A Hypothesis Regarding Neurosecretory Inhibition of Stress Mediators by Colchicine in Preventing Stress-Induced Familial Mediterranean Fever Attacks.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease characterized by recurrent episodes of fever and serositis. Colchicine (Col) has a crucial role in the prevention of amyloidosis and FMF attacks. The effect of Col on innate immune cells is based on the inhibition of the microtubule system. The microtubule system is also very important for neurosecretory functions. The inhibitory effect of Col on neurosecretory functions is an overlooked issue. Considering that the neuroimmune cross-talk process plays a role in the development of inflammatory diseases, the effect of Col on the neuronal system becomes important. FMF attacks are related to emotional stress. Therefore, the effect of Col on stress mediators is taken into consideration. In this hypothetical review, we discuss the possible effects of Col on the central nervous systems (CNS) and peripheral nervous systems (PNS) in light of mostly experimental study findings using animal models. Studies to be carried out on this subject will shed light on the pathogenesis of FMF attacks and the other possible mechanisms of action of Col apart from the anti-inflammatory features.

Hypercalcemia in IgG4-related disease: coincidental or associated? Case based review.

Immunoglobulin (Ig) G4-related disease (IgG4RD) is a chronic autoimmune disorder characterized by dense lymphoplasmacytic infiltrations and fibrosis of storiform pattern. The most typical manifestations include major salivary or lacrimal gland involvement, autoimmune pancreatitis, and retroperitoneal fibrosis. While the increase in IgG4 is the typical feature of the disease, hypercalcemia has been rarely reported in IgG4RD so far, only one of these cases has been shown parathyroid gland involvement (isolated involvement). In this study, we present a 43-year-old female patient with weight loss, pancreatic mass, lymphadenopathy, nodular lesion in the lung, hypercalcemia, and also increased level of serum IgG4. Histopathological investigation following parathyroidectomy revealed a dense lymphoplasmacytic infiltrate with an IgG4 to IgG ratio of > 50% in the fat tissue surrounding the parathyroid gland, particularly at the perivascular areas. This is the first systemic IgG4RD case in combination with hypercalcemia in the literature who was detected to have parathyroid adenoma. Our aim in this review is to emphasize that, although rarely, IgG4RD may be accompanied by hypercalcemia and parathyroid gland may be one of its target sites.

Evaluation of hyperferritinemia causes in rheumatology practice: a retrospective, single-center experience.

Hyperferritinemia may develop due to various reasons such as inflammation, infection, or malignancy. The purpose of the study to explore the prevalence and to figure out the causes of general hyperferritinemia and extreme hyperferritinemia as detected through the ferritin measurements requested by the rheumatology department. Adult patients at the age of 18 years and older with at least one serum ferritin level measurement at or above 500 ng/mL as requested by the rheumatology department between January 2010 and December 2019 were evaluated retrospectively. Hyperferritinemia was detected in 4.7% of 11,498 serum ferritin tests. The mean age of 242 patients found to have hyperferritinemia was 53.7 ± 17.1 years; of the patients, 63.2% were female, and the mean serum ferritin value was 2820 ± 5080 ng/mL. The most common cause of hyperferritinemia was rheumatological diseases with a ratio of 59.1%, which was followed by infections, iron overload, and solid malignancy. Among the rheumatologic diseases, adult-onset Still's disease (AOSD), rheumatoid arthritis, and vasculitis were the cause accounting for hyperferritinemia. Ferritin levels were significantly higher in the AOSD group compared to the other rheumatologic disease groups (p < 0.0001). While extreme hyperferritinemia (ferritin ≥ 10,000 ng/mL) rate in our cohort was 0.2%, the most common cause was AOSD (15/17). In patients with hyperferritinemia, 3 month mortality was found to be 8.7%. CRP level was identified as the only independent predictor for the 3 month mortality in all patients [OR 1.088 (95% CI 1.004-1.178), p = 0.039]. Although rheumatologic disease activation and infections are the most common causes, the other causes should also be considered for the differential diagnosis.

