Persistent Müllerian Duct Syndrome Diagnosed Incidentally: A Case Report.

Persistent Müllerian Duct syndrome is a rare male disorder of sexual development. The phenotypically and genotypically male patient presents with female internal organs (i.e., uterus, cervix, fallopian tubes and upper part of vagina) due to deficiency of anti-mullerian hormone or insensitivity of tissues to Anti Mullerian Hormone. We present a 19 year old male who came with complaint of right iliac fossa pain. He was investigated for acute appendicitis and on imaging, he was diagnosed to have bilateral cryptorchidism with rudimentary uterus. Computed tomography followed by pelvic ultrasonography was done which indicated two testes in abdomen and a soft tissue density structure, identified as a rudimentary uterus located posterior to the urinary bladder. CT scan findings were further confirmed by magnetic resonance imaging pelvis. A trial of stepwise orchidopexy followed by orchidectomy with removal of rudimentary uterus was performed laparoscopically. Additionally, he was counselled for long term sex hormone replacement and reproductive failure in future.

Levothyroxine absorption test followed by directly observed treatment on an outpatient basis to address long-term high thyrotropin levels in a hypothyroid patient: a case report.

BACKGROUND: For the treatment of hypothyroidism, patients are usually placed on lifelong levothyroxine replacement therapy. Achieving clinical and biochemical euthyroid status is sometimes difficult because of several factors, including poor compliance or poor absorption of levothyroxine in the gut mucosa. CASE PRESENTATION: We present the case of a 45-year-old South Asian female with hypothyroidism on lifelong levothyroxine replacement. However, on her multiple follow-up visits over the past 2 years, it was noted that her thyrotropin level was never controlled and was not in range. A thorough history was unyielding in terms of compliance regarding levothyroxine medication and use of over-the-counter pills or mineral supplements that may interfere with the absorption of levothyroxine. Hence, we performed levothyroxine absorption test to rule out any malabsorption as well as document pseudo-malabsorption favoring drug nonadherence. Levothyroxine absorption test resulted in more than 56% absorption of levothyroxine; therefore, the patient was put on weekly directly observed treatment strategy resulting in normalization of thyrotropin levels on successive follow-ups. CONCLUSION: Directly observed treatment to replace levothyroxine once a week can be used as an alternative by health care professionals in patients in whom compliance to daily levothyroxine is the hidden cause of persistently raised thyrotropin. This strategy can reduce undue health burden on the patient and improve adherence to self-medication under confident supervision of the treating physician.

Levothyroxine dosages during pregnancy among hypothyroid women. An experience from a tertiary care center of Karachi, Pakistan, based on data from Maternal Hypothyroidism on Pregnancy Outcomes Study (MHPO-5).

OBJECTIVES: The dosage of levothyroxine (LT4) during pregnancy differs among different ethnic groups worldwide. These differences are due to variations in geographical iodine distribution, autoimmunity, and variations in thyrotropin (TSH) targets for pregnancy. To the best of our knowledge, we report the levothyroxine dosage prescribed during pregnancy in hypothyroid women, for the first time from Pakistan. RESULTS: Levothyroxine dosage of 280 hypothyroid women during pregnancy were reviewed. The median LT4 dosages prescribed before conception was 85.7 mcg per day which increased by 14.3 mcg per day in the first trimester (P 0.001). A significant difference in dosage was observed between controlled and uncontrolled TSH groups in the first trimester (P 0.05). Lower LT4 dosage was prescribed for subclinical hypothyroid women as compared to overt hypothyroid cases, whereas dosages did not differ according to autoimmune status in the latter part of gestation.

Metastatic choriocarcinoma in a young woman presenting as thyroid storm: a case report.

