scholarly journals Synergistic cortisol suppression by ketoconazole–osilodrostat combination therapy

2021 ◽  
Vol 2021 ◽  
Author(s):  
Vincent Amodru ◽  
Thierry Brue ◽  
Frederic Castinetti
Keyword(s):  
Side Effects ◽  
Combination Therapy ◽  
Cushing Syndrome ◽  
List Type ◽  
Adrenocorticotrophic Hormone ◽  
Financial Costs ◽  
Adrenocortical Hyperplasia ◽  
Cortisol Suppression ◽  
Learning Points ◽  
Very High

Summary 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. Learning points 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.

scholarly journals Carbimazole induced rhabdomyolysis

2021 ◽  
Vol 2021 ◽  
Author(s):  
Niamh O’Donnell ◽  
Aisling McCarthy ◽  
Ken Thong
Keyword(s):  
Adverse Effect ◽  
Creatine Kinase ◽  
Side Effects ◽  
Temporal Relationship ◽  
Early Recognition ◽  
Antithyroid Drug ◽  
Graves Disease ◽  
List Type ◽  
Musculoskeletal Complaints ◽  
Learning Points

Summary Carbimazole is a commonly used antithyroid drug (ATD), which is associated with several well-established side effects. However, Carbimazole-induced rhabdomyolysis is rarely reported in the literature. We report a 27-year-old male who presented with upper limb myalgia and significantly raised creatine kinase elevation, 1-month post commencement of Carbimazole for Graves’ disease. Carbimazole was ceased with subsequent clinical and biochemical improvement. Though the pathophysiology remains unclear, we hope to raise awareness regarding this rare adverse effect with a view to promote early recognition and prompt discontinuation of the offending medication caused by a commonly used medication in endocrinology. Learning points Musculoskeletal complaints can relate to unidentified and untreated hyperthyroidism. However one must be mindful that the treatment for these disorders can too induce myopathies. ATD-induced myopathy should be considered when there is a temporal relationship between introduction of ATDs and the onset of symptoms. If ATD-induced myopathy is being considered, other causes of myopathy should still be outruled. Prompt discontinuation of potentially offending medications may provide resolution of symptoms and avoid significant consequences.

scholarly journals Sirolimus therapy in a child with partially diazoxide-responsive hyperinsulinaemic hypoglycaemia

2016 ◽  
Vol 2016 ◽  
Author(s):  
Kah-Yin Loke ◽  
Andrew Sng Anjian ◽  
Yvonne Lim Yijuan ◽  
Cindy Ho Wei Li ◽  
Maria Güemes ◽  
...  
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Viral Gastroenteritis ◽  
List Type ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Glucose Levels ◽  
Capillary Glucose ◽  
Clinically Significant ◽  
Learning Points

Summary Hyperinsulinaemic hypoglycaemia (HH), which causes persistent neonatal hypoglycaemia, can result in neurological damage and it’s management is challenging. Diazoxide is the first-line treatment, albeit not all patients will fully respond to it, as episodes of hypoglycaemia may persist and it entails unpleasant adverse effects. Sirolimus, an mTOR inhibitor, has reportedly been successful in treating children with severe diffuse HH, thus obviating the need for pancreatectomy. We report a girl with HH, with a novel heterozygous ABCC8 gene missense mutation (c.4154A>T/ p.Lys1385Thr), who was initially responsive to diazoxide therapy. After 11 months of diazoxide treatment, she developed intermittent, unpredictable breakthrough episodes of hypoglycaemia, in addition to generalized hypertrichosis and weight gain from enforced feeding to avoid hypoglycaemia. Sirolimus, which was commenced at 15 months of age, gradually replaced diazoxide, with significant reduction and abolition of hypoglycaemia. The hypertrichosis resolved and there was less weight gain given the reduced need for enforced feeding. Sirolimus, which was administered over the next 15 months, was well tolerated with no significant side effects and was gradually weaned off. After stopping sirolimus, apart from hypoglycaemia developing during an episode of severe viral gastroenteritis, the capillary glucose concentrations were maintained >3.5 mmol/L, even after a 10 h fast. Sirolimus may have a role in the treatment of partially diazoxide-responsive forms of HH who experience breakthrough hypoglycaemia, but the long-term safety and efficacy of sirolimus are not established. Learning points: Conventional treatment of diffuse HH with diazoxide is not always effective in controlling hypoglycaemia and can be associated with unpleasant side effects. Sirolimus was successfully used to abolish recurrent hypoglycaemia in partially diazoxide-responsive HH, with resolution of unacceptable diazoxide-associated side effects. Sirolimus was well tolerated with no clinically significant side effects. Shortly after stopping sirolimus, the capillary glucose levels remained normoglycemic.

