BIR British Institute of Radiology
OXFORD
Endocrine hypertension: the role of imaging in diagnosis and management
Mohammed Azfar Siddiqui, MD1,*®, Irfan Amir Kazi, MD10, Frank H. Miller, MD2, Pardeep K. Mittal, MD3, Esra Demirtas, MD4, Khaled M. Elsayes, MD5, Ayman Nada, MD6
1Department of Radiology, University of Missouri, Columbia, Missouri 65212, United States
2Department of Radiology, Northwestern Memorial Hospital, Chicago, Ilinois 60611, United States
3Department of Radiology and Imaging, Medical College of Georgia, Augusta, Georgia 30912, United States
4Department of Endocrinology, University of Missouri, Columbia, Missouri 65212, United States
5Department of Abdominal Imaging, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States 6Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, Missouri 63110, United States
*Corresponding author: Mohammed Azfar Siddiqui, MD, Department of Radiology, University of Missouri Hospital, 1 Hospital Drive, Columbia, MO 65212, United States (drazfarsiddiqui@gmail.com)
Abstract
Endocrine hypertension is an uncommon but treatable cause of secondary hypertension. It results from excessive hormone production by the endocrine glands or due to ectopic hormone production. The causes of abnormal hormonal production can be congenital or acquired. Specific syndromes can also predispose to the development of endocrine hypertension. Extensive catecholamine production can occur due to pheochro- mocytomas and paragangliomas (PPGLs). Excessive aldosterone secretion by the adrenal cortex commonly occurs due to idiopathic (bilateral) adrenal hyperplasia or aldosterone-producing adrenal adenomas. Excessive cortisol production can occur secondary to abnormalities in the adre- nal gland, the pituitary gland, or ectopic hormone production, or it can be caused by exogenous steroid intake. Other endocrine conditions that can lead to hypertension include acromegaly, primary hyperparathyroidism, hyperthyroidism, and hypothyroidism. Imaging plays a vital role in di- agnosing the cause of endocrine hypertension, leading to appropriate management. The clinical presentation and laboratory investigations serve as a guide to the appropriate imaging investigation that needs to be performed to confirm a diagnosis.
Keywords: endocrine hypertension; pheochromocytoma; paraganglioma; aldosterone producing adenoma; Cushing syndrome; adrenocortical carcinoma.
Introduction
Endocrine hypertension, a subtype of secondary hypertension, accounts for 5%-10% of cases and mainly affects individuals under 40 years.1 The clinical signs are often non-specific, reflect- ing the underlying endocrine disorder responsible for the hyper- tension. Although endocrine hypertension is rare, identifying the root cause can lead to a cure, significantly reducing cardio- vascular and related morbidities. Unlike primary hypertension, imaging is crucial in diagnosing secondary hypertension, partic- ularly when endocrine involvement is suspected. Accurate diag- nosis through imaging enables targeted medical or surgical treatment, improving outcomes.
Endocrine hypertension results from excessive hormone production by various endocrine glands and can be the first sign of several endocrine disorders.2 Hormone overproduc- tion may be congenital-often due to enzyme deficiencies- or acquired, resulting from gland dysfunction, hormone therapy, or hormone-secreting tumours, which may be in typ- ical or ectopic sites.
This review explores the underlying conditions causing en- docrine hypertension, focusing on clinical features, lab find- ings, imaging, and management (Figure 1). The causes of endocrine hypertension are summarized in Table 1.
Adrenal gland-dependent causes
The adrenal gland has 2 main parts: the medulla, producing cat- echolamines (eg, adrenaline, noradrenaline), and the cortex,
with 3 zones-glomerulosa, fasciculata, and reticularis-pro- ducing mineralocorticoids (eg, aldosterone), glucocorticoids (eg, cortisol), and androgens, respectively.3 Overproduction of cortisol leads to Cushing syndrome, while excessive aldosterone causes Conn syndrome. Pheochromocytomas and paraganglio- mas (PPGLs), tumours arising from medullary chromaffin cells, are key contributors to endocrine hypertension.
