Thyroglobulin Levels in Patients who have Undergone Hemithyroidectomy for Differentiated Thyroid Cancer. An Assessment of Levels and Trends at a Tertiary Referral Centre.

Subramanian Kannan Serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels are used to monitor patients with differentiated thyroid cancer (DTC) after total thyroidectomy with or without radioiodine (RAI) ablation. However, they are also measured in patients who are treated with thyroid lobectomy (TL)/hemithyroidectomy (HT). Data on the levels of Tg and its trend in those undergoing TL/HT is sparse in India. We reviewed retrospective data of DTC patients who underwent TL/HT and were followed-up with postoperative Tg levels between 2015 and 2020. Out of 247 patients, 17 had undergone either TL or HT, which included papillary thyroid cancer ( n = 12), follicular thyroid cancer ( n = 4), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 1 patient. All patients with DTC had tumor size < 4 cm (T1/2, clinical N0, Mx). The median follow-up was 15 months (range, 1-125) and the median Tg level was 7.5 ng/mL (interquartile range [IQR]; 3.6, 7.5) and ranged from 0.9 to 36.7 ng/mL. The median thyroid-stimulating hormone (TSH) level was 2.03 IU/L (IQR; 1.21, 3.59) and it ranged from 0.05 to 8.54 IU/L. As of last follow-up, none of them underwent completion thyroidectomy; however, eight patients had a decline in Tg ranging from 8 to 64%, four patients had increase in Tg ranging from 14 to 145%, three patients had stable Tg, and one of them had an increase in TgAb titers. As per American Thyroid Association (ATA) response-to-treatment category, six patients had indeterminate response, five patients had biochemical incomplete response, four patients had excellent response, and two did not have follow-up Tg and TgAb levels. While absolute values of Tg were well below 30 ng/mL in almost all patients with HT/TL, the Tg trends were difficult to predict, and only 23% of patients were able to satisfy the criteria for "excellent response" on follow-up. We suggest keeping this factor in mind in follow-up and while counselling for HT in patients with low-risk DTC.

Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis.

BACKGROUND AND AIMS: No meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD). METHODS: Electronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events. RESULTS: Data from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: -5.41 to -2.36); P < 0.01; I2 = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: -3.26 to -3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to -6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to -1.23); P = 0.04; I2 = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: -8.45 to -2.61); P < 0.01; I2 = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: -5.87 to -1.23); P < 0.01; I2 = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: -14.64 to -3.34); P = 0.002; I2 = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to -0.45); P = 0.002; I2 = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76-7.06); P = 0.14; I2 = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69-1.65); P = 0.77; I2 = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33-4.22); P = 0.003; I2 = 24%], diarrhea [RR 2.05 (95%CI: 1.17-3.60); P = 0.01; I2 = 66%], nausea [RR 4.98 (95%CI: 3.23-7.67); P < 0.001; I2 = 0%] and vomiting [RR 3.90 (95%CI: 1.75-8.68); P < 0.01; I2 = 54%] were higher with semaglutide. CONCLUSION: This meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.

Development of a Low-cost NGS Test for the Evaluation of Thyroid Nodules.

Ultrasound-guided fine needle aspiration cytology (FNAC) is the preferred method of identifying malignancy in palpable thyroid nodules using the Bethesda reporting system. However, in around 30-40% of FNACs (Bethesda categories III, IV, and V), the results are indeterminate and surgery is required to confirm malignancy. Out of those who undergo surgery, only 10-40% of patients in these categories are found to have malignancies, thus proving surgery to be unnecessary for some patients or to be incomplete in others. While molecular testing on thyroid FNAC material is part of the American Thyroid Association (ATA) guidelines in evaluating thyroid nodules, it is currently unavailable in India due to cost constraints. In this study, we prospectively collected FNAC samples from sixty-nine patients who presented with palpable thyroid nodules. We designed a cost-effective next-generation sequencing (NGS) test to query multiple variants in the DNA and RNA isolated from the fine needle aspirate. The identification of oncogenic variants was considered to be indicative of malignancy, and confirmed by surgical histopathology. The panel showed an overall sensitivity of 81.25% and a specificity of 100%, while in the case of Bethesda categories III, IV, and V, the sensitivity was higher (87.5%) and the specificity was established at 100%. The panel could thereby serve as a rule-in test for the diagnosis of thyroid cancer and therefore help identify patients who require surgery, especially in the indeterminate Bethesda categories III, IV, and V.