scholarly journals Cushing syndrome: uncovering Carney complex due to novel PRKAR1A mutation

2019 ◽  
Vol 2019 ◽  
Author(s):  
Catherine D Zhang ◽  
Pavel N Pichurin ◽  
Aleh Bobr ◽  
Melanie L Lyden ◽  
William F Young ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Carney Complex ◽  
Pathogenic Variant ◽  
Endocrine Tumors ◽  
List Type ◽  
Pathogenic Variants ◽  
Adrenal Imaging ◽  
Unenhanced Computed Tomography ◽  
Learning Points ◽  
Tomography Scan

Summary Carney complex (CNC) is a rare multiple neoplasia syndrome characterized by spotty pigmentation of the skin and mucosa in association with various non-endocrine and endocrine tumors, including primary pigmented nodular adrenocortical disease (PPNAD). A 20-year-old woman was referred for suspected Cushing syndrome. She had signs of cortisol excess as well as skin lentigines on physical examination. Biochemical investigation was suggestive of corticotropin (ACTH)-independent Cushing syndrome. Unenhanced computed tomography scan of the abdomen did not reveal an obvious adrenal mass. She subsequently underwent bilateral laparoscopic adrenalectomy, and histopathology was consistent with PPNAD. Genetic testing revealed a novel frameshift pathogenic variant c.488delC/p.Thr163MetfsX2 (ClinVar Variation ID: 424516) in the PRKAR1A gene, consistent with clinical suspicion for CNC. Evaluation for other clinical features of the complex was unrevealing. We present a case of PPNAD-associated Cushing syndrome leading to the diagnosis of CNC due to a novel PRKAR1A pathogenic variant. Learning points: PPNAD should be considered in the differential for ACTH-independent Cushing syndrome, especially when adrenal imaging appears normal. The diagnosis of PPNAD should prompt screening for CNC. CNC is a rare multiple neoplasia syndrome caused by inactivating pathogenic variants in the PRKAR1A gene. Timely diagnosis of CNC and careful surveillance can help prevent potentially fatal complications of the disease.

scholarly journals IgG4-related thyroiditis: a case report and review of literature

2014 ◽  
Vol 2014 ◽  
Author(s):  
Mahmud Abo Salook ◽  
Carlos Benbassat ◽  
Yulia Strenov ◽  
Amit Tirosh
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Systemic Disease ◽  
Hashimoto's Thyroiditis ◽  
List Type ◽  
Review Of Literature ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Aggressive Form ◽  
Learning Points ◽  
Very High

Summary A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patient's complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimoto's thyroiditis. Learning points IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them. IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimoto's thyroiditis. Patients with suspected IgG4-thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible.

scholarly journals Rare association of insulin autoimmune syndrome with ankylosing spondylitis

2015 ◽  
Vol 2015 ◽  
Author(s):  
Nishant Raizada ◽  
S H Rahaman ◽  
D Kandasamy ◽  
V P Jyotsna
Keyword(s):  
Ankylosing Spondylitis ◽  
Serum Insulin ◽  
High Serum ◽  
List Type ◽  
Rare Association ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Learning Points ◽  
Very High ◽  
Hyperinsulinemic Hypoglycaemia