Pheochromocytoma and paraganglioma
Pheochromocytomas and paragangliomas are rare catecholamine-producing tumours-pheochromocytomas arise in the adrenal medulla (80%-85%), while paraganglio- mas occur along the sympathetic chain (15%-20%).4,5 Although rare, these tumours are more prevalent in hyperten- sive patients (0.2%-0.6%).1 Pheochromocytomas and para- gangliomas are classified as adrenergic (producing epinephrine and norepinephrine) or noradrenergic (mainly norepinephrine).6,7 Some head and neck paragangliomas are non-functional, though a few can produce dopamine.2 Approximately 80%-85% of PPGLs are sporadic, while the rest are associated with genetic conditions such as familial pheochromocytoma-paraganglioma syndrome, multiple en- docrine neoplasia, neurofibromatosis, and von Hippel- Lindau disease.1,8 Genetic testing is advised for patients with family history or young age.8 Clinically, PPGLs cause epi- sodic headaches, palpitations, sweating, and hypertension,
Simplified Systematic Approach to Endocrine Hypertension with Emphasis on the Role of Imaging
History: Episodic, sustained, accelerated, malignant hypertension
Examination: Features of Cushing disease, acromegaly, hyperparathyroidism, pheochromocytoma (neurocutaneous manifestation), or Congenital Adrenal Hyperplasia (ambiguous genitalia)
Pheochromocytoma and Paraganglioma
Primary Hyperaldosteronism
ACTH-dependent Cushing syndrome
ACTH-independent Cushing syndrome
Acromegaly
Thyroid and parathyroid disease
Screening test:
1 Metanephrines -+PRA and -+PAC Abnormal PPGL genes
ĮK*, Alkalosis, Į PRA and 1PAC; Aldosterone suppression test
ODST, LNSC, 24 hr UFC, ACTH
ODST, LNSC, 24 hr UFC, ACTH
Serum IGF-I and GH; OGTT
TSH, Free T4, TPO-Ab, and TRAB; PTH,Ca2+, PO4.
Imaging:
Adrenal and extradrenal imaging
Adrenal imaging and AVS
Pituitary MRI, IPSS, Dotatate scan/whole body CT
Adrenal imaging and AVS
Pituitary MRI
Thyroid scan, Ultrasound thyroid/parathyroid/KUB, 4D-CT, 99Tc-MIBI
and may lead to cardiovascular emergencies like stroke or myocardial infarction.9,10
Diagnosis and imaging
Routine PPGL screening is not recommended for all hyper- tensive patients but is advised in those with paroxysmal symptoms, resistant hypertension, or a relevant family his- tory.2 Biochemical testing, such as plasma-free or urinary fractionated metanephrines, is highly sensitive and should precede imaging.
CT and MRI are first-line tools, especially for abdominal and pelvic tumours, where 95% of PPGLs are found.1,5 Tumours often appear as round or oval masses with necrosis, cystic changes, or calcifications (Figure 2).11 However, imaging alone cannot reliably distinguish PPGLs from other adrenal lesions, or benign from malignant aetiologies. Pheochromocytomas can have a similar washout to adenomas, which can lead to false positives, but clinical findings often help differentiate them. Approximately 10%-17% of PPGLs are malignant, and malig- nancy is confirmed only in cases of local invasion or distant me- tastasis. Historically, metaiodobenzylguanidine scans were used when CT and MRI were inconclusive. Now new PET tracers like 68Ga- and 64CU-DOTATATE offer superior sensitivity for detecting metastases and recurrence.9,12 Imaging is critical for pre-operative assessment, especially in bilateral, multifocal, or metastatic cases where complete resection may not be possible.
