Retrospective application of a validated algorithm for estimation of adrenal gland volume after computed tomography on 46 dogs undergoing adrenalectomy.

Canine adrenal gland volume can be predicted based on body weight and computed tomography (CT) measurements using a validated algorithm. Use of this algorithm to detect adrenal pathology, including hyperplasia, hypoplasia and neoplasia, in clinical cases has not been described. The objective of this study was to illustrate application of the algorithm by estimating subject-specific adrenal gland volume in a historical cohort of dogs with known adrenal disease. Forty-six dogs that underwent CT and subsequent adrenalectomy were included. Clinical records and CT images from dogs that underwent adrenalectomy and histologic examination of the excised adrenal gland(s) were reviewed. Normal adrenal gland volumes for each dog were estimated using the algorithm, and compared with measured volumes of the affected glands. Linear measurement of the largest lesion diameter was also recorded. Fifty-eight adrenal glands were removed from 46 dogs, with pathology confirmed in all glands. Pathology included 28 adenomas, 13 carcinomas, 11 pheochromocytomas and 6 other benign pathologies. The volume of all removed adrenal glands was measured to be larger than the expected normal volume estimated by the algorithm, ranging from 1.1 to 212.9 times larger than estimated. Adrenal glands with malignant and benign pathology showed variable volumes with overlapping ranges recorded. Assessment of the dimensions of any focal lesion against a cut-off of 20 mm failed to discriminate malignancy. This study illustrates and supports the application of a validated volumetric algorithm for estimation of subject-specific adrenal gland volume to identify the presence of pathology and as a tool to assist clinical decision-making.

Primary Hyperaldosteronism in a Normotensive Patient: A Case Report.

Introduction: Primary aldosteronism (PA) is a clinical syndrome characterized by hypertension, suppressed plasma renin activity (PRA), elevated plasma aldosterone concentration (PAC), and spontaneous hypokalemia. Case Presentation: We present a 37-year-old normotensive female with hypokalemia, high plasma aldosterone level, and suppressed renin. The patient was treated with eplerenone and potassium chloride supplement. Further investigation with a computed tomography (CT) scan revealed a mass in the left adrenal. Laparoscopic adrenalectomy led to the diagnosis of adrenal adenoma. Conclusions: Primary aldosteronism should be among the differential diagnoses in normotensive patients presenting with severe hypokalemia.

A Rare Case of Giant Bilateral Adrenal Myelolipomas in a Patient With Classical Congenital Hyperplasia.

Congenital adrenal hyperplasia (CAH) is caused by genetic defects in the enzymes involved in cortisol biosynthesis in the adrenal gland and, in more than 90% of cases, due to a deficiency in the 21-hydroxylase enzyme. Classical CAH due to 21-hydroxylase deficiency is a severe form of the disease that presents with cortisol deficiency and is further categorized into salt-wasting or simple-virilizing types. Appropriate steroid replacement has been shown to effectively treat patients with classical CAH and prevent complications. Individuals who receive inadequate treatment or fail to comply with their prescribed steroid hormone regimen are susceptible to the development of adrenal myelolipomas. Myelolipomas are benign tumors composed of both adipose and hematopoietic tissues. While documented cases of adrenal myelolipomas exist in medical literature, instances of large bilateral myelolipomas remain exceedingly rare. This case report highlights a 40-year-old female patient with a known history of classical congenital adrenal hyperplasia who presented with unusually large bilateral adrenal myelolipomas. A diagnostic CT scan of the abdomen and pelvis revealed a 13.4 x 10.8 cm myelolipoma on the left adrenal gland and a 10 x 8.6 cm myelolipoma on the right adrenal gland. Prior to her presentation, the patient experienced recurrent nausea and vomiting, along with left upper quadrant pain, over five months. Hormonal assessments indicated significantly elevated serum androgen levels, suggesting inadequate management of her CAH. In this report, we present a rare case of symptomatic bilateral large adrenal myelolipomas, underscoring the significance of adhering to treatment regimens, diagnostic assessments, and management for adrenal myelolipomas in individuals diagnosed with CAH.

A case of celiac plexus block causing iatrogenic Cushing's syndrome.

Treatment with corticosteroids can lead to iatrogenic Cushing's syndrome when used for longer intervals and in high doses. Less common administration routes may conceal the exposure, raising the possibility of misdiagnosis and mismanagement.

Isotretinoin-unresponsive acne as a sign of a congenital disorder: a case of 21-hydroxylase deficiency.

Acne is a multifactorial and common disorder among young people and a frequent reason for dermatology consultation. When moderate-to-severe acne is not responsive to conventional treatments, oral isotretinoin is a very effective solution. However, there are cases in which this treatment fails to produce the expected results. In this case, an 18-year-old male patient with acne, unresponsive to traditional acne therapies, experienced only a partial benefit from oral isotretinoin. Endocrinology consultation and hormonal work-up revealed androgen metabolism anomalies suggestive of a non-classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. In this case report, the authors discuss when to suspect, how to diagnose, and how to manage similar cases.

Two Cases of Adrenal Cysts Lined by Thyroid Follicular Epithelium: Addressing Cellular Origin and Malignancy Concerns.

Adrenal cysts lined by thyroid follicular epithelium are rare, with only 14 reported cases of "ectopic thyroid tissue" to date. While the primary consideration for differential diagnosis is thyroid carcinoma metastasis, exclusion of metastases is determined based on the absence of a primary thyroid lesion, serological euthyroidism, lack of thyroglobulin elevation, and absence of epithelial atypia. Herein, we report 2 cases of adrenal cysts lined by thyroid follicular epithelium. Case 1 was a 60-year-old woman with a right adrenal cyst. Case 2 was a 51-year-old man with a left adrenal cyst. Over time, both cysts became larger, necessitating an adrenalectomy. Cystic epithelia were lined with thyroid follicular epithelium, exhibiting moderate atypia. Human bone marrow endothelial cell marker-1 and galectin-3 were focally positive; CK19 was positive in Case 1, and all 3 markers were positive in Case 2, previously reported as an immunophenotype of thyroid carcinoma. CD56 expression was positive in both cases. Targeted next-generation sequencing revealed several low-frequency mutations; however, no major driver alterations for thyroid cancer were detected. Adrenal cysts can be lined by thyroid follicular epithelium. Challenges arise in determining the malignant or benign nature of adrenal cysts.

Robotic Resection in Succinate Dehydrogenase Subunit B (SDHB)-Mutated Hereditary Paraganglioma: A Case Report of Two Patients and A Literature Review.

Autosomal dominant hereditary paraganglioma-pheochromocytoma syndrome (HPPS) is a rare genetic disorder characterized by neuroendocrine tumor development associated with pathogenic variants in succinate dehydrogenase (SDH) enzyme complex genes. Particularly, HPPS linked to SDHB mutation poses a significant clinical challenge due to its association with aggressive tumor features and a high risk of malignancy. Our report underscores the diversity in the presentation of patients with SDHB-mutated paraganglioma and the feasibility of managing it with a minimally invasive surgical approach. In the first case, a 17-year-old female was diagnosed with a metabolically active, poorly differentiated extra-adrenal retroperitoneal paraganglioma that required challenging robotic resection. Cascade genetic testing revealed an SDHB mutation not only in her but also in three family members, pointing to the inherited nature of the syndrome. Conversely, the second case involves a 37-year-old male with an asymptomatic well-differentiated left paraaortic paraganglioma incidentally found during an unrelated medical examination. Robotic converted-to-open resection allowed the successful removal of the mass. Subsequent germline testing confirmed a deleterious SDHB mutation, initiating a process of familial cascade testing. Both patients remained symptom- and recurrence-free at 12 and six months, respectively. Through these cases, and supported by a literature review, we highlight the variable clinical presentations of HPPS, arising from the same genetic alteration. The successful application of minimally invasive surgical techniques, combined with genetic evaluation, emphasizes the necessity for a comprehensive, tailored approach to treatment and surveillance. This strategy not only addresses the immediate clinical needs but also fosters proactive management of at-risk family members, ensuring a multidisciplinary approach to this complex hereditary condition.

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma.

BACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

A Large Benign Adrenocortical Adenoma Cosecreting Testosterone and Cortisol.

Most adrenal incidentalomas are benign neoplasms of the adrenal cortex. While the majority are nonfunctional, many secrete cortisol. Androgen- or estrogen-secreting adenomas are rare. A 44-year-old female, with history of hypertension and prediabetes, presented with worsening acne, hirsutism, secondary amenorrhea for 2 years, and a 40-pound weight gain. Laboratory evaluation showed high 24-hour urine free cortisol, suppressed adrenocorticotropic hormone (ACTH) level, indicative of ACTH independent Cushing syndrome, and elevated testosterone and androstenedione. Abdominal computed tomography (CT) revealed a 6.3 × 5.2 × 5.6 cm left adrenal mass. Patient underwent left open adrenalectomy. Pathology revealed benign adrenocortical adenoma. Postoperatively there was a significant improvement in her blood pressure and blood sugar levels, resumption of menses, and complete resolution of hyperandrogenism and hypercortisolism. We describe a patient with an adrenal adenoma cosecreting cortisol and androgen, leading to Cushing syndrome and significant virilization. Adrenal masses secreting androgens are less common and concerning for adrenocortical carcinoma (ACC). Patients with adrenal masses cosecreting multiple hormones should undergo workup expediently since ACC confers poor outcomes.

Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis.

Chronic fatigue syndrome (CFS) causes great harm to individuals and society. Elucidating the pathogenesis of CFS and developing safe and effective treatments are urgently needed. This paper reviews the functional changes in the hypothalamus-pituitary-adrenal (HPA) axis in patients with CFS and the associated neuroendocrine mechanisms. Despite some controversy, the current mainstream research evidence indicates that CFS patients have mild hypocortisolism, weakened daily variation in cortisol, a weakened response to the HPA axis, and an increase in negative feedback of the HPA axis. The relationship between dysfunction of the HPA axis and the typical symptoms of CFS are discussed, and the current treatment methods are reviewed.

Two cases of atraumatic adrenal hemorrhage: A review of active management, conservative management, and challenges faced.

Adrenal hemorrhage (AH) is an uncommon and potentially disastrous affliction that carries an accepted mortality risk of 15%. Variable symptomatology can cause a diagnostic dilemma and may be missed. We present 2 cases of right-sided AH; both cases were initially presumed to be renal colic. Case 1 was an 86-year-old gentleman, presenting with right flank pain found to have a right-sided atraumatic AH. He presented with hemorrhagic shock, requiring angioembolization of the bleeding vessel. Case 2 was a 62-year-old gentleman who presented with right flank pain and was found to have a right-sided atraumatic AH. He was hemodynamically stable and successfully managed conservatively. Adrenal hemorrhage is a potentially fatal affliction that may be missed. CT scans are the recommended imaging modality during an acute presentation due to wider availability and fast assessment. We demonstrate a hemodynamically stable patient managed with a 'watch and wait' approach and an unstable patient managed with resuscitation followed by urgent angioembolization.

Comparative analysis of salivary cortisol measurements using different assay methods in relation to serum-free cortisol measurement.

Objectives: Salivary cortisol reflects the biologically active form of serum cortisol, offering a noninvasive evaluation method for the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) is known for its specificity, immunoassays (IA) are commonly used because of their simplicity. This study aimed to assess the performance of salivary cortisol measurement using both IA and LC-MS/MS in comparison to serum-free cortisol measurement. Methods: Assay results for 188 saliva and 94 serum samples from 47 participants were analyzed. Salivary samples collected at different time points were analyzed using IA and LC-MS/MS. Serum samples were analyzed for cortisol, cortisol-binding globulin, and free cortisol. The statistical analyses included correlations and method comparisons. Results: The diurnal salivary cortisol profiles exhibited a comparable circadian rhythm pattern; however, the concentrations measured using IA were consistently higher than those measured using LC-MS/MS. The correlation analysis revealed robust associations among salivary cortisol (IA), salivary cortisol (LC-MS/MS), and serum-free cortisol levels (LC-MS/MS). However, the method comparison revealed a systematic bias between IA and LC-MS/MS in salivary cortisol measurement. Conclusions: This study contributes to the ongoing debate on assay techniques by affirming the suitability of IA and LC-MS/MS for salivary cortisol measurement to assess dynamic changes in HPA axis activity. The identified systematic bias emphasizes the importance of selecting methods based on specific research or clinical requirements.

Excessive pickle consumption: beware of adrenal crisis.

Adrenal insufficiency (AI) is one of the most life-threatening disorders resulting from adrenal cortex dysfunction. Symptoms and signs of AI are often nonspecific, and the diagnosis can be missed and lead to the development of AI with severe hypotension and hypovolemic shock. We report the case of a 13-year-old child admitted for cardiac arrest following severe hypovolemic shock. The patient initially presented with isolated mild abdominal pain and vomiting together with unexplained hyponatremia. He was discharged after an initial short hospitalization with rehydration but with persistent hyponatremia. After discharge, he had persistent refractory vomiting, finally leading to severe dehydration and extreme asthenia. He was admitted to pediatric intensive care after prolonged hypovolemic cardiac arrest with severe anoxic encephalopathy leading to brain death. After re-interviewing, the child's parents reported that he had experienced polydipsia, a pronounced taste for salt with excessive consumption of pickles lasting for months, and a darkened skin since their last vacation 6 months earlier. A diagnosis of autoimmune Addison's disease was made. Primary AI is a rare life-threatening disease that can lead to hypovolemic shock. The clinical symptoms and laboratory findings are nonspecific, and the diagnosis should be suspected in the presence of unexplained collapse, hypotension, vomiting, or diarrhea, especially in the case of hyponatremia.

Naloxone increases conditioned fear responses during social buffering in male rats.

Social buffering is the phenomenon in which the presence of an affiliative conspecific mitigates stress responses. We previously demonstrated that social buffering completely ameliorates conditioned fear responses in rats. However, the neuromodulators involved in social buffering are poorly understood. Given that opioids, dopamine, oxytocin and vasopressin play an important role in affiliative behaviour, here, we assessed the effects of the most well-known antagonists, naloxone (opioid receptor antagonist), haloperidol (dopamine D2 receptor antagonist), atosiban (oxytocin receptor antagonist) and SR49059 (vasopressin V1a receptor antagonist), on social buffering. In Experiment 1, fear-conditioned male subjects were intraperitoneally administered one of the four antagonists 25 min prior to exposure to a conditioned stimulus with an unfamiliar non-conditioned rat. Naloxone, but not the other three antagonists, increased freezing and decreased walking and investigation as compared with saline administration. In Experiment 2, identical naloxone administration did not affect locomotor activity, anxiety-like behaviour or freezing in an open-field test. In Experiment 3, after confirming that the same naloxone administration again increased conditioned fear responses, as done in Experiment 1, we measured Fos expression in 16 brain regions. Compared with saline, naloxone increased Fos expression in the paraventricular nucleus of the hypothalamus and decreased Fos expression in the nucleus accumbens shell, anterior cingulate cortex and insular cortex and tended to decrease Fos expression in the nucleus accumbens core. Based on these results, we suggest that naloxone blocks social buffering of conditioned fear responses in male rats.

Familial hyperaldosteronism: an European Reference Network on Rare Endocrine Conditions clinical practice guideline.

We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant.

Spontaneous Adrenal Hemorrhage in a Pregnant Woman With Glucocorticoid Resistance Syndrome.

Glucocorticoid resistance syndrome is a rare disorder with no genetically proven cases reported from India; in addition, there are no descriptions available regarding its management during pregnancy. A 27-year-old woman, hypertensive since the age of 17 years, presented with hypokalemic paresis. She reported regular menses and acne. On investigation, she had elevated serum cortisol that remained unsuppressed after a low-dose dexamethasone suppression test. Genetic analysis revealed a novel, homozygous missense variant in exon 5 of the NR3C1 gene confirming glucocorticoid resistance syndrome. She was managed with oral dexamethasone followed by tapering of antihypertensive drugs. A year later, she conceived with assisted reproductive techniques when dexamethasone was replaced with prednisolone, necessitating the reintroduction of antihypertensive drugs to maintain normotension and potassium supplements to manage hypokalemia. She presented with acute abdomen at 36 weeks of gestation; evaluation revealed right adrenal hemorrhage, which was managed conservatively. Postpartum, the right adrenal lesion reduced in size and an underlying right adrenal myelolipoma was unveiled.

Monitoring adrenal insufficiency through salivary steroids: a pilot study.

BACKGROUND: Various glucocorticoid replacement therapies (GRTs) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. METHODS: Control subjects (CSs, n = 28) and AI patients receiving hydrocortisone (HC, n = 9), cortisone acetate (CA, n = 23), and dual-release hydrocortisone once (DRHC-od, n = 10) and twice a day (DRHC-td, n = 6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Addison disease-specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaire results predictors were evaluated with multiple regression analysis. RESULTS: Compared with controls, all GRTs resulted in glucocorticoid overexposure in the morning. Hydrocortisone, CA, and DRHC-td caused overexposure also in afternoon and evening. Compared with other treatments, CA determined increased Z-score-07:00 (P < .001), DRHC-td determined increased Z-score-AUC07:00→14:00 (P = .007), and DRHC-od induced lower Z-score-AUC14:00→23:00 (P = .015). Z-scores-AUC14:00→16:00 ≥ .619 best predicted questionnaire scores. CONCLUSIONS: None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF, and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.

Sleep rebound leads to marked recovery of prolonged sleep deprivation-induced adversities in the stress response and hippocampal neuroplasticity of male rats.

BACKGROUND: Sleep disturbances are not only frequent symptoms, but also risk factors for major depressive disorder. We previously reported that depressed patients who experienced "Hypersomnia" showed a higher and more rapid response rate under paroxetine treatment, but the underlying mechanism remains unclear. The present study was conducted to clarify the beneficial effects of sleep rebound through an experimental "Hypersomnia" rat model on glucocorticoid and hippocampal neuroplasticity associated with antidepressive potency. METHODS: Thirty-four male Sprague-Dawley rats were subjected to sham treatment, 72-h sleep deprivation, or sleep deprivation and subsequent follow-up for one week. Approximately half of the animals were sacrificed to evaluate adrenal weight, plasma corticosterone level, hippocampal content of mRNA isoforms, and protein of the brain-derived neurotrophic factor (Bdnf) gene. In the other half of the rats, Ki-67- and doublecortin (DCX)-positive cells in the hippocampus were counted via immunostaining to quantify adult neurogenesis. RESULTS: Prolonged sleep deprivation led to adrenal hypertrophy and an increase in the plasma corticosterone level, which had returned to normal after one week follow-up. Of note, sleep deprivation-induced decreases in hippocampal Bdnf transcripts containing exons II, IV, VI, and IX and BDNF protein levels, Ki-67-(+)-proliferating cells, and DCX-(+)-newly-born neurons were not merely reversed, but overshot their normal levels with sleep rebound. LIMITATIONS: The present study did not record electroencephalogram or assess behavioral changes of the sleep-deprived rats. CONCLUSIONS: The present study demonstrated that prolonged sleep deprivation-induced adversities are reversed or recovered by sleep rebound, which supports "Hypersomnia" in depressed patients as having a beneficial pharmacological effect.