Pituitary Adenoma

Content of This Page

1- Introduction

2- Causes

3- Symptoms

4- Types of Pituitary Adenoma

5- Clinical Presentation

6- Investigations & Lab Results

7- Complications

8- Treatment

9- Prognosis

Introduction

A pituitary adenoma is a benign (noncancerous) tumor that arises from the cells of the anterior pituitary gland. It is one of the most common types of intracranial tumors. These adenomas vary in size and hormonal activity—they can be either:

Functioning (hormone-secreting), causing symptoms due to excess hormone production, or
Non-functioning (non-secreting), presenting mainly because of their size and pressure on nearby structures.

Pituitary adenomas can cause a wide range of clinical problems, including hormonal imbalances and mass effects such as headaches and vision problems due to compression of the optic chiasm.

Causes

Genetic mutations
- Sporadic mutations in pituitary cells lead to uncontrolled growth.
- MEN1 syndrome (Multiple Endocrine Neoplasia type 1): A hereditary condition caused by mutations in the MEN1 gene, increasing the risk of pituitary adenomas along with parathyroid and pancreatic tumors.
- AIP gene mutations: Associated with familial isolated pituitary adenomas (often GH-secreting).
Hormonal factors
- Some evidence suggests that hormones like estrogen may promote pituitary cell proliferation, which might partly explain the higher incidence of prolactinomas in women.
Unknown triggers
- In many cases, the exact cause remains idiopathic (unknown).
Environmental and other factors
- No clear environmental cause has been established.
- Radiation exposure to the brain may increase the risk of developing pituitary tumors, but this is rare.

Symptoms

-Symptoms due to Hormone Overproduction (Functioning Adenomas)

Prolactinoma (most common)
- Women: Amenorrhea, galactorrhea (milk secretion), infertility
- Men: Decreased libido, erectile dysfunction, sometimes gynecomastia
Growth Hormone (GH)-secreting adenoma
- In adults: Acromegaly (enlarged hands, feet, facial bones, coarse facial features)
- In children: Gigantism (excessive growth and height)
ACTH-secreting adenoma
- Causes Cushing’s disease: Weight gain, moon face, buffalo hump, hypertension, glucose intolerance, purple striae
TSH-secreting adenoma (rare)
- Symptoms of hyperthyroidism: Weight loss, heat intolerance, palpitations, anxiety

2. Symptoms due to Mass Effect

Headache (most common)
Visual disturbances, especially bitemporal hemianopsia (loss of peripheral vision) caused by compression of the optic chiasm
Diplopia or other cranial nerve palsies (if cavernous sinus involved)

3. Symptoms due to Hypopituitarism

Fatigue, weakness
Secondary hypothyroidism (cold intolerance, weight gain)
Secondary adrenal insufficiency (hypotension, weakness)
Hypogonadism (loss of libido, amenorrhea)

4. Pituitary Apoplexy (Acute Presentation)

Sudden headache
Visual loss
Ophthalmoplegia (eye movement problems)
Altered consciousness

Types of Adenoma

I. Based on Hormonal Activity

1. Functioning (Hormone-secreting) Adenomas

These produce excess hormones, leading to specific clinical syndromes.

Type	Hormone Secreted	Clinical Syndrome
Prolactinoma	Prolactin	Galactorrhea, amenorrhea, infertility
Somatotroph adenoma	Growth hormone (GH)	Acromegaly in adults, gigantism in children
Corticotroph adenoma	ACTH	Cushing’s disease
Thyrotroph adenoma	TSH	Secondary hyperthyroidism
Gonadotroph adenoma	LH/FSH	Usually nonfunctioning clinically

2. Non-functioning (Non-secreting) Adenomas.

II. Based on Size

Type	Size
Microadenoma	<10 mm
Macroadenoma	≥10 mm
Giant adenoma	>40 mm

III. Based on Cell Origin (Histological Types)

Lactotroph adenoma → Prolactin
Somatotroph adenoma → GH
Corticotroph adenoma → ACTH
Thyrotroph adenoma → TSH
Gonadotroph adenoma → LH, FSH
Null cell adenoma → No hormone production (non-functioning)

Clinical Presentation

1. Symptoms Due to Hormonal Excess (Functioning Adenomas)

-Prolactinoma (Prolactin-secreting)

Women:
- Amenorrhea
- Galactorrhea
- Infertility
Men:
- Decreased libido
- Erectile dysfunction
- Occasionally gynecomastia