Summary Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycaemia, which is known to occur in association with the use of sulfhydryl-containing drugs and autoimmune disorders. We describe a patient with hitherto an unreported association of IAS with ankylosing spondylitis. We have also performed and described a simplified method of polyethylene glycol (PEG) precipitation of an insulin bound antibody in the serum. Learning points IAS should be considered in differential diagnosis of endogenous hyperinsulinemic hypoglycaemia. Ankylosing spondylitis can be associated with IAS apart from several other autoimmune diseases. Very high serum insulin levels (100–10 000 μU/ml) are frequently seen in IAS. When faced with very high serum insulin before suspecting insulinoma, it is advisable that PEG precipitation of serum be done to identify antibody bound insulin. A clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.

EFFICACY OF CARVEDILOL COMBINED WITH ENDOSCOPIC VARICEAL LIGATION IN THE PREVENTION OF RECURRENT VARICEAL BLEEDING IN PATIENTS OF CIRRHOSIS

2016 ◽  
pp. 23-30
Author(s):  
Van Huy Tran ◽  
Thi Ngoc Diep Bui
Keyword(s):  
Side Effects ◽  
Beta Blocker ◽  
Variceal Bleeding ◽  
Poor Prognosis ◽  
Oesophageal Varices ◽  
Endoscopic Variceal Ligation ◽  
Efficacy And Safety ◽  
Orthostatic Hypertension ◽  
Key Words Carvedilol ◽  
Very High

Background: The recurrent variceal bleeding is still very high with a very poor prognosis. The combination of a non-selective beta-blocker and endoscopic variceal ligation (EVL) is still a standard therapy for the prevention, but many patients showed no response to propranolol. Carvedilol is a new, non-selective beta-blocker having intrinsic alpha-blocker activity, but the data about the efficacy and safety of carvedilol is still very limited. This study is aimed at assessing the efficacy and safety of carvedilol combined with EVL in the prevention of recurrent variceal bleeding. Patients and methods: 33 patients having variceal bleeding were enrolled. All patients received carvedilol and were performed the EVL until variceal eradication. All the patients were followed after 9 months. Results: rate of variceal eradication of oesophageal varices was 87.88%; the recurrence rate of variceal bleeding was 12.12% after 9 months. The side effects of carvedilol were rare and not severe, including vertiges, headache, and orthostatic hypertension. Conclusion: Carvedilol combined with EVL appeared as a relatively safe and effective in the prevention of recurrent variceal bleeding in patients of cirrhosis. Key words: carvedilol, variceal bleeding, EVL

scholarly journals Carbon dioxide levels in neonates: what are safe parameters?

2021 ◽  
Author(s):  
Sie Kei Wong ◽  
M. Chim ◽  
J. Allen ◽  
A. Butler ◽  
J. Tyrrell ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Systematic Review ◽  
Side Effects ◽  
Preterm Infants ◽  
Periventricular Leukomalacia ◽  
List Type ◽  
Permissive Hypercapnia ◽  
Prisma Statement ◽  
Carbon Dioxide Levels ◽  
Online Software

Abstract There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5–64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0–7.3 kPa: 45.0–54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. Impact There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5–7 kPa was inferred following systematic review.

EEG Synchronized TMS for Individualized Therapy in Major Depressive Disorder

2011 ◽  
Vol 26 (S2) ◽  
pp. 1144-1144
Author(s):  
Y. Jin ◽  
J. Phillips ◽  
Yueqin Huang ◽  
Steven Heurta
Keyword(s):  
Major Depressive Disorder ◽  
Side Effects ◽  
Depressive Disorder ◽  
Active Treatment ◽  
Rating Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Stimulus Frequency ◽  
List Type ◽  
Major Depressive ◽  
Double Blind

