Study sheet: Pituitary Adenomas

📋 Course Outline

1. Definition and Epidemiology
2. Tumorigenesis and Classification
3. Radiological Classifications
4. Immunohistochemical and Prognostic Classification
5. Tumor Syndrome and Apoplexy
6. Hyperprolactinemia and Prolactinoma
7. Acromegaly and Somatotroph Adenoma
8. Other Functional and Deficient States

📖 1. Definition and Epidemiology

🔑 Key Concepts & Definitions

• Pituitary adenoma : a benign tumor arising from the pituitary gland and classified by size and hormonal function

★ Must-know

• Since 2017, pituitary adenomas have also been called pituitary neuroendocrine tumors (PitNETs) because some can be aggressive and create oncological problems.

• The prevalence of pituitary adenomas is 78 to 94 per 100,000 inhabitants, and the incidence is 4 per 100,000 inhabitants per year.

Further detail

• Pituitary adenomas represent 10% of brain tumors, and 15% to 40% are gonadotroph adenomas.

💡 Memory Hook

“Adenoma” sounds benign, whereas PitNETs can be aggressive.

📖 2. Tumorigenesis and Classification

★ Must-know

• The gsp oncogene, caused by an activating mutation of the alpha subunit of G proteins, is present in 40% of somatotroph adenomas.

• Germline mutations of the AIP gene cause some familial pituitary adenomas but do not appear to be involved in sporadic tumorigenesis.

📌 Functional pituitary adenomas secrete hormones, whereas nonfunctional adenomas do not produce clinically evident hormone hypersecretion.

Further detail

• Other abnormalities include:
  • PTTG overexpression
  • reduced CDKN2A expression
  • promoter-region hypermethylation

💡 Memory Hook

Genetic and epigenetic abnormalities → pituitary tumor development.

📖 3. Radiological Classifications

★ Must-know

📌 A microadenoma measures less than 10 mm, whereas a macroadenoma measures more than 10 mm.

• Hardy stage A is strictly intrasellar, stage B extends suprasellarly toward the optic chiasm, stage C extends infrasellarly into the sphenoid sinus, and stage D extends laterally toward the cavernous sinus or retro-sellarly.

• In the Knosp classification, grade 1 has no cavernous invasion, grade 2 permits complete surgical resection, grade 3 extends beyond the external carotid tangent, and grade 4 completely surrounds the internal carotid artery.

Further detail

• Sellar grades are:
  • Grade 1: normal sella and intact floor
  • Grade 2: enlarged sella with local erosion
  • Grade 3: destroyed sella with invasive extension

💡 Memory Hook

Size → extension → cavernous invasion.

📖 4. Immunohistochemical and Prognostic Classification

★ Must-know

• The immunohistochemical families are (Osamura R, Grossman A, Korbonits M, Kovacs K, Lopes M, Matsuno A, et al., 2017):

  • PIT1
  • Tpit
  • SF1

• Immunohistochemistry detects pituitary hormonal content including prolactin, TSH, GH, ACTH, FSH, LH, and the alpha subunit, especially when hormone expression is weak, negative, or discordant. — Trouillas J, Jaffrain-Rea ML, Vasiljevic A, Raverot G, Roncaroli F, Villa C., How to classify the pituitary neuroendocrine tumors (PitNET)s in 2020, 2020

• Trouillas grades are:

  • Grade 1a: noninvasive and nonproliferative
  • Grade 1b: noninvasive and proliferative
  • Grade 2a: invasive and nonproliferative
  • Grade 2b: invasive and proliferative
  • Grade 3: metastatic pituitary carcinoma

Further detail

• An atypical adenoma is suggested by Ki-67 above 3%, more than 2 mitoses per 10 high-power fields, and p53 positivity in more than 10 nuclei per 10 high-power fields.

💡 Memory Hook

Invasion describes spread, whereas proliferation describes cellular activity.

📖 5. Tumor Syndrome and Apoplexy

★ Must-know

• The tumor syndrome may include:

  • retro-orbital headaches
  • visual disturbances
  • reduced visual acuity
  • visual-field defects
  • cavernous sinus syndrome

• Pituitary apoplexy presents abruptly with severe headache, meningeal syndrome, possible ocular motor paralysis, confusion or coma, and acute visual disturbance caused by chiasmal compression.

