Location:

• In between eyes, behind nose

• Brain base

• Located in the pituitary fossa

• Relationship to the hypothalamus (above the pituitary stalk)

• Enclosed in a bony box →bony erosion when there is expansion

Surrounding Structures:

• Hypothalamus: Control of pituitary function →Around the third ventricle at the base of the brain and above the pituitary stalk. 

• Pituitary Stalk: Pathway to the hypophyseal portal system (blood supply)

• Optic Chiasm: Located immediately above the pituitary fossa; clinical importance in expansile lesions →problems with sight caused. More involved in suprasellar extensions.

• Sphenoid Sinus: Located inferior to the pituitary fossa

• Cavernous Sinus: Lateral extension of lesions may involve vascular and nervous structures (cranial nerves III, IV, VI). More involved in later extensions.

• Temporal Lobes: Rare lateral extension can reach

• Cerebral ventricles: Injuries can interrupt the flow of cerebrospinal fluid (CSF), leading to hydrocephalus

Divided into adenohypophysis & neurohypophysis, separated by the pars intermedia

Adenohypophysis (endocrine function)

• Tissue Type: Glandular epithelial

• Staining: Stains darker due to high cellularity

• Cell types: 

  • Chromophils (strongly staining cytoplasm):

    • Acidophils (red-staining):

      • Somatotrophs – secrete GH

      • Lactotrophs – secrete Prolactin

    • Basophils (purple-blue staining):

      • Corticotrophs – secrete ACTH, MSH

      • Thyrotrophs – secrete TSH

      • Gonadotrophs – secrete LH, FSH

  • Chromophobes (poorly staining cytoplasm):

    • Possibly degranulated chromophils or stem-like cells

  • Erythrocytes

Pars Intermedia 

• Located between anterior and posterior lobes

• Contains colloid-filled cysts (remnants of Rathke’s pouch)

• Contains basophilic cells and sometimes lymphocytes

• May extend into neurohypophysis

Neurohypophysis (storage function)

• Tissue Type: Neural tissue

• Staining: Pale/light staining due to unmyelinated axons and low nuclei count

• Components: 

  • Unmyelinated axons: originate in the hypothalamus (supraoptic & paraventricular nuclei)

  • Herring bodies:

    • Dilated nerve terminals storing:

      • Oxytocin

      • Antidiuretic hormone (ADH) / Vasopressin

    • Released into nearby capillaries

  • Pituicytes:

    • Glial support cells

    • Highly branched; help maintain structure

Hypothalamus as Controller: Secretes releasing and inhibiting hormones that regulate the pituitary (Table 19.3, Figure 19.7). 

• Appetite, thirst, thermal regulation and sleeping/waking involved.

• Combination centre of neural and endocrine functions to control the release of pituitary hormone-releasing factors.

• Role in circadian rhythm, menstrual cyclicity and responses to stress/exercise/mood. 

• Through the portal system

• VIP, neuropeptide Y and nitric oxide can also alter pituitary secretion 

  
  

  Anterior Pituitary: 

⬆️ Can Cause Hyperprolactinemia

• Antidopaminergics:

  • Antipsychotics: Chlorpromazine, Haloperidol, Risperidone

  • Antiemetics: Metoclopramide, Domperidone, Prochlorperazine

⬆️ Affect Cortisol Physiology

• Estrogens (e.g. OCPs): Increase CBG, elevating total cortisol

• Steroids (e.g. prednisone): Chronic use → Cushingoid features, HPA axis suppression

• Anabolic steroids: Suppress gonadotropin secretion

⬆️/⬇️ Affect Thyroid Axis

• Levothyroxine (excessive use): Causes suppression of TSH

⬇️ Therapeutic Dopamine Agonists

• Cabergoline, Bromocriptine: Inhibit PRL → treatment of hyperprolactinemia

🔄 Drugs That Affect ADH (Vasopressin)

