Stimulation Test Research Articles

Hypothalamic Hamartoma Presenting as Gelastic Epilepsy: When it Goes Unnoticed

A 5-year-old boy presented with episodes of ocular retroversion occurring over the past 4 weeks. Further investigation revealed frequent bilateral epileptiform frontal activity on electroencephalogram and a nodular formation in the hypothalamus on cerebral computed tomography scan. Magnetic resonance imaging characterized the lesion as a hamartoma of the tuber cinereum. After questioning, episodes of unprovoked laughter since the first year of life, consistent with gelastic seizures, were reported. During follow-up, an increase in testicular volume was noted, and a GnRH stimulation test confirmed the diagnosis of central precocious puberty. The boy underwent treatment with antiepileptic drugs and GnRH analogs. Surgical resection of the hamartoma was performed, resulting in cessation of seizures and behavior’s improvement. Hypothalamic hamartomas can present with precocious puberty and gelastic epilepsy. Diagnosis is challenging and often the symptoms go unnoticed for years. Long-term follow-up and multidisciplinary management are essential for optimal patient care and monitoring.

Clinical, Biochemical and Molecular Characteristics of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by the deficiency of one of the enzymes involved in cortisol synthesis. Between 90% and 99% of cases of CAH are caused by 21-hydroxylase deficiency (21-OHD) caused by mutations in CYP21A2. Although 21-OHD has been historically divided into classical and non-classical forms, it is now thought to show a continuous phenotype. In the classical form, the external genitalia in females becomes virilized to varying degrees. If the disease is not recognized, salt wasting crises in the classical form may threaten life in neonates. Children experience accelerated somatic growth, increased bone age, and premature pubic hair in the simple virilizing form of classical 21-OHD. Female adolescents may present with severe acne, hirsutism, androgenic alopecia, menstrual irregularity or primary amenorrhea in the non-classical form. Diagnosis of CAH is made by clinical, biochemical and molecular genetic evaluation. In cases of 21-OHD, the diagnosis is based on the 17-hydroxyprogesterone (17-OHP) level being above 1000 ng/dL, measured early in the morning. In cases with borderline 17-OHP levels (200-1000 ng/dL), it is recommended to perform an adrenocorticotropic hormone (ACTH) stimulation test. Genotyping in cases with CAH should be performed if the adrenocortical profile is suspicious or if the ACTH stimulation test cannot be performed completely. After diagnosis, determining the carrier status of the parents and determining which parent the mutation was passed on from will help in interpreting the genetic results and determining the risk of recurrence in subsequent pregnancies.

Adrenal hypoandrogenism in adolescents with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) affects 1 in 10,000 children, with its molecular causes largely unknown. Adult studies suggest that low androgen levels induce ovarian insufficiency, but data on about this in children is limited. This study aims to assess the prevalence of low androgen levels in childhood POI and its relationship with adrenal insufficiency. Idiopathic POI adolescents were categorized into two groups based on DHEAS and total testosterone (TT) measured by chemiluminescence. Low androgen group (LAG) was defined using cut-offs according to Tanner pubarche staging. Demographic, clinical, and laboratory data were compared. Morning cortisol <7 mcg/dL and/or ACTH >96 or <5 pg/mL were planned to undergo ACTH stimulation testing, with a peak cortisol response <18 mcg/dL considered insufficient. Forty-three adolescents, mean age 15.5±1.3 years with a 46, XX karyotype, normal FMR1 mutation, FSH levels >40 mIU/mL, and low AMH levels were included. In 14 cases (37.8 %), DHEAS and TT were low. In the LAG, pubarche was absent in seven patients, and initial height SDS was significantly lower. Morning cortisol ranged from 7.9 to 23.5 mcg/dL, with an ACTH of 29.4±9.7 pg/mL. No differences in adrenal steroids or correlations between DHEAS and ACTH were observed. Diminished androgen levels are prevalent in children with idiopathic POI. The potential for this condition to increase the risk of adrenal insufficiency and its impact on secondary ovarian insufficiency remains unclear. This study, the first of its kind in children, underscores the potential role of genetic factors in zona reticularis and ovarian development.