BACKGROUND: Thyroid storm is an endocrine emergency and life-threatening condition discovered in 1926. There is no specific laboratory parameter that can differentiate or distinguish between thyroid storm and primary hyperthyroidism. Diagnosis is made on a clinical scoring system, including the Burch-Wartofsky point scale and Japanese Thyroid Association scoring system. The management is early diagnosis, immediate initiation of anti-thyroid medications, intensive care monitoring, and prevention of multiorgan failure. CASE PRESENTATION: A 30-year-old Pakistani female presented with complaint of headache, vomiting, and generalized weakness for 3 weeks. She had an episode of seizure-like activity at home, and so was rushed to the emergency department. A detailed thyroid examination revealed a soft, nontender gland with no enlargement or bruit and no exophthalmos. Her thyroid-stimulating hormone was extremely low, with high free triiodothyronine and thyroxine. Thyroglobulin was 425 ng/ml (normal reference range ≤ 55 ng/ml), and thyroid-stimulating hormone receptor antibody was 0.87 IU/L (normal reference range 0-1.75 IU/L). She had high levels of beta-human chorionic gonadotropin hormone on initial presentation. Transvaginal ultrasound showed no intrauterine pregnancy, but an echogenic focus was found adherent to the right ovary with no vascularity. With the chief complaint of headache, she underwent magnetic resonance imaging of the brain that showed multiple scattered hemorrhagic lesions in supratentorial and infratentorial brain parenchyma that were highly suspicious for metastases. Computed tomography scan of the chest, abdomen, and pelvis revealed multiple neoplastic lesions in the lung, liver, spleen, and kidneys. A Tru-Cut liver biopsy showed linear cores of liver tissue with metastatic carcinoma with morphological features consistent with choriocarcinoma. Our patient scored 65 on the Burch-Wartofsky point scale. As per the Japanese Thyroid Association scoring system, our patient met the criteria for a "definite thyroid storm." She had initiated propranolol to achieve adequate control of her heart rate and dexamethasone. Carbimazole was started to control her thyroid function. Her thyroid function after 2 weeks of treatment showed significant improvement. Methotrexate and etoposide were given for choriocarcinoma. She made a good recovery and was discharged home. She will undergo rehabilitation along with ongoing chemotherapy (methotrexate and etoposide weekly till beta-human chorionic gonadotropin levels normalize). Unless her source of beta-human chorionic gonadotropin is carefully under control, she will continue to take anti-thyroid medications. CONCLUSION: Choriocarcinoma is not only associated with hyperthyroidism but can induce thyroid storm. Beta-human chorionic gonadotropin is directly associated with promoting thyroid dysfunction. Patients with gestational trophoblastic disease should be under close surveillance to prevent thyroid storms.

Neonatal outcomes and congenital anomalies in pregnancies affected by hypothyroidism.

BACKGROUND: Maternal hypothyroidism has been reported to have concerns over neonatal outcomes, not only in the context of neurocognitive development but also in the short term as birth weight and neonatal jaundice. PATIENTS AND METHODS: We conducted a cross-sectional retrospective study on 638 cases who delivered live births in the Aga Khan University Hospital after ethical approval. Data were collected on hypothyroid pregnant females who were diagnosed before conception or during their antenatal visits during the year 2008-2016. Neonatal outcomes were noted for birth weight, maturity, and neonatal jaundice, neonatal hypothyroidism, neonatal respiratory distress syndrome, sepsis, hypocalcaemia, congenital anomalies, need for intensive care admission, and neonatal death. Subgroup analysis was performed on the timing of diagnosis of maternal hypothyroidism. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Neonatal jaundice was the most common neonatal outcome (37.6%) in our cohort of 662 live births. Nearly 15% required intensive care unit admission, however, neonatal death was very rare. The most common clinically significant congenital anomalies were cardiovascular defects, whereas Mongolian spots were the commonest congenital condition to report. There is a statistically significant association between low birth weight (OR 1.86, 95% CI 1.0-3.2, p ≤ 0.05) and congenital anomalies (OR 2.39, 95% CI 1.4-4.0, p ≤ 0.05) with women diagnosed with hypothyroidism before pregnancy. CONCLUSION: We report the neonatal outcomes and spectrum of congenital anomalies of hypothyroid pregnancies diagnosed before and during conception for the first time from the region of Pakistan.KEY MESSAGEOverall, none of the neonates of hypothyroid pregnancies developed congenital hypothyroidism.Cardiovascular defects in these neonates imply extensive screening and monitoring during pregnancy.Low birth weight and congenital anomalies are associated with the timings of diagnosis of hypothyroidism in pregnancy.