Primary hyperaldosteronism (Conn syndrome)
Primary hyperaldosteronism (PHA) is the most common cause of secondary hypertension, affecting 5%-10% of patients, typically aged 30-60 years.1,2 Hypokalaemia, once considered a hallmark of PHA, is now seen in fewer than 25% of cases.1º The Endocrine Society 2025 clinical practice guidelines recommend expanded screening for PHA in all individuals with hypertension, a major shift from prior guid- ance that focused on high-risk groups.13
Aetiology of PHA
Primary hyperaldosteronism is commonly caused by idio- pathic hyperaldosteronism (IHA), resulting from bilateral adrenal hyperplasia (60%-66%), or aldosterone-producing adrenal adenomas (APA) (30%-35%).1 Less common causes include unilateral adrenal hyperplasia, familial hyperaldoster- onism, adrenocortical carcinoma, and ectopic aldosterone secretion. 1,14
Adrenal adenoma
Adrenal cortical adenomas are the most common benign adrenal tumours, often found incidentally on imaging.5,15 They may be hormonally inactive or can lead to clinical syn- dromes like hypercortisolism, hyperaldosteronism, or, rarely, virilization. Aldosterone-producing adrenal adenomas are ad- enomas that produce excess aldosterone. Adrenal cortical ad- enomas can occur in any age group but are most frequently
| Causes of endocrine hypertension based on the organ affected | |
| 1. Adrenal | a. Pheochromocytoma and paraganglioma b. Primary hyperaldosteronism i. Idiopathic (bilateral) adrenal hyperplasia ii. Adrenal adenoma (aldosterone-producing) iii. Adrenal carcinoma (aldosterone-producing) iv. Unilateral adrenal hyperplasia v. Familial hyperaldosteronism |
| c. Adrenal Cushing syndrome (ACTH-indepen- dent Cushing syndrome) i. Adrenal adenoma (cortisol producing) | |
| ii. Adrenal carcinoma (cortisol producing) | |
| iii. ACTH-independent macronodular adrenal hyperplasia | |
| iv. Primary pigmented nodular adrenocorti- cal disease | |
| d. Congenital adrenal hyperplasia | |
| i. 11ß-hydroxylase deficiency | |
| ii. 17a-hydroxylase deficiency | |
| 2. Pituitary | a. Cushing disease (ACTH-dependent Cushing syndrome) b. Acromegaly |
| 3. Parathyroid 4. Thyroid | Primary hyperparathyroidism a. Hyperthyroidism b. Hypothyroidism |
| 5. Other causes | a. Ectopic Cushing syndrome (ACTH-dependent Cushing syndrome) |
| i. Small cell lung cancer | |
| ii. Lung carcinoid | |
| iii. Thymic neuroendocrine tumour | |
| iv. Pancreatic neuroendocrine tumour v. Ovarian steroid cell tumour | |
| b. Renovascular hypertension (secondary hyperaldosteronism) c. Obstructive sleep apnea | |
found in young adults. Typically, they appear as oval, homo- geneous masses <2 cm16 (Figure 3A-C). The unenhanced CT attenuation value ≤10 HU is reported to have high sensitivity (79%) and specificity (96%) for diagnosing adrenal cortical adenomas.5,17 These adenomas typically show mild contrast enhancement and rapid washout. Atypical features include haemorrhage, calcification, necrosis, or large size. When CT is inconclusive, chemical shift MRI is useful; adenomas show signal dropout on opposed-phase imaging (Figure 3A and C).18,19 However, metastases from clear cell renal carcinoma and hepatocellular carcinoma may also display signal drop- out due to intravoxel lipid.20,21
Adrenocortical carcinoma
Adrenocortical carcinoma is a rare, aggressive tumour often di- agnosed late, with large size and metastases in about 33% of cases.17,22 It shows a bimodal age distribution, affecting chil- dren under 5 and adults over 40, and is more common in females. Most cases are sporadic, but some are linked to genetic syndromes. Functional carcinomas (60%) are more common in children and often secrete multiple hormones, including andro- gens, cortisol, oestrogens, and aldosterone. Cushing syndrome combined with virilization often suggests malignancy, while hyperaldosteronism is rare, occurring in only 2% of cases. In contrast, adenomas usually produce 1 hormone class.22,23
Imaging typically reveals large, heterogeneous unilateral masses with necrosis and haemorrhage17(Figure 3D). Calcification is seen in 20%-30% of cases.17,24 Non-necrotic
