Evaluation of pulmonary side effects in prolactinoma patients treated with cabergoline.

INTRODUCTION: Cabergoline (CAB) is the most used dopamine agonist in the treatment of prolactinomas. Studies related to the treatment of Parkinson's disease have shown that dopamine agonists can lead to fibrotic syndromes affecting the heart and the lung. The aim of this study was to evaluate the possible pulmonary side effects of CAB in prolactinoma patients. MATERIAL AND METHODS: Chest X-ray imaging and pulmonary function parameters like forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity for carbon monoxide (DLCO) were evaluated in 73 prolactinoma patients. The cumulative dose of CAB and the total duration of CAB use were also calculated, and all data were reviewed retrospectively. RESULTS: The median cumulative CAB dose was 192 mg, and the median duration of CAB use was 64 months. Only 13 patients (17%) among this cohort had abnormal DLCO results that could be an indirect sign of pulmonary fibrosis. These abnormal DLCO results were found not to be associated with cumulative CAB dose in these 13 patients. CONCLUSIONS: CAB appears to be safe in terms of pulmonary functions with a median cumulative dose of 192 mg in prolactinoma patients.

Expression of vascular endothelial growth factor in follicular cell-derived lesions of the thyroid: Is NIFTP benign or precancerous?

Objective: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in physiological and pathological angiogenesis of the thyroid. The aim of the current study was to determine the expression characteristics of VEGF in follicular cell-derived lesions of the thyroid and to assess whether a new entity noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is precancerous. Material and Methods: Patients diagnosed with 33 follicular adenomas (FA), 41 invasive follicular variant papillary thyroid cancer (IN-FVPTC), and 40 NIFTP in surgical resection materials were evaluated retrospectively. Immunostaining was performed on 5-µm paraffin tissue sections. The percentages of immunostaing for VEGF were evaluated on pathological materials. We used a percentage of labeled thyrocytes score (0, no labeling; 1, <30%; 2, 31-60%; 3, >60%) and an intensity score (0, no staining; 1, weak; 2, intermediate; 3, strong). The sum of two scores were accepted as the total score. Results: Mean ages of the FA, IN-FVPTC, and NIFTP groups were 44.7 ± 11.7 years, 46.9 ± 13.6 years, 43.2 ± 15.4 years, respectively and the mean VEGF immunostaining scores were 44.7 ± 29.3, 50.2 ± 32.54, 4 ± 26.3 respectively. Although there was no statistically significant difference (p= 0.347), the total score of the NIFTPs was higher than the scores of the FA (mean= 3.9 ± 1.8) and IN-FVPTC(mean= 4.3 ± 1.9) groups with a mean value of 4.6 ± 1.7. This result was remarkable. There was no statistically significant difference between tumor diameters and staining percentages (p= 0.750). Conclusion: Even if there were no statistical differences for VEGF immunostaining, it was high in NIFTPs. Since we know the role of VEGF in tumorigenesis, we can hypothesize that NIPTP can be precancerous. Our argue should be corroborated by a large prospective study.

Subacute Thyroiditis Following SARS-CoV-2 Vaccines: Six Cases Report and Review of the Literature.

Subacute thyroiditis (SAT) is an inflammatory disease of the thyroid that develops following viral upper respiratory tract infections. SARS-CoV-2 virus, the cause of COVID-19, binds to the Angiotensin-Converting Enzyme-2 (ACE2) molecule expressed on the target cell surface. Thyroid gland shows high levels of ACE2 expression. The cases of SARS-CoV-2-related subacute thyroiditis and Graves' disease have been reported. It has recently been noted that vaccines for SARS-CoV-2 also induce autoimmune and inflammatory reactions. We present six (4 male, 2 female) cases of SAT that developed after mRNA and inactivated SARS-CoV-2 vaccines. And we have reviewed the literature. SAT was seen in 5 patients after mRNA vaccine, in one after inactivated vaccine. Their clinic and laboratory findings suggested to SAT. They were treated with nonsteroid anti-inflamatory drugs and/or methylprednisolone.They recovered within few weeks. Out patients did not have permanent hypothyroidism after SAT. The history of SARS-CoV-2 vaccination should be questioned in patients with subacute thyroiditis in pandemic days.

