Early Morning Cortisol Levels Research Articles

Evaluation of early morning cortisol levels compared to short synacthen test to assess adrenal function

Evaluation of early morning cortisol levels compared to short synacthen test to assess adrenal function

Feminizing adrenocortical adenoma in a girl from a resource-limited setting: a case report

BackgroundAn adrenocortical tumor is a rare tumor in pediatrics, which can be functional or nonfunctional. Functional tumors present with virilization, feminization, or hypercortisolism. Feminizing adrenal tumors, though rare in pediatrics, need to be excluded in any child presenting with features of feminization. Case presentationWe report a case of a 4-year-old Sudanese girl who presented with gradually progressive bilateral breast enlargement and accelerated growth since the age of 6 months. The family had sought medical advice several times in numerous health facilities without much gain. Investigations showed pubertal luteinizing hormone levels, high estradiol E2, and dehydroepiandrosterone sulfate, with normal early morning cortisol level. Abdominal ultrasound revealed a right-sided hypoechoic suprarenal mass. Abdominal computed tomography scan showed a right adrenal mass. The diagnosis of feminizing adrenal neoplasm was confirmed and right adrenalectomy was done. Histopathological examination of the resected adrenal gland showed adrenocortical adenoma. The patient was started on gonadotrophin-releasing hormone agonist for secondary central precocious puberty.ConclusionAdrenocortical tumors, though rare in pediatrics, are a documented cause of precocious puberty; biochemical and imaging screening protocol should be adopted for patients with precocious puberty, even in a resource-limited setting, for early detection and treatment.

A rare case of macroprolactinoma in a patient with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.

SummaryA 17-year-old lady presented with primary amenorrhoea, headache, nausea and lethargy. She had delayed pubertal development that also includes under-developed breast (Tanner Stage 2). Hormonal investigations showed a high serum prolactin level of 1 680 000 mIU/L (normal value: 45–375 mIU/L), with low oestradiol, progesterone, follicular-stimulating hormone and luteinizing hormone. Early morning cortisol level was 206 nmol/L (normal value: >450 nmol/L), thyroxine was 7.5 pmol/L (normal value: 9.0–24.0 pmol/L) with TSH 5.091 mIU/L (normal value: 0.4–4.5 mlU/L). A pituitary MRI showed a 2.7 (AP) × 3.7 (W) × 4.6 cm (CC) macroadenoma, with invasion into the left cavernous sinus and encasement of cavernous portion of the left internal carotid artery. MRI pelvis showed absent uterus, cervix and 2/3 upper vagina confirming Mullerian hypoplasia. Cytogenetics showed 46XX. These findings were suggestive of Mayer–Rokitansky–Kauser–Hauser (MRKH) syndrome with the presence of a pituitary macroprolactinoma and panhypopituitarism. She was treated with hydrocortisone, levothyroxine and cabergoline. Repeated MRI showed a reduction in tumour size by approximately 50%. This case illustrated a rare coexistence of these two conditions, being only the third reported case in the world. In addition, this would be the first case of a functioning pituitary adenoma in a patient with MRKH syndrome.Learning pointsComprehensive hormonal and radiological investigations are important in the management of a young patient with primary amenorrhoea.Coexistence pathology of two separate pathologies should be considered in patient presenting with primary amenorrhoea.Early diagnosis of MRKH or any disorders of sex development should be treated early, providing pharmacological, surgical, psychological and emotional support to the patient and reducing risk of associated complications.Abnormal pituitary hormones, particularly panhypopituitarism, would impose greater impact not only psychologically but also metabolically leading to cardiovascular, morbidity and mortality risks in this patient if not treated early.A multidisciplinary approach is necessary for patients presenting with MRKH to ensure appropriate treatments and follow-up across the lifespan of the patient.

Transsphenoidal pituitary adenoma resection: do early post-operative cortisol levels predict permanent long-term hypocortisolism?