Central Adrenal Insufficiency: Etiology and Diagnostic Approach

Central adrenal insufficiency (CAI) occurs due to a pituitary gland disorder (secondary AI) or hypothalamic dysfunction (tertiary AI). It is a potentially life-threatening condition that has many congenital and acquired causes. Adrenocorticotropic hormone deficiency may be isolated or more commonly it can be accompanied by other pituitary hormone deficiencies or midline defects. The signs and symptoms of CAI are associated with glucocorticoid deficiency. A three-step diagnostic approach including dynamic stimulation tests is recommended in the evaluation of patients with suspected CAI. Here, members of the ‘Adrenal Working Group’ of ‘The Turkish Society for Pediatric Endocrinology and Diabetes’ present an evidence-based review with good practice points and recommendations for etiology and diagnostic approach in children and adolescents with CAI.

Hyperandrogenism in polycystic ovary syndrome and adrenal hyperplasia: finding differences to make a specific diagnosis.

Polycystic Ovary Syndrome (PCOS) and Adrenal hyperplasia (CAH) are two pathologic conditions sharing several clinical features (hirsutism, acne, polycystic ovary morphology, metabolic alterations, ovulatory dysfunctions) and especially hyperandrogenism as a common clinical hallmark. Therefore, making a differential diagnosis of the two conditions still remains a great medical challenge. In particular, the comparison discussed in this review referred to non-classical form of adrenal hyperplasia (NCAH), which regards the adult population, and the Endocrine Metabolic Syndrome (EMS), following the new set of PCOS diagnostic criteria proposed by the Experts Group on Inositol and Clinical Research, and on PCOS (EGOI-PCOS). To support this review, a literature search was conducted using PubMed, Google Scholar and Web of Science, supplemented by articles known to the authors. Keywords included: polycystic ovary syndrome, non-classical adrenal hyperplasia, hyperandrogenism, and 17-Hydroxyprogesterone. Considering the different pathophysiology of the two conditions, the recommended strategy to differentiate diagnosis is testing the blood values of 17-hydroxyprogesterone (17-OHP) in fertile aged women with suspicious hyperandrogenism. Basal values of 17-OHP higher than 2ng/mL likely indicate NCAH, while values lower than 2ng/mL exclude the diagnosis of NCAH; in case of borderline values stimulation test with adrenocorticotropic hormone may eventually confirm the diagnosis. This review contributes to make the differential diagnosis between hyperandrogenic PCOS and NCAH clearer, thus also aiming to achieve tailored therapeutic approaches for patients with hyperandrogenism.

Does clonidine stimulate copeptin in children?

Abstract Objectives Copeptin is secreted in isomolar amounts along with AVP. Its stability makes it a perfect biomarker of AVP deficiency. In children, dynamic GH tests were shown to stimulate copeptin. Here, we retrospectively studied the effect of clonidine on copeptin release. Methods This is a monocentric retrospective analysis of donated residual serum samples from 42 children with suspected growth hormone deficiency (GHD) who underwent clonidine stimulation between 2020 and 2023. Copeptin was measured in baseline, 30-, 60-, 90- and 120-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. Results There were 20 patients with GHD and 22 without; no patient had polyuria-polydipsia syndrome. Median age was 6.7 years (quartiles; 5.6–7.8), and the median height was −2.92 SDS (−3.42 to −2.34). The median baseline level of copeptin was 5.6 pmol/L (3.4–9.6). Median copeptin mildly decreased to 4.5 pmol/L (3.0–10.0) after 30 min; this change was not significant (p=0.45). Thereafter, median values remained low at 4.6, 4.6, and 4.6 pmol/L (60, 90, and 120 min). There was no correlation between baseline copeptin levels and the diagnosis of GHD. Conclusions The clonidine stimulation test does not stimulate copeptin release and is not suitable for the assessment of AVP deficiency in children.

Pituitary abnormalities in patients with pediatric growth hormone deficiency in a single tertiary center.

