Unexpected but Not Uncommon - a Case of Adrenal Insufficiency

Abstract Background: Herbal remedies are widely available and whilst portrayed as generally harmless, they may contain a variety of potent medications that can cause unintended and potentially serious consequences. This danger is further amplified as their use is typically inadvertently not divulged to clinicians, such as in this case. Clinical Case: A 65-year-old gentleman was referred to Endocrinology for assessment of adrenal insufficiency (AI) as a cause of his lethargy. He was found to have serum cortisol levels of 38 nmol/L and 68 nmol/L (150 – 700 nmol/L) on two separate mornings. No identified recent use of inhaled, topical, intra-articular or oral exogenous steroid therapy was noted. He had an inadequate response to Synacthen stimulation with peak serum cortisol of 150 pmol/L at 60-minutes (Adequate response – Post-Synacthen cortisol >430 pmol/L). Baseline plasma ACTH was low - 1.1 pmol/L(2.0 – 10 pmol/L) and secondary (pituitary) AI was suspected. He had normal thyroid function and prolactin. The patient subsequently admitted to taking an herbal medication, “Montalin” for a few months. It was obtained over-the-counter in Indonesia for symptomatic relief of “muscle pains”. The tablet underwent analysis to investigate for presence of corticosteroid components. An intact Montalin capsule was partly dissolved and the soluble content was diluted and analysed via LCMS/MS. Presence of dexamethasone/betamethasone was confirmed at an approximate concentration of 69.8 nmol/L constituting 0.548mg and 0.81% of the tablet. At the time, betamethasone and dexamethasone could not be distinguished due to stereoisomerism, but since has been confirmed to be dexamethasone. The patient likely had suppression of the hypothalamic-pituitary-adrenal axis from unintended exogenous corticosteroid use, causing a picture of secondary AI. He requires ongoing corticosteroid replacement pending recovery of endogenous production. Although Montalin is marketed as an herbal over-the-counter medication it was confirmed to be adulterated with a potent corticosteroid. An alert issued by the Singaporean government details two further cases of adverse effects from Montalin and warns against its use. Conclusion: Herbal remedies with undisclosed potent ingredients may unknowingly cause serious adverse effects. With advances in LCMS/MS technology, laboratory analysis of either the tablets or the patient’s serum could be utilised to identify potential exogenous corticosteroid exposure.

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The Effects of Four Label Design Parameters on Perceived Reliability, Efficacy and Intent to Purchase of Over-the-counter Medication

Proceedings of the Human Factors and Ergonomics Society Annual Meeting ◽

10.1177/154193129804200605 ◽

1998 ◽

Vol 42 (6) ◽

pp. 546-549 ◽

Cited By ~ 1

Author(s):

Marc L. Resnick

Keyword(s):

Medical Care ◽

Prescription Drugs ◽

Herbal Remedies ◽

Design Parameters ◽

Over The Counter ◽

Medical Needs ◽

Intent To Purchase ◽

Counter Medication ◽

The Government ◽

The Cost

The cost of medical care has been skyrocketing for many years. One solution being promoted by both the government and medical industry is to increase the effectiveness and prevalence of self care and prevention. By managing for their own medical needs, patients can significantly reduce the cost of their medical care by replacing expensive prescription drugs with over-the-counter (OTC) products. The establishment of the Office of Alternative Medicine by the National Institutes of Health has legitimized the inclusion of herbal remedies in this plan. However, the labeling guidelines for OTC products are vague and under constant debate. This research evaluates the effects of several label content parameters regarding indication and effectiveness claims. Subjects were provided with labels for fictitious herbal and chemical medical products and asked to report their perceptions of the reliability of the claim, the products' effectiveness, and their likelihood of purchasing the product. Parameters included the originator of the claim (FDA, doctor groups, Harvard University and athletes), usability factors, product type (chemical, herbal), and disorder. The results have significant implications for the development of labeling guidelines for consumer-focused products.

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Inhaled Corticosteroids and Secondary Adrenal Insufficiency

The Open Respiratory Medicine Journal ◽

10.2174/1874306401408010093 ◽

2014 ◽

Vol 8 (1) ◽

pp. 93-100 ◽

Cited By ~ 14

Author(s):

Vishnu Sannarangappa ◽

Ryan Jalleh

Keyword(s):

Adrenal Insufficiency ◽

Inhaled Corticosteroids ◽

Case Reports ◽

Serum Cortisol ◽

Paediatric Population ◽

Early Morning ◽

Endogenous Production ◽

Life Threatening ◽

Patient Groups ◽

High Doses

Inhaled corticosteroids (ICS) have been used as first line treatment of asthma for many decades. ICS are a form of exogenous glucocorticosteroids that can suppress the endogenous production of glucocorticosteroids, a condition known as adrenal suppression (AS). As a result, cessation, decreasing the dose or changing the type of ICS may trigger features of adrenal insufficiency (AI). AI may cause a spectrum of presentations varying from vague symptoms of fatigue to potentially life threatening acute adrenal crises. This article reviews the current literature on ICS and AI particularly in adults (although majority of data available is from the paediatric population). It aims to increase awareness of the potential risk of AI associated with ICS use, delineate the pathogenesis of AI and to provide recommendations on screening and management. From our literature review, we have found numerous case reports that have shown an association between ICS and AI particularly in children and patients using high doses. However, there have also been reports of AI in adults as well as in patients using low to moderate doses of ICS. To conclude, we recommend screening for AI in select patient groups with an initial early morning serum cortisol. If results are abnormal, more definitive testing such as the low dose corticotropin stimulation test may be done to confirm the diagnosis.

