# Isolated Adrenocorticotropic Hormone Deficiency Mimicking Systemic Sclerosis: A Diagnostic Challenge in Patients With Rheumatoid Symptoms

## TL;DR

A case of isolated ACTH deficiency mimicked systemic sclerosis, but was correctly diagnosed and treated with hydrocortisone, improving symptoms like joint swelling and skin changes.

## Contribution

This case highlights the diagnostic challenge of IAD presenting with rheumatoid symptoms and emphasizes the importance of adrenal function testing in such patients.

## Key findings

- Hydrocortisone therapy improved symptoms of joint swelling, skin sclerosis, and thyroid dysfunction in a patient with IAD.
- IAD can mimic autoimmune diseases like systemic sclerosis, leading to potential misdiagnosis.
- Thyroid dysfunction in IAD patients may resolve with cortisol replacement therapy.

## Abstract

Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is characterized by selective impairment of ACTH secretion while other anterior pituitary hormones remain unaffected. It is more common in men in their fifties, with autoimmune mechanisms likely playing a major role. Symptoms include fatigue, weight loss, and appetite loss. Some IAD patients also experience rheumatoid symptoms, such as muscle pain and joint stiffness. A 74-year-old male patient with type 2 diabetes mellitus developed worsening symptoms, including impaired consciousness, fatigue, and edema. A month before hospitalization, he was diagnosed with primary hypothyroidism and started on levothyroxine. However, his symptoms worsened, with finger contractures and joint swelling, prompting referral to our hospital. On admission, he showed signs of general malaise and facial changes. His skin showed sclerosis without characteristic features of systemic sclerosis (SSc), such as Raynaud’s phenomenon or digital ulcers. His lab tests showed negative autoantibodies for collagen diseases, and the patient did not meet the criteria for SSc. Further investigation revealed hyponatremia, hypoglycemia, and low ACTH and cortisol levels, indicating anterior pituitary hormone deficiency. Imaging confirmed an intact pituitary gland and hypothalamus. The patient was diagnosed with IAD and began intravenous hydrocortisone, which improved his symptoms, including hyponatremia, hypoglycemia, and hypotension. His skin sclerosis and joint swelling also improved. Thyroid function normalized, and levothyroxine was discontinued. After physical therapy, the patient was discharged. The symptoms of IAD are primarily related to cortisol deficiency. It is often managed with hydrocortisone supplementation, which leads to rapid improvement of clinical symptoms. Autoimmune mechanisms, including the presence of anti-pituitary antibodies, are thought to play a significant role in its pathogenesis. However, this case lacked anti-pituitary antibodies and other typical causes such as opioid use or immune checkpoint inhibitors. Thyroid dysfunction can occur in IAD patients, as cortisol suppresses the thyrotropin-releasing hormone (TRH)-thyroid-stimulating hormone (TSH) axis. In this case, the patient's thyroid dysfunction was resolved after hydrocortisone therapy. Rheumatoid symptoms, such as joint pain and skin changes, can also be present in IAD, leading to misdiagnosis as systemic diseases like SSc. Hydrocortisone therapy successfully improved these symptoms, highlighting the need for adrenal function testing in patients with unexplained rheumatoid symptoms. Some cases of IAD can mimic autoimmune diseases like SSc, complicating diagnosis and delaying treatment. It is important to consider IAD in patients with unexplained joint and skin symptoms. Additionally, thyroid hormone therapy may unmask adrenal insufficiency, underscoring the importance of evaluating adrenal function before initiating treatment.