A Middle-aged Adult with Persistent Fatigue and Hyperpigmentation
Published : Apr 12, 2024


Addison’s disease is a rare endocrine illness caused by inadequate adrenal activity resulting from multiple reasons. It most commonly presents with weight loss. Patients suffering from this disease may need hospitalization if their condition worsen. Autoimmune polyendocrine syndromes (APS) types I & II sometimes exhibit a high prevalence of coexistence with these autoimmune disorders. Here, we describe a patient who had been referred to gastrointestinal services previously due to episodes of vomiting associated with weight loss and who contacted the medical staff for help. After a thorough review of the patient’s medical history and subsequent biochemical evaluations, the patient was diagnosed with Addison’s disease. This allowed for a reevaluation of the underlying causes of the patient’s vomiting and weight loss. Furthermore, the patient displayed various simultaneous endocrine and immunological disorders. 


Addisons disease, Endocrine diseases, Adrenocorticotropic hormone, Autoimmune polyendocrine syndromes, Fluid resuscitation 


Compared to endocrine diseases such as diabetes and/or thyroid illness, Addison’s disease is less prevalent [1]. Nevertheless, acute admissions necessitate careful assessment given to the substantial mortality and morbidity rates that are linked with them [1]. Diagnosing this condition can pose significant challenges due to its diverse manifestation like Addison’s disease with mineralocorticoid–only deficiency, Addison’s disease with spontaneous resolution, Addison’s disease with symptomatic mineralocorticoid deficiency (not glucocorticoid), Addison’s disease in the course of anti-phospholipid syndrome, or Addison’s disease with presentation as intractable nausea/vomiting, often necessitating referrals to this specialized fields prior to reaching a definitive diagnosis [2,3]. The timely diagnosis of Addison’s crisis is of utmost importance, as a significant number of patients are diagnosed only upon admission for acute condition. The presence of comorbidities in Addison’s disease has been well-documented, highlighting the importance of early detection and timely intervention upon diagnosis [3]. 

Case Presentation

A 38-year-old female patient visited a physician’s office with a complaint of persistent vomiting 5 to 15 times a day for the last three months. The patient also complained of associated nausea, anorexia, and loss of weight. She had regular bowel movements and did not experience any issues with urination. However, she had seen substantial weight reduction in the past few months. The patient has had a past medical history of hypothyroidism and was referred to a gastroenterologist due to persistent episodes of vomiting. An esophagogastroduodenoscopy (OGD) was performed on the patient, revealing the presence of gastritis. Subsequently, the patient was initiated on PPI (proton pump inhibitor) medication. The blood test yielded negative results for tissue transglutaminase antibodies, while positive results were observed for stomach parietal cell antibodies. Consequently, a CT (computed tomography) enterograph was arranged for the patient. 


The patient was diagnosed with chronic gastritis. Her blood test revealed hypokalemia. She had hypotension that was believed to be caused by dehydration. The patient received intravenous fluids as a treatment and was subsequently released on antiemetic medication. 


The patient followed up after a period of four months when she continued to experience vomiting that was progressed to hematemesis. The new symptoms were believed to be caused by a Mallory-Weiss tear. Patient reported a continuous weight reduction from 50 kg to 41 kg and fatigue. She reported experiencing right-sided abdominal pain. She refuted any allegations of thyroxine abuse and/or voluntary vomiting. She exhibited uncertainty over any pertinent familial background. The patient was a habitual smoker and refuted any consumption of alcohol. 


Upon assessment, she exhibited a thin physique, low blood pressure, and tachycardia. She exhibited clinical dehydration and hyperpigmentation on her palms as shown in figure 1. 


Figure 1 

Case Management

The patient was initiated on IV hydrocortisone at a dosage of 100 mg, administered four times day, along with fluids, leading to eventual amelioration. 


Fluid resuscitation is essential for replenishing intravascular volume, which is accomplished by administering normal saline intravenously. Dextrose is used to treat low blood sugar levels, while it is crucial to rectify deficiencies in both glucocorticoids and mineralocorticoids. The initial physiological intervention entails the administration of hydrocortisone. Maintenance therapy aims to maintain both glucocorticoid and mineralocorticoid levels at a physiological level. 


Patient showed a low concentration of insulin-like growth factor (IGF). Both the pituitary MRI and abdominal CT scans revealed normal findings, indicating no adrenal abnormalities.

The patient was released on oral hydrocortisone and fludrocortisone pills and provided with instruction on the significance of adhering to the prescribed regimen. Patient relapsed in six months.  


This example underscores the significance of conducting a thorough examination of prior admissions and considering alternative differential diagnosis, particularly in instances while the presenting illness exhibits similarities. The individual was originally directed to gastroenterologists, resulting in successive admissions being attributed to gastrointestinal factors, despite the presence of modest amelioration in symptoms. Nevertheless, due to the persistent decrease in body weight without any apparent explanation identified in prior examinations, it was crucial to eliminate alternative diagnoses. Consequently, the diagnosis of Addison’s illness was ultimately established nearly one year after the onset of symptoms. 


Addison’s illness is an uncommon disorder, occurring in around 4 million individuals annually in the western side population [2]. Diagnosing this condition can pose significant challenges and may be overlooked due to the manifestation of non-specific signs or symptoms [3]. 


