16. 1. Peptide hormones synthesized in the hypothalamus (in the supraoptic & paraventricular
nuclei) axonal transport and accumulate in axons in the pars nervosa.
17. High mag of the Posterior Pituitary – axons, capillaries, and pituicytes
18. High mag of the Posterior Pituitary – note Herring Bodies (arrow)
19. High mag of the Anterior Pituitary – note eosinophilic and basophilic cells
24. Clinical Manifestations of Pituitary Disease;
Hyperpituitarism;
• pituitary adenoma,
• hyperplasia
• carcinomas of anterior pituitary,
• secretion of hormones by nonpituitary tumors,
• hypothalamic disorders.
Hypopituitarism;
• Destructive processes, ischemic injury, surgery or radiation,
• inflammatory reactions,
• Nonfunctional pituitary adenomas.
Local mass effect
• radiographic abnormalities of the sella turcica,
• compress decussating Optic chiasma & nerves
• Elevated intracranial pressure
pituitary apoplexy
Diseases of the posterior pituitary
25. Hyperpituitarism:
• Pituitary adenoma, (most common cause of
hyperpituitarism).
• Other uncommon causes;
• hyperplasia
• carcinomas of the anterior pituitary,
• secretion of hormones by nonpituitary tumors,
• hypothalamic disorders.
26. Pituitary Adenomas
• The most common cause of hyperpituitarism
• Classified on the basis of
- Functioning or nonfunctioning.
- type of hormone(s) produced.
• Prolactin and GH are most commonly over-produced by
adenomas.
• Large pituitary adenomas, and particularly
nonfunctioning ones, may cause hypopituitarism as
they encroach on and destroy adjacent anterior
pituitary parenchyma.
• Endocrine effect & Mass effect.
27. Pituitary adenomas
• Adults, (35 to 60) years of age.
• microadenomas <1 cm
• macroadenomas >1 cm.
• Silent & hormone-negative adenomas, macroadenomas.
• autopsy studies; prevalence of pituitary adenomas to 14%,
although the vast majority of these lesions are incidentally
diagnosed microadenomas (“pituitary incidentaloma”).
28. • Prolactinomas (lactotroph adenomas)
• the most frequent type of hyperfunctioning
pituitary adenoma, (30% of all clinically
recognized cases).
• Dystrophic calcification, “pituitary stone”.
• S. prolactin conc. correlate with size of the
adenoma
Lactotroph Adenoma
29. Prolactinomas.
A; E/M of a sparsely granulated prolactinoma. The tumor cells contain abundant
granular ER (indicative of active protein synthesis) and small numbers of electron-dense
secretory granules.
B, E/M of densely granulated GH -secreting adenoma. The tumor cells are filled with
numerous large, electron-dense secretory granules.
31. • 2nd most common functioning
pituitary adenoma.
Gigantism is the result of GH
hypersecretion before the closure of
the epiphyseal plates (childhood).
• Generalized increase in body size with
disproportionately long arms and legs
Acromegaly is over secretion of GH in
adulthood
– Continued growth of boney, CT,
leads to disproportionate
enlargement of tissue..
Somatotroph Adenomas
37. Corticotroph Adenomas
• Excess production of ACTH by functioning
corticotroph adenomas
• leads to adrenal hypersecretion of cortisol
& hypercortisolism (Cushing syndrome).
39. Local mass effects
• Elevated intracranial pressure.
• X – Ray abnormalities of the sella turcica.
• Visual field abnormalities (bitemporal hemianopsia).
• pituitary apoplexy ; acute hemorrhage into an
adenoma, with rapid enlargement.
• Diseases of the post. pituitary often associated with
increased or decreased secretion of ADH.
Pituitary Adenomas
44. Pituitary adenoma. This massive, nonfunctional adenoma has grown far beyond the
sella turcica and distorted the overlying brain. Nonfunctional adenomas tend to be
larger at the time of diagnosis than those that secrete a hormone.
46. Genetic abnormalities with pituitary adenomas
• G-protein mutations;
• G proteins play a role in signal transduction,
transmitting signals from cell surface receptors
(GHRH receptor) to intracellular effectors (adenyl
cyclase), &then to 2nd messengers (cAMP).
• cAMP, acts as a potent mitogenic stimulus for a
variety of endocrine cell types (pituitary gland,
thyroid & parathyroid gland), promoting cellular
proliferation and hormone synthesis and secretion
47. Pituitary adenomas
• The majority of pituitary adenomas are
sporadic in nature,
• Only 5% of cases of an inherited
predisposition (MEN1)
49. • lactotroph hyperplasia, such as when there is interference with
normal dopamine inhibition of prolactin secretion. This may occur
as a result of damage to the dopaminergic neurons of the
hypothalamus, damage to the pituitary stalk (e.g., due to head
trauma), or drugs that block dopamine receptors on lactotroph
cells.
• Any mass in the suprasellar compartment may disturb the normal
inhibitory influence of the hypothalamus on prolactin secretion,
resulting in hyperprolactinemia.
• Therefore, a mild elevation in serum prolactin in a person with a
pituitary adenoma does not necessarily indicate a prolactin-
secreting tumor.
• Other causes of hyperprolactinemia include several classes of
drugs (such as dopamine antagonists), estrogens, renal failure,
and hypothyroidism.
• Prolactinomas are treated by surgery or, more commonly, with
bromocriptine, a dopamine receptor agonist that causes the
lesions to diminish in size.