Association of thyroid antibodies status on the outcomes of pregnant women with hypothyroidism (maternal hypothyroidism on pregnancy outcomes, MHPO-4).

BACKGROUND: Autoimmunity increases with age and is often commonly evaluated in women of the reproductive age group. Prevalence of thyroid antibodies is common even in euthyroid pregnant women. We aim to compare the association of thyroid antibody status on the maternal and neonatal outcomes in pregnant women with hypothyroidism. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital. Information was collected on pregnant women who have been diagnosed with hypothyroidism before conception or during their antenatal period. Laboratory data were recorded for thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and thyroid-stimulating hormone levels. Maternal and neonatal outcomes were also noted from medical file records. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Overall, 146 out 718 cases were included for final analysis. Thyroid peroxidase antibodies were positive in 66.4% and anti-thyroglobulin was positive in 52.1% cases, whereas 43.8% of cases had both antibodies positive. Pre-gestational diabetes was significantly associated with thyroid autoimmunity. There was a 73% less chance of gestational hypertension for thyroid autoimmune groups. Gestational diabetes and maternal (chronic) hypertension were found to have an independent effect on postpartum hemorrhage. Hypertensive disorders in pregnancy were found to have an independent risk for premature birth. CONCLUSION: Our study reports a 74.7% prevalence of positive thyroid antibodies in hypothyroid pregnant women, with higher association with pre-gestational diabetes. Gestational hypertension was least likely to occur in thyroid autoimmune groups. None of the outcomes were independently associated with worse outcomes.

Localizing an occult insulinoma by selective calcium arterial stimulation test: first ever experience and a new dimension to diagnosis in Pakistan.

Insulinomas are rare, usually benign, solitary tumours accounting for 60% of islet cell tumours. These tumours can be difficult to localize preoperatively due to their small size. We present a challenging case of a 40 year old male with frequent hypoglycaemic spells and endogenous hypoglycaemia who presented as a diagnostic dilemma. Patient had an occult insulinoma with inconclusive CT Abdomen, MRI Abdomen and Octreotide scan. The final localization of the tumour was made by selective arterial calcium stimulation testing (SCAT), done for the first time in Pakistan at Aga Khan University Hospital. This was followed by successful distal pancreatectomy as localizd by SACT yielding a well differentiated neuroendocrine tumour. After surgery patient made a robust recovery with no further hypoglycaemic symptoms. Hence successful localization and management of occult insulinomas can be challenging but can be achieved with the advent of newer invasive modalities.

Relation of Copeptin with Diabetic and Renal Function Markers Among Patients with Diabetes Mellitus Progressing Towards Diabetic Nephropathy.

BACKGROUND: Arginine vasopressin (AVP) plays an important role in the pathophysiology of Diabetes Mellitus (DM) and its related complications like diabetic nephropathy. Copeptin is considered as a reliable surrogate biomarker of AVP. If raised levels of copeptin in diabetic patients are detected earlier, prognosis of DM can be improved by timely modulating the treatment strategy. AIMS OF THE STUDY: The study is therefore planned to assess copeptin levels in different groups of DM and in healthy controls to suggest a better and reliable biomarker for progressive stages of DM. METHODS: Subjects were recruited as controls, pre diabetes, DM without nephropathy and diabetic nephropathy. Serum copeptin levels were measured by ELISA. While, Blood Urea Nitrogen (BUN), creatinine, Glycosylated Hemoglobin (HbA1c) and spot urinary albumin creatinine ratio (UACR) were done using spectrophotometry. Statistical analysis was done using ANOVA and Pearson's correlation tests on SPSS. RESULTS: The average copeptin levels were 215.096 pg/mL. Copeptin levels were significantly elevated in subjects with positive family history of DM (p = 0.025), levels were also raised in pre diabetes kpatients (252.85 pg/mL) as compared to other groups. Copeptin levels were also correlated with HbA1c r = 0.171 (p = 0.101), BUN r = 0.244 (p = 0.007), creatinine r = 0.215 (p = 0.018), UACR r = 0.375 (p = <0.001) and GFR r = 0.215 (p = <0.019). CONCLUSION: The significant correlation of copeptin with diabetic and renal biomarkers, along with its positive association with family history of DM support its' role as an early and reliable biomarker of DM and its associated nephropathy.

