Diagnosis and treatment outcomes of Cushing's disease during pregnancy.

PURPOSE: We report a case of a pregnant woman with Cushing's disease (CD) and performed a systematic review of literature on diagnosis, treatment, maternal and fetal outcomes of CD in pregnancy. METHODS: A PubMed search was performed for manuscripts in English language from inception till June 2020. Cases of CD with hypercortisolism during pregnancy were included and categorized into three groups based on treatment received. Data on diagnostic modalities, CD remission, materno-fetal outcomes were analysed. RESULTS: Fifty-five patients of CD with 62 pregnancies were analysed. 24-h urinary free cortisol(UFC) was elevated by a mean of 5.4 ± 4.2 fold upper limit of normal non-pregnant level. 12/19 (63.1%) CD patients had more than threefold elevation of UFC measured during pregnancy. Mean midnight serum cortisol was 753.7 ± 270.5 nmol/l. At a midnight serum cortisol cut off of 440 nmol/l, 15/16 patients were correctly identified as CD. 23.2% underwent trans-sphenoidal surgery (group 1), 16.1% received only medical treatment (group 2) while 60.7% received no treatment (group 3) during pregnancy. Remission rates for CD in groups 1 and 2 were 76.9% and 77.8%, respectively. Adverse maternal and fetal outcomes were seen in 53.9% and 59.3% of the patients, respectively and were not significantly different between groups, although, lesser live births and greater pregnancy losses were seen in group 3. CONCLUSION: Midnight serum cortisol had better sensitivity than UFC for diagnosing hypercortisolism due to CD during pregnancy. In general, CD should be treated during pregnancy in order to optimize maternal and fetal outcomes as a trend towards increased live births is seen in treated subjects.

Pituitary Dysfunction Following Snakebite Envenomation: A Clinico-Radiological Assessment of 15 Cases and Review of the Literature.

Background: Snakebite envenomation (SE) is an important tropical disease in India, causing significant morbidity and mortality among patients. The hormonal deficiencies due to the involvement of the pituitary in case of SE can present in either acute or delayed setting. Hypopituitarism (HP) is often an underrecognized and relatively rarely reported complication of this neglected disease. Methods: We present here the data of 15 patients diagnosed to have HP following systemic SE and are being currently followed-up in the Endocrinology outpatient department of a tertiary care hospital of South India. The study was approved by the Institute ethics committee, and informed onsent was taken from all the study patients. The study was a record-based retrospective analysis of the patients with HP following SE. Clinical data including lag time in diagnosis and type of snake were determined. Further, hormonal data including all the anterior pituitary functions (thyroid stimulating hormone, free T4, cortisol, insulin-like growth factor (IGF-1) luteinizing hormone, follicular-stimulating hormone, testosterone; prolactin) and water deprivation test to determine diabetes insipidus (DI) in patients with polyuria on follow-up were extracted from the records and the hospital information system. An experienced neuroradiologist examined the magnetic resonance imaging (MRI) findings of the pituitary. Results: The mean age of the patients was 43 ± 9 years and 80% were male. Around 90% of patients belonged to upper-lower socioeconomic status according to the modified Kuppuswamy scale. The commonest snake species reported was Russell's viper. Thirteen patients had delayed HP. The median duration from snakebite to onset of HP symptoms was 1 year (range 0.33-10 years). However, the median time from snakebite to the diagnosis of HP was 7 years (range 1-13 years). Central hypothyroidism and hypogonadism were present in all subjects. However, central hypocortisolism was noted in 93% of patients. Low IGF-1 was noted in all the six patients where data were available. One patient had partial central DI. Thirteen out of 15 patients had reduction of pituitary volume in MRI. Conclusion: HP in patients with SE can appear slowly and the diagnosis is frequently delayed for years. Following snakebite, multiple pituitary hormone deficiencies associated with radiological abnormalities like a significant reduction in the pituitary volume are common.

Extranodal NK/T cell lymphoma presenting as palatal perforation with oronasal fistula.

