Anxiety and Depressive Symptoms, Arthralgia, and Marked Liver-Test Abnormalities as Presenting Features of Probable Celiac Disease in Primary Care: A Case Report

1. Introduction

Celiac disease (CD) is a chronic immune-mediated disorder triggered by exposure to gluten-containing grains in genetically predisposed individuals. Although historically regarded as an intestinal disease, contemporary guidelines and reviews emphasize that CD may behave as a multisystem disorder with gastrointestinal, hematologic, hepatic, musculoskeletal, endocrine, neurologic, and psychiatric manifestations [1,2,3]. Population studies estimate that CD affects approximately 1% of many populations, although the prevalence varies by geography, age, sex, method of ascertainment, and whether diagnosis is based on serology or biopsy [2,3].

The diagnosis is often straightforward when chronic diarrhea, weight loss, iron deficiency, and positive serology are accompanied by confirmatory duodenal histology. However, recognition is more challenging when the first clinical concern is psychiatric distress or when abnormal liver tests and musculoskeletal symptoms dominate the presentation. Systematic review evidence has reported associations between CD and depression, anxiety, eating disorders, autism-spectrum disorder, and attention-deficit/hyperactivity disorder, but causality and mechanisms remain incompletely defined [4]. Abnormal aminotransferases and other liver biochemical abnormalities are also reported in CD, and some cases improve after treatment with a strict gluten-free diet (GFD), although alternative causes must be considered [5].

This case report describes an adult patient presenting to family medicine with new anxiety and depressive symptoms, gastrointestinal symptoms, weight loss, arthralgia, severe liver-test abnormalities, and strongly positive tissue transglutaminase IgA (tTG-IgA). The purpose is to strengthen recognition of nonclassical CD in primary care while also illustrating a common real-world challenge: diagnostic and follow-up uncertainty when the patient declines specialist referral and confirmatory endoscopy.

2. Case Presentation

2.1. Reporting Framework and De-Identification

This manuscript was prepared as a single-patient, de-identified reflective case report from routine primary care. The narrative is organized using the core CARE case-report elements, including patient information, clinical findings, diagnostic assessment, intervention, follow-up, discussion, and limitations [6]. Potentially identifying details have been minimized; for example, the patient age is presented as an age range rather than an exact age.

2.2. Patient Information and Presenting Concerns

A woman in her early sixties with a past medical history of hypothyroidism and glaucoma presented to her family physician because of a deterioration in mental health. She described low mood, anhedonia, persistent somnolence, and high levels of generalized anxiety. Before seeking medical review, she had tried several over-the-counter or natural products, including vitamin B12, vitamin D3, and valerian drops. She and her family were also concerned that her alcohol consumption had increased.

During the same clinical encounter, she reported poor appetite, unintentional weight loss, abdominal bloating, diarrhea, and flatulence. She also described pain and swelling involving multiple joints, including the hands, ankles, and knees. She requested review for mental health treatment.

2.3. Clinical Findings and Initial Investigations

The family physician ordered a broad initial panel to investigate psychiatric symptoms in the context of weight loss, gastrointestinal symptoms, polyarthralgia, and systemic features. Tests included complete blood count, electrolytes, C-reactive protein, iron studies, liver enzymes, thyroid-stimulating hormone (TSH), tTG-IgA, ferritin, fasting glucose, hemoglobin A1C, calcium, uric acid, lipid profile, and radiographs of the hands and knees. Mirtazapine 15 mg nightly was initiated for mood, sleep, and appetite symptoms.

Table 1. Abnormal investigations identified during the initial assessment.

