Hormone Stimulation Test Research Articles

Atypical hypoadrenocorticism presenting with hypoglycaemic seizures and bilateral cortical blindness in a dog

AbstractA 4‐year‐old, neutered, female Jack Russell terrier cross was presented for an acute onset of obtundation, severe hypoglycaemia and generalised tonic‐clonic seizure activity. Baseline cortisol and subsequent adrenocorticotropic hormone stimulation testing confirmed hypoadrenocorticism, which was atypical as there were no electrolyte abnormalities present during hospitalisation or in the 6‐month follow‐up period. The dog responded to glucocorticoid monotherapy. To our knowledge, this is the only confirmed case of atypical hypoadrenocorticism presenting for hypoglycaemic seizures and bilateral cortical blindness in a dog. Hypoadrenocorticism (typical or otherwise) should be considered in dogs presenting for hypoglycaemic seizures.

Adrenal gland involvement in 11-ketotestosterone production analyzed using LC-MS/MS.

11-ketotestosterone (11KT), which is derived by the bioconversion of testosterone via 11β-hydroxytestosterone (11OHT), is a potent agonist of the human androgen receptor. The adrenal gland is considered an important organ in 11KT production because CYP11B1, which catalyzes testosterone to 11OHT, is expressed in the adrenal glands. The present study aimed to demonstrate adrenal gland involvement in 11KT production in prepubertal children, a topic which has not yet been addressed by any previous studies. Three, retrospective, observational studies were performed. Study 1 enrolled patients aged 8 months to 7 years with severe Kawasaki disease (KD) who were treated with mPSL pulse. Studies 2 and 3 included patients who had received a corticotropin-releasing hormone (CRH) stimulation test and adrenocorticotropic hormone (ACTH) stimulation test, respectively. Samples were collected before and after treatment or drug administration, and serum 11KT, 11OHT, and other 11-oxygenated androgens were measured by LC-MS/MS. Steroid hormone values before and after medication were analyzed using the Wilcoxon signed rank test. Studies 1, 2, and 3 included twenty patients with severe KD, eight patients with a CRH stimulation test, and eight patients with an ACTH stimulation test, respectively. Study 1 demonstrated that the median (IQR) 11KT level was significantly higher before, than after, mPSL pulse (0.39 (0.28-0.47) nmol/L versus 0.064 (0.012-0.075) nmol/L; P < 0.001). Studies 2 and 3 indicated no significant difference in the median 11KT value before and after the CRH or ACTH stimulation test while the 11OHT value was significantly higher after the test. In conclusion, the mediation of 11KT production by ACTH demonstrated the importance of the adrenal glands in the synthesis of this androgen in prepubertal children.

The effects of cannabidiol on immune function and health parameters in senior horses

Cannabidiol (CBD) has potential to reduce pain and inflammation in humans leading to the interest of use in equine. The purpose of this study was to determine the effects of CBD on immune function by measuring inflammatory cytokines and antibody responses to vaccination, as well as other health parameters in senior horses. Horses were orally-dosed with CBD (2 mg/kg: 13 horses) or control (soy oil: 14 horses) daily for 90 days, from July 2021 to November 2021. Peripheral blood samples were collected on days 0, 30, 60, and 90 before administering treatments. On day 90 all horses were kept on treatment and vaccinated with an equine influenza vaccine and blood samples were collected post-vaccination on days 14 and 21. For all time points, plasma samples were analyzed for determination of CBD and metabolites, 7-OH CBD and 7-COOH CBD, using tandem mass spectrometry. For time points 0, 30, 60 and 90, blood samples were analyzed for CBC and chemistry. Additionally, peripheral blood mononuclear cells (PBMC) were isolated, stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, stained intracellularly for interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) then analyzed via flow cytometry. Real-time PCR (RT-PCR) analyzed both stimulated PBMCs and whole blood for cytokine gene expression. Inflammatory proteins C-reactive protein, interleukin 1 receptor agonist, and prostaglandin E2 were measured with equine-specific enzyme linked immunosorbent assays. Thyrotropin-releasing hormone stimulation test and oral sugar test were performed on all horses before and after the study to analyze metabolic function. Hemagglutination inhibition (HI) titers were measured for immune responses pre- and post-vaccination. All data were analyzed using either a paired t-test or a two-way repeated measures analysis of variance (significance P < 0.05). Plasma concentrations of CBD and metabolites were determined with 7-COOH CBD, the most significant metabolite, in CBD treated horses compared to control treated horses. A significant decrease was determined for whole blood inflammatory cytokine expression of IFN-γ at day 60, and for IL6 at day 60 and 90 for CBD-treated horses when compared to control horses. CBD did not significantly affect any other immune factors, HI titers, or health parameters. This study demonstrated that treatment with CBD reduced some inflammatory cytokine production with no negative side effects as measured by CBC or chemistry profiles. This study reveals the initial understanding of CBD in the horse, however more in-depth research is needed to fully understand its efficacy on the health of the horse.

