DR. ROOPAM JAIN, Professor & Head, Department of Pathology & Blood Bank

1. PITUITARY GLAND
PATHOLOGY
DR. ROOPAM JAIN
PROFESSOR & HEAD
DEPT. OF PATHOLOGY & BLOOS BANK

2. NEUROENDOCRINE SYSTEM
• This system forms a link between endocrine
glands and nervous system.
• The cells of this system elaborate polypeptide
hormones; owing to these biochemical
properties, it has also been called as APUD cell
system (acronym for Amine Precursor Uptake
and Decarboxylation properties).

3. Cells comprising this system are as under:
1. Neuroendocrine cells which are present in the gastric
and intestinal mucosa and elaborate peptide
hormones.
2. Neuroganglia cells lie in the ganglia cells in the
sympathetic chain and elaborate amines.
3. Adrenal medulla elaborates epinephrine an
norepinephrine.
4. Parafollicular C cells of the thyroid secrete calcitonin.
5. Islets of Langerhans in the pancreas (included in both
endocrine and neuroendocrine systems) secrete
insulin.
6. Isolated cells in the left atrium of the heart secrete
atrial natriuretic (salt-losing) peptide hormone.

4. THE ENDOCRINE SYSTEM
• Anatomically, the endocrine system consists of
6 distinct organs: pituitary, adrenals, thyroid,
parathyroids, gonads, and pancreatic islets
(neuroendocrine system).

5. • Human hormones are divided into 5 major classes
which are further grouped under two headings
depending upon their site of interactions on the target
cell receptors (whether cell membrane or nuclear
receptor):
Group I: Those interacting with cell-surface membrane
receptors:
1. Amino acid derivatives: thyroid hormone,
catecholamines.
2. Small neuropeptides: gonadotropin-releasing hormone
(GnRH), thyrotropin-releasing hormone (TRH),
somatostatin, vasopressin.

6. Group II: Those interacting with intracellular nuclear
receptors:
3. Large proteins: insulin, luteinising hormone (LH),
parathormone hormone.
4. Steroid hormones: cortisol, estrogen.
5. Vitamin derivatives: retinol (vitamin A) and vitamin D.
• The synthesis of these hormones and their precursors
takes place through a prescribed genetic pathway that
involves: transcription → mRNA → protein synthesis →
post- translational protein processing → intracellular
sorting/ membrane integration → secretion.

7. • Endocrine organs and the presence of feedback controls.
• Both positive and negative feedback controls exist for
each endocrine gland having a regulating (R) and
stimulating (S) hormone.
• Those acting through hypothalamic-pituitary axis include:
thyroid hormones on TRH-TSH axis, cortisol on CRH-ACTH
axis, gonadal steroids on GnRH-LH/FSH axis and insulin-like
GH on GHRH-GH axis.
• Those independent of pituitary control (shown by
interrupted arrows) have also feedback controls by calcium
on PTH, and hypoglycaemia on insulin release by pancreatic
islets.

9. PITUITARY
GLAND

10. PITUITARY GLAND
• The pituitary gland is composed of two
morphologically and functionally distinct
components: the anterior lobe
(adenohypophysis) and the posterior lobe
(neurohypophysis).

11. HISTOLOGY AND FUNCTIONS
A. ANTERIOR LOBE (ADENOHYPOPHYSIS)
• It is composed of round to polygonal epithelial cells
arranged in cords and islands having fibrovascular stroma.
• These epithelial cells, depending upon their staining
characteristics and functions, are divided into 3 types, each
of which performs separate functions:
1. Chromophil cells with acidophilic granules ---comprise
about 40% of the anterior lobe and are chiefly located in
the lateral wings. The acidophils are further of 2 types:
i) Somatotrophs (GH cells) which produce growth hormone
(GH).
ii) Lactotrophs (PRL cells) which produce prolactin (PRL). Cells
containing both GH and PRL called mammosomatotrophs
are also present.