Presentations and Outcomes of Thyroid Storm.

The aim of this study is to describe the characteristics and outcome of thyroid storm patients presenting at two tertiary care centres of Karachi, i.e. at Dow University of Health Sciences; and Liaquat National Hospital, Karachi, from December 2018 to May 2019. All patients between 18-70 years of age, who were admitted with thyroid storm and fulfilled the Burch- Wartofsky criteria, were inducted. Demographics including age, gender, clinical presentations, systemic symptoms, clinical examination of the thyroid and laboratory findings were reviewed from the file records to identify factors associated with mortality using the available data. Overall, five (62.5%) out of eight patients were female. The mean age was 43 ±1.67 years. Infections were the most common comorbid condition followed by cardiovascular and gastrointestinal diseases. The in-hospital mortality rate was 87.5% (n=07).

Maternal characteristics and outcomes affected by hypothyroidism during pregnancy (maternal hypothyroidism on pregnancy outcomes, MHPO-1).

BACKGROUND: Hypothyroidism in pregnancy is an arena of ongoing research, with international conflicts regarding screening, management, and outcomes. Various studies have described the outcomes depending on geographical and international diagnostic criteria. No study has been conducted in this regard from the region of Pakistan. Therefore, we aim to report the clinical features and maternal outcomes of hypothyroid pregnancies and compare the maternal outcomes between uncontrolled and controlled TSH levels in the preconception as well as the gestational period. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital after ethical approval. We collected information on pregnant females who have diagnosed hypothyroidism before conception or during their antenatal period. We noted the maternal characteristics and maternal comorbidities. Laboratory data were recorded for thyroid stimulating hormone levels before conception and during gestation. We recorded maternal outcomes as pregnancy loss (including miscarriage, stillbirth/intrauterine death, medical termination of pregnancy and ectopic pregnancy), gestational hypertension, pre-eclampsia, postpartum hemorrhage, placental abruption, and modalities of delivery. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Among 708 hypothyroid women 638 had live births. Postpartum hemorrhage was the most frequent maternal outcome (38.8%). The emergency cesarean section occurred in 23.4% of cases. We determined TSH levels in 53.2, 56.7, 61.7 and 66.6% of cases in preconception, 1st, 2nd, and 3rd trimester periods. A significant association existed between cesarean section and preconception thyrotropin levels > 2.5 mIU/L, whereas postpartum hemorrhage was significantly associated with thyrotropin levels > 2.5 mIU/L in the preconception and third trimester. CONCLUSION: Successful live births in our patients were complicated by maternal postpartum hemorrhage and a frequent number of emergency cesarean section.

Hypopituitarism other than sellar and parasellar tumors or traumatic brain injury assessed in a tertiary hospital.

OBJECTIVE: Data regarding the etiology, clinical and biochemical patterns in hypopituitarism is scant for Pakistan. We describe the characteristics of patients with hypopituitarism other than sellar and parasellar tumors or traumatic brain injury from a tertiary care center in Pakistan. METHODS: We conducted a retrospective descriptive study in the Aga Khan University Hospital, Karachi, Pakistan. We studied all patients presenting with hypopituitarism, between January 2004 and December 2013. Clinical, hormonal and imaging data pertinent to the study was collected according to inclusion criteria. RESULTS: Forty-two patients presented to the endocrinology clinics at the Aga Khan University Hospital during the study period. Thirty-seven patients (88.1%) were females. Mean age ± standard deviation of the participants was 53.8 ± 14.7 years. Sixteen patients had secondary infertility and all were females; a majority of patients in this group had Sheehan's syndrome (n=8) followed by empty sella syndrome (n=3), partial empty sella syndrome (n=2), idiopathic cause (n=2) and tuberculoma (n=1). Eighteen females (48.6%) reported inability to lactate. CONCLUSIONS: Non-traumatic hypopituitarism was more common in women, with Sheehan syndrome being the most common cause of hypopituitarism in our study (35.7%). Secondary hypothyroidism was the most common hormonal deficiency. The most commonly reported symptom was weakness.