Isolated growth hormone deficiency in children with vertically transmitted short stature: What do the genes tell us?

The growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that children diagnosed with GHD form a heterogeneous group with growth disorder frequently independent on GH function. No study evaluating the complex etiology of growth failure in children with diagnosed GHD has been performed thus far. To discover genetic etiology of short stature in children with diagnosed GHD from families with short stature. Fifty-two children diagnosed with primary GHD and vertically transmitted short stature (height SDS in the child and his/her shorter parent <-2 SD) were included to our study. The GHD diagnosis was based on growth data suggestive of GHD, absence of substantial disproportionality (sitting height to total height ratio <-2 SD or >+2 SD), IGF-1 levels <0 for age and sex specific SD and peak GH concentration <10 ug/L in two stimulation tests. All children were examined using next-generation sequencing methods, and the genetic variants were subsequently evaluated by American College of Medical Genetics standards and guidelines. The age of children at enrollment into the study was 11 years (median, IQR 9-14 years), their height prior to GH treatment was -3.0 SD (-3.6 to -2.8 SD), IGF-1 concentration -1.4 SD (-2.0 to -1.1 SD), and maximal stimulated GH 6.3 ug/L (4.8-7.6 ug/L). No child had multiple pituitary hormone deficiency or a midbrain region pathology. Causative variant in a gene that affects growth was discovered in 15/52 (29%) children. Of them, only 2 (13%) had a genetic variant affecting GH secretion or function (GHSR and OTX2). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (ACAN, COL1A2, COL11A1, COL2A1, EXT2, FGFR3, NF1, NPR2, PTPN11 [2x]), in one (7%) a genetic variant impairing IGF-1 action (IGFALS) and in two (12%) a variant in miscellaneous genes (SALL4, MBTPS2). In children with vertically transmitted short stature, genetic results frequently did not correspond with the clinical diagnosis of GH deficiency. These results underline the doubtful reliability of methods standardly used to diagnose GH deficiency.

Effectiveness of Pelvic Ultrasonography in the Diagnosis of Central Precocious Puberty and Its Differentiation from Similar Conditions

Background: Differentiation of patients with central precocious puberty (CPP) from healthy individuals and patients with CPP-like conditions [isolated premature thelarche (IPT) and isolated premature adrenarche (IPA)] is important for selecting an appropriate treatment. The gonadotropin-releasing hormone stimulation test is used as the gold standard for differentiating CPP from other conditions. Despite its high specificity, this test has disadvantages, such as low sensitivity, time-consuming sampling, and need for multiple blood samples. Objectives: This study aimed to investigate the use of pelvic ultrasonography (US) and its parameters in distinguishing CPP patients from those with similar conditions and healthy individuals. Patients and Methods: In this case-control study, a total of 183 patients, who were referred to the endocrinology department of Ali Asghar Hospital in Tehran, Iran for the evaluation of CPP, were recruited cconsecutively from 2015 to 2019. All the participants were Iranians and classified based on the clinical and laboratory findings. Pelvic US parameters were evaluated in all groups. One-way analysis of variance (ANOVA) was used to compare the mean values of continuous variables between the groups. Moreover, a post-hoc test was performed for pairwise comparisons between the groups if the result of ANOVA test was statistically significant. Finally, the receiver-operating characteristic (ROC) curve analysis was performed to determine the best cutoff points for US parameters. Results: Of 183 children, 62 were allocated to the control group (33.87%), 93 to the CPP group (50.81%), 16 to the IPT group (8.74%), and 12 to the IPA group (6.55%). The results showed no significant difference between the groups regarding chronological age and body mass index, while the bone age (107.76 ± 19.81 months) (P &lt; 0.001) and height (129.53 ± 8.97 cm) were significantly higher in the CPP group compared to the other groups (P = 0.003). All US parameters were significantly different between the CPP and control groups. There were also significant differences between CPP patients and those with IPT and IPA in terms of all parameters, except for the cervical anteroposterior diameter and ovarian volume. The best parameters for differentiating CPP from other conditions were the uterine volume (cutoff value, 1.40; 75.27% sensitivity; 75.56% specificity), uterine transverse diameter (cutoff value, 13.5 mm; 72.04% sensitivity; 71.11% specificity), and fundus/cervix (F/C) ratio (cutoff value, 0.98; 78.49% sensitivity; 70% specificity). Conclusion: The pelvic US parameters can improve the diagnosis of CPP and play an auxiliary role in distinguishing the treatment needed. Based on the findings, the best diagnostic parameter and its cutoff value can vary depending on ethnicity and type of study.

Clinical and molecular characterization of a patient with MBTPS1 related spondyloepiphyseal dysplasia: Evidence of pathogenicity for a synonymous variant.

A novel autosomal recessive skeletal dysplasia resulting from pathogenic variants in membrane-bound transcription factor peptidase, site 1 (MBTPS1) has been recently delineated. To date, only three patients have been reported. In this study, we reported the clinical and molecular features of a Chinese boy who was diagnosed with spondyloepiphyseal dysplasia. The effects of variants on mRNA splicing were analyzed through transcript analysis in vivo and minigene splice assay in vitro. The proband mainly showed short stature, special facial features, cataract, hernias, and serious sleep apnea syndrome. Growth hormone stimulation tests suggested the boy had growth hormone deficiency. Imaging examinations suggested abnormal thoracolumbar vertebrae and severely decreased bone mineral density. Genetic analysis of MBTPS1 gene revealed two novel heterozygous variants, a nonsense mutation c.2656C > T (p.Q886*, 167) in exon 20 and a synonymous variant c.774C > T (p.A258=) in exon 6. The transcript analysis in vivo exhibited that the synonymous variant c.774C > T caused exon 6 skipping. The minigene splice assay in vitro confirmed the alteration of MBTPS1 mRNA splicing and the exon skipping was partially restored by an antisense oligonucleotide (ASO) treatment. Notably, we report a Chinese rare case of spondyloepiphyseal dysplasia and validate its pathogenic synonymous variant in the MBTPS1 gene.

Sensitivity of Different ACTH and Cortisol Concentration Values in Corticotropin-Releasing Hormone Based Tests in Cushing’s Disease

ABSTRACT Purpose In Cushing’s disease (CD) patients, the aim of the present study is to confirm sensitivity of several ACTH and cortisol concentration values in different time points, during corticotropin-releasing hormone (CRH) stimulation test and during CRH stimulation following dexamethasone suppression (DEX-CRH) test. Methods We retrospectively analyzed cortisol and ACTH concentration increment during CRH and DEX-CRH tests in 23 patients with confirmed CD. Cortisol and ACTH concentrations were determined immediately before, 15 min and 30 min after CRH stimulation. We evaluated the sensitivity of different cutoff values including those reported in previous studies, in the diagnosis of CD. Results During DEX–CRH test, 15 min serum cortisol concentration of 1.4 μg/dl (38 nmol/L) had a sensitivity of 90.9%, and serum cortisol concentration ≥1.27 μg/dl (35 nmol/L) had a sensitivity of 100%. For plasma ACTH, sensitivity of 100% was obtained using ACTH ≥3.5pmol/L (16 pg/ml) at 30 min. During CRH test, 35% increase from baseline in ACTH concentration had a sensitivity of 72.7%. Twenty percent increase in cortisol 30 minutes after stimulation yielded a sensitivity of 85.7%. The best sensitivity of ACTH and cortisol increment was obtained 15 min after stimulation, using 19% and 9% increase, respectively (sensitivity of 100% and 92.8%, respectively). Conclusion During CRH and DEX-CRH tests, the study findings agree with the good sensitivity of ACTH and cortisol cutoff values suggested in previous studies; yet, other cutoff values may give a higher diagnostic sensitivity.

Brain structure alterations in girls with central precocious puberty.

Central precocious puberty (CPP) is puberty that occurs at an unusually early age with several negative psychological outcomes. There is a paucity of data on the morphological characteristics of the brain in CPP. This study aimed to determine the structural differences in the brain of patients with CPP. We performed voxel- and surface-based morphometric analyses of 1.5 T T1-weighted brain images scanned from 15 girls with CPP and 13 age-matched non-CPP controls (NC). All patients with CPP were diagnosed by gonadotropin-releasing hormone (GnRH) stimulation test. The magnetic resonance imaging (MRI) data were evaluated using Levene's test for equality of variances and a two-tailed unpaired t-test for equality of means. False discovery rate correction for multiple comparisons was applied using the Benjamini-Hochberg procedure. Morphometric analyses of the brain scans identified 33 candidate measurements. Subsequently, increased thickness of the right precuneus was identified in the patients with CPP using general linear models and visualizations of cortical thickness with a t-statistical map and a random field theory map. The brain scans of the patients with CPP showed specific morphological differences to those of the control. The features of brain morphology in CPP identified in this study could contribute to further understanding the association between CPP and detrimental psychological outcomes.

The hypothalamic-pituitary-adrenal axis response to ovine corticotropin-releasing-hormone stimulation tests in healthy and hospitalized foals.

The hypothalamic-pituitary-adrenocortical axis (HPAA) response to sepsis can be impaired in critical illness. Corticotropin-releasing hormone (CRH) stimulation test might assess HPAA function in foals. To evaluate plasma cortisol, ACTH, arginine vasopressin (AVP), and endogenous CRH (eCRH) response to different doses of ovine CRH (oCRH). Healthy (n=14) and hospitalized (n=15) foals <7 days of age. In this prospective randomized study, oCRH (0.1, 0.3, and 1μg/kg) was administered intravenously and blood samples were collected before, 15, 30, 60, and 90 minutes after administration of oCRH to determine plasma hormone concentrations. The hormonal response was evaluated as the difference (Delta; μg/dL or pg/mL) or percent change between baseline hormone concentration and each time point after oCRH stimulation. Cortisol concentrations increased from baseline at 15 minutes with 0.1 and 0.3μg/kg and at 30 and 60 minutes from baseline with 1μg/kg oCRH (P < .05) in healthy and hospitalized foals. ACTH concentrations increased from baseline at 15 minutes with 0.1μg/kg and at 30 minutes with 1μg/kg oCRH (P < .05) in hospitalized foals. Delta cortisol 0 - 30, ACTH 0 - 30, and eCRH 0 - 30 was higher for the 1μg/kg compared with 0.1μg/kg oCRH in healthy foals (P < .05). Delta ACTH 0 - 15 and eCRH 0 - 30 was higher for the 1μg/kg compared with the lower doses of oCRH in hospitalized foals (P < .05). Cortisol, ACTH, and eCRH concentrations increased in response to administration of all doses of oCRH. One microgram per kilogram of oCRH appears to be optimal for the assessment of HPAA in healthy and hospitalized foals.

Trismus due to myotonia associated with hyperadrenocorticism in a dog.

We present the report of trismus due to hyperadrenocorticism-associated myotonia diagnosed by electromyography in a dog. An intact female Miniature Dachshund, 13 years and 9 months old, presented with stiff gait and trismus as well as polyuria and polydipsia. Abdominal ultrasonography showed enlarged adrenal glands. An adrenocorticotropic hormone stimulation test revealed an exaggerated response. Based on these findings, this case was diagnosed with hyperadrenocorticism. Electromyography revealed myotonic discharge in the temporalis muscle and limbs. Therefore, trismus was considered to be caused by hyperadrenocorticism-associated myotonia, and the case was treated with oral trilostane (1.3 mg/kg, once daily). During the 4-month follow-up period, despite the partial improvement in stiff gait, trismus did not recover. Long-term data on more cases are warranted to assess the prognosis and clinical characteristics of trismus due to hyperadrenocorticism-associated myotonia.

Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.

ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mechanism of this treatment. Four patients with new mutations were reported based on clinical data and genetic tests. We investigated the expression and Gene Ontology biological process enrichment of ACAN and GH pathways based on GTEx databases through bioinformatics analyses. The effect of ACAN on the growth hormone response evaluated in ATDC5 cells with a growth hormone stimulation test. Four mutations were reported in this study: c.619C > A, c.1967A > G, c.1888G > A, and c.1308_1309del. All patients' heights were under -2.5 SD, with one had advanced bone age, and two had GH deficiency. Two individuals received growth hormone therapy acquired variable levels of height SD score improvement. ACAN and the GH pathway were strongly associated; ACAN does not affect GHR but regulates the response to GH. Downregulating ACAN inhibited ATDC5 cell proliferation induced by GH. ACAN is associated with the GH pathway, revealing the potential mechanism underlying GH-targeted treatment for ACAN mutation-induced short stature. GH-promoting therapies may increase patients' heights.

Variations in cortisol response in patients with known and suspected adrenal insufficiency.

