Kisspeptin deficiency leads to abnormal adrenal glands and excess steroid hormone secretion.

Knockout mice for the kisspeptin receptor, Kiss1r (Kiss1r-/-) and its ligand kisspeptin, Kiss1 (Kiss1-/-) replicate the phenotype of isolated hypogonadotropic hypogonadism (IHH) associated with variants of these genes in humans. A recent report suggests that kisspeptin may be involved in human fetal adrenocortical development and function. Herein, we characterized the adrenal function and morphology in Kiss1-/- mice that do not go through normal puberty. Two fetal markers were expressed in eosinophilic cells potentially derived from the X-zone that should disappear at puberty in male mice and during the first pregnancy in female animals. Although the hypercorticosteronism observed in Kiss1-/- females corrected overtime, hyperaldosteronism persisted at 14 months and correlated with the overexpression of Star. To determine if KISS1 and KISS1R genes are involved in the development of primary aldosteronism (PA) and hypercortisolism [Cushing's syndrome (CS)] in humans, we sequenced these 2 genes in 65 patients with PA and/or CS. Interestingly, a patient with CS presented with a germline KISS1 variant (p.H90D, rs201073751). We also found three rare variants in the KISS1R gene in three patients with PA: p.C95W (rs141767649), p.A189T (rs73507527) and p.R229R (rs115335009). The two missense variants have been previously associated with IHH. Our findings suggest that KISS1 may play a role in adrenal function in mice and possibly adrenocortical steroid hormone secretion in humans, beyond its recently described role in human fetal adrenocortical development.

Polimiopatia hipocalêmica e hipertensão secundária a hiperaldosteronismo primário felino / Hypokalemic polymyopathy and secondary hypertension to feline primary hyperaldosteronism

O hiperaldosteronismo se define pela hipersecreção de aldosterona pelas suprarrenais, resultando em excesso de sódio e redução de potássio sanguíneo. Esta hipersecreção deve-se à síntese autônoma de aldosterona por células adrenais hiperplásicas ou neoplásicas, que agem independentemente da estimulação pelo sistema renina-angiotensina. A doença acomete felinos de adultos maduros a idosos. O excesso de aldosterona culmina em hipertensão sistêmica e/ou hipocalemia, que levam à fraqueza muscular e alterações oculares. O diagnóstico é baseado em exames laboratoriais e de imagem, e o tratamento pode ser clínico ou cirúrgico. O prognóstico é considerado favorável quando as medicações são capazes de melhorar as manifestações clínicas ou quando é possível realizar o procedimento cirúrgico. O presente trabalho visa relatar o caso de um felino macho de 13 anos, castrado, sem raça definida, com hipocalemia persistente secundária a um presuntivo tumor adrenal.

Hyperaldosteronism is defined by the hypersecretion of aldosterone by the adrenal glands resulting in excess sodium and reduced blood potassium. This hypersecretion is due to the autonomous synthesis of aldosterone by hyperplastic or neoplastic adrenal cells, which act independently of stimulation by the renin-angiotensin system. The disease affects felines in the age group from mature adults to the elderly. The excess of aldosterone culminates in systemic hypertension and/or hypokalemia, which leads to muscle weakness and ocular changes. The diagnosis is based on laboratory and imaging tests and treatment can be clinical or surgical. The prognosis is considered favorable when the medications are able to improve the clinical manifestations or when it is possible to perform the surgical procedure. The present paper aims to report the case of a 13-year-old male cat, castrated, crossbred, with persistent hypokalemia secondary to a presumptive adrenal tumor.

Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness.

