This document provides an overview of hyperpituitarism, which is defined as excessive secretion of one or more pituitary hormones. The most common cause is a hormone-producing pituitary adenoma arising in the anterior lobe. Pituitary adenomas can be functional (hormone-producing) or nonfunctional and may cause hyperfunction of growth hormone (gigantism and acromegaly), prolactin, or ACTH (Cushing's syndrome). Other conditions like craniopharyngioma or metastatic carcinoma can also cause a mass effect by compressing surrounding structures. The document discusses various pituitary adenoma subtypes and hypersecretory syndromes in detail.

1. FRONT E
I R
Lecture 1:
Hyperpituitarism:

2. Overview:
• The major disorders of an endocrine gland are:
1. Hyperfunction.
2. Hypofunction.
3. Benign and malignant tumours, which
themselves may cause disordered function.
• There are several important general considerations
in endocrine pathology:
1st disease of one endocrine gland cannot usually be
considered in isolation, because it almost always has
implications for other endocrine glands.

3. 2nd one hormone may have many diverse clinical
effects, so that malfunction of one endocrine gland
may produce numerous clinical features.
3rd the same hormone may be produced in more
than one site; thus, ectopic hormone production by
tumours of non-endocrine tissues may simulate
primary endocrine disease.

4. Hyperpituitarism:
• Is defined as excessive secretion of one or more of
the pituitary hormones.
• Causes of hyperpituitarism include:
• Adenomas ‘functioning (hormone-secreting)’.
• Hyperplasia.
• Carcinoma.
• Hypersecretion may be due to diseases of the
anterior pituitary, posterior pituitary or
hypothalamus.
Extremely rare

5. Pituitary Adenomas:
• The most common cause of hyperpituitarism is a
hormone producing adenoma arising in the anterior
lobe.
• Pituitary adenomas are uncommon, constituting about
10% of primary intracranial neoplasms.
• They occur at all ages but are most common in the age
group of 20 to 50 years. They occur in men slightly
more frequently than in women.
• About 30% are nonfunctional (null cell adenoma),
causing destruction of the normal gland.
• About 30% secrete prolactin.
• About 25% secrete growth hormone.

6. • About 10% secrete ACTH.
• About 5% secrete thyrotropin or gonadotropins.
• Pituitary adenomas secrete more than one
hormone.
• Some salient features of pituitary adenomas are as
follows:
1= Pituitary adenomas are classified on the basis of
hormone(s) produced by the neoplastic cells.

7. 2= Pituitary adenomas can be functional (hormone
producing) or nonfunctioning (not producing
hormone), or silent (i.e., demonstration of hormone
production at the tissue level only, without clinical
manifestations of hormone excess).
3= Pituitary adenomas are designated as
microadenomas if they are less than 1 cm in
diameter and macroadenomas if they exceed 1 cm in
diameter.
4= Nonfunctioning adenomas are likely to come to
clinical attention at a later stage and are, therefore,
more likely to be macroadenomas.

8. • Pathogenesis:
1. G-protein mutations are one of the most common
genomic alterations in pituitary adenomas.
2. An inherited predisposition (MEN1, CDKN1B,
PRKAR1A, and AIP).
3. Molecular abnormalities associated with aggressive
behavior include aberrations in cell cycle checkpoint
genes (cyclin D1, mutations of TP53, and epigenetic
silencing of the retinoblastoma gene (RB)).
4. Rare, activating mutations of the RAS oncogene are
observed in rare pituitary carcinomas.

9. Normal pituitary gland:
District cell types.
Presence of reticular b/w cells.
Abnormal pituitary gland:
One cell types.
Absence of reticular b/w cells.

11. • Clinical feature:
1. Dull headache.
2. Visual field defects, typically superior quadrant
bitemporal hemianopia.
3. Large neoplasms compress the more peripheral part
of the chiasm, the optic nerves (causing blindness)
the hypothalamus, and sometimes the third
ventricle, resulting in hydrocephalus.
4. Infiltrative neoplasms may open into the paranasal
sinuses (with a high risk of meningitis) or the
cavernous sinus (producing thrombosis with orbital
edema and congestion).
• Diagnosis:
• By radiological examination.