Adrenal insufficiency (AI) is a relatively rare disease. While the adrenocorticotropic hormone (ACTH) stimulation test remains as one of the commonly used diagnostic test for AI, to date there is no consensus on the cortisol cutoff value post-ACTH stimulation test. This study aimed to investigate and characterize the cortisol response after the standard ACTH stimulation test in a group of Saudi Arabian patients. A single center retrospective study was conducted on Saudi Arabian adult patients who underwent ACTH stimulation test at the endocrinology clinics of King Abdulaziz Medical City in Riyadh, Saudi Arabia between 2015 and 2018. Demographic, clinical and biochemical variables were collected and analyzed. A total of 154 medical records of patients (44 males, 110 females, mean age 44.4 ± 17.0 years) were included in the study. All patients underwent ACTH stimulation test. Fatigue was the most common symptom of participants. Type 1 diabetes was the most frequent comorbidity. Cortisol levels were significantly lower in patients who received corticosteroid replacement therapy, and, within the context of ACTH stimulation tests, were useful in diagnosing AI in patients with vague symptoms and signs. For basal cortisol, the cutoff of ≤258.5 has a sensitivity and specificity of 69.2% and 58.6%, respectively. For 30-minute, the cutoff of ≤386 sensitivity and specificity are 61.5% and 69.0%. For 60-minute, the cutoff of ≤491.5 has a sensitivity and specificity of 61.5% and 65.5%, respectively. Higher cortisol cutoff values have better sensitivity. Patients with AI present with mostly nonspecific symptoms, with type 1 diabetes as the most common comorbidity. The cortisol level cutoffs obtained from Arab patients who underwent ACTH stimulation tests showed wide variability for its utility in AI diagnosis. Further studies to evaluate the optimal cortisol cutoff values for AI diagnosis in this population are needed.

CANDIDA PANOPHTHALMITIS WITH IATROGENIC HYPERADRENOCORTICISM IN TWO DOGS

Two adult poodles were referred for severe corneal ulcers in both eyes (oculi uterque [OU]) for 1.5 months, and swollen eyelids for approximately 1 week. Ophthalmic examination revealed diffuse corneal edema with grayish deposit and ulcer, uveitis, glaucoma, grayish deposit and necrosis on the third eyelid and conjunctiva, eyelids necrosis, eyelid-eyeball adhesions, and blindness. Cytological examination of the conjunctiva and cornea revealed neutrophilic inflammation, and a bacterial culture revealed Staphylococcus aureus. An adrenocorticotropic hormone stimulation test was performed, strongly indicating iatrogenic hyperadrenocorticism. No improvement was observed after 2 weeks of antibiotic treatment. Fungal cultures from the cornea and conjunctiva were positive for Candida spp. Specific antifungal treatment included topical 5% natamycin eye drops (OU six times daily) and oral itraconazole (5[Formula: see text]mg/kg q12[Formula: see text]h). The grayish deposits of the conjunctiva and cornea were sloughed off, thus facilitating the healing of corneal and eyelids ulcers, over the next 3–4 weeks. Phthisis bulbi and eyelid-eyeball adhesions developed in both dogs after 6 months of follow-up. Based on the fungal isolation by culture, clinical signs, and response to antifungal treatment, Candida spp. panophthalmitis was diagnosed. Fungi should be considered a potential organism in panophthalmitis, especially with a medical history of steroids and antibiotic use. This case report demonstrates the grayish deposits of the cornea, conjunctiva, and third eyelid as possible characteristics of Candida infection in the dogs. To our knowledge, this is the first report of Candida panophthalmitis with iatrogenic hyperadrenocorticism in dogs.

547. Risk factors that can predict adrenal insufficiency in fever of unknown origin

Abstract Background Adrenal insufficiency is one of the causes of fever of unknown origin (FUO), however, it is often mistaken for an infectious disease, leading to unnecessary antibiotic use. The purpose of this study is to find out risk factors that can predict adrenal insufficiency in FUO patients so that set a target to recommend the adrenocorticotropic hormone (ACTH) stimulation test. Methods This study was conducted retrospectively in a tertiary hospital with 846 beds in South Korea. All adult inpatients (age ≥ 19 years) who have requested a consult with the department of infectious disease (ID) for FUO between 1 July, 2019 and 30 June, 2020 were included in the study. Among them, those who underwent an ACTH stimulation test and had a fever of 37.8°C or higher within 48 hours of the ACTH stimulation test were finally included in the study subjects. Results A total of 202 FUO patients were enrolled and 61 (30.1%) were finally diagnosed with adrenal insufficiency. Patient with adrenal insufficiency had higher charlson comorbidity index score than others (2.36±1.88 vs. 1.85±2.06, P=0.016). In addition, higher proportion of patients who used immunosuppressant (31.1% vs. 6.4%, P&amp;lt; 0.001) and/or corticosteroid (19.7% vs. 3.5%, P&amp;lt; 0.001) within 3 months were observed in adrenal insufficiency group. Patients with adrenal insufficiency tended to show hypotension (21.3% vs. 10.6%, P=0.044), lower white blood cell count [10^3/uL] (9.27±6.30 vs. 10.54±5.82, P=0.025), lower hemoglobin (4.38±9.96 vs. 1.70±2.10, P=0.023), lower albumin (8.25±0.94 vs. 8.49±0.60, P=0.009), and higher creatinine (1.39±1.61 vs. 1.05±1.57, P=0.044) than those without adrenal insufficiency. In a multivariate analysis, use of immunosuppressant within 3 months (OR 6.06, 95% CI 1.82–20.13, P = 0.003), use of corticosteroid within 3 months (OR 8.23, 95% CI 1.35–50.17, P = 0.022), sodium ≥ 136.7 (OR 3.43, 95% CI 1.49–7.88, P = 0.004), and calcium ≥ 8.4 (OR 0.31, 95% CI 0.14-0.71, P = 0.005) were proven to be factors that can predict adrenal insufficiency in FUO patients. Conclusion When FUO patients have a history of immunosuppressant/corticosteroid use within 3 months, and/or shows sodium ≥ 136.7, or calcium &amp;lt; 8.4 at initial laboratory test, performing ACTH stimulation test is recommended. Disclosures All Authors: No reported disclosures.

