Vincent AmodruAix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics, Institut MarMaRa, Marseille, France Assistance Publique – Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Marseille, France
Thierry BrueAix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics, Institut MarMaRa, Marseille, France Assistance Publique – Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Marseille, France
Frederic CastinettiAix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics, Institut MarMaRa, Marseille, France Assistance Publique – Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Marseille, France
Here, we describe a case of a patient presenting with adrenocorticotrophic hormone-independent Cushing’s syndrome in a context of primary bilateral macronodular adrenocortical hyperplasia. While initial levels of cortisol were not very high, we could not manage to control hypercortisolism with ketoconazole monotherapy, and could not increase the dose due to side effects. The same result was observed with another steroidogenesis inhibitor, osilodrostat. The patient was finally successfully treated with a well-tolerated synergitic combination of ketoconazole and osilodrostat. We believe this case provides timely and original insights to physicians, who should be aware that this strategy could be considered for any patients with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.
Ketoconazole–osilodrostat combination therapy appears to be a safe, efficient and well-tolerated strategy to supress cortisol levels in Cushing syndrome.
Ketoconazole and osilodrostat appear to act in a synergistic manner.
This strategy could be considered for any patient with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.
Considering the current cost of newly-released drugs, such a strategy could lower the financial costs for patients and/or society.
We report the onset of acute Charcot neuroarthropathy during pregnancy in two patients with type 1 diabetes using retrospective review of case notes. We describe for the first time the onset of acute Charcot neuroarthropathy during pregnancy in two patients with type 1 diabetes. Pregnancy may promote the onset and worsening of a number of diabetic complications. A link between pregnancy and the onset of acute Charcot neuroarthropathy is demonstrated for the first time in this report.
Patients with already diagnosed sensitive neuropathy can develop an active phase of Charcot neuroarthropathy during pregnancy.
The rapid correction of hyperglycaemia may induce an active phase of Charcot neuroarthropathy during pregnancy.
Multiple endocrine metastases are a rare but possible complication of lung adenocarcinoma (LAC). Pituitary metastasis is a rare condition with poor clinical expression. Diabetes insipidus (DI) is its most common presenting symptom. Here we report an original case of a pituitary stalk (PS) metastasis from LAC presenting as central DI followed by adrenal insufficiency (AI) from bilateral adrenal metastasis, without known evidence of the primary malignancy. A 45-year-old woman whose first clinical manifestations were polyuria and polydipsia was admitted. She was completely asymptomatic with no cough, no weight loss or anorexia. Chest radiography was normal. Brain MRI showed a thick pituitary stalk (PS). DI was confirmed by water restriction test and treated with vasopressin with great clinical results. Explorations for systemic and infectious disease were negative. Few months later, an acute AI led to discovering bilateral adrenal mass on abdominal CT. A suspicious 2.3 cm apical lung nodule was found later. Histopathological adrenal biopsy revealed an LAC. The patient received systemic chemotherapy with hormonal replacement for endocrinological failures by both vasopressin and hydrocortisone. We present this rare case of metastatic PS thickness arising from LAC associated with bilateral adrenal metastasis. Screening of patients with DI and stalk thickness for lung and breast cancer must be considered. Multiple endocrine failures as a diagnostic motive of LAC is a rare but possible circumstance.
Adrenal metastasis is a common location in lung adenocarcinoma; however, metastatic involvement of the pituitary stalk remains a rare occurrence, especially as a leading presentation to diagnose lung cancer.
The posterior pituitary and the infundibulum are the preferential sites for metastases, as they receive direct arterial blood supply from hypophyseal arteries.
Patients diagnosed with diabetes insipidus due to pituitary stalk thickness should be considered as a metastasis, after exclusion of the classical systemic and infectious diseases.
The diagnosis of an endocrinological metastatic primary lung adenocarcinoma for patients without respiratory symptoms is often delayed due to a lack of correlation between endocrinological symptoms and lung cancer.
The main originality of our case is the concomitant diagnosis of both endocrinological failures, as it was initiated with a diabetes insipidus and followed by an acute adrenal insufficiency.
Mitotane (o,p′-DDD) is the standard treatment for advanced adrenocortical carcinoma (ACC). Monitoring of plasma mitotane levels is recommended to look for a therapeutic window between 14 and 20mg/L, but its positive predictive value requires optimization. We report the case of an ACC patient with a history of dyslipidemia treated with mitotane in whom several plasma mitotane levels >30mg/L were found together with an excellent neurological tolerance. This observation led us to compare theoretical or measured o,p′-DDD and o,p′-DDE levels in a series of normolipidemic and dyslipidemic plasma samples to explore potential analytical issues responsible for an overestimation of plasma mitotane levels. We demonstrate an overestimation of mitotane measurements in dyslipidemic patients. Mitotane and o,p′-DDE measurements showed a mean 20% overestimation in hypercholesterolemic and hypertriglyceridemic plasma, compared with normolipidemic plasma. The internal standard p,p′-DDE measurements showed a parallel decrease in hypercholesterolemic and hypertriglyceridemic plasma, suggesting a matrix effect. Finally, diluting plasma samples and/or using phospholipid removal cartridges allowed correcting such interference.
Hypercholesterolemia (HCH) and hypertriglyceridemia (HTG) induce an overestimation of plasma mitotane measurements.
We propose a routine monitoring of lipidemic status.
We propose optimized methodology of measurement before interpreting high plasma mitotane levels.
Hypoglycemia is a common medical emergency. It is the most frequent complication induced by anti-diabetic treatment. However, it can be observed in other conditions unrelated to diabetes such as insulinoma, autoimmune disorders, and neoplasia. Herein, we report the case of a rare cause of severe and recurrent hypoglycemia in a 77-year-old woman with a malignant solitary fibrous tumor (MSFT). A 77-year-old woman was admitted to the emergency department for loss of consciousness induced by severe hypoglycemia. Her standard laboratory findings were unremarkable. HbA1c, albumin, renal, liver, thyroid, and adrenal function tests were normal. Cerebral CT scan was also normal. At the time of confirmed hypoglycemia, the serum level of insulin and C-peptide was low. On the basis of the past medical history and the absence of other comment etiologies, a paraneoplastic cause was suspected. Thus, the diagnosis of a non-islet cell tumor-induced hypoglycemia (NICTH) was established by the presence of incompletely processed precursors of IGF2 (big IGF2) in plasma electrophoresis. However, the IGF1 level was low. Therapy with corticosteroids improved hypoglycemia and clinical symptoms. NICTH is a rare cause of hypoglycemia. It should be considered in patients with mesenchymal or malignant epithelial tumors suffering from recurrent episodes of hypoglycemia. The diagnosis will be established in the case of low serum insulin concentrations and elevated levels of big IGF2. Treatment with corticosteroids, GH, or both can improve hypoglycemic symptoms and restore plasma glucose to normal levels.
NICTH is a very rare condition that should be considered in patients known to have mesenchymal or malignant epithelial tumors and suffering from recurrent episodes of hypoglycemia.
The diagnosis of an NICTH is established on the basis of the hypoinsulinemic hypoglycemia, the MSFT history, and the presence of paraneoplastic secretion of IGF1 or an immature form of IGF2.
Treatment with corticosteroids, GH, or both can improve hypoglycemic symptoms and restore plasma glucose to normal levels in NICTH.