A 26 years old female presented with fever, nasal stuffiness with blood stained purulent discharge, nasal twang in voice along with non-healing palatal ulcers since three months. Examination revealed a paramidline perforation in the hard palate causing oronasal fistula formation. Histopathology and immunohistochemistry suggested a diagnosis of extranodal Natural Killer (NK)/T cell lymphoma. Multi-agent chemotherapy was instituted. We report this extremely rare case of Non-Hodgkin's Lymphoma (NHL) of the extranodal NK/T cell variety presenting as palatal perforation.

Pre-Ovulatory Hormones on Day of Human Chorionic Gonadotropin Trigger and Assisted Reproductive Technique Outcomes in Different Ovarian Response Groups.

BACKGROUND: Evidence regarding impact of pre-ovulatory hormone levels on assisted reproductive technique (ART) outcomes in different ovarian response groups is sparse. AIMS: The objective of this study was to evaluate and compare the association between pre-ovulatory hormonal profile and ART outcomes in different ovarian responses. SETTING AND DESIGN: This is a single-centre retrospective cohort study of 273 non-donor fresh ART cycles between January 2013 and June 2016. MATERIALS AND METHODS: Data on clinical profile, basal and peak hormonal levels, characteristics of controlled ovarian stimulation and ART outcomes were collected. Progesterone elevation (PE) was defined as pre-ovulatory serum progesterone >1.5 ng/mL or progesterone to oestradiol ratio >1. The association between peak hormonal levels and ART outcomes in poor (≤4 oocytes retrieved), intermediate (5-13 oocytes retrieved) and high (≥14 oocytes retrieved) ovarian responders was analysed and compared. STATISTICAL ANALYSIS: Continuous and categorical variables were summarised as median (interquartile range) and percentages, respectively, and compared using Kruskal-Wallis H-test or Mann-Whitney U-test and Chi-square test or Fisher's exact test, respectively. RESULTS: The incidence of PE, by both criteria and clinical pregnancy rates (35.7%, 36.8% and 18.6% in high, normal and poor responders, respectively; P = 0.073), was similar among the three response groups. Except fertilisation rates in normo-responders, PE did not influence ART outcomes in any response group. Furthermore, there were no differences between peak hormone concentrations or incidence of PE between those who conceived and those who did not. CONCLUSION: Pre-ovulatory sex steroid levels do not seem to be the primary determinant of ART outcomes in any ovarian response category; hence, decision to freeze all embryos in the event of PE should be tailored.

EIQ: EEG based IQ test using wavelet packet transform and hierarchical extreme learning machine.

BACKGROUND: The use of electroencephalography has been perpetually incrementing and has numerous applications such as clinical and psychiatric studies, social interactions, brain computer interface etc. Intelligence has baffled us for centuries, and we have attempted to quantify using EEG signals. NEW METHOD: This paper aims at devising a novel non-invasive method of measuring human intelligence. A newly devised scoring scheme is used to ultimately generate a score for the subjects. Wavelet packet transform approach for feature extraction is applied to 5 channel EEG data. This approach uses db-8 as the mother wavelet. Hierarchical extreme learning machine is used for classification of the EEG signals. RESULT: 80.00% training accuracy and 73.33% testing accuracy was measured for the classifier. The average sensitivity and specificity across all three classes was measured to be 0.8133 and 0.8923 respectively. An aggregate score was determined from the classification of EEG data. The power spectral analysis of the EEG data was conducted and regions of the brain responsible for various activities was confirmed. In the memory test, theta and beta bands exhibit high power, for arithmetic test, alpha and beta bands are strong, whereas in linguistic test, theta, alpha and beta bands are equally strong. COMPARISON: The traditional IQ test determines intelligence indirectly, based on the score obtained from Wechsler test. In this paper an attempt is made to measure intelligence based on various brain activities - memory, arithmetic, linguistic. CONCLUSION: A new method to measure intelligence using direct approach by classifying the EEG signals is proposed.

The effect of hypothyroidism on serum irisin level in patients with nondiabetic chronic kidney disease: A pilot study with a cross-sectional design.

Both chronic kidney disease (CKD) and hypothyroidism are associated with decreased serum irisin level. The presence of hypothyroidism may influence serum irisin level in CKD patients. The objective of this study was to evaluate the effect of hypothyroidism on serum irisin level in patients with nondiabetic CKD. Two hundred nondiabetic CKD patients aged between 18 and 65 years with glomerular filtration rate <60 mL/min/1.73 m2 were included in this study. Forty-three (21.5%) patients had hypothyroidism (overt and subclinical both). Forty hypothyroid and forty euthyroid CKD patients matched for age and Body Mass Index underwent body composition, biochemical [fasting plasma glucose (FPG) and C-reactive protein], and hormonal (fasting irisin and insulin) evaluation. Body composition analysis including visceral adipose tissue was done by dual-energy X-ray absorptiometry. Homeostatic model assessment 2 insulin resistance was calculated from FPG and insulin levels. The median serum irisin levels were not significantly different between hypothyroid and euthyroid CKD patients [95 (47.74-261.52) vs. 66 (28.25-224.50) ng/mL, P = 0.30]. There was also no difference in renal function, body composition and other metabolic parameters between the two groups. To conclude, the presence of hypothyroidism does not alter serum irisin level in patients with nondiabetic CKD.

Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the limitations of the currently available assays to measure progesterone at low ranges, caution should be applied to adopt specific cutoff values above which the effect of progesterone rise could be considered detrimental and to recommend "freeze-all" based solely on pre-defined cutoff points.

Assessment of insulin injection techniques among diabetes patients in a tertiary care centre.

AIMS: The efficacy of insulin therapy in diabetes depends on proper storage and injection technique. The purpose of this study was to assess the practice of insulin administration among diabetes patients in a tertiary care center. MATERIALS AND METHODS: This observational study was done in Endocrinology department of a tertiary care center during April-June 2015. The consecutive patients using insulin for at least three months by either syringe or pen were recruited. All of them underwent a survey by the questionnaire which focused on key insulin injection parameters. RESULTS: One hundred and sixty eight (74.67%) patients were storing insulin vials properly. The thigh was the most common site of insulin injection and 209(92.89%) study participants were rotating at the injection sites. Only 48.57% (34/70) subjects were mixing insulin properly before injection. The practice of hand washing and the cleaning of the injection site was practiced by 158(70%) & 171(76.44%) subjects respectively. One hundred and fifty six (69%) patients were injecting with the proper skin fold and 123(55%) subjects were injecting insulin at 90° angle. The majority of patients (91%) were throwing the needle and syringes directly into the garbage and public drainage system. CONCLUSIONS: There was a significant gap between the insulin administration guidelines and current insulin injection practice. The diabetic education and counseling about proper insulin injection techniques should be provided to all diabetic subjects.

Phenytoin Induced Osteopathy -Too Common to be Neglected.

Anticonvulsants have the broad spectrum of side effects on the bone that are collectively known as osteopathy. Anticonvulsant induced osteopathy can have detrimental consequences. We present an unusual case that uniquely highlights both adverse effects of phenytoin on bone metabolism and side effects of its overtreatment. A 29-year-old lady came for evaluation of metabolic bone disease. Since last one year, she had severe bilateral hip pain resulting in restriction of movements. She was taking phenytoin 300 mg daily for last ten years for a seizure disorder. During evaluation at another center, she was diagnosed to have vitamin D deficiency, osteomalacia and secondary hyperparathyroidism. She received recombinant parathormone, high doses of vitamin D along with phenytoin. She presented at our centre with persistent pain and hypervitaminosis D. We stopped recombinant PTH, vitamin D and changed phenytoin to levetiracetam. Her condition improved over next six months with normalization of vitamin D. Thus, patients on phenytoin should be actively screened for side effects and the appropriate preventive and correctional measures should be undertaken. While managing these side effects overtreatment should be avoided.

Papillary thyroid microcarcinoma in Graves' disease presenting as a cystic neck mass.

The presentation of papillary thyroid microcarcinoma (PTMC) as a solitary cystic neck mass is uncommon. Additionally, its association with Graves' disease is very rare. We report a case of occult PTMC, who presented with a cystic neck mass in the background of Graves' disease without any goiter. Imaging like ultrasound of neck, single photon emission computed tomography-CT (SPECT-CT), and technetium scan failed to detect any lesion in the thyroid, which was picked up only by the contrast-enhanced computed tomography (CECT) of neck. The patient underwent total thyroidectomy with right modified lymph node dissection. Our case highlights the presentation of metastatic PTMC as a differential diagnosis of a cystic neck mass even in a patient with Graves' disease without any thyroid enlargement.