pituitary gland diseases (1)

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ENDOCRINE SYSTEM
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PITUITARY GLAND

• Anatomy base of brain in sella turcica
• Wt 500 mg

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• Division
• Anterior lobe ( adenohypophysis)
• Polygonal cells- according to staining features
• 1. Chromophil cells with acidophilic granules
• i. Somatotrophs ( GH cells)- producing GH
• ii. Lactotrophs (PRL cells)- producing
  prolactin

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• 2. Chromophil cells with basophilic granules
  comprising of
• i. Gonadotrophs ( FSH-LH cells)
• ii. Thyrotrophs (TSH cells)
• iii. Corticotrophs ( ACTH-MSH cells) producing
• ACTH, melanocyte stimulating hormone, beta-
  lipoprotein and beta-endorphin

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• 3. Chromophobe cells without visible granules
• Under light microscope contain no granules
• On EM sparsely granulated corticotrophs,
  thyrotrophs and gonadotrophs seen

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• ALL THE FUNCTIONS OF THE ADENOHYPOPHYSIS ARE
  UNDER THE INDIRECT CONTROL OF THE HYPOTHALAMUS
• (Through stimulatory and inhibitory factors
  synthesized by hypothalamus reaching anterior
  lobe through capillary portal blood)

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• Posterior lobe (neurohypophysis)
• Composed of nerve fibres
• Granules contain of neurosecretory material made
  of vasopressin ( antidiuretic hormone) and
  oxytocin
• Granules produced by cells of the hypothalamus
  but stored in posterior lobe

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• Functions
• ADH-
• Reabsorption of water from renal tubules (
  maintenace of of osmolality of plasma)
• Deficiency results into diabetes inspidus
• 2. Oxytocin
• contraction of mammary myoepithelial cells with
  ejection of milk and uterine contraction at term

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• The pituitary gland and hypothalamus so closely
  interlinked that diseases of pituitary gland
  involve hypothalamus and vice versa.

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• Hyperpituitarism
• Oversecretion of one or more of pituitary
  hormones
• Causes
• Diseases of anterior pituitary
• Posterior pituitary OR
• hypothalamus

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Hyperfunction of anterior pituitary

1. Gigantism and acromegaly
2. Hyperprolactinaemia
3. Cushing syndrome

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• Gigantism and Acromegaly
• Sustained overproduction of GH
• Gigantism
• GH occurs before fusion of epiphyses in
  prepuberty
• Features excessive and proportionate growth of
  the child

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• Acromegaly (enlargement of extremities)
• Overproduction of GH in adults
• Enlargement of hands and feet
• Courseness of facial features with increase in
  soft tissues
• Prominent supra-orbital ridges and lower jaw
• Protrusion of lower teeth in front of upper teeth
  on clenching

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• Other features
• Enlargement of tongue and lips
• Thickening of skin and kyphosis
• TSH secretion in some leads to thyrotoxicosis

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• 2. Hyperprolactinaemia
• Excessive production of prolactin by a lactotroph
  adenoma
• Rarely from hypothalamic inhibition of PRL
  secretion by drugs such as
• chlorpromazine
• reserpine
• methyldopa

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• In female causes amenorrhoea-galactorrhoea
  syndrome
• Infertility and expression of a drop of milk
  from breast
• not related to pregnancy or puerperium
• In male causes impotence or reduced libido

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• Cushings syndrome
• Pituitary dependant syndrome from ACTH
  over-secretion
• Commonly by ACTH secreting adenoma

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• Symptoms
• Cushings disease (and Cushing's syndrome)
  produce a wide range of symptoms, including

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• Changes in physical characteristics of the body
• Fullness and rounding of the face (so-called
  "moon facies")
• Added fat on back of neck (so-called "buffalo
  hump")
• Skin changes with easy bruising
• Purplish stretch marks on the abdomen ("abdominal
  striae")

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• Excessive weight gain
• Red cheeks
• Excess hair growth on the face, neck, chest,
  abdomen, and thighs
• Generalized weakness and fatigue wasting of
  muscles
• Menstrual disorders

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• Decreased fertility and/or sex drive
• High blood pressure
• Diabetes mellitus
• Mood and behavior disorders

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• Diagnosis
• Clinical Examination
• Hormonal diagnosis
• The first step in diagnosing Cushing's disease is
  to confirm the presence of excessive cortisol
  secretion
• ACTH blood levels are elevated in Cushing's
  disease
• An elevated ACTH levels alone is not diagnostic
  for Cushing's disease,
• since ACTH can be produced by cancerous tumors
  elsewhere in the body (ectopic ACTH production)