-Growth Hormone (GH)-Secreting Adenoma

In adults (Acromegaly):
- Enlargement of hands, feet, jaw, and facial bones
- Coarse facial features
- Deep voice
- Hyperhidrosis (excess sweating)
- Hypertension and diabetes
In children (Gigantism):
- Excessive linear growth before epiphyseal plate closure

-ACTH-Secreting Adenoma (Cushing’s Disease)

Central (truncal) obesity
Moon face
Buffalo hump
Purple abdominal striae
Muscle weakness
Hypertension
Glucose intolerance or diabetes
Menstrual irregularities and hirsutism

-TSH-Secreting Adenoma (Rare)

Symptoms of hyperthyroidism:
- Weight loss
- Heat intolerance
- Palpitations
- Tremor
- Anxiety

2. Symptoms Due to Mass Effect (Typically in Macroadenomas)

Headache (due to local pressure)
Visual field defects:
- Classically bitemporal hemianopsia (loss of peripheral vision)
- Due to compression of the optic chiasm
Cranial nerve palsies (if cavernous sinus is involved)
Rarely, hydrocephalus in very large tumors

3. Symptoms Due to Pituitary Hormone Deficiency (Hypopituitarism)

Fatigue and weakness
Loss of libido, infertility
Menstrual disturbances in women
Erectile dysfunction in men
Cold intolerance and weight gain (due to secondary hypothyroidism)
Hypotension and hyponatremia (due to secondary adrenal insufficiency)

4. Pituitary Apoplexy (Acute Presentation)

Sudden severe headache
Visual loss or diplopia
Nausea and vomiting
Altered mental status
Medical emergency requiring urgent intervention

Investigations & Lab Results

Investigations for Pituitary Adenoma

1. Hormonal Assays (Baseline and Stimulated Tests)

These tests help identify if the tumor is functional (secreting hormones) or non-functional.

a. Prolactin

↑ Elevated in prolactinomas
Mildly elevated in non-functioning macroadenomas due to stalk effect

b. IGF-1 (Insulin-like Growth Factor 1)

↑ Elevated in GH-secreting adenomas (acromegaly or gigantism)
More stable marker than GH itself

c. GH Suppression Test

Oral glucose tolerance test (OGTT): Failure of GH suppression confirms acromegaly

d. ACTH and Cortisol

24-hour urinary free cortisol: ↑ in Cushing’s disease
Low-dose dexamethasone suppression test: Failure to suppress cortisol
ACTH level: ↑ or inappropriately normal in ACTH-secreting tumors

e. TSH, Free T3, Free T4

↑ TSH + ↑ T3/T4: Suggests TSH-secreting tumor (central hyperthyroidism)

f. LH, FSH, Estradiol/Testosterone

Variable results in gonadotroph adenomas
Often low levels in non-functioning tumors due to hypopituitarism

g. Other pituitary hormones

May test for ADH, oxytocin, or others if clinically indicated

2. Imaging Studies

a. MRI of the Pituitary with Contrast (Gold Standard)

Determines tumor size, location, and extent
Assesses compression of optic chiasm
Distinguishes microadenoma (<10 mm) from macroadenoma (≥10 mm)

b. Visual Field Testing (Perimetry)

Indicated if there is visual disturbance or a large macroadenoma
May show bitemporal hemianopsia (optic chiasm compression)

3. Other Investigations

Electrolytes, renal function: Especially if cortisol or ADH abnormalities suspected
Bone density scan: In GH or cortisol excess (risk of osteoporosis)
Inferior petrosal sinus sampling: Occasionally used to localize ACTH source

Complications

1. Due to Tumor Mass Effect

Visual disturbances:
- Most commonly bitemporal hemianopsia (compression of the optic chiasm)
- Can progress to permanent vision loss if untreated
Headache:
- From stretching of dura mater
Cranial nerve palsies:
- Invasion into the cavernous sinus can affect CN III, IV, V1/V2, or VI
Hydrocephalus:
- Rare; occurs in large tumors compressing the third ventricle

2. Endocrine Complications

a. Hormonal Overproduction

Cushing’s disease → Metabolic syndrome, hypertension, diabetes, osteoporosis
Acromegaly → Cardiomegaly, obstructive sleep apnea, arthritis, diabetes
Prolactinoma → Infertility, osteoporosis (from hypogonadism)

b. Hormonal Deficiency (Hypopituitarism)

Due to compression of normal pituitary tissue
Can lead to:
- Adrenal insufficiency → Hypotension, hyponatremia, fatigue
- Hypothyroidism → Cold intolerance, bradycardia, weight gain
- Hypogonadism → Infertility, loss of libido
- Growth hormone deficiency → Decreased muscle mass, fatigue (in adults)