tumour areas usually have CT attenuation >10 HU, distin- guishing them from adenomas.22,25 On MRI, these tumours of- ten appear heterogeneous due to internal haemorrhage and necrosis and may contain microscopic fat, leading to signal loss on out-of-phase imaging, mimicking an adenoma.26 Macroscopic fat is rare, but when present, follow-up imaging or biopsy may be necessary.27 These tumours frequently invade adjacent structures and metastasize via blood or lymphatics. CT or MRI is crucial for evaluating local and distant spread, as well as guiding surgical decisions. FDG-PET imaging shows moderate uptake, which aids in differentiating adrenocortical carcinoma from adrenal adenomas and is especially useful for detecting metastatic disease.5,
Adrenal cortical hyperplasia
Adrenal cortical hyperplasia (ACH) is the benign enlarge- ment of one or both adrenal glands. Lingam et al. proposed an algorithm for diagnosing ACH using adrenal limb width measurements, reporting 100% specificity with a 5 mm cut- off and 100% sensitivity with a 3 mm cut-off.29 The clinical manifestations of ACH depend on the hormones secreted by the adrenal cortex, which can lead to conditions like adrenal Cushing syndrome or hyperaldosteronism.5 IHA is associated with bilateral hyperplasia, most commonly in those over 40, while unilateral hyperplasia is rare. 1,16
Adrenal hyperplasia can be diffuse or nodular (Figure 3E). Diffuse hyperplasia maintains the adrenal shape and is usually smooth. Aside from IHA, rare causes of diffuse hyperplasia include Adrenocorticotropic Hormone (ACTH) or corticotropin-releasing hormone (CRH) overproduction.30 Nodular hyperplasia can be either micronodular or macronod- ular, with the latter being more visible on gross examination. It is typically bilateral and multifocal.5
Evaluation and management of PHA
The distinction between APAs and IHA is crucial for manage- ment, as the former is typically treated with surgery, while the latter is managed medically.16 The evaluation of PHA is discussed in Figure 3F.10,31-34
Adrenal Cushing syndrome
Cushing syndrome results from excess cortisol, caused by ei- ther exogenous glucocorticoid use (more common) or endog- enous overproduction from pituitary, adrenal, or ectopic sites. Endogenous cases, though rarer, often lead to hyperten- sion in up to 80% of patients.35,36 In this section, adrenal causes are discussed. Pituitary and ectopic causes are addressed later in their respective sections. The diagnostic ap- proach to Cushing syndrome is outlined in Figure 4A.35,37,38
Adrenal Cushing syndrome, also referred to as ACTH- independent Cushing syndrome, results from autonomous cor- tisol secretion by the adrenal glands. It is most commonly caused by adrenal adenomas and less frequently due to adrenal carcinomas, ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) or primary pigmented nodular adreno- cortical disease (PPNAD).37 The imaging characteristics of adrenal adenomas and carcinomas are discussed in the preced- ing section, while AIMAH and PPNAD are addressed below.
ACTH-independent macronodular adrenocortical hyperplasia
This rare condition accounts for less than 1% of adrenal causes of Cushing syndrome. It is characterized by marked adrenal
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enlargement with multiple nodules, ranging from 1 to 5 cm. Imaging typically shows hypo-attenuating nodules and periph- eral enhancement, a feature that distinguishes AIMAH from adrenal adenomas and carcinomas (Figure 4B).35
Primary pigmented nodular adrenocortical disease
This inherited condition is linked to Carney complex, a disor- der associated with cardiac and cutaneous myxomas, skin pigmentation, and pituitary tumours. On imaging, the adre- nal glands are normal in size but display small bilateral nod- ules, with atrophy of the intervening glands.5,3
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive disorders caused by enzymatic defects in adrenal steroidogenesis. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common type
(95% cases) but is not associated with hypertension. Congenital adrenal hyperplasia due to 116-hydroxylase defi- ciency (5% cases) and 17a-hydroxylase deficiency (rare) are associated with hypertension due to hypersecretion of deoxy- corticosterone.40 Imaging shows non-specific diffuse bilateral adrenal enlargement with preserved shape.5
