Morphologic and Molecular Characterization of Adrenals and Adrenal Rest Affected by Congenital Adrenal Hyperplasia.

Introduction: Adrenocortical hyperplasia and adrenal rest tumor (ART) formation are common in congenital adrenal hyperplasia (CAH). Although driven by excessive corticotropin, much is unknown regarding the morphology and transformation of these tissues. Our study objective was to characterize CAH-affected adrenals and ART and compare with control adrenal and gonadal tissues. Patients/Methods: CAH adrenals, ART and control tissues were analyzed by histology, immunohistochemistry, and transcriptome sequencing. We investigated protein expression of the ACTH receptor (MC2R), steroidogenic (CYP11B2, CYP11B1, CYB5A) and immune (CD20, CD3, CD68) biomarkers, and delta-like 1 homolog (DLK1), a membrane bound protein broadly expressed in fetal and many endocrine cells. RNA was isolated and gene expression was analyzed by RNA sequencing (RNA-seq) followed by principle component, and unsupervised clustering analyses. Results: Based on immunohistochemistry, CAH adrenals and ART demonstrated increased zona reticularis (ZR)-like CYB5A expression, compared to CYP11B1, and CYP11B2, markers of zona fasciculata and zona glomerulosa respectively. CYP11B2 was mostly absent in CAH adrenals and absent in ART. DLK1 was present in CAH adrenal, ART, and also control adrenal and testis, but was absent in control ovary. Increased expression of adrenocortical marker MC2R, was observed in CAH adrenals compared to control adrenal. Unlike control tissues, significant nodular lymphocytic infiltration was observed in CAH adrenals and ART, with CD20 (B-cell), CD3 (T-cell) and CD68 (macrophage/monocyte) markers of inflammation. RNA-seq data revealed co-expression of adrenal MC2R, and testis-specific INSL3, HSD17B3 in testicular ART indicating the presence of both gonadal and adrenal features, and high expression of DLK1 in ART, CAH adrenals and control adrenal. Principal component analysis indicated that the ART transcriptome was more similar to CAH adrenals and least similar to control testis tissue. Conclusions: CAH-affected adrenal glands and ART have similar expression profiles and morphology, demonstrating increased CYB5A with ZR characteristics and lymphocytic infiltration, suggesting a common origin that is similarly affected by the abnormal hormonal milieu. Immune system modulators may play a role in tumor formation of CAH.

Pituitary Surgery: Changing the Paradigm in Veterinary Medicine in the United States.

Medical management is currently the most common treatment for pituitary-dependent hyperadrenocorticism and hypersomatotropism/acromegaly in veterinary medicine. Medical management does not provide a cure for either disease process, and rarely is pituitary imaging a part of initial diagnostics. Early pituitary imaging in animals with clinically functional pituitary tumors provides a baseline assessment, allows monitoring of tumor changes, and permits radiation and surgical planning. Surgery is the only treatment for pituitary tumors that has curative intent and allows for a definitive diagnosis. Surgical removal of pituitary tumors via transsphenoidal hypophysectomy is an effective treatment for clinical pituitary tumors in patients exhibiting endocrine abnormalities associated with pituitary-dependent hyperadrenocorticism and hypersomatotropism. Surgery, however, is rarely pursued until patients have failed medical management, and often not until they are showing neurologic signs, making surgical success challenging. It is well documented that dogs surgically treated when the pituitary mass is small have a lower mortality, a lower recurrence rate, and a longer survival than those with larger pituitary masses. Providing owners with the option of early pituitary imaging in addition to medical, surgical, and radiation treatment options should be the standard of care for animals diagnosed with pituitary-dependent hyperadrenocorticism or hypersomatotropism.

Impaired dexamethasone resorption in two patients with pseudo-Cushing after bariatric surgery: Implications for immunosuppressive treatment.