50. Prolactinemia;
• Galactorrhea,
• amenorrhea,
• Infertility
• loss of libido
• Diagnosis of an adenoma is made more readily in women
than in men, especially between the ages of 20 & 40,
because of the sensitivity of menses to disruption by
hyperprolactinemia.
• Prolactinoma underlies almost a 1/4 of cases of
amenorrhea.
• In contrast, in men and older women, the hormonal
manifestations may be subtle, allowing the tumors to
reach considerable size (macroadenomas) before being
detected clinically.
51. GROWTH HORMONE CELL (SOMATOTROPH)
ADENOMAS
• the 2nd most common type of functioning pituitary
adenoma.
Bihormonal mammosomatotroph adenomas that
express both GH and prolactin are being increasingly
recognized with the availability of better IHC
reagents.
52. • GH stimulate the hepatic secretion of insulin-like growth factor 1 ,
which causes many clinical manifestations.
• Gigantism
• Acromegaly;
- growth in skin, soft tissues, viscera (thyroid, heart, liver, and
adrenals); & bones of the face, hands, and feet.
- Bone density may be increased (hyperostosis) in both the spine
and the hips.
- Enlargement of the jaw results in protrusion (prognathism), with
broadening of the lower face.
- These changes develop for decades before being recognized,
hence the opportunity for the adenomas to reach substantial size.
• GH excess is also correlated with a variety of other disturbances,
including gonadal dysfunction, DM, M. weakness, hypertension,
arthritis, CHF, and an increased risk of GIT cancers.
53. Diagnosis
• History & physical exam
• Elevated serum GH & insulin-like growth
factor 1 “IGF-1”.
Failure to suppress GH in response to an
oral load of glucose (sensitive test for
acromegaly).
– Prolactin levels as well as other pituitary
function tests
– MRI or CT & visual field tests to determine size
and position of the adenoma.
– Bone scan
54. Hypopituitarism
• Hypothalamus or pituitary diseases..
• Tumors (pituitary or non pituitary).
• Trauma & subarachnoid hemorrhage
• Pituitary surgery or radiation
• Ischemia, Sheehan syndrome, postpartum necrosis
• Pituitary apoplexy (stroke).
• Cysts (Rathke’s cleft)
• Genetic defects (pit-1 gene mutations)
Most cases of hypofunction arise from lesions of
the anterior pituitary.
55. • GH deficiency;
• Children dwarfism.
• Adult many clinical picture.
• Gonadotropin (LH and FSH) deficiency;
• amenorrhea and infertility in women and decreased libido,
• impotence, and loss of pubic and axillary hair in men.
• TSH and ACTH deficiencies result in symptoms of
hypothyroidism and hypoadrenalism, respectively
56. Dwarfism
• Child height 14cm less
than average.
• Adult height of less
than 4 feet 10 inches
(58 in; 147 cm)
57. Dwarfism
NOTE:
• Achondroplasia; AD, short extremities,
accounts for 70% of dwarfism cases, mutation in
FGFR, inhibiting bone growth.
• Spinal TB;
• Cretinism.
• Down syndrome
• GH deficiency.
58. Hypopituitarism (Adult)- GH
• Lack of GH leads to:
– Increased CV
disease
– Excessive tiredness
– Anxiety
– Depression
– Reduced “quality of
life”
– Possible premature
death
60. Posterior Pituitary Syndromes
Diabetes Insipidus (DI)
• ADH deficiency
• head trauma, tumors, surg, & inflamm. of hypothal. & pituit.
• Central DI
• Nephrogenic DI, renal tubular unresponsiveness to circulating
ADH.
• The clinical manifestations of the two diseases are similar;
• Polyuria, Thirst, Polydipsia.
• large Vo. of dilute urine with low sp. gravity.
• Increased S. Na+ & osmolality
• Patients who can drink water can generally compensate for urinary losses;
otherwise may develop life-threatening dehydration.
61. Syndrome of inappropriate ADH (SIADH) secretion.
• ADH excess causes resorption of excessive amounts of free
water, resulting in hyponatremia.
• Causes of SIADH;
• Ectopic ADH (SCC lung),
• drugs,
• CNS disorders, (infections and trauma).
• S & S ; hyponatremia, cerebral edema, and neurologic
dysfunction.
• Although total body water is increased, blood volume remains
normal, and peripheral edema does not develop.
62. Hypothalamic Suprasellar Tumors
• The most common are gliomas & craniopharyngiomas.
Craniopharyngioma;
• derived from remnants of Rathke pouch.
• Slow-growing , 1% to 5% of intracranial tumors
• Bimodal age distribution, (5 to 15 years) & 65 years or
older.
• S & S:
• Headaches
• visual disturbances,
• children might present with pituitary hypofunction and GH deficiency.
64. Summary
• Hyperpituitarism
■ The most common cause of hyperpituitarism is anterior lobe pituitary
adenoma.
■ Pituitary adenomas can be macroadenomas (>1 cm) or microadenomas.
■ Functioning adenomas are associated with distinct endocrine signs and
symptoms,
• while nonfunctioning (silent) adenomas typically present with mass
effects, including visual disturbances.
■ Lactotroph adenomas secrete prolactin and can present with
amenorrhea, galactorrhea, loss of libido, and infertility
■ Somatotroph adenomas secrete GH and present with gigantism in
children and acromegaly in adults, impaired glucose tolerance, and
diabetes mellitus.
■ Corticotroph adenomas secrete ACTH and present with Cushing
syndrome and hyperpigmentation.
■ The two distinctive morphologic features of most adenomas are their
cellular monomorphism and absence of a reticulin network.
