Niemann-Pick Disease With Bilateral Adrenal Mass.

Niemann-Pick disease (NPD) is a heterogeneous group of lysosomal storage disorders with autosomal recessive inheritance pattern. There are 4 types of NPD. Patients with NPD type B generally have better prognosis, allowing them to survive into adulthood. They have a widespread clinical presentation, affecting multiple organs but rarely neurological involvement. Here, we describe the case of a 38-year-old woman with unexplained hepatosplenomegaly and young hypertensive intracranial bleed. Evaluation for young hypertension further revealed a nonfunctional bilateral adrenal mass and gross hepatosplenomegaly. NPD was confirmed through dried blood spot investigation. It showed low activity of acid sphingomyelinase and genetic testing also detected 2 pathogenic mutations. She is being managed by a multidisciplinary team for supportive treatment that includes regular symptoms monitoring and genetic counseling.

International multicenter survey on screening and confirmatory testing in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. DESIGN: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. RESULTS: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. CONCLUSIONS: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.

Use of Combination of Oral Levothyroxine and Liothyronine in Severe Hypothyroidism With Massive Pericardial Effusion.

Thyroid hormone plays an important role in cardiovascular function. Pericardial effusions are commonly seen in cases of severe hypothyroidism. However, large to massive pericardial effusions with cardiac tamponade are exceptionally rare. Herein, we present two cases of severe hypothyroidism with massive pericardial effusion. Our first case demonstrates that a patient with large pericardial effusion can be managed conservatively with aggressive thyroid hormone replacement therapy. In our second case, pericardiocentesis was performed in addition to thyroid hormone replacement therapy as the underlying aetiology of effusion could not be reasonably limited to hypothyroidism. These two cases served to highlight and demonstrate rapid normalisation of thyroid function test by using aggressive oral thyroid hormone replacement therapy using liothyronine, in combination with levothyroxine, which led to resolution of pericardial effusion and prevent its re-accumulation.

The Effect of DPP4 Inhibitor on Glycemic Variability in Patients with Type 2 Diabetes treated with twice-daily Premixed Human Insulin.

OBJECTIVE: To evaluate the effect of adding DPP4 inhibitor (DPP4-i) on glycemic variability (GV) in patients with type 2 diabetes mellitus (T2DM) treated with premixed human insulin (MHI). METHODOLOGY: We conducted a prospective study in patients with T2DM on twice-daily MHI with or without metformin therapy. Blinded continuous glucose monitoring was performed at baseline and following 6 weeks of Vildagliptin therapy. RESULTS: Twelve patients with mean (SD) age of 55.8 (13.1) years and duration of disease of 14.0 (6.6) years were recruited. The addition of Vildagliptin significantly reduced GV indices (mmol/L): SD from 2.73 (IQR 2.12-3.66) to 2.11 (1.76-2.55), p=0.015; mean amplitude of glycemic excursions (MAGE) 6.94(2.61) to 5.72 (1.87), p=0.018 and CV 34.05 (8.76) to 28.19 (5.36), p=0.010. In addition, % time in range (3.9-10 mmol/l) improved from 61.17 (20.50) to 79.67 (15.33)%, p=0.001; % time above range reduced from 32.92 (23.99) to 18.50 (15.62)%, p=0.016; with reduction in AUC for hyperglycemia from 1.24 (1.31) to 0.47 (0.71) mmol/day, p=0.015. Hypoglycemic events were infrequent and the reduction in time below range and AUC for hypoglycemia did not reach statistical significance. CONCLUSION: The addition of DPP4-I to commonly prescribed twice-daily MHI in patients with T2DM improves GV and warrants further exploration.

Recurrent cavernous sinus thrombosis: a rare complication of Cushing disease.