• Desmopressin is a synthetic form of the vasopressin hormone

• ⬆️ ADH: SSRIs, TCAs, carbamazepine, chlorpropamide → SIADH risk

• ⬇️ ADH: Lithium, alcohol, phenytoin → risk of DI

Transsphenoidal resection: First-line for many adenomas (e.g. non-functioning, GH, ACTH, TSH-secreting)

Transcranial: For large/complex suprasellar tumors (e.g. craniopharyngiomas)

Always replace cortisol before thyroxine to avoid adrenal crisis

Visual Field Testing

• Test: Automated perimetry

• Use: Checks for optic chiasm compression

• Important in macroadenomas, craniopharyngiomas

• Classical finding: Bitemporal hemianopia

  
  

Basal Blood Hormone Levels

• Taken fasting, in the morning

• Can assess all anterior pituitary axes

• Stress, illness, time of day can affect results

Tumours are the most common cause of pituitary disease.

Most are benign pituitary adenomas.

Investigations:

• MRI of the pituitary →Gold standard + Shows mass right away 

  • Problem: Sometimes incidentalomas happen, so the MRI detects a small lesion that is not a tumor.

• Visual Fields →Formally by computed perimetry or Goldmann perimetry + clinical assessment confrontational using a small red pin as target

  • Common seen lesions: temporal quadrantanopia and bitemporal hemianopsia 

• Hormone levels

Most common cause: prolactinoma 

• PRL > 200 μg/L usually suggests prolactinoma.

• Microadenomas: more common in females

• Macroadenomas: similar distribution in both sexes

Other causes: pregnancy, lactation, stress, dopamine antagonists, opiods, CCB, renal failure, hypothyroidism, stalk compression, trauma

Clinical features: 

• Women: 

  • Amenorrhea, oligomenorrhea

  • Galactorrhea

  • Infertility

  • Osteopenia (chronic hypoestrogenism)

• Men: 

  • Low libido, erectile dysfunction

  • Infertility

  • Visual field defects (macroadenoma)

  • Galactorrhea is rare

  • Chronic: ↓ muscle mass, sparse beard growth

Diagnosis: 

• Fasting morning serum prolactin:

  • Normal < 20 μg/L in men, < 25 μg/L in women

• Rule out secondary causes:

  • TSH, T4 (exclude hypothyroidism)

  • Renal function

  • Pregnancy test

• Imaging: Pituitary MRI for suspected adenoma

Treatments: 

• First-line: Dopamine agonists (e.g. cabergoline, bromocriptine)

• Address underlying causes

• Surgery: Transsphenoidal resection for drug-resistant macroadenomas or acute optic compression

Most common cause: Somatotroph adenoma (GH-secreting pituitary tumor)

Rare cause: Ectopic GHRH/GH secretion (e.g. pancreatic or lung tumors)

Clinical features: 

• Skeletal changes:

  • Frontal bossing, prognathism, enlarged hands/feet, increased shoe/ring size

  • Widened tooth spacing, jaw malocclusion

  • Gigantism if onset before epiphyseal fusion (in children)

• Soft tissue features:

  • Coarse facial features, thickened skin

  • Enlarged nose, lips, tongue

  • Heel pad thickening

• Visceromegaly:

  • Cardiomegaly, LVH, arrhythmias

  • Thyroid enlargement

• Metabolic:

  • Insulin resistance, diabetes mellitus

Diagnosis: 

• Serum IGF-1: screening test (elevated in acromegaly)

• Oral glucose tolerance test (OGTT):

  • GH levels fail to suppress after glucose load

• MRI of pituitary

Treatments: 

• Surgery: Transsphenoidal resection

• Medical therapy:

  • Somatostatin receptor ligands (SRLs): octreotide, lanreotide

  • GH receptor antagonist: pegvisomant

  • Dopamine agonists (less effective)

• Radiation: adjunctive in residual/recurrent disease

Most common endogenous cause: Corticotrope pituitary adenoma

Exogenous corticosteroids = most common overall cause (iatrogenic), ectopic ACTH (small cell lung carcinoma), adrenal tumours 

Clinical features: 

• Central obesity, moon face, buffalo hump

• Purple striae

• Proximal muscle weakness

• Thin skin, easy bruising

• Hypertension, glucose intolerance, osteoporosis

• Menstrual irregularities, mood changes

Diagnosis: 

• Initial screening (choose ≥2):

  • 24-hour urinary free cortisol

  • Overnight dexamethasone suppression test

  • Late-night salivary cortisol

• ACTH assay:

  • High ACTH = ACTH-dependent

  • Low ACTH = ACTH-independent (suggests adrenal source)

• MRI: to visualize pituitary lesion (may require inferior petrosal sinus sampling if imaging inconclusive)

Treatments: 

• Transsphenoidal surgery (for pituitary adenoma)

• Medical therapy (when surgery not feasible or as bridge):

  • Steroidogenesis inhibitors: ketoconazole, metyrapone

  • Pituitary-directed agents: pasireotide

• Radiation or bilateral adrenalectomy in refractory cases

Very rare, typically macroadenomas

Often locally invasive

Clinical features: 

• Features of thyrotoxicosis: weight loss, heat intolerance, palpitations, anxiety, goiter

• May have mass effect (visual disturbances, headache)

Diagnosis: 

• TSH, Free T4, Free T3:

  • Inappropriate normal or elevated TSH in the setting of high free T4/T3

• May measure α-subunit (elevated in TSH-omas)

• MRI: confirms pituitary adenoma

Treatments: 

• Transsphenoidal surgical resection (first-line)

• May require somatostatin analogs (octreotide) or radiotherapy if residual tumor

Partial or complete deficiency of one or more anterior pituitary hormones

Progression (often sequential): GH → FSH/LH → TSH → ACTH

Causes:

• Pituitary tumors or surgery

• Radiation

• Traumatic brain injury

• Infiltrative diseases

• Vascular causes (Sheehan's syndrome, apoplexy)

Usually acquired: pituitary tumors, surgery, irradiation, trauma, infiltrative disease

Clinical features: 

• Body composition: ↓ Lean body mass, ↑ Fat mass (especially visceral), ↑ Waist-to-hip ratio

• Metabolic: hyperlipidemia & insulin resistance

• Quality of life: fatigue, depression, low self-esteem, poor concentration

• Cardiovascular: ↑ Atherosclerosis risk, ↑ Blood pressure, ↓ Cardiac output

Diagnosis: 

• IGF-1: often low

• Stimulation testing: insulin tolerance test, GHRH-arginine test

Treatments: 

• GH replacement:

  • Subcutaneous recombinant GH

  • Monitor IGF-1 levels, lipids, glucose, and body composition

Most common hormonal deficiency in hypopituitarism

Causes:

• Genetic disorders

• Hypothalamic dysfunction: anorexia, stress, excessive exercise

• Stalk compression, trauma, tumors

Clinical features: 

• Women:

  • Oligomenorrhea or amenorrhea

  • Infertility

  • ↓ Vaginal secretions, ↓ libido

  • Breast atrophy, osteoporosis

• Men:

  • ↓ Libido and erectile function

  • Infertility

  • ↓ Muscle mass, weakness

  • ↓ Beard/body hair growth

  • Testicular atrophy, soft consistency

  • Fine facial wrinkles, osteoporosis

Diagnosis: 

• Sex hormone levels:

  • ↓ Estradiol/testosterone

  • Low or inappropriately normal FSH/LH

• MRI: assess for structural lesion

• Evaluate other pituitary hormones

Treatments: 

• Men:

  • Testosterone replacement (IM/transdermal)

  • For fertility:

    • hCG + FSH injections (stimulate spermatogenesis)

    • Pulsatile GnRH (if hypothalamic cause)

