Synacthen Stimulation Test Research Articles

The study of serum cortisol in patients prescribed glucocorticoid in Hue University of Medicine and Pharmacy Hospital

Background: The adrenal disorders such as adrenal insufficiency and Cushing syndrome may be life-threatening unless patients are diagnosed and treated timely. Taking exogenous glucocorticoid (GC) interfered with the interpretation of the level of serum cortisol in either diagnosis of adrenal insufficiency or evaluation the function of hypothalamic-pituitary-adrenal axis. Objectives: 1) Evaluating the difference between the level of basal serum cortisol before and after taking GC. 2) Evaluating the level of basal serum cortisol in patients who were prescribed physiological dose of GC when withdrawn. Materials and method: This is a cross-sectional study that enrolled patients prescribed GC. It obtained the levels of basal serum cortisol before and after taking GC. In 2nd objective, the level of basal serum cortisol was measured in patients who were diagnosed with GC-induced adrenal insufficiency and prescribed physiological dose of GC when withdrawn temporarily. Results: The values of basal serum cortisol when taking hydrocortisone and prednisolone were higher than before prescribed (p < 0.05). In contrast, the values of basal serum cortisol when taking fluticasone were lower than before prescribed (p < 0.05). Even inhaled fluticasone could affect the level of basal serum cortisol. In GC-induced adrenal insufficiency patients prescribed physiological dose of GC, the group of patients with the values of cortisol when withdrawn < 100 nmol/L accounted for 61.9% while ones with the values 100 - 375 nmol/L accounted for 38.1%. The analysis of ROC curve shows that the duration of physiological-dose-GC prescription could predict the levels of basal serum cortisol when withdrawn and hypothalamic-pituitary-adrenal axis recovery with optimal cut-off of duration is 13 months (Sensitivity: 100%, specificity: 92.3%). Conclusion: Exogenous glucocorticoid could affect the results of basal serum cortisol. The duration of physiologic-dose-GC prescription could predict that hypothalamic-pituitary-adrenal axis recovery in patients with glucocorticoid-induced-adrenal insufficiency could be happened and who could achieve adequate response of Synacthen stimulation test. Key words: cortisol, glucocorticoid, hydrocortisone, methylprednisolone, fluticasone, dexamethasone, cross-reactivity.

The 1 μg Synacthen stimulation test in the diagnosis of secondary adrenal insufficiency in patients with Rathke's cleft cyst and empty sella syndrome.

Rathke's cleft cyst (RCC) and primary empty sella syndrome (PESS) are usually incidental findings on magnetic resonance imaging (MRI) scans. In most cases, these lesions do not cause mass effect symptoms and do not require surgical intervention. In patients with RCC or PESS, it is important to exclude secondary adrenal insufficiency (SAI), which may be a life-threatening condition. The incidence of SAI was assessed in patients with RCC or PESS detected by MRI, using the 1 μg Synacthen stimulation test. A total of 38 patients were analysed. Test results were linked to clinical symptoms and the type of cystic lesion. Assuming that cortisol levels < 14.6 μg/dL in Synacthen test are the criterion of SAI diagnosis, SAI was diagnosed only in 2 patients (5%). Adopting the traditional criterion of cortisol levels < 18 μg/dL, SAI would be diagnosed in 7 patients (18.4 %). Dizziness (Chi2 = 3.89; p = 0.049) and apathy (Chi2 = 3.87; p = 0.049) were significantly more frequent in the PESS group than in the RCC group. The incidence of SAI in the general patient population with empty sella syndrome and Rathke's cleft cysts is low. The 1 μg Synacthen test seems to be a valuable tool in the diagnosis of SAI among patients with RCC and PESS. Further studies are necessary to determine the sensitivity and specificity of the 1 μg Synacthen test with the standardization of test protocol and considering the cortisol level at the 20-minute timepoint. PESS patients report dizziness and apathy more frequently than RCC patients, which does not result from the disturbance of the hypothalamic-pituitary-adrenal axis, but probably from the different pathogenesis of these cystic lesions.