Combined Arginine and Insulin Stimulation Elicits a Robust and Consistent Copeptin Response in Short Children

Introduction: Copeptin, co-secreted with arginine vasopressin, is regulated by osmotic and volume stimuli but also responds to intravenous arginine and insulin-induced hypoglycemia. The serum copeptin response to the latter agents has been studied in adults but only to a limited extent in children. The objective of this study was to describe the copeptin response to combined arginine and insulin in children with normal posterior pituitary function. Methods: We conducted a prospective, single-arm assessment of serum copeptin concentrations in children (age 7–16 years, n = 38) undergoing growth hormone stimulation testing with an arginine-insulin tolerance test (AITT) for short stature or growth deceleration in a tertiary referral center. After overnight fasting, arginine (500 mg/kg) was administered between 0 and 30 min intravenously (IV) followed by insulin (0.1 units/kg IV) at 60 min. Copeptin serum concentrations were measured at baseline (0 min), at the post-arginine peak (60 min), and at the post-insulin peak (90 min; 30 min post-insulin), respectively. The main outcome was the peak copeptin concentration. Results: Mean ± SD copeptin concentrations increased from 9.9 ± 5.0 pmol/L at 0 min to 13.2 ± 5.8 pmol/L at 60 min (p < 0.0001 vs. 0 min) and 27.7 ± 14.2 pmol/L at 90 min (p < 0.0001 vs. 0 and 60 min). There was no significant correlation between copeptin concentrations and age, BMI, pubertal status, cortisol, growth hormone, or glucose concentrations. Discussion/Conclusion: Arginine and insulin appear to have an additive and consistent effect resulting in significant stimulation of copeptin secretion in children. The AITT may be a useful tool to evaluate for normal posterior pituitary function in this age-group, with potential implications for the evaluation of polyuria-polydipsia syndrome.

Growth hormone responses during arginine and clonidine stimulation test: Correlations with patients' auxological and metabolic parameters in a single centre study

BackgroundChildren with auxological parameters defining a ‘short stature’ is routinely subjected to various blood tests and, if necessary, to growth hormone stimulation test (GHST) for differentiating GH deficiency (GHD) and other causes of stunted growth. AimThis retrospective monocentric study aimed to evaluate any correlations between GH peaks during GHST in children assessed for short stature and their auxological/metabolic parameters, highlighting differences between GHD and idiopathic short stature. Patients and methodsWe reviewed the medical records of 74 children with short stature (height lower than the third percentile according to standardized growth curves for the Italian population) managed at the Pediatric Day Hospital of our Department of Life Sciences and Public Health in Università Cattolica Sacro Cuore, Rome, who performed at least two GHSTs, using arginine and clonidine as stimulants, for assessment of GH secretion. The results of a total number of 161 GHSTs, performed in 42 children diagnosed with GHD and in 32 children with other causes of short stature, were analyzed. ResultsWe found significantly lower serum levels of insulin growth factor-1 (IGF-1) and increased levels of thyroid-stimulating hormone (TSH) in children with GHD, without other metabolic differences in comparison to children with other causes of short stature. There was also a correlation between triglycerides and GH peak during arginine test, while fT4 and LDL concentrations correlated with GH peak during the third test, if performed. Pre-test BMI (rho −0.274, p = 0.01) and weight (rho −0.251, p = 0.03) have influenced GH peak during clonidine stimulation test. Metabolic and auxological parameters could influence GH peak during clonidine and arginine stimulation tests and must be taken into account when interpreting GHST results.