Investigation	Finding and interpretation
Hemoglobin	118 g/L; reference 120-160 g/L; mild anemia.
Ferritin	1538 ug/L; reference 20-300 ug/L; marked hyperferritinemia.
Alkaline phosphatase	445 U/L; reference 30-145 U/L; cholestatic component.
Gamma-glutamyl transferase	1479 U/L; reference 8-35 U/L; severe elevation.
Alanine aminotransferase	104 U/L; reference 1-40 U/L; hepatocellular component.
Aspartate aminotransferase	256 U/L; reference 8-32 U/L; hepatocellular component.
Thyroid-stimulating hormone	21.99 mIU/L; reference 0.2-4.00 mIU/L; uncontrolled hypothyroidism.
tTG-IgA	>250 kIU/L; reference 0.0-14.9 kIU/L; strongly positive, >16 times the upper limit of normal.

Abbreviations: tTG-IgA, tissue transglutaminase immunoglobulin A.

Table 1. Abnormal investigations identified during the initial assessment.

Investigation	Finding and interpretation
Hemoglobin	118 g/L; reference 120-160 g/L; mild anemia.
Ferritin	1538 ug/L; reference 20-300 ug/L; marked hyperferritinemia.
Alkaline phosphatase	445 U/L; reference 30-145 U/L; cholestatic component.
Gamma-glutamyl transferase	1479 U/L; reference 8-35 U/L; severe elevation.
Alanine aminotransferase	104 U/L; reference 1-40 U/L; hepatocellular component.
Aspartate aminotransferase	256 U/L; reference 8-32 U/L; hepatocellular component.
Thyroid-stimulating hormone	21.99 mIU/L; reference 0.2-4.00 mIU/L; uncontrolled hypothyroidism.
tTG-IgA	>250 kIU/L; reference 0.0-14.9 kIU/L; strongly positive, >16 times the upper limit of normal.

Abbreviations: tTG-IgA, tissue transglutaminase immunoglobulin A.

Radiographs of the hands and knees demonstrated mild osteoarthritis and mild osteopenia, without evidence of erosive or inflammatory arthropathy. Because of weight loss and markedly abnormal blood tests, CT imaging of the abdomen and pelvis was requested to exclude malignancy. The patient declined colonoscopy and gastroscopy despite encouragement. CT abdomen/pelvis showed severe diffuse hepatic steatosis and mild pancreatic atrophy, with no evidence of malignancy.

2.4. Diagnostic Assessment and Differential Diagnosis

The clinical picture prompted a broad differential diagnosis. Psychiatric symptoms could have represented a primary anxiety or depressive disorder, but the accompanying weight loss, gastrointestinal symptoms, polyarthralgia, thyroid dysfunction, anemia, and markedly positive tTG-IgA suggested a systemic driver. Other important considerations included uncontrolled hypothyroidism, alcohol-related liver injury, metabolic dysfunction-associated fatty liver disease, autoimmune liver disease, inflammatory arthropathy, malignancy, hyperferritinemia related to liver disease or inflammation, and iron overload.

The strongly positive tTG-IgA result, obtained before the patient began dietary gluten restriction, substantially increased suspicion for CD in the setting of compatible gastrointestinal and extraintestinal symptoms. However, because the patient declined upper endoscopy with duodenal biopsy, the case should be described as probable CD or a working diagnosis of CD rather than histologically confirmed CD. Current adult guidelines generally support diagnosis using a combination of clinical features, celiac-specific serology, and duodenal histopathology while the patient is consuming gluten [1,7]. This distinction is clinically important because starting a GFD before confirmatory testing may reduce the yield of later serology or biopsy.

2.5. Therapeutic Intervention and Follow-Up

The patient was advised to start a strict GFD and to stop alcohol consumption. Her levothyroxine dose was increased to address the elevated TSH. Referral to a dietitian and gastroenterologist was recommended, but she declined both at that stage. Follow-up continued in the community. Over approximately six months, she experienced near-complete resolution of most symptoms.

