Endocrinology has long been a vibrant field of medical research focused on unraveling the intricate details of hormonal interactions and the myriad of diseases that result from their dysregulation. In recent years, a subset of disorders collectively referred to as ‘pseudoendocrine syndromes’ has garnered increasing attention from not just endocrinologists but a growing body of “web-based experts”. Each pseudoendocrine syndrome poses unique challenges and raises important questions regarding the scope and complexity of endocrine regulation and the broader physiological implications of hormonal imbalance. In this article, we will delve into the available scientific literature and provide a comprehensive overview of these syndromes, from their epidemiology and clinical presentation to their underlying pathophysiological theories and therapeutic options. Furthermore, we hope to highlight areas of uncertainty and controversy, thereby setting the stage for future research directions.
Adrenal Fatigue (AF) has recently gained immense traction within alternative medicine circles. Proponents of adrenal fatigue suggest that chronic stress causes adrenal gland weakness, leading to nonspecific symptoms, including fatigue, body aches, and sleep disruption; however, mainstream medical authorities – The Endocrine Society specifically – do not recognize AF as an official endocrine disorder.
Evidence supporting adrenal fatigue remains scarce and often anecdotal. No research studies have conclusively established a connection between chronic stress and reduced adrenal function and adrenal fatigue, and there are no established diagnostic criteria or laboratory tests that reliably detect it. The Endocrine Society issued a statement emphasizing that adrenal fatigue is not a legitimate medical condition, and no scientific basis supports its diagnosis or treatment. Furthermore, adrenal insufficiency – an endocrine disorder – should never be confused with adrenal fatigue as the former can pose life-threatening dangers necessitating proper diagnosis and therapy. Although scientific evidence has not proven adrenal fatigue, numerous over-the-counter adrenal supplements are being sold as treatments. These supplements typically consist of vitamins, minerals, and herbs found within adrenal gland extracts; they could potentially have unintended negative side effects.
Some adrenal supplements contain ingredients that interfere with normal adrenal function, leading to reduced hormone production. Prolonged use may even result in real adrenal insufficiency, which requires urgent medical intervention; the US Food and Drug Administration recently warned the public of the risks posed by over-the-counter supplements like Artri King, which contains high concentrations of dexamethasone.
Individuals who diagnose and self-treat their adrenal fatigue could be overlooking other medical conditions that are potentially responsible for their symptoms, like anemia. By solely treating adrenal fatigue as an answer, they might miss an opportunity for proper medical intervention to address what lies at its core, causing their discomfort.
Relative Adrenal Insufficiency
Relative adrenal insufficiency (RAI) is a controversial phenomenon that has been increasingly recognized in critically ill patients, particularly in those with severe septic shock. It is described as a state where the adrenal glands produce an insufficient amount of cortisol relative to the body’s needs during periods of extreme stress, such as severe sepsis. In severe septic shock, the overwhelming systemic infection and inflammation can lead to profound alterations in the HPA axis, resulting in inadequate cortisol production required to meet the body’s stress response[4,5]. Several factors may contribute to the development of RAI in septic shock, including:
- Impaired cortisol synthesis: Inflammation can inhibit the enzymes responsible for cortisol synthesis, reducing the overall production of the hormone.
- Altered cortisol metabolism: Inflammation can also affect the metabolism of cortisol, increasing its clearance from the body.
- Reduced cortisol availability: High levels of circulating inflammatory mediators can lead to increased cortisol binding to its carrier protein, reducing the availability of free, biologically active cortisol availability.
Diagnosing RAI in septic shock is challenging due to the lack of universally accepted diagnostic criteria. A commonly used diagnostic test is the adrenocorticotropic hormone (ACTH) stimulation test, which measures the adrenal glands’ ability to produce cortisol in response to ACTH administration. However, the interpretation of the test results is subject to debate, and there is no consensus on the cortisol cutoff levels that indicate RAI[3,6].
Some experts propose the use of dynamic tests, such as the delta cortisol or the cortisol-to-ACTH ratio, to assess adrenal function more accurately. These tests take into account the baseline cortisol levels and the individual patient’s physiological response to stress.
The optimal dosing, duration, and tapering of glucocorticoids in RAI are not well-established, and the management strategies may vary depending on the severity of the septic shock and the individual patient’s response to treatment.