Pituitary-dependent causes
Cushing disease (ACTH-dependent Cushing syndrome)
Cushing disease, caused by pituitary adenomas, is the most common cause of ACTH-dependent Cushing syndrome. These adenomas are now classified as Pituitary Neuroendocrine Tumours or PitNETs according to the 2021 and 2022 World Health Organization Classification of Central Nervous System and Endocrine and Neuroendocrine
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Average: 13.67 (HU)
F
Clinical Suspicion
· Hypertension ± hypokalemia
· Resistant hypertension
· Adrenal incidentaloma with hypertension
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E
Screening
· Aldosterone-to-Renin Ratio (ARR)
Confirmatory Tests (when needed)
· Oral sodium loading test
· Saline infusion test
· Fludrocortisone suppression test
· Captopril challenge test
Localization
· Adrenal CT or MRI (cannot reliably
distinguish unilateral vs bilateral disease)
· Adrenal Venous Sampling (when indicated)-
gold standard before surgery
· 11C-metomidate PET/CT(less accurate; investigational)
Management
Surgery or medical therapy based on the pathology, individual characteristics and patient preferences
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Clinical suspicion of Cushing syndrome
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Confirm hypercortisolism (≥ 2 abnormal tests)
. 24-hr urinary free cortisol
Exclude:
· Low-dose dexamethasone suppression test
· Exogenous steroid use
· Late-night salivary cortisol
· Pseudo-Cushing states
Plasma ACTH
Low ACTH (ACTH-independent)
Normal/High ACTH (ACTH-dependent)
Adrenal CT/MRI
Pituitary MRI
· Adenoma
Inferior petrosal sinus sampling (IPSS)
· Carcinoma
Tumor
No tumor
· Hyperplasia
Negative IPSS
Chest/ Abdomen CT
Tumor
No tumor
Ga-68 Dotatate PET-CT
Tumours.41 Pituitary adenomas are usually microadenomas (<10mm), appearing as focal hypo-enhancing nodules on early dynamic pituitary MRI (Figure 5A).35 In the delayed phase, the adenoma may appear hypo-enhancing, iso-
enhancing, or hyper-enhancing relative to the normal pitui- tary gland (Figure 5B). On unenhanced MRI, detecting microadenomas can be challenging, with asymmetrical bulki- ness of the gland or deviation of the pituitary infundibulum
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sometimes being the only indicators. 42,43 Pituitary macroade- nomas (>10 mm) are a less common cause. MRI sensitivity is limited, with 40%-50% of microadenomas not detected, so bilateral inferior petrosal sinus sampling is often needed to confirm pituitary ACTH excess.44 Newer imaging techni- ques, like golden-angle radial sparse parallel imaging, have shown promise in improving the detection of microadenomas and distinguishing them from cysts. Functional MRI techni- ques, such as intravoxel incoherent motion, offer insights into perfusion and can be helpful in ambiguous cases.41, 41,45
Acromegaly
Acromegaly is a rare disorder caused by excess growth hor- mone (GH), typically presenting in adults aged 30-50 years. Hypertension is seen in 20%-40% of cases.2 Over 95% of cases result from GH-secreting pituitary adenomas. Rare causes include ectopic GH or Growth Hormone-Releasing Hormone (GHRH) production by neuroendocrine tumours (eg, small cell lung cancer or pancreatic cancer). Exogenous GH-induced acromegaly in athletes is extremely rare. 46
Screening and diagnosis
Screening is recommended in hypertensive patients with typi- cal acromegalic features, especially acral and facial fea- tures.2,46 Diagnosis is confirmed biochemically, followed by pituitary MRI to evaluate tumour size and extension. 46
Pituitary macroadenomas (>10 mm) are seen in up to 77% of cases, appearing as solid, enhancing masses.46,47 The pres- ence of haemorrhage, cystic changes, or necrosis may compli- cate imaging findings. Large tumours extending beyond the sella may display a “snowman” or “figure of eight” shape due to indentation at the diaphragma sellae (Figure 5℃).47 On FDG PET-CT, macroadenomas show high uptake, unlike normal pituitary tissue.48 If no pituitary tumour is detected, contrast-enhanced CT of the chest, abdomen, and pelvis should be performed to evaluate other potential GH- secreting tumours.
