ACTA ENDOCRINOLOGICA (BUC)

Objective: Co-existence of Cushing disease and Rathke?s Cleft Cyst (RCC) has been reported in a few cases in the literature so far. We herein describe a rare condition of Cushing disease that might originate from epithelium of RCC. \r\nCase: A 48-year-old woman was admitted to the hospital with complaints of headache, weakness, and weight gain. The patient underwent endoscopic transsphenoidal surgery due to Cushing Disease. Histopathological examination revealed cyst contents and walls compatible with RCC, and normal adenohypophysis and neurohypophysis tissues. Immunhistochemical staining with ACTH, GH, and prolactin were positive on the epithelium of the cyst. \r\nConclusion: In our case Cushing disease might be associated with hormonal activity derived from cyst wall of RCC or disappearance of a small microadenoma during surgical or pathological processing. According to recent data, origin of this lesion and histogenetic link between RCC with Cushing disease could not be explained.

Background. Advances in imaging techniques have led to increasing discovery of\r\nadrenal and pituitary &#8220;incidentalomas&#8221;, tumors with normal endocrine function and no\r\ncompression mass effects. We evaluated the age at diagnosis (AD) in patients with benign\r\nnon-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors,\r\nin a series of patients from a national center of endocrinology. Methods. From 2,123\r\nconsecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009,\r\n2,069 patients were analysed. The study groups included: group A - 137 patients with\r\nadrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI).\r\nControl groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or\r\nbenign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary\r\nsecreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was\r\ndone by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or\r\npneumoencephalography before 1981. Results. Mean age AD is more advanced in patients\r\nwith AI (53 ? 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ? 13.1 years, range\r\n10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors,\r\nbut similar in patients with adrenal malignancy. There is an age-related increase in the\r\nproportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among\r\npatients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal\r\ntumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have\r\nNFA. AD in NFA (49.3 ? 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01).\r\nAD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0\r\n? 2.8 yr) and only in 0.7% of PI, p<0.01 (follow-up 3.1 ? 2.5 yr).\r\nConclusions. Adrenal non-functioning benign tumors show a clear association with ageing,\r\nin contrast with pituitary incidentalomas. It seems unlikely that most pituitary incidentalomas in\r\nyoung patients become large NFA, whose development seems to be also age-related. It is tempting\r\nto suggest that pituitary tumorigenesis starts earlier than adrenal tumorigenesis.

Context. As we progress into the COVID-19 pandemic, it has become apparent that this infection is associated with a multitude of systemic effects, some involving the thyroid gland. The thyroid is also frequently affected in the HCV chronic infection. Objective. The objective of this study is to determine the effects of COVID-19 infection on the presence and severity of thyroid disorders associated with chronic HCV infection, at short and mid-term follow-up. Design. We prospectively evaluated patients with documented HCV- associated thyroid disease (with sustained virologic response after antiviral therapy). Subjects and Methods. The study group consisted of 42 patients with HCV- associated thyroid disease, diagnosed with COVID -19 infection between April and October 2020. We determined serum values of thyroidstimulating hormone, freeT3, free T4, anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies at one and three months after resolution of infection and compared them to the baseline characteristics of the patient. We also evaluated the changes in thyroid substitution treatments or antithyroid drugs. Results. At baseline, out of the 42 patients, 5 presented hypothyroidism under levothyroxine substitution therapy, while 2 presented hyperthyroidism under methimazole therapy; 37 patients had positive antithyroid antibodies. At one month follow-up, we note an increase in serum values of antibodies, with a decrease in TSH, freeT3 and freeT4 levels, correlated with the severity of COVID-19 infection. Two patients required discontinuation of levothyroxine. At 3 months follow-up, lower levels of antithyroid antibodies were recorded, with an increase in TSH levels. No medication doses were adjusted at this time. Conclusion. Among the systemic effects of COVID-19, the impact of thyroid dysfunction should not be underestimated, especially in the presence of pre-existing conditions, such as HCV infection.