Further detail

📌 Emergency imaging in suspected pituitary apoplexy demonstrates an adenoma undergoing necrosis or hemorrhage.

💡 Memory Hook

Mass effect → headache, visual defects, and cranial nerve dysfunction.

📖 6. Hyperprolactinemia and Prolactinoma

★ Must-know

• Causes include:

  • prolactinoma
  • pituitary stalk disconnection
  • medications
  • renal failure
  • liver failure
  • polycystic ovary syndrome
  • hypothyroidism

• In women, hyperprolactinemia may cause galactorrhea, menstrual disturbances, amenorrhea in 90% of cases, infertility, reduced libido, and dyspareunia due to vaginal dryness.

• Dopamine agonists include:

  • bromocriptine
  • quinagolide
  • cabergoline

Further detail

📌 For macroadenomas, surgery is considered when medical treatment is intolerable or ineffective, visual-field improvement is absent, or neurological pituitary apoplexy occurs.

💡 Memory Hook

Prolactinoma secretion differs from stalk-disconnection hyperprolactinemia.

📖 7. Acromegaly and Somatotroph Adenoma

★ Must-know

• Acromegaly may cause:

  • enlarged extremities
  • thick oily skin
  • characteristic facial changes
  • sweating
  • headaches
  • joint pain
  • hypertension
  • sleep apnea
  • carpal tunnel syndrome

• The diagnosis of acromegaly is supported when the growth hormone nadir after oral glucose tolerance testing is greater than 0.1 micrograms per liter, equivalent to 1 IU per liter.

📌 Treatment of somatotroph adenoma is often surgical, with radiotherapy after surgical failure and medical therapy when surgery or radiotherapy is contraindicated or before surgery for invasive tumors.

Further detail

• Complications include:
  • myocardial hypertrophy
  • glucose intolerance
  • sleep apnea
  • acromegalic arthropathy
  • colonic polyposis

💡 Memory Hook

A progressively enlarged hand with a ring that no longer fits.

📖 8. Other Functional and Deficient States

★ Must-know

• Clinical features include:

  • proximal and abdominal muscle wasting
  • thin bruisable skin
  • wide purple striae
  • rounded erythematous face
  • osteoporosis
  • hypertension
  • glucose intolerance
  • hypokalemia
  • hypercalciuria

• In corticotroph adenoma, cortisol is elevated with loss of its circadian rhythm, the low-dose suppression tests are negative, and ACTH is elevated but suppressible with the high-dose test.

📌 Anterior pituitary insufficiency should be sought in every patient with a pituitary adenoma and presents with signs of deficiency in each pituitary axis.

• MRI is the reference examination for detecting pituitary microadenomas and macroadenomas, and the clinical diagnosis of acromegaly may be delayed by 4 to 10 years.

Further detail

• Thyrotroph adenoma is very rare, representing less than 1% of pituitary adenomas, and presents with tumor syndrome, hyperthyroidism, elevated free T4, and nonsuppressed normal or elevated TSH.

• Gonadotroph adenoma may cause amenorrhea or ovarian hyperstimulation in premenopausal women, hypogonadism or testicular stimulation in men, and elevated FSH and LH.

💡 Memory Hook

Corticotroph → thyrotroph → gonadotroph → anterior pituitary failure.

📊 Synthesis Tables

Main Pituitary Adenoma Types

Type	Typical hormonal or clinical features	Main treatment mentioned
Prolactinoma	Hyperprolactinemia, galactorrhea, menstrual or sexual dysfunction	Dopamine agonists; surgery in selected cases
Somatotroph adenoma	Acromegaly and elevated GH/IGF-1	Surgery, radiotherapy, or medical therapy
Corticotroph adenoma	Cortisol excess and Cushing features	Diagnostic suppression testing; treatment is directed at the adenoma
Thyrotroph adenoma	Hyperthyroidism with nonsuppressed TSH	Somatostatin analogue or surgery
Gonadotroph adenoma	Tumor syndrome with altered FSH/LH effects	Surgery, radiotherapy, or medication