Parathyroid-dependent causes
Primary hyperparathyroidism
Primary hyperparathyroidism is the most common cause of hypercalcemia-related hypertension, present in up to 50% of cases.2 While often asymptomatic, symptoms may include polyuria, polydipsia, nausea, renal stones, osteoporosis, and peptic ulcers. All patients with both hypertension and hyper- calcemia should be screened with serum parathyroid hor- mone and 24-h urinary calcium.2
Causes and diagnosis
Solitary parathyroid adenoma accounts for about 85% of cases. Other causes include parathyroid hyperplasia (10%), multiple parathyroid adenomas (4%), and parathyroid carci- noma (1%).5º Surgical treatment is typically required for pri- mary hyperparathyroidism, regardless of the underlying cause. Imaging is used to localize solitary adenomas, enabling minimally invasive surgeries like video-assisted endoscopic parathyroidectomy or unilateral open parathyroidectomy. In cases of multi-glandular disease, bilateral neck exploration is needed.50,51
Imaging techniques
Ultrasound and 99mTc-sestamibi scintigraphy are commonly used for pre-operative localization of parathyroid adenomas, with similar sensitivities and specificities (Figure 6).52 When used together, these modalities can increase sensitivity to 95%, although sensitivity is lower for multiple or ectopic adenomas and parathyroid hyperplasia.5º On ultrasound, ad- enomas are typically oval, homogeneous, hypoechoic, 8- 15 mm in size, with a characteristic teardrop or triangular shape, internal rim vascularity, and polar feeding vessel, help- ing distinguish them from thyroid nodules and lymph nodes. 3,51
On 99mTc-sestamibi scintigraphy, parathyroid adenomas show high tracer uptake and delayed washout, distinguishing them from thyroid tissue.53 CT and MRI are used to evaluate ectopic glands or in patients who have had failed previous surgeries. Recent advancements in high-resolution CT and 4- dimensional CT (4DCT) improve diagnostic accuracy for these cases. 4-Dimensional CT involves 3 phases: non-
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RIGHT PARATHYROID TRANS
LEFT PARATHYROID SAG
contrast, arterial, and venous/delayed, to assess parathyroid gland density, enhancement characteristics, and washout pat- terns. This allows for distinguishing between ectopic and orthotopic glands and differentiating single vs multi- glandular disease. It also helps identify features like the “polar sign,” which indicates an enlarged inferior thyroid ar- tery near an adenoma.‘
Alternative imaging methods
Four-dimensional MRI is an alternative to 4DCT, particu- larly for patients with contraindications to CT or iodinated contrast. It uses similar phases but offers superior soft tissue contrast and avoids radiation, making it valuable for specific patient populations. However, it may have limitations, such as longer acquisition times and lower sensitivity in detecting small adenomas or ectopic glands. 54,55
For difficult cases, selective venous sampling may be employed for disease localization. New hybrid imaging tech- niques, such as single-photon emission CT and PET-CT, are becoming increasingly useful, combining anatomical and functional imaging.50,51
Emerging PET tracers
Emerging PET tracers are proving to be useful in localizing parathyroid adenomas, especially in cases where traditional imaging is negative or discordant. For example, 11C-choline PET/CT has shown a high sensitivity (98.8%) and positive pre- dictive value (91.3%) for identifying adenomas. Similarly, 18F-fluorocholine PET/CT has demonstrated excellent detec- tion rates of 96% per patient and 90% per lesion. It offers advantages like higher spatial resolution and faster scan times compared to conventional methods. Furthermore, the novel tracer 68Ga-trivehexin PET/CT has shown promise in detect- ing hyperfunctioning parathyroid tissue, even in cases where other PET tracers and MIBI scans have failed. This suggests its potential to improve lesion detection and guide more effective surgical interventions in primary hyperparathyroidism.56-5
Thyroid-dependent causes Hyperthyroidism
Common causes include Graves’ disease, toxic multinodular goitre, toxic adenoma, and thyroiditis. Women are more
frequently affected, with a prevalence of 0.5%-1.0%.2 About one-third of patients exhibit predominantly systolic hyperten- sion.3 Screening with serum thyroid-stimulating hormone (TSH) and free thyroxine is recommended for hypertensive patients with suspected hyperthyroidism.2