Relevance of inferior petrosal sinus sampling in the diagnosis of Cushing's syndrome: a case report.

Non-specific signs and symptoms of Cushing's syndrome (CS) can pose a diagnostic challenge. We report the case of a man referred to the service of endocrinology for suspected CS. Hypercortisolism was confirmed on CS screening tests, whereas diagnostic tests confirmed the presence of adrenocorticotropin (ACTH) -dependent CS. The corticotropin-releasing hormone stimulation (CRH) test was performed to determine whether CS hadan endogenous or ectopic origin. Since the CRH and the magnetic resonance imaging (MRI) test were negative, IPSS was performed and suggested that CS was originated in the pituitary glands. Transsphenoidal pituitary resection was carried out. Histopathological analysis confirmed the cortitotrope origin of the tumor. The etiological study and differential diagnosis of CS are complex processes that involve a variety of biochemical and imaging tests. It is important that a sequence of biochemical screening and diagnostic tests is performed, along with studies for establishing the location of the lesion, to determine whether CS has an adrenal, pituitary or ectopic origin. Despite its good diagnostic performance, the results of biochemical tests may not be conclusive, especially in ACTH-dependent CS. In the case reported, the inconclusive results obtained in the CRH test rendered an invasive procedure (IPSS) necessary, which ultimately confirmed diagnosis.

Adrenocorticotropic hormone-producing pituitary adenoma with pituitary apoplexy treated by surgical decompression: a case report

BackgroundPituitary-dependent hypercortisolism (PDH) is one of the most common endocrine disorders in veterinary medicine. However, there are few reports on pituitary tumor apoplexy (PTA) in dogs and no reports on its surgical intervention in veterinary medicine. Accordingly, the appropriate treatment is unknown. Herein, a case of PDH and PTA in a dog treated surgically is described.Case presentationA mongrel female dog (spayed; age, 8 years and 8 months; weight, 6.1 kg) with persistently elevated alkaline phosphatase underwent adrenocorticotropic hormone (ACTH) stimulation testing (post-stimulation cortisol: 20.5 μg/dL), abdominal ultrasonography (adrenal gland thickness: left, 5.7 mm; right, 8.1 mm), and brain magnetic resonance imaging (MRI) (pituitary-to-brain ratio [PBR], 0.61) at the referral hospital, resulting in a diagnosis of PDH (day 0). On day 9, the dog visited XXXX for the preparation of pituitary surgery to treat PDH. However, on days 10–15, the dog developed a loss of energy and appetite, bloody diarrhea, vomiting, and a decreased level of consciousness. However, on day 16, the dog’s condition recovered. A preoperative MRI scan performed on day 52 (the day of surgery) showed apoplexy in the dorsal pituitary region (PBR, 0.68). Based on the PTA findings, the risks of surgery were described to the owner, and approval was obtained. At the time of trans-sphenoidal surgery, a partial pituitary resection was performed with preservation of the PTA area due to adhesions between the PTA area of the right side of the pituitary and surrounding tissues. The resected pituitary tissue was diagnosed as an ACTH-producing adenoma, with necrotic and hemorrhagic findings. As of day 290, endogenous ACTH and cortisol levels did not exceed the reference range.ConclusionsThe acute signs that occurred on days 10–15 were most likely caused by PTA. Therefore, when signs similar to those detected in acute hypoadrenocorticism are observed in dogs with PDH, it is necessary to include PTA as a differential diagnosis. Trans-sphenoidal surgery may be effective in PDH-affected dogs that develop PTA, but careful attention should be paid to tissue adhesions secondary to hemorrhage that may occur after PTA.

ODP399 Growth Hormone Peak did not predict presence of Pituitary Stalk Interruption Syndrome