• Women:

  • Cyclic estrogen + progesterone (HRT)

  • For fertility:

    • Gonadotropin injections

    • Pulsatile GnRH (if hypothalamic)

Extensions from pituitary or hypothalamus can produce visual defects 

• Upward expansion: suprasellar extension 

• Lateral extension: involves vascular & nervous structures in the cavernous sinus, rarely reaches the temporal lobe 

• Lateral, anterior, or posterior expansion must cause bony erosion 

  
  

Craniopharyngioma is a benign, slow-growing, suprasellar tumor

Arises from epithelial remnants of Rathke’s pouch, an embryologic precursor of the anterior pituitary

Epidemiology: 

• Bimodal age distribution:

  • Common in children (5–14 years) and older adults (50–75 years)

• Most cases in children present before age 15

• No strong gender predilection

Pathology: 

• Composition: cystic & solid components, often calcified, epithelial-lined cysts filled with "machine oil"-like cholesterol-rich fluid

• Histological types: 

  • Adamantinomatous: children, calcifications, cysts, "wet keratin", and cholesterol crystals

  • Papillary: adults, less cystic, rare calcifications 

Clinical features: due to mass effect and hypopituitarism

• Headache

• Vomiting (↑ intracranial pressure)

• Papilledema

• Visual field defects: classically bitemporal hemianopsia due to optic chiasm compression

• Growth failure (in children, due to GH deficiency)

• Delayed puberty

• Sleep disturbances, personality changes, behavioral issues

• ~90% of patients develop hypopituitarism: ↓ GH, TSH, ACTH, LH/FSH

• Can lead to diabetes insipidus 

Diagnosis: 

• MRI:

  • Shows cystic mass, often suprasellar, with variable solid components

  • Can reveal relationship to optic chiasm, hypothalamus, and pituitary

• CT scan:

  • Best for detecting calcifications, seen in ~90% of cases (especially in adamantinomatous type)

• Endocrine workup:

  • Comprehensive pituitary hormone panel to assess for deficiencies

Treatments: 

• Surgical Resection:

  • Approach depends on tumor size and location:

    • Transcranial approach for large/suprasellar tumors

    • Transsphenoidal approach for intrasellar/accessible lesions

  • Goal: Maximal safe resection, though complete excision is often difficult due to tumor adherence to vital structures (optic chiasm, hypothalamus)

• Radiation Therapy:

  • Post-operative radiotherapy (e.g., proton therapy or stereotactic radiosurgery):

    • Reduces risk of recurrence, which is common

• Hormone Replacement Therapy:

  • Lifelong pituitary hormone replacement usually required:

    • Hydrocortisone, levothyroxine, growth hormone, sex hormones, possibly desmopressin (DDAVP) if diabetes insipidus develops

Prognosis: 

• Generally good long-term survival, especially with early treatment

• High recurrence rate (~20–30%), especially if resection is incomplete

• Requires lifelong follow-up

Ischemic infarction of the pituitary due to severe postpartum hemorrhage

Pathophysiology 

• During pregnancy: Pituitary enlarges and becomes more vascular

• Massive blood loss leads to hypoperfusion and infarction

• Results in hypopituitarism, often pan-hypopituitarism

Clinical Features 

• Failure to lactate (↓ prolactin)

• Amenorrhea or oligomenorrhea

• Fatigue, hypotension

• Symptoms of hypothyroidism, adrenal insufficiency, and hypogonadism

Diagnosis

• History of severe postpartum hemorrhage

• Hormone panel: ↓ ACTH, TSH, FSH/LH, GH, prolactin

• MRI: May show empty sella or pituitary atrophy

Treatment

• Lifelong hormone replacement:

  • Hydrocortisone

  • Levothyroxine

  • Estrogen/progesterone or testosterone

  • GH (optional depending on needs)

Kallmann’s Syndrome: Isolated gonadotropin deficiency