Screening for phaeochromocytoma in patients with acute cerebrovascular disease: Is it necessary?

INTRODUCTION: Phaeochromocytoma may present with uncontrolled hypertension leading to haemorrhagic stroke (HS), ischaemic stroke (IS) and transient ischaemic attack (TIA). False elevation in the levels of CATS/ METS has been reported in acute cerebrovascular disease. Our aim was to analyse the frequency and pattern of elevations of CATS/METS in patients with acute cerebrovascular disease and to determine associated factors. MATERIALS AND METHODS: This is a retrospective study of 112 samples of CATS/ METS received by the laboratory over a two-year period, from patients with acute cerebrovascular disease. CATS/METS were measured using LC/MS/MS method. Clinical details and CATS/METS level were obtained from the database. Mann-Whitney U test and Kruskal Wallis test were used for statistical analysis. These statistical analyses were performed using SPSS v.20.0 (IBM Corp., Armonk, NY, USA). RESULTS: Of the 112 patients, 39% had HS, 54% had IS and 7% had TIA. A total of 29% of patients had elevated CATS/ METS. Elevated levels of CATS/METS were noted in 41% and 25% of HS and IS patients, respectively (p=0.53). Median norepinephrine, epinephrine and metanephrine levels in HS were significantly higher than IS (p< 0.05). Systolic blood pressure was higher in those who had elevated CATS/ METS (p=0.04). Only for two patients with elevated CATS/METS repeat testing was performed. Age, diastolic blood pressure and the time of sample collection in relation to the presentation, for CATS/METS were not significantly different between groups that had elevated levels of CATS/ METS versus those who did not. CONCLUSION: We noted that CATS/METS were elevated in one-third of patients, especially in patients with high systolic blood pressure. Increase in CATS/METS should be appropriately followed up with repeat testing. Since false elevation in CATS/METS has been reported in cerebrovascular disease, screening for phaeochromocytoma is best deferred for a month.

Maternal lipids are associated with newborn adiposity, independent of GDM status, obesity and insulin resistance: a prospective observational cohort study.

OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs. DESIGN: Prospective observational cohort study. SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia. POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT. METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records. MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile. RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile. CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy. TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.

Continuous glucose monitoring results in lower HbA1c in Malaysian women with insulin-treated gestational diabetes: a randomized controlled trial.

AIMS: To determine if therapeutic, retrospective continuous glucose monitoring (CGM) improves HbA1c with less hypoglycaemia in women with insulin-treated gestational diabetes mellitus (GDM). METHODS: This prospective, randomized controlled, open-label trial evaluated 50 women with insulin-treated GDM randomized to either retrospective CGM (6-day sensor) at 28, 32 and 36 weeks' gestation (Group 1, CGM, n = 25) or usual antenatal care without CGM (Group 2, control, n = 25). All women performed seven-point capillary blood glucose (CBG) profiles at least 3 days per week and recorded hypoglycaemic events (symptomatic and asymptomatic CBG < 3.5 mmol/l; non-fasting < 4.0 mmol/l). HbA1c was measured at 28, 33 and 37 weeks. In Group 1, both CGM and CBG data were used to manage diabetes, whereas mothers in Group 2 were managed based on CBG data alone. RESULTS: Baseline characteristics (age, pre-pregnancy BMI, HbA1c , total insulin dose) were similar between groups. There was a lower increase in HbA1c from 28 to 37 weeks' gestation in the CGM group [∆HbA1c : CGM + 1 mmol/mol (0.09%), control + 3mmol/mol (0.30%); P = 0.024]. Mean HbA1c remained unchanged throughout the trial in the CGM group, but increased significantly in controls as pregnancy advanced. Mean HbA1c in the CGM group was lower at 37 weeks compared with controls [33 ± 4 mmol/mol (5.2 ± 0.4%) vs. 38 ± 7 mmol/mol (5.6 ± 0.6%), P < 0.006]. Some 92% of the CGM group achieved an HbA1c ≤ 39 mmol/mol (≤ 5.8%) at 37 weeks compared with 68% of the control group (P = 0.012). Neither group experienced severe hypoglycaemia. CONCLUSION: CGM use may be beneficial in insulin-treated GDM because it improves HbA1c compared with usual antenatal care without increasing severe hypoglycaemia. (Clinical Trials Registry No.: NCT02204657).

Hypopituitarism in a Dengue Shock Syndrome Survivor without known Pituitary Adenoma.

Dengue infection is endemic in South East Asia and parts of the Americas. Dengue hemorrhagic fever is characterized by vascular permeability, coagulation-disorders and thrombocytopenia, which can culminate in hypotension i.e. dengue shock syndrome. Hypopituitarism arising as a complication of dengue is extremely rare. Hemorrhagic pituitary apoplexy of pre-existing pituitary adenomas has been rarely reported in dengue. We describe an uncommon case of hypopituitarism in a dengue shock syndrome survivor without known pituitary adenoma. A 49 years old nulliparous lady (from Kuala Lumpur, Malaysia) presented with typical symptoms of hypocortisolism. Postural hypotension was evident with normal secondary sexual characteristics. Further history revealed that she survived an episode of dengue shock syndrome 6 years ago where premature menopause developed immediately after discharge, and subsequently insidious onset of multiple hormonal deficiencies indicative of panhypopituitarism. There were no neuro-ophthalmological symptoms suggestive of pituitary apoplexy during hospitalization for severe dengue. Magnetic resonance imaging of the pituitary 6 years later revealed an empty sella. Autoimmune screen and anti-thyroid peroxidase antibodies were negative. We describe a rare possible causative association of severe dengue with panhypopituitarism without known pituitary adenoma, postulating pituitary infarction secondary to hypotension (mimicking Sheehan's syndrome), or a direct viral cytopathic effect. Subclinical pituitary apoplexy secondary to asymptomatic pituitary hemorrhage however cannot be excluded. Future research is required to determine the need for and timing of pituitary axis assessment among dengue shock syndrome survivors.

Hypothalamic pituitary dysfunction amongst nasopharyngeal cancer survivors.

PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors. METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function. RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01. CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.