Because several interventions occurred close together - initiation of mirtazapine, thyroid-dose adjustment, alcohol-cessation advice, and initiation of a GFD - improvement in mood and systemic symptoms cannot be attributed solely to gluten withdrawal. Ongoing follow-up would ideally include repeat tTG-IgA, liver enzymes, ferritin and iron studies, complete blood count, TSH, vitamin B12, folate, vitamin D, calcium status, and bone-health assessment. Persistent liver-test abnormalities despite reduced alcohol intake and a strict GFD should prompt reassessment for fatty liver disease, autoimmune liver disease, biliary disease, iron overload, medication effects, and other hepatobiliary causes [5,8].

Table 2. Condensed timeline of the clinical course.

Time point	Clinical events and decisions
Index primary-care visit	New anxiety and depressive symptoms, somnolence, reduced appetite, weight loss, bloating, diarrhea, flatulence, and polyarthralgia; broad laboratory testing and radiographs requested; mirtazapine started.
Within five days	Blood tests showed mild anemia, marked ferritin elevation, severe liver-test abnormalities, elevated TSH, and strongly positive tTG-IgA.
Early follow-up	CT abdomen/pelvis requested because of weight loss and abnormal laboratory findings. The patient declined colonoscopy and gastroscopy.
After CT imaging	CT showed severe diffuse hepatic steatosis and mild pancreatic atrophy, without malignancy. Working diagnosis of probable CD was made; GFD, alcohol cessation, levothyroxine adjustment, and community monitoring were initiated.
Approximately six months	Most symptoms had nearly resolved during community follow-up. Specialist and dietitian involvement remained recommended.

Abbreviations: CD, celiac disease; CT, computed tomography; GFD, gluten-free diet; tTG-IgA, tissue transglutaminase immunoglobulin A; TSH, thyroid-stimulating hormone.

Table 2. Condensed timeline of the clinical course.

Time point	Clinical events and decisions
Index primary-care visit	New anxiety and depressive symptoms, somnolence, reduced appetite, weight loss, bloating, diarrhea, flatulence, and polyarthralgia; broad laboratory testing and radiographs requested; mirtazapine started.
Within five days	Blood tests showed mild anemia, marked ferritin elevation, severe liver-test abnormalities, elevated TSH, and strongly positive tTG-IgA.
Early follow-up	CT abdomen/pelvis requested because of weight loss and abnormal laboratory findings. The patient declined colonoscopy and gastroscopy.
After CT imaging	CT showed severe diffuse hepatic steatosis and mild pancreatic atrophy, without malignancy. Working diagnosis of probable CD was made; GFD, alcohol cessation, levothyroxine adjustment, and community monitoring were initiated.
Approximately six months	Most symptoms had nearly resolved during community follow-up. Specialist and dietitian involvement remained recommended.

Abbreviations: CD, celiac disease; CT, computed tomography; GFD, gluten-free diet; tTG-IgA, tissue transglutaminase immunoglobulin A; TSH, thyroid-stimulating hormone.

3. Discussion

3.1. Why This Case Is Clinically Important

This case is clinically relevant for primary care because the patient did not present simply with classic malabsorptive symptoms. Instead, psychiatric distress was the concern that brought her to medical review, while gastrointestinal symptoms, weight loss, polyarthralgia, autoimmune thyroid disease, anemia, osteopenia, and liver-test abnormalities emerged as part of a wider pattern. The combination of these features justified celiac serology and avoided treating the presentation as an isolated mental health episode.

The case also demonstrates why diagnostic language matters. In an adult, a very high tTG-IgA result with compatible symptoms is highly suggestive, but the absence of confirmatory duodenal biopsy leaves residual uncertainty. This uncertainty is transparent in this work, particularly because the patient started dietary treatment and improved clinically. This article therefore aims at framing the diagnosis as probable CD, describing the reasoning, and acknowledging that biopsy refusal limited diagnostic certainty.

3.2. Psychiatric Manifestations and Quality of Life

The psychiatric manifestations of CD are increasingly recognized, although the direction and mechanisms of association remain debated. Proposed contributors include chronic inflammation, micronutrient deficiency, gut-brain axis effects, sleep disturbance, dietary burden, and the psychosocial impact of chronic symptoms. A systematic review and meta-analysis reported increased risks of several psychiatric conditions among people with CD, including depression and anxiety [4]. A later prospective multicentre study found that quality of life, anxiety, and depression scores improved after diagnosis, particularly among patients adhering to a GFD [9].