Transsphenoidal surgery provides a minimal invasive treatment for pituitary adenoma. Our aim is to evaluate the endocrinological outcomes after adenoma resection focusing on the corticotroph function, and to identify prognostic factors for an impaired hypothalamic–pituitary–adrenal-axis function (HPA) and the reliability of postoperative early morning serum cortisol measurements. We performed a retrospective analysis of all patients treated for pituitary adenoma from April 2006 to January 2019 in our neurosurgical department. Pituitary function was assessed pre- and postoperatively as well as at 6 weeks to 12 weeks and at 1-year follow-up. Two hundred eleven patients were included. Nine percent of the patients recovered from a preoperative adrenal insufficiency, 10.4% developed a new need for hormone substitution, and a long-term deficiency of the hypothalamic–pituitary–adrenal-axis was observed in 30.9%. Cortisol measurements 5 days after surgery had a lower area under the curve (AUC) than cortisol levels detected after 6 to 12 weeks (AUC 0.740 vs. AUC 0.808) in predicting an intact corticotrope function. The cut-off value determined for cortisol measured after 6 weeks was 6.95 µg/dl (sensitivity of 94%, specificity of 68%). Postoperative early morning cortisol levels seem to be less sensitive and specific in predicting long-term corticotroph function than measurements after 6 weeks and 1 year, emphasizing the importance of endocrine follow-up testing.

Adrenal Insufficiency in Children With Nephrotic Syndrome on Corticosteroid Treatment

Background: Adrenal insufficiency can result from impaired functions at all levels of hypothalamic-pituitary-adrenal (HPA) axis. We here studied risk factors associated with adrenal insufficiency in children receiving prolonged exogenous steroid treatment for nephrotic syndrome.Method:We performed low-dose Synacthen tests (LDSTs, 0.5 μg/m2) in children with steroid-sensitive nephrotic syndrome 4–6 weeks after discontinuation of the corticosteroid therapy. We measured early morning serum cortisol levels at baseline and at intervals of 10, 20, 30, and 60 min following the stimulation test. We defined normal HPA axis stimulation responses as those with peak cortisol cut-off values >550 nmol/L.Result:We enrolled 37 children for this study research. All children enrolled had normal early morning cortisol levels. However, 13 (35.1%) demonstrated HPA axis suppression (by LDST) 4–+6 weeks after discontinuation of oral prednisolone. Nephrotic syndrome diagnosed before 5 years of age (OR, 0.75; 95% CI, 0.57–0.99; p = 0.043), and steroid-dependence [OR, 5.58; 95% confidence interval (CI), 1.06–29.34; p = 0.042] were associated with increased risk of developing adrenal suppression after steroid discontinuation.Conclusion:HPA axis suppression, may go unnoticed without proper screening. A normal early morning cortisol level (275–555 nmol/L) does not exclude adrenal insufficiency in children with steroid-sensitive nephrotic syndrome. Further screening with LDSTs, particularly in children younger than 5 years at diagnosis, may be warranted.

SAT-370 Clinical Characteristics and Metabolic Features of Patients with Subclinical Cushing's Syndrome and Its Correlation with Cortisol Level

Objective The aim of this study was to examine the clinical characteristics and metabolic features of subclinical Cushing’s syndrome (SCS), and to investigate the association of the cortisol level with the metabolic features in patients with SCS. Methods 52 patients with non-functioning adenoma (NFA), 45 patients diagnosed with SCS and 61 patients with overt adrenal Cushing’s syndrome (CS) participated in this study. Clinical data and endocrine function of the patients as well as histological findings were all reviewed. Results 1) The average age of patients with SCS was 52.56±13.25 years, 68.9% patients were female. No difference was detected in age, gender and BMI between patients with SCS and NFA (P > 0.05). Compared to patients with SCS, CS was more common in younger and female patients (43.90±13.83, 83.6%). The prevalence of diabetes mellitus, hypertension, and osteopenia/osteoporosis were significantly higher in patients with SCS compared to those with nonfunctioning tumors (57.8% vs 32.7%, 73.3% vs 53.8%, 41.2% vs 19.2%; P < 0.05). No difference was detected between SCS and CS patients in the prevalence of metabolic disease. 2) Compared to patients with NFA, plasma ACTH level is lower in patients with SCS (P < 0.05). Whereas, the midnight cortisol level and cortisol level after 1mg overnight dexamethasone suppression is higher in SCS than NFA (P < 0.05). No difference was detected between SCS and NFA in 24h urinary free cortisol and early-morning cortisol level (P > 0.05). Compared to SCS, the derangement of ACTH-cortisol axis is more prominent in CS patients demonstrated as suppressed plasma ACTH level and elevated plasma and 24h urine cortisol level. 3) In SCS cohort, SBP, FBG and HbA1c correlated positively with 24h urinary free cortisol (r =0.394, P =0.021; r =0.426, P =0.011, r =0.398, P =0.015; respectively). When controlling for age and gender, the correlation was also significant (P < 0.05). No correlations were found between BMI, TG, HDL and 24h urinary free cortisol. Conclusion Patients with SCS showed slight derangement of the circadian rhythm of cortisol and cortisol excess, and increased prevalence of metabolic disease. Furthermore, the cortisol level was related closely to blood glucose and blood pressure. Our findings might suggestive in therapeutic decision making (conservative vs surgery approach) in patients with SCS.

