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Hyperpituitarism

Definition Signs, Symptoms (related to Mass Effect)

Result of Excess Secretion of Trop hic Hormone s Pituitary Adenoma
Most commonly by Pituitary Adenoma ↓
↑ in Size
Less common cause s ↓
Hyperplasias, Carcinomas of Adenohypophysis Changes in Intrasellar Pressure
Extra-pituitary Tumours Extend in Suprasellar Direction
Hypothalamic Disorders Lateral Mass Invasion
Extension into Sphenoid Sinus
Pituitary Adenoma Compress Pituitary Stalk
Direct Hypothalamic Encroachment
Definition Changes in Intrasellar Pressure
Abnormal growths that develop in pituitary gland ↓

Cause Excessive, Low produ ction of certain hormones Stretch Dural Plate
↓
Characteristics Headache
Non-can cerous Extend in Suprasellar Direction
Non-spreading growths ↙ ↓ ↘
Remain con fined to pituitary gland or surrounding tissues Obstruction of Compression of Direct Invasion of
Does not spread to other parts of the body CSF Flow Optic Chiasm Optic Nerves
↓ ↓ ↓
Headache Bitemporal Visual Loss
Classification
Hemianopia
Lactotroph Adenomas (P RL)
Lateral Mass Invasion
Somatotroph Adenomas (GH)
(Impinges on Cavernous Sinus )
Corticotroph Adenomas (ACTH) ↓
Others Compress Neural Contents
• Gonadotroph Adenomas (LH, FSH) ↙ ↘

• Thyrotroph Adenomas (TSH) CN III, IV, VI Palsies Effects on CN V 1 , CN V 2

Etiology, Pathogenesis
Etiology (Unknown)
Uncontrolled cell growth in pituitary
gland causing tumour
↓
↓ Facial Sensation
Diplopia (Double Vision)
Pathogenesis Ptosis (Dropping of upper eyelid)
Oncogenes Extension into Sphenoid Sinus
Tumour Suppressor Gene ↙ ↘

Growth Factors Invade Palate Roof Invade Temporal, Frontal Lobes

↓ ↓
Oversecretion of Hypothalamic Nasopharyngeal Obstruction Personality Disorder
regulating hormones Anosmia (Loss Ability to Smell)
Compress Pituitary Stalk
Genetic Abnormalities in Pituitary Adenomas ↓
G-Protein Mutation Compress Portal Vessels
↓
Multiple Endocrine Neoplasia (MEN) Syndrome
Disrupt Pituitary Access to Hypothalamic Hormone
Activation of RAS Oncogene ↙ ↘
Overexperssion of r-MYC on cogene Disrupt Inhibition to Dopamine Concurrent Loss of
↓ other Pituitary Hormones
Risk Factor ↑ Prolactin
↓
Age Family History Hyperprolactinaemia
Older Adults MEN Type I

Epidemiology
10% of all intracranial neoplasms
Adults Normal Eye Field Bilateral Hemianopsia
Common types of secreting tumours
GH
Prolactin
Rare
FSH CN VI Palsy CN IV Palsy
LH

Gross Microscopic
Types Uniform, Polygonal cells
Microadenoma (< 1cm) Nuclei Oval→Round
Macroadenoma (>1cm) Cytoplasm Ptosis (Dropping of Eyelid)
Grey Tan Acidophilic (Pale Pink) Double Vision
Relatively Firm Basophilic
May extend into Suprasellar Region Cell Arrangement Signs, Symptoms (related to Hormonal Changes)
Invade various structures Nests Lactotroph ade nomas Somatotroph Corticotroph
Compress Optic Chiasm Cords (PRL) Adenomas (GH) Adenomas (ACTH)
Prominent Vascularity Hyperprolactinemia Acromegaly Cushing’s Syndrome

Complications (Tu mour Growth begin to approach 1cm in diameter)

Vision Loss
Permanent Hormone Imbalance
Sudden Bleeding into Tumour (Pituitary Apoplexy)
• Sudden, Severe Headache
• Sudden Vision Problems
• Symptoms of Hypopituitarism
o Lightheadedness
o Vomiting
o Cold Intolerance
o Excessive Thirst
o Fatigue
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Lactotroph Ade noma (PRL) Somatotroph Adenoma (GH)