12. 2. Chromophil cells with basophilic granules----constitute about 10%
of the anterior lobe and are mainly found in the region of median
wedge.
The chromatophils include 3 types of cells:
i) Gonadotrophs (FSH-LH cells) which are the source of the FSH and LH
or interstitial cell stimulating hormone (ICSH).
ii) Thyrotrophs (TSH cells) are the cells producing TSH.
iii) Corticotrophs (ACTH-MSH cells) produce ACTH, melanocyte
stimulating hormone (MSH), β-lipoprotein and β-endorphin.
3. Chromophobe cells without visible granules----comprise the
remainder 50% of the adenohypophysis.
These cells by light microscopy contain no visible granules, but on
electron microscopy reveal sparsely granulated corticotrophs,
thyrotrophs and gonadotrophs.

13. B. POSTERIOR LOBE (NEUROHYPOPHYSIS)
• The neurohypophysis is composed mainly of interlacing
nerve fibres in which are scattered specialised glial cells
called pituicytes. These nerve fibres on electron
microscopy contain granules of neurosecretory
material made up of 2 octapeptides— vasopressin or
antidiuretic hormone (ADH), and oxytocin, both of
which are produced by neurosecretory cells of the
hypothalamus but are stored in the cells of posterior
pituitary.
1. ADH
2. Oxytocin

14. There are six terminally differentiated cell
types in the anterior pituitary, including:
• Somatotrophs, producing growth hormone (GH)
• Mammosomatotrophs, producing GH and prolactin (PRL)
• Lactotrophs, producing PRL
• Corticotrophs, producing adrenocorticotropic hormone (ACTH) and
pro-opiomelanocortin (POMC), melanocytestimulating hormone
(MSH)
• Thyrotrophs, producing thyroid-stimulating hormone (TSH)
• Gonadotrophs, producing follicle-stimulating hormone (FSH) and
luteinizing hormone (LH).

15. HYPERPITUITARISM
• Hyperpituitarism is characterised by oversecretion of one or more of
the pituitary hormones.
• Such hypersecretion may be due to diseases of the anterior
pituitary, posterior pituitary or hypothalamus.

16. HYPERPITUITARISM
A. HYPERFUNCTION OF ANTERIOR PITUITARY
• Three common syndromes of adenohypophyseal hyperfunction are:
gigantism and acromegaly, hyperprolactinaemia and Cushing’s
syndrome.

17. GIGANTISM AND ACROMEGALY
• Result from sustained excess of growth hormone (GH), most
commonly by somatotroph (GH-secreting) adenoma.

18. Gigantism
• When GH excess occurs prior to epiphyseal closure, gigantism is
produced.
• Occurs in prepubertal boys and girls and is much less frequent than
acromegaly.
• The main clinical feature in gigantism is the excessive and proportionate
growth of the child.
• There is enlargement as well as thickening of the bones resulting in
considerable increase in height and enlarged thoracic cage.

19. Acromegaly
• Overproduction of GH in adults following cessation of bone growth.
• The term ‘acromegaly’ means increased growth of extremities
(acro=extremity). There is enlargement of hands and feet, coarseness of
facial features with increase in soft tissues, prominent supraorbital
ridges and a more prominent lower jaw which when clenched results in
protrusion of the lower teeth in front of upper teeth (prognathism).
• Other features include enlargement of the tongue and lips, thickening of
the skin and kyphosis.
• Sometimes, a few associated features such as TSH excess resulting in
thyrotoxicosis, and gonadotropin insufficiency causing amenorrhoea in
the females and impotence in the male, are found.

20. PROLACTINAEMIA
• Prolactinaemia is lactotroph (PRLsecreting) pituitary adenoma,
also called prolactinoma having excessive production of prolactin.
• Occasionally, hyperprolactinaemia results from hypothalamic inhibition of
PRL secretion by certain drugs (e.g. chlorpromazine, reserpine and
methyl-dopa).
• In the female, hyperprolactinaemia causes amenorrhoea-galactorrhoea
syndrome characterised clinically by infertility and expression of a drop
or two of milk from breast.
• In the male, it may cause impotence or reduced libido.
• These features result either from associated inhibition of gonadotropin
secretion or interference in gonadotropin effects.