Primary amenorrhoea secondary to two different syndromes: a case study.

Turner syndrome is a relatively common chromosomal abnormality presenting as primary amenorrhoea in gynaecological and endocrine clinics, caused by complete or partial X monosomy in some or all cells. Mayer-Rokitansky-Kuster-Hauser syndrome is another common cause of primary amenorrhoea characterised by Mullerian agenesis of varying degrees. We report a case of an 18-year-old girl, who presented with primary amenorrhoea, absence of secondary sexual characteristics and short stature. Hormonal profile confirms hypergonadotrophic hypogonadism. Karyotyping was consistent with Turner syndrome (45,XO). In addition, radiological imaging of the pelvis showed the absence of both ovaries as well as the uterus, cervix and vagina. This patient had therefore presented with two different syndromes as the cause of her primary amenorrhoea, which is extremely rare in a single patient. Moreover, oestrogen replacement therapy will trigger the development of secondary sexual characteristic and promote bone growth, but induction of menstruation and fertility is impossible.

Diabetic ketoacidosis characteristics and differences In type 1 versus type 2 diabetes patients.

BACKGROUND: Diabetes is undoubtedly one of the most challenging health problems of the 21st century. It is well known that diabetes once develop can lead to several complications. Diabetic ketoacidosis (DKA) is one of the life-threatening complications of diabetes. This study was designed to determine the frequency of DKA in diabetes patients and find out the clinical and biochemical determinants of DKA. METHODS: This descriptive study was conducted at Aga Khan University Hospital (AKUH) Karachi, Pakistan from January 2010 to February 2016. All known or newly diagnosed diabetic patients of >16 years of age irrespective of gender and type of diabetes were included. Information regarding patient's demographics, presenting symptoms, precipitating causes of DKA, biochemical profiles and outcome at the time of discharge was collected. RESULTS: Majority (54.7%) had moderate and 12.4% had severe DKA at presentation. Previous history of DKA was found higher in type 1 diabetes patients (T1DM) (14%) as compare to (4%) type 2 diabetes patients (T2DM) (p<0.05). DKA severity was observed more (12%) in newly diagnosed (T1DM) (p<0.05). Comorbidities were found more (81%) in (T2DM) (p<0.05) Mortality was also observed higher in Type 2 diabetes patients (p<0.05). CONCLUSIONS: Majority of the diabetics had moderate to severe DKA at presentation. Mortality and morbidity related with DKA was found considerably higher among patients with T2DM while infection, myocardial infarction and stroke found as triggering factors in these patients.

Typical graves' ophthalmopathy in primary hypothyroidism.

Graves ophthalmopathy (GO) usually occurs in a close temporal relationship with hyperthyroidism. It is rare in patients with normal thyroid function (euthyroid GO) and in patients with hypothyroid forms of thyroid autoimmune diseases (hypothyroid GO). We report a 52-years old man presenting in our endocrine clinic with diagnosed primary hypothyroidism 3 months back during evaluation for glaucoma. He was later referred by an ophthalmologist to exclude Grave's eye disease, where he had presented with chief complaints of bilateral prominent eyes. On examination there was only bilateral exophthalmos with marked chemosis. Magnetic resonance imaging (MRI) of the orbits showed typical findings of GO. Grave's ophthalmopathy is a rare condition to come across in patients with primary hypothyroidism, and is being first time reported from Pakistan. Patients with hypothyroidism and Graves ophthalmopathy can be successfully treated with steroids in a similar manner as in patients with GO associated with hyperthyroidism.

Idiopathic hypogonadotropic hypogonadism reversal after testosterone replacement in a 34-year-old male.