Diagnostic performance of an automated immunoassay for salivary cortisol

Automated immunoanalysis (AI) is an interesting alternative for measuring salivary cortisol, as the gold standard HPLC-MS/MS method is not yet readily available. The aim of this study was to evaluate the diagnostic performance of salivary cortisol immunoassay on the iSYS immunoanalyzer in adrenal dynamic tests. Cortisol was measured on iSYS and on HPLC-MS/MS in saliva samples collected after 1mg-dexamethasone suppression test (DST) in 115 patients suspected of Cushing syndrome, and during Synacthen® stimulation test (SST) in 108 patients suspected of adrenal insufficiency. Concentrations on AI correlated well with HPLC-MS/MS (Spearman r=0.9496; P<0.0001), but with a significant positive bias. ROC analysis of salivary cortisol identified optimal cut-off values on AI and HPLC-MS/MS of respectively 3.5 and 0.77nmol/L for DST and 32.6 and 13.8nmol/L at T60 after SST. Automated immunoassays for salivary cortisol are suitable in daily practice but require determination of specific cut-off and reference values.

Dehydroepiandrosterone sulfate to cortisol ratio as a prognostic factor in cirrhotic patients with spontaneous bacterial peritonitis

BackgroundChronic liver disease and decompensated cirrhosis are associated with serious complications; spontaneous bacterial peritonitis is considered one of them that may lead to sepsis and adrenal insufficiency. This trial aimed to study the role of dehydroepiandrosterone sulfate (DHEAS) and DHEAS/cortisol ratio for assessing cirrhotic patients’ adrenal function and as a possible prognostic factor in cirrhotic cases with spontaneous bacterial peritonitis (SBP).Patients and methodsIt was a prospective cohort trial carried out on 100 patients in the Internal Medicine Department, Tanta University Hospital, from June 2021 to July 2022 divided into 2 studied patient groups: group I, 50 cases with liver cirrhosis and sterile ascites; and group II, 50 cases with liver cirrhosis and SBP. Adrenal function was evaluated using serum cortisol levels (9 A.M, 9 P.M, and post synacthen stimulation test), DHEAS level, and DHEAS/cortisol ratio.ResultsThe cirrhotic patients with SBP have significantly decreased DHEAS, decreased DHEAS/cortisol ratio, and high cortisol level post stimulation compared with patients with sterile ascites, cirrhotic cases with decreased DHEAS/cortisol ratio (< 0.65) had elevated C-reactive protein (CRP) levels, a higher model for end-stage liver disease (MELD) score and Child–Pugh score had higher hospital mortality. Both DHEAS and the DHEAS/cortisol ratio were significant predictors of hospital mortality (area under the receiver operating characteristic curve 0.267 and 0.298, respectively). The cirrhotic patients with SBP had decreased DHEAS and DHEAS/cortisol ratio but higher hospital mortality, compared to the cirrhotic patients with sterile ascites.ConclusionsIt was found that a significant increase in cortisol level was after synacthen stimulation, decreased DHEAS, and low DHEAS to cortisol ratio in the cirrhotic patients with spontaneous bacterial peritonitis and was associated with high mortality compared to cirrhotic patients without spontaneous bacterial peritonitis.

Real world evidence supports waking salivary cortisone as a screening test for adrenal insufficiency.

Worldwide, adults and children are at risk of adrenal insufficiency largely due to infectious diseases and adrenal suppression from use of anti-inflammatory glucocorticoids. Home waking salivary cortisone is an accurate screening test for adrenal insufficiency, it has potential to reduce costs, and patients prefer it to the adrenocorticotropin (ACTH) (synacthen) stimulation test. We carried out a service evaluation of home waking salivary cortisone in clinical care to identify implementation barriers. Service evaluation in a centre where 212 patients referred for adrenal insufficiency had a waking salivary cortisone. Problems encountered during testing were recorded and patient feedback, via focus groups,collected. From all patients providing a waking salivary cortisone 55% had a normal test, 23% adrenal suppression, and 22% an equivocal result requiring a clinical centre ACTH stimulation test. The median (interquartile range [IQR]) for the time of the saliva sample was 07:40 (07:00-08:40). The median (IQR) days between collection and (i) delivery to local laboratory was1 (0.25-2) day; (ii) reporting by local laboratory was 13 (11-18) days. Patients considered the test is "easy to do" and preferred it to the inpatient ACTH stimulation test. The principal challenge to clinical implementation was results reporting to clinicians due to delays at the local laboratory. This service evaluation provides real-world evidence that home waking salivary cortisone is an effective, practical screening test for adrenal insufficiency. It identified key barriers to testing implementation that need to be addressed when introducing the test to a health service.

Serum 21-Deoxycortisol for Diagnosis of Nonclassic Congenital Adrenal Hyperplasia in Women With Androgen Excess.

Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies. We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17-hydroxyprogesterone (17OHP). A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by receiver operating characteristic analysis. Basal 17OHP, stimulated 17OHP, and 21DF were measured in 99, 85, and 42 participants, respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L, and 13.6 for stimulated 17OHP, 21DF, and the ratio (21DF + 17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5%, and 85.0%, respectively. LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS.

Prolonged Adrenal Insufficiency after Unilateral Adrenalectomy for Cortisolic Adenoma

Background: The suppression of the hypothalamic-pituitary-adrenal axis by cortisol-secreting adrenocortical tumors is well recognized and requires peri- and postoperative hydrocortisone substitution. Case Presentation: A 48-year-old female patient with hypertension and progressive weight gain, the clinical signs of hypercorticism motivated a hormonal workup revealing an independent ACTH Cushing’s syndrome: with urinary free cortisol (UFC) at 649 nmol/24h (4× normal), adrenocorticotropin hormone (ACTH) at 1.5 ng/l. The rest of the hormonal workup was not performed due to a lack of financial means. An Adrenal CT scan showed a 4 cm right adrenal adenoma. The patient underwent a right adrenalectomy with an adrenal adenoma on pathological examination. The contralateral side was normal. The patient was treated with hydrocortisone 30 mg/d for 6 weeks then 15 mg/d, during the monitoring we noted a persistence of the adrenal insufficiency for now 4 years. Basal cortisol levels during follow-up were very low (synacthen stimulation tests. Conclusion: Adrenal cortisol tumors are recognized by suppression, the duration of hypothalamic-pituitary-adrenal axis suppression is variable from 11 to 60 months depending on the series, which depends on the duration, severity of hypercortisolism, tumor size and other unknown factors. A longer follow-up of these patients is necessary to look for recovery of the contralateral adrenal gland.

Peak cortisol level on synacthen stimulation test in cushing's disease

Peak cortisol level on synacthen stimulation test in cushing's disease

17-Hydroxyprogesterone Response to Standard Dose Synacthen Stimulation Test in CYP21A2 Heterozygous Carriers and Non-carriers in Symptomatic and Asymptomatic Groups: Meta-analyses

Objective:Standard dose synacthen stimulation test (SDSST) is a gold standard screening test for evaluating adrenal gland function. Despite studies using SDSST to identify heterozygosity in CYP21A2, the reliability of the test for this purpose is still controversial. Therefore, the meta-analyses were performed to determine the differences in 17-hydroxyprogesterone (17-OHP) responses to standard dose (0.25 mg) SDSST in the diagnosis of CYP21A2 heterozygous individuals, with or without clinical signs of androgen excess disorders.Methods:PubMed and MEDLINE databases were searched. A total of 1215 subjects (heterozygous carriers n=669, mutation-free controls n=546) were included in the meta-analyses.Results:Basal 17-OHP median/mean levels were 4.156 (3.05-10.5)/5.241 (±2.59) nmol/L and 3.90 (2.20-9.74)/4.67 (±2.62) nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Stimulated 17-OHP median/mean levels were 17.29 (14.22-37.2)/19.51 (±7.63) nmol/L and 9.27 (7.32-15.9)/10.77 (±3.48) nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Basal 17-OHP median/mean levels were 3.21 (2.64-4.78)/3.33 (±0.84) nmol/L and 3.12 (1.82-3.6)/2.83 (±0.71) nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. Stimulated 17-OHP median/mean levels were 14.16 (12.73-16.37)/14.16 (±1.37) nmol/L and 6.26 (4.9-8.23)/6.48 (±1.2) nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. The cut-off levels for stimulated 17-OHP were 10.48 nmol/L and 13.48 nmol/L for asymptomatic heterozygous and symptomatic heterozygous, respectively.Conclusion:The meta-analyses support the idea that stimulated 17-OHP level has potential for use in identifying CYP21A2 carriers. Besides, considering differences in the basal and stimulated 17-OHP levels in symptomatic heterozygous individuals compared to those who were asymptomatic heterozygous could increase the accuracy of the test.

Basal serum cortisol levels predict a normal response to the Synacthen stimulation test in hospitalised patients.

