Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus.

OBJECTIVES: The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS. CASE PRESENTATION: We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction. CONCLUSIONS: We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Subacute Thyroiditis in Active COVID-19 Infection: A Report of Two Cases With a Systematic Review of the Literature.

Subacute thyroiditis (SAT) is a self-limiting inflammatory condition of the thyroid gland with distinct symptoms and a predictable outcome. During the current COVID-19 pandemic, there have been multiple isolated reports of SAT either during the active viral illness or following recovery. Here, we report two such cases of COVID-19 infection presenting with SAT. A 65-year-old male presented with a two-week history of anterior neck pain, odynophagia, high-grade fever (38.9°C), sweating, palpitations, and tremulousness. At physical examination, the patient presented with a slightly increased heart rate and a tender and enlarged thyroid on palpation. Laboratory examination showed high C-reactive protein levels, with elevated erythrocyte sedimentation rate, and thyroid function tests were suggestive of thyrotoxicosis. Ultrasonography showed a heterogeneous thyroid gland with ill-defined hypoechoic areas, and thyroid scintigraphy showed reduced uptake, confirming the diagnosis of SAT. In another case, a 52-year-old male presented with fever, cough, and myalgias, and was diagnosed with mild COVID-19 pneumonia, and managed conservatively. After two weeks, the patient had a recurrence of high-grade fever, odynophagia, palpitations, and tremors. Examination revealed tachycardia, hyperhidrosis, and a tender and enlarged thyroid on palpation. Thyroid function tests revealed low thyroid-stimulating hormone, with normal total T4 and total T3. Ultrasonography examination showed a heterogeneous thyroid gland with bilateral ill-defined hypoechoic areas. In our systematic review, including 103 SAT cases, it has been suggested that SAT should be recognized as an uncommon extra-pulmonary clinical manifestation of COVID-19 infection and clinicians need to be aware of the association. Pending larger multicentric studies, management of the condition has to be on a case-by-case basis.

Spectrum of EGFR mutation and its relation with high-risk predictors in thyroid cancer in Kashmiri population: 2 years prospective study at a tertiary care hospital.

BACKGROUND: EGFR mutation has not been extensively studied in thyroid cancer. This study was conducted to study spectrum of EGFR mutation in thyroid cancer in Kashmiri population for possible therapeutic purpose. METHODS: It was 2 years prospective cross-sectional study conducted at a tertiary care center in which histologically confirmed, untreated thyroid cancers were included. These specimens were subjected to EGFR mutation analysis by AS-PCR method. RESULTS: There were a total 60 patients with preponderance of females [44(73%) vs 16(27%)]. Most were in the age group of less than 45 years (75%). Most of these patients were non-smokers [50(83.3%) vs 10 (17.3%)]. Papillary thyroid carcinoma (PTC) was the commonest type 48(80%), rest was follicular type (FTC) 12(20%). Well-differentiated carcinoma (WDC) was common than poorly differentiated (PDC) [41(68.4%) vs 19 (31.6%)]. Lymph node metastasis and vascular invasion were present in 32 (53.4%) and 17 (28.4%) respectively. Thirty-two (53.3%) patients were having 15 bp deletion in exon 19 of EGFR. These deletions were common in PTC than FTC, 29(60.5%) vs 3(25%) which was statistically significant (p = 0.04, CI = 0.2). The total mutational rate of T790M in EGFR tyrosine kinase domain (exon 20) was found to be only 8.4% (5 of 60). Only 4 (8.3%) of these mutations were detected in PTC and rest in FTC (1 of 12). Twenty-six (43.3%) of exon 21 were positive for L858R mutation in EGFR tyrosine kinase domain. Married persons and PDC were significant predictors of L858R mutation in EGFR tyrosine kinase domain in thyroid cancer as this was statistically significant in them with p = 0.04, 0.03 respectively. CONCLUSION: In our population, PTC is common in females with half of population harboring EGFR mutation and it is statistically significant in poorly differentiated carcinoma and in married individuals. It implies that EGFR may be used in thyroid cancer as a possible therapeutic agent in our set of population.