A 34-year-old male presented to the endocrinology clinic with the complaint of the absence of facial, axillary and pubic hairs. Further history revealed absent ejaculations and decreased early morning erections. The patient had no history of headaches, visual problems or anosmia. On physical examination, there were sparse facial, axillary and pubic hairs, bilateral gynaecomastia, stretch penile length of 5 cm and bilateral testicular volume of 10 mL. Laboratory investigations showed low luteinising hormone, follicular stimulating hormone and testosterone with normal prolactin and thyroid profile. MRI of the pituitary gland showed no evidence of pituitary microadenoma or macroadenoma. The patient was started on testosterone injections. After 9 months of testosterone replacement, the patient's testicular size increased to 20 mL bilaterally and his penile length increased to the mean adult size for his age with normal testosterone and luteinising hormone. He was, thus, advised to discontinue testosterone therapy.

Incidental metastatic mediastinal atypical carcinoid in a patient with parathyroid adenoma: a case report.

BACKGROUND: Atypical carcinoid arising from the mediastinal tissue is a rare neuroendocrine tumor and an association with parathyroid adenoma is very unusual. We report an unusual case of atypical carcinoid of mediastinum with metastasis in a patient presenting with parathyroid adenoma, which is the first case to be reported from Pakistan. CASE PRESENTATION: A 51-year-old Pakistani man was seen in postoperative intensive care after right parathyroidectomy and mediastinal mass resection for the management of postoperative hypocalcaemia. He had a background history of dyspnea. Examination was unremarkable. Preoperative laboratory evaluation revealed a calcium level of 12.7 mg/dl, phosphate of 1.9 mg/dl, serum albumin of 4.8 g/dl, alkaline phosphate of 94 U/L, and serum intact parathyroid hormone level 413.8 pg/ml. A technetium-99m sestamibi parathyroid scan showed right parathyroid increased tracer uptake. Further workup revealed a large mediastinal mass which was diagnosed as atypical carcinoid after Tru-Cut biopsy. He underwent right-sided parathyroidectomy and resection of the mediastinal mass. The histopathology confirmed it to be a parathyroid adenoma and atypical carcinoid tumor of his mediastinum with metastasis in his lymph node and parathyroid gland. Somatostatin receptor scintigraphy revealed a well-defined focus in his left hypochondriac region consistent with a somatostatin receptor scintigraphy-avid tumor. He was started on everolimus and planned for octreotide therapy. CONCLUSIONS: We describe an incidental finding of atypical carcinoid of the mediastinum in a patient diagnosed as having parathyroid adenoma. Clinical manifestations of neuroendocrine syndromes are challenging. Some tumors cluster in a non-classic description with other common neoplasms. They rarely present in isolation, remain clinically silent, and need aggressive workup with the aid of imaging and histopathology.

SODIUM AND WATER IMBALANCE AFTER SELLAR, SUPRASELLAR, AND PARASELLAR SURGERY.

OBJECTIVE: To report the frequency of sodium and water disturbances (SWDs) in patients undergoing sellar, suprasellar, and parasellar surgery (SSPS). METHODS: We conducted a cross-sectional, retrospective study on 115 patients in the Aga Khan University Hospital after ethical approval. Patients were 16 years old or older undergoing pituitary or sellar surgeries. We collected data on basic sociodemographic characteristics and clinical indication for surgery. We noted laboratory values for serum electrolytes, plasma and urine osmolality, urine sodium, and 24-hour fluid balance from the immediate postoperative day until discharge and follow-up. We recorded medical management plans. We also recorded diabetes insipidus (DI), syndrome of inappropriate antidiuretic hormone (SIADH), cerebral salt wasting (CSW), triphasic response, and hyponatremia, according to the diagnostic definitions. Finally, we performed data analysis using Statistical Package for the Social Sciences, version 19.0. RESULTS: Of 115 patients, there were 61.7% males, mean age 42.3 ± 13.86 years, 91.3% had pituitary adenoma (73.0% nonfunctioning), and 86.1% underwent transsphenoidal surgical approach. Transient DI occurred from days 1 to 6, peaking with 57.4% on day 2. Permanent DI and SIADH were rare. We did not note typical triphasic response or CSW in any of the patients. However, isolated hyponatremia occurred in 11%, and 20.9% had DI with hyponatremia. CONCLUSION: Transient DI is the most common postoperative SWD after SSPS. Hyponatremia occurred alone and following DI. This is the first study describing postoperative SWDs after different sellar surgeries in Pakistan. ABBREVIATIONS: ADH = antidiuretic hormone CSW = cerebral salt wasting DI = diabetes insipidus SIADH = syndrome of inappropriate antidiuretic hormone SSPS = sellar, suprasellar, and parasellar surgery SWD = sodium and water disturbance.