Graves’ disease presents with a diffusely enlarged thyroid gland with an increased heterogeneous echotexture and a rel- ative absence of nodularity on ultrasound (Figure 7A). Colour Doppler shows increased vascularity, often referred to as thyroid inferno (Figure 7B). CT and MRI show non- specific gland enlargement, while I-123 thyroid scan reveals diffusely increased uptake.59
Hypothyroidism
Sub-clinical hypothyroidism affects 4.3%-8.5% of the popula- tion and may cause up to 1% of diastolic hypertension cases.2 Serum TSH levels correlate positively with blood pressure. Hashimoto’s thyroiditis is the leading cause, along with medi- cations, surgery, radiation, congenital causes, and iodine defi- ciency.2,60 Patients with suspected hypothyroidism should be screened by measuring serum TSH and free thyroxine levels.2
Ultrasound typically shows a diffusely enlarged gland with heterogeneous echotexture, hypoechoic micronodules, and echogenic septations (Figure 7C and D). Vascularity on Doppler ranges from decreased to markedly increased. Reactive cervical lymphadenopathy is common.6
Other causes
Ectopic ACTH production
Ectopic ACTH production from non-pituitary tumours accounts for approximately 20% of ACTH-dependent Cushing syndrome cases, while CRH-producing tumours rep- resent less than 1% of cases.35
1) Small cell lung cancer is the most common primary pulmo- nary neuroendocrine neoplasm, comprising 13%-15% of all lung cancers.62,63 The typical presentation is a large hilar or mediastinal mass (Figure 8A and B), often with necrosis, haemorrhage, and invasion (eg, SVC obstruction).64
2) Lung carcinoid tumours: These tumours, although rare, are the second most common pulmonary neuroendo- crine tumours and are associated with Cushing syn- drome in about 2% of cases. They appear as central
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lung masses, sometimes with calcification or post- obstructive atelectasis. (Figure 8C and D). 65-67
3) Thymic neuroendocrine tumours: These comprise 2%- 5% of all thymic epithelial tumours; 33%-40% present with Cushing syndrome.68 These tumours often present as large anterior mediastinal masses with symptoms re- lated to local invasion or metastasis (Figure 8E and F). Imaging cannot reliably distinguish them from other thymic epithelial neoplasms. 68,6
4) Pancreatic neuroendocrine tumours: These rare tumours, accounting for 1%-2% of pancreatic tumours, are another potential source of ectopic ACTH produc- tion. These appear as well-defined solid hypervascular masses (Figure 8G). Larger lesions may show heteroge- neity due to cystic degeneration, necrosis, fibrosis, and calcification. A hypervascular rim helps differentiate these tumours from other cystic pancreatic neoplasms.70
5) Ovarian steroid cell tumours: These rare tumours, less than 0.1% of ovarian tumours, can also be associated with Cushing syndrome in 6%-10% of cases.71,72 These are typically solid unilateral tumours, often with cystic changes (Figure 8H). MRI is preferred due to the small size of these tumours. 62,63
Secondary aldosteronism and renovascular hypertension
Reduced blood flow to the kidneys can cause an increase in blood pressure, a condition known as renovascular hyperten- sion. The reduced perfusion stimulates activation of the re- nin-angiotensin-aldosterone system, leading to elevated aldosterone levels. This represents secondary hyperaldoster- onism, because excess aldosterone is a response to increased renin release rather than a primary adrenal abnormality.73
Obstructive sleep apnoea
Obstructive sleep apnoea (OSA) results from recurrent upper airway collapse during sleep, leading to intermittent hypox- emia, hypercapnia, and sleep disruption. Obstructive sleep apnoea is a strong independent risk factor for hypertension. Several studies have demonstrated that elevated aldosterone levels correlate with greater OSA severity in patients with resistant or difficult-to-treat hypertension, suggesting a bidi- rectional interaction between OSA and the renin-angioten- sin-aldosterone system.74
Conclusion
Endocrine hypertension, a subset of secondary hypertension caused by hormone excess, may be the first sign of various endocrine disorders. Although imaging has a limited role in primary hypertension, it is essential for detecting the underly- ing causes of endocrine hypertension. Accurate diagnosis enables targeted medical and surgical treatments that can cure hypertension and reduce cardiovascular risk and complications.
Funding
None declared.
Conflicts of interest
None declared.
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