Two cases of middle-aged female patients treated by gastric bypass surgery for weight loss presented to our clinic for a follow-up examination 3-6 months after the surgical procedure (a mini gastric bypass and a modified single anastomosis sleeve-ileostomy). In both patients increased ACTH levels and either high serum cortisol or an increased urinary cortisol excretion was apparent and triggered further endocrine testing. Serum cortisol could not be suppressed adequately by 2 and 4 mg dexamethasone in the standardized oral overnight suppression test while midnight salivary cortisol dropped well below the desired cut-off. This led to the hypothesis of an impaired dexamethasone resorption and could be further substantiated by suppression of serum cortisol below the cut-off by an intravenous dexamethasone application. The data presented point to an impairment of enteral synthetic corticosteroid resorption in patients after gastric bypass surgery and could be of importance for individuals in need for immunosuppressive treatment. In view of the growing number of bariatric procedures, pharmacokinetics of corticosteroids and other drugs should be tested in clinical trials.

ACTH-dependent Hypercortisolemia in a Patient with a Pituitary Microadenoma and an Atypical Carcinoid Tumour of the Thymus.

Cushing's syndrome (CS) is a set of clinical symptoms which occur as a result of hypercortisolemia. Endogenous ACTH-dependent CS related to an ectopic ACTH-secreting tumour constitutes 12%-17% of CS cases and is one of the most common causes of paraneoplastic syndromes. This study presents a case of a 31 year-old man with diabetes, hypertension, rosacea, purple stretch marks and hypokalemia. Findings of diagnostic procedures include high concentrations of cortisol and ACTH, pituitary microadenoma and a tumour in the anterior mediastinum. Dynamic hormone tests determined the source of excess hormone secretion and ectopic ACTH-dependent CS was diagnosed. Due to increasing symptoms of superior vena cava syndrome, an emergency resection of almost the whole tumour was performed, with only a small part of the upper pole left because of the proximity of large vessels and a risk of damaging them. On the basis of histopathological tests, an atypical carcinoid tumour of the thymus was identified. Immediately after the surgical procedure, there was a significant reduction of clinical and laboratory traits of hypercortisolemia, yet, during the 46 weeks of postoperative observation, despite chemotherapy, the progression of residual masses of the tumour occurred with metastases and increased hormone indices. The presented case shows and discusses the differentiation of ACTH-dependent hypercortisolemia and its causes, difficulties in surgical therapy and chemotherapy, as well as prognosis for atypical carcinoid of the thymus, which is a rare disease.

[Surgical treatment of ACTH-ectopic syndrome]. / Khirurgicheskoe lechenie AKTG-éktopicheskogo sindroma.

ACTH-ectopic syndrome is a severe, multiple-symptom disease characterized by secretion of adrenocorticotropic hormone (ACTH) by ectopic tumor, increased release of adrenal cortical hormones and clinical picture of hypercorticism. Diagnosis and treatment of ACTH-ectopic syndrome is still difficult problem despite the achievements of modern medicine. There are several unresolved issues including optimal diagnostic algorithm, indications for various surgical procedures and their optimal dates. This review is devoted to these questions.

Hyperadrenocorticism Caused by a Pituitary Ganglioglioma in a Dog.

An 11-year-old castrated male Chihuahua dog was presented with complaints of polyuria, polydipsia, abdominal enlargement, and alopecia. Hyperadrenocorticism was diagnosed on the basis of clinical signs, blood tests, adrenocorticotropin-stimulation test results, and an elevated serum adrenocorticotropin concentration. Contrast-enhanced magnetic resonance imaging showed that the pituitary gland was enlarged, compatible with a pituitary macroadenoma. Pituitary-dependent hyperadrenocorticism was suspected, and transsphenoidal hypophysectomy was thus performed for complete resection of the tumor. After surgery, the serum adrenocorticotropin concentration normalized and the hyperadrenocorticism resolved. Histological and immunocytochemical analyses revealed a benign tumor composed of mature neuronal cells and glial cells, suggestive of a ganglioglioma with immunolabeling for adrenocorticotropin. Careful analysis of the resected tumor revealed no pituitary adenoma tissue. The clinical and histopathologic findings indicated that the ganglioglioma was directly responsible for the hyperadrenocorticism. This is the first case of hyperadrenocorticism caused by a ganglioglioma in a dog.

Sympathomimetic Toxidromes and Other Pharmacological Causes of Acute Hypertension.

PURPOSE OF REVIEW: Acute drug-induced hypertension, sympathomimetic toxicity, and other hyperadrenergic states can be caused by both xenobiotic toxicity and withdrawal. This manuscript is a selective review of the recent literature regarding pharmacologic causes of hypertensive emergencies and other hyperadrenergic states. RECENT FINDINGS: We will discuss designer stimulants, alpha2 and baclofen agonist withdrawal, and the clinical entity known as posterior reversible encephalopathy syndrome (PRES). Additionally, we examine the controversial "unopposed alpha" phenomenon which may result from use of beta-adrenergic antagonist in the presence of stimulant toxicity. These topics encompass clinical situations and disease entities that are increasingly encountered and are often either unanticipated or under-recognized.

Hipercortisolismo cíclico por adenoma hipofisario / Cyclic hypercortisolism due to pituitary adenoma

A case study of a 41 years old woman with cyclic hypercortisolism is explained. AT the beginning, its manegment was shrinking the tumor, however afterward she needs medical treatment during cycles. The fluctuating clinical and discrepant bioquemical findings make it hard to diagnose. A review of this rare disorder is explained.

Diurnal Plasma Cortisol Measurements Utility in Differentiating Various Etiologies of Endogenous Cushing Syndrome.

Cortisol diurnal variation may be abnormal among patients with endogenous Cushing syndrome (CS). The study objective was to compare the plasma cortisol AM/PM ratios between different etiologies of CS. This is a retrospective cohort study, conducted at a clinical research center. Adult patients with CS that underwent adrenalectomy or trans-sphenoidal surgery (n=105) were divided to those with a pathologically confirmed diagnosis of Cushing disease (n=21) and those with primary adrenal CS, including unilateral adrenal adenoma (n=28), adrenocortical hyperplasia (n=45), and primary pigmented nodular adrenocortical disease (PPNAD, n=11). Diurnal plasma cortisol measurements were obtained at 11:30 PM and midnight and at 7:30 and 8:00 AM. The ratios between the mean morning levels and mean late-night levels were calculated. Mean plasma cortisol AM/PM ratio was lower among CD patients compared to those with primary adrenal CS (1.4±0.6 vs. 2.3±1.5, p<0.001, respectively). An AM/PM cortisol ratio≥2.0 among patients with unsuppressed ACTH (>15 pg/ml) excludes CD with a 85.0% specificity and a negative predictive value (NPV) of 90.9%. Among patients with primary adrenal CS, an AM/PM cortisol≥1.2 had specificity and NPV of 100% for ruling out a diagnosis of PPNAD. Plasma cortisol AM/PM ratios are lower among patients with CD compared with primary adrenal CS, and may aid in the differential diagnosis of endogenous hypercortisolemia.

Long-term outcome after adrenalectomy for incidentally diagnosed subclinical cortisol-secreting adenomas.

BACKGROUND: The management of subclinical cortisol-secreting adenomas (SCSAs) is controversial, and available evidence to assess the superiority of an operative versus a nonoperative approach is lacking. The aim of this work was to report the postoperative results and the long-term outcomes for patients with incidentally diagnosed SCSAs and to compare the results with those of patients who underwent an operation for cortisol-secreting adenomas (CSAs). METHODS: From 1994-2011, 107 consecutive patients underwent laparoscopic unilateral adrenalectomy for either an SCSA (n = 39) or a CSA (n = 68). Preoperatively, all patients underwent standardized clinical, hormonal, and imaging assessments. Patients were followed up for ≥2 years with serial assessments of body weight, blood pressure, and glycated hemoglobin, HbA1c. RESULTS: Operative resection of SCSAs and CSAs did not significantly differ regarding operative time, conversion rate, overall operative and medical morbidity, and duration of stay. For SCSAs, the comparison between preoperative status and 2-year assessment showed a median weight loss of 6% (P < .001), a decrease in the median HbA1c of 15% (P < .001), and an improvement or normalization of blood pressure in 50% of the patients. The same significant beneficial metabolic effects of the operation with even greater improvement were observed in patients with CSAs. CONCLUSION: Laparoscopic unilateral adrenalectomy for SCSA is associated with low morbidity, no mortality, and significant improvement of various aspects of metabolic syndrome. Until additional evidence from prospective randomized controlled studies is obtained, laparoscopic unilateral adrenalectomy should be considered a valid option in the care of patients with SCSA.

Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury.

BACKGROUND: Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome. METHODS: Blood was sampled from 166 isolated TBI patients (aged 45 ± 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine [interleukin (IL)-1ß, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] and chemokine [IL-8, eotaxin, eotaxin-3, IFN-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1ß, thymus activation regulated chemokine (TARC)] concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines [epinephrine (Epi), norepinephrine (NE)] were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (≤4) outcomes. RESULTS: Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF-α, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL-1ß, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated with IL-1ß, IL-10, TNF-α, eotaxin, IL-8, IP-10, and MCP-1. CONCLUSIONS: Our results provide further evidence that exaggerated SNS activation acutely after isolated TBI in humans may contribute to harmful peripheral inflammatory cytokine/chemokine dysregulation. These findings are consistent with a potentially beneficial role for therapies aimed at modulating the inflammatory response and hyperadrenergic state acutely post-injury.

[Use of 18F-FDG-positron emission tomography in presurgical evaluation of nonspecific or suspectious adrenal masses in non-oncologic patients]. / Utilidad de la tomografía de emisión de positrones con 18F-fluorodesoxiglucosa en la evaluación prequirúrgica de masas adrenales con características radiológicas inespecíficas o sospechosas de malignidad en pacientes sin cáncer.

BACKGROUND AND OBJECTIVE: Our purpose was to assess the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in pre-surgical characterization of adrenal masses. These masses were incidentally discovered in non-oncologic patients or during the study of endocrine hormone overproduction. These nodular lesions showed nonspecific or suspicious radiological features in the imaging tests routinely performed (CT and/or MRI). PATIENTS AND METHODS: This is a cross-sectional and prospective study in 12 patients with adrenal masses which were radiologically non-specific or suspicious for malignancy before adrenalectomy. An 18F-FDG-PET was made and quantitative FDG uptake (SUVmax) in the adrenal region (adrenal SUVmax) and liver (liver SUVmax), and the ratio SUVmax adrenal/liver was calculated. These parameters were related to the pathological findings. We evaluated the accuracy of the test by receive operating curves (ROC). RESULTS: The ROC to discriminate between benign and malignant lesions showed that the SUVmax was a better parameter than size or SUVmax adrenal/liver ratio. Using a SUVmax cutoff value≥3.1, sensitivity, specificity, positive and negative predictive value of the test were 100, 67, 50 and 100%, while a SUVmax adrenal/liver ratio≥1.8 showed a sensitivity, specificity, positive and negative predictive value of 67, 100, 100 and 90%, respectively. The presence of a SUVmax adrenal/liver ratio≥1.8 showed a statistically significant association with carcinoma occurrence. CONCLUSION: 18F-FDG-PET may be useful in the characterization of nonspecific or suspicious adrenal masses discovered in patients without a previous history of cancer. Its use in some cases could avoid unnecessary interventions.

Serum paraoxonase 1 and butyrylcholinesterase in dogs with hyperadrenocorticism.

The aim of this study was to evaluate serum activities of paraoxonase 1 (PON1) using three substrates; (1) 4-nitrophenylacetate (PON1n), (2) phenylacetate (PON1p), and (3) 5-thiobutyl butyrolactonase (PON1t), and butyrylcholinesterase (BChE) in dogs with hyperadrenocorticism (HAC). Serum activities of PON1 and BChE were higher in dogs with HAC than healthy dogs. There were strong positive correlations between PON1 activity measured with the three different substrates. This study demonstrated increased serum PON1 and BChE activities in dogs with HAC that could be attributed to the direct effect of glucocorticoids and lipid mobilisation.

