Addison's disease caused by adrenal tuberculosis may lead to misdiagnosis of major depressive disorder: A case report

BACKGROUND Addison’s disease(AD)is a rare but potentially fatal disease in Western countries,which can easily be misdiagnosed at an early stage.Severe adrenal tuberculosis(TB)may lead to depression in patients.CASE SUMMARY We report a case of primary adrenal insufficiency secondary to adrenal TB with TB in the lungs and skin in a 48-year-old woman.The patient was misdiagnosed with depression because of her depressed mood.She had hyperpigmentation of the skin,nails,mouth,and lips.The final diagnosis was adrenal TB that resulted in the insufficient secretion of adrenocortical hormone.Adrenocortical hormone test,skin biopsy,T cell spot test of TB,and adrenal computed tomography scan were used to confirm the diagnosis.The patient’s condition improved after hormone replacement therapy and TB treatment.CONCLUSION Given the current status of TB in high-burden countries,outpatient doctors should be aware of and pay attention to TB and understand the early symptoms of AD.

Occult Adrenal Insufficiency in Patients with Chronic Renal Disease

Background: Addison’s disease is a rare disorder of the adrenal cortex that leads to inadequate production of cortisol initially followed by aldosterone and androgens. Its manifestations are usually slow and non-specific with potential for life-threatening adrenal crisis following hypermetabolic demands (infection, trauma, surgery). Patients: Over the past 10 years, 19 CRD-patients were diagnosed with occult PAI in our center. Results: Unprovoked hypotension was the most common manifestations of occult PAI and was the unmasking event in 11 (58%). It was without significant cardiac and/or severe systemic sepsis and was refractory to isotonic saline infusions. Equal number of the remaining patients (n = 2) presented with persistent and inexplicable electrolytes abnormalities viz. 1) hyponatremia despite restricted oral fluid intake, lack of dehydration and massive fluid overload, as well as 2) hyperkalemia despite potassium-restricted diet, hyperkalemic drugs and adequate therapy with Furosemide and low-potassium dialysis-baths. On the other hand, similar proportions presented with unprovoked 3) progressive weight loss, decrease appetite and cachexia as well as 4) frequent hypoglycemic attacks. All patients were treated and were medically stable after 29 (2 - 60) months of follow up. Autoantibodies to 21-hydroxylase enzyme were positive in 16 (90%). At diagnosis, and subsequent follow up, only 7 patients (37%) had multi-endocrine dysfunction of whom 2 with type 1 and 5 with type 2. Conclusion: High index of suspicion should be exerted in diagnosis of PAI in patients with CRD, since its clinical picture is similar to CRD manifestations and complications. In those patients, confirmatory tests and specific management can save their lives. .

Congenital lipoid adrenal hyperplasia with Graves'disease:A case report

BACKGROUND Congenital adrenal hyperplasia(CAH),which is caused by a mutation of the steroidogenic acute regulatory(StAR)gene.Affected patients are usually characterized by adrenal insufficiency in the first year of life,salt loss,glucocorticoid and mineralocorticoid deficiency,and female external genitalia,regardless of chromosomal karyotype.Patients with non-classical lipoid CAH usually develop glucocorticoid deficiency and mild mineralocorticoid deficiency at 2-4 years of age.CASE SUMMARY Herein,We report the case of a woman with non-classic lipoid CAH combined with Graves’disease.Her chromosome karyotype was 46,XX,and highthroughput sequencing revealed two missense variants in the StAR gene:c.229C>T(p.Q77X)and c.814C>T(p.R272C),which were inherited from both parents(non-close relatives).The patient was treated for Graves’disease in a timely manner and the dosage of glucocorticoid was adjusted during the treatment of Graves’disease.CONCLUSION This is the first case of non-classic lipoid CAH combined with Graves’disease reported in the Chinese population.In addition to conventional glucocorticoid replacement therapy,timely adjustments were made to the dosages of thyroid hormone and glucocorticoid to avoid adrenal crisis as a consequence of the increased demand and accelerated metabolism of glucocorticoids when the patient was diagnosed with Graves’disease.