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• Dexamethasone is a powerful drug that acts
  similar to, but is more potent than cortisol
• In normal individuals, 1 mg of dexamethasone will
  suppress ACTH production (lowering the ACTH level
  in the blood)
• The pituitary tumor cells producing ACTH in
  Cushing's disease often also respond to the
  dexamethasone, leading to a temporary reduction
  in blood ACTH levels
• Ectopic ACTH production is not suppressed by
  dexamethasone

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Hyperfunction of posterior pituitary and
hypothalamus

• Lesions uncommon
• Inappropriate release of ADH and precocious
  puberty

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• Inappropriate ADH secretion
• Manifests as clinically by passage of
  concentrated urine due to increased reabsorption
  of water and loss of sodium in urine
• Outcome is hyponatraemia
• haemodilution
• and expansion of intra and
  extracellular fluid volume

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• Precocious puberty
• By a tumour in hypothalamus or pineal gland with
  premature release of gonadotropins
• Premature development of genitalia in male and in
  female
• growth of pubic and axillary hair
• Breast growth and onset of menstruation in female

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Hypopituitarism

• Deficiency of one or more of pituitary hormones
• Hypofunction of anterior pituitary
• Due to destruction of more than 75 of the
  gland
• By lesions or pressure and destruction from

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• Lesions include
• Non-secretory ( chromophobe) adenomas
• Metastatic carcinoma
• Craniopharyngioma
• Postpartum ischaemic necrosis ( Sheehans
  syndrome)
• Empty sella syndrome
• Rarely tuberculosis

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• Panhypopituitarism
• 3 most common causes
• 1. Sheehans syndrome and Simmonds disease
• Due to postpartum necrosis- Sheehans syndrome
• Similar process without pregnancy and in males -
  Simmonds disease

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• Clinical manifestations of Sheehans syndrome
• Failure of lactation following delivery due to
  deficiency of prolactin
• Loss of axillary and pubic hair
• amenorrhoea
• sterility
• loss of libido
• Concomitant deficiency of TSH and ACTH may result
  into hypothyroidism and adrenocortical
  insufficiency

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• 2. Empty sella syndrome
• Appearance of an empty sella and features of
  panhypopituitarism
• A result of herniation of subarachnoid space into
  sella tusica developmentally
• Other causes Sheehans syndrome
• infarction and
• scarring in adenoma
• irradiation damage or
• surgical removal

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• Pituitary dwarfism
• Severe deficiency of GH in children before growth
  is complete leading to growth retardation and
  dwarfism
• A result of inherited autosomal recessive
  disorder
• Less often, a pituitary adenoma,
• craniopahryngioma,
• infarction or
• trauma to pituitary

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• Inherited form manifests as
• Appearance at one year of age
• Proportionate retardation in growth of bones
• Normal mental status
• Poorly developed genitalia
• Delayed puberty
• Episodes of hypoglycaemia

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Hypofunction of posterior pituitary

• Uncommon
• Most significant is diabetes inspidus as outlined
  earlier

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Pituitary tumours

• Of anterior pituitary more common than posterior
  pituitary
• Adenomas commonest
• Primary and metastatic tumours rare
• Craniopharyngioma and granular cell tumour other
  rare benign tumours

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• All whether benign or malignant cause symptoms
  in two ways
• 1. Pressure effects
• Expansion of lesion, destroying gland by pressure
• Causes erosion and enlargement of sella turcica
• Upward extension of the tumour damaging optic
  chiasma, optic nerve and neurohypophysis

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• 2. Hormonal effects
• Excess of hormone production will lead to
  hyperpituitarism
• Infarction and destruction

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• Pituitary adenomas
• Most common tumours
• Classified according to their HE staining
  characteristics of granules- considered
  inadequate
• Ultra-structural and immunohistochemical
  characteristic has provided a functional
  classification

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Moprhologic and Functional classification of
pituitary tumours

1. Lactotroph adenoma - prolactin-
   amenorrhoea-galactorrhoea
2. Somatotroph adenoma - GH- acromegaly, gigantism
3. Mixed somatotroph -lactotroph PRL GH
4. Corticotroph adenoma
5. Gonadotroph adenoma
6. Thyrotroph adenoma

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Non functional adenoma
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• Craniopharyngioma
• Benign tumour arising from remnants of Rathkes
  pouch
• More common in children and young adults
• It arises from nests of odontogenic
  (tooth-forming) epithelium within the
  suprasellar/diencephalic region

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• Histologically, craniopharyngiomas resemble
  adamntinomas (the most common tumors of the
  tooth).
• Patients may present with bitemporal inferior
  quadrantanopia leading to bitemporal hemianopia
  , as the tumor may compress the optic chiasma

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• Histology shows nests of squamous epithelium
  bordered by radially arranged cells.
• It is frequently accompanied by calcium
  deposition and may have a microscopic papillary
  architecture.

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• Prognosis
• Craniopharyngiomas are generally benign but are
  known to recur after resection.

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