21. CUSHING’S SYNDROME Pituitary-
dependent Cushing’s
• syndrome results from ACTH excess.
• Most frequently, it is caused by corticotroph (ACTH-secreting) adenoma.

23. B. HYPERFUNCTION OF POSTERIOR
PITUITARY AND HYPOTHALAMUS
• Lesions of posterior pituitary and hypothalamus are uncommon.
• Two of the syndromes associated with hyper - function of the
posterior pituitary and hypothalamus are:
• inappropriate release of ADH
• and precocious puberty

24. INAPPROPRIATE RELEASE OF ADH
• manifests clinically by passage of concentrated urine due to
increased reabsorption of water and loss of sodium in the urine,
consequent hyponatraemia, haemodilution and expansion of
intra- and extracellular fluid volume.
• Inappropriate release of ADH occurs most often in paraneoplastic
syndrome e.g. in oat cell carcinoma of the lung, carcinoma of the
pancreas, lymphoma and thymoma.
• lesions of the hypothalamus such as trauma, haemorrhage & meningitis
may produce ADH hypersecretion.
• Rarely, pulmonary diseases such as tuberculosis, lung abscess,
pneumoconiosis, empyema and pneumonia may cause overproduction of
ADH.

25. PRECOCIOUS PUBERTY
• A tumour in the region of hypothalamus or the pineal gland may result
in premature release of gonadotropins causing the onset of pubertal
changes prior to the age of 9 years.
• The features include
• premature development of genitalia both in the male and in the female,
• growth of pubic hair and axillary hair.
• In the female, there is breast growth and onset of menstruation

26. HYPOPITUITARISM

27. HYPOPITUITARISM
• usually deficiency of one or more of the pituitary hormones affecting
either anterior pituitary, or posterior pituitary and hypothalamus.

28. A. HYPOFUNCTION OF ANTERIOR
PITUITARY
• Adenohypophyseal hypofunction is invariably due to destruction of the
anterior lobe of more than 75% because the anterior pituitary possesses
a large functional reserve.
• This may result from anterior pituitary lesions or pressure and
destruction from adjacent lesions.
• Lesions of the anterior pituitary include nonsecretory (chromophobe)
adenoma, metastatic carcinoma, craniopharyngioma, trauma,
postpartum ischaemic necrosis (Sheehan’s syndrome), emptysella
syndrome, and rarely, tuberculosis.
• deficiency of anterior pituitary hormones - two important syndromes are
panhypopituitarism & dwarfism

29. PANHYPOPITUITARISM
• major anterior pituitary insufficiency is called panhypopituitarism.
• 3 most common causes of panhypopituitarism are:
• non-secretory (chromophobe) adenoma (discussed later),
• Sheehan’s syndrome and Simmond’s disease,
• and empty-sella syndrome

30. Sheehan’s syndrome and Simmond’s
disease
• Pituitary insufficiency occurring due to postpartum pituitary (Sheehan’s)
necrosis is called Sheehan’s syndrome
• The main pathogenetic mechanism underlying Sheehan’s necrosis is the
enlargement of the pituitary occurring during pregnancy which may be
followed by hypotensive shock precipitating ischaemic necrosis of the
pituitary.

31. Sheehan’s syndrome and Simmond’s
disease
• Other mechanisms hypothesised are: DIC following delivery, traumatic
injury to vessels, and excessive haemorrhage.
• Patients with long-standing diabetes mellitus appear to be at greater
risk of developing this complication.
• The first clinical manifestation of Sheehan’s syndrome is failure of
lactation following delivery which is due to deficiency of prolactin.
• Subsequently, loss of axillary and pubic hair, amenorrhoea, sterility and
loss of libido.
• Concomitant deficiency of TSH and ACTH may result in hypothyroidism
and adrenocortical insufficiency.