ACTA ENDOCRINOLOGICA (BUC)

Idiopathic infantile hypercalcemia (IIH) is a rare, parathyroid hormone (PTH)–independent disorder of calcium metabolism. It is most often caused by mutations in the CYP24A1 gene that impair vitamin D catabolism. We report a 70-year-old male with persistent hypercalcemia (Ca 13.2 mg/dL) and low-normal PTH levels. Extensive evaluation excluded malignancy, granulomatous disease, and vitamin D intoxication. Genetic analysis revealed a homozygous CYP24A1 variant (c.233G>T; p.Gly78Val), consistent with CYP24A1 deficiency. Bisphosphonate therapy with zoledronic acid rapidly and sustainably normalized calcium levels for 10 months. The patient’s daughter was a heterozygous carrier. This confirmed autosomal-recessive inheritance. This case illustrates an atypical late-onset presentation of CYP24A1 deficiency. It emphasizes the importance of considering this diagnosis in adults with PTH-independent hypercalcemia, especially when seasonal variation and family history are present. Recognition of CYP24A1 deficiency at all ages highlights the need for genotype-based terminology rather than the misleading label "infantile" hypercalcemia.

Objective. Pituitary metastases are a rare entity, account for 1% of all intracranial metastases. This study aims to report a pituitary metastasis (PM) from bladder cancer and to provide a review of PM characteristics. Method. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed using PubMed for studies published between January 2014 and January 2024. Results. One hundred twenty eight patients (66 females, 62 males) were identified in the literature over the past decade. Median age was 61 years. The most common primary malignancies were lung cancer (24.2%) and breast cancer (21.1%). The most common symptom was visual impairment (46.1%). Deficiencies in adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) and gonadotropin hormones were diagnosed in 46%, 40.4%, 35% of cases, respectively. Diabetes insipidus (DI) was present in 33.6% of cases and panhypopituitarism was present in 21.9% of cases. PM management included transsphenoidal surgery alone (25%), transsphenoidal surgery combined with radiotherapy (16.4%), radiotherapy alone (10.2%), or observation without intervention (10.9%). The median survival following the diagnosis of PM was 6 months. Conclusion. While PM remain a infrequent entity, prolonged lifespan of cancer patients has led to increased detection. Patients frequently present with visual disturbance,diabetes insipidus and anterior pituitary hormone deficiency. No standardized treatment guidelines exist. Surgery and/or radiotherapy are used as palliative modalities rather than curative treatments. The prognosis is generally poor and is mostly related to the stage and type of the primary tumor.

Iodine deficiency in a geographical area can be quantified, not only by urinary iodine\r\nexcretion, but also through the incidence of elevated TSH levels measured in newborns. We\r\nmeasured the TSH level in 3015 newborns, in a partial screening realized in Mures County\r\nduring the years 2001–2006. The law for the universal salt iodization with increased KIO3\r\nlevel (34 ? 8.5 mg/kg) was adopted in Romania in 2002, and implemented in practice\r\nstarting with December 2003. We compared TSH levels of 2,454 children born in the years\r\n2001-2003, before the universal salt iodization, with those of 561 children born in 2004-\r\n2006 after the implementation of the law of universal salt iodization. An elevated TSH\r\nlevels (over 10 mUI/L, according to the WHO criteria) was revealed in 8.23 %( 199/2,454)\r\nnewborns during 2001-2003, as compared to 9.62% (54/561) subjects born during 2004-\r\n2006 (p=NS). Based on both criteria and results, Mures County is a region with a\r\nmoderately mild iodine deficiency. However, the mean value of TSH levels (over 12\r\nmUI/L) obtained during 2001-2003, (19.81 ? 2.63 mUI/L, X ? SD, n= 145) significantly\r\ndecreased in the second period (15.63 ?7.35 mUI/L, n=34) (p= 0.02), i.e. a medium decrease\r\nwith 4.18 mUI/L. While the moderate increase of TSH levels (10-12 mUI/L) is an indicator\r\nof iodine deficiency, higher concentrations (>20 mUI/L) usually indicate the coexistence of\r\na hypothyroidism due to the low iodine supply. We observed an important decrease of the\r\nhypothyroidism induced by iodine deficiency: when during the first period its incidence was\r\n2.49%, in the second one it decreased to 1.46% (p=ns). In conclusion, after increasing the\r\niodine-content by universal salt iodization, the incidence of elevated TSH level (and the\r\ncorresponding hypothyroidism) did not decrease in newborns, but the mean value of higher\r\nthan normal TSH presented a statistically significant decrease, reflecting the improvement\r\nin iodine supplementation.