The occurrence of diagnostic delays is a frequent phenomenon, wherein patients may seek consultation from multiple healthcare practitioners, such as gastroenterologists and/or psychiatrists, prior to receiving an accurate diagnosis [4,5]. 


The presence of a diverse range of symptoms suggests that the diagnosis can be ascribed to alternative disorders, perhaps leading to the oversight of key characteristics such as pigmentation in the skin and/or mucous membranes, although their presence may not constantly be evident [6]. 


The potential relevance of anorexia and/or hypotension should be acknowledged, as these conditions are non-specific and can be attributed to different diagnosis, for example underlying infection. 


Investigations might yield numerous indications to the doctor, leading them to suspect the presence of Addison’s disease. The patient might exhibit hyponatremia and/or hyperkalemia, hypoglycemia, and eosinophilia during regular blood testing [7]. 


Elevated TSH levels can be a characteristic, and in certain cases, the onset of thyroxine might exacerbate Addison’s disease [8]. 


A healthcare professional may this after suspecting the diagnosis and contemplate a stochastic cortisol level. Nevertheless, this assertion may be erroneous because of the circadian cycle of cortisol synthesis, characterized by heightened levels in the morning time and diminished levels/volume at midnight, as well as an upsurge in production during periods of stress [9]. A diagnosis of Addison’s disease should be made when this is an abnormally low level of cortisol, and this can be validated by conducting a hydrocortisone trial. 


The primary diagnostic test is a brief synacthen test, although it might provide challenges in emergency situations because of the need for quick initiation of intravenous hydrocortisone. Prior to administering steroids, it is important to measure the levels of cortisol & ACTH (adrenocorticotropic hormone). 


Synacthen and/or synthetic ACTH (also known as tetracosactrin) could be delivered IV or IM in the non-acute environment. A standard test is measuring initial cortisol levels at 0 minutes, followed by administering 250 μg of tetracosactrin, and subsequently reassessing cortisol levels at 30 minutes (and 60 minutes in certain instances). The range indicating the presence of intact adrenal gland function has exhibited variability, spanning from 400 to 550 nmol/L. However, the prevailing consensus is that the optimal level is 525 nmol/L [10,11]. 


Approximately 50% of individuals diagnosed with Addison’s illness receive their diagnosis after experiencing an acute adrenal insufficiency. It is a critical medical situation that frequently occurs when an untreated or insufficiently treated subjects with Addison’s illness experiences an infection or these types of stress. In this state, individuals exhibit acute illness characterized by significant dehydration, circulatory shock, or hypotension [4]. 


Addison’s disease is known to have autoimmune connections. In her eponymous condition [12], Thomas Addison provided a description of the coexistence of pernicious anemia and vitiligo. Approximately half of individuals diagnosed with Addison’s illness exhibit comorbid autoimmune conditions, with thyroid illness being the most prevalent among them [13]. 


APS (Autoimmune Polyendocrine Syndrome) is a term used to describe the condition of various endocrine gland crisis that is linked to autoimmune illness [14]. However, it is employed to define syndromes that are characterized by the coexistence of two or more problems specific to one organ. Additionally, APS type I is characterized by the existence of genetic heredity, specifically the AIRE (autoimmune regulator) gene, while APS type II is characterized by polygenic inheritance. Blizzard and Neufeld conducted a classification of this condition into four primary categories, which were determined based on investigations / clinical observations [17]. However, the two most prominent syndromes identified are APS categories I & II [15,16]. 


APS kind I is a hereditary disorder that is primarily associated with Addison’s illness, hypoparathyroidism, and persistent candidiasis. Nevertheless, these are additional characteristics that are commonly observed, such as pernicious anemia, hepatitis atrophic gastritis, type 1 diabetes, and vitiligo [18]. 


APS kind II, also known as Schmidt’s syndrome, exhibits a high prevalence compared to kind I and is linked to many medical diseases such as Addison’s illness, autoimmune thyroid illness, and insulin-dependent diabetic. The individual in question is linked to the human leukocyte antigen (HLA), specifically HLA DR3 and DR4. 


Addison disease is an uncommon endocrine illness that is typically associated with autoimmunity in developed nations but is commonly connected with tuberculosis in developing nations. Typical symptoms of Addison disease include difficulty swallowing, lethargy, amenorrhea, loss of weight, hypotension, abdominal pain, nausea, vomiting, weak and fragile nails, and hair that is either absent or sparsely distributed. Hyperpigmentation caused by ACTH melanogenesis is an indicator of Addison disease. As a first indicator, you may notice pigmentation inside the mouth on the gums, vermillion border of the lip, buccal mucosa, palate, and tongue. It is crucial to diagnose Addison’s disease early on to provide appropriate medical care. 


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Author Information

Bhandhavi Vasireddy PharmD, Author, medtigo. 

Rabia Akram PharmD, Medical content writer, medtigo.

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Conflict of Interest Statement

The image used in this article is representative and not of the actual patient whose case has been discussed.


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Additional Information

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Cite this Article

Bhandhavi V, & Rabia A. (2024). A middle-aged adult with persistent fatigue and hyperpigmentation. medtigo Journal, 2(1). https://doi.org/10.5281/zenodo.10891346

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