Abstract Background Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary gland characterized by a triad of the thin or interrupted pituitary stalk, aplasia, or hypoplasia of the anterior pituitary and absent or ectopic posterior pituitary. This can be associated with midline defects and pituitary endocrine deficiencies, ranging from isolated growth hormone deficiency to combined pituitary hormone deficiency. PSIS is a rare entity with an estimated incidence rate of 0.5/1,000,000 births. Clinical case: A 3-year-old neurodevelopmentally appropriate male was initially seen at the PCP office for growth failure. After birth, the patient appeared to have normal growth parameters, as he was in the 61st percentile for length and at the 19th percentile for weight. His growth velocity trended downwards, as he dropped to the 34th percentile at nine weeks old and the 2nd percentile by nine months old. PCP records showed that the patient was at the 10th percentile for height at one year old, but by 18-months, he had fallen below the 1st percentile. His mid-parental height was 175cm, between 25th and 50th percentile. Initial workup showed elevated TSH 9.12 mIU/ml (0.5-4.3 mIU/mL) with negative thyroid antibodies, thus started on 25 mcg of levothyroxine. The screen for systemic disease and inflammatory markers was negative. Insulin-like growth factor 1 (IGF-1) was low at &amp;lt;16 ng/mL (24-148 ng/mL) and insulin-like growth factor binding protein-3 (IGFBP-3) was normal at 1.2mcg/ml (0.7-3.6)A growth hormone (GH) stimulation test was obtained due to suboptimal growth, short stature, and undetectable IGF-1 level. The patient failed his GH stimulation study with a GH peak of 5.1 ng/mL (&amp;gt;10) after clonidine and 2ng/ml (&amp;gt;10) after arginine. A clinical and biochemical diagnosis of GHD was made, an MRI was ordered to evaluate for anatomic cause. Brain MRI showed an ectopic posterior pituitary gland with an absent infundibulum, suggesting PSIS. The patient was started on GH therapy with excellent response. He is currently growing well on a low dose of somatropin, around 0.234mg/kg/week. Conclusion PSIS is a congenital pituitary anatomical defect with a heterogeneous presentation. It is typically encountered in infancy and childhood, possibly progressing to panhypopituitarism by adulthood. Diagnosis can be delayed, as brain MRI imaging is not always obtained based on growth hormone peaks. As seen in our patient, the severity of GHD based on peak levels did not adequately predict the presence of brain anomalies. Historically, severe GHD (&amp;lt;5 ng/mL) is strongly associated with brain MRI abnormalities, but GH levels may not suffice to determine the severity of the disease. Based on our findings, we recommend obtaining brain MRI in all patients diagnosed with GHD to identify critical anatomical abnormalities, like PSIS, that require long-term close monitoring of pituitary function. Presentation: No date and time listed

ODP301 Corticotroph Macroadenomas with Extensions to Third Ventricle: Four Case Reports

Abstract Background Pathophysiology of corticotroph macroadenomas has not been elucidated. In this study, we present four cases of adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas with extensions to the third ventricle (TV) and investigate their clinical and pathological characteristics. Case 1 A male in his seventies went to a hospital because of a fall. Upon performing computed tomography, a tumor was incidentally noted. Pituitary MRI revealed a macroadenoma with extension to TV. He presented with Cushingoid features (CF). His basal ACTH level was 112 pg/mL, and urinary free cortisol (UFC) was 129.1 μg/day. Cortisol was not suppressed in the 0.5 mg dexamethasone suppression test (0.5 mg DST). ACTH level increased in the corticotropin-releasing hormone (CRH) stimulation test and the desmopressin (DDAVP) stimulation test. He was diagnosed with Cushing's disease (CD), and endoscopic transsphenoidal surgery (ETSS) was performed. Pathological findings showed densely granulated corticotroph adenoma (DGCA). Somatostatin receptor type 5 (SSTR5) was negative, and ubiquitin-specific protease 8 (USP8) was not mutated. Case 2 A female in her fifties had a visual field defect and pigmentation of the face. MRI revealed a macroadenoma with extension to TV. She presented with CF. Her basal ACTH level was 57.9 pg/mL, and UFC was 259.7 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH level increased in the CRH test and the DDAVP test. She was diagnosed with CD. Pathological findings showed DGCA. SSTR5 was moderate positive, and USP8 was suspected to be mutated. Case 3 A female in her fifties had a throbbing headache. MRI showed a macroadenoma with extension to TV. She did not present with CF. Her basal ACTH level was 71.8 pg/mL, and UFC was 134.3 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH showed response to the CRH test and the DDAVP test. She was diagnosed with subclinical Cushing's disease (SCD) and sparsely granulated corticotroph adenoma (SGCA). SSTR5 was slightly positive, and USP8 was not mutated. Case 4 A male in his fifties had general malaise and polyuria. MRI showed a macroadenoma with extension to TV. He did not present with CF. His basal ACTH level was 179 pg/mL, and UFC was 187.4 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH did not show response to the CRH test and the DDAVP test. He was diagnosed with SCD, and the tumor had oncocytic changes. SSTR5 was negative, and USP8 was not mutated. Conclusion The findings from these case reports suggest that phenotypes of CD and SCD are associated with the differences between SGCA and DGCA. Moreover, it is also suggested that USP8 mutations correlate with SSTR5 expression in macroadenomas that extend to the TV. Presentation: No date and time listed