A 14-year-old girl who presented in 2017 with headache, unilateral right eye ptosis and secondary amenorrhoea had an initial workup consistent with non-functioning pituitary macroadenoma. She underwent debulking of pituitary tumour in October 2017. Postoperatively, she developed recurrent cavernous sinus thrombosis. In view of recurrent thrombosis, she was reinvestigated and was found to have adrenocorticotropic hormone-dependent Cushing. Follow-up MRI 1 year after initial presentation showed that there was structural recurrence of pituitary macroadenoma. She subsequently underwent a petrosal craniotomy for debulking of tumour. Postsurgery she remained biochemically Cushingnoid. MRI 5 months after second surgery showed an enlarging pituitary mass which was deemed inoperable. A multidisciplinary meeting discussion consensus for treatment included radiotherapy and somatostatin analogue, pasireotide. She completed 30 cycles of radiotherapy and MRI post radiotherapy showed reduction in the size of the macroadenoma. Currently, she is waiting for pasereotide initiation.

Diabetes emergencies around Ramadan study (DEARS) - A multi-center study of diabetes emergencies admitted before, during and after Ramadan in Malaysia.

OBJECTIVE: The objective of this study was to determine admissions for diabetes emergencies among patients who fasted or planned to fast one month before, during and one month after Ramadan 2019 in public hospitals in Malaysia. MATERIALS AND METHODS: This was a cross sectional prospective study done in 18 public hospitals in Malaysia from 7/4/2019 to 2/7/2019. Data was collected prospectively with universal sampling. All adult Muslim patients with previous diagnosis of diabetes, who were admitted for hypoglycemia, DKA or HHS were included if they had fasted and had intentions to fast. RESULTS: 295 admissions for diabetes emergencies were analyzed. The pre-Ramadan period recorded the highest number of admissions (119) followed by during (106) and post-Ramadan (70). Admissions for hyperglycemic emergencies accounted for 2/3 of total admissions. 37% of admissions for hypoglycemia occurred during pre-Ramadan period compared to 32.1% during Ramadan. Contributing factors included use of sulphonylurea (59.6%), presence of nephropathy (54.5%) and past history of hypoglycemia (45.5%). Admissions for DKA were more common than HHS (119 versus 77) and highest during Ramadan period (36.1%). Most of the admissions for hyperglycemic emergencies were among those with Type 2 diabetes (75.9% for DKA and 97.4% for HHS). Only 31.5% of patients admitted for diabetes emergencies recalled having received Ramadan advice in the past. DISCUSSION: Admissions for diabetes emergencies were highest during pre-Ramadan period followed by Ramadan and post-Ramadan period. This suggests that fasting during Ramadan does not increase admissions for diabetes emergencies.

The DAR 2020 Global survey: Ramadan fasting during COVID 19 pandemic and the impact of older age on fasting among adults with Type 2 diabetes.

OBJECTIVES: The DAR Global survey of Ramadan-fasting during the COVID-19 pandemic aimed to describe the characteristics and care in participants with type 2 diabetes (T2D) with a specific comparison between those <65 years and ≥65 years. METHODS: Participants were consented to answer a physician-administered questionnaire following Ramadan 2020. Impact of COVID-19 on the decision of fasting, intentions to fast and duration of Ramadan and Shawal fasting, hypoglycaemia and hyperglycaemia events were assessed. Specific analysis comparing age categories of <65 years and ≥65 years were performed. RESULTS: Among the 5865 participants, 22.5% were ≥65 years old. Concern for COVID-19 affected fasting decision for 7.6% (≥65 years) vs 5.4% (<65 years). More participants ≥65 years old did not fast (28.8% vs 12.7%, <65 years). Of the 83.6%, participants fulfilling Ramadan-fasting, 94.8% fasted ≥15 days and 12.6% had to break fast due to diabetes-related illness. The average number of days fasting within and post-Ramadan were 27 and 6 days respectively, regardless of age. Hypoglycaemia and hyperglycaemia occurred in 15.7% and 16.3% of participants respectively, with 6.5% and 7.4% requiring hospital care respectively. SMBG was performed in 73.8% of participants and 43.5% received Ramadan-focused education. CONCLUSION: During the COVID-19 pandemic, universally high rates of Ramadan-fasting were observed regardless of fasting risk level. Glycemic complications occurred frequently with older adults requiring higher rates of acute hospital care. Risk stratification is essential followed by pre-Ramadan interventions, Ramadan-focused diabetes education and self-monitoring to reduce and prevent complications, with particular emphasis in older adults.

