8. Pituitary Disorders
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ENDOCRINE DISORDERS
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The Players
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The Endocrine System
Exocrine glands - transport their hormones to target
tissues via ducts.
Endocrine glands:
release their hormones directly into the blood
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Organs
• Pituitary
• Thyroid
• Parathyroids
• Adrenals
• Endocrine pancreas
Diseases
Non-neoplastic
too much hormone
too little hormone
Neoplastic
benign
malignant
Endocrine Pathology
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Pituitary gland
• “The Master Gland”
– Produces many hormones.
– Primary function is to control other glands & body systems
– Secretion is controlled by the hypothalamus
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Pituitary
60 mg
Midline structure in sella turcica
Anterior and posterior lobes
Connected to the hypothalamus by a stalk
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HYPOTHALAMUS AND POSTERIOR PITUITARY
HYPOTHALAMUS
NEUROSECRETORY
NEURONS
ANTERIOR
PITUITARY
POSTERIOR
PITUITARY VASOPRESSIN
OXYTOCIN
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HYPOTHALAMUS AND ANTERIOR PITUITARY
HYPOTHALAMUS
NEUROSECRETORY
NEURONS
• TSH
•ACTH
•PROLACTIN
•GROWTH
HORMONE
•LH
•FSH
POSTERIOR
PITUITARY
ANTERIOR
PITUITARY
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EMBRYOLOGY
• Anterior lobe (adenohypophysis) – Embryologically from Rathke pouch
– Histologic cell types = Eosinophilic cytoplasm (acidophil), basophilic cytoplasm (Basophil), or poorly staining cytoplasm (chromophobe) cells
• Posterior lobe (neurohypophysis) – Embryologically derived from an outpouching of the floor of the
third ventricle
– has nerve cell bodies in hypothalamic nuclei
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PITUITARY GLAND
ANTERIOR PITUITARY POSTERIOR PITUITARY
Acidophilic, basophilic cells
and chromophobes Nerve endings
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PITUITARY GLAND
Green = stimulatory
Red = inhibitory
AcidophilProlactin (PRL)Dopamine
BasophilThyroid Stimulating
Hormone (TSH)
Thyrotropin Releasing
Hormone (TRH)
BasophilAdrenocorticotropic
Hormone (ACTH)
Corticotropin Releasing
Hormone (CRH)
AcidophilGrowth Hormone (GH)Growth Hormone
Releasing Hormone
(GRH)
BasophilLuteinizing Hormone
(LH)
Follicular Stimulating
Hormone (FSH)
Gonadotropin Releasing
Hormone (GnRH)
Cell typeCorresponding Anterior
Pituitary Hormone(s)
Hypothalamic Releasing
HormoneHypothalamic
hormone Pituitary hormone Cell type
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Pituitary hormones
– hormonal production is controlled predominantly by hypothalamus
– primary hypothalamic control of Prolactin secretion is inhibitory,
– while others have stimulatory effect
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Negative feedback loops : control the secretion of pituitary hormones
Hypothalamus TRH
Pituitary TSH
Thyroid T3, T4
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Disorders of Pituitary
Hyperpituitarism
Hypopituitarism
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• Definition: too much anterior pituitary hormone(s)
• Most common cause: Pituitary adenoma
Other causes :
Pituitary hyperplasia, carcinoma, hypothalamic disorders
Hyperpituitarism
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Pituitary adenoma
• Etiology is unknown
• 10-15% of all primary brain tumors
• 20-25% of pituitary glands at autopsy found to have adenomas
• 70% of adenomas secrete hormones
• 3% of those with MEN-I develop pituitary adenomas
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Epidemiology
• Vary in size
• Microadenomas < 10 mm
• Macroadenomas > 10 mm – cause problems due to mass effect
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Pituitary adenoma : Symptoms
– Functioning/ Non-functioning
– Mass effects:
– Earliest changes - radiographic abnormalities of the sella turcica
– visual field abnormalities- bitemporal hemianopsia
– Elevated intracranial pressure - headache, nausea, and vomiting
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* FUNCTIONING : 70%
- Prolactin cell adenoma (Lactotroph adenoma / Prolactinoma ) : most common functioning pituitary adenomas : 30%
- GH ( Somatotroph ) adenoma : second most common
- ACTH producing (Corticotroph adenoma)
- FSH / LH-producing ( Gonadotroph adenoma)
- TSH-producing (Thyrotroph adenoma)
- Mixed ( plurihormonal ) adenoma
* NON-FUNCTIONING : 30%
Pituitary adenoma
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Prolactinoma
In women
Secondary amenorrhoea : Prolactin inhibits
GnRH
Galactorrhoea
In Men Loss of libido
Labs: Prolactin levels > 200 ng/mL
Decreased FSH and LH
Treatment: Dopamine analogues/Surgery
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Growth hormone adenoma