Prospective evaluation of a week one overnight metyrapone test with subsequent dynamic assessments of hypothalamic-pituitary-adrenal axis function after pituitary surgery.

SummaryObjective To determine whether an overnight metyrapone test (OMT) within the first week postpituitary surgery can definitively assess the hypothalamic-pituitary-adrenal (HPA) axis, compared with subsequent dynamic tests and glucocorticoid requirement at 6 months. Design Prospective study measuring morning cortisol levels on days 3 and 4 post-operatively, OMT day 5-7 and week 6, week 6 250 μg short Synacthen test (SST) and week 7 insulin tolerance test (ITT). Patients and Measurements Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) were followed for at least 6 months. 46% had pre-operative adrenal insufficiency. Primary outcome: week 1 OMT compared to glucocorticoid requirement at 6 months. Secondary outcomes: the performance of ITT as a “definitive” test and all tests compared to glucocorticoid requirement at 6 months. Results Week 1 OMT showed concordance with ITT at week 7 of 78% and glucocorticoid requirement at 6 months of 81% respectively which was not significantly different from post-operative morning cortisol levels; 37% of participants with an abnormal OMT on day 6 had a normal OMT at week 6. All HPA axis tests showed similar concordance with glucocorticoid requirement at 6 months of 80%-85%. Conclusions Overnight metyrapone test within the first week after pituitary surgery was no better than an early morning cortisol level at predicting glucocorticoid requirement at 6 months. OMT at week 6 demonstrated recovery of HPA axis in a substantial proportion of participants who failed earlier assessments; thus, definitive testing should be delayed until 6 weeks post-operatively.

Prospective evaluation of a week one overnight metyrapone test with subsequent dynamic assessments of hypothalamic-pituitary-adrenal axis function after pituitary surgery.

To determine whether an overnight metyrapone test (OMT) within the first week postpituitary surgery can definitively assess the hypothalamic-pituitary-adrenal (HPA) axis, compared with subsequent dynamic tests and glucocorticoid requirement at 6months. Prospective study measuring morning cortisol levels on days 3 and 4 post-operatively, OMT day 5-7 and week 6, week 6 250μg short Synacthen test (SST) and week 7 insulin tolerance test (ITT). Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) were followed for at least 6months. 46% had pre-operative adrenal insufficiency. week 1 OMT compared to glucocorticoid requirement at 6months. the performance of ITT as a "definitive" test and all tests compared to glucocorticoid requirement at 6months. Week 1 OMT showed concordance with ITT at week 7 of 78% and glucocorticoid requirement at 6months of 81% respectively which was not significantly different from post-operative morning cortisol levels; 37% of participants with an abnormal OMT on day 6 had a normal OMT at week 6. All HPA axis tests showed similar concordance with glucocorticoid requirement at 6months of 80%-85%. Overnight metyrapone test within the first week after pituitary surgery was no better than an early morning cortisol level at predicting glucocorticoid requirement at 6months. OMT at week 6 demonstrated recovery of HPA axis in a substantial proportion of participants who failed earlier assessments; thus, definitive testing should be delayed until 6weeks post-operatively.

The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors

Numerous studies have linked severe stress to the development of major depressive disorder (MDD) and suicidal behaviors. Furthermore, recent preclinical studies from our laboratory and others have demonstrated that in rodents, chronic stress and the stress hormone cortisol cause oxidative damage to mitochondrial function and membrane lipids in the brain. Mitochondria play a key role in synaptic neurotransmitter signaling by providing adenosine triphosphate (ATP), mediating lipid and protein synthesis, buffering intracellular calcium, and regulating apoptotic and resilience pathways. Membrane lipids are similarly essential to central nervous system (CNS) function because cholesterol, polyunsaturated fatty acids, and sphingolipids form a lipid raft region, a special lipid region on the membrane that mediates neurotransmitter signaling through G-protein-coupled receptors and ion channels. Low serum cholesterol levels, low antioxidant capacity, and abnormal early morning cortisol levels are biomarkers consistently associated with both depression and suicidal behaviors. In this review, we summarize the manner in which nutrients can protect against oxidative damage to mitochondria and lipids in the neuronal circuits associated with cognitive and affective behaviors. These nutrients include ω3 fatty acids, antioxidants (vitamin C and zinc), members of the vitamin B family (Vitamin B12 and folic acid), and magnesium. Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors. A growing body of studies suggests the intriguing possibility that regular consumption of these nutrients may help prevent the onset of mood disorders and suicidal behaviors in vulnerable individuals, or significantly augment the therapeutic effect of available antidepressants. These findings have important implications for the health of both military and civilian populations.

History of Stress-related Health Changes: A Cue to Pursue a Diagnosis of Latent Primary Adrenal Insufficiency

Routine delays in the diagnosis of primary adrenal insufficiency (PAI) are well known and conceivably attributable to the absence of cues, other than anti-adrenal autoantibodies, to pursue subclinical PAI. Subclinical PAI is latent unless the afflicted patient encounters stress such as an acute illness, surgery, psychosocial burden, etc. It remains to be demonstrated whether a history of stress-related health changes is a useful cue to pursue a diagnosis of latent PAI. The patients were selected for a history of recurrent symptoms, i.e., gastrointestinal symptoms, fatigue, or lassitude, aggravated by stress and alleviated by the removal of stress, and signs, i.e., weight loss, hypotension, and hyperpigmentation. As the early morning cortisol levels were low or low-normal and the adrenocorticotropic hormone (ACTH) levels were within the reference ranges, provocation tests, i.e., insulin-induced hypoglycemia tests and low-dose (1 μg) corticotropin tests (LDTs), were used to estimate the hypothalamus-pituitary-adrenal (HPA) axis status. Patients with the HPA axis dysfunction on two provocation tests were supplemented with physiologic doses of glucocorticoids (GCs). The effects of GC supplementation on stress-related health changes were observed. The ACTH levels after insulin-induced hypoglycemia were higher and the cortisol levels were lower in the patients than in the control subjects. The cortisol levels in the patients were increased less significantly by LDT than those observed in the control subjects. Stress-related health changes ceased to recur and signs, i.e., a low body weight, hypotension, and hyperpigmentation, were ameliorated following GC supplementation. A history of stress-related health changes is useful as a cue to pursue latent PAI in patients with low or low-normal early morning cortisol levels.

Atypical Hypocortisolism

To report a patient who had developed reversible hypocortisolism during the use of quetiapine. Early morning cortisol levels were measured on two separate days. In addition, the patient underwent testing with intravenous synthetic adrenocorticotropic hormone (1 mcg tetracosactide) before and after tapering of quetiapine. Pituitary function was assessed and magnetic resonance imaging (MRI) was performed. The patient had low early morning cortisol levels at presentation when using quetiapine. Tetracosactide testing indicated hypocortisolism. A MRI of the pituitary was unremarkable. The patient was treated temporarily with hydrocortisone and quetiapine was tapered. After quetiapine had been discontinued, the patient's cortisol production had returned to normal. Although lowering cortisol levels has been previously reported, this is the first report of hypocortisolism associated with the use of quetiapine. It is possible symptoms of malaise in patients who use quetiapine could be attributed to quetiapine-related hypocortisolism.

Hypoandrogenism in association with diminished functional ovarian reserve

Is diminished functional ovarian reserve (DFOR) associated with low androgen levels? Low androgen levels are associated with DFOR at all ages. Androgen supplementation via dehydroepiandrosterone (DHEA) has been reported to improve functional ovarian reserve (FOR); pregnancy rates in IVF cycles are associated with how well DHEA converts to testosterone (T); and androgen effects through the androgen receptor have been demonstrated in mice to beneficially affect early stages of follicle maturation. In a controlled cohort study we investigated consecutive women presenting to our center with two forms of DFOR, premature ovarian aging/occult primary ovarian insufficiency (POA/OPOI) and physiologic diminished ovarian reserve (DOR). As controls for POA/OPOI patients, infertile women with normal age-specific FOR were recruited. The study involved 140 women with POA/OPOI, defined as age <38 years and abnormally low FOR by age-specific FSH and/or anti-Müllerian hormone (AMH), 166 women with DOR, defined as women age >40 years. Forty-nine control patients <38 years demonstrated normal FOR by FSH and/or AMH. In all three patient groups dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), total testosterone (TT) and free testosterone (FT) at the time of initial presentation to our fertility center were assessed. In a small subgroup of women early morning cortisol levels were also assessed. DHEAS marginally varied between the three groups (P = 0.04), with older women with DOR actually demonstrating higher levels than controls (P = 0.03). TT differed between the three groups more profoundly (P = 0.005), with women with POA/OPOI demonstrating significantly lower levels than controls (P = 0.009). Adjustment for body mass index, age and race in principle maintained observed differences in TT between groups, while adjustment for FMR1 (fragile X mental retardation 1) genotypes/sub-genotypes eliminated all differences. All three patient groups demonstrated low morning cortisol levels. While results support lower androgen levels in women with DOR, and even more so in women with POA/OPOI, presented data should be viewed as preliminary, considering the known variability of androgen levels and the small number of women in whom morning cortisol levels were available. Especially at young ages DFOR appears associated with significant hypoandrogenism (low T) in comparison with young control patients with normal FOR, raising the question whether this hypoandrogenism originates in adrenals or ovaries. POA/OPOI, thus, phenotypically mimics the polycystic ovary syndrome, where similar questions arise, though in regard to hyperandrogenism. This research was supported by the Foundation for Reproductive Medicine, a not-for-profit medical research foundation and intramural funds from the Center for Human Reproduction. N.G. and D.H.B are members of the Board of the Foundation for Reproductive Medicine. N.G., A.W. and D.H.B. received research support, lecture fees and travel support from a variety of pharmaceutical and medical device companies, none in any way related to the issues discussed in this manuscript. N.G. and D.H.B. are listed as co-inventors on two, already granted US user patents, which claim therapeutic benefits from DHEA supplementation in women with DFOR and DOR: both authors are also listed on additional pending patents in regard to DHEA supplementation and on pending patents, claiming diagnostic and therapeutic benefits from the determination of CGG repeats on the FMR1 gene. N.G. is the owner of the Center for Human Reproduction, where this research was performed.

Stress, cortisol, and nighttime blood pressure dipping in nonhypertensive Black American women.

Black American women have among the highest hypertension (HTN) rates in the world. Research suggests that nighttime might be a critical period of vulnerability for the development of HTN in Blacks. In the present study, personal factors (age, body fat, income, family history), psychological factors (stress, emotions, and John Henryism), and physiological factors (salivary cortisol and blood pressure [BP]) were explored in 30 Black women, ages 26-51 years. Data were collected in participants' homes. BP was monitored while participants were awake and asleep. Cortisol samples were obtained within the first hour after awakening. The usual pattern for BP is a drop or dipping of 10-20% during sleep; however, the BP for about a third of the subjects did not dip adequately during sleep. Though not statistically significant, this nondipping was clinically relevant and was associated with positive family history of HTN, more stress, lower positive and higher negative affect scores, and higher early morning cortisol levels. These findings add to the HTN risk profile and support the need to further explore the relationship between nondipping nighttime BP and cardiovascular disease in Black women.

Patterns of salivary cortisol levels can manifest work stress in emergency care providers

To develop objective assessments of work fatigue, we investigated the patterns of changes in salivary cortisol levels in emergency care providers working extended work shifts. Fourteen subjects, comprising seven physicians and seven physician assistants, provided unstimulated saliva samples at regular intervals over the course of a 24-h work shift and over their subsequent free day. There was a significant time effect, with early morning cortisol levels being significantly attenuated following the work shift. Native diurnal variations varied by gender, with the female subjects manifesting greater cortisol levels. Physicians also had higher cortisol profiles even though their wake-rest cycles were similar to those of the physician assistants. Our results suggest that temporal changes, as well as diurnal similarities, in the salivary cortisol patterns can reflect work-related stress and recovery. In particular, early morning cortisol levels may manifest individual reactivity to work stressors as well as sleep deprivation.

Early Morning Cortisol Levels as Predictors of Short- and Long-Term Adrenal Function after Endonasal Transsphenoidal Surgery for Pituitary Adenomas and Rathke's Cleft Cysts

Introduction: Patients undergoing pituitary adenoma or Rathke's cleft cyst (RCC) removal are often administered perioperative glucocorticoids regardless of lesion size and preoperative ACTH/cortisol levels. To minimize unnecessary glucocorticoid therapy, we describe a protocol in which patients with normal preoperative serum cortisol and ACTH levels are given glucocorticoids only if postoperative day 1 or 2 (POD1 or POD2) cortisol levels fall below normal.

Lost in the Mist: Acute Adrenal Crisis Following Intranasal Fluticasone Propionate Overuse

Introduction. Acute adrenal crisis in relation to nasal steroid overuse has been reported very scantly in English medical literature and remains an underdiagnosed condition. Case presentation. A 55 year-old male presented with altered mental status, retrograde amnesia, fluid refractory hypotension, abdominal pain, fever, and chest pain. Physical examination revealed amnesia, bradypsychia, tachycardia, decreased muscle tone and hyporeflexia. Overuse of nasal steroid was suspected by history. Random early morning cortisol level was < 0.2 mcg/dL. The patient was started on hydrocortisone and within 24 hours he had a full recovery. Conclusion. This one-of-a-kind case describes acute adrenal crisis secondary to withdrawal from inhaled nasal corticosteroids overuse in a patient with particular risk factors. Prevention and early recognition of this disorder can significantly reduce its morbidity and mortality.

A longitudinal assessment of the effect of inhaled fluticasone propionate therapy on adrenal function and growth in young children with asthma

Fluticasone proprionate (FP) is increasingly used to treat very young children with asthma. Its safety in terms of effects on the hypothalamic pituitary axis (HPA) and growth in this age group is uncertain. Eleven children (median (range) age 10 (5.6-24.3) months) presenting with recurrent wheeze and family history of asthma were studied prospectively for a period of 18 months. Children received daily-inhaled FP 250 microg via a spacer device. No other corticosteroid therapy was administered prior to or during the study. A Short Standard Synacthen Test (SST) (125 microg) was performed pretreatment, and after 6 and 18 months. Weight (Wt), height (Ht), and body mass index (BMI) were measured at 3-6 monthly intervals. Fasting early morning and peak cortisol levels remained within the normal reference range with therapy. There were no changes in Ht SDS, whereas both Wt SDS (baseline 0.05 (-2.17 to 0.52) vs. +18 months 0.68 (-0.5 to 1.36) P < 0.02) and BMI SDS (-0.22 (-1.73 to 0.75) vs. 0.86 (0.03 to 1.99) P < 0.005) increased after 18 months of treatment. Daily treatment with inhaled FP 250 microg in young children with asthma appears to have no adverse effects on the HPA or on linear growth, however, treatment is associated with increases in body Wt and BMI in young children.