3. Pituitary Apoplexy (Acute Hemorrhage or Infarction)

Sudden, severe headache
Visual loss or double vision
Altered mental status or coma
Endocrine emergency — can cause acute adrenal insufficiency
Requires urgent surgical and medical management

4. Post-treatment Complications

Diabetes insipidus:
- After surgery if posterior pituitary is affected
CSF leak:
- Postoperative complication after transsphenoidal surgery
Recurrence of tumor:
- Especially in incomplete resections
Radiation-induced hypopituitarism:
- After radiotherapy

Treatment

1. General Principles

Treatment depends on:
- Hormone activity (functioning vs non-functioning)
- Size and location (micro vs macroadenoma)
- Presence of symptoms (mass effect, hypopituitarism)
Goals: Normalize hormone levels, relieve mass effect, preserve pituitary function

2. Medical Treatment

a. Prolactinomas

First-line: Dopamine agonists
- Cabergoline (preferred due to better tolerance)
- Bromocriptine
Mechanism: Inhibit prolactin secretion and reduce tumor size
Surgery rarely needed unless resistant or intolerant to medication

b. Growth Hormone-Secreting Adenomas (Acromegaly)

Medical therapy used if surgery is incomplete or not possible:
- Somatostatin analogs: Octreotide, lanreotide
- GH receptor antagonist: Pegvisomant
- Dopamine agonists: May be used adjunctively

c. ACTH-Secreting Adenomas (Cushing’s Disease)

Adrenal steroidogenesis inhibitors (if surgery fails or not possible):
- Ketoconazole, metyrapone, mitotane
Pasireotide: Somatostatin analog that suppresses ACTH

d. TSH-Secreting Adenomas

Somatostatin analogs (e.g., octreotide) to suppress TSH
Often require surgery

3. Surgical Treatment

Transsphenoidal Surgery (TSS)

First-line for most macroadenomas and functioning tumors (except prolactinomas)
Minimally invasive; preferred for tumors with visual symptoms
High success rate in microadenomas
Possible complications: CSF leak, diabetes insipidus, hypopituitarism

4. Radiation Therapy

Used if:
- Surgery is incomplete or contraindicated
- Tumor recurs or persists
- Tumor is not responsive to medical therapy
Types:
- Conventional radiotherapy
- Stereotactic radiosurgery (e.g., Gamma Knife)

5. Hormone Replacement Therapy

For patients with hypopituitarism, provide:
- Hydrocortisone (for cortisol deficiency)
- Levothyroxine (for TSH deficiency)
- Sex hormone replacement (estrogen/progesterone or testosterone)
- Desmopressin (for diabetes insipidus, if needed)
- Growth hormone (in selected adult patients)

Prognosis

1. General Prognosis

Benign tumors: Most pituitary adenomas are noncancerous and slow-growing.
Good overall prognosis with appropriate treatment.
Prognosis depends on:
- Tumor size (micro vs macroadenoma)
- Hormone activity
- Response to treatment (surgery, medical therapy)
- Presence of complications (e.g., hypopituitarism, visual damage)

2. Prognosis by Type

a. Prolactinomas

Excellent prognosis with dopamine agonists
Tumor size often shrinks, and hormone levels normalize
Surgery rarely needed

b. GH-Secreting Adenomas (Acromegaly)

Prognosis improves with early diagnosis and control of GH levels
Delayed treatment increases risk of cardiovascular disease, diabetes, and mortality
Lifelong monitoring required

c. ACTH-Secreting Adenomas (Cushing’s Disease)

More serious prognosis due to systemic complications (hypertension, diabetes, infections)
Successful surgery can be curative, but recurrence is possible
Increased cardiovascular and metabolic risk even after remission

d. Non-Functioning Adenomas

Good prognosis if detected early and surgically resected
May cause long-term hypopituitarism
Risk of recurrence if tumor not fully removed

3. Factors Affecting Prognosis

Favorable Factors	Poor Prognostic Indicators
Small tumor size (microadenoma)	Large tumor (macroadenoma/giant adenoma)
Early diagnosis	Delayed or missed diagnosis
Good response to medical therapy	Invasive or recurrent tumor
Successful complete surgical resection	Incomplete resection or rapid growth
No hypopituitarism or apoplexy	Permanent endocrine dysfunction, apoplexy

4. Long-Term Considerations

Lifelong endocrine follow-up often required
Risk of tumor recurrence, especially for non-functioning or incompletely resected adenomas
May need repeat imaging, hormone testing, and possible radiation or repeat surgery