15. • Three common syndromes of adenohypophyseal
hyperfunction are:
• Gigantism and acromegaly.
• Hyperprolactinaemia
• Cushing’s syndrome.

16. Gigantism:
• When GH excess occurs prior to epiphyseal closure,
gigantism is produced.
• Gigantism, occurs in prepubertal boys and girls and is much
less frequent than acromegaly.
• Causes:
• Adenomas.
• Clinical feature:
1. Increase in size and disproportionate long arms and legs.
2. Enlarged thoracic cage.
3. Thickening of the bones.
4. Some times hypertension.

17. • On microscopic examination
• Growth hormone– producing adenomas are composed
of densely or sparsely granulated cells, and
immunohistochemical staining demonstrates growth
hormone within the cytoplasm of the
neoplastic cells. Small amounts of immunoreactive
prolactin often are present as well.
• Diagnosis:
• Failure to suppress GH level with an oral load of
glucose.
• IGF-1 levels are elevated.

19. Acromegaly:
• There is overproduction of GH in adults following cessation
of bone growth and is more common than gigantism.
• The term ‘acromegaly’ (acro=extremity) (mega =
enlargement).
• Causes:
• Adenomas.
• Clinical feature:
• Enlargement of hands and feet,
• Coarseness of facial features with increase in soft tissues.
• Prominent supraorbital ridges.
• More prominent lower (prognathism).
• Separation of teeth.

22. • Enlargement of the tongue and lips, thickening of the skin and
kyphosis.
• Enlarged visceral organ.
• Sometimes, a few associated features such as TSH excess
resulting in thyrotoxicosis.
• Gonadotropin insufficiency causing amenorrhoea in the
females and impotence in the male.
• Other feature associated with both gigantism and
acromegaly are
Generalized muscle weakness.
Hypertension.
Arthritis.
Congestive heart failure.
Increased risk for gastrointestinal cancers.
• Diagnosis:
• Same in gigantism.

25. • Treatment:
1. Octreotide (somatostatin analog that suppresses
GH release),
2. GH receptor antagonists (Pegvisomant).
3. Surgery.

26. Hyperprolectinemia:
• Is the excessive production of prolactin (PRL), most
commonly by lactotroph (PRL-secreting) adenoma, also
called prolactinoma.
• (30% of all pituitary tumours).
• Cuases:
• Adenoma.
• Drugs that suppress hypothalamic inhibition of PRL
secretion (e.g. chlorpromazine, reserpine and methyl-dopa).
• Clinical feature:
• In the female,
• amenorrhoea-galactorrhoea - infertility syndrome, not
related to pregnancy or puerperium.

28. • In the male, it may cause impotence or reduced
libido.
• Diagnosis:
• Raised serum prolactin levels >200 ng/mL.
• Mild prolactin increases are seen with compression of
the hypothalamus by any pituitary adenoma (the ‘stalk
effect’).
• Brain MRI.
• Point of interest:
• Differential diagnosis of hyperprolactinemia include:
oDrugs.
oPrimary hypothyroidism.
oPregnancy.

29. Stalk effect:
• Secretion of all of the anterior pituitary hormones,
except prolactin, is stimulated by delivery of releasing
hormones, including TRH, gonadotropin-releasing
hormone (GnRH), and corticotropin-releasing hormone
(CRH), from the hypothalamus via the hypophyseal
portal system. Secretion of prolactin, however, is
tonically inhibited by the delivery of dopamine via the
same portal system. A mass pressing on the stalk will
prevent dopamine from reaching the pituitary gland,
thus causing increased levels of prolactin without
actually producing prolactin. In general, however, the
level of prolactin in the “stalk effect” does not equal
that produced by a prolactin secreting adenoma. This
stalk effect will, simultaneously, cause inhibition of
secretion of the other anterior pituitary hormones.

