Pituitary & Adrenal Pathology

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Pituitary embryology

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Pituitary normal anatomy:

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normal fresh pituitary

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Review of cell types in the anterior pituitary:

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normal pituitary
chromophobes
acidophils
basophils

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IHC stain for GH in the pituitary.

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Types of Pituitary adenomas by their staining features, and what they secrete:

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TYPE HORMONE
-Chromophobe GH, PRL, ACTH, FSH, LH, TSH

-Acidophil GH, PRL

-Basophil ACTH, FSH/LH, TSH

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Types of Pituitary adenomas by what they secrete:

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Type
Prolactin (PRL) 20-30%
Growth hormone (GH) 5
PRL/GH 5
ACTH 10-15
LH/FSH 10-15
Null cell 20
TSH 1
Plurihormonal 15

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PITUITARY ADENOMAs--Describe Mass Effects:

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*Sella expansion, bone erosion, disruption of diaphragm sella

*Visual field abnormalities (bilateral hemianopsia)

*Elevated intracranial pressure (nausea, vomiting, headache)

*Hypopituitarism

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PITUITARY MICROADENOMA (< 1cm)
-probably an incidental finding at autopsy

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PITUITARY MACROADENOMA (> 1cm)

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PITUITARY ADENOMA
-bland architecture
-not much pleomorphism
-not much mitotic activity

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Main PRLoma clinical features:

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Females: Galactorrhea, amenorrhea, infertility

Males: Loss of libido, impotence

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IMMUNOPEROXIDASE STAIN (PROLACTINoma)

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Gonadotroph Adenomas:

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Produce LH and FSH
Secrete hormones inefficiently
Neurological symptoms predominate

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Null Cell Adenomas:

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Up to 20% of all adenomas
Neurological symptoms predominate

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TSH Adenomas:

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1% of all adenomas
Hyperthyroidism

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PITUITARY ADENOMAS: key points:

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*10-15% of intracranial neoplasms

*Incidental findings in 25% of normal individuals (mostly prolactin-producing microadenomas)

*Defining feature of MEN1--associated with parathyroid and pancreatic tumors

*G-protein mutations

*Majority are benign

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Describe the POSTERIOR PITUITARY:

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*Modified glial cells (pituicytes) and axonal processes from nerve cells in supraoptic and paraventricular nuclei

*ADH (vasopressin) and oxytocin

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HYPOPITUITARISM:

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*Result from diseases of hypothalamus or pituitary

*Occurs when 75% of pituitary is destroyed!!!

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Causes of hypopituitarism:

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*Tumors and other mass lesions
*Prior surgery or irradiation
*Rathke cleft cyst
*Pituitary apoplexy
*Ischemic necrosis of pituitary/Sheehan syndrome
*Empty sella syndrome
*Genetic defects
*Infiltrative disorders
*Infections

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PITUITARY INFARCT (*)
-Typical scenario: pregnant pt who develops complication with lots of hemorrhage and hypotension, resulting in pituitary infarcts.
-Why? Pituitary proliferation due to PRL production makes it vulnerable to hemorrhage; doesn't produce enough blood vessels for itself [Sheehan's]

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EMPTY SELLA:
-Widely opened sellar diaphragm
-increased CSF pressure compresses pituitary

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EMPTY SELLA with compressed pituitary due to high CSF pressure

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SUPRASELLAR DISORDERS:

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*Associated with sleep disturbances, hunger, hypogonadism or precocious puberty

*Etiology: craniopharyngioma, dermoid cyst, ependymoma, meningioma, trauma, encephalitis

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CRANIOPHARYNGIOMA
-they get cystic, calcified (can be seen on x-ray), they ooze an oily fluid like machine oil

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CRANIOPHARYNGIOMA
Arrows = Palisaded Nuclei
-epithelial cells surrounded by reticular-like network
-may come from rathke's pouch remnants

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Adrenal anatomy:

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Arrow = medulla (about 10% of volume)

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arrow points to a vein

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CUSHING’S SYNDROME

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ADRENOCORTICAL HYPERFUNCTION\HYPERCORTISOLISM (Cushing Syndrome):

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Any condition that produces an elevation in glucocorticoids

1. Administration of exogenous glucocorticoids
2. Primary hypothalamic - pituitary disease
associated with hypersecretion of ACTH
3. Hypersecretion of cortisol by adrenal
adenoma, carcinoma or nodular hyperplasia
4. Secretion of ectopic ACTH by a non-
endocrine tumor

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Frequency of different causes of Cushing's syndrome in adults:

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PRIMARY PIGMENTED NODULAR ADRENAL CORTICAL
DISEASE (PPNAD) AKA Carney Complex: autosomal dominant disorder with myxomas of heart and skin, hyperpigmentation of skin, endocrine hyperactivty
(e.g. Cushing Syndrome)

P = Pigmented (lipofuscin) nodule

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PRIMARY HYPOTHALAMIC-PITUITARY DISEASE ASSOCIATED WITH ACTH HYPERSECRETION:

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*Accounts for 70-80% of cases of endogenous hypercortisolism
*Called Cushing’s disease
*F:M = 5:1 with onset in early adulthood
*ACTH producing micro-or macro-adenomas

*Some patients may have hyperplasia of ACTH producing cells which may be primary or may result from hypothalamic corticotropin releasing hormone-producing tumor

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Adrenocortical hyperplasia. The adrenal cortex (bottom) is yellow, thickened, and multinodular as a result of hypertrophy and hyperplasia of the lipid-rich zonae fasciculata and reticularis. The top shows a normal adrenal for comparison.

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ADRENOCORTICAL HYPERPLASIA ASSOCIATED WITH CUSHING’S DISEASE

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HYPERSECRETION OF CORTISOL BY ADRENAL CORTICAL TUMORS (ACTH INDEPENDENT) CUSHING’S SYNDROME:

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*Includes cases of adrenal cortical adenomas, cortical carcinoma and rare cases of primary hyperplasia

*Accounts for 10-20% of cases of endogenous Cushing’s syndrome

*Adenomas are more common than carcinomas in adults, but cortical carcinomas predominate in children

*ACTH levels are typically low

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ADRENOCORTICAL ADENOMA

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ADRENOCORTICAL ADENOMA

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ADRENOCORTICAL ADENOMA
* indicates lipid

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ATROPHIC ADRENAL CORTEX ADJACENT TO ADENOMA
-indicates a functional adenoma

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ADRENOCORTICAL CARCINOMA
-really uncommon, like 1:2,000,000
-arrow=calcification

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ADRENOCORTICAL CARCINOMA
K = Kidney; S = Spleen
-really uncommon, like 1:2,000,000

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ADRENOCORTICAL CARCINOMA
arrows indicate mitotic figures

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METASTATIC ADRENOCORTICAL CARCINOMA--they can go to the lungs

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ECTOPIC ACTH PRODUCTION:

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*Accounts for 10% of cases of endogenous Cushing’s syndrome

*Responsible tumors: small cell lung carcinoma (most common), pancreatic endocrine tumors, medullary thyroid carcinoma

*Tumors may produce ACTH and corticotropin releasing hormone

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PRIMARY HYPERALDOSTERONISM:

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*Autonomous overproduction of aldosterone with suppression of renin-angiotensin system and decreased plasma renin activity

*Primary hyperaldosteronism can be caused by:
- Adrenocortical neoplasm (usually an adenoma associated with Conn’s syndrome)
- Primary adrenocortical hyperplasia (idiopathic hyperaldosteronism)

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Chart of primary hyperaldosteronism causes:

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ALDOSTERONOMA/CLINICAL FEATURES:

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Hypertension

Hypokalemia

Low serum renin

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ALDOSTERONE PRODUCING ADENOMAS: size/demographics/appearance--

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*Less than 2cm in diameter
*F>M
*Bright yellow
*Cells resemble those of fasciculata or glomerulosa

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ALDOSTERONOMA

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ALDOSTERONOMA
-Cells that look like adrenal cells

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ADRENAL CORTICAL HYPOFUNCTION:

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*Primary
-Autoimmune disorder
-Infectious diseases (TB, Histoplasmosis)
-Infiltrative diseases (amyloidosis)
-Enzymatic defects in steroid hormone biosynthesis
-Acute adrenal insufficiency (WFS)

*Secondary
-Pituitary or hypothalamic disorders with decreased ACTH or CRH

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AUTOIMMUNE ADRENALITIS
-adrenal gland was totally atrophied; some cells still look like adrenal cells

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HISTOPLASMOSIS
H = Hemorrhage; N = Necrosis

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Summary of adrenal product synthesis:

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*This shows 21-OHlase deficiency.

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CONGENITAL ADRENAL HYPERPLASIA
Black Arrows = Adrenals; K = Kidneys
*The adrenals are HUGE (too much ACTH)

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*METASTATIC CARCINOMA IN ADRENAL GLANDS

*The left adrenal is massively enlarged due to metastatic disease. The right adrenal is also involved to a lesser extent.

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WATERHOUSE FRIDERICHSEN SYNDROME:

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*Overwhelming bacterial infection (typically N. meningitidis)

*Rapidly progressive hypotension leads to shock

*Disseminated intravascular coagulation with widespread purpura develops

*Rapidly developing adrenal cortical insufficiency associated with massive bilateral adrenal hemorrhage occurs

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WATERHOUSE-FRIDERICHSEN SYNDROME
A = Adrenals; K = Kidneys
*Associated with meningococcus

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PARAGANGLIONIC SYSTEM:

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1) Adrenal Medulla
2) Extra-Adrenal Paraganglia
a. Branchiomeric (head and neck)
b. Intravagal (vagus nerve)
c. Aorticosympathetic

*Tumors of Adrenal Medulla are called pheochromocytomas (intra-adrenal paraganglioma)

*Tumors of Paraganglionic Cells are called paragangliomas (extra-adrenal pheochromocytoma)

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pheochromocytoma

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"nests" of cells surrounded by vasculature in a pheochromocytoma

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PHEOCHROMOCYTOMA - RULE OF 10’S:

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10% - familial (actually more like 25%)
10% - extra-adrenal
10% - bilateral
10% - malignant (actually lower than this)
10% - develop in childhood

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MEN2 ASSOCIATED PHEOCHROMOCYTOMA

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FAMILIAL SYNDROMES ASSOCIATED WITH PHEOCHROMOCYTOMA / PARAGANGLIOMA:

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*MEN2A
*MEN2B
*Von Hippel-Lindau
*Von Recklinghausen

*Succinate dehydrogenase mutations --> familial paragangliomas

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INCIDENTAL ADRENAL ADENOMA (INCIDENTALOMA)

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MACRONODULAR HYPERPLASIA (CUSHING DISEASE)

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METASTATIC LUNG ADENOCARCINOMA

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ADRENOCORTICAL CARCINOMA

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ADRENOCORTICAL CARCINOMA

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ADRENOCORTICAL HYPERPLASIA

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DIFFUSE AND MICRONODULAR HYPERLASIA (CUSHING DISEASE)

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Adrenal carcinoma. The bright yellow tumor dwarfs the kidney and compresses the upper pole. It is largely hemorrhagic and necrotic.

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Pheochromocytoma. The tumor is enclosed within an attenuated cortex and demonstrates areas of hemorrhage. The comma-shaped residual adrenal is seen below.

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CRANIOPHARYNGIOMA

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Schematic representation of the various forms of Cushing syndrome, illustrating the three endogenous forms, as well as the more common exogenous (iatrogenic) form. ACTH, adrenocorticotropic hormone.

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RARE CAUSES OF CUSHING’S SYNDROME:

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Macromodular hyperplasia

Primary pigmented nodular adrenal disease

McCune Albright Syndrome

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PITUITARY PATHOLOGY/CUHSHING’S DISEASE

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Adrenocortical adenoma. The adenoma is distinguished from nodular hyperplasia by its solitary, circumscribed nature. The functional status of an adrenocortical adenoma cannot be predicted from its gross or microscopic appearance.

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BILATERAL ADRENAL HEMORRHAGE

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Acute adrenal insufficiency caused by severe bilateral adrenal hemorrhage in an infant with overwhelming sepsis (Waterhouse-Friderichsen syndrome). At autopsy the adrenals were grossly hemