Adenomas: Symptoms, Types, Causes and Treatment

Adenomas are benign (non-cancerous) tumors that arise from glandular tissue in various organs, including the colon, pituitary gland, liver, and more. While benign, adenomas can have significant health implications due to their potential for malignant transformation, hormonal effects, or local tissue disruption. In this article, we’ll explore the symptoms, types, underlying causes, and available treatments for adenomas, drawing on current research to provide a comprehensive guide for patients, caregivers, and clinicians.

Symptoms of Adenomas

Adenomas can present with a wide variety of symptoms, or sometimes remain silent and only be discovered incidentally. The symptoms largely depend on the size, location, and hormonal activity of the adenoma. Understanding these symptoms is crucial for early detection and effective management.

Organ/System	Key Symptoms	Impact	Source
Pituitary gland	Visual changes, headache, hormonal issues (e.g. amenorrhea, galactorrhea, acromegaly)	Hormonal dysregulation, mass effect	2 12
Colon/Rectum	Rectal bleeding, changes in bowel habits, often asymptomatic	Risk of malignancy	4 5 7
Liver	Abdominal pain, fullness, incidental finding	Risk of hemorrhage or malignancy	3 6 16
Uterus (Adenomyosis)	Pelvic pain, heavy menstrual bleeding, anxiety/depression	Reduced quality of life	1

Table 1: Key Symptoms

Symptom Variability by Organ

Pituitary Adenomas
Pituitary adenomas are among the most common intracranial tumors. Their symptoms are typically categorized into two groups:

• Mass effect symptoms: Headache and visual disturbances due to pressure on adjacent brain structures, especially the optic chiasm.
• Hormonal symptoms: Depending on the hormone secreted by the tumor, symptoms can include:
  • Prolactinomas: Amenorrhea, galactorrhea, infertility in women; loss of libido, erectile dysfunction in men.
  • Growth hormone–secreting adenomas: Enlargement of hands/feet, facial changes (acromegaly), joint pain.
  • ACTH-secreting adenomas: Features of Cushing’s disease (weight gain, hypertension, diabetes).
  • Non-functioning adenomas: Often present late with symptoms of mass effect alone 2 12.

Colorectal Adenomas
Most colorectal adenomas are asymptomatic and discovered during routine colonoscopy. However, larger polyps may cause:

• Rectal bleeding
• Change in bowel habits (e.g., constipation, diarrhea)
• Rarely, abdominal pain or obstruction

Importantly, adenomas are pre-malignant lesions, meaning early detection and removal are essential for colorectal cancer prevention 4 5 7.

Hepatic (Liver) Adenomas
Liver adenomas often remain silent. When symptoms do occur, they may include:

• Right upper quadrant pain or abdominal fullness
• Symptoms related to acute hemorrhage from tumor rupture (rare but potentially life-threatening)

Liver adenomas are frequently found incidentally during imaging for unrelated reasons 3 6 16.

Uterine Adenomyosis (Adenoma-like Lesions)
Adenomyosis, while not a classic adenoma, shares features of benign glandular overgrowth and causes:

• Pelvic pain
• Heavy menstrual bleeding (menorrhagia)
• Negative impacts on mental health, including increased risk of anxiety and depression due to chronic pain 1.

Impact on Quality of Life

The symptoms of adenomas can significantly affect physical and mental well-being. For example, pituitary adenomas may cause infertility, body image changes, or metabolic complications, while adenomyosis can reduce quality of life due to chronic pain and psychological distress 1 12. In the case of colorectal adenomas, the most concerning risk is progression to malignancy, often without symptoms until advanced stages 4 5.

Types of Adenomas

Adenomas are a diverse group of tumors, classified by organ of origin, histological features, and molecular characteristics. Understanding these distinctions is essential for diagnosis, risk assessment, and management.

Adenoma Type	Location/Origin	Distinctive Features	Source
Pituitary adenoma	Pituitary gland	Hormone-secreting or nonfunctioning; micro/macro	2 10 12
Colorectal adenoma	Colon/rectum	Tubular, villous, tubulovillous, serrated subtypes	4 5 7 11
Hepatic adenoma	Liver	Inflammatory, HNF1α-mutated, β-catenin-mutated subtypes	3 6 16
Sessile serrated adenoma	Colon/rectum	Precursor to colorectal carcinoma, various dysplasia patterns	5
Endocrine adenomatosis	Multiple glands	Familial, affects pituitary, parathyroids, pancreas	8

Table 2: Main Types of Adenomas

Pituitary Adenomas

Pituitary adenomas are classified by:

• Size:
  • Microadenomas (<10 mm)
  • Macroadenomas (≥10 mm)
• Hormonal activity:
  • Functioning (e.g., prolactin, growth hormone, ACTH, TSH)
  • Nonfunctioning (do not secrete active hormones)
• Special variants:
  • “Silent” subtype 3 adenomas (now recognized as aggressive, plurihormonal Pit-1 lineage adenomas) 2
  • Familial isolated pituitary adenomas (FIPA) due to AIP gene mutations 10

Colorectal Adenomas

Colorectal adenomas encompass several histological types:

• Conventional adenomas:
  • Tubular (most common, lowest risk of malignancy)
  • Villous (higher malignant potential)
  • Tubulovillous (intermediate features)
• Serrated adenomas:
  • Traditional serrated adenomas
  • Sessile serrated adenomas (SSA): Important precursors to colorectal carcinoma, especially with dysplasia 5
• Molecular subtypes:
  • Consensus molecular subtypes (CMS): CMS3 (metabolic), CMS1 (MSI-immune), CMS2 (canonical), CMS4 (mesenchymal; not seen in adenomas) 4

Hepatic (Liver) Adenomas

Recent advances have led to the classification of hepatic adenomas into:

• Inflammatory subtype
• Hepatocyte nuclear factor 1α (HNF1α)-mutated subtype
• β-catenin-mutated subtype: Associated with higher risk of malignant transformation

The subtypes differ in imaging features, risk profiles, and management strategies 3 6 16.

Sessile Serrated Adenomas

These lesions, found in the colon, have distinct morphological patterns of dysplasia (minimal deviation, serrated, adenomatous, not otherwise specified) and are important in the serrated pathway to colorectal cancer. Loss of MLH1 expression is a key marker for malignant risk 5.

Endocrine Adenomatosis Syndromes

Some individuals inherit syndromes that predispose to multiple adenomas in different endocrine organs (pituitary, parathyroids, pancreatic islets), often due to dominant genetic mutations 8 10.

Causes of Adenomas

The development of adenomas is multifactorial, involving genetic predisposition, environmental exposures, and molecular changes. Understanding these causes helps guide prevention and screening strategies.

Cause Type	Example/Mechanism	Associated Adenoma	Source
Genetic mutation	NTHL1, APC, AIP, MMR gene mutations	Colorectal, pituitary	7 10 11
Environmental factors	Hormonal drugs (e.g., oral contraceptives), obesity, chronic inflammation	Hepatic, colorectal	3 6 9 16
Syndromic inheritance	Familial adenomatosis syndromes	Multiple endocrine glands	8 10
Molecular pathways	WNT pathway, β-catenin activation, MMR deficiency	Colorectal, hepatic	3 4 7 11

Table 3: Main Causes of Adenomas

Genetic Mutations

Hereditary Syndromes & Mutations

• AIP gene mutations: Increase risk of familial isolated pituitary adenomas, particularly in children and young adults 10.
• NTHL1 mutation: Homozygous loss-of-function in this base-excision repair gene causes adenomatous polyposis and colorectal cancer in a recessive pattern 7.
• MMR gene mutations: Inherited mutations in mismatch repair genes (as in Lynch syndrome) lead to early MMR deficiency and predispose individuals to multiple colorectal adenomas and early-onset cancer 11.
• APC gene mutations: Classic familial adenomatous polyposis (FAP) is caused by APC mutations, resulting in hundreds to thousands of colorectal adenomas and high cancer risk 7 11.

Environmental and Lifestyle Factors

• Hormonal exposure (e.g., oral contraceptives): Long-term use is associated with hepatic adenomas, particularly in women of reproductive age 6 16.
• Obesity and metabolic syndrome: Associated with increased risk of hepatic and colorectal adenomas 3 6 16.
• Chronic inflammation: Inflammatory bowel disease (IBD), such as ulcerative colitis, raises the risk of developing colorectal adenomas 14.

Molecular and Cellular Pathways

• WNT/β-catenin pathway: Activation leads to uncontrolled cell proliferation, particularly in colorectal and hepatic adenomas. β-catenin-mutated liver adenomas carry a higher risk of malignant progression 3 4 11.
• Mismatch repair deficiency: Leads to microsatellite instability (MSI) and accumulation of mutations, driving the adenoma-carcinoma sequence in Lynch syndrome 11.
• MLH1 loss: In sessile serrated adenomas, loss of MLH1 function is a key event in progression to carcinoma 5.

Adenoma-Carcinoma Sequence

Colorectal adenomas are the classic precursor to colorectal cancer. The progression is driven by accumulations of mutations (e.g., APC, KRAS, TP53), environmental carcinogens, and molecular pathway dysregulation 9.

Treatment of Adenomas

Treatment options for adenomas are tailored to the organ involved, adenoma type, size, symptoms, and risk of malignant transformation or complications.

Adenoma Type	First-Line Treatment	Additional Options	Source
Pituitary adenoma	Surgery (transsphenoidal), medical therapy (for prolactinomas)	Radiation, observation	12 13 15
Colorectal adenoma	Endoscopic polypectomy	Surgical resection (if advanced), surveillance	14
Hepatic adenoma	Observation (small, asymptomatic), resection (>5 cm or high risk)	Embolization (for bleeding), lifestyle modification	3 6 16
Sessile serrated adenoma	Endoscopic removal	Surveillance, surgery (if advanced)	5
Endocrine adenomatosis	Surgical excision, medical therapy	Genetic counseling	8 10

Table 4: Treatment Options for Adenomas

Pituitary Adenomas

Management principles:

• Prolactinomas: First-line therapy is dopamine agonists (cabergoline, bromocriptine); surgery reserved for resistant cases.
• Other functional adenomas: Surgery (transsphenoidal resection) is primary, sometimes followed by medical therapy (e.g., somatostatin analogues for GH or TSH-secreting tumors, ketoconazole for ACTH tumors).
• Radiation therapy: Considered when surgery and/or medications fail or for residual/recurrent disease; radiosurgery is preferred for smaller lesions 12 13 15.
• Nonfunctioning adenomas: Surgical removal if causing symptoms; otherwise, monitoring may be sufficient.

Long-term follow-up is crucial due to risk of recurrence and delayed complications such as hypopituitarism 13 15.

Colorectal Adenomas

• Endoscopic polypectomy is the standard for most adenomas detected during colonoscopy.
• Surveillance colonoscopy is necessary to monitor for recurrence or new lesions, especially in high-risk individuals.
• Surgical resection may be needed for large, sessile, or dysplastic lesions, or if malignancy is suspected.
• In patients with IBD, endoscopic removal is effective, but ongoing surveillance is essential due to elevated cancer risk 14.

Hepatic (Liver) Adenomas

• Observation: For small (<5 cm), asymptomatic lesions without high-risk features.
• Lifestyle modification: Discontinuation of oral contraceptives, weight loss.
• Surgical resection: Indicated for tumors >5 cm, β-catenin mutated subtype, male patients, or symptomatic cases (pain, bleeding).
• Embolization: In cases of acute hemorrhage to stabilize the patient before elective resection 3 6 16.

Surveillance imaging is important for monitoring growth or malignant transformation.

Sessile Serrated Adenomas

• Endoscopic removal is recommended for all detected lesions due to rapid progression risk in some cases.
• Pathological evaluation for dysplasia and MLH1 status guides further management.
• Follow-up colonoscopy is needed due to increased risk of metachronous lesions 5.

Endocrine Adenomatosis Syndromes

• Surgical removal or medical management of symptomatic hormone-secreting adenomas.
• Genetic counseling for affected families.
• Regular screening for early detection in at-risk relatives 8 10.

Conclusion

Adenomas are common benign glandular tumors with diverse presentations, risks, and management strategies. Early detection and tailored therapy are essential to prevent complications, especially malignant transformation.

Key Points:

• Adenoma symptoms vary by site, from silent to causing hormonal or mass effect symptoms.
• Major types include pituitary, colorectal (conventional and serrated), hepatic, and syndromic forms.
• Causes include genetic mutations (e.g., APC, AIP, MMR), environmental factors, and molecular pathway disruptions.
• Treatments range from endoscopic removal and surgery to medical therapy and surveillance, with strategies individualized by adenoma type and risk profile.
• Long-term monitoring is crucial, particularly for syndromic adenomas and those at high risk of recurrence or cancer.

Awareness of the diversity and significance of adenomas enables informed decisions for both patients and healthcare providers, ultimately improving outcomes through prevention, early detection, and appropriate treatment.