Ovotesticular disorder of sexual development due to 47,XYY/46,XY/45,X mixed gonadal dysgenesis in a phenotypic male presenting as cyclical haematuria: clinical presentation and assessment of long-term outcomes.

Ovotesticular disorder of sexual differentiation (OTDSD) is a rare cause of disorder of sexual differentiation predominantly having 46,XX karyotype, female phenotype and ambiguous genitalia. We report a 15-year-old having male body habitus, axillary and pubic hair, well-developed penis and right-descended testis with history of penoscrotal hypospadias correction, presenting with three episodes of cyclical haematuria, who biochemically had normal serum testosterone (338 ng dl(-1) ) which increased following hCG stimulation (614 ng dl(-1) ), elevated estradiol (17.35 pg ml(-1) ) along with elevated luteinising hormone (11.3 mIU l(-1) ) and follicle-stimulating hormone (31 mIU l(-1) ). Ultrasonography followed by micturating cystourethrogram and cystoscopy confirmed the presence of prostate, uterus, cervix and vagina draining into the urogenital sinus continuing till the penile urethra and left intra-abdominal gonad. Patient underwent hysterectomy and left gonadectomy. Histopathologic study of resected gonad confirmed presence of ovotestis. Low estradiol (1.2 pg ml(-1) ) following gonadectomy confirmed the ovotestis origin of estradiol. Chromosomal analysis revealed complex karyotype predominant being 47,XYY (50%) followed by 46,XY (26%) and 45,X (24%). This is perhaps the first report of 47,XYY/46,XY/45,X causing OTDSD in a phenotypic male.

Diabetes insipidus as a presenting manifestation of Rathke's cleft cyst.

Rathke's cleft cysts (RCC) are cystic sellar and suprasellar lesions derived from remnants of Rathke's pouch, lined by cuboidal or columnar epithelium. RCC are usually asymptomatic but can present with headache, visual impairment, panhypopituitarism and hypothalamic dysfunction. Diabetes Insipidus as a presenting symptom of RCC is reported, but rare. We present a case of a 48-year-old male presenting with polyuria and on investigations found to have central diabetes insipidus due to a sellar RCC. Patient underwent transsphenoidal surgery with complete excision with resolution of his symptoms. His polyuria resolved post-surgery without vasopressin replacement, which has never been reported.

Huge bilateral ovarian cysts in adulthood as the presenting feature of Van Wyk Grumbach syndrome due to chronic uncontrolled juvenile hypothyroidism.

Juvenile primary hypothyroidism causing cystic ovaries and pseudoprecocious puberty (Van-Wyk Grumbach syndrome (VWGS)) is well documented in literature. There are only a few reports of primary hypothyroidism presenting as ovarian cysts in adults. Here we present a case of huge bilateral ovarian cysts in adulthood as the presenting feature of VWGS due to chronic uncontrolled juvenile hypothyroidism. Large uniloculor right ovarian cyst (119 × 81 × 90 mm) and a multicystic left ovary (55 × 45 × 49 mm) were detected in a 24 year lady with secondary amenorrhea, galactorrhea, and palpable abdominal mass with history of neonatal jaundice, delayed milestones, short stature, and precocious menarche at age of 7.5 years age. She had elevated levels of cancer antigen (CA)-125 which normalized post levothyroxine supplementation. Elevated CA-125 may lead to misdiagnosis of ovarian carcinoma and inadvertent treatment. Bilateral ovarian cysts in adults are a rare presentation of juvenile hypothyroidism. It is necessary to screen for primary hypothyroidism in patients presenting with bilateral ovarian cysts to prevent unnecessary evaluation and treatment.

Primitive neuroectodermal tumor of adrenal: clinical presentation and outcomes.

Primitive neuroectodermal tumor (PNET) of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm) on computed tomography (CT) was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE). This is the first report of adrenal peripheral PNET (pPNET) from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.