The short Synacthen test (SST) is widely used to assess the hypothalamus-pituitary-adrenal axis in the outpatient setting. However, in the inpatient setting, technical difficulties to adhere to the protocol may pose a challenge for using this test. To find the most suitable basal serum cortisol (BSC) cut-off for predicting an adequate response to the SST in non-critically inpatients without conducting the actual test. Information was retrieved retrospectively from medical files of 197 patients who had had a 250 μg SST between the years 2000 and 2016 at the Shaare Zedek Medical Center. BSC, electrolytes, creatinine, thyroid-stimulating hormone, blood counts and blood pressure values were evaluated for a correlation with the results of the SST. A BSC cut-off of 280 nmol/L provides a negative predictive value of 94% for adrenal insufficiency (AI). Using a cut-off of 380 nmol/L increases the sensitivity to 96% and yields a negative predictive value of 95.8%. In this study, we found two suitable BSC cut-offs for predicting an adequate response to the SST in hospitalised patients. We suggest using the lower cut-off (280 nmol/L) for patients with a low level of suspicion for AI and using the higher cut-off (380 nmol/L) for patients with a higher level of suspicion. A BSC above this cut-off makes the diagnosis of AI very unlikely and precludes the need for a Synacthen test.

Clinical profile, etiology, and diagnostic challenges of primary adrenal insufficiency in Sudanese children: 14-years' experience from a resource limited setting.

Primary adrenal insufficiency (PAI) in children is an uncommon condition. Congenital adrenal hyperplasia (CAH) is the commonest cause followed by autoimmune disorders. Diagnosis and management are challenging especially in resource-limited settings. Studies from Africa are scanty and here we describe for the first time the clinical presentation, possible etiologies, and challenges in diagnosis and management of PAI in a large cohort of Sudanese children. This was a descriptive hospital-based study where all patients diagnosed with PAI between 2006 and 2020 were reviewed. The diagnosis was based on clinical presentation, low morning cortisol±high adrenocorticotropic hormone (ACTH), or inadequate response of cortisol to synacthen stimulation. Challenges faced in diagnosis and management were identified. From 422 PAI suspected patients, 309 (73.2%) had CAH, and 33 (7.8%) had PAI-like symptoms and were not furtherly discussed. Eighty patients (19%) had fulfilled the study criteria: 29 had Allgrove syndrome, nine auto-immune polyendocrinopathy syndrome, seven adrenoleukodystrophy, and one had an adrenal hemorrhage. Hyperpigmentation was the cardinal feature in 75 (93.8%) while the adrenal crisis was not uncommon. Lack of diagnostic facilities has obscured the etiology in 34 (42.5%) patients. PAI is not uncommon in Sudanese children where genetic causes outweigh the autoimmune ones. Many cases were missed due to nonspecific presentation, lack of awareness, and difficult access to tertiary health care facilities. In addition to the clinical findings, early morning cortisol±ACTH levels can be used in diagnosis where facilities are limited particularly synacthen stimulation test.

Synacthen Stimulation Test Following Unilateral Adrenalectomy Needs to Be Interpreted With Caution.

BackgroundCortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.MethodsData were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing’s syndrome were excluded.ResultsThe median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.ConclusionsSynacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Overt and Subclinical Adrenal Insufficiency in Pulmonary Tuberculosis

BackgroundTuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency. MethodsThis cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required. ResultsEighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (μg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease. ConclusionThe prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.

Early Basal Cortisol Level as a Predictor of Hypothalamic-Pituitary-Adrenal (HPA) Axis Function After Pituitary Tumor Surgery.

The purpose of this study was to evaluate the clinical relevance of the early postoperative basal cortisol level in assessing the postoperative hypothalamic-pituitary-adrenal (HPA) axis function after pituitary tumor surgery. We performed a prospective observational study that enrolled 83 patients operated for pituitary adenoma or other sellar lesions at the University Hospital Center Zagreb between December 2013 and April 2017 (44 nonfunctioning pituitary adenomas, 28 somatotropinomas, 5 craniopharyngiomas, 2 prolactinomas resistant to medical therapy and 4 other lesions - Rathke's cleft cyst, arachnoid cyst, chondroma and gangliocytoma). Exclusion criteria were Cushing's disease, chronic therapy with glucocorticoids prior to surgery and preoperative adrenal insufficiency. Early postoperative basal cortisol levels (measured on the second postoperative day) and the Synacthen stimulation test (performed 3 months after the surgery with the peak cortisol level of>500 nmol/L considered as a normal response) were analyzed to assess HPA axis function during follow-up. ROC analysis showed a cut-off of the basal cortisol level of ≥300 nmol/L measured on the second postoperative day to predict normal postoperative HPA axis function with the sensitivity of 92.31%, specificity of 87.14% and positive predictive value of 57.14%. The basal cortisol level on the second postoperative day is a valuable tool to predict integrity of the HPA axis after pituitary tumor surgery. Our data suggest that the cortisol level of ≥300 nmol/L accurately predicts adrenal sufficiency and that in these patients glucocorticoid therapy can be withdrawn.