INTRODUCTION: Adrenal incidentalomas are lesions that are incidentally identified while scanning for other conditions. While most are benign and hormonally non-functional, around 20% are malignant and/or hormonally active, requiring prompt intervention. Malignant lesions can be aggressive and life-threatening, while hormonally active tumours cause various endocrine disorders, with significant morbidity and mortality. Despite this, management of patients with adrenal incidentalomas is variable, with no robust evidence base. This project aimed to establish more effective and timely management of these patients. METHODS: We developed a web-based, electronic Adrenal Incidentaloma Management System (eAIMS), which incorporated the evidence-based and National Health Service-aligned 2016 European guidelines. The system captures key clinical, biochemical and radiological information necessary for adrenal incidentaloma patient management and generates a pre-populated outcome letter, saving clinical and administrative time while ensuring timely management plans with enhanced safety. Furthermore, we developed a prioritisation strategy, with members of the multidisciplinary team, which prioritised high-risk individuals for detailed discussion and management. Patient focus groups informed process-mapping and multidisciplinary team process re-design and patient information leaflet development. The project was partnered by University Hospital of South Manchester to maximise generalisability. RESULTS: Implementation of eAIMS, along with improvements in the prioritisation strategy, resulted in a 49% reduction in staff hands-on time, as well as a 78% reduction in the time from adrenal incidentaloma identification to multidisciplinary team decision. A health economic analysis identified a 28% reduction in costs. CONCLUSIONS: The system's in-built data validation and the automatic generation of the multidisciplinary team outcome letter improved patient safety through a reduction in transcription errors. We are currently developing the next stage of the programme to proactively identify all new adrenal incidentaloma cases.

Horseshoe adrenal gland associated with spinal and vascular anomalies.

Horseshoe (or butterfly) adrenal gland (HAG) is an exceedingly rare congenital abnormality compared to horseshoe kidney. Here we present computed tomography findings of HAG in a 70-year-old man, associated with some spinal and vascular abnormalities; in addition, a brief review of HAG in adult people is presented. In our case, spinal anomalies included a severe scoliosis, a "butterfly" deformation of Th9 vertebra and the presence of a "split lumbosacral thecal sac" at L5 level. As regards, vascular anomalies, they were noted: the origin of the left common carotid artery from the innominate artery and the absence of celiac trunk with separate origin of three branches directly off the aorta (a splenic artery, a left gastrohepatic trunk and a right hepatic-pancreaticoduodenal artery).

Prenatal glucocorticoids exposure and fetal adrenal developmental programming.

Clinically, we apply synthetic glucocorticoids to treat fetal and maternal diseases, such as premature labor and autoimmune diseases. Although its clinical efficacy is positive, the fetus will be exposed to exogenous synthetic glucocorticoids. Prenatal adverse environments (such as xenobiotics exposure, malnutrition, infection, hypoxia and stress) can cause fetuses overexposure to excessive endogenous maternal glucocorticoids. The level of glucocorticoids is the key to fetal tissue maturation and postnatal fate. A large number of studies have found that prenatal glucocorticoids exposure can lead to fetal adrenal dysplasia and dysfunction, continuing after birth and even into adulthood. As the core organ of fetal-originated adult diseases, fetal adrenal dysplasia is closely related to the susceptibility and occurrence of multiple chronic diseases, and there are also obvious gender differences. However, its intrauterine programming mechanisms have not been fully elucidated. This review summarizes recent advances in prenatal glucocorticoids exposure and fetal adrenal developmental programming alterations, which is of great significance for explaining adrenal developmental toxicity and the intrauterine origin of fetal-originated adult diseases.

Pheochromocytoma arising in the settingof adrenal-renal fusion.

Adrenal-renal fusion is an anomaly misclassified as a renal tumor due to the absence of pathognomonic radiographic features. Herein, we report a case of a 61-year-old male who underwent a right radical nephrectomy for a presumed renal malignancy. Pathologic evaluation demonstrated a pheochromocytoma in the context of adrenal-renal fusion. Neoplastic transformation of fused adrenal tissue is rare but not unheard of and is typically adrenal cortical in origin. To our knowledge, this is the first description of a pheochromocytoma originating from an adrenal-renal fusion. The clinical presentation did not raise a high index of suspicion for the ultimate diagnosis rendered.

Simultaneous occurrence of primary aldosteronism due to aldosteronoma and ectopic meningioma in the adrenal gland: A case report.