There is controversy as to whether brain magnetic resonance imaging (MRI) should be performed on all children with growth hormone deficiency (GHD) including those judged to have mild GHD. This study was aimed to determine the frequency of pituitary or intracranial abnormalities in pediatric GHD and to identify risk factors that may predict pituitary or intracranial abnormalities. A total of 95 pediatric GHD patients were included. Their medical records and brain magnetic resonance (MR) images were reviewed retrospectively. Abnormal pathogenic MR images were found in 14 patients (14.7%), including 10 (10.5%) with pituitary hypoplasia and 4 (4.2%) with pituitary stalk interruption syndrome. Serum levels of insulin-like growth factor-I (IGF-I), IGF-I standard deviation score (SDS), insulin-like growth factor binding protein 3 (IGFBP3), and growth hormone (GH) peak level of GH stimulation test were statistically significantly lower in the group with abnormal brain MRI. The frequency of abnormal MRI was statistically significantly higher in the complete GHD group. IGF-1 SDS showed the highest area under the curve which can predict the presence of brain abnormality with a sensitivity of 85% and a specificity of 71.4%, if IGF-1 SDS was less than -1.365. IGF-1, IGFBP3, and GH peak levels also showed good sensitivity of over 80% for predicting brain abnormalities with cutoff values of 70.285 ng/mL, 1,604 ng/mL, and 4.205 ng/mL, respectively. The sensitivity and specificity of each cutoff value of IGF-1, IGF-1 SDS, IGFBP3, and GH peak levels were good and statistically significant in predicting brain MRI abnormalities. However, it was insufficient to predict all brain abnormalities with these variables. Therefore, we would like to recommend performing a brain MRI if a child is diagnosed with GHD.

Can we predict hypoadrenocorticism in dogs with resting hypocortisolemia? A predictive model based on clinical, haematological, and biochemical variables

BackgroundA resting cortisol concentration (RC) higher than 2.0 μg/dL (55 nmol/L) is commonly used to rule out hypoadrenocorticism (HA). However, there is a significant overlap of RC between dogs with HA and those with other diseases. There is a need for data to help increase the suspicion of HA.Hypothesis/objectivesTo create a predictive model based on clinical, haematological and biochemical variables to increase the likelihood of diagnosis of hypoadrenocorticism.AnimalsNinety-two dogs with RC &amp;lt;2.0 μg/dL, and an adrenocorticotropic hormone stimulation test (ACTHst) performed.MethodsMulticentric retrospective cohort study with review of medical records of client-owned dogs presented to two referral centres, between January 2018 and March 2022. Dogs were divided into two groups (HA and not HA), based on ACTHst results. Descriptive analysis was performed along with a predictive model, using univariable and multivariable logistic regression analysis.ResultsOf the 92 included dogs, hypoadrenocorticism was diagnosed in 29 patients (32.2%) based on ACTHst results (HA group). Acute gastrointestinal signs, anorexia and lethargy were more prevalent in the HA group. Creatinine, BUN, ALT, and potassium were higher, and albumin, sodium and Na/K ratio were lower in the HA group. Multivariate analysis developed a robust model in which lethargy (OR 5.25), anorexia (OR 3.69), albumin (OR 0.32), and sodium (OR 0.84) concentrations allowed the prediction of HA.Conclusions and clinical importanceIn dogs with resting hypocortisolemia, the combination of anorexia and lethargy, along with low sodium and albumin concentrations, should raise the suspicion of hypoadrenocorticism. The variables identified in this study may help clinicians to identify dogs with hypoadrenocorticism in daily clinical practice.

Comparative Analysis of Vestibular Dysfunction and Compensation in Ramsay-Hunt Syndrome and Vestibular Neuritis.

To investigate vestibular loss and compensation in Ramsay-Hunt syndrome with dizziness (RHS-D) and vestibular neuritis (VN). Retrospective cohort study from 2019 to 2023. Tertiary care neurotology practice. Patients with RHS-D or VN who underwent videonystagmography, including cervical vestibular evoked myogenic potential (cVEMP), caloric stimulation, rotary chair, and oculomotor testing, were reviewed and stratified by vertigo etiology. The main outcome measures were rates and severity of vestibular loss, as measured by cVEMP and caloric stimulation, and of vestibular compensation, as measured by rotary chair and oculomotor testing. Ten patients were found to have RHS-D and 22 with VN. Caloric and cVEMP abnormalities were noted in 100 and 70% of RHS-D patients compared to 60 and 20% with VN (P = .029 and P = .034, respectively). RHS-D patients were significantly more likely to present with concurrent caloric and cVEMP abnormalities compared to VN (70 and 13%, respectively; P = .009). Vestibular loss appeared more severe in RHS-D compared to VN suggested by significantly lower mean bithermal slow phase velocity sum (3.8 and 21 degrees per second, respectively), greater canal paresis (78.7 and 40.2%, respectively), and greater cVEMP amplitude asymmetry (64 and 31%, respectively) (P = .014, P < .001, and P = .053, respectively). Regarding vestibular compensation, abnormal gain asymmetry was present in 88% of RHS-D patients with a mean asymmetry of 31.2 compared to 11% in VN with a mean of 14.0 (P = .019 and P = .003, respectively). Compared to VN, RHS-D patients appear to suffer from a more profound vestibular loss and a worsened ability to compensate for such deficits.

