Geethalakshmi Sampathkumar

Purpose To screen for maturity-onset diabetes of the young (MODY) variants in subjects with an early age of onset and positive family history of diabetes mellitus. Methods 60 subjects with onset of diabetes between 3 and 30 years of age and parental history (onset < 35 years) of diabetes were recruited after excluding autoimmune, pancreatic and syndromic forms of diabetes. Detailed pedigree chart and clinical data were recorded. MODY genetic testing (MODY 1–13) was performed and variant classification was done adhering to the ACMG guidelines. Results Baseline characteristics of subjects were as follows: mean age of onset of diabetes 19.9 ± 7 years, mean duration of diabetes 6.3 ± 6.8 years, BMI 23.3 ± 3 kg/m² and C-peptide 1.56 ± 1.06 nmol/l. Four out of sixty (6.6%) were positive for variants classifiable as pathogenic/likely pathogenic: one patient with HNF4Ac.691C > T, (p.Arg231Trp), two with HNF 1A c.746C > A(p.Ser249Ter) and c.1340C > T(p.Pro447Leu), and one with ABCC8 c.4544C > T (p.Thr1515Met). MODY 1 and MODY 3 variants were documented in the paediatric age group (< 18 years). Conclusion A genetic diagnosis of MODY could be confirmed in only 6.6% (4/60) of patients clinically classifiable as MODY. This is less than that reported in clinically diagnosed MODY subjects of European descent. Newly published population data and more stringent criteria for assessment of pathogenicity and younger age of onset of type 2 diabetes in Indians could have contributed to the lower genetic confirmation rate. Apart from variants in the classical genes (HNF1A, HNF4A), a likely pathogenic variant in a non-classical gene (ABCC8) was noted in this study.

Objectives Myxedema crisis, a fatal complication of severe hypothyroidism, is extremely rare in children and treatment guidelines are lacking. Since availability of intravenous levothyroxine is limited in resource poor settings, myxedema crisis can be treated with oral levothyroxine and/or oral liothyronine (if necessary), in the absence of cardiac risk factors, thus hastening the recovery and significantly decreasing the associated morbidity and mortality. In the background of untreated hypothyroidism, a possible association of ovarian hyperstimulation syndrome (OHSS) and reactive pituitary hyperplasia should be kept in mind, thus preventing unnecessary interventions. Case presentation A 13-year-old girl child with Down syndrome, presented with myxedema crisis, as initial presentation of untreated hypothyroidism. Conclusions Annual screening, timely diagnosis of hypothyroidism, and early initiation of thyroid hormone supplementation will prevent associated physical and neurocognitive morbidity in children, especially those with Down syndrome. Importance of oral liothyronine supplementation in myxedema crisis, has been highlighted in this case report.

Polycystic ovary syndrome is the most common cause of hyperandrogenism in young females. Other causes are congenital adrenal hyperplasia (CAH), androgen-producing tumours and drugs. The severity and tempo of virilisation help in distinguishing the tumoural from non-tumoural causes. We report a rare case of non-classic CAH and androgen-producing ovarian tumour in the same patient, causing hyperandrogenism. A 15-year-old female patient presented with secondary amenorrhea, excessive facial hair growth and clitoromegaly for 6 months. Due to severe virilisation, tumoural aetiology was considered. Investigations showed marked elevation of testosterone and mild elevation of 17 hydroxy progesterone (17OHP). Imaging confirmed right ovarian tumour. Adrenocorticotropic hormone stimulated 17OHP, was elevated confirming the diagnosis of underlying non-classic CAH. Surgical removal of the tumour was followed by improvement in hyperandrogenism, but persistent elevation of 17OHP confirmed the underlying presence of non-classic CAH.

Unilateral adrenal metastases without disseminated disease has rarely been reported in differentiated thyroid carcinoma (DTC). A 72-year-old female presented with vague abdominal discomfort and loss of appetite of 2 months duration. She had undergone left hemithyroidectomy for a benign thyroid nodule 18 years ago. A contrast CT of the abdomen showed a large left adrenal mass measuring 11×9 cm, suspicious of adrenocortical carcinoma. Hormonal evaluation was in keeping with a non-functional tumour. The patient underwent left adrenalectomy, histopathology of which revealed metastatic well-differentiated thyroid carcinoma. Ultrasound of thyroid done postoperatively showed a subcentimetric hypoechoic lesion with increased vascularity and microcalcifications in the right thyroid bed. Histopathology from a completion thyroidectomy specimen was consistent with follicular variant of papillary thyroid carcinoma. She was treated with high-dose radioiodine ablation therapy and has remained disease-free on follow-up for more than a year.

Perrault syndrome is a rare disease comprising pure gonadal dysgenesis (46 XX) and sensorineural hearing loss in females and deafness alone in affected males. It is an autosomal recessive disorder. Over the years many additional features like marfanoid habitus and central nervous system findings have also been reported. Herein we report a case of sporadic Perrault syndrome in 18-year-old female who presented to our hospital with deaf mutism and primary amenorrhoea. On evaluation, the patient had hypergonadotropic hypogonadism, streak gonads and a normal karyotype (46 XX). Audiologic evaluation showed sensorineural deafness. The patient was started on hormone replacement therapy. She is on regular follow up. We present this case for its infrequent incidence and also to add to the ever expanding clinical spectrum of this disease.