Cardiovascular risk factors at age 30 following pre-term birth

Recent epidemiological evidence has shown increased rates of cardiovascular mortality and associated risk factors in those born small. However, scarce information exists concerning cardiovascular risk factors in adulthood following pre-term birth, or distinguishing the relative contributions of length of gestation and fetal growth to small size at birth. Prospective follow-up of 458 30-year-olds whose mothers took part in a randomized controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (147 born at term, 311 born pre-term). Follow-up assessments included anthropometry, blood pressure, blood lipids, early morning cortisol levels and 75 g oral glucose tolerance test. Gestational age at birth, pre-term birth, and birth weight z-score were not associated with serum cholesterol, triglyceride or cortisol at age 30 (P > 0.1 for all). However, pre-term birth was associated with increased systolic blood pressure (3.5 mmHg, 95% CI 0.9-6.1 mmHg, P = 0.009) and insulin resistance at age 30 [Log (Insulin area under the curve) = 0.17, 95% CI 0.05-0.28, P = 0.006]. Low gestational age at birth was also associated with these outcomes, whereas birth weight, adjusted for gestational age, was not. Adults who were born moderately pre-term have increased blood pressure and insulin resistance at 30 years of age. Pre-term birth rather than poor fetal growth is the major determinant of this association. As both the incidence of pre-term birth and survival amongst those born pre-term are increasing, this group may contribute an increasing proportion to overall cardiovascular disease burden.

Early Morning Cortisol Levels as a Predictor of Remission After Transsphenoidal Surgery for Cushing’s Disease

We describe the use of serum cortisol and ACTH levels on postoperative d 1 and 2 as remission predictors after transsphenoidal surgery for Cushing's disease (CD). Morning cortisol and ACTH levels were drawn daily after surgery; glucocorticoids were withheld until evidence of hypocortisolemia. Early remission was defined retrospectively as a subnormal morning cortisol level [< or =140 nmol/liter (< or =5 microg/dl)] on postoperative d 1 or 2 and sustained remission as subsequent eucortisolemia. Of 40 consecutive adults with CD (mean age 39 yr), 80% achieved early remission. Of 39 patients with a minimum follow-up of 14 months (mean 33 months), 31 (79.5%) achieved sustained remission at a mean follow-up of 32 months, including 30 of 31 (97%) with early remission and one of eight (12%) without early remission (P < 0.0001). Sustained remission was achieved in 26 of 28 (93%) patients having their first operation, compared with five of 11 (45%) with a prior unsuccessful operation (P < 0.001). For the 32 patients in early remission vs. the eight in nonremission, mean nadir cortisol levels were 57.6 +/- 33.0 (2.05 +/- 1.2 microg/dl) vs. 631.1 +/- 352.2 nmol/liter (22.9 +/- 12.8 microg/dl) (P < 0.0001), and nadir ACTH levels were 11.9 +/- 6.5 vs. 64.1 +/- 54.6 ng/liter (P < 0.001). Of 31 patients with sustained remission, 100% had subnormal morning cortisol levels, whereas 31% had subnormal ACTH levels (P < 0.0001). Serum morning cortisol levels on postoperative d 1 and 2 without glucocorticoid replacement provide a safe, simple, and reliable measure of early remission for CD and are predictive of sustained remission. This method allows for consideration of a repeat operation during the same hospitalization in patients with persistent hypercortisolemia.

Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial

Antenatal betamethasone treatment is widely used for the prevention of neonatal respiratory distress syndrome in preterm infants and substantially reduces neonatal mortality and morbidity. Fetal exposure to excess glucocorticoids has been proposed as one of the core mechanisms of the fetal origins of adult disease hypothesis. We assessed whether antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome affects cardiovascular risk factors at 30 years of age. We followed up at age 30 years 534 individuals whose mothers participated in a double-blind, placebo-controlled, randomised trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Mothers received two doses of betamethasone or placebo given by intramuscular injection 24 h apart. Follow-up assessments included anthropometry; measurement of blood pressure, blood lipids (after overnight fasting), and early morning cortisol levels; and a 75 g oral glucose tolerance test. There were no differences between those exposed to betamethasone and to placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease. After a 75 g oral glucose tolerance test, participants exposed to betamethasone had higher plasma insulin concentrations at 30 min (60.5 vs 52.0 mIU/L; ratio of geometric means 1.16 [95% CI 1.03 to 1.31], p=0.02) and lower glucose concentrations at 120 min (4.8 vs 5.1 mmol/L; difference -0.26 mmol/L [-0.53 to 0.00], p=0.05) than did those exposed to placebo. Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no clinical effect on cardiovascular risk factors at 30 years of age. Thus, obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.