Refractory Arterial Hypotension in a Patient with COVID-19: Could the Hypothalamic-Pituitary-Adrenal Axis Be Involved? Case Report and Mini Review

Neuro-endocrinological manifestations rarely are described in cases of SARS- CoV-2. We describe a case of a previously hypertensive patient who presented COVID-19 and developed refractory arterial hypotension. In the investigation, low levels of ACTH and cortisol were observed, suggesting secondary adrenal insufficiency as the cause of refractory hypotension.

Corticosteroid-Induced Adrenal Insufficiency in Africa: Report of Nine Cases at the Internal Medicine/Endocrinology-Diabetology Department of Pikine NHC

Introduction: Prolonged corticosteroid therapy is labeled as the main cause of corticotropic adrenal insufficiency. However, the current frequency of this complication remains unknown. The objective of our study was to assess its epidemiologic, diagnostic, therapeutic, and evolutionary aspects of our practice. Methodology: A 60-month retrospective study was performed from May 2014 to April 2020 in the Pikine National Hospital Centre. Data were obtained from the medical records of patients with corticosteroid-induced adrenal insufficiency. Epidemiologic, diagnostic, therapeutic, and evolutionary parameters, and data related to corticotherapy were recorded. Patients with basal plasma cortisol levels <50 ng/ml or a plasma cortisol level less than double of the basal cortisolaemia one H after administration of synachtene 250 were included. Results: Medical records were obtained from nine patients, comprising six women and three men. The mean age of the patients was 48 years. Long-term corticosteroid therapy was used for self-medication in six patients and artificial bleaching in the remaining three patients. Betamethasone was the most commonly used drug in four patients, followed by clobetasol in three patients. Corticotropic insufficiency was revealed as a result of acute decompensation in five patients. All patients presented with a pseudo-cushingoid pattern. Diagnosis of corticotropic adrenal insufficiency was confirmed by measuring basal plasma cortisol levels of <50 ng/ml in seven patients. A standard Synachtene test was performed on two patients. All patients benefited from hydrocortisone supplementation. In the short-term, the outcome was unremarkable for all patients. Medium and long-term progression could be assessed in only three patients. Two patients showed persistent suppression with a 6- and 9-month follow-up. One patient was readmitted after one month due to an adrenal crisis following voluntary discontinuation of hydrocortisone treatment. Conclusion: Post-corticosteroid therapy adrenal insufficiency remains a concern in our practice and is favoured by the non-compliance of providing rules by pharmacies and the parallel drug market.

Prolonged Adrenal Insufficiency after Unilateral Adrenalectomy for Cortisolic Adenoma

Background: The suppression of the hypothalamic-pituitary-adrenal axis by cortisol-secreting adrenocortical tumors is well recognized and requires peri- and postoperative hydrocortisone substitution. Case Presentation: A 48-year-old female patient with hypertension and progressive weight gain, the clinical signs of hypercorticism motivated a hormonal workup revealing an independent ACTH Cushing’s syndrome: with urinary free cortisol (UFC) at 649 nmol/24h (4× normal), adrenocorticotropin hormone (ACTH) at 1.5 ng/l. The rest of the hormonal workup was not performed due to a lack of financial means. An Adrenal CT scan showed a 4 cm right adrenal adenoma. The patient underwent a right adrenalectomy with an adrenal adenoma on pathological examination. The contralateral side was normal. The patient was treated with hydrocortisone 30 mg/d for 6 weeks then 15 mg/d, during the monitoring we noted a persistence of the adrenal insufficiency for now 4 years. Basal cortisol levels during follow-up were very low (<3 μg/dl) ruling out the need for synacthen stimulation tests. Conclusion: Adrenal cortisol tumors are recognized by suppression, the duration of hypothalamic-pituitary-adrenal axis suppression is variable from 11 to 60 months depending on the series, which depends on the duration, severity of hypercortisolism, tumor size and other unknown factors. A longer follow-up of these patients is necessary to look for recovery of the contralateral adrenal gland.

