The Use of Prednisolone versus Dual-Release Hydrocortisone in the Treatment of Hypoadrenalism

The introduction of adrenocortical extract in 1930, improved life expectancy to between two and five years with further increases seen with the introduction of cortisone acetate from 1948. Most patients are now treated with synthetic hydrocortisone, and incremental advances have been made with optimisation of daily dosing and the introduction of multi-dose regimens. Today there remains a significant mortality gap between individuals with treated hypoadrenalism and the general population. It is unclear whether this gap is a result of glucocorticoid over-replacement, under-replacement or loss of the circadian and ultradian rhythm of cortisol secretion, with detrimental risk of excess glucocorticoid at later times in the day. The way forwards involves replacement of the diurnal cortisol rhythm with better glucocorticoid replacement regimens. The steroid profile produced by both prednisolone and dual-release hydrocortisone (Plenadren), provide a smoother glucocorticoid profile than standard oral multidose regimens of hydrocortisone and cortisone acetate. The individualisation of prednisolone doses and lower bioavailability of Plenadren offer reductions in total steroid exposure. Although there is emerging evidence of both treatments offering better cardiometabolic outcomes than standard glucocorticoid replacement regimens, there is a paucity of evidence involving very low dose prednisolone (2-4 mg daily) compared to the larger doses (~7.5 mg) historically used. Data from upcoming clinical studies on prednisolone will therefore be of key importance in informing future practice.

Potency of gastrointestinal colonization and virulence of Candida auris in a murine endogenous candidiasis

Background Candida auris infections have recently emerged worldwide, and this species is highly capable of colonization and is associated with high levels of mortality. However, strain-dependent differences in colonization capabilities and virulence have not yet been reported. Objectives In the present study, we aimed to clarify the differences between clinically isolated invasive and non-invasive strains of C. auris. Methods We evaluated colonization, dissemination, and survival rates in wild C57BL/6J mice inoculated with invasive or non-invasive strains of C. auris under cortisone acetate immunosuppression, comparing with those of Candida albicans and Candida glabrata infections. We also evaluated the potency of biofilm formation. Results Stool fungal burdens were significantly higher in mice inoculated with the invasive strains than in those infected with the non-invasive strain. Along with intestinal colonization, liver and kidney fungal burdens were also significantly higher in mice inoculated with the invasive strains. In addition, histopathological findings revealed greater dissemination and colonization of the invasive strains. Regarding biofilm-forming capability, the invasive strain of C. auris exhibited a significantly higher capacity of producing biofilms. Moreover, inoculation with the invasive strains resulted in significantly greater loss of body weight than that noted following infection with the non-invasive strain. Conclusions Invasive strains showed higher colonization capability and rates of dissemination from gastrointestinal tracts under cortisone acetate immunosuppression than non-invasive strains, although the mortality rates caused by C. auris were lower than those caused by C. albicans.

Case Report: Ipilimumab-Induced Panhypophysitis: An Infrequent Occurrence and Literature Review

BackgroundImmune checkpoint inhibitors (ICIs), by unleashing the anticancer response of the immune system, can improve survival of patients affected by several malignancies, but may trigger a broad spectrum of adverse events, including autoimmune hypophysitis. ICI-related hypophysitis mainly manifests with anterior hypopituitarism, while the simultaneous involvement of both anterior and posterior pituitary (i.e., panhypophysitis) has rarely been described.Case PresentationIn June 2015, a 64-year-old man affected by liver metastases of a uveal melanoma was referred to us due to polyuria and polydipsia. Two months prior, he had started ipilimumab therapy (3 mg/kg iv every 21 days). The treatment was well-tolerated (only mild asthenia and diarrhea were reported). A few days before the fourth cycle, the patient complained of intense headaches, profound fatigue, nocturia, polyuria (up to 10 L urine/daily), and polydipsia. Laboratory tests were consistent with adrenal insufficiency, hypothyroidism, and transient central diabetes insipidus. The pituitary MRI showed an enlarged gland with microinfarcts, while the hypophyseal stalk was normal, and the neurohypophyseal ‘bright signal’ in T1 sequences was not detected. The treatment included dexamethasone (then cortisone acetate at replacement dose), desmopressin, and levothyroxine. Within the next five days, the symptoms resolved, and blood pressure, electrolytes, glucose, and urinalysis were stable within the normal ranges; desmopressin was discontinued while cortisone acetate and levothyroxine were maintained. The fourth ipilimumab dose was entirely administered in the absence of further side effects.ConclusionAs ICIs are increasingly used as anticancer agents, the damage to anterior and/or posterior pituitary can be progressively encountered by oncologists and endocrinologists in their clinical practice. Patients on ICIs and their caregivers should be informed about that risk and be empowered to alert the referring specialists early, at the onset of panhypopituitarism symptoms, including polyuria/polydipsia.