RATIONALE: Primary aldosteronism due to aldosteronoma is the most common form of secondary hypertension, with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Diagnosis is a clinical challenge with simultaneous occurrence of primary ectopic meningioma in the adrenal gland. To our knowledge this is the first reported case of simultaneous occurrence of aldosteronomas and ectopic meningioma in the adrenal gland based on literatures. PATIENT CONCERNS: A 30-year-old man presented with resistant hypertension for one year. The computed tomographic scans were suggestive of left adrenal gland hyperplasia. INTERVENTION: The patient underwent partial unilateral laparoscopic adrenalectomy. DIAGNOSIS: The histopathological examination of the resected sample confirmed primary ectopic meningioma in adrenal gland and aldosterone producing adenoma (APA). The saline load test, captopril test, and plasma aldosterone/renin ratio were indicative of primary aldosteronism (PA). OUTCOMES: The patient had controlled blood pressure postoperatively. LESSONS: The patient was diagnosed with PA due to APA and nonfunctional primary ectopic meningioma in the adrenal gland which is very rare and dealt with unilateral laparoscopic adrenalectomy.

Pneumatosis coli after partial ligation of congenital portosystemic shunt in a dog.

Pneumatosis coli is a rare intestinal disorder in dogs that is characterized by submucosal or subserosal emphysema of the colon. An 8-year-old castrated male Shih Tzu developed anorexia and hematochezia after undergoing surgery for a congenital splenophrenic shunt. Abdominal radiographic examination revealed linear radiolucency throughout the wall of the large intestine. Results of abdominal computed tomography revealed intramural gas tracking along the colon and rectum. Based on these findings, a diagnosis of pneumatosis coli was made. The dog was treated with antibiotics, but the general condition gradually deteriorated, and the dog died 6 days after the day of diagnosis. It was suspected that portal hypertension following partial ligation of congenital portosystemic shunt may have been associated with pneumatosis coli in this case.

Variations in vascular anatomy and unilateral adrenal agenesis in a female cadaver with situs inversus totalis.

PURPOSE: Situs inversus totalis is mirror transposition of thoracic and abdominal organs. Very few reports have been published on anatomic dissections of cadavers with this condition. METHODS: This work describes a case of situs inversus totalis identified during the anatomical dissection of a 91-year-old woman. RESULTS: Thoracic and abdominal viscera were inverted, but otherwise normal. The aorta originated from the right ventricle, which exhibited characteristics of the systemic ventricle. The pulmonary artery originated from the left ventricle, which had a tricuspid valve, three papillary muscles, thick trabeculae, a supraventricular crest, and septomarginal trabecula. The atrial situs was concordant with ventricular morphology. Lungs and paranasal sinuses were not suggestive of Kartagener's syndrome. Only the right adrenal gland was present, and variations in vascular anatomy were observed. The latter included: the celiac trunk branching into a phrenic artery, the splenic artery and a right gastric artery; the common hepatic artery originating from the superior mesenteric artery; and, on the left side, two inferior thyroid arteries, both originating from thyrocervical trunk. The occurrence of a double inferior thyroid artery and agenesis of adrenal gland was never communicated in situs inversus. Embryonic origin of celiac trunk and superior mesenteric artery variations could be explained by the separation at higher levels of the longitudinal anastomoses formed between the four roots of omphalomesenteric artery. CONCLUSION: It can be hypothesized that this phenomenon could occur more frequently in situs inversus than in situs solitus. However, the number of cases investigated in such detail is too small to draw firm conclusions.

News about the genetics of congenital primary adrenal insufficiency.

Primary adrenal insufficiency (PAI) is characterized by impaired production of steroid hormones due to an adrenal cortex defect. This condition incurs a risk of acute insufficiency which may be life-threatening. Today, 80% of pediatric forms of PAI have a genetic origin but 5% have no clear genetic support. Recently discovered mutations in genes relating to oxidative stress have opened the way to research on genes unrelated to the adrenal gland. Identification of causal mutations in a gene responsible for PAI allows genetic counseling, guidance of follow-up and prevention of complications. This is particularly true for stress oxidative anomalies, as extra-adrenal manifestations may occur due to the sensitivity to oxidative stress of other organs such as the heart, thyroid, liver, kidney and pancreas.