Cytopathology-histopathology correlation and the effect of nodule diameter on diagnostic performance in patients undergoing thyroid fine-needle aspiration biopsy.

INTRODUCTION: Although thyroid fine-needle aspiration biopsy (FNAB) is established to have a good overall sensitivity and specificity, various outcomes have been reported on its performance in large nodules. The aim of the study was to evaluate the diagnostic performance of FNAB and the effect of the nodule diameter on its diagnostic performance. MATERIALS AND METHODS: The outcomes of a total of 7319 patients who underwent FNAB over the course of 5 years were analyzed retrospectively and 648 patients who had undergone post-FNAB thyroidectomy or lobectomy were included in the study. FNAB results were classified according to the Bethesda system. After evaluating the compatibility between cytology and pathology results, all-nodules and diameter-based (<4 cm and ≥4 cm) sensitivity, specificity, false positivity, false negativity, and accuracy rates of FNAB were calculated. RESULTS: Sensitivity of FNAB was 85.4% for all nodules, 88.3% for nodules <4 cm, and 75.8% for nodules >4 cm (P < 0.001). Specificity was 58.4% for all nodules, 49.3% for nodules <4 cm, and 75.1% for nodules >4cm (P < 0.001). While false positivity was 41.6% for all nodules, it was 50.7% for nodules smaller than 4 cm and was 24.9% for nodules larger than 4 cm (P < 0.001). False negativity was 14.6% for all nodules and was 11.7% for nodules smaller than 4 cm and 24.2% for nodules larger than 4 cm (P < 0.001). Finally, among the entire set of nodules, the accuracy was 64.4%, which was 59.2% in nodules smaller than 4 cm, and 75.2% in nodules larger than 4 cm (P < 0.001). CONCLUSION: Despite a higher rate of false negativity, FNAB has higher specificity and accuracy in large nodules than those in the small nodules. Nodule diameter should not be used alone as a criterion to recommend thyroidectomy to the patient.

The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Evaluation of Incidental Thyroid Nodules in Cancer Patients.

OBJECTIVE: Frequency of thyroid cancer in incidental thyroid nodules identified by imaging techniques in cancer patients is higher than that in the normal population. In the retrospective study, we have both investigated the incidence of thyroid cancer in incidentally identified nodules and compared the imaging techniques to determine whether there is any difference between them in detection of malign nodules. METHODS: A total of 7319 patients who underwent thyroid fine-needle aspiration biopsy (FNAB) were included in the study. The data of 174 patients who had previously been diagnosed with a hematologic or solid malignancy prior to the FNAB procedure and had incidentally identified thyroid nodules were evaluated retrospectively. RESULTS: Eighty-six (49.5%) of the incidental nodules were identified with ultrasonography (USG), 62 (35.6%) with positron emission tomography (PET) or PET/computed tomography (PET/CT), and 26 (14.9%) with CT. As a result of thyroidectomy, papillary carcinoma was identified in 8 (4.6%) patients, and metastasis to the thyroid of a primary cancer was found in 3 (1.7%) patients. While the papillary carcinoma proportion in the nodules identified by USG was 3.4%, PET/CT was 8.9%. A cut-off maximal standardized uptake value of 11.6 in PET/CT indicated malignancy achieving a sensitivity of 83.3% and a specificity of 91.1%. CONCLUSION: Whether the nodule in the incidental thyroid nodules of cancer patients is identified using USG or PET/CT, the risk of thyroid cancer is similar. However, cancer risk is higher in the event of a higher focal uptake in the nodules identified by PET/CT.

Parathyroid hormone in washout fluid seems to be superior to cytology for localization of the lesion in MIBI-negative patients with primary hyperparathyroidism

Background/aim: Primary hyperparathyroidism (PHPT) is characterized by increased calcium (Ca) and parathyroid hormone (PTH) levels. Surgical removal of the culprit hyperfunctioning parathyroid gland is the preferred treatment. In this study, we aimed to determine whether PTH-washout or cytological examination of suspicious lesions was superior in MIBI-negative patients diagnosed with PHPT.Materials and methods: We retrospectively evaluated the medical records of 98 patients diagnosed with PHPT. Seventy-six patients who had positive parathyroid scintigraphy and who did not undergo parathyroidectomy in our center due to various reasons were excluded. We evaluated the remaining 22 patients with negative scintigraphy. Medical records including PTH levels in serum and washout fluid of fine-needle aspiration biopsy (FNAB), biochemical data, cytological results of FNAB, and histologic reports were reviewed.Results: The patients had a mean age of 50 +- 9 (31-72) years, serum Ca of 10.9 +- 0.5 (10.3-12.7) mg/dL, serum PTH of 285 +- 156 (107.2-679) pg/mL, and PTH of washout fluid of 19,523 +- 38,632 (1410-166,000) pg/mL. Cytological evaluation revealed insufficient material in 9 patients and cells of indeterminate origin in 4 patients.Conclusion: Our results showed that when evaluating ambiguous lesions on neck ultrasound, measuring the PTH level in washout fluid of FNAB is a reliable and effective method for diagnosis of parathyroid lesions and is superior to FNAB for localization.

Markers of Subclinical Cardiovascular Disease in Nonfunctional Adrenal Incidentaloma Patients without Traditional Cardiovascular Risk Factors.

Introduction: Data regarding cardiovascular risk in patients with non-functional adrenal incidentaloma (NFAI) are limited. The objectives of this study are to investigate markers of subclinical cardiovascular disease like carotid intima media thickness (CIMT), pulse wave velocity (PWV), augmentation index (AIx), soluble CD40 ligand (sCD40L) and leptin levels in NFAI patients without traditional cardiovascular risk factors and healthy control group. Methods: This study involved 35 patients with NFAI (11 males, 24 females; mean age, 52.4±7.7 years) and 35 healthy subjects as control group (11 males, 24 females; mean age, 51.8±7.2 years). CIMT was evaluated by ultrasonographical methods. PWV and AIx were measured with TensioClinic arteriograph system. Serum leptin and sCD40L levels were measured by ELISA. Results: In NFAI patients group; CIMT (p<0.001), PWV (p<0.001), AIx brachial (p<0.001) and AIx aorta (p=0.008) were found higher than the control group. Cortisol levels after 1mg dexamethasone suppression test (DST) were higher (p=0.006) and DHEASO4 levels were lower (p=0.008) in NFAI patients than control group. We found that CIMT had positive correlation with age (r=0.484, p<0.005), triglycerides (r=0.378, p<0.005) and cortisol level after 1 mg DST (r=0.346, p<0.005); PWV had positive correlation with total cholesterol (r=0.338, p<0.005) triglycerides (r=0.335, p<0.05) and insulin levels (r=0.426, p<0.005); AIx brachial had a positive correlation with triglycerides (r=0414, p<0.05) and negative correlation with DHEASO4 (r=-0.380, p<0.005); leptin levels had a positive correlation with body mass index (r=0.541, p<0.001) and HOMA-IR index. Conclusion: We showed that subjects with NFAI without traditional cardiovascular risk factors featured several disturbances (CIMT, PWV and AIx) compared to the control group that could be attributable to increased cardiovascular risk.

A novel truncating AIP mutation, p.W279*, in a familial isolated pituitary adenoma (FIPA) kindred.

Familial isolated pituitary adenomas (FIPA) constitute 2-3% of pituitary tumours. AIP is the most commonly mutated gene in FIPA. We herein report a novel germline mutation of the AIP gene in a family with FIPA. We present two patients, a father and his 12-year-old daughter, diagnosed clinically and using laboratory measures with acromegaly-gigantism. Both underwent transsphenoidal hypophyseal surgery for macroadenomas. We initially detected a novel heterozygous germline AIP mutation, c.836G>A (p.W279*), in the father's DNA. We then found the same mutation in his affected daughter. Pituitary adenomas associated with AIP mutations mostly present as FIPA (68%) at an early age (78% occur at <30 years old). They are often growth hormone (GH) - or prolactin - secreting macroadenomas (88%) that have already extended beyond the sella at the time of diagnosis. Acromegalic cases are resistant to somatostatin analogues and multimodal management is frequently essential to control the disease. Our patients had normalized GH/IGF-1 values soon after surgery, although enough time may not have elapsed to reach final cure. While penetrance of the disease can be as low as 10% in FIPA, especially children and young patients with somatotropinoma and prolactinoma should be surveyed for inactivating mutations or deletions in AIP. Determining the causative mutations may be of assistance in early diagnosis, treatment success, and genetic counseling.

An unusual case in endocrinology practice: Suture granuloma.

OBJECTIVE: Suture granuloma, the rare complication of thyroidectomy, results from the use of nonabsorbable suture materials. Despite its typical ultrasound images and benign course, it carries utmost importance in the diff erential diagnosis of lymph nodes, recurrent nodules, and recurrence in the case of thyroid cancers. Subject and Results. Fifty four years old female patient, who underwent bilateral thyroidectomy in July 2010, was diagnosed with multinodular goiter and incidentally discovered micropapillary carcinoma (2 mm). Four years later, she was readmitted to hospital due to painless swelling in the right and left anterior neck region. Ultrasonography revealed nodules with irregular boundaries, containing micro- and macro-calcifications and hyperechoic lines in both sides of the thyroid bed and isthmus. Fine needle aspiration biopsy was performed in the right and left sided mass and the cytological examination was compatible with the diagnosis of the suture granuloma. CONCLUSIONS: Suture granuloma should be considered in the differential diagnosis of the local recurrence.

Parathyroidectomy in asymptomatic primary hyperparathyroidism reduces carotid intima-media thickness and arterial stiffness.

OBJECTIVE: Although an International Workshop has suggested that cardiovascular assessment in asymptomatic primary hyperparathyroidism (PHPT) patients is not necessary, improvements in risk factors of subclinical atherosclerosis have been shown following parathyroidectomy. The objectives of this study were to determine whether parathyroidectomy in asymptomatic PHPT patients causes any change in carotid intima-media thickness (CIMT), arterial stiffness [pulse wave velocity (PWV)] and soluble CD40 ligand (sCD40L) levels. DESIGN: Prospective study evaluating female patients diagnosed with asymptomatic PHPT in a single centre over a 6-month period. PATIENTS: A total of 48 subjects were included: 17 hypercalcaemic (HC, mean age: 51 ± 8 years, Ca: 2·73 ± 0·17 mmol/l) and 16 normocalcaemic (NC, mean age: 58 ± 7 years, Ca: 2·30 ± 0·10 mmol/l) PHPT patients, and 15 healthy controls (mean age: 52 ± 4 years, Ca: 2·27 ± 0·07 mmol/l). MEASUREMENTS: Biochemical tests, CIMT, PWV and sCD40L levels were compared at baseline and 6 months after parathyroidectomy (PTx). RESULTS: At baseline, CIMT and PWV values in the HC and NC patients were higher than in the control group. While there was a significant reduction in CIMT (601 ± 91 µm vs 541 ± 65 µm, P = 0·006) and PWV (9·6 ± 1·8 vs 8·4 ± 1·5 m/s, P = 0·000) in the hypercalcaemic group at the end of the 6th month after PTx, no change was observed in normocalcaemic group (P = 0·686 and P = 0·196 respectively). No differences were observed in sCD40L levels between patient and control groups or between baseline and 6 months in patients undergoing parathyroidectomy. CONCLUSION: Parathyroidectomy leads to an improvement in the structural and functional impairment associated with atherosclerosis in the vascular wall in asymptomatic hypercalcaemic PHPT patients.