Hyperandrogenism caused by ovarian Leydig cell tumour: finding the needle in a haystack.

Leydig cell tumours (LCTs) of the ovary are rare ovarian tumours that usually present with hyperandrogenism. Conventional radiological imagings are helpful in localising these tumours. However, some tumours may be too small to be localised before curative surgical removal. It is important to identify these androgen-secreting neoplasms which originate mostly from adrenals or ovaries because they are potentially malignant and require specific treatment. When conventional imagings are unrevealing, selective ovarian and adrenal venous sampling (SOAVS) is the next option. We report a case of LCT that was localised by SOAVS after results from other imaging modalities remained inconclusive.

Lessons of the month: Not just morning sickness.

A 34-year-old woman (gravida 4; para 3) at 17 weeks of pregnancy presented with abnormal behaviour for 3 weeks associated with difficulties in walking. She had been admitted 2 months prior with hyperemesis gravidarum and was also diagnosed with thyrotoxicosis. Vomiting and poor oral intake persisted after discharge. She was euthyroid otherwise. Clinical examination revealed a dehydrated and confused patient. She had nystagmus and ataxic gate. Magnetic resonance imaging of the brain showed symmetrical signal changes of posteromedial part of thalamus. A diagnosis of Wernicke's encephalopathy (WE) was made and intravenous thiamine was given leading to gradual improvement of symptoms. Her thyroid function test normalised without any treatment. WE can occur in severe hyperemesis gravidarum. Prompt recognition of WE and replacement with thiamine is important to prevent neurological sequelae and mortality. Gestational transient thyrotoxicosis, which is self-limiting, is more prominent in patients with hyperemesis gravidarum and requires only symptomatic treatment.

Co-Occurrence of Exogenous and Endogenous Cushing's Syndromes-Dilemma in Diagnosis.

Approach to patients who manifest with features of Cushing's syndrome often begin with exclusion of exposure to excessive exogenous source of glucocorticoids (GC). Most guidelines advocate no further assessment if excessive exogenous GC use is present. We present a case of a 66-year-old lady who was noted to have typical features of Cushing's syndrome. As she gave a very clear history of ingesting exogenous GC for a year, no further work up was undertaken. Despite cessation of GC for a year, she continued to have thin skin and easy bruising. Upon admission for hypertensive emergency, her clinician took note of her changes and investigated her for endogenous Cushing's syndrome. Her cortisol post overnight dexamethasone suppression test was 707 nmol/l. Post low dose dexamethasone suppression test yielded a cortisol of 1133.2 nmol/l. 24 hours urine cortisol was 432.2 nmol/l. Plasma ACTH was 1.1 pmol/l, indicating an ACTH independent Cushing's syndrome. We proceeded with Computed tomography scan (CT scan) of adrenals which revealed a right adrenal adenoma measuring 4.4 × 3.4 × 4.0 cm. Right retroperiteneoscopic adrenalectomy was done. Histopathology examination was consistent with adrenal cortical adenoma with foci of myelolipoma. Post adrenalectomy she developed hypocortisolism secondary to contralateral adrenal suppression which lasted up to the present date. Her cutaneous and musculoskeletal manifestations improved substantially. Co-occurrence of endogenous and exogenous Cushing's syndromes is uncommon but should be considered in patients whose Cushingnoid features do not resolve after cessation of exogenous GC.

Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus.

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, ß-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG-BCIV)/BCOG). RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1 but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001). CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM. TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254.

Ectopic ACTH syndrome - Experience with Etomidate.

For ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), when surgery is not feasible, or in cases of severe biochemical disturbances, immunosuppression or mental instability, medical therapy with agents such as etomidate is indicated. We present our experience in using etomidate for a 41-year old female with EAS secondary to a malignant mediastinal paraganglioma. We were able to demonstrate that etomidate can be used effectively to control severe hypercortisolism in a lower dose than previously described.