Full Text

1. Introduction

Hypertension is one of the most prevalent chronic medical conditions worldwide, affecting approximately 30–45% of adults globally and a leading risk factor for cardiovascular morbidity and mortality [1]. The majority of cases are classified as primary (essential) hypertension, with no identifiable secondary cause. However, secondary hypertension, accounting for 5–10% of cases, results from specific, potentially reversible conditions such as renal artery stenosis, primary aldosteronism, pheochromocytoma, and endocrine disorders including Cushing’s syndrome [2]. Among these, Cushing’s syndrome—caused by prolonged exposure to excessive glucocorticoids—is an uncommon but clinically significant cause that can lead to resistant hypertension and multiple systemic complications if undiagnosed [3].

Cushing’s disease is a subset of Cushing’s syndrome, resulting from an ACTH-secreting pituitary adenoma, representing the most common endogenous cause [4]. It is characterized by the chronic overproduction of cortisol, which affects metabolism, cardiovascular function, and neuro-ophthalmologic structures. Clinical features often develop insidiously and overlap with common disorders such as obesity, metabolic syndrome, and diabetes, which may delay diagnosis [5]. Hypertension in Cushing’s syndrome is multifactorial, involving cortisol-induced activation of mineralocorticoid receptors, increased vascular sensitivity to catecholamines, and altered renal sodium retention [6]. Moreover, pituitary adenomas can exert mass effects on surrounding structures, leading to neurological signs including visual field defects, which may go unnoticed initially [7]. This report illustrates the importance of a systematic approach in a hypertensive patient presenting for routine care, emphasizing the need for detailed clinical assessment, appropriate biochemical testing, and imaging to identify rare but serious secondary causes such as Cushing’s disease.

2. Case presentation

A 50-year-old woman with a 5-year history of hypertension presented to the primary health care clinic requesting adjustment of her antihypertensive medications, as her blood pressure remained poorly controlled despite adherence to a regimen of amlodipine 10 mg once daily. She reported increased fatigue over the past 6 months and mild weight gain, primarily in the trunk and face. She denied headaches, muscle weakness, easy bruising, or skin changes. The patient was not aware of any visual disturbances.

On examination, her blood pressure was 160/95 mmHg, heart rate 84 bpm, and body mass index (BMI) was 31 kg/m², indicating obesity. Physical examination revealed a rounded “moon face,” central obesity with a dorsocervical fat pad (“buffalo hump”), and mild facial plethora. There were no striae or proximal muscle weakness noted. Neurological examination was unremarkable except for subtle bitemporal visual field defects detected on confrontation testing, which she had not noticed previously.

Given the resistant hypertension and phenotypic features suggestive of hypercortisolism, biochemical screening for Cushing’s syndrome was initiated. An overnight 1 mg dexamethasone suppression test (DST) revealed a morning serum cortisol level of 12 µg/dL (normal <1.8 µg/dL), indicating failure to suppress cortisol secretion. Morning plasma ACTH was elevated at 68 pg/mL (reference range: 10–60 pg/mL), consistent with ACTH-dependent Cushing’s syndrome. 24-hour urinary free cortisol was markedly elevated at 450 µg/day (normal range: 20–90 µg/day).

To localize the source of ACTH excess, magnetic resonance imaging (MRI) of the pituitary gland was performed. It demonstrated a 7 mm pituitary microadenoma extending superiorly and compressing the optic chiasm. The presence of bitemporal hemianopia on visual field testing correlated with the anatomical findings. The patient was referred urgently to an endocrinologist and neurosurgeon for further evaluation and management, including consideration of transsphenoidal surgical resection of the pituitary adenoma.

3. Discussion

This case highlights several important clinical lessons in the evaluation of hypertension and the identification of secondary causes, particularly Cushing’s disease. The initial presentation of poorly controlled hypertension is common in primary care and often attributed to essential hypertension. However, the presence of additional signs such as central obesity, moon face, and facial plethora should alert clinicians to the possibility of hypercortisolism, especially when hypertension is resistant to standard treatment [8].

The diagnostic approach in suspected Cushing’s syndrome requires a high index of suspicion and systematic testing. The low-dose overnight dexamethasone suppression test is widely accepted as a sensitive screening tool. Failure to suppress serum cortisol after dexamethasone administration is indicative of endogenous cortisol excess [9]. Elevated plasma ACTH helps differentiate between ACTH-dependent and ACTH-independent causes, guiding further localization studies [10].

Pituitary adenomas causing Cushing’s disease can exert mass effects, including optic chiasm compression leading to bitemporal hemianopia, as seen in this patient. Such visual field defects may develop insidiously and remain unnoticed by the patient, underscoring the need for careful neurological examination in suspected cases [11]. MRI remains the imaging modality of choice for pituitary adenomas, although small microadenomas may occasionally be missed, necessitating invasive procedures like inferior petrosal sinus sampling in uncertain cases [12].

Hypertension in Cushing’s syndrome results from cortisol’s activation of mineralocorticoid receptors, increased vasoconstrictor responsiveness, and renal sodium retention. It is often difficult to control without addressing the underlying hypercortisolism, as illustrated by this case [13].

Early diagnosis and intervention in Cushing’s disease are critical to prevent cardiovascular complications, metabolic derangements, and progressive visual loss. Transsphenoidal surgery is the preferred treatment modality, offering remission in most cases [14]. This case also emphasizes the role of primary care providers in recognizing signs of secondary hypertension and initiating appropriate workup.

Conclusion

In patients with hypertension, particularly when resistant to standard therapy and accompanied by suggestive clinical features, a systematic and comprehensive evaluation for secondary causes such as Cushing’s disease is essential. This case demonstrates how detailed history, physical examination, and targeted biochemical and radiological investigations can lead to timely diagnosis. Early identification and treatment of Cushing’s disease can significantly improve patient outcomes by reversing hypercortisolism and preventing complications.

Declarations

Conflicts of Interest: The authors declare that they have no conflicts of interest related to this study.

Funding: None.

Acknowledgements: None.

Author Contributions: A.M.A.-H. conceived and designed the study. F.A.-S. and S.E. collected the data and conducted the literature review. K.N. and N.Y.S. performed the data analysis and interpretation. A.M.A.-H. drafted the manuscript, and all authors contributed to revising the final version. All authors read and approved the final manuscript.

Patient Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The patient was informed about the purpose of the report, and confidentiality was ensured.

Ethics Approval: This case report did not require formal ethics committee approval as it involved a single patient and was conducted in accordance with institutional guidelines and the Declaration of Helsinki.

Data Availability: All relevant data supporting the findings of this case report are included within the article. Additional data are available from the corresponding author upon reasonable request.