Background. Paget Disease (PD) is usually asymptomatic and discovered incidentally, it is known that it is exhibited low to high grade increased F-18 FDG uptake. Aim. In this study, we investigated the distinguishability of FDG PET/CT in incidental PD cases from other bone diseases and at different stages of the disease. Patients and Methods. In this cross-sectional, descriptive study, “Paget” identification associated with PET/ CT reports was found in 69 of 18,119 studies (~3.8%). Of the 45 patients (33 males and 12 females) eligible for inclusion in the study, 35.6% had monostotic and 64.4% had polyostotic disease (p>0.5). There was no statistically significant difference in biochemical parameters between groups. Results. According to the radiological appearance of the patients, 36 were in the mixed stage and 9 were in the blastic stage. Only the difference in ALP and creatinine values between the groups was statistically significant. SUVmax, SUVmean and HU values were found to be statistically significantly higher in pagetoid bones compared to control bone lesions. For SUVmax for PD bone lesion we found the 2.55 cutoff point with a sensitivity of 91% and a specificity of 84%. Conclusion. The specific radiological appearance of bone lesions and the evaluation of metabolic activity compared to normal bone seem to help differentiate PD from other lesions. Prospective studies are needed in the differentiation of FDG's disease stage and treatment response evaluation. The ability to differentiate between benign and malignant FDG avid bone lesions in oncological patients’ enables appropriate patient management, including avoiding unnecessary additional invasive procedures such as bone biopsy.

Background. Skull metastasis has not been reported from mixed medullary follicular thyroid carcinoma (MMFTC). Objective. To present a patient with expansile lytic skull metastasis. Case report. A 61 year lady is presented with goiter for 7 years and 8 cm diameter painful swelling over frontal bone for 18 months, aspiration from which revealed sheets and clusters of polygonal cells, similar to aspiration from hypoechoic nodule in right thyroid lobe. Serum calcitonin (569pg/mL) and carcinoembryonic antigen (11.2ng/mL) were elevated. Histopathology of 3.8×3.1cm nodule in thyroidectomy specimen revealed irregular islands of small polygonal tumor cells with extracellular amyloid deposits (suggesting medullary thyroid carcinoma (MTC)), intermingled with thyroid follicular cells showing capsular and vascular invasion (follicular thyroid carcinoma (FTC)). Immunohistochemistry of the thyroid tumor was negative for calcitonin and for thyroglobulin. Post-operative serum calcitonin and stimulated thyroglobulin were respectively 97 pg/mL and 11.5 ng/mL. I131 whole body scan revealed intense uptake in region of the skull metastasis with small uptake in thyroid bed. She received 150 mCi of I131with resolution of pain, heaviness, throbbing, reduction in swelling size, and lack of disease progression. Conclusions. Skull metastasis was the presenting feature of MMFTC which improved with I131 therapy. Patients with lytic skull metastasis should be evaluated for occult thyroid malignancy.

Context. Injury and functional disorders in pituitary gland after COVID-19 still need elucidation. Objective. To investigate pituitary functions, particularly hypothalamic pituitary adrenal (HPA) axis after COVID-19 infection. Methods. This study was conducted at a university hospital between May and October 2021. Patients who had COVID-19, were enrolled as study group, three months after recovery. Participants who do not have COVID-19 diagnosis, with similar characteristics were included as control group. Blood samples were taken on the morning at 08 AM. Adrenal stimulation test was performed with 1 μg of ACTH (Synacthen). Results. The study group included 50 patients and control group was 49 cases. One (2%) out of the 50 patients with 8 a.m. serum cortisol below 5 μg/dL. Low serum ACTH levels were detected in 7 (14%) participants in patient group. Stimulation with 1 μg of ACTH (Synacthen) test was performed for 2 (4%) of 50 patients with serum cortisol below 10 μg/dL. Both patients achieved a peak cortisol of over 12.5 μg/dL after stimulation. Standard deviation (SD) score for insulin like growh factor-1 (IGF-1) was lower than –2 SD for age and gender in 7 (14%) patients. TSH levels was mildly increased in five (10%) patients. There was no significant difference in baseline pituitary hormone levels in study and control groups. Conclusion. Basal pituitary hormone levels and HPA axes were found to be preserved and competently functioning in patients who experienced mild/moderate COVID-19. However, symptoms observed after COVID-19 episode were evident in substantial amount of patients in this study and these symptoms were not associated with changes in pituitary gland function.

Objective. Obese people may have nutritional deficiencies, although they are exposed to excessive food intake. We aim to assess relationship of vitamin D, B12, and folic acid levels and dietary vitamin intake and insulin resistance in obese people. Design. This case-control study was performed at the obesity outpatient clinics between March 2014 and April 2015. Subjects and Methods. We included 304 nondiabetic obese subjects in patient group and 150 normal weight individuals in control group. Patients were questioned in detail about their food intake. Results. Mean age of obese patients was 37.3±10.1 years, the mean duration of obesity was 7.9±5.4 years, and the percentage of female patients was 65.8%. Mean vitamin D, B12, and folic acid levels were significantly lower in patients than in controls. Vitamin D deficiency (<20 ng/mL) in 69.7%, vitamin B12 deficiency (<200 pg/mL) in 13.5%, and folic acid deficiency (<4 ng/mL) was found in 14.2% of the patients. BMI negatively correlated with vitamin D, B12, and folic acid levels. B12 levels negatively correlated with duration of obesity. Insulin resistance was found in 55.9% of patients and HOMA-IR levels negatively correlated with vitamin D and B12 levels. While dietary vitamin D and folic acid intakes were inadequate in all of patients, only 28.3% of patients had inadequate vitamin B12 intake. There was no relation between vitamin levels and dietary vitamin intakes. Conclusions. The study reveals that vitamin D, B12, and folic acid levels were low and poor vitamin D and B12 status were associated with insulin resistance in nondiabetic obese patients.