Objective. A partial or complete deficiency of hormone secretion by pituitary gland (hypopituitarism) is commonly seen after a pituitary apoplexy caused by an infarction of a pituitary adenoma or pituitary hyperplasia (as in Sheehan’s syndrome). Hypopituitarism may also follow surgery, when hypovolemia, anticoagulation, fat/ air/bone marrow microemboli can provoke a pituitary infarction/hemorrhage. Other causes of abrupt hypophyseal hypoperfusion, as hypovolemia during a septic shock, could also contribute. In the last mentioned situation, due to the complex endocrine-immune interrelation, sepsis could be masked and improperly managed. Case report. We report a case of a 72 years-old Caucasian woman, previously healthy, who underwent an orthopedic surgery for a femoral fracture. This event apparently triggered a central-origin hypothyroidism, misinterpreted as “post-surgical psychosis”, which, in turn, masked a symptomatology of a subsequent severe sepsis. The patient was admitted in the infectious diseases department with a severe gut-origin sepsis, needing surgery and long course antibiotics. The pituitary insufficiency was reversed. Conclusion. Pituitary apoplexy is an uncommon but potentially life-threatening disease, and could be precipitated by successive events – in our case an orthopedic surgery and a subsequent severe sepsis. It needs recognizing (has intrinsic severity and could mask other serious conditions), treat and monitor (could progress and/or reverse).

Thyroid tumors are the most frequently reported endocrine malignancies. However thyroid collision tumors are rare pathological findings, representing less than 1% of thyroid cancers. In our case, a 50-year-old female patient presented with a complaint of neck swelling. During the exams, nodules were identified in both thyroid lobes. Pathologic analysis of a fine-needle aspiration biopsy(FNA) has been obtained from a 60×50 mm hypoechoic nodule raised suspicion of oncocytic carcinoma(OC). Another FNA was performed on a 17×11 mm hypoechoic solid nodule, revealing features of medullary thyroid carcinoma (MTC). Preoperative whole-body scans indicated no evidence of metastases. The patient subsequently underwent total thyroidectomy and central lymph node dissection. Pathological examination revealed OC, MTC, papillary microcarcinoma (PTMC), simultaneous metastasis of MTC and papillary thyroid carcinoma (PTC) to the same lymph node. The patient's calcitonin level was normalized postoperatively and I-131 ablation therapy was administered to the patient in the ATA high risk category. The patient was monitored under levothyroxine suppression. The simultaneous occurrence of OC, MTC and PTMC of the thyroid gland along with metastases of PTC and MTC in the same lymph node are reported in this case. To the best of our knowledge, this association had not been previously reported in the literature.

Background. Dyspepsia is a popular complication in many disease, including diarrhea or constipation. This finding of antir- ghrelin serum can be used to improve the discomfort of patients. Objective. To study the effects of anti-r-ghrelin serum on plasma acylatedghrelin, growth hormone (GH) and insulinlike growth factor-1 (IGF-1) concentration, and mechanism of gastrointestinal (GI) motility (e.g. gastric emptying and intestinal transit) in female rats. Subjects and Methods. Female rats (estrus cycle confirmed) were fasted overnight and treated with i.p (intraperitoneal) injection anti-r-ghrelin serum, cholecystokinin 1 (CCK1) receptor antagonist, and ghrelin receptor antagonist (cortistatin-8, CST-8) to examine the GI motility. The concentration of plasma acylated ghrelin, GH, and IGF-1 was analyzed by ELISA assay. Results. Our data showed that (1) treatment with anti-r-ghrelin serum (diluted 1:100) inhibited the gastric emptying (12.12±2.191 %) but increased the concentration of acylated ghrelin (34.54±3.506 pg/ mL), GH (259.2±24.60 ng/mL) and IGF-1 (1033.9±33.66 ng/mL); (2) the CCK1 receptor antagonist, lorglumide (5 and 10 mg/mL/ kg) reversed the inhibition of gastric emptying (31.95±2.425 % and 30.50±3.624 %) and increased the concentration of plasma acylated ghrelin (101.8±9.422 pg/mL) and GH (508.5±44.11 ng/mL); (3) the ghrelin receptor antagonist, CST-8 under the doses of 1, 20, 40, 100 μg/mL/kg, promoted the gastric emptying (25.85±3.197 % to 33.43±2.513 %) in female rats. Conclusion. Anti-r-ghrelin serum both induced the concentration of plasma acylated-ghrelin, GH and IGF-1 as well as inhibited the GI motility by CCK1 receptor in female rats.

A 48-year-old female presented with severe chronic hypothyroidism despite progressively increasing doses of levothyroxine. Poor adherence was suspected based on previous laboratory investigations. A low dose thyroxine absorption test using 400 μg of levothyroxine taken orally was performed. FT4 increased by 4.7 pmol/L at 3 hours and 6.6 pmol/L at 5 hours, following ingestion, effectively ruling out malabsorption. Her cardiac hemodynamic profile, measured noninvasively, also improved following levothyroxine intake, further supporting our diagnosis. Poor adherence was successfully managed by implementing twice weekly visits by a registered nurse and an improvement in both thyroid function tests and cardiac parameters was seen at the one-month follow-up visit. We suggest using a lower dose thyroxine absorption test, owing to its efficacy in establishing diagnosis and a safer alternative compared to higher doses in particular in high-risk cardiac patients.

Obstructive sleep apnea consists in recurrent episodes of partial obstruction of the upper airways which can determine cessation of breathing during sleep causing intermittent hypoxia. The obstructive sleep disorders are encountered predominantly in obese patients with or without metabolic syndrome, that can affect the quality of life and life expectancy by increasing the cardiovascular risk of coronary artery disease, conductance disturbances, malignant arrhythmias, promoting atherogenic processes, determining sudden death and impairing several domains of cognitive function.

Objective. To describe the correlations between serum 25(OH) vitamin D and anthropometric and metabolic parameters in adult outpatients of both sexes with different BMI coming from an urban community. Subjects and Methods. 264 subjects referred for obesity assessment participated – 109 men and 155 women (20-60 years). Body weight and height, waist circumference (WC), blood pressure were recorded. Body composition was assessed by bioelectrical impedance (BIA) on a Tanita BC 420 MA analyzer (Tanita Inc., Japan). Serum 25(OH)D Total, Insulin, High-sensitivity C-reactive protein, blood glucose, total, HDL-cholesterol and triglycerides were measured. The insulin resistance index was calculated (HOMA-IR). Participants with BMI>25.0 kg/m2 underwent standard 75 g OGTT. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). Results. Normal weight was found in 27.2 % of the participants, 24.6 % had overweight, 29.2 % -class I obesity, and 18.9 % – class II or III. Vitamin D was weakly and inversely correlated to different variables in the whole group – such as weight, WC, WC/Height, % body fat and HOMA-IR index (r=-0.231, -0.283, -0.307, -0.339, -0.328 respectively, all p<0.001). Building subgroups based on BMI led to loss of significance. Backward analysis revealed Total-C/LDL-C ratio, and LDL-C/HDL-C ratio as strongest predictors of serum vitamin D (p=0.001; R2=0.204). Conclusion. The association of vitamin D with blood pressure, plasma lipids, glucose and insulin is very weak on an individual level. However, several obesity indices (WC, WC/height ratio, % Body fat from BIA) might be used as a screening tool for subjects at risk for vitamin D deficiency.

The introduction of tumor necrosis factor-alpha (TNF-α) targeting drugs has given new opportunities in the treatment of various inflammatory rheumatic diseases and has been the most important development in the treatment of ankylosing spondylitis (AS). However, the increasing use and longer follow-up periods of treatment also pose risks of developing various adverse effects, ranging from common ones, including infections, to uncommon thyroid neoplasms. Adalimumab (ADA), a fully human monoclonal antibody targeted against TNF-α, is indicated for AS. We describe the case of a patient with AS who developed a papillary thyroid carcinoma (PTC) while on therapy with ADA. Cervical lymphadenopathy and a heterogeneous nodule in the right thyroid lobe were detected in the 48-year-old female patient who had been using ADA (40 mg subcutaneously every 2 weeks) for 2 years with the diagnosis of AS. Fine-needle aspiration cytology confirmed PTC. ADA treatment was discontinued, and a total thyroidectomy surgery was performed. We believe that the thyroid gland should also be taken into consideration while screening for malignancy before and during TNF inhibitors (TNFi).