EVIDENCE FOR ADRENAL DYSFUNCTION CONTRIBUTING TO PERACUTE MORTALITY SYNDROME IN RED PANDA (AILURUS FULGENS).

Red pandas (Ailurus fulgens) are endangered with extinction due to deforestation and habitat fragmentation. Reported causes of unexpected death in managed red pandas include kidney, liver, gastrointestinal, and cardiac disease. A previously undetailed syndrome, red panda peracute mortality syndrome, may be emerging, as red pandas have died unexpectedly, with no clear cause of death identified at necropsy. This case series describes the clinical and postmortem findings of five red pandas at Brookfield Zoo with abnormal adrenal size and associated histologic lesions as possible contributing factors to acute death. Antemortem clinical signs consisted of thin body condition, vomiting, intermittent diarrhea, neck ventroflexion, ataxia, and electrolyte abnormalities. Mortality may have been due to abnormal adrenal function, resulting in fatal electrolyte disturbances. Antemortem adrenocorticotropic hormone (ACTH) stimulation tests indicated an inappropriate response to ACTH with persistently low cortisol and aldosterone levels after cosyntropin administration. Clinical improvement was seen when red pandas were provided steroids, but all cases were eventually fatal. Further study is needed to understand red panda peracute mortality syndrome and associated adrenal dysfunction.

DO HEALTHY COQUEREL'S SIFAKAS IN CAPTIVITY HAVE UNUSUALLY LOW CIRCULATING CORTISOL?

Cortisol, and other glucocorticoids, are routinely used as markers of physiological stress in wildlife. Typically, stress activates the hypothalamic-pituitary-adrenal (HPA) axis, with adrenocorticotropic hormone (ACTH) signaling the adrenal glands to release cortisol. Nevertheless, recent anecdotes in captive Coquerel's sifakas (Propithecus coquereli), strepsirrhine primates that are difficult to maintain under human care, may challenge the assumption that physiological stress universally increases circulating cortisol. Here, the authors ask if low circulating cortisol and minimal response to adrenal stimulation might be hallmarks of outwardly healthy sifakas in captivity. Comparative ACTH stimulation or control tests were performed in 10 Coquerel's sifakas and six ring-tailed lemurs (Lemur catta) at the Duke Lemur Center (DLC). At baseline, sifakas had average cortisol concentrations of just 0.67 µg/dl, whereas those of ring-tailed lemurs averaged 12.53 µg/dl. Stressful pre-experiment procedures, including kenneling and handling, activated the HPA axis in ring-tailed lemurs, masking further cortisol release from ACTH administration; however, neither these procedures nor exogenous ACTH raised cortisol concentrations in sifakas. Additionally, cortisol in dozens of serum samples from DLC sifakas banked over 17 yr was assayed. Across samples, cortisol concentrations averaged just 0.49 µg/dl and did not vary by animal sex, age, or housing condition. Comparable samples from two individual sifakas in sepsis at the end of life (4.28 and 21.88 µg/dl) indicate that the assay does capture meaningful variation in cortisol in captive sifakas, although robust biological validation is needed. Currently there is a lack of comparative data from wild Coquerel's sifakas that might determine if these unusual endocrine patterns are characteristic of the species or a function of captivity. If the latter, chronic stress in captivity could lead to a downregulated HPA axis, with persistent hypocortisolism perhaps contributing to the Coquerel's sifaka's susceptibility to infection under human management.

Performance of dehydroepiandrosterone sulfate and baseline cortisol in assessing adrenal insufficiency.

Diagnosing adrenal insufficiency (AI) often requires complex testing which can be time consuming and expensive. Dehydroepiandrosterone sulfate (DHEAS) is a promising marker of hypothalamic-pituitary-adrenal (HPA) axis function, however its diagnostic performance has not yet been evaluated in a large-scale study. Evaluate the performance of DHEAS and baseline cortisol in assessing AI. Single-center retrospective cohort study. Referral center. Adults who underwent Cosyntropin stimulation testing (CST) between 2005-2023 and had DHEAS measured within 3 months prior to CST. Area under receiver operating characteristic curve (AUROC) for DHEAS and baseline cortisol. Prevalence of AI based on various DHEAS and baseline cortisol concentrations. Among 1135 patients, 195 (17.2%) had AI. Both baseline cortisol and DHEAS independently had good diagnostic performance with AUROC 0.81 (95% CI 0.77-0.84) and 0.81 (95% CI 0.78-0.85), respectively. Time of CST performance had no significant effect on diagnostic accuracy of baseline cortisol while recent glucocorticoid use decreased diagnostic performance of DHEAS (AUROC 0.72 vs 0.83). Only 1.2% of patients with baseline cortisol ≥10 mcg/dL had AI based on CST. Among patients with baseline cortisol between 5-9.9 mcg/dL, only 1.3% had AI if DHEAS was ≥60 mcg/dL. Conversely, the majority (72.2%) of patients with both baseline cortisol <5 mcg/dL and DHEAS <25 mcg/dL were found to have AI. DHEAS has good diagnostic performance in assessing AI. Measuring both baseline cortisol and DHEAS concentrations may eliminate the need for further dynamic testing in many patients.

Adult height in girls with idiopathic central precocious puberty treated with triptorelin.

Idiopathic central precocious puberty (CPP) precipitates epiphyseal fusion of growth plates in long bones, leading to reduced adult stature. Gonadotropin-releasing hormone analogues (GnRHa) are the treatment of choice for idiopathic CPP, but their benefit on height gain is unclear. We aimed to elucidate the effects of GnRHa treatment on adult height in girls with idiopathic CPP. This prospective observational descriptive study analyzed data of girls with idiopathic CPP diagnosed at 55 centers in Spain between January 1, 1998 and December 31, 2012 included in the Spanish Society for Pediatric Endocrinology's national registry. We included girls with idiopathic CPP (thelarche < 8 years, positive LHRH stimulation test, bone age > 1 year older than chronological age, and normal brain imaging) treated with triptorelin (3.75 mg monthly, adjusted according to LHRH test results and clinical findings). We assessed weight, height, BMI, and secondary sexual characteristics every 6 months and bone age every 12 months until adult height (AH) was attained. The primary outcome was the difference between AH and target height (TH). A total of 465 girls (18.90% adopted) were included; we analyzed data recorded at treatment end in 358 girls and at AH in 216. Mean difference between AH and TH was -1.5 (95%CI: -2.56- -0.45) cm and between AH and PAH 2,57 (95%CI:-3.56- -1.58) cm. GnRHa treatment helps preserve genetic growth potential in girls with idiopathic CPP.

A Child with Non-Growth Hormone-Deficient Short Stature with Chromosome 2 Deletion of 2q35-36.1: A Case Report and Literature Review of Haploinsufficiency of Epha4 Gene

AbstractNon-growth hormone-deficient short stature is a group of growth developmental disorders with complex pathophysiological mechanisms involving multiple pathways, including abnormalities in the growth hormone/insulin-like growth factor 1 signal pathway. We report a 4-year-old girl with severe growth and developmental delay: her height was 91 cm (&lt;–3 standard deviation [SD]), and her growth rate was 3 to 4 cm/year (&lt;–2 SD). Growth hormone stimulation tests indicated a normal peak growth hormone level (11.1 μg/L), while insulin-like growth factor-1 levels were reduced (7.98 nmol/L, &lt;–1SD). Whole exome sequencing and copy number variation analysis revealed a 3.19 Mb deletion at 2q35-q36.1 on chromosome 2, encompassing all coding regions of the Epha4 gene. This study suggests an association between Epha4 gene deletion and non-growth hormone-deficient short stature, highlighting the importance of further research on this gene and its related signaling pathways to understand the molecular mechanisms of the disease and potential therapeutic approaches.

A Rare Cause of Precocious Puberty - Testotoxicosis

Background: Testotoxicosis, also known as familial male-limited precocious puberty (FMPP), is a rare cause of gonadotropin-independent precocious puberty in boys due to an activating mutation in the luteinizing hormone (LH))/choriogonadotropin receptor (LHCGR) gene. Case report: A 3-year 2-month-old boy presented with acne, pubic hair, phallic growth, height accelerations, and aggressiveness. At physical examination, his height was 106cm (+2.36 SDS) and weight was 16kg (+0.77 SDS). He had Tanner stage 2 pubic hair, stretched penile length was 6 cm (&gt;2 SDS), and both testicular volumes were 5mls. Bone age was advanced at 7 years old. Testosterone level was high at 17nmol/L and the gonadotropin-releasing hormone (GnRH) stimulation test was suggestive of peripheral precocious puberty. Whole exome sequencing identified a heterozygous pathogenic variant c.1691A&gt;G (p.Asp564Gly) in the LHCGR gene which supports the diagnosis of testotoxicosis. The child was started on both aromatase inhibitor, anastrozole, and anti-androgen, spironolactone. At 6 months of treatment, there was a halt in pubertal progression with reduced height velocity from 9cm/year to 6cm/year. Conclusion: Without intervention, the patient will have rapid progressive skeletal maturation and virilization which will result in compromised final adult height and psychosocial distress.

Low-added sugar dietary intervention study to mitigate glucose intolerance and improve body composition in adults with cystic fibrosis: a protocol of a double-blind, randomised study

IntroductionPeople with cystic fibrosis (PwCF) are at high risk for developing cystic fibrosis (CF)-related diabetes (CFRD), which worsens morbidity and mortality. Although the pathological events leading to the development of...

RNA-seq reveals changes in the transcriptome of the breast muscle of adult female chickens in response to heat stress

BackgroundHeat stress has caused significant impacts on the poultry industry globally. Tianjin-monkey Chicken (TM) is a local naked neck chicken genetic resource in China, characterized by its heat stress resistance due to a low feather coverage.ResultsWe conducted heat stress stimulation tests on TM and a normal feathered chicken (Jingfen No. 6 Layer, JF), and the breast muscle tissues were collected for transcriptome sequencing. A total of 157 differentially expressed genes (DEGs) and 1435 DEGs were respectively obtained from the comparisons of JFN-vs-JFT and TMN-vs-TMT. GO enrichment analysis found that biological process (BP) terms including phospholipid homeostasis, regulation of aggrephagy, positive regulation of aggrephagy, and negative regulation of lipase activity may be closely related to heat stress resistance in JF chickens. While catabolism-related BP terms were mainly enriched for DEGs of TM, such as catabolic process, protein catabolic process and cellular catabolic process. KEGG pathway analysis showed that the MAPK signaling pathway was enriched both in TM and JF with high connectivity. In addition, some pathways with higher connectivity (Metabolic pathways, FoxO signaling pathway, TGF-beta signaling pathway and AMPK signaling pathway) may be closely associated with resistance to heat stress in JF. In Tianjin-monkey Chicken, we also identified several pathways potentially involved in heat stress regulation, including Ubiquitin mediated proteolysis, Autophagy-animal and Regulation of actin cytoskeleton. Protein-Protein Interaction Networks (PPI) for the 24 co-differentially expressed genes revealed four key genes (Klf9, Asb2, Tmem164 and Arrdc2) associated with heat stress both in JF and TM.ConclusionsOur findings will enrich the research on heat stress resistance in chicken skeletal muscle, while also providing a theoretical basis for the genetic improvement of heat stress resistance in chickens.

Pergolide mesylate administration does not decrease blood thyroid hormone concentrations and thyroid function in horses.

Pergolide, labeled for the treatment of pituitary pars intermedia dysfunction, is 90% protein bound and might cause a decrease in blood thyroid hormone concentrations by displacing them from binding proteins. This study investigated the effect of pergolide on the equine thyroid function. This was an analytic, observational, cohort study. Six horses (17 to 24 years old and 530 to 599 kg) received 1 mg of pergolide mesylate orally once a day from days 1 to 6. Total T4 (tT4) was measured daily from day 0 to 11 (before, during, and after pergolide treatment). Thyrotropin-releasing hormone (TRH) stimulation tests were conducted on days 0 and 6. Total T3 (tT3), tT4, and free T4 by equilibrium dialysis (fT4) were measured at baseline and 2 hours (tT3) and 4 hours (tT3, T4, and fT4) after TRH administration. The effect of pergolide on thyroid hormone concentration was determined by ANOVA, with P < .05 considered significant. No effect of pergolide was detected on tT4 during and after treatment. Administration of TRH resulted in significant increases in tT3 (effect size: +165.8 ng/dL [95% CI, 109.4 to 222.2 ng/dL]), tT4 (+1.162 µg/dL [95% CI, 0.7135 to 1.610 µg/dL]), and fT4 (+1.195 µg/dL [95% CI, 0.7195 to 1.670 µg/dL]). There was, however, no significant effect of pergolide on any thyroid hormone concentration. Pergolide has no detected effect on blood thyroid hormone concentrations and equine thyroid function. Protein-bound agents do not necessarily affect thyroid hormone concentrations. In horses with pituitary pars intermedia dysfunction, low thyroid hormone concentrations are likely due to the condition itself, not pergolide treatment.

Diagnosis of naturally-occurring Cushing's syndrome by primary care veterinarians in selected European countries.

Several tests are available to diagnose naturally-occurring Cushing's syndrome in dogs but there is a paucity of information on how primary care veterinarians (PCVs) use or interpret them. Determine how PCVs from selected European countries diagnose Cushing's syndrome in dogs. Cross-sectional survey study assessing testing protocols used by PCVs for screening and differentiation of Cushing's syndrome. Two thousand one hundred and seventy-eight responses from 9 European countries were included. When Cushing's syndrome was suspected, 98.7% of respondents perform endocrine testing, whereas 1.2% rely on a treatment trial. Among the former, 59.9% reported performing screening tests in the absence of supportive clinical signs but with consistent clinicopathological abnormalities. Of 2150 respondents who performed endocrine testing, 66.6% report always using the same initial screening tests regardless of their pretest suspicion of disease. The tests most reported are the ACTH stimulation test (34.8%), low-dose dexamethasone suppression test (LDDST; 30.4%) or a combination of different tests (25.2%). In the absence of financial constraint, 1419 (66.0%) respondents always attempted differentiation, using abdominal ultrasonography (81.0%) and LDDST (46.1%). Overall, 69.8% of respondents reported offering referral to a specialist in ≤20% of cases suspected or diagnosed with Cushing's syndrome over the previous 5 years. Testing protocols vary among PCVs. Almost 60% of respondents potentially screen dogs without consistent clinical signs, raising concerns for overdiagnosis. A proportion never attempt differentiation, which likely affects prognosis. Cases are rarely referred to a specialist, reflecting that Cushing's syndrome is mainly managed in primary care practices. These results suggest that there is room for further education of PCVs.

Paraneoplastic Cerebellar Degeneration and Symptomless Lambert–Eaton Myasthenic Syndrome With SOX‐1 Antibodies

ABSTRACTA 62‐year‐old man was diagnosed with paraneoplastic cerebellar degeneration (PCD) at a previous hospital due to cerebellar ataxia, positive serum SOX‐1 antibodies, and small cell lung cancer. Although the tumor has shrunk by chemotherapy, the cerebellar ataxia progressed and left him unable to walk. Lambert–Eaton myasthenic syndrome (LEMS) was suspected, because nerve conduction studies showed that reduced compound muscle action potential amplitudes disproportionate to muscle weakness. PCD‐LEMS with SOX‐1 antibodies was diagnosed on the basis of waxing by high‐frequency repetitive nerve stimulation test and high P/Q‐type voltage‐gated calcium channel antibody levels. Immunoglobulin therapy and 3,4‐diaminopyridine contributed to improved activities of daily living by improving muscle weakness masked by cerebellar symptoms. In patients with SOX‐1 antibodies, investigating for tumors and LEMS is necessary, even if muscle weakness is not noticeable.