30. • Treatment:
1. Bromocriptine (dopamine agonist).
2. Cabergoline.

31. Cushing’s syndrome:
• Pituitary-dependent Cushing’s syndrome results
from ACTH excess. Most frequently, it is caused by
corticotroph (ACTH-secreting) adenoma.
• Cushing’s syndrome is discussed under diseases of
the adrenal gland.
Other functioning adenomas:
• Other endocrine secreting adenomas, e.g. of
thyroidstimulating hormone (TSH), luteinizing
hormone (LH) and follicle-stimulating hormone
(FSH), are extremely rare.

32. SEMESTER OF READING

34. SYNDROME OF INAPPROPRIATE
ANTIDIURETIC HORMONE (SIADH):
• Syndrome caused by hyperfunctioning of the posterior
pituitary gland resulting in increased levels of antidiuretic
hormone (ADH).
• Causes:
1. Ectopic ADH (commonly secreted by small cell lung
carcinoma).
2. Non-neoplastic diseases of the lung (e.g., tuberculosis,
pneumonia, pneumoconiosis, empyema).
3. Central nervous system disorders (e.g., meningitis,
abscess, head trauma).
4. Injury to the hypothalamus or posterior pituitary gland.
• Mechanism: Increased retention of water by increased ADH
leads to hyponatremia.

35. • Clinical feature:
• Expansion of intra- and extracellular fluid volume.
• Oedema is not usually seen as free water is evenly
distributed to all body compartments.
• Headache.
• Anorexia, vomiting.
• Confusion (when sodium level is 115–120 mEq/L).
• Stupor; coma and seizures (when sodium level is < 110
mEq/L).
• Delirium and dementia.
• Diagnosis:
• Hyponatremia, decreased serum osmolarity.
• inappropriately concentrated urine ( 100 mOsm/kg).
• low blood urea nitrogen (BUN).

36. • Treatment:
1. fluid restriction.
2. Oral NaCl.
3. Low dose of Loop diuretics.
4. 0.25–0.50 g/kg per day of urea.
5. Conivaptan (ADH receptor antagonist)

37. MASS EFFECT:
• Mass effect, in general, refers to the effects of a tumor
based upon its mass and the involvement of adjacent
structures.
• The pituitary gland is such a small organ surrounded by
numerous vital and important structures that mass
effects caused by lesions in the pituitary gland are of
vital importance in DIAGNOSIS.
• Mass effects are most common with null adenomas
and other space-occupying lesions of the pituitary
gland and surrounding region.

38. • Types of mass effect:
1. Visual field abnormalities: Pressure on the optic chiasm
due to a mass lesion produces bitemporal hemianopsia.
2. Elevated intracranial pressure, which causes headache
and nausea and vomiting.
3. Obstructive hydrocephalus: Due to blockage of
ventricular system.
4. Cranial nerve palsies: Due to impingement upon adjacent
cranial nerves.
5. Diabetes insipidus: Due to destruction of posterior
pituitary gland.
6. Hypothalamic disturbances: Disorders of thirst, appetite,
temperature regulation, behavior, and consciousness.
Causes of mass effect:
■ Pituitary adenomas: Most often null cell adenomas are the
type of adenoma that can grow to a size large enough to
cause mass effect.
■ Metastatic carcinoma.
■ Craniopharyngioma

39. Craniopharyngioma:
• Epidemiology: Two age ranges; one at 5–15 years
of age and another at the sixth decade or older.
Craniopharyngiomas are the most common cause
of hypothalamic disturbances in children.
• Two types: Adamantinomatous (commonly calcify)
and papillary (rarely calcify).
• Important points regarding craniopharyngioma
■ Derived from Rathke pouch.
■ Most are suprasellar.
■ Prognosis is dependent upon completeness of
surgical excision.