Metabolic Effects of Cortisone Acetate vs Hydrocortisone in Patients With Secondary Adrenal Insufficiency

Context Pharmacokinetic properties of cortisone acetate (CA) and hydrocortisone (HC) differ because CA needs to be converted into cortisol to become active. Objective This work analyzed the metabolic consequences of switching CA to an equivalent daily dose of HC in patients with secondary adrenal insufficiency (SAI). Design This was a post hoc analysis from a prospective study including individuals with hypopituitarism receiving growth hormone replacement. Data were collected before and after a switch from CA to an equivalent dose of HC (switch group). Two control groups were included: patients continuing CA replacement (CA control group) and adrenal-sufficient hypopituitary patients (AS control group). Results The analysis included 229 patients: 105, 31, and 93 in the switch, CA control, and AS control groups, respectively. After the change from CA to HC, increases in mean body weight (1.2 kg; P < .05), waist circumference (2.9 cm; P < .001), body fat measured by dual-energy x-ray absorptiometry (1.3 kg; P < .001), and glycated hemoglobin (0.3%; P < .05) were recorded in the switch group. The increase in mean waist circumference was greater than in the AS control group (0.9 cm; P < .05). Mean body fat increased in the switch group but not in the CA control group (–0.7 kg; P < .05). Conclusions A switch from CA to an equivalent dose of HC was associated with a worsened metabolic profile, suggesting that HC has a more powerful metabolic action than CA based on the assumption that 20 mg HC equals 25 mg CA.

Reversibility of Acute Adrenal Insufficiency after hip Replacement: A Case Series

Background: Acute adrenal insufficiency is a rare but potentially lethal condition that is important to identify promptly and treat with replacement therapy. It can be due to adrenal hemorrhage that can occur after major orthopedic surgery. Few data are available about potential recovery of adrenal function, as well as both timing and modality of cortisone acetate withdrawal, probably due to the assumption that adrenal failure is definitive. A not massive adrenal damage can justify a partial, or potentially complete, recovery of adrenal function. Methods: We had recently described a case of acute adrenal insufficiency, which developed shortly after hip replacement; the patient was able to discontinue cortisone acetate treatment 46 months after the diagnosis and remained untreated up to five years later. We found other two cases of acute adrenal insufficiency that developed about one week after major orthopedic surgery. We followed such patients for about three years, repeatedly reassessing adrenal imaging and cortisol response to 250 µg ACTH test, in order to ascertain the real need of lifetime substitutive treatment with cortisone acetate. Results: Acute adrenal insufficiency partially reverted during the follow up for both patients. We observed a reduction in adrenal glands’ volume and a progressive improvement of cortisol basal levels, without response (or with a poor one) to ACTH stimulation, as well as with ACTH basal levels persistently above the normal range after 36 and 28 months respectively after the acute event. Conclusions: The present finding suggests that patients developing acute adrenal insufficiency after major orthopedic surgery must undergo long-term surveillance, in order to establish if steroid replacement has to be continued, or if it can be safely withdrawn.

Xác định đồng thời 07 glucocorticoid trong mỹ phẩm bằng sắc ký lỏng khối phổ hai lần (LC-MS/MS)

Phương pháp sắc ký lỏng hiệu năng cao kết hợp với đầu dò khối phổ ba tứ cực sử dụng kỹ thuật ion hóa phun điện tử (LC-ESI-MS/MS) để xác định và định lượng đồng thời 7 glucocorticoids gồm hydrocortisone acetate (HCA), cortisone acetate (COA), prednison (PDS), prednisolone (PDL), methylprednisolone (MPL), dexamethasone (DEX)) và fluocinolone acetonid (FLA) đã được xây dựng và thẩm định. Phương pháp có thể được sử dụng để xác định các glucocorticoid trộn trái phép trong mỹ phẩm dạng kem và dạng gel bôi. Các chất phân tích trong mẫu được chiết lặp với ethyl acetate, làm sạch bằng cột chiết pha rắn C18 và phân tích trên sắc ký lỏng khối phổ hai lần. Các hợp chất được phân tách bằng sắc ký lỏng pha đảo kết hợp với rửa giải gradient nồng độ: 0,1% acid formic trong nước và acetonitril. Giới hạn phát hiện và giới hạn định lượng cho PDS, PDL và FLA lần lượt là 0,3 µg/g và 0,6 µg/g và đối với những chất khác là 0,03 và 0,12 µg/g. Độ lặp lại dưới 23% và độ thu hồi trong khoảng 80-110% đáp ứng yêu cầu Châu Âu theo EC-657/2002. Phương pháp được ứng dụng thành công để phân tích 20 mẫu mỹ phẩm trên thị trường Việt Nam. Kết quả cho thấy có khoảng 20% mẫu thử chứa glucocorticoid với nồng độ dao động từ 0,175 đến 16,2 µg/g.