Sonographic Detection of Accessory Adrenal Tissue in Neonates.

OBJECTIVES: The purpose of this study was to describe the incidence and appearance of accessory adrenal tissue in neonates, as diagnosed by high-resolution sonography, and increase the awareness of this entity. METHODS: We examined the adrenal glands in 153 neonates referred for renal and urinary tract sonography at our institution between January 2014 and January 2015. All kidneys and adrenal glands, except for ectopic kidneys, were scanned with the neonate prone and a linear array transducer with frequency of 11 or 14 MHz. RESULTS: In 9 neonates (5.9%), sonography showed a round, well-defined structure adjacent to the adrenal gland with a hyperechoic center and hypoechoic periphery, similar to the echogenicity of the normal adrenal medulla and cortex, respectively. The largest diameter of the structure measured 2.9 to 4.5 mm. On follow-up studies, which were available for 7 neonates, the structure was not evident, and the suprarenal area was normal. CONCLUSIONS: Accessory adrenal tissue can be identified in the suprarenal area in neonates with high-resolution sonography. Radiologists and sonographers caring for neonates should be aware of this finding and not confuse it with disease.

Direct and indirect imaging features of adrenohepatic fusion.

It is difficult to make a correct diagnosis when a lesion arising from adrenohepatic fusion occurs. Also, the anatomical characteristics may lead to various radiological features so that it is frequent to under- or over-treat a lesion from adrenohepatic fusion. Adrenohepatic fusion is characterized by the close intermixture of hepatocytes and adrenocortical cells with rare or no formation of a peri-adrenal capsule. The purpose of this clinical perspective was to describe the direct and indirect imaging features of adrenohepatic fusion and show their clinical implications for patient care.

Fetal suprarenal masses--assessing the complementary role of magnetic resonance and ultrasound for diagnosis.

OBJECTIVE: To assess the value and complementary roles of fetal MRI and US for characterization and diagnosis of suprarenal masses. MATERIALS AND METHODS: We conducted a multi-institutional retrospective database search for prenatally diagnosed suprarenal masses between 1999 and 2012 and evaluated the roles of prenatal US and fetal MRI for characterization and diagnosis, using postnatal diagnosis or surgical pathology as the reference standard. Prenatal US and fetal MRI were assessed for unique findings of each modality. RESULTS: The database yielded 25 fetuses (gestational age 20-37 weeks) with suprarenal masses. Twenty-one fetuses had prenatal US, 22 had MRI, 17 had both. Postnatal diagnoses included nine subdiaphragmatic extralobar sequestrations, seven adrenal hemorrhages, five neuroblastomas (four metastatic), two lymphatic malformations, one duplex kidney with upper pole cystic dysplasia, and one adrenal hyperplasia. Ultrasound was concordant with MRI for diagnoses in 12/17 (70.6%) cases. Discordant diagnoses between US and MRI included three neuroblastomas and two adrenal hemorrhages. In the three neuroblastomas US was equivocal and MRI was definitive for neuroblastoma, demonstrating heterogeneous, intermediate-signal solid masses and liver metastases. In the two cases of adrenal hemorrhage US was equivocal and MRI was definitive with signal characteristics of hemorrhage. In 2/4 neuroblastomas, Doppler US demonstrated a systemic artery suggesting extralobar sequestration; however MRI signal characteristics correctly diagnosed neuroblastoma. All cases of extralobar sequestration were correctly diagnosed by US and MRI. CONCLUSION: US and MRI both accurately detect suprarenal masses. MRI complements US in equivocal diagnoses and detects additional findings such as liver metastases in neuroblastoma.

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3ß-hydroxysteroid dehydrogenase (3ß-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3ß-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming.