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Adrenal crisis is the most extreme presentation form of adrenal insufficiency and represents a life-threatening endocrinological emergency. This situation can be triggered by different causes including the use of CYP3A4-inducing drugs, which accelerate hydrocortisone clearance. We describe the case of an 85-year-old woman with secondary adrenal insufficiency and chronic renal disease, who presented symptoms compatible with adrenal crisis (asthenia, adynamia, severe hyponatremia associated with neurological symptoms and hypotension) nine days after the start of modafinil treatment. The clinical picture improved rapidly with the suspension of modafinil and the administration of intravenous hydrocortisone. After ruling out the possible triggering causes (infectious, ischemic, pulmonary thromboembolism and failure to take hydrocortisone), it was interpreted that modafinil precipitated the symptoms of adrenal insufficiency by increasing the steroid clearance. Modafinil has the ability to induce the activity of CYP3A4 and consequently decrease the bioavailability of hydrocortisone. We emphasize the need to adjust steroid dose replacement in subjects receiving metabolism-inducing drugs.La crisis adrenal es la forma más extrema de presentación de la insuficiencia adrenal y representa una urgencia endocrinológica que llega a poner en riesgo la vida. Esta situación puede ser desencadenada por diferentes causas, entre las cuales se incluye el uso de fármacos inductores del CYP3A4, que aceleran la depuración de la hidrocortisona. Describimos el caso de una mujer de 85 años, con antecedentes de insuficiencia adrenal secundaria y enfermedad renal crónica, que presentó síntomas compatibles con crisis adrenal (astenia, adinamia, hiponatremia grave con síntomas neurológicos e hipotensión arterial) luego de nueve días del inicio de tratamiento con modafinilo. El cuadro clínico mejoró rápidamente con la suspensión del modafinilo y la administración de hidrocortisona endovenosa. Luego de descartar las posibles causas desencadenantes (infecciosas, isquémicas, tromboembolismo pulmonar y omisión en la toma de hidrocortisona), se interpretó que el modafinilo precipitó los síntomas de insuficiencia adrenal al aumentar la depuración del corticoide. El modafinilo tiene la capacidad de inducir la actividad del CYP3A4 y, en consecuencia, disminuir la biodisponibilidad de la hidrocortisona. Recalcamos la necesidad de ajustar la dosis de reemplazo de corticoides en sujetos que reciben fármacos inductores del metabolismo.

Carney complex is a multiple neoplasia syndrome having endocrine and non-endocrine manifestations. Diagnostic criteria include myxoma, lentigines, and primary pigmented nodular adrenocortical disease, amongst other signs/symptoms. In most cases it is an autosomal dominant disease, and diagnosis therefore requires study and follow-up of the family members. Inactivating mutations of the PRKAR1A gene were identified as the main cause of the disease, although since 2015 other disease-related genes, including PRKACA and PRKACB activating mutations, have also been related with Carney complex. This review will address the genetic aspects related to Carney complex.

Severe Cushing syndrome (SCS) is considered an emergency that requires immediate treatment to lower serum cortisol levels. Fluconazole may be considered an alternative treatment in Cushing syndrome when ketoconazole is not tolerated or unavailable. We report a 39-year-old woman with a history of partial pancreaticoduodenectomy due to a periampullary neuroendocrine tumor with locoregional extension. Three years after surgery, she developed liver metastases and was started on 120 mg of lanreotide/month, despite which, liver metastases progressed in the following 6 months. The patient showed extreme fatigue, muscle weakness, delirium, moon face, hirsutism and severe proximal weakness. Laboratory tests showed anemia, hyperglycemia and severe hypokalemia. 24-h urinary free cortisol: 2152 nmol/day (reference range (RR)

Summary We present the case of a 25-year-old male with a history of neurofibromatosis type 1 and bilateral pheochromocytoma 4 years after kidney transplantation that was successfully treated with simultaneous bilateral posterior retroperitoneoscopic adrenalectomy. Learning points: Hypertensive patients with NF1 should always be screened for pheochromocytoma. Pheochromocytoma is rarely associated with transplantation, but it must be ruled out in patients with genetic susceptibility. Posterior retroperitoneoscopic adrenalectomy (PRA) allows more direct access to the adrenal glands, especially in patients with previous abdominal surgeries.

Carney complex is a multiple neoplasia syndrome having endocrine and non-endocrine manifestations. Diagnostic criteria include myxoma, lentigines, and primary pigmented nodular adrenocortical disease, amongst other signs/symptoms. In most cases it is an autosomal dominant disease, and diagnosis therefore requires study and follow-up of the family members. Inactivating mutations of the PRKAR1A gene were identified as the main cause of the disease, although since 2015 other disease-related genes, including PRKACA and PRKACB activating mutations, have also been related with Carney complex. This review will address the genetic aspects related to Carney complex.

Adrenocorticotropin (ACTH) independent bilateral macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal) and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon) tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide) was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.La hiperplasia adrenal macronodular bilateral independiente de ACTH (HAMIA) es una causa infrecuente de Síndrome de Cushing, caracterizada por lesiones adrenales bilaterales, hipercortisolismo y ACTH plasmática suprimida. La síntesis de cortisol estaría regulada a través de ligandos de receptores asociados a proteína G que se expresan en forma aberrante en la corteza de las glándulas adrenales. El objetivo de este trabajo es analizar la presencia del receptor de glucagón en tejido adrenal de un paciente con diagnóstico de Síndrome de Cushing asociado a hiperplasia adrenal bilateral independiente de ACTH. Se realizaron tests de estímulos fisiológicos y farmacológicos para evaluar la respuesta en la secreción de cortisol. Como resultado se observó respuesta significativa del cortisol posterior al estímulo con glucagón. El paciente presentó buena evolución clínica y bioquímica al tratamiento con ketoconazol. La administración del análogo de somatostatina (octreotide) redujo los niveles de cortisol. Finalmente, la curación se logró posteriormente a la adrenalectomía bilateral. Mediante el estudio de PCR en Tiempo Real se halló la presencia del receptor de glucagón en tejido adrenal del paciente. Según nuestro conocimiento, es el primer paciente descripto de HAMIA vinculado a la expresión ilícita de receptores de glucagón.

A 25-year-old man arrived at the emergency room of his community hospital complaining of abdominal pain, headaches, and palpitations that had appeared suddenly while he was playing soccer. He had no history of hypertension. An abdominal ultrasound revealed a tumor located in the right adrenal gland. He was subsequently transferred to our hospital for further evaluation. On admission, he presented acute pulmonary edema with severe hypertension (blood pressure, 220/120 mm Hg). He was admitted to the coronary care unit. Intravenous vasodilators and loop diuretics were administered, with rapid recovery of clinical status. ECG showed sinus rhythm, a heart rate of 80 bpm, and T-wave inversion in the DI, DII, and AVL leads. Transthoracic echocardiography revealed left …

Previously unsuspected pituitary tumors (incidentalomas) were analyzed in autopsies (4.8–27%) and magnetic resonance imaging (MRI) (10–37%), most of them being micro-pituitary incidentalomas (PI). However, patients with PIs sometimes had macroadenomas which may relate to previously unsuspected neurological and/or endocrine abnormalities. This study aims to establish the incidence of macro- vs. micro-PIs, the need for medical and/or surgical treatment and the neurological and endocrine dysfunction in a retrospective evaluation of patients with PIs studied over six years (1994–2000). Thirty-eight of 46 patients with PIs (22 males), aged 16–77, were followed for a mean of 3.2 years. Initial hormonal testing, ophthalmologic evaluation and MRI were repeated during follow-up. Twenty-nine (63%) of 46 patients had macro-PIs and 17 (17%) micro-PIs. Twenty-three males (75%) had macro-PIs, 10 (34.5%) with visual field defects. Consultations leading to PI diagnosis were chronic headache (28%), cranial trauma (15.3%), sinusitis (13%) and stroke (13%). Partial deficiencies of the anterior pituitary function were confirmed in 19 PIs (41.3%), with secondary hypogonadism prevailing (30%). Seven PIs (15%) were prolactinomas treated with dopamine agonists. Seventeen PIs (37%) underwent surgery. Immunohistochemical analysis showed gonadotrophinomas (30%), plurihormonal non-secreting adenomas (40%), and pituitary adenomas not reacting to any of the anterior pituitary hormone antibodies (30%). One operated macro-PI was a craniopharyngioma. Our data show a high percentage of PIs are macro-incidentalomas against expectations from necropsy and imaging studies. Most macro-PIs are found in males and are clinically non-functioning adenomas, 37% requiring surgery and hormonal substitution.

The online version of the original article can be found underdoi:10.1007/s11102-005-0007-x.P. Fainstein Day M. Guitelman R. Artese L. Fiszledjer A. Chervin N. M. Vitale G. Stalldecker V. De Miguel D. Cornalo´ A. Alfieri M. S. Mallea-GilNeuroendocrinology Department of the Argentine Societyof Endocrinology and Metabolism, Buenos Aires (Departamentode Neuroendocrinolog´ia de la Sociedad Argentina deEndocrinolog ´ia y Metabolismo, Buenos Aires), Diaz Velez,3889, 1200 Buenos Aires, ArgentinaP. Fainstein Day (&)Lezica 3954, 1202 Buenos Aires, Argentinae-mail: patricia.fainstein@hospitalitaliano.org.ar