For clinicians, the practical lesson is not that anxiety or depression alone should trigger universal CD testing. Rather, CD should be considered when anxiety or depression coexists with gastrointestinal symptoms, weight loss, anemia, arthralgia, autoimmune thyroid disease, unexplained liver-test abnormalities, osteopenia, infertility, neuropathy, or a family history of CD. This selective approach is consistent with guideline-based targeted testing [1].

3.3. Liver-Test Abnormalities and Hyperferritinemia

The liver-test pattern in this case was striking, especially the severe gamma-glutamyl transferase elevation, elevated alkaline phosphatase, transaminase abnormalities, marked hyperferritinemia, increased alcohol intake, and CT evidence of severe hepatic steatosis. CD can be associated with elevated aminotransferases and with autoimmune or cryptogenic liver disease, and some liver biochemical abnormalities may improve after a GFD [5]. However, in this patient, fatty liver and alcohol exposure are strong competing explanations and should not be overlooked.

A prudent interpretation is that CD may have contributed to the multisystem presentation, but the liver abnormalities require independent follow-up. Repeat liver enzymes and ferritin after alcohol reduction, GFD initiation, and thyroid correction would help determine whether the abnormalities were transient, related to hepatic steatosis or alcohol, related to inflammation, or suggestive of another process. Persistently abnormal findings should prompt a structured liver workup and/or hepatology referral.

3.4. Primary Care Management Implications

Primary care physicians are often the first clinicians to integrate psychiatric, gastrointestinal, endocrine, musculoskeletal, and laboratory clues. In suspected CD, patients should ideally remain on a gluten-containing diet until diagnostic testing is complete [1,7]. Initial evaluation commonly includes tTG-IgA with total IgA or additional IgG-based testing when IgA deficiency is suspected; positive tests are usually followed by gastroenterology assessment and duodenal biopsy in adults [1,7].

After diagnosis or a highly probable diagnosis, management extends beyond simply advising a GFD. High-quality care includes dietitian-led education, assessment for nutritional deficiencies, monitoring of symptoms and serology, review of thyroid disease and other autoimmune comorbidities, bone-health assessment when indicated, and attention to mental health and dietary adherence. Recent follow-up guidance emphasizes symptom resolution, weight and nutritional status, serologic response, prevention of long-term morbidity, and multidisciplinary support involving clinicians and dietitians [8].

3.5. Strengths and Limitations

The main strength of this case is its realistic primary-care perspective. It illustrates how CD can be suspected when psychiatric symptoms are embedded within a broader multisystem presentation. It also highlights patient autonomy and the real-world challenge of managing probable CD when specialist referral, endoscopy, or dietitian support is declined.

The limitations are substantial and should be clearly acknowledged. This is a single case report and cannot establish causality. Duodenal biopsy was not performed, total IgA and endomysial antibody results were not reported, and no repeat serology, liver enzymes, ferritin, TSH, or nutritional markers are available in the current draft. The patient underwent several simultaneous interventions, making it impossible to attribute symptom improvement to the GFD alone. Finally, the very abnormal liver tests and severe hepatic steatosis require follow-up that is not captured in the original case narrative.

4. Conclusions

This case supports a targeted screening approach for CD in adults presenting with anxiety or depressive symptoms when there are additional gastrointestinal, systemic, autoimmune, musculoskeletal, hematologic, hepatic, or bone-health clues. The combination of gastrointestinal symptoms, weight loss, arthralgia, autoimmune thyroid disease, mild anemia, osteopenia, marked liver-test abnormalities, and strongly positive tTG-IgA made CD a clinically important consideration in this patient. Because confirmatory endoscopy was declined, this work presents the diagnosis as probable CD and emphasizes transparent follow-up.