Pathology of Endocrine System

April. 10. 2015

Endocrine system

• Pituitary gland (Hypophysis).

Adenohypophysis

Neurohypophysis.

• Thyroid gland

• Parathyroid glands.

• Adrenal Glands

• Pancreatic islets

• Pineal gland

PITUITARY PATHOLOGY

• Clinical features; - Endocrine effects.- mass effects.

• Adenoma; Functioning, nonfunctioning • Hypo-pituitrism• Post. Pituitary Syndrome.• Hypothalamic (Suprasellar) tumors.

Pituitary Gland

The pituitary is located below the brain, in the hypophyseal fossa of sphenoid bone.

Low magnification – the entire Pituitary Gland

Posterior Pituitary Pars Intermedia Anterior Pituitary

Pars TuberalisPituitary Stalk

Pituitary development

ANTERIOR PITUITARY

• ACIDOPHILS

– GROWTH HORMONE*

– PROLACTIN

• BASOPHILS ….target.

– TSH

– ACTH

– LH, FSH

• Chromophobe

• OXYTOCIN (contracts uterine SM).

• VASOPRESSIN (ADH) (main effects on kidney, concentrates urine, vasoconstriction, gluconeogenesis, platelet aggregation, release of Factor-VIII and vWb factor)

POSTERIOR PITUITARY

Normal pituitary

HYPOTHALAMIC-HYPOPHYSEAL

PORTAL SYSTEM

• Vessels pass from hypothalamus to Ant. Pituitary (via stalk of pituitary).

• Carry hypothalamic regulator hormones.

1. Peptide hormones synthesized in the hypothalamus (in the supraoptic & paraventricular nuclei) axonal transport and accumulate in axons in the pars nervosa.

High mag of the Posterior Pituitary – axons, capillaries, and pituicytes

High mag of the Posterior Pituitary – note Herring Bodies (arrow)

High mag of the Anterior Pituitary – note eosinophilic and basophilic cells

Anterior pituitary, LM, trichrome stain

Growth HormoneACTH

Immunohistochemictry of the Anterior Pituitary

Somatotrophs, GH, form 1/2 of all cells in ant. pit.

Associated SyndromeHormonePituitary Cell Type

Cushing syndromeACTH and other

POMC-derived peptides

Corticotroph

Gigantism (children)

Acromegaly (adults)

GHSomatotroph

Galactorrhea &

amenorrhea (in females)

Sexual dysfunction,

infertility

ProlactinLactotroph

GH & PRLMammosomatotrophs

HyperthyroidismTSHThyrotroph

Hypogonadism, mass

effects, and

hypopituitarism

FSH, LHGonadotroph

Anterior Pituitary Six differentiated cell types

Posterior Pituitary Disorders

Hormone Increased Decreased

Oxytocin Precipitates

childbirth,

excess milk

Prolonged

childbirth,

diminished milk

ADH

(vassopressin)

Increased BP,

decreased

urinary output,

edema.

SIADH

Diabetes

insipidus, dilute

urine &

increased urine

output

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

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.

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.

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”).

• Prolactinomas (lactotroph adenomas)

• the most frequent type of hyperfunctioningpituitary adenoma, (30% of all clinically recognized cases).

• Dystrophic calcification, “pituitary stone”.

• S. prolactin conc. correlate with size of the adenoma

Lactotroph Adenoma

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.

G

A

L

A

C

T

O

R

R

H

E

A

• 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

GIGANTISM

(excess somatotropin [GH] BEFORE

epiphyseal

closure)

ACROMEGALY:

(excess somatotropin[GH] AFTER epiphyseal closure)

30 – 50 Years old

Corticotroph Adenomas

• Excess production of ACTH by functioning corticotroph adenomas

• leads to adrenal hypersecretion of cortisol

& hypercortisolism (Cushing syndrome).

MOON FACIES

BUFFALO HUMP

STRIAE

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

BITEMPORAL

HEMIANOPSIA

Pituitary adenoma. This massive, nonfunctional adenoma has grown far beyond thesella turcica and distorted the overlying brain. Nonfunctional adenomas tend to belarger at the time of diagnosis than those that secrete a hormone.

Pituitary adenoma. The monomorphism of cells, & absence of reticulin network.

Normal Pituitary;mixture of cells.

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 (adenylcyclase), &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

Pituitary adenomas

• The majority of pituitary adenomas are sporadic in nature,

• Only 5% of cases of an inherited predisposition (MEN1)

Hyperprolactinemia

• Physiologic; Pregnancy; lactating women, Stress.Baby crying.

• Pathological;Pituitary adenomasOther rare causes; (hyperplasia, interference with Dopamine).

• 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 lactotrophcells.

• 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.

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.

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.

• 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.

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

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.

• 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

Dwarfism• Child height 14cm less than average.

• Adult height of less than 4 feet 10 inches (58 in; 147 cm)

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.

Hypopituitarism (Adult)- GH

• Lack of GH leads to:– Increased CV

disease– Excessive tiredness– Anxiety– Depression– Reduced “quality of

life”– Possible premature

death

POSTERIOR pituitary

• Diabetes insipidus.

• SIADH (Syndrome of Inappropriate Anti- Diuretic Hormone)

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.

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.

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.

Craniopharyngioma - cystic spaces, calcifications, and "wet" keratin

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.

Quiz