloproteinase-9 (MMP-9) promoter -1562C/T functional polymorphism is associated with an increased risk to develop micropapillary thyroid carcinoma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of tumor initiation and progression. The MMP-9 promoter -1562C/T functional polymorphism increases gene expression and was identified as a susceptibility factor for various cancers. OBJECTIVE: To evaluate the influence of the MMP-9 promoter genotype on the risk of developing papillary thyroid cancer (PTC) and to correlate cancer patient genotype with the clinical and pathological phenotype. METHODS: We evaluated 236 patients with nodular thyroid disease pre-thyroidectomy (119 benign disease, 117 PTC). Genomic DNA was isolated from whole blood and the MMP-9 -1562C/T genotype was evaluated by PCR-RFLP analysis. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium for all groups. The T allele was significantly more frequent in cancer compared to benign disease (17.5% vs 10.1%), p= 0.019. Patients with the CT or CT+TT genotype had an increased risk of developing PTC, specifically micropapillary thyroid carcinoma (MPTC) (CT genotype: OR = 6.467, p= 0.00006; CT+TT: OR = 6.859, p= 0.00002), but not more advanced stages (CT: p= 0.094; CT+TT: p= 0.157). The -1562C/T genotype did not significantly correlate with tumor histological subtype, invasion or TNM stage. CONCLUSION: The MMP-9 -1562C/T functional polymorphism may indicate susceptibility to develop thyroid cancer, specifically intrathyroidal clinically non-relevant MPTC. This suggests that although this genotype might be a predisposing factor, other genetic/epigenetic events are needed for cancer progression.

Thresholds of Basal- and Calcium-Stimulated Calcitonin for Diagnosis of Thyroid Malignancy.

Since medullary thyroid carcinoma is an aggressive cancer, it is important to have an early detection based on stimulated calcitonin (CT), especially when basal-CT is slightly elevated. The objective of this work was to set specific thresholds for basal-CT- and calcium-stimulated calcitonin for prediction of thyroid malignancy in female population. The study included 2 groups: group A-women with elevated basal-CT (>9.82 pg/ml) and group B-women with normal basal-CT (control group). After calcium stimulation test precise protocol, histopathological reports of those that required surgery were correlated with both basal and stimulated calcitonin. The best basal and stimulated calcitonin cut-offs for distinguishing female patients with medullary thyroid carcinoma or C-Cell-hyperplasia from other pathologies or normal cases were: 12.9 pg/ml, respectively 285.25 pg/ml. For basal-CT above 30 pg/ml, malignancy was diagnosed in 9/9 patients (100%): 9 MTC. For stimulated calcitonin above 300 pg/ml, malignancy was diagnosed in 17/21 patients (80.95%): 12 MTC and 5 papillary thyroid carcinomas. The smallest nodule that proved to be medullary thyroid carcinoma had only 0.56/0.34/0.44 cm on ultrasound, with no other sonographic suspicious criteria. In conclusion, we have identified in Romanian female population basal and stimulated calcitonin thresholds to discriminate medullary thyroid carcinoma or C-Cell-hyperplasia from other cases. We recommend thyroid surgery in all women with stimulated calcitonin above 285 pg/ml. Further studies on larger groups are necessary to establish and confirm male and female cut-offs for early diagnosis of medullary thyroid carcinoma, and interestingly, maybe for macro-papillary thyroid carcinomas alike. The calcium administration has minimum side-effects, but continuous cardiac monitoring is required.

Safety of calcitonin stimulation tests with calcium.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is an aggressive form of thyroid cancer. Early detection is essential because only complete resection of the thyroid tumor and any local metastases can cure MTC. Calcitonin (CT) is a marker used for diagnosis of MTC. In controversial cases of slightly elevated CT levels, stimulation tests have shown their utility, but their safety should also be taken into account. OBJECTIVE: Our aim is to present our own experience regarding the safety of CT stimulating tests. MATERIALS AND METHODS: We applied a specific protocol of calcium stimulation test in 176 patients after informed consent (115 women with a median age of 46 years, range 21-79; 61 men with a median age of 54 years, range 22-78). We recorded the side effects and a further analysis was performed. RESULTS: The most frequent side effects noted were hot flashes in 159 out of 176 patients (90.34%), followed by dysgeusia (32/176) and bradycardia (10/176). Severe bradycardia was reported in only one patient (0.568%), which was rapidly reversible. There was no correlation between patients' age, weight, height, body mass index, basal CT or peak stimulated CT, and grade of severity, but men were more likely to develop cardiovascular side effects than women, namely, bradycardia, tachycardia, ventricular or atrial extrasystoles, hypertension, hypotension, or angina (p = 0.024), with an odds ratio of 2.94 (CI: 1.11-7.76). We recommend thyroid surgery in all women with sCT above 285 pg/ml. CONCLUSION: The calcium stimulation test is well tolerated, with few adverse reactions. The test should be performed with appropriate precautions (i.e., ECG monitoring during and after the test) to minimize the possibility of a serious event.

Calcitonin Stimulation Tests: Rationale, Technical Issues and Side Effects: A Review.

Calcitonin (CT) stimulation tests have great value and could help to: differentiate thyroid causes of elevated CT apart from non-thyroid sources, determine whether the patients with slightly elevated basal CT could/could not be candidates for surgery, and indicate the right moment for prophylactic thyroidectomy in children with MEN syndromes when with normal basal CT. This triggered the requests for development of CT stimulation tests, taking into consideration their safety and aimed us to write a systematic review of literature regarding the rationale, technical issues, and side effects of CT stimulating tests used for diagnosis of MTC. After a thorough review of the literature, we classified the reported side effects by severity, as defined by United States Food and Drug Administration. A statistical analysis was performed using IBM SPSS Statistics version 20. Various side effects were noticed during stimulation tests that differ by intensity, duration and severity, depending on types of substances and protocols used. The side effects after pentagastrin test were significantly more severe than those reported after calcium stimulation test (p=0.0396). There are also significant gender-specific differences in side effects induced by stimulation tests. In conclusion, we recommend performing Ca CT stimulation test when needed, considering preventive evaluation of some clinical, instrumental, and biochemical aspects of each patient. Precise instructions should be followed before a stimulation test and furthermore continuous cardiac monitoring is essential during and after the test to minimize the possibility of a serious event.

Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer.

BACKGROUND: Lung metastases may worsen overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study). PATIENTS AND METHODS: 392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to open-label lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated. RESULTS: Lenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions ≥1.0 cm (n = 199), ≥1.5 cm (n = 150), ≥2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57-1.01; P = 0.0549). Median OS for lung metastases of ≥1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47-0.85; P = 0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of ≥1.0 cm, ≥1.5 cm, ≥2.0 cm and <2.0 cm; median OS was shorter in the ≥2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1-49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of ≥1.0 cm after adjustment for baseline characteristics. CONCLUSIONS: Lenvatinib treatment resulted in longer OS in patients with lung metastases of ≥1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of ≥1.0 cm. SOURCE STUDY REGISTRATION: ClinicalTrials.Gov Identifier: NCT01321554.

Collision tumors of the thyroid. A special clinical and pathological entity.

Thyroid collision tumors are rare entities that designate two histologically and morphologically distinct tumors that occur simultaneously or as metastases from other organs within the thyroid. Medullary and papillary carcinoma co-occurrence is the most frequent. Several theories tried to explain the pathogenic mechanisms underlining collision tumors, including the theory which assumes that one tumor predisposes the other, stem cell theory, and random effect theory, but their combination better explains the origin of these tumors. Hypotheses about common genetic behavior responsible for the pathogenesis have also been suggested, such as the involvement of germline mutation of RET (Rearranged during Transfection) proto-oncogene in medullary thyroid carcinoma and papillary thyroid carcinoma coexistence, but there is controversy on this topic. Management of thyroid collision tumors is challenging owing to the presence of two distinct tumors with different biological aggressiveness, treatments options, and prognosis, and needs to be individualized.

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform. AIMS: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. DESIGN: On-line survey in endocrine centres throughout Europe. PATIENTS AND METHODS: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. RESULTS: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. CONCLUSION: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

Serum Matrix metalloproteinase-9 (MMP-9) can help identify patients with papillary thyroid cancer at high risk of persistent disease: Value and limitations of a potential marker of neoplasia.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of invasion and metastasis in neoplasia. In thyroid cancer expression levels correlate with aggressiveness but data on peripheral MMP-9 levels are less definitive. OBJECTIVE: Prospective study evaluating serum MMP-9 in the diagnosis and prognosis of papillary thyroid cancer. METHODS: Serum samples of MMP-9 were drawn before surgery in 185 consecutively enrolled patients with nodular thyroid disease, stratified on pathology as benign disease (N= 88) and papillary thyroid cancer (N= 97). Serum MMP-9 was measured by an immunometric assay. RESULTS: MMP-9 levels were not different between benign vs malignant pathology (p= 0.3). In papillary thyroid cancer there was no significant difference in MMP-9 levels between histologies, TNM stage and invasive/non-invasive cancers. High-risk patients with multiple features of aggressiveness had significantly higher MMP-9 levels compared to low-intermediate risk patients (767.5 ± 269.2 ng/ml vs 563.7 ± 228.4 ng/ml, p= 0.019). A cut-off of 806 ng/ml distinguished high from low-intermediate risk patients with a sensitivity of 60% and a specificity of 87.36%, p= 0.018. In patients with available follow-up data (N= 78), MMP-9 was higher in patients who required ⩾ 2 doses of 131I therapy (p= 0.009) and in those with biochemical evidence of persistent disease/who required additional therapy to achieve disease-free status (p= 0.017). CONCLUSION: Serum MMP-9 is not useful in the diagnosis of PTC, but preliminary data shows that high pre-surgical serum MMP-9 levels may identify patients at higher risk of persistent disease who require intensive treatment. Large volume prospective studies are required to confirm this observation.

Alterations of regulatory factors and DNA methylation pattern in thyroid cancer.

PURPOSE: DNA methylation plays an important role in thyroid oncogenesis. The aim of this study was to investigate the connection between global and local DNA methylation status and to establish the levels of important DNA methylation regulators (TET family and DNMT1) in thyroid tumours: follicular adenoma-FA, papillary thyroid carcinoma-PTC (classic papillary thyroid carcinoma-cPTC and papillary thyroid carcinoma follicular variant fvPTC). METHODS: Global DNA methylation profile in thyroid tumours tissue (41 paired samples) was assessed by 5-methylcytosine and 5-hydroxymethylcytosine levels evaluation (ELISA), along with TETs and DNMT1 genes expression quantification. Also, it was investigated for the first time TET1 and TET2 promoter's methylation in thyroid tumours. BRAF V600E mutation and RET/PTC translocation testing were performed on all investigated samples. In vitro studies upon DNA methylation in K1 thyroid cancer cells were performed with demethylating agents (5-AzaC and vitamin C). RESULTS: TET1 and TET2 displayed a significantly reduced gene expression level in PTC, while DNMT1 gene presented a high level of expression. PTC samples presented increased levels of 5-methylcytosine and low levels of 5-hydroxymethylcytosine. 5-methylcytosine levels were associated with TET1/TET2 expression levels. TET1 gene expression was significantly lower in patients positive for BRAF mutation and with RET/PTC rearrangement. TET2 gene was found hypermethylated in thyroid carcinoma patients overall, especially in PTC-follicular variant samples (p= 0.0002), where TET2 gene expression levels were significantly reduced (p= 0.0031). Furthermore, the data indicate for all thyroid cancer patients a good sensitivity (81.08%) and specificity (86.49%) regarding the use of TET1 (p< 0.0001), and TET2 (71.79%, 64.10%, p= 0.0001) hypermethylation as biomarkers for thyroid oncogenesis. CONCLUSIONS: These results suggest that TET1/TET2 gene expression and methylation may serve as potential diagnostic tools for thyroid neoplasia. Our study showed that the methylation of TET1 increases in malignant thyroid tumours. fvPTC patients presented lower methylation levels compared to cPTC and could be a discriminatory factor between two cancer types and benign lesions. TET2 is a poorer discriminator between FA and fvPTC, but it can be useful for cPTC identification. K1-cells treated with demethylating agents showed a demethylation effect, especially upon TET2 gene. The cumulative effect of L-AA and 5-AzaC proved to have a potent combined demethylating effect on genes promoter's activation and could open new perspectives for thyroid cancer therapy.

Selenium involvement in mitochondrial function in thyroid disorders.

Selenium (Se), an important oligoelement, is a component of the antioxidant system. Over the last decade, it has been ever more frequently discussed in the context of thyroid disorders. Graves' disease and Hashimoto's thyroiditis, differentiated thyroid cancer, and even endemic goiter may have common triggers that are activated by excess reactive oxygen species (ROS), which are involved in various stages of the pathogenesis of thyroid disorders. Most oxidative events occur in mitochondria, organelles that contain enzymes with Se as a cofactor. Mitochondria are responsible for the production of ATP in the cell and are also a major site of ROS production. Thyroid hormone status (the thyroid being the organ with the highest concentration of Se in the body) has a profound impact on mitochondria biogenesis. In this review, we focus on the role of Se in mitochondrial function in thyroid disorders with impaired oxidative stress, since both thyroid hormone synthesis and thyroid dysfunction involve ROS. The role of Se deficiency or its excess in relation to mitochondrial dysfunction in the context of thyroid disorders is therefore of interest.

Partial Adrenalectomy - Arguments for the Minimally Invasive Surgical Approach.

Background: Partial adrenalectomy has been widely performed in the last decades in order to diminish the number of patients who would become lifetime dependent of hormonal replacement. Method: between 2016 and 2018 seven patients were submitted to minimally invasive partial adrenalectomy in Ponderas Academic Hospital. Results: the median age at the time of surgery was 56 years (range 42-67 years) while the indications for partial adrenalectomy (PA) were represented by Conn's syndrome in four cases, bilateral pheochromocytoma in one cases and nonfunctional adrenal tumors in two cases. Preoperatively successful adrenal vein sampling was performed in one case. The indocyanine green test (ICG) as well as intraoperative ultrasound were used each in three cases. The transperitoneal approach was used for PA in all patients, laparoscopic in five and robotic assisted in two patients. No conversion to open surgery or to total suprarenalectomy was encountered. Conclusions: minimally invasive surgery seems to be a safe and effective method to perform partial adrenalectomy. Moreover, development of novel technologies such as adrenal vein sampling, indocyanine green test or intraoperative ultrasound seem to increase the feasibility of the method as well as the number of cases who could benefit from the type of approach. Use of new technology?

Treatment for benign thyroid nodules with a combination of natural extracts.

Benign thyroid nodules are among the most common endocrine disorders. Recent advances in diagnostic imaging and pathology have significantly contributed to better risk stratification of thyroid nodules. However, current treatment options, beyond surgical approaches are limited. The following placebo-controlled study presents, to the best of our knowledge, the first results of a non-invasive therapy for benign thyroid nodules. The efficacy and safety of a supplement containing spirulina, curcumin and Boswellia in euthyroid patients with benign thyroid nodules, was assessed by a 3 month, double-blind, placebo-controlled study which was completed by 34 patients. Patients with benign (FNAB documented) single thyroid nodules between 2 and 5 cm were evaluated in a prospective placebo-controlled cross-over trial, across 12 weeks (3 visits with six-week intervals). At each visit, the target thyroid nodule was recorded in two dimensions. In addition, plasma levels of thyroid stimulating hormone, free thyroxine and copper were assessed. The mean initial nodule area at V1 was 4.38±3.14 cm2, at V2 3.87±2.79 cm2, and at V3 3.53±2.84 cm2; P<0.04. Administration of the active substances (n=34) was followed by a mean area decrease of 0.611 cm2±0.933 (SD), while placebo administration (n=29) was followed by a mean decrease of 0.178 cm2±0.515 (SD), (P=0.027). The presented findings suggest that the combination of spirulina-curcumin-Βoswellia is effective in reducing the size of benign thyroid nodules. However, additional studies are needed in order to elucidate the exact mechanisms through which the suggested supplement facilitates a decrease in the size of benign thyroid nodules.

Adult growth hormone deficiency in CEE region: Heterogeneity of the patient pathway.

OBJECTIVES: Adult growth hormone deficiency (AGHD) is a rare disease characterised by abnormal body composition, reduced strength and exercise capacity and impaired psychological wellbeing. An advisory board of leading Central and Eastern European (CEE) endocrinologists was assembled to gain insights into the status of AGHD care in the CEE region. Topics of discussion included the position of adult hypopituitarism/AGHD in health system priorities, availability and affordability of treatments, awareness of AGHD, practice guidelines used in CEE countries and provisions for long-term care of patients. DESIGN: Prior to the meeting, the advisors were asked to summarise, using an itemised survey questionnaire, the usual standards of care for patients with AGHD in their country. At the meeting, the panel of experts discussed the findings and thereby elucidated similarities and differences among CEE countries; these were compared with international guideline-recommended practices for AGHD. RESULTS: All CEE countries involved reported having some type of infrastructure in place for care of patients with GHD transitioning from adolescence to adulthood. Most countries reported having at least one specialist centre for patients with AGHD. The main variations across the region included initial entry into healthcare systems, tests required to confirm AGHD diagnosis and medication reimbursement by health authorities. Most CEE countries relied on international society-led guidelines, while some countries have developed national guidelines. CONCLUSION: The CEE Adult Endocrinology Advisory Board meeting recognised considerable diversity in the care and patient pathways for AGHD across CEE countries. Additional work is needed to optimise care of patients with AGHD in the CEE region.