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Pituitary Gland Pathology

Anatomy Functions of Hormones

Small Bean-Shaped Organ
Located at Base of Brain
Within Sella Turcica
Close proximity to Optic Chiasm
Beneath Hypothalamus, attached by Pituitary Stalk
1cm in GD
0.5 gm in weight
Anterior Lobe Posterior Lobe
(Adenohypophysis) (80% of Gland) (Neurohypophysi s)
Cell Types Modified Glial cells (Pituicytes),
Somatotrophs (GH) Axonal Processes
Lactotrophs (Prolactin) Oxytocin
Corticotrophs (ACTH) Vasopressin (ADH)
Thyrotrophs (TSH)
Gonadotrophs (FSH, LH)

Acidophili c – (A) Pink

Secrete GH, Prolactin Resemble Neural Tissue
Basophilic – (B) Dark Purple Glial cells
Secrete ACTH, TSH, Gonadotrophins Nerve Fibers
Chromophobe – (C) Pale Staining Nerve Endings
Few Secretary Activities Intra-Axonal Neurosecretory Granules

Anterior Pituitary Posterior Pituitary

Larger Portion Smaller Portion Symptoms of Pituitary Diseases
Hyperpituitarism
Excessive Secretion of Trophic Hormone s
Functional Adenoma of Anterior Pituitary
Hyperplasia of Anterior Pituitary
Carcinomas of Anterior Pituitary
(Rare, Non-Fun ctional, Metastasis – Lymph Nodes, Bones, Liver)
Secretion of Hormones by Non-Pituitary Tumours
Certain Hypothalamic Disorders
Hypopituitarism
Deficiency of Tropic Hormones due to Destructive process of Pituitary Gland
Local Mass Effects
On Optic Chiasm resulting visual field abnormalities
Cranial Nerve compression
↑ Intracranial Pressure
Pituitary Apoplexy (Haemorrhage)

Multiple Endocrine Ne oplasia Syndrome (MEN Syndrome)

Group of Genetically Inherited Diseases resulting in Proliferative lesions
(Hyperplasia/ Adenoma/ Carcinoma) of Multiple Endocrine Organs
MEN I MEN IIa MEN IIb
Pituitary Adenoma
Parathyroid Hyperplasia Hyperplasia
Adenoma
Pancreas Hyperplasia
Adenoma/ Ca
Adrenal Cortical Hyperplasia Pleochromocytoma Pleochromocytoma
Thyroid C-Cell Hyperplasia C-Cell Hyperplasia
Medullary Ca Medullary Ca

NH – Neurohypophysis (Posterior) AH – Adenohypophysis (Anterior)

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Hyperpituitarism - Pituitary Adenoma

Definition Histology
10% of Intracranial Neoplasm Monomorphi c, Uniform, Polygonal cells arrayed in Sheets/ Cords
Adult – 30-50 y/o Supporting Connective Tissue/ Reticulin is sparse (soft gelatinous consistency)
Isolated Lesions (mostly) Nuclei – Uniform, Pleomorphic
Most common cause of Hyperpituitarism Cytoplasms (depending on type, amount of secretary product)
Functional, Non-Functional (Silent) Acidophilic
3% - Associated with MEN Type I Basophilic
Associated with Gene Abnormalities Chromoph obic
Cellular monomorphis m, Absence of signifi cant Reticulin Network distinguish
Genetic Abnormalities from Non -Neoplastic Anterior Pituitary Parenchyma (Pituitary Hyperplasia)
Monoclonal in origin (Single Somatic Cells) Classification based on Hormone s Produced by Neoplastic Cells
G-Protein Mutation detected by Immunohistochemical (IHC) stains on tissue sections
Mutation in α-subunit of G-Protein (Signal Transduction)
Interferes with its GTPase activity
Activation of cAMP generation, Unchecked Cellular Proliferation
Association with MEN-I Syndrome
Aggressive Pituitary Adenoma
Mutation of RAS oncogene
Over Expression of c-MYC oncogene

Gross Morphol ogy

Soft, Well-circums cribed lesion, con fined to Sella Turcica
Larger lesions
Extend into Suprasellar region
Compress Optic Chiasm
Compress adjacent structures – Cranial Nerves
Invasive Adenoma (30%) Adenohypophyseal Adenoma
Nonencaps ulated Small round cells
Infiltrate Adjacent Bone, Dura, Brain, Nasopharynx, Nasal Cavity Small round Nuclei
Pink to Blue cytoplasm
Cells are monotonously arranged
Absence of Reticulu m Network
Reticulin Stain

Normal Hyperplasia Adenoma

Normal Acinar Expanded Acini of Total breakdown of
architecture Hyperplasia Reticulin Fiber network

Pituitary Adenoma Brain, Pituitary Adenoma Types of Pituitary Adenoma

Circumscribed Mass Lesion
(in Sella Turcica)
Compressing Optic Chias m Prolactin Cell Adenoma (20-30%)
Growth Hormone Cell Adenoma (5%)
Mixed GH-Prolactin Adenoma (5%)
ACTH Cell Adenoma (10-15%)
Gonadotroph Cell Adenoma (10 -15%)
Null Cell Adenoma (20%)
TSH Hormone Cell Adenoma (1%)
Other Pleurihormonal Adenoma (15%)

Pituitary Adenoma
Massive, Nonfunctional Adenoma
Grow beyond confines of Sella Turcica
Pituitary Adenoma H&E
Distorted the overlying brain

Growth Hormone (GH) +ve ACTH +ve

Prolactin +ve PIT-1 +ve

(Pituitary specific tra nscripti on factor res pons ible
for pitu itary development, hormone producti on i n
mammals)
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Prolactinoma (Lactotroph Adenoma) Growth Hormone Adenoma (Somatotrophic Adenoma )

Hyperfunctioning Adenoma (most common ) 2nd most common functioning Adenoma
Female ↑ - 20-40 y/o Microscopic
Amenorrhea, Galactorrhea, Loss of Libido, Infertility Granulated cells which are Acidophilic or Chromophobic
Microscopic IHC
Weakly Acidophilic/ Chromophobic cells
IHC

GH within Cytoplasm of cells

Gigantism/ Acromegaly
Within secretory granules in cytoplasm of cells
Persistent Hypersecretion of GH
Stimulate Hepatic Secretion of
Corticotroph Cell Ade noma (ACTH)
Insulin-like Growth Factor-I (IGF-I/ Somatomedin C)
Basophilic or Chromophobi c
Gigantism Acromegaly
↑ ACTH – Hypersecretion of Adrenal Cortisol
Children before Closure of Epip hyses After Closure of Epiphyses
Hypercortisolism → Cushing Syndrome
Due to ↑ GH, IGF-1 ↑ GH
(Due to excess ACTH by Pituitary)
Generalized ↑ in body size Growth most conspicuous i n
24h Urine Free Cortisol Level ↑
Disproportionately Long Arms, Legs Skin, Soft Tissue, Viscera (Thyroid,
Loss of N ormal Diurnal pattern of Cortisol Secretion Heart, Liver, Adrenal), Bones of Face,
Hypercortisolism (Cushing Syndrome) Hands, Feet
Central Obesity ↑ Bone Density (Hyperostosis)
Moon Face Spine, Hips
Weakness, Fatigability
Enlargement of Jaw
Hirsutism
Protrusion (Prognathism)
Plethora
Broadening of Lower Face
Hypertension
Enlarged Hands, Feet
Glucose Intolerance
Broad, Sausage-like Fingers
Osteoporosis
Neuropsychiatric Abnormalities Gonadal dysfunction
Menstrual Abnormalities Diabetes Mellitus
Skin Striae Generalised Muscle Weakness
IHC Hypertension
Arthritis
CHF
↑ Risk of GI Bleeding
Diagnosis
↑ Serum GH, IGF-1 Level
Failure to suppress GH Production in
response to oral load of glucose

Broadening of Lower Face

Protrusion of Jaw (Prognathism)
Mandibular overgrowth

Other Pituitary Adenoma

Gonadotroph Adenoma (LH, FSH) Hand of Acromegaly
Thyrotroph Adenoma (TSH) Widen
Nonfunctioning Adenoma (25%) Thickened
Null cell Adenoma (Hormone –ve Adenoma) Stubby
Clinically Silent counterparts of functioning Adenomas
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Hypopituitarism

Definition
↓ Secretion of Pituitary Hormones
result from diseases of Hypothalamus, Pituitary
Destructive Lesions of Pituitary (mostly)
75% of Parenchyma is Lost, Absent
Hypopituitarism + (Evidence of) Posterior Pituitary Dysfunction
in form of Diabetes Insipidus
Almost always Hypothalamic origin
Causes
1. Tumours, Other Mass Lesions
2. Pituitary Surgery, Radiation
3. Pituitary Apoplexy
Sudden haemorrhage into gland
Results in rapid enlargement of gland
Neurosurgical emergency
Cause sudden death
4. Ischaemic Necrosis of Pituitary (Sheehan Syndrome)
Post-partum necrosis of Anterior Pituitary
5. Rathke Cleft Cyst
Lined by Ciliated Cuboidal Epithelium
with occasionally Goblet cells, Anterior Pituitary Cells
6. Empty Sella Syndrome
Destruction of Part/ All of Pituitary Gland in Ablation by Surgery,
Radiation
7. Genetic Defects
Mutation in Pit-1 Transcription factor
8. Tumours in Hypothalamus
Craniopharyngiomas
Malignant tumours that Metastasize to Pituitary
9. Inflammatory disorders, Infections
Sarcoidosis, TB Meningitis

Posterior Pituitary Syndromes

Diabetes Insipidus
Deficiency of ADH → Polyuria
Inability of Kidneys to Reabsorb H2O properly from urine
Result from
• Head Trauma
• Tumours
• Surgery
• Inflammatory disorders – Hypothalamus, Pituitary
2 Forms
• Central
• Nephrogenic (renal tubular unresponsiveness to circulating ADH)
Syndrome of Inappropriate ADH Secretion (SIADH)
Resorption of excessive amounts of free H2O
• Hyponatremia
• Cerebral Oedema
Ectopic ADH secretion by Malignant Neoplasms

Hypothalamic Suprasellar Tumours

Tumour/ Tumour-like lesions in Sellar region
Induce Hypofu nction/ Hyperfun ction of Anterior Pituitary, Diabetes Insipidus
Gliomas – sometime arising in the Chiasm
Craniopharyngiomas
Derived from Vestigial Remnants of Rathke pouch
Epithelial neoplasm confined to region of Sella Turcica
Comprising 3-5% of all Intracranial Neoplasms
Admantinomatous Papillary
Nest/ Cords of Stratified Squamous Compose d of both Solid, Papillae
Epithelium embedded in Spongy lined by Well Differentiated
Reticulum Squamous Epithelium