Disease Activity May Not Affect the Prognosis of Coexisting Thyroid Cancer in Acromegalic Patients.

Acromegaly is known to be associated with high incidence of malignancies probably due to the mitogenic effects of IGF-1. Differentiated thyroid cancer (DTC) is reported to be one of the most frequent malignancies associated with acromegaly. But there is no data about the clinical course of DTC in acromegalic patients. In this study, we evaluated the course of DTC in 14 acromegalic patients retrospectively. Fourteen papillary thyroid cancer patients without acromegaly, who were matched with the acromegalic patient group for age, gender and properties of thyroid cancer, were investigated as the control group. We identified no change in the course and treatment responses of DTC in association with the acromegaly activity, gender, age and disease duration, and all patients were found to be in remission for DTC at the time of investigation. Retrospective analysis of this cohort suggests that the activity of acromegaly may not affect the treatment responses and prognosis of coexisting DTC.

BRAFV600E Mutation: Has It a Role in Cervical Lymph Node Metastasis of Papillary Thyroid Cancer?

BACKGROUND: The BRAFV600E mutation is common in papillary thyroid cancer (PTC). Lymph node metastasis (LNM) may be associated with poor prognosis. However, the LNM mechanism remains unclear. OBJECTIVES: Our aim was to evaluate the prevalence of the BRAFV600E mutation in primary tumors and accompanying LNM at the time of diagnosis. METHODS: This retrospective study included 51 PTC patients (40 women, 11 men; mean age 40.0 ± 16.5 years; range 6-81) who underwent total thyroidectomy accompanied by a lateral neck dissection due to preoperatively detected LNM. Real-time PCR was used for the detection of the BRAFV600E mutation in specimens from primary thyroid tumors and metastatic lymph node tumors. RESULTS: The prevalence of the BRAFV600E mutation was 64.7% (n = 33) in primary tumors and 47.1% (n = 24) in metastatic lymph nodes. Of 33 patients with BRAFV600E-positive primary tumors, 18 (54.5%) had BRAFV600E-positive metastatic lymph nodes. Of 18 patients with BRAFV600E-negative primary tumors, 6 (33.3%) had BRAFV600E-positive metastatic lymph nodes. The presence of the BRAFV600E mutation in the primary tumor did not affect the tumor size, but the diameter of metastatic lymph nodes significantly increased (by nearly 3 mm) with the presence of BRAFV600E in LNM (p = 0.01). CONCLUSIONS: In our study, the BRAFV600E mutation did not show a one-to-one correspondence. This indicates that the presence of BRAFV600E in the primary tumor is not clonal and addresses the role of intratumor heterogeneity in PTC tumorigenesis. This supports the theses that mutations occur in the later stages of tumorigenesis, might be subclonal, and develop de novo, or that some other factors may be involved in the development of metastasis.

Mesothelial derived adenomatoid tumour in a location devoid of mesothelium: adrenal adenomatoid tumour.

This is a case report of a 40-year-old man with an adrenal mass that was found incidentally on routine check-up examination. MRI showed a 30 × 51 × 57 mm cystic-semisolid heterogeneous mass; hormonal functions were within normal limits. Operative removal was planned because of the large size of the mass. Histopathological and immunohistochemical findings were consistent with adenomatoid tumour. The patient was disease-free at 1 year follow-up. We present this case with its radiological and histological characteristics under the review of the literature.

The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.

Intraoperative ultrasonography is useful in surgical management of neck metastases in differentiated thyroid cancers.

Differentiated thyroid carcinomas are the most common malignancies of endocrine organs. Metastases to cervical lymph nodes occur in 20-50% of cases. Recurrence and survival rates are closely related to the type of surgery performed. High-resolution ultrasonography (USG) is a sensitive imaging method used to detect occult lymph node metastases in patients with thyroid cancer. We evaluated how intraoperative USG affected surgical success. This was a retrospective study comparing two groups of patients with thyroid carcinoma who underwent cervical lymph node dissection. A total of 101 patients (33 males and 68 females) were included. Group 1 included 53 patients who underwent surgery with intraoperative USG guidance. Group 2 included 48 patients who underwent surgery without the use of USG. All patients were followed up (mean 23 months; range 5-44 months) with thyroglobulin measurements and USG evaluations. Group 1 (intraoperative USG) had a residual/recurrent tumor rate of 1.9% (1/53 patients). Group 2 had a residual/recurrent tumor rate of 12.5% (6/48 patients). A statistically significant difference appeared between the residual/recurrent tumor rates in Groups 1 and 2 (p<0.05). In addition to its classical use in diagnosis and follow-up, intraoperative use of high-resolution USG can improve surgical success and may decrease the number of residual/recurrent tumors encountered during follow-up.