Adrenocorticotrophic hormone causes an increase in cortisol, but not parathyroid hormone, in dogs.

Dogs with spontaneous disorders of glucocorticoid production often have marked disturbances in calcium homeostasis. For example, hypercalcaemia is frequently observed in dogs with hypoadrenocorticism and secondary hyperparathyroidism is a common feature of canine hyperadrenocorticism. The mechanism(s) by which glucocorticoids modulate calcium homeostasis in dogs remains ill-defined. The hypothesis of this study is that a marked increase in serum cortisol concentrations would lead to an immediate negative calcium balance state which would drive a compensatory increase in parathyroid hormone (PTH) concentrations. This hypothesis was investigated by measuring serum cortisol and plasma PTH concentration in 19 dogs before and after administration of adrenocorticotrophic (ACTH) hormone. Post ACTH administration, there was a significant increase in serum cortisol, but not PTH, concentrations. The results of this study do not support the hypothesis that an increase in endogenous glucocorticoids influences calcium balance sufficiently to cause an immediate, compensatory increase in parathyroid hormone concentration.

Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism.

A wide variety of autocrine/paracrine bioactive signals are able to modulate corticosteroid secretion in the human adrenal gland. These regulatory factors, released in the vicinity of adrenocortical cells by diverse cell types comprising chromaffin cells, nerve terminals, cells of the immune system, endothelial cells, and adipocytes, include neuropeptides, biogenic amines, and cytokines. A growing body of evidence now suggests that paracrine mechanisms may also play an important role in the physiopathology of adrenocortical hyperplasias and tumors responsible for primary adrenal steroid excess. These intra-adrenal regulatory systems, although globally involving the same actors as those observed in the normal gland, display alterations at different levels, which reinforce the capacity of paracrine factors to stimulate the activity of adrenocortical cells. The main modifications in the adrenal local control systems reported by now include hyperplasia of cells producing the paracrine factors and abnormal expression of the latter and their receptors. Because steroid-secreting adrenal neoplasms are independent of the classical endocrine regulatory factors angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism and hypercortisolism, these lesions have long been considered as autonomous tissues. However, the presence of stimulatory substances within the neoplastic tissues suggests that steroid hypersecretion is driven by autocrine/paracrine loops that should be regarded as promising targets for pharmacological treatments of primary adrenal disorders. This new potential therapeutic approach may constitute an alternative to surgical removal of the lesions that is classically recommended in order to cure steroid excess.

Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

Feline pituitary-dependent hyperadrenocorticism and insulin resistance due to a plurihormonal adenoma.

A 12-year-old female spayed domestic short-haired cat presented for lethargy, poor hair coat, alopecia, difficulty walking, and mild polyuria/polydipsia. The cat's skin tore easily in the neck area during routine restraint for blood draw. Physical examination, blood analysis, and ultrasound imaging were all consistent with pituitary-dependent hyperadrenocorticism (PDH) with secondary insulin-resistant diabetes mellitus, which was nonketotic. Insulin therapy, fluids, and diet change were initiated for the diabetes mellitus and the owner reported improvement in clinical signs although the blood glucose measurements remained elevated. Surgical repair of the torn skin was successful. Although a guarded prognosis was given to the owner because of an advanced stage of hyperadrenocorticism, and the limited treatment options currently available for feline PDH, trilostane was agreed on as an initial therapeutic option. The day trilostane was to be initiated, the cat presented with dyspnea and the owner chose to euthanize. Because of the rarity of hyperadrenocorticism disease in the cat, permission was obtained by the owner for a necropsy to confirm suspected PDH as the underlying cause for insulin resistance and skin fragility syndrome.

Isolated Cushing's syndrome in early infancy due to left adrenal adenoma: an unusual aetiology.

