ACTA ENDOCRINOLOGICA (BUC)

Background. NR5A1 [Steroidogenic factor 1 (SF1)] is a nuclear receptor that is essential for the development of gonads and adrenal glands as well as the establishment of steroidogenesis in these organs. The clinical findings of the mutations of NR5A1 gene in 46, XY individuals are variable. Virilization at puberty can be seen in some of the 46, XY children who have a female phenotype and are raised as female. A girl aged 13 years and 10 months old was brought by the family for deepening of her voice. On physical examination, her breast development was Tanner stage 2, axillary hair (+) and pubic hair was Tanner stage 4. She had labioscrotal fusion and 4.4 cm phallus (External Masculinisation Score was 6). Hypergonadotropic hypogonadism, low AMH and high testosterone levels were detected in laboratory tests. Uterus was not visualized in pelvic ultrasonography. Karyotype analysis was reported as 46, XY. Sequence analysis of the NR5A1 gene revealed a novel heterozygote c.1075_1089del (p.Leu359_Leu363del) variant. The patient was raised as a female and oestrogen replacement was started following gonadectomy. Conclusion. It should be kept in mind that virilization may develop at puberty in individuals with 46, XY disorder of sexual development due to NR5A1 mutation.

Context. Gender identity, psychosexual function, psychiatric adjustment and quality of life have been investigated in congenital adrenal hyperplasia(CAH) patients. Objective. We aimed to investigate gender identity problems and the psychiatric disorders and associated factors in children and adolescents with CAH patients. Subjects and methods. Forty-five children and adolescents with CAH were included in the study. Psychiatric comorbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children – Present and Lifetime Version. Gender identity problems were investigated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Results. The mean age of the sample was 11.02 years (SD: 3.25, range: 6–18). 51.1% of the patients had at least one lifetime comorbid psychiatric disorder. The most common diagnoses were anxiety disorders, attention deficit hyperactivity disorder(ADHD), tic disorders and enuresis nocturna. Tic disorders and ADHD were higher in males but they were not statistically significant. Two female patients were diagnosed with gender dysphoria and 18.5% of females showed variably masculinized behaviors. The girls with gender identity problems expressed lower satisfaction with their sex than other girls and boys. Conclusions. Children and adolescents with CAH had many psychiatric disorders, especially neurodevelopmental disorders. ADHD and tic disorders should be kept in mind during assessment especially in male patients. Gender dysphoria and masculine behaviors seem to be common in female patients with CAH so they should be carefully investigated.

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.

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.

Lingual thyroid is a rare developmental disorder, and it is the result of failure of the thyroid gland to descend from the tongue root to its normal site. The ectopic thyroid with a functioning gland is even rarer. In this case, we present a 44-year-old female patient with a complaint of foreign body sensation, progressive dysphagia and dyspnea due to ectopic thyroid tissue. Her complaints were totally resolved after L-thyroxine treatment. Here we report a patient with functioning ectopic thyroid tissue who had had bilateral subtotal thyroidectomy 10 years ago due to multinodular goiter. In conclusion, if progressive\r\ndysphagia, dyspnea, and foreign body sensation occurs in a patient who had thyroidectomy and living in an endemic goiter region, lingual thyroid may be underlying disorder.

Zygomycosis is a frequently fatal infection in the immunocompromised and diabetic host. A 12 year old girl with type 1 diabetes presented in diabetic ketoacidosis and consolidation of right lung along with thymic abscess causing persistent respiratory symptoms. A diagnosis of\r\nmucormycosis was made on smear examination of the thymic aspirate. Intravenous amphotericin along with surgical excision of the abscess resulted in clinical cure. Thymic involvement as seen in this case is an extremely rare occurrence in a diabetic patient which has not been\r\nreported in literature so far .