Optimal effective doses of cabergoline and bromocriptine and valvular leasions in men with prolactinomas.

OBJECTIVES: Prolactinoma is the most common pituitary adenoma, and dopamine agonists( BRC, and CAB) is the primary therapy. Recently, the increased prevalance of cardiac valvular disease in patients treated with DAs for Parkinson's disease has raised concerns about the safety of this drug in patients with prolactinoma. CAB and pergolide are frequently reported to cause valvulopathy, there are very few studies showing this side effect in BRC administiration which has less potent agonism of 5-HT2B receptors. Male patients who are known to have higher prevalance of macroadenomas compared to women. The dosage of DAs administered were rarely evaluated. METHODS: We performed a retrospective chart to evaluate the medical management and treatment outcomes of male patients with macro/giant prolactinomas. We evaluated 22 patients with prolactinoma managed with DAs therapy alone for at least 1 year. All patients were followed for a mean of 61 months. Pretreatment echocardiographic examination were not available at that time. RESULTS: None of them had any resistance or intolerance to DAs. The mean tumor shrinkage was 62%. In three patients the macroprolactinoma disappeared, in two patients the tumor shrinkage was 93% and 70%. The DAs therapy was discontinued in these patient. After a follow up neither MRI showed a recurrence or enlargement of the adenoma, nor prolactin levels showed any elevation. The echocardiography were performed at the last visit of each patient and no valvulopathy in any of the patients on DAs therapy were detected. CONCLUSIONS: DAs are effective, and safe for valve morphology with mean cumulative doses of 155 mg CAB, and 7 301 mg BRC in patients with macroprolactinoma.

BRAF(V600E) mutation in Turkish patients with papillary thyroid cancer: strong correlation with indicators of tumor aggressiveness.

Papillary thyroid cancer (PTC) constitutes more than 90% of the thyroid cancers. MAP kinase/ERK pathway plays an important role in the development of several cancers. BRAF which is a member of Raf-kinase family activates this way. BRAF gene activating mutations lead to neoplastic transformation in thyroid follicle cells. In PTC, this mutation itself is a poor prognostic sign independent of other clinicopathological characteristics. We evaluated BRAF(V600E) mutation and clinical-pathological characteristics in Turkish population with PTC. We assessed 109 patients with PTC (88 female, 21 male). The average age was 38.7 ± 9.9 (17-71). BRAF(V600E) mutation was detected using polymerase chain reaction and fluorescent melting curve analysis. The results show that BRAF(V600E) mutation rate was found in 39.45% of our patients. We observed that BRAF(V600E) mutation was significantly higher in men, in tumors larger than 1 cm in size, and in patients with classical PTC. Moreover, statistically significant correlations of BRAF(V600E) with indicators of tumor aggressiveness such as thyroid capsular invasion, multifocality, lymph node metastasis, and extrathyroidal spread were found. Patient groups below and over the age of 45 did not differ in mutation frequency. Patients with micro-PTC were evaluated separately, it was found that BRAF(V600E) mutation was more frequent in the classic type and that lymph node metastasis rate significantly increased when the mutation was present. We concluded that BRAF(V600E) was correlated with indicators of tumor aggressiveness in our study population. This fact is taken into consideration in treatment and follow-up of our patients with PTC and positive BRAF(V600E) mutation.

Expression of Ki-67, p53 and vascular endothelial growth factor (VEGF) concomitantly in growth hormone-secreting pituitary adenomas; which one has a role in tumor behavior ?