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An association between heart rate variability and serum cortisol, dehydroepiandrosterone-sulfate, as an index of stress status and adrenal insufficiency

Korean Institute for Functional Medicine ◽

10.32581/jkifm.2019.2.28 ◽

2019 ◽

Vol 2 ◽

pp. 28-34

Author(s):

Jin-Kyung Park ◽

Jong-Seok Kim ◽

Eun-kyung Suh ◽

Yun-Kyung Lee ◽

Yong-Jae Lee ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Adrenal Insufficiency ◽

Serum Cortisol ◽

Dehydroepiandrosterone Sulfate

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Potential of Mirabegron and its Extended-release Formulations for the Treatment of Overactive Bladder Syndrome

Current Drug Metabolism ◽

10.2174/1389200221666200425211139 ◽

2020 ◽

Vol 21 (2) ◽

pp. 79-88 ◽

Cited By ~ 1

Author(s):

Pankaj Mandpe ◽

Bala Prabhakar ◽

Pravin Shende

Keyword(s):

Clinical Trials ◽

Overactive Bladder ◽

Adverse Effects ◽

Symptomatic Relief ◽

Phase Iii ◽

Overactive Bladder Syndrome ◽

Modified Release ◽

Blurred Vision ◽

Antimuscarinic Drugs ◽

Tablet Dosage

Background: Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision, constipation, dizziness etc. Mirabegron is the first approved β3-adrenoreceptor agonist, used as mono or in combination therapies for overactive bladder syndrome. Objective: The present review provides an insight into the mechanism, pharmacokinetics, toxicokinetics, clinical trials and the development of various conventional and modified-release dosage forms of mirabegron for the treatment of overactive bladder syndrome. Results: The clinical trials of phase II and phase III of mirabegron demonstrated symptomatic relief from the overactive bladder without disturbing the micturition cycle. To date, mirabegron showed promising results for safety, tolerability and efficacy in patients with overactive bladder syndrome. The modified-release tablet dosage form of mirabegron appear to be a proficient and suitable replacement for antimuscarinics and revealed the tremendous potential to overcome the adverse effects of conventional antimuscarinic drugs like Oxybutyline chloride ER, Detrol LA, VESIcare, etc. Conclusion: Mirabegron shows a distinct mode of action, i.e., targeting β3-adrenoreceptors and improving bladder storage without altering void contractions. The limited side effects, high safety, efficacy and tolerability of mirabegron present an adequate substitute to antimuscarinics. However, long-term analysis and clinical studies are prerequisites for assessing the safety, tolerability and efficacy profile of mirabegron.

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Hormones in international meat production: biological, sociological and consumer issues

Nutrition Research Reviews ◽

10.1079/nrr200246 ◽

2002 ◽

Vol 15 (2) ◽

pp. 293-314 ◽

Cited By ~ 32

Author(s):

Hugh Galbraith

Keyword(s):

Biological Activity ◽

Adverse Effects ◽

Good Practice ◽

Current Status ◽

Current Evidence ◽

Meat Production ◽

International Consensus ◽

Free Radical Damage ◽

Endogenous Production ◽

Human Pathology

AbstractBeef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds (‘hormones’) to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17β and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17β as a carcinogen in certain tissues. Now subject to a ‘permanent’ EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate proliferation in cells maintaining receptivity. Mathematical models describing quantitative relationships between consumption of small amounts of oestrogens in meat in addition to greater concentrations from endogenous production, chemical stoichiometry at cellular level and human pathology have not been developed. Such an approach will be necessary to establish ‘molecular materiality’ of the additional hormone intake as a component of relative risk assessment. The other hormones, although generally less well researched, are similarly subject to a range of tests to determine potentially adverse effects. The resulting limited international consensus relates to the application of the ‘precautionary principle’ and non-acceptance by the European Commission of the recommendations of the Codex Alimentarius Commission, which determined that meat from cattle, hormone-treated according to good practice, was safe for human consumers. The present review considers the hormone issue in the context of current international social methodology and regulation, recent advances in knowledge of biological activity of hormones and current status of science-based evaluation of food safety and risk for human consumers.

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Salicylate toxicity from chronic bismuth subsalicylate use

BMJ Case Reports ◽

10.1136/bcr-2020-236929 ◽

2020 ◽

Vol 13 (11) ◽

pp. e236929

Author(s):

Sheliza Halani ◽

Peter E Wu

Keyword(s):

Emergency Department ◽

Adverse Effects ◽

Hearing Impairment ◽

Reference Range ◽

The Elderly ◽

Intravenous Fluids ◽

Over The Counter ◽

Bismuth Subsalicylate ◽

Salicylate Concentration ◽

History Of

A 79-year-old man presented to the emergency department with a 1-week history of worsening confusion, falls and hearing impairment. An initial workup for infectious, metabolic and structural causes was unrevealing. However, further history discovered that he had been ingesting one to two bottles of Pepto-Bismol (bismuth subsalicylate) daily for gastro-oesophageal reflux symptoms. On his second day of admission, the plasma salicylate concentration was 2.08 mmol/L (reference range 1.10–2.20 mmol/L), despite no sources of salicylate in hospital. He was diagnosed with chronic salicylate toxicity and Pepto-Bismol use was discontinued. The patient was treated supportively with isotonic intravenous fluids only and plasma salicylate concentration fell to less than 0.36 mmol/L. Concurrently, all his symptoms resolved. This case highlights the potential adverse effects of over-the-counter medications. The diagnosis of chronic salicylate toxicity is challenging, specifically in the elderly and in undifferentiated presentations, as it can be missed if not suspected.

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