Detecting patients with Cushing's syndrome: The importance of initial test selection.

BACKGROUND AND OBJECTIVES: The recommended initial tests for suspected Cushing's syndrome are late-night salivary cortisol (LNSC), 24-hour urinary free cortisol (UFC) and the 1 mg overnight dexamethasone suppression test (ONDST). These tests have higher sensitivity and specificity than serum cortisol. The aim of this study was to determine the relative frequency of these requested tests in primary care. METHOD: Initial test selection for investigation of Cushing's syndrome was audited by reviewing pathology request forms for cortisol tests made to a major community-based laboratory in 2019. Those with hypertension or adrenal incidentaloma as the documented indication for testing were included. RESULTS: In 214 of 272 cases (78.7%; 95% confidence interval: 73.2%, 83.3%) initial testing was by measurement of serum cortisol alone. DISCUSSION: The relatively infrequent selection of the higher sensitivity tests (ONDST, UFC and LNSC) for investigation of suspected Cushing's syndrome signifies a risk of delayed or missed diagnosis, with important implications for morbidity and mortality.

Approach to the diagnosis of secondary hypertension in adults.

Presentations that should raise suspicion of secondary hypertension include early-onset, severe or resistant hypertension. A suggestive family history or clinical clues can point to a specific secondary cause. The most common causes and associations are renal disease, primary aldosteronism and obstructive sleep apnoea. Medicines, illicit substances and alcohol may also be responsible. The assessment of patients begins with history taking and examination, to look for clinical clues. Laboratory tests include electrolytes, urea, creatinine and the aldosterone:renin ratio, urinalysis and the urine albumin:creatinine ratio. Abnormal results should prompt further investigation. Initial testing for primary aldosteronism is best done before starting potentially interfering antihypertensive drugs. If the patient is already taking interfering antihypertensive drugs that cannot be stopped, the interpretation of the aldosterone:renin ratio must consider the presence of those drugs. Specialist advice can be sought if needed.

Where in the world? Latitude, longitude and season contribute to the complex co-ordinates determining cortisol levels.

OBJECTIVE: Cortisol is a critical stress hormone with circadian rhythms synchronized by light. There are seasonal differences in expression of pro-inflammatory genes and in some diseases moderated by glucocorticoids. As light changes with season and with latitude and longitude, we assessed changes in population cortisol associated with these parameters. DESIGN: Retrospective data audit. PATIENTS: Populations across 4 states of Australia over 3 years. MEASUREMENTS: Serum cortisol levels, age, gender, time of collection, sunrise time, season and location were determined. RESULTS: In 4 geographically separate populations (n = 84 937), sunrise time and time of sample collection were the most important factors influencing median cortisol. Over 2 hours in the morning cortisol could decrease by up to 76 nmol/L, and for each hour that sunrise time advanced there was up to 6.9% increase in cortisol. A cyclic seasonal pattern of cortisol was confirmed each year in all populations with autumn/winter cortisol highest compared to spring/summer with differences of up to 44 nmol/L. There was less change in cortisol in latitudes closer to the equator but cortisol progressively increased from 25 to 30°S of the equator. In more southerly latitudes, seasonal cortisol variation also increased, and over the entire latitude range, there was up to 50 nmol/L change in cortisol. Longitude variation within a time zone had a minimal effect on median cortisol. CONCLUSIONS: Location, time of year and time of day are important influences on population cortisol levels. Elevated autumn/winter morning cortisol levels are likely due to sampling closer to the circadian peak due to later sunrise time. Understanding how the environment can influence cortisol levels may further our knowledge of physiology and disease.

Quantifying the intraindividual variation of antimüllerian hormone in the ovarian cycle.

OBJECTIVE: To quantify intraindividual variability of antimüllerian hormone (AMH) as analytical and biological coefficients of variation and assess the effects of variation on clinical classification. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Thirty-eight women referred by general practitioners. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Total intraindividual variability (CVW), analytical (CVA) and biological variability (CVI) for each woman and for AMH ranges: low (<5 pmol/L), reduced (5-10), moderate (>10-30) and high (>30 pmol/L), with calculation of proportion of women crossing clinical cutoffs and expected variability around each cutoff. RESULT(S): Cycling women (n = 38) contributed 238 blood samples (average 6 samples each). The average total intraindividual AMH variability was 20% (range: 2.1% to 73%). Biological variation was 19% (range: 0 to 71%) and at least twice the analytical variation of 6.9% (range: 4.5% to 16%). Reclassification rates were highest in women with low (33%) or reduced AMH (67%) levels. Expected variations around the 5, 10, and 30 pmol/L cutoffs were 3-7, 7-13, and 20-40 pmol/L, respectively. In a woman with mean AMH in the 10-30 pmol/L range, the span of results that could occur was 7-40 pmol/L. CONCLUSION(S): Total variation in AMH was 20%, and the majority of this was biological. Changes in AMH resulted in reclassification in 29% of women and occurred most frequently in those with low and reduced AMH. In cycling women, the variability in AMH should be considered by clinicians, especially if a result is close to a clinical cutoff.

Nostrils of healthy volunteers are independent with regard to Staphylococcus aureus carriage.

The right and left nares of healthy adults (n = 251) were swabbed separately to determine carriage of Staphylococcus aureus in each nostril. Carriers were significantly more likely to carry S. aureus in one nostril than in both. Of those carrying S. aureus in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of S. aureus.

GC/MS identification of toxic pyrrolizidine alkaloids in traditional remedies given to two sets of twins.

Neo- and perinatal mortality is high in most of Africa. Twins are at particular risk of perinatal mortality. The contribution of traditional remedies is seldom addressed. The case histories of two sets of twins who were treated with traditional remedies are described. The herbal remedies were analysed using gas chromatography-mass spectrometry. In one family, both siblings survived, albeit with hepatic damage. In the other family, one twin died within 24 h and the second one month after admission with a diagnosis of veno-occlusive liver disease (VOD). In both cases, the presence of the toxic pyrrolizidine alkaloid retrorsine, which is known to lead to VOD, was identified. Health-care workers should be aware of the possibility of traditional medicine administration as a cause of illness, specifically in twin births.