Bilateral macronodular adrenocortical disease as a part of McCune Albright Syndrome (MAS) is the most common cause of endogenous Cushing's syndrome (CS) in infancy. Adrenocortical tumors causing CS in infancy are extremely rare. We report the case of a girl with CS who presented at age 4 months with obesity and growth retardation. Her 8 am paired cortisol and adrenocorticotropic hormone levels were 49.3 µg/dL and <1 pg/mL, respectively with non-suppressed serum cortisol (41 µg/dL) on high-dose dexamethasone suppression test. Abdominal computed tomography scan demonstrated a 5.3x4.8x3.7 cm homogenous left adrenal mass with distinct borders. Laparotomy following pre-operative stabilization with ketoconazole 200 mg/day, revealed a 7.5x5x4 cm lobulated left adrenal mass with intact capsule and weighing 115 grams. Histopathology showed small round adrenal tumor cells with increased nucleo-cytoplasmic ratio and prominent nucleoli. The cells were separated by fibrous septae without any evidence of vascular or capsular invasion- findings consistent with adrenal adenoma. On the 8th post-operative day, after withholding hydrocortisone supplementation, the 8 am cortisol level was <1 µg/dL, suggestive of biochemical remission of CS. The patient improved clinically with a 7.5 kg weight loss over the next 3.5 months. This is perhaps the youngest ever reported infant with CS due to adrenal adenoma. Lack of clinical and biochemical evidence of hyperandrogenism as well as the benign histology in spite of the large tumor size (>7 cm diameter; 115 g) are some of the unique features of our patient.

Enfermedad de Cushing en la edad pediátrica. Tratamiento y evolución / Cushing’s syndrome in pediatric age. Treatment and evolution

El síndrome de Cushing endógeno es infrecuente en pediatría. La causa principal son los tumores hipofisarios productores de corticotropina (enfermedad de Cushing). Debe sospecharse en todo niño con una ganancia ponderal injustificada asociada a una disminución de la velocidad de crecimiento. La primera opción terapéutica en la enfermedad de Cushing es la adenomectomía transesfenoidal, seguida de la radioterapia si persiste el hipercortisolismo. Tras el tratamiento pueden asociarse alteraciones hipofisarias que precisen terapia sustitutiva; el déficit de hormona del crecimiento en niños puede originar un crecimiento recuperador insuficiente. Presentamos el caso de una niña de casi 11 años de edad, con ganancia ponderal injustificada, estancamiento del crecimiento, virilización y miopatía proximal. Mediante las determinaciones hormonales se confirmó un hipercortisolismo dependiente de corticotropina. La resonancia magnética craneal puso de manifiesto un microadenoma hipofisario, que se resecó mediante adenomectomía transesfenoidal, con remisión clínica y analítica. Previamente se había instaurado tratamiento con ketoconazol para controlar el hipercortisolismo. Al cabo de 4 años no había signos de recidiva (AU)

Endogenous Cushing’s syndrome is rare endocrine disorders in pediatric age whose most common cause are the pituitary tumors producers of adrenocorticotropin (ACTH) (Cushing’s syndrome, CS). This disease must be suspected in any children with unjustified weight gain associated with a decrease in the speed of growth. The first therapeutic option in the CS is the transsphenoidal adenomectomy, followed by radiotherapy if CS persists. After the treatment pituitary disorders can be associated which will need a substitutive therapy, growth hormone deficit can cause an inadequate catch-up growth in children. We report the case of a nearly 11 years-old girl with unjustified weight gain, growth stagnation, signs of virilization and proximalmyopathy. Through hormonal determinations was confirmed an ACTH-dependent hypercortisolism was confirmed. The cranial MRI showed a pituitary micro adenoma that was removed through transsphenoidal adenomectomy with clinical and analytic remission. Before surgery, ketoconazole was used in order to control hypercortisolism. There were no signs of relapse four years later (AU)

A case report of steroid cell tumour of the ovary--not otherwise specified variant with hyperandrogenism, hypercortisolism, hyperprolactinemia and hyperestrogenemia.

Here, we report a case of Steroid cell tumour of ovary--Not otherwise specified variant, who presented with evidences of hyperandrogenism, hypercortisolismn and hyperprolactinemia and hyperestrogenemnia. All hormone abnormalities were resolved after Right Salpingo-Oopherectomy.