Background. Thyroid hormone resistance (RTH) is defined as a decrease in response to thyroid hormones in the target tissue. Most patients present with nonspecific findings. In this article, we aimed to represent a 22-yearold female patient who presented with palpitation, fatigue, and heat intolerance. She was thought to have thyroid hormone resistance and her genetic examination revealed NM_001128177.1 (THRβ): c.1034G > A (p.Gly345Asp) pathogenic variation in the THRβ gene. Case report. A 22-year-old female patient presented with complaints of fatigue, heat intolerance and palpitations. She was taking Propranolol twice daily at admission. Her family history revealed hypothyroidism in her grandmother. Her physical examination results were as follows: height 160 cm, weight 65 kg, body mass index 25.4kg/m2, body temperature 36.5˚C, respiratory rate 18/min, heart rate 86 beats/min, blood pressure 120/80 mmHg. Her palms were sweaty. The heart sounds were normal, and no heart murmur was auscultated. The laboratory results were TSH: 5.31uU/mL, fT3: 6.83 pg/mL, and fT4: 2.43 ng/dL. THRβ gene mutation analysis was requested for our patient whose clinical history and laboratory results were compatible with thyroid hormone resistance. The pathogenic variation NM_001128177.1(THRβ):c.1034G>A (p.Gly345Asp) was detected after analysis. Conclusion. A diagnosis of RTH requires high clinical suspicion and a genetic mutation analysis should be requested in the case of clinical suspicion. In this way, unnecessary anti-thyroid treatment can be prevented.

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient’s health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

Context. COVID-19 is more than a respiratory infection, with deep implications regarding multiple systems and organs. Thyroid damage is frequent in COVID-19 and may overlap previous HCV or HCC associated diseases. Objective. The objective of this study is to determine the effects of COVID-19 in patients with HCV associated HCC and thyroid comorbidities. Design. We performed a retrospective study of the thyroid function tests and autoantibodies in patients with HCV-associated HCC prior and during COVID-19. Subjects and Methods. We included 52 consecutive patients with HCV-associated HCC and documented thyroid disease, diagnosed with COVID -19 between April and October 2020. Serum values of thyroidstimulating hormone, free T3, free T4, anti-thyroglobulin antibodies and anti-thyroid peroxydase antibodies were determined and compared to baseline levels. Results. At baseline, 44 patients had positive antithyroid antibodies, 6 had hypothyroidism in substitution and 2 had hyperthyroidism under treatment. During COVID-19 we found an increase in serum values of antithyroid antibodies, and decreased levels of TSH, freeT3 and freeT4 levels. Specific therapies were discontinued in one patient with hyperthyroidism and 3 patients with hypothyroidism. Conclusion. There is a significant impact of COVID-19 on the thyroid homeostasis; a long-term prognostic value for patients with HCC infected with COVID-19 required further extensive research.

A 62 years old woman was diagnosed with multinodular toxic goiter and primary hyperparathyroidism/ left parathyroid adenoma by hormonal assessment, ultrasound and nuclear thyroid/parathyroid scans. Cervical ultrasound illustrated a multinodular aspect of the thyroid with solid nodules and cystic-component nodules; the larger one represented a multinodular complex with necrosis areas in the left thyroid lobe, ACR TI-RADS score 4 (moderately suspicious). Functional nuclear imaging was performed for accurate differential diagnosis between thyroid vs. parathyroid localization, between cold vs. hot nodules, and eventually, for guiding the choice of a subsequent Fine- Needle Aspiration Biopsy (FNAB). Scans described an early intense 99mTc-sestaMIBI uptake with no 99mTc-pertechnetate uptake in the left thyroid lobe larger nodule. Due to the suspicion of malignancy for this nodule, we performed an additional scan (1 hour before the classical 2 hours parathyroid delayed scan). The intense uptake persists in both delayed scans suggesting no malignant phenotype and which was confirmed after surgery by benign histology. In conclusion, using a 99mTc-sestaMIBI personalized protocol, related to the radiotracer cellular uptake mechanisms: 1 hour scan (supplementary image, corresponding to the maximum uptake pattern of 99mTc-sestaMIBI for cancer cells) and 2 hours scan (for parathyroid washout evaluation) may avoid unnecessary extensive thyroid surgery.