Glucocorticoid induced adrenal insufficiency is common in steroid treated glomerular diseases - proposed strategy for screening and management

BackgroundGlucocorticoids (GCs) are frequently used to treat glomerular diseases but are associated with multiple adverse effects including hypothalamic-pituitary-adrenal axis inhibition that can lead to adrenal insufficiency (AI) on withdrawal. There is no agreed GC tapering strategy to minimise this risk.MethodsThis is a single centre retrospective study, between 2013 to 2016, of patients with glomerular disease on GC therapy for more than 3 months screened for GC induced AI with short synacthen stimulation tests (SSTs) done prior to complete GC withdrawal. We investigated the prevalence of AI, predictors, choice of screening tool and recovery.ResultsBiochemical evidence of GC induced AI was found in 57 (46.3%) patients. Total duration of GC did not differ between those with and without AI (p = 0.711). Patients with GC induced AI had a significantly lower pre-synacthen baseline cortisol as compared to patients without AI. A cut off pre-synacthen baseline cortisol of ≥223.5 nmol/l had a specificity of 100% for identifying individuals without biochemical AI. Patients with GC induced AI took a mean of 8.7 ± 4.6 months (mean ± SD) to recover. Patients with persistent AI had a significantly lower index post-synacthen cortisol measurement.ConclusionsWe demonstrate that biochemically proven GC induced AI is common in patients with glomerular diseases, is not predicted by daily dose or duration and takes a considerable time to recover. The study supports the use of morning basal cortisol testing as an appropriate means to avoid the need for SSTs in all patients and should be performed in all patients prior to consideration of GC withdrawal after 3 months duration.

Diabetes insipidus and panhypopituitarism in a neonate with congenital toxoplasmosis

Objectives – Although congenital toxoplasmosis (CTox) is asymptomatic in most cases, some infants/neonates present with variable clinical manifestations, including anaemia, jaundice, hepatosplenomegaly, seizures, hydrocephalus, chorioretinitis and sensorineural deafness. Involvement of the hypothalamic-pituitary axis is rarely reported with CTox. Case report – We present a full term baby girl who was admitted to the hospital on the 15th day of her life, due to an intense tremor and irritability. Brain ultrasound and CT exam revealed calcifications of the brain parenchyma and severe ventriculomegaly. Serological and molecular findings (positive specific immunoglobulin M and immunoglobulin G antibodies, polymerase chain reaction) confirmed CTox. After diagnosis was established, specific therapy with pyrimethamine, sulfodiazine and folic acid was started. On the fifth day of hospitalisation, laboratory findings revealed high serum sodium and chloride, high serum osmolality, low urine osmolality and low urine specific gravity. Since these findings strongly suggested the diagnosis of diabetes insipidus (DI) in this new born, further endocrinological workup was performed to assess the pituitary function. An ACTH (synacthen) stimulation test showed a low basal cortisol level with a positive response after administration of synacthen. The free thyroxin level was also low and repeated prolactin levels were high. On the basis of these findings, it was concluded that this new born has panhypopituitarism and diabetes insipidus. Hormonal substitution therapy with hydrocortisone, L-thyroxine and desmopressin was started and gradual normalization of electrolytes and hormonal status was noted. Conclusion – A continuous endocrinological monitoring of a child with CTox is important and necessary for early detection, timely therapy and prevention of severe sequelae.

A time-adjusted cortisol cut-off can reduce referral rate for Synacthen stimulation test whilst maintaining diagnostic performance.

Cortisol cut-offs can predict requirement for Synacthen stimulation tests (SST). We assessed the performance of a standard cortisol cut-off (375nmol/L) across the morning and compared this with a time-adjusted cut-off. Retrospective audit PATIENTS: Community reference set (n=12 550) and SST patients (n=757). In the reference population, time-specific cortisol medians were calculated and used to convert cortisol to time-adjusted Multiples of the Median (MoM). In 757 SST patients, the predictive performance of a standard cortisol cut-off (375nmol/L) and its time-adjusted MoM equivalent were compared. Median cortisol decreased by ~30nmol/L per hour between 0700 and 1200h. In the reference population, proportions below the 375nmol/L cut-off increased throughout the morning (range 35%-64%), whereas using the time-adjusted MoM cut-off proportions were consistent (range 46%-50%), with a 17% maximal difference in referral rates between the two cut-offs after 1100h. A similar pattern was noted in the SST cohort. When a cortisol MoM cut-off was used to predict SST success, the excess proportion of patients tested and misclassification rates were lower and more consistent than when the standard cut-off was used. A median cortisol of 375nmol/L equated to 444 and 313nmol/L before 0800 and after 1100 h, respectively. The use of a standard cortisol cut-off results in 17% more patients being referred for SST later in the morning. A time-adjusted cortisol cut-off provides consistent and lower referral rates, whilst maintaining similar or better performance than a standard single cut-off in predicting outcome of SST.