IntroductionEfficacy of conventional repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD) is limited. The authors report here on an alternative treatment using low energy synchronized TMS (sTMS) at the intrinsic frequency of subjects’ alpha electroencephalogram (EEG).ObjectivesEstablish efficacy and safety profile of sTMS in MDD.Aim(1)Examine the clinical effectiveness of sTMS.(2)Identify adverse effects associated with sTMS.MethodsFifty-two MDD subjects with 17-item Hamilton Depression Rating Scale (HAMD17) scores >17 were enrolled into a randomized, sham controlled, double-blind trial. Current medication remained unchanged during the trial. Depressive symptoms were evaluated by HAMD17 administered weekly.EEGs were recorded at baseline to determine the stimulus frequency and at week 4 to evaluate the physiological effect. sTMS was delivered through three 6000-G cylindrical neodymium magnets synchronously rotating at a rate equal to the subject's intrinsic alpha frequency.ResultsForty-five subjects completed at least 1 week of treatment and were evaluable. Those who received active treatment had superior clinical response to sham (t = 2.54, P = 0.01), where 55.2% in the active treatment group were clinical responders versus 12.5% in sham (X2 = 7.82, P = 0.005). No significant side effects were reported. The clinical improvement was correlated with the degree of EEG improvement (r = .46, P = 0.009).ConclusionsA therapeutic effect in MDD subjects can be achieved through administration of sTMS at the subject's alpha EEG frequency. Because of minimal side effects, this appears to be a safe and effective treatment option.

Topical clobetasol: an overlooked cause of Cushing syndrome

2021 ◽  
Vol 21 ◽  
Author(s):  
Sergio Ghirardo ◽  
Laura De Nardi ◽  
Alberto Tommasini ◽  
Egidio Barbi ◽  
Gianluca Tornese
Keyword(s):  
Side Effects ◽  
Chronic Granulomatous Disease ◽  
Oral Mucositis ◽  
Cushing Syndrome ◽  
Prolonged Treatment ◽  
Granulomatous Disease ◽  
Oral Corticosteroids ◽  
Severe Oral Mucositis

: We describe the case of an 11-year-old boy affected by chronic granulomatous disease complicated by a Crohn’s like colitis needing prolonged treatment with oral corticosteroids. His therapy for the control of severe oral mucositis was based on topical clobetasol, which did not decrease once the steroids were discontinued. Two years after the oral interruption of the steroids, cushingoid characteristics persisted, the cause of which, after a thorough investigation, was found to be the persistence of the topical clobetasol oral gel. Several studies investigated the efficacy of topical clobetasol for immuno-related mucositis, but little is known about its pharmacokinetics and side effects. In this report, we have reviewed the literature, defining a maximum putative dose of clobetasol mucosal gel to avoid Cushing syndrome.

scholarly journals On the Albedo of Snow in Antarctica: A Contribution to I.A.G.O.

1988 ◽  
Vol 34 (116) ◽  
pp. 19-25 ◽  
Author(s):  
Gerd Wendler ◽  
John Kelley
Keyword(s):  
Simple Model ◽  
Diurnal Variation ◽  
Austral Summer ◽  
Cloud Amount ◽  
Mechanical Action ◽  
List Type ◽  
Solar Elevation ◽  
Solar Noon ◽  
Terre Adélie ◽  
Very High

AbstractAs part of a larger experiment, detailed albedo measurements were carried out during the austral summer of 1985-86 in the dry-snow zone (1560 m) of Terre Adélie, eastern Antarctica. The following results were found:(1)Mean albedo values were high (around 82.6%). On clear days, the albedo showed some dependency on the solar elevation. The dependency was slight for solar elevations above 12° but became larger with low Sun angles.(2)The albedo was found to be a function of cloud amount and type, increasing with the amount and thickness of clouds. In white-out conditions, very high albedos were found (>90%).(3)The albedo showed a dependency on the type of snow. New snow displayed higher values than older snow, whose crystals had been destroyed by mechanical action.(4)A simple model was developed to assess the influence of sastrugi on the albedo. This model could explain the asymmetric diurnal variation about solar noon of the measured albedo above a sastrugi field.The above four dependencies might explain the considerable discrepancies which can be found in the literature concerning the snow albedo of Antarctica.

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