Early Identification and Diagnosis of Adrenal Crisis after Retroperitoneal Laparoscopic Unilateral Adrenalectomy

The occurrence of adrenal crisis after retroperitoneal laparoscopic unilateral adrenalectomy is usually concealed.If not timely diagnosis and treatment,it may cause shock,and even lead to death.It is very difficult to distinguish the clinical manifestations of adrenal crisis from nausea,vomiting,fatigue,gas separation from the lower diaphragm,abdominal pain,hypotension,hypertension,fever and hypothermia after operation.This makes it very difficult to identify and diagnose adrenal crisis early.This article mainly discusses the early recognition,diagnosis and treatment of adrenal crisis after unilateral adrenalectomy by retroperitoneoscope.

Empty Sella Turcica Syndrome: About a Case Revealed by Adrenal Insufficiency

Background: Empty sella turcica corresponds to an arachnocele which may be complete or partial, primary or secondary. The primary form is rarer. Its cause is unknown, but etiological factors have been identified. The prevalence of this condition is variable, depending on techniques of diagnosis. It may be detected fortuitously on imaging or in the presence of neurological, ocular or endocrine manifestations. Aim: We aim to report a case of empty sella turcica syndrome revealed by adrenal insufficiency in a young African black woman. Case presentation: It was an overweight young woman with signs of intracranial hypertension associated with central adrenal insufficiency. The diagnosis of empty sella was confirmed by magnetic resonance imaging. Secondarily, she developed a hypo metabolism syndrome and biology confirmed central hypothyroidism. After correction of the adrenal cortical deficit, the treatment of the thyroid deficit was administered. Evolution was favourable clinically and biologically. Conclusion: The empty sella turcica is rare and its revelation by a central adrenal insufficiency is even more. The case we report is a perfect illustration.

Adrenal Insufficiency by Adrenoleukodystrophy

The X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disorder due to mutations in the ABCD1 gene. Objective: To report a case of a 19-year-old man with adrenal insufficiency due to adrenoleukodystrophy. Method: Case report and literature review. Result: A previously healthy 19-year-old male patient was admitted to the emergency room with nausea and vomiting for 5 days, who progressed to abdominal pain, severe asthenia, and fever (38.5°C). He referred progressive darkening of the skin, oral mucosa, tongue and nail bed of the hands and feet, observed in the last 6 years. Emergency laboratory evaluation showed severe hyponatremia and hyperkalemia, which, together with decreased plasma cortisol, directed the investigation to causes of adrenal insufficiency. High ACTH (Adrenocorticotropic hormone) and very long chain fatty acid levels closed the diagnosis. Discussion: ALD is characterized by progressive demyelination in the central and peripheral nervous system and adrenal insufficiency consequence to the accumulation of very long chain fatty acids (VLCFA) in the adrenal. The overall incidence of ALD is 1:17,000. Adrenal insufficiency may be the first symptom of ALD in boys and adults. The diagnosis is based on the measurement of VLCFA plasma levels. Allogeneic bone marrow transplantation is the only treatment that provides a permanent cure when the procedure is performed at an early stage of brain demyelination, i.e. when patients are asymptomatic, although brain magnetic resonance imaging (MRI) is abnormal. Treatment of Addison’s disease is obligatory, but does not change the course of neurological symptoms.

Sepsis-associated liver injury:Mechanisms and potential therapeutic targets

In this editorial,we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury(SLI)and its treatment.SLI is a serious complication of sepsis,primarily caused by microcirculatory disturbances,the gut-liver axis,and inflammatory responses.Specific treatment recommendations for SLI are lacking.The gut-liver axis represents a potential therapeutic target,with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function.Although immunomodulatory therapies are being explored,anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits.Statins may reduce liver inflammation and prevent injury in sepsis,but their clinical application is limited.Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients,indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency.Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results,likely due to inadequate assessment of the immune status of the host.Future research should prioritize the development of personalized immunotherapy tailored to patients’immune profiles,focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

New determinants of prognosis in bacterial infections in cirrhosis

Despite major advances in the knowledge and management of liver diseases achieved in recent decades,decompensation of cirrhosis still carries a high burden of morbidity and mortality.Bacterial infections are one of the main causes of decompensation.It is very important for clinical management to be aware of the population with the highest risk of poor outcome.This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently.Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines.Moreover,it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and,in infected patients,with the degree of sepsis.It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection,severe sepsis,hepatorenal syndrome and death.We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis.

The procalcitonin-to-cortisol ratio is a potential prognostic predictor in sepsis with abdominal source:a retrospective observational study

BACKGROUND:The aim of the study was to investigate the procalcitonin-to-cortisol ratio(P/C ratio)as a prognostic predictor among septic patients with abdominal source.METHODS:We retrospectively enrolled 132 post-surgery patients between 18 and 90 years old with sepsis of the abdominal source.On the second day of sepsis onset,cortisol,procalcitonin(PCT),Acute Physiology and Chronic Health Evaluation(APACHE)II score,Sequential Organ Failure Assessment(SOFA)score,C-response protein(CRP),and other baseline characteristics were collected.In addition,the length of ICU stay,length of mechanical ventilation(MV)days,length of shock days,and 28-day mortality were also recorded.Univariate analysis was performed to screen potential risk factors.Stratified analysis was used to identify the interaction among the risk factors.Multivariate analysis was also utilized to demonstrate the relationship between the risk factors and mortality.The receiver operator characteristic(ROC)curve analysis was conducted to evaluate the risk factors.A restricted cubic spline(RCS)demonstrated the association between survival outcome and the P/C ratio variation.RESULTS:A total of twenty-nine patients died,and 103 patients survived within 28 d.There were significant differences in cortisol,PCT,P/C ratio,interleukin(IL)-6,SOFA,and APACHE II scores between the survival and non-survival groups.No significant interaction was observed in the stratified analysis.Logistic regression analysis revealed that P/C ratio(P=0.033)was significantly related to 28-day mortality.Based on ROC curves,P/C ratio(AUC=0.919)had a higher AUC value than cortisol or PCT.RCS analysis depicted a positive relationship between survival possibility and P/C ratio decrement.CONCLUSION:P/C ratio might be a potential prognostic predictor in septic patients with abdominal sources.

Persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery:A case report

BACKGROUND Empty sella is an anatomical and radiological finding of the herniation of the subarachnoid space into the pituitary fossa leading to a flattened pituitary gland.Patients with empty sella may present with various symptoms,including headache due to intracranial hypertension and endocrine symptoms related to the specific pituitary hormones affected.Here,we report a female patient who developed persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery.CASE SUMMARY A 47-year-old woman underwent vocal cord polypectomy under general anesthesia with endotracheal intubation.She denied any medical history,and her vital signs were normal before the surgery.Anesthesia and surgery were uneventful.However,she developed dizziness,headache and persistent hypotension in the ward.Thus,intravenous dopamine was started to maintain normal blood pressure,which improved her symptoms.However,she remained dependent on dopamine for over 24 h without any obvious anesthesia-and surgery-related complications.An endocrine etiology was then suspected,and further examination showed a high prolactin level,a low normal adrenocorticotropic hormone level and a low cortisol level.Magnetic resonance imaging of the brain revealed an empty sella.Therefore,she was diagnosed with empty sella syndrome and secondary adrenal insufficiency.Her symptoms disappeared one week later after daily glucocorticoid supplement.CONCLUSION Endocrine etiologies such as pituitary and adrenal-related dysfunction should be considered in patients showing persistent postoperative hypotension when anesthesia-and surgery-related factors are excluded.

Plasma 17-hydroxyprogesterone/cortisol ratio is not a predictor of systemic hypotension in extremely premature infants

Background/aims: To determine whether the 17-hydroxyprogesterone (17-OHP)/cortisol ratio as a marker of immature11-beta hydroxylase activity can predict severe systemic hypotension in preterm neonates. Methods: Serum cortisol and 17-OHP concentrations were measured in capillary blood deposited on blotter paper on day 3 post-natal age (Day 3) in infants less than 32 weeks postmenstrual age (PMA). The predictive value of 17-OHP/cortisol ratio for a first episode of systemic hypotension occurring after Day 3 (FESH) was evaluated. Results: Of 105 infants included, 14 patients (13%) presented a FESH. Neither the 17-OHP/cortisol ratio, nor the 17-OHP or cortisol concentrations were associated with the occurrence of a FESH when adjusted for potential confounding factors. 17-OHP and cortisol were inversely associated to PMA (r = ﹣0.36 and ﹣0.40, respectively). Cortisol, but not 17-OHP, was associated with the type of hospitalization unit, the respiratory support and the presence of a patent ductus arteriosus. The 17-OHP/cortisol ratio was associated with the type of hospitalization unit only. Conclusions: The 17-OHP/ cortisol ratio at Day 3 did not predict the occurrence of a first episode of systemic hypotension after Day3 inpreterm neonates.

Relationship between adrenal function and prognosis in patients with severe sepsis

Background It is known that the hypothalamic-pituitary-adrenal （HPA） axis is highlighted by stimulation, such as sepsis, trauma, etc, when corticortropin increases and plasma cortisol levels enhance. Relative adrenal insufficiency is not uncommon in critically ill patients and may occur in severe sepsis patients with high plasma cortisol levels. It has been demonstrated that a short corticotropin test has a good prognostic value and is helpful in identifying patients with septic shock at high risk for death, but it has not been established for all severe sepsis patients, especially in China. The aim of this study is to explore the relationship between adrenal function and prognosis in patients with severe sepsis. Methods This prospective study was conducted between July and December 2004 in 6 teaching hospitals. Two hundred and forty patients with severe sepsis were enrolled in this study. A short corticotropin stimulation test was performed in all patients by intravenous injection of 250 pg of corticotropin. Blood samples were taken immediately before the test （TO）, 30 （T30） and 60 （T60） minutes afterward, and the plasma cortisol concentration was measured by radio-immunoassay. At the onset of severe sepsis, the following parameters were recorded： age, sex, Acute Physiology and Chronic Health Evaluation （APACHE） II, heart rate, mean arterial pressure （MAP）, arterial partial pressure of oxygen （PaO2）/fraction of inspired oxygen （FiO2）, peripheral blood of hemoglobin, platelets and leukocyte concentration and the number of organ failure. Patients were designated into two groups （survival and non-survival groups） according to the 28-day mortality. Relative adrenal insufficiency was defined as the difference between TO and the highest value of T30 or T60 （△Tmax） ≤9 μg/dl. Results （1） Two hundred and forty patients with severe sepsis were included in this study, with 134 patients in the survival group and 106 in the non-survival group. The 28-day mortality was 44.2%. （2） Between the survival group and non-survival group age, APACHE II, peripheral blood of platelets, the number of organ failures, TO and ATmax showed significant differences. TO was （23±10） μg/dl and （36＋18） μg/dl in the survival group and nonsurvival group respectively. △Tmax was （18±9） and （10±8） μg/dl in the survival group and non-survival group respectively. The areas under the ROC curve for TO and ATmax were both 0.72, and the area under the ROC curve for APACHE II was 0.70. By multivariate analysis age, TO, the number of organ failures and relative adrenal insufficiency （△Tmax ≤9 μg/dl） were independent predictors of death. （3） The incidence of relative adrenal insufficiency was 38.3% in total, 19.4% in the survival group and 62.3% in the non-survival group （P〈0.001）. The 28-day mortality was 71.7% among the relative adrenal insufficiency patients but 27.0% among normal adrenal function patients. Conclusions The prevalence of relative adrenal insufficiency is high in severe sepsis. Relative adrenal insufficiency has a good prognostic value for severe sepsis.

Clinical and molecular genetic analysis of a Chinese family with congenital X-linked adrenal hypoplasia caused by novel mutation 1268del A in the DAX-1 gene

Congenital X-linked adrenal hypoplasia （AHC） is a rare disease characterized by primary adrenal insufficiency before adolescence and by hypogonadotropic hypogonadism （HHG） during adolescence. In this paper, we present a Chinese family with AHC. Two brothers, misdiagnosed with adrenal insufficiency of unknown etiology at the age of 9, were correctly diagnosed with AHC when delayed puberty, HHG, and testicular defects were observed. We investigated the clinical features and identified the dosage-sensitive sex reversal AHC critical region of the X chromosome gene 1 （DAX-1） mutation in this kindred. Direct sequencing of the DAX-1 gene revealed that the two siblings have a novel mutation （1268delA） of which their mother is a heterozygous carrier. This mutation causes a frameshift and a premature stop codon at position 436, encoding a truncated protein. It is important to increase knowledge of the mutational spectrum in genes related to this disease, linking phenotype to genotype.