Severe paraneoplastic hypoglycemia secondary to a gastrointestinal stromal tumour masquerading as a stroke.

SummaryWe report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0′) 390 nmol/l, Cort (30′) 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period.Learning pointsNICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms.NICTH can masquerade as other pathologies thus causing diagnostic confusion.Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential.Mutational analysis of GISTs should be carried out in all cases as it guides treatment decision.Tailored management of hypoglycaemia, in this case using growth hormone and targeted cyto-reductive therapy, minimizes the risk of possible life-threatening complications.

Adrenal suppression in patients taking inhaled glucocorticoids is highly prevalent and management can be guided by morning cortisol.

ContextUp to 3% of US and UK populations are prescribed glucocorticoids (GC). Suppression of the hypothalamo–pituitary–adrenal axis with the potential risk of adrenal crisis is a recognized complication of therapy. The 250 μg short Synacthen stimulation test (SST) is the most commonly used dynamic assessment to diagnose adrenal insufficiency. There are challenges to the use of the SST in routine clinical practice, including both the staff and time constraints and a significant recent increase in Synacthen cost.MethodsWe performed a retrospective analysis to determine the prevalence of adrenal suppression due to prescribed GCs and the utility of a morning serum cortisol for rapid assessment of adrenal reserve in the routine clinical setting.ResultsIn total, 2773 patients underwent 3603 SSTs in a large secondary/tertiary centre between 2008 and 2013 and 17.9% (n=496) failed the SST. Of 404 patients taking oral, topical, intranasal or inhaled GC therapy for non-endocrine conditions, 33.2% (n=134) had a subnormal SST response. In patients taking inhaled GCs without additional GC therapy, 20.5% (34/166) failed an SST and suppression of adrenal function increased in a dose-dependent fashion. Using receiver operating characteristic curve analysis in patients currently taking inhaled GCs, a basal cortisol ≥348 nmol/l provided 100% specificity for passing the SST; a cortisol value <34 nmol/l had 100% sensitivity for SST failure. Using these cut-offs, 50% (n=83) of SSTs performed on patients prescribed inhaled GCs were unnecessary.ConclusionAdrenal suppression due to GC treatment, particularly inhaled GCs, is common. A basal serum cortisol concentration has utility in helping determine which patients should undergo dynamic assessment of adrenal function.

Effects of leukemia inhibitory receptor gene mutations on human hypothalamo-pituitary-adrenal function.

Stuve-Wiedemann syndrome (STWS) (MIM #601559) is a rare autosomal recessive disorder caused by mutations in the leukemia inhibitory factor receptor (LIFR) gene. STWS has a diverse range of clinical features involving hematopoietic, skeletal, neuronal and immune systems. STWS manifests a high mortality due to increased risk of sudden death. Heterodimerization of the LIFR mediates leukemia inhibitory factor (LIF) signalling through the intracellular Janus kinase (JAK)/STAT3 signalling cascade. The LIF/LIFR system is highly expressed in and regulates the hypothalamo-pituitary-adrenal (HPA) axis. HPA function was investigated in three STWS patients to characterise consequences of impaired LIF/LIFR signalling on adrenal function. Six genetically proven STWS patients from four unrelated Turkish families were included in the study. Sudden death occurred in three before 2years of age. Basal adrenal function tests were performed by measurement of early morning serum cortisol and plasma ACTH concentrations on at least two different occasions. Low dose synacthen stimulation test and glucagon stimulation tests were performed to explore adrenal function in three patients who survived. All patients carried the same LIFR (p.Arg692X) mutation. Our oldest patient had attenuated morning serum cortisol and plasma ACTH levels at repeated measurements. Two of three patients had attenuated cortisol response (<18μg/dl) to glucagon, one of whom also had borderline cortisol response to low dose (1μg) ACTH stimulation consistent with central adrenal insufficiency. STWS patients may develop central adrenal insufficiency due to impaired LIF/LIFR signalling. LIF/LIFR system plays a role in human HPA axis regulation.