Low T3 syndrome
Low T3 syndrome, also known as Wilson’s Syndrome, is a controversial pseudoendocrine condition characterized by low levels of triiodothyronine (T3) and normal levels of thyroxine (T4) and thyroid-stimulating hormone (TSH). Although some alternative health practitioners argue that this condition is a legitimate and underdiagnosed cause of fatigue, weight gain, and other nonspecific symptoms, current consensus guidelines do not recognize Wilson’s Syndrome as a legitimate endocrine disorder.
Dr. Denis Wilson first proposed Wilson’s Syndrome as a possible explanation for a subset of hypothyroid patients presenting with nonspecific symptoms such as fatigue, weight gain, brain fog, and cold intolerance, but with normal TSH and T4 levels. He hypothesized that these patients might have a deficiency in the conversion of T4 to the more biologically active T3 hormone, leading to a state of “functional hypothyroidism” that goes undetected by conventional thyroid function tests. It is worth noting that this is not the same condition as the previously described deiodinase deficiency state (Thr92Ala).
The proposed pathophysiology of Wilson’s Syndrome involves a decreased conversion of T4 to T3 in peripheral tissues, leading to low serum T3 levels. This decrease may be due to various factors such as stress, inflammation, or illness. However, no clear causative mechanism has been established, and the relationship between low T3 levels and the reported symptoms remains speculative at best.
Diagnosing Wilson’s Syndrome is beset with various challenges, as no universally accepted diagnostic criteria exist. Low T3 levels, normal T4 and TSH levels, and a constellation of nonspecific symptoms primarily define the condition. However, these symptoms are common and can be caused by numerous other medical conditions, making it difficult to determine whether a true association exists between low T3 levels and the reported symptoms.
Moreover, transient fluctuations in thyroid hormone levels can occur in healthy individuals and in response to various stressors, such as illness, surgery, or fasting. These fluctuations typically resolve without intervention and do not warrant treatment.
The treatment for Wilson’s Syndrome, as proposed by Dr. Wilson, involves the administration of time-released T3 hormone, often using a protocol called the “Wilson’s Temperature Syndrome Protocol.” However, there is no scientific evidence supporting the efficacy or safety of this treatment approach. Moreover, using T3 hormone supplementation in patients with normal TSH levels can lead to overtreatment and potential harm, such as the development of hyperthyroidism or cardiac complications.
Hashimoto Encephalopathy (HE), also referred to as Steroid Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT), is a rare but potentially reversible neurological disorder associated with autoimmune thyroiditis that manifests with cognitive dysfunction, psychiatric symptoms, seizures and focal neurological deficits. The condition may be immune-mediated; early recognition and prompt treatment with corticosteroids could result in significant improvement or even complete resolution of symptoms.
Patients diagnosed with Hashimoto encephalopathy may present with an array of neurological and psychiatric symptoms that include cognitive impairment, memory loss, confusion, hallucinations, mood disturbances, seizures, ataxia, and focal neurological deficits. These may appear suddenly or gradually over time and fluctuate over time – it typically affects middle-aged women more frequently than other age groups.
Hashimoto encephalopathy can typically be diagnosed on clinical suspicion and the presence of elevated thyroid peroxidase (TPO) antibodies – commonly seen among those suffering from autoimmune thyroiditis; however, elevated TPO antibodies alone do not confirm a diagnosis, as they may also exist among people without neurological symptoms.
Lumbar puncture and cerebrospinal fluid (CSF) analysis can aid in diagnosing and ruling out other potential causes of encephalopathy, such as infections or inflammation conditions. CSF analysis may show signs of Hashimoto encephalopathy, such as mild to moderate lymphocytic pleocytosis, elevated protein levels, or the presence of oligoclonal bands; however, these results are nonspecific and could occur as part of any number of other inflammatory or autoimmune conditions.
Other diagnostic tests, including brain imaging (MRI) and electroencephalography (EEG), may reveal nonspecific abnormalities that support the diagnosis of Hashimoto encephalopathy, but they cannot stand alone as conclusive tests[15,16].
Prompt therapy with corticosteroids such as prednisone or intravenous methylprednisolone is the cornerstone of treatment for Hashimoto encephalopathy. Steroids appear to exert their therapeutic effect by reducing inflammation and modulating immune response; most patients respond quickly with either significant improvement or complete resolution of symptoms as soon as starting on steroids; however, some may require long-term immunosuppressive therapy
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2. Research, C. for D.E. and (2022) Public Notification: Artri King contains hidden drug ingredients. FDA.
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This was first published on June 24, 2023 and Last Updated on June 24, 2023 by MyEndoConsult