Hyperpituitarism
Definition
Result of Excess Secretion of Trophic Hormone s
Most commonly by Pituitary Adenoma
Less common cause s Hyperplasias, Carcinomas of Adenohypophysis
Extra-pituitary Tumours
Hypothalamic Disorders
Pituitary Adenoma
Definition
Abnormal growths that develop in pituitary gland
Cause Excessive, Low production of certain hormones
Characteristics
Non-cancerous
Non-spreading growths
Remain confined to pituitary gland or surrounding tissues
Does not spread to other parts of the body
Classification
Lactotroph Adenomas (PRL)
Somatotroph Adenomas (GH)
Corticotroph Adenomas (ACTH)
Others
• Gonadotroph Adenomas (LH, FSH)
• Thyrotroph Adenomas (TSH)
Etiology, Pathogenesis
Etiology (Unknown) Pathogenesis
Uncontrolled cell growth in pituitary
gland causing tumour
Oncogenes
Tumour Suppressor Gene
Growth Factors
Oversecretion of Hypothalamic
regulating hormones
Genetic Abnormalities in Pituitary Adenomas
G-Protein Mutation
Multiple Endocrine Neoplasia (MEN) Syndrome
Activation of RAS Oncogene
Overexperssion of r-MYC oncogene
Risk Factor
Age Family History
Older Adults MEN Type I
Epidemiology
10% of all intracranial neoplasms
Adults
Common types of secreting tumours
GH
Prolactin
Rare FSH
LH
Gross Microscopic
Types
Microadenoma (< 1cm)
Macroadenoma (>1cm)
Uniform, Polygonal cells
Nuclei Oval→Round
Cytoplasm
Acidophilic (Pale Pink)
Basophilic
Grey Tan
Relatively Firm
May extend into Suprasellar Region
Invade various structures
Compress Optic Chiasm
Cell Arrangement
Nests
Cords
Prominent Vascularity
Signs, Symptoms (related to Mass Effect)
Pituitary Adenoma ↓
↑ in Size ↓
Changes in Intrasellar Pressure
Extend in Suprasellar Direction
Lateral Mass Invasion
Extension into Sphenoid Sinus
Compress Pituitary Stalk
Direct Hypothalamic Encroachment
Changes in Intrasellar Pressure ↓
Stretch Dural Plate ↓
Headache
Extend in Suprasellar Direction ↙ ↓ ↘
Obstruction of
CSF Flow
Compression of
Optic Chiasm
Direct Invasion of
Optic Nerves ↓ ↓ ↓
Headache Bitemporal
Hemianopia
Visual Loss
Lateral Mass Invasion
(Impinges on Cavernous Sinus) ↓
Compress Neural Contents ↙ ↘
CN III, IV, VI Palsies Effects on CN V1, CN V2 ↓ ↓ Facial Sensation
Diplopia (Double Vision)
Ptosis (Dropping of upper eyelid)
Extension into Sphenoid Sinus ↙ ↘
Invade Palate Roof Invade Temporal, Frontal Lobes ↓ ↓
Nasopharyngeal Obstruction Personality Disorder
Anosmia (Loss Ability to Smell)
Compress Pituitary Stalk ↓
Compress Portal Vessels ↓
Disrupt Pituitary Access to Hypothalamic Hormone ↙ ↘
Disrupt Inhibition to Dopamine Concurrent Loss of
other Pituitary Hormones ↓ ↑ Prolactin
↓ Hyperprolactinaemia
Normal Eye Field
Bilateral Hemianopsia
CN VI Palsy
CN IV Palsy
Ptosis (Dropping of Eyelid)
Double Vision
Signs, Symptoms (related to Hormonal Changes)
Lactotroph ade nomas
(PRL)
Somatotroph
Adenomas (GH)
Corticotroph
Adenomas (ACTH)
Hyperprolactinemia Acromegaly Cushing’s Syndrome
Complications (Tumour 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)
Prolactinoma
Most common type of Pituitary Adenoma
Arising from Lactotrope cells that produce Prolactin
Common in
20 – 50 y/o (Children rare)
Women ↑
Symptoms due to ↑ Prolactin in blood (Hyperprolactinaemia)
Signs, Symptoms
Male Female
Erectile Dysfunction Irregular Menstrual (Oligomenorrhea)
↓ Body Hair Lack of Menstrual (Amenorrhea)
Gynecomastia (uncommon) Milk discharge (Galactorrhea) when
not pregnant or breastfeeding
Both Sex
Osteoporosis
Loss of Interest in Sexual Activity (↓ Libido)
Infertility
Pathophysiol ogy Lactotroph Adenoma
↓
Excessive Prolactin pr oduction by tumour cel l
↓
Hyperprolactinemia
↙ ↓ ↘
↑ Actio n of Pr olactin Inhibit effect of
Gonadotrophin hormone
on Gonad
↓ Estrogen
↓Testostero ne ↓
Proliferatio n of
Ductal Tissue in Breast
↓
↙ ↘ ↓ Bone Density
↓ No FSH No LH ↓
↑ Milk Secre@on ↓ ↓ Osteoporos is
↓ No Stimulation of
Sertoli Ce ll
No Ovulation
Galactorrhea ↓
↓ No Follicu lar Growth
No Spermatogenesis ↓
↓ Amenorrhea
↓ Libid o
(Impotence)
Hyperprolactinaemia
Present earlier in women – due to Menstrual disturbances
Causes Pathological (common) Drugs Physiological
Suprasellar pituitary mass
extension
Drug-induced
hypersecretion (Dopamine
recepto r blockers)
Pregnancy
Lactation
1° Hypothyroidism Stress
Dopamine synthesis
inhibitors (Methyldopa)
Sleep
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
Rule out 1° Hypothyroidism causing TRH-induced Prolactin excess
MRI/ CT Scan
Size, Extension of Tumour
Management
Correct underlying cause
If not possible, then Therapeutic 1st
, 2nd
line
Therapeutic 1st
line Therapeutic 2nd
line
Dopamine Agonist therapy
(shrink majority of prolactin secreting
macroadenomas)
Surgical
(macroadenoma s cystic or patient
intolerant of dopamine agonists)
Radiotherapy
Somatotroph Adenoma (GH)
Gigantism
Hypersecretion of GH before Epiphyses close
Prepubertal children
Caused by
Pituitary Adenoma (GH-producting adenoma)
(Somatotroph Adenoma may be large when patient seek clinical attention)
Clinical Features
Generalized ↑ Body Size
(Disproportionately long arms, legs)
Accompanied by evidence of Acromegaly
Pathophysiol ogy GH secreting adenoma(s) of Pituitary
GH Releasing Hormone, GH Secreting Neoplasms
(eg. Cardnoid Tumors)
↓
↑ GH Secretion
↙ ↘
Direct Eff ects
(Anti-Insulin effects)
Indirect Effects
(Insulin-like effects)
↓ ↓
Induction of Insulin Resistance
(in Peripherals)
Hyperinsulinism
Lipolysis
Ketogenesis
Hyperglyc aemia
Na+, H2O Retention
↑ IGF-1 Production
↓
Induction of Protein Synthesis
Amino Acid Transportation
Muscle Mass, Cartilage, Bone Growth
DNA, RNA Synthesis
Cell Proliferation
Acromegaly
Due to Pituitary Tumour in almost all cases
Hyperplasia due to excess GHRH (very rare)
Clinical Features Prominent Supraorbital Ridge
Prognathism
Interdental separation
Large Tongue
Hirsutism
Thick greasy skin
Spade-like Hands, Feets
Tight Rings
Carpal Tunnel Syndrome
Visual Fields Defect
Investigations Measure GH Levels during an Oral Glucose Test
Normal – Plasma GH Suppressed < 5ng/mL
Acromegaly – Plasma GH is Not Suppressed
Management
1st
Line 2nd
Line
Trans-Sphenoidal Surgery Radiotherapy
Somatostatin Analogues
• Octreotide, Lanreotide
• Slow release injection every week
Dopamine Agonists
GH Receptor Agonists
Daily self injection for patients who
fail to suppress following analogue
therapy
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Cushing’s Syndrome (Hyperadrenocorticolism, Hypercorticolism)
Definition
Chronic exposure to excessive circulating levels of Glucocorticoid
Usually small adenomas at time of diagnosis
Cushing’s Syndrome Cushing’s Disease
Adrenal Hypersecretion of Cortisol ACTH Excess due to Excessive
production by Pituitary
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
(80%)
Iatrogenic Alcohol excess
Adrenal Adenoma Major Depressive Illness
Iatrogenic Adrenal Carcinoma 1° Obesity
Clinical Features (Exaggeration of known actions of Glucocorticoids)
Early Manifestation
Hypertension
Weight Gain
With Time
Truncal Obesity
Moon Facies
Buffalo Hump (accumulation of fat in posterior neck, back)
↓ Muscle Mass
Proximal Limb Weakness
Mimic Diabetes Mellitus
Hyperglycaemia
Glucosuria
Polydipsia
Abdominal Area
Skin is Thin, Fragile, Easily Bruised
Cutaenous Striae
Osteoporosis
Backache
↑ Suscep@ble to Fractures
↑ Risk of Infections
Additional Manifestation
Hirsutism
Menstrual Abnormalities
Mental Distrubances (mood swings, depression, frank psychosis )
Pathophysiol ogy
ACTH-Producing Adenoma
in Pituitary
Anterior Pituitary gland contain
area of Corticotroph ↘ ↙
Excessive Secretion of ACTH
Stimulation of Adrenal Gland to produce ↑ Glucocorticoid
Bilateral Adrenal Gland Hyperplasia
Hypercorticolism
Investigations
Management
1st
Line – Surgery 2nd
Line – Radiotherapy
Trans-sphenoidal Surgery
(treatment of choice in
Cushing’s Disease)
Used in Children
(Prevent Nelson’s Syndrome)
Nelson’s Syndrome
• Bilateral Adrenalectomy in Pituitary
dependent Cushing’s syndrome
• Absence of –ve feedback
suppression by ↑ Cortisol level
• Aggressive Pituitary
Macroadenoma, very ↑ ACTH
levels causing Pigmentation
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