Prolactinoma Gigantism
Most common type of Pituitary Adenoma Hypersecretion of GH before Epiphyses close
Arising from Lactotrope cells that produce Prolactin Prepubertal children
Common in Caused by
20 – 50 y/o (Children rare) Pituitary Adenoma (GH-produ cting adenoma)
Women ↑ (Somatotroph Adenoma may be large when patient seek clinical attention)
Symptoms due to ↑ Prolactin in blood (Hyperprolactinaemia) Clinical Features
Generalized ↑ Body Size
Signs, Symptoms (Disproportionately long arms, legs)
Male Female Accompanied by evidence of Acromegaly
Erectile Dysfunction Irregular Menstrual (Oligomenorrhea) Pathophysiol ogy
↓ Body Hair Lack of Menstrual (Amenorrhea) GH secreting adenoma(s) of Pituitary
Gynecomastia (uncommon) Milk discharge (Galactorrhea) when GH Releasing Hormone, GH Secreting Neoplasms
not pregnant or breastfeeding (eg. Cardnoid Tumors)
↓
Both Sex ↑ GH Secretion
Osteoporosis ↙ ↘
Loss of Interest in Sexual Activity (↓ Libido) Direct Eff ects Indirect Effects
Infertility (Anti-Insulin effects) (Insulin-like effects)
↓ ↓
Induction of Insulin Resistance ↑ IGF-1 Production
Pathophysiol ogy (in Peripherals) ↓
Lactotroph Adenoma
↓ Hyperinsulinism Induction of Protein Synthesis
Excessive Prolactin pr oduction by tumour cel l Lipolysis Amino Acid Transportation
↓ Ketogenesis Muscle Mass, Cartilage, Bone Growth
Hyperprolactinemia Hyperglyc aemia DNA, RNA Synthesis
↙ ↓ ↘ Na+, H2O Retention Cell Proliferation
↑ Actio n of Pr olactin Inhibit effect of ↓ Estrogen
↓ Gonadotrophin hormone ↓Testostero ne
Proliferatio n of on Gonad ↓
Ductal Tissue in Breast ↙ ↘ ↓ Bone Density Acromegaly
↓ No FSH No LH ↓ Due to Pituitary Tumour in almost all cases
↑ Mi lk SecreƟon ↓ ↓ Osteoporos is
↓ No Stimulation of No Ovulation Hyperplasia due to excess GHRH (very rare)
Galactorrhea Sertoli Ce ll ↓ Clinical Features
↓ No Follicu lar Growth Prominent Supraorbital Ridge
No Spermatogenesis ↓
↓ Amenorrhea Prognathism
↓ Libid o Interdental separation
(Impotence) Large Tongue
Hirsutism
Hyperprolactinaemia Thick greasy skin
Present earlier in women – due to Menstrual disturbances Spade-like Hands, Feets
Causes Tight Rings
Pathological (common) Drugs Physiological Carpal Tunnel Syndrome
Suprasellar pituitary mass Drug-induced Pregnancy Visual Fields Defect
extension hypersecretion (Dopamine Lactation
recepto r blockers) Investigations
1° Hypothyroidism Stress
Measure GH Levels during an Oral Glucose Test
Dopamine synthesis Sleep
inhibitors (Methyldopa) Normal – Plasma GH Suppressed < 5ng/mL
Acromegaly – Plasma GH is Not Suppressed
Investigation
Pregnancy Test
Rule out ↑ Prolactin due to Pregnancy
Basal Prolactin Levels
mU/L
< 500 Normal upper limit
500-1000 Stress, Drugs
1000-5000 Drugs, Microprolactinoma
> 5000 Macroprolactinoma
Gonadal Function Test
Diagnosis, Treatment of Gonadal functions
T4, TSH Measurement Management
Rule out 1° Hypothyroidism causing TRH-induced Prolactin excess 1st Line 2nd Line
MRI/ CT Scan Trans-Sphenoidal Surgery Radiotherapy
Size, Extension of Tumour Somatostatin Analogues
• Octreotide, Lanreotide
Management • Slow release injection every week
Correct underlying cause Dopamine Agonists
If not possible, then Therapeutic 1st , 2nd line GH Receptor Agonists
Therapeutic 1st line Therapeutic 2nd line Daily self injection for patients who
Dopamine Agonist therapy Surgical fail to suppress following analogue
(shrink majority of prolactin secreting (macroadenoma s cystic or patient therapy
macroadenomas ) intolerant of dopamine agonists)
Radiotherapy
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Cushing’s Syndrome (Hyperadrenocorticolism, Hypercorticolism)

Definition Pathophysiol ogy

Chronic exp osure to excessive circulating levels of Glucocorticoid ACTH-Producing Adenoma Anterior Pituitary gland contain
Usually small adenomas at time of diagnosis in Pituitary area of Corticotroph
↘ ↙
Cushing’s Syndrome Cushing’s Diseas e
Excessive Secretion of ACTH
Adrenal Hypersecretion of Cortisol ACTH Excess due to Excessive
Stimulation of Adrenal Gland to produce ↑ Glucocorticoid
production by Pituitary
Bilateral Adrenal Gland Hyperplasia
Hypercorticolism

Investigations

Epidemiology
Rare (1-3 cases per million population per year)
Females ↑
Peak Age – 25 – 40 y/o

Etiology
ACTH Dependent Non-ACTH De pende nt Pseudo-Cushing’s
Syndrome
Corticotroph Adenomas Iatrogenic Alcohol excess
Management
(80%) Adrenal Adenoma Major Depressive Illness
1st Line – Surgery 2nd Line – Radiotherapy
Iatrogenic Adrenal Carcinoma 1° Obesity
Trans-sphenoidal Surgery Used in Children
(treatment of choice in (Prevent Nelson’s Syndrome)
Clinical Features (Exaggeration of known actions of Glucocorticoids)
Cushing’s Disease) Nelson’s Syndrome
Early Manifestation
• Bilateral Adrenalectomy in Pituitary
Hypertension
dependent Cushing’s syndrome
Weight Gain
• Absence of –ve feedback
With Time
suppression by ↑ Cortisol level
Truncal Obesity
• Aggressive Pituitary
Moon Facies
Macroadenoma, very ↑ ACTH
Buffalo Hu mp (accumulation of fat in posterior neck, back)
levels causing Pigmentation
↓ Muscle Mass
Proximal Limb Weakness
Mimic Diabetes Mellitus
Hyperglycaemia
Glucosuria
Polydipsia
Abdominal Area
Skin is Thin, Fragile, Easily Bruised
Cutaenous Striae
Osteoporosis
Backache
↑ SuscepƟble to Fractures
↑ Risk of Infections
Additional Manifestation
Hirsutism
Menstrual Abnormalities
Mental Distrubances (mood swings, depression, frank psychosis )