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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