OBJECTIVE: In many pituitary tumor, immunohistochemical studies have been shown to be correlated with different aspects of tumor behavior.There is no study up to date in which markers of Ki-67, p53, VEGF were evaluated concomitantly in GH-secreting adenomas.This study aims to determine which marker has a major role in tumor behavior and whether these markers have a cut-off value to distinguish invasive adenoma from non-invasive pituitary adenoma. METHODS: Fourty-seven acromegalic patients operated by the same neurosurgeon were included in this study.Twenty-one patients(5micro/16 macro) had non-invasive adenomas and 26 had invasive macroadenomas.Eight patients(6 invasive macroadenomas, 2 microadenomas) were treated with OCT-LAR until one month prior to surgery with treatment duration range of 3-11 months.These patients were excluded from the study group as the noninvasive and invasive adenomas were compared.A separate analysis was performed in invasive adenomas to compare OCT(+) and OCT(-)patients. RESULTS: Both Ki-67 and p53 expressions showed no correlation with the invasive character of adenomas, but VEGF expression in invasive adenomas was significantly higher with respect to noninvasive group.Our study has taken intermediate staining (>25 %)for VEGF as a cut off value for invasive adenomas.It was also observed that the decrease in VEGF staining in OCT pretreated invasive adenomas was significantly more than those not treated with OCT. CONCLUSION: VEGF becomes an independent stimulator of angiogenic growth and progression for GH-secreting adenomas with >25% cytoplasmic immunoreactivity.This cut-off value may be useful in determination of prognosis and appropriate treatment strategy.A short term preoperative OCT treatment may be useful as adjunctive therapy especially for locally invasive GH- secreting adenomas.

Primary antiphospholipid syndrome presenting as hyponatremic hypertensive syndrome and acute adrenal insufficiency following it: a rare case.

Hyponatremic hypertensive syndrome (HHS) is rare and is characterized with hypertension together with hyponatremia, hypokalemia and low plasma osmolarity and considered to be based on renal ischemia. It can rarely develop due to antiphospholipid syndrome (APS). We reported a case of 43-year-old man with unilateral renal artery stenosis due to primary APS. He presented with a hypertensive hyponatremic episode. First, he was treated with antihypertensive drugs. Further, radiological imaging showed enlargement of bilaterally adrenal glands that mimic adrenal masses. Unilateral nephrectomy and adrenalectomy were performed. Pathological examination revealed necrosis in the adrenal tissue and thrombosis in its artery. After operation, acute adrenal insufficiency developed in the patient because of hemorrhagic infarction of bilaterally adrenal glands. He improved after intravenous hydrocortisone treatment. His therapy was maintained with oral prednisolone and fludrocortisone. This patient with HHS, due to primary APS, is the first case in literature and acute adrenal insufficiency is a rare complication of APS.

Differences in risk factors for acute coronary syndromes between men and women.

OBJECTIVE: The aim of this study is to evaluate the presence of risk factors for coronary heart diseases in men and women in our population. MATERIAL AND METHODS: 414 patients (335 men, 79 women) admitted to our coronary intensive care unit with the diagnosis of acute coronary syndrome were evaluated for risk factors. RESULTS: 74.7% of women and 84.8% of men were observed to belong to sex-specific risk groups. This finding was statistically significant (P = 0.005). Prevalence of hypertension was significantly higher in women (58.2%) than in men (28.1%) (P = 0.0001). Prevalence of diabetes mellitus in women was (51.9%) and significantly higher than in men (28.1%, P = 0.0001). Smoking was 2.5 times higher in men: 77.0% and 31.6%, respectively (P = 0.0001). Body mass index was high in both groups and in women exceeded that of men (P = 0.0001). CONCLUSION: The fact that risk factors for acute coronary syndromes were frequently observed in male and female patients presenting with acute coronary syndromes warned us to arrange our health policy towards the priority of the prevention of these risk factors.

Association between chronic urticaria and thyroid autoimmunity.

The association between chronic idiopathic urticaria (CIU) and thyroid autoimmunity has most often been suggested in studies investigating thyroid microsomal antibodies, which are less sensitive and specific than anti-thyroperoxidase antibodies, moreover these studies were not case-control studies in large series. By comparing a large patient series presenting with CIU with a large numbered control group we aimed to learn the extent of autoimmune thyroid disease. We compared the frequency of thyroid autoantibodies in 140 patients with CIU with 181 age-and sex-matched volunteers. Thyroid function tests and thyroid autoantibodies were measured by chemiluminescent immunometric assay in study groups. The frequency of thyroid autoantibodies was significantly higher in patients with CIU than that in healthy controls (29.28 %/5.52%; p < 0.001). Of 41 patients, 10 had thyroid dysfunction and the other cases were euthyroid. The higher frequency of these antibodies in our patients shows that there was a strong association between CIU and thyroid autoimmunity.

Hyponatremia as the presenting manifestation of Sheehan's syndrome in elderly patients.

BACKGROUND AND AIMS: Hyponatremia is not a disease in itself, but a manifestation of a variety of disorders and side-effects of diuretics; alternatively, it may be the only manifestation of hypopituitarism or hypothyroidism. In our experience, diagnosis of hypopituitarism in hyponatremic patients is often overlooked, especially in the elderly. METHODS: We report here data from five elderly multiparous women (mean age 69 yr; range 62-78 yr) with a past history of complicated delivery, in whom initial symptoms were due to hyponatremia (serum sodium less than 128 mEq/L) who went undiagnosed and untreated for a long time (up to 42 years) after the initial event. RESULTS: Initial hormonal levels indicated hypopituitarism, and magnetic resonance imaging led to diagnosis of empty sella in all patients, so that they were diagnosed as suffering from Sheehan's syndrome (SS). The occurrence of sodium and water disorders associated with SS depends on the degree of pituitary damage, time of onset since the initial pituitary insult, and concurrent medical conditions which also play a role in sodium and water balance. In these patients, clinical condition and hyponatremia improved rapidly after glucocorticoid substitution. L-thyroxine was appropriately substituted subsequently. CONCLUSIONS: We suggest that, especially in elderly patients, much more attention should be paid to patients' past history. Early recognition of severe hyponatremia due to hypopituitarism with adrenal insufficiency is critical, and treatment with hydrocortisone results in safe and improved quality of life.

Comparison of surgical techniques for treatment of benign toxic multinodular goiter.

Controversy remains regarding the best surgical approach for toxic multinodular goiter (MNG). The aim of this study was to evaluate the results of various thyroid operations for managing toxic MNG. A group of 100 patients with toxic MNG were divided into three groups and managed with total thyroidectomy (TT; group I, n-17), near-total thyroidectomy (NTT; group II, n = 48), or bilateral subtotal thyroidectomy (BST; group III, n = 35). Patients were compared with regard to age, gender, surgical operations, complications, thyroid hormone status, duration of hospitalization, and the reoperation rate for incidentally found thyroid carcinomas. There were 14 men (14%) and 86 women (86%) with a mean age of 47.03 +/- 13.56 years (range 19-77 years). After the operation two patients had a hematoma, and one patient had a seroma. Four patients had unilateral vocal cord paralysis, and one had permanent paralysis. Moreover, 18 patients had transient and 2 patients permanent hypocalcemia. There was no significant difference between the groups regarding complications (p < 0.05). Permanent hypothyroidism was achieved in all patients in group I and 44 patients (92%) in group II, whereas in group III only 10 (29%) patients had hypothyroidism. Conversely, hyperthyroidism, both subclinical and clinical, was noted only in group III (12 patients, 34%) during follow-up. We think that TT and NTT are safe, effective approaches in the treatment of toxic MNG, preventing recurrence of thyrotoxicosis and reoperation for incidentally found thyroid cancers. The complication rates for TT and NTT were similar to that for BST. Hence these operation should be considered for patients referred for surgical treatment of toxic MNG.

Co-secretion of aldosterone and cortisol by an adrenocortical carcinoma.

We report a rare case of adrenocortical carcinoma. A 26-year-old woman presented with hypokalemia and hypertension due to hyperaldosteronism. She had no signs of Cushing's syndrome. Endocrinological data showed excess of aldosterone production and nonsupressible cortisol production on 2 mg of dexamethasone. Magnetic resonance imaging showed left adrenal tumor. Transabdominal left adrenalectomy was performed and histopathological diagnosis was adrenocortical carcinoma. Her blood pressure and hypokalemia returned to normal after adrenalectomy. There is no recurrence after 36 months. We want to emphasis the importance of adrenal tests before the operation even if there are no signs of excess cortisol production.