Context. As the life expectancy prolongs, malignancy has become an important issue in renal transplant recipients (RTRs). Thyroid cancer is the most common endocrine malignancy with ongoing increase in incidence all over the world. Objective and design. This is a cross-sectional study that investigates the thyroid disorders and the prevalence of thyroid nodule and cancer in RTRs. Subjects and methods. 204 RTRs were evaluated for the thyroid diseases with ultrasonography, serum thyroid stimulating hormone, free T4, free T3 levels, antithyroglobulin antibody and anti-thyroid peroxidase antibody levels; FNAB was carried if required. Results. 191 patients (94.1%) had normal thyroid function. Subclinical hypothyroidism was diagnosed in 11 patients, subclinical hyperthyroidism in 1 patient and low T3 syndrome in 4 patients. The FNAB was performed in 17 (27.9%) from 61 patients with thyroid nodule. The cytological examination of biopsy materials revealed that 2 (11.8%) nodules were suspicious for malignancy, 13 (76.5%) were benign, and 2 (11.8%) with non diagnostic cytology. Thyroid cancer prevalence was 0.2% in Turkey but we detected that 0.98% of RTRs had thyroid cancer. Conclusions. Screening the RTRs for thyroid disorders is necessary, so that early diagnosis and appropriate treatment of thyroid disease and cancer may improve the quality of life.

Background. The aim of the present study was to measure the effects of raloxifene on bone metabolism and strength in orchiectomized male rats. Materials/Methods. Forty-three 4-month-old Wistar albino male rats were used and divided into 3 groups as orchiectomy (ORCX; n=23), sham (n=15), and control (n=5). Raloxifene (10 mg/kg/day) and methylcellulose (0.5 mL/day, as a vehicle treatment) treatments were initiated 2 months after ORCX for 2 months, then the rats were sacrificed. The left femur and fourth lumbar vertebrae (LV4) were measured to assess the effects of the orchiectomy and the raloxifene treatment and maintenance regimens. Bone strength was assessed using a compression test for the vertebrae and a three-point bending test for the femurs (N/mm). Results. Raloxifene increased femoral and vertebral bone strength in osteoporotic rats, but this increase was not statistically significant. Bone strength was found to be 267.44±18.03 in the femurs of the ORCXraloxifene group and 246.32±49.37 in the femurs of the ORCX-C group (p>0.05). Vertebral bone strength was 147.78±09.51 in the ORCX-raloxifene group and 114.61±05.93 in ORCX-C group (p=0.488). Raloxifene also increased the femoral and vertebral bone density compared with the control group, but the change was not significant. While raloxifene significantly decreased the serum osteocalcin levels (p=0.007), it did not decrease the carboxyterminal cross-linking telopeptide of bone collagen (CTX) levels significantly (p=0.066). Conclusions. Raloxifene caused a statistically significant decrease in serum osteocalcin levels and a non-significant reduction in NTX levels in orchiectomized rats.

Adipose tissue is a major store of energy for the human body. Polycystic ovary syndrome (PCOS) patients are more prone to abnormal production of some regulatory proteins secreted from the adipose tissue. This study aims to investigate serum levels of adiponectin and their correlation with metabolic and endocrine indices in PCOS. Patients and methods. This study was conducted on 61 women with PCOS and 17 healthy women whose age and body mass index (BMI) were matched. Adiponectin serum levels were assessed and correlated with parameters of metabolic and hormonal disturbances. Results. In PCOS women, serum levels of insulin, HOMA-IR, testosterone, LH, and LH/FSH were significantly higher, while SHBG was lower than in healthy women. Lower adiponectin was observed in both PCOS groups compared to the control group. Serum levels of adiponectin correlated inversely with BMI (r=- 0.56; p<0.001),WC(r = -0.452;p<0.001), insulin levels (r= - 0.409; p<0.001), HOMA-IR (r= -0.368; p<0.001), and free androgen index (FAI) (r= - 0.53; p<0.001). A positive correlation was found between adiponectin and LH (r= 0.35; p<0.001), LH/FSH ratio (r= 0.33; p<0.001) and SHGB (r= 0.51; p<0.001). Serum adiponectin levels are decreased in women with PCOS compared to the control group. The decrease in adiponectin concentration indicates its potential role in metabolic disorders in the pathogenesis of PCOS, as well as in the development and progression of insulin resistance in PCOS patients.