Functions of growth hormone:
• Stimulates liver synthesis of insulin growth factor 1(IGF-1)
• Stimulates gluconeogenesis and amino acid uptake in muscle
• Functions of IGF 1:
• Stimulates growth of bone (linear and lateral) , cartilage and soft tissue
IGF 1
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Clinical features
In children : Gigantism : due to increase in
linear growth
In adults : Acromegaly Increase in lateral growth (as the
epiphyses have fused ) Prominent jaw, frontal bossing,
macroglossia Other findings
– diabetes mellitus – hypertension – Arthritis, generalised muscle
weakness – Congestive heart failure – gastrointestinal carcinoma
Labs: Increased GH and IGF1 : not suppressed by glucose TREATMENT: Surgery/Radiation
GIGANTISM ACROMEGALY
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ACTH adenoma
• Leads to hypercortisolism : Cushings syndrome
• Cushings syndrome caused by excess secretion of ACTH by pituitary is called CUSHINGS DISEASE
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GROSS MICROSCOPY
Well circumscribed lesion-
Small lesion : confined to the
sella tursica,
larger lesions extend beyond,
compress optic chiasma
Uniform cells in sheets, with
uniform nuclei,cytoplasm
acidophilic/basophilic/
chromophobic depending on the
cell type
PITUITARY ADENOMA
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Summary : Functioning pituitary Adenomas
• Prolactin – Amenorrhea, galactorrhea, impotence
• Growth hormone – Gigantism and acromegaly
• Corticotropin – Cushing’s disease
• TSH - Hyperthyroidism
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• Definition: too little anterior pituitary hormone(s) Many Causes:
• Empty sella syndrome: can occur from Surgery/Radiation
• Head trauma
– Pituitary destruction : due to a non – functioning pituitary adenoma / pituitary carcinoma / other tumor eg: Craniopharyngioma
– Ischemic necrosis (Sheehans syndrome)
– Hypothalamic lesions: tumors , both anterior and posterior hormone deficiency
Hypopituitarism
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Sheehans Syndrome
- Postpartum necrosis of the anterior pituitary
– Most common form of clinically significant ischemic necrosis of the anterior pituitary
– During pregnancy anterior pituitary enlarges to almost twice its normal size not accompanied by an increase in blood supply
– relative anoxia of the pituitary is worsened by further reduction by obstetric hemorrhage or shock & precipitate infarction
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Gonadotrophin deficiency
Growth hormone deficiency
TSH deficiency ACTH deficiency
- Children have
growth delay -
dwarfism
- Adults have
hypoglycemia
Arginine and sleep
stimulation test:
No increase in GH ,
normally GH is
released at 5 am
-Cold intolerance,
constipation
TRH stimulation
test:
-No increase in
TSH
-Decreased
cortisol
-Hypoglycemia
Metapyrone
stimulation test:
-No increase in
ACTH
ANTERIOR PITUITARY HYPOFUNCTION
In children:
Delayed puberty
Adult femalies:
Sec amenorrhoea
In Males :
impotence
Gn RH
stimulation test :
No increase in
FSH and LH
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Sponge Bob, why is panhypopituitarism
so rare?
Why, Clucky, it’s because the pituitary has such a
big reserve!
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Posterior pituitary syndromes
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POSTERIOR PITUITARY SYNDROMES
ADH Deficiency (Diabetes Insipidus)
Inappropriate ADH Secretion (SIADH)
Due to ADH Decreased reabsorption of free water
ADH Increased reabsorption of free water
Results in
Cannot concentrate urine
Cannot dilute urine
Clinical manifestations
Polyuria and polydypsia Oliguria
Urine specific gravity
Low High
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POSTERIOR PITUITARY SYNDROMES
Serum Na
levels
Hypernatremia
Hyponatremia (life-threatening) : brain swelling
Causes
Hypothalamic disease Transection of pituitary stalk ( as in trauma) Posterior pituitary lesions ( eg metastases)
MCC is ectopic ADH secretion by a small cell carcinoma of lung TB and pneumonia can cause ectopic ADH secretion
Treatment ADH administration Fluid restriction
ADH Deficiency
(Diabetes Insipidus)
Inappropriate ADH
Secretion (SIADH)
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HYPOTHALAMIC SUPRASELLAR TUMORS
• CRANIOPHARYNGIOMA:
• Benign tumor derived from Rathkes pouch
• Extends into sella tursica and destroys the pituitary gland
• Common cause of hypopituitarism in children
• Can involve posterior pituitary also
• Pressure symptoms may be seen
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Craniopharyngioma
Microscopy Gross
• Cystic structures lined by palisaded epitheium resembling tooth enamel
• Loose stellate reticulum
• Solid/cystic tumor with calcification
lumen contains machine oil like contents