Three siblings with familial non-medullary thyroid carcinoma: a case series.

BACKGROUND: In 2015, thyroid carcinoma affected approximately 63,000 people in the USA, yet it remains one of the most treatable cancers. It is mainly classified into medullary and non-medullary types. Conventionally, medullary carcinoma was associated with heritability but increasing reports have now begun to associate non-medullary thyroid carcinoma with a genetic predisposition as well. It is important to identify a possible familial association in patients diagnosed with non-medullary thyroid carcinoma because these cancers behave more destructively than would otherwise be expected. Therefore, it is important to aggressively manage such patients and screening of close relatives might be justified. Our case series presents a diagnosis of familial, non-syndromic, non-medullary carcinoma of the thyroid gland in three brothers diagnosed over a span of 6 years. CASE PRESENTATIONS: We report the history, signs and symptoms, laboratory results, imaging, and histopathology of the thyroid gland of three Pakistani brothers of 58 years, 55 years, and 52 years from Sindh with non-medullary thyroid carcinoma. Only Patients 1 and 3 had active complaints of swelling and pruritus, respectively, whereas Patient 2 was asymptomatic. Patients 2 and 3 had advanced disease at presentation with lymph node metastasis. All patients underwent a total thyroidectomy with Patients 2 and 3 requiring a neck dissection as well. No previous exposure to radiation was present in any of the patients. Their mother had died from adrenal carcinoma but also had a swelling in the front of her neck which was never investigated. All patients remained stable at follow-up. CONCLUSIONS: Non-medullary thyroid carcinoma is classically considered a sporadic condition. Our case report emphasizes a high index of suspicion, a detailed family history, and screening of first degree relatives when evaluating patients with non-medullary thyroid carcinoma to rule out familial cases which might behave more aggressively.

Euglycaemic diabetic ketoacidosis in a patient with type 2 diabetes started on empagliflozin.

Diabetes ketoacidosis (DKA) is largely associated with type 1 diabetes and has hyperglycaemia as a cardinal feature. We discuss the case of a 42-year-old man, a patient with type 2 diabetes, who presented to the emergency room, with nausea, vomiting and abdominal pain. He had recently changed his diabetes medications and started on an SGLT2 inhibitor (empagliflozin) along with metformin, pioglitazone, liraglutide and self-adjusted exogenous insulin. DKA was suspected in the wake of clinical examination and lab findings but glucose levels were below the cut-off for DKA; therefore, he was diagnosed with euglycaemic DKA. He was successfully managed with intravenous hydration and insulin infusion. We discuss the link of SGLT2 inhibitors with DKA and the pathophysiology behind euglycaemic DKA.

Comparison of frequency of insulin resistance in patients with chronic obstructive pulmonary disease with normal controls.

OBJECTIVE: To compare mean homeostatic model assessment of insulin resistance (HOMA-IR) in patients with and without chronic obstructive pulmonary disease (COPD). METHODS: A Case control analytic study was conducted in medical outpatient department of Medial Unit-II of Dow University of Health Sciences from April 2013 to September 2013. All patients with the diagnosis of COPD were included as cases. Controls were age match healthy individuals with minor illnesses. Age, weight, height and forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio were documented. Fasting blood glucose and fasting insulin levels were done. Body mass index (BMI) and IR was calculated using the formulas. HOMA-IR was compared between cases and controls. RESULTS: Forty COPD patients were compared with thirty five age match controls. HOMA-IR was found to be higher in cases as compared to controls (2.85 v/s 2.00) with a p value <0.000. CONCLUSION: COPD is one of the chronic debilitating diseases in our region with various extra-pulmonary complications. We found IR to be present higher in COPD patients compared with healthy controls. Evaluating the pulmonary function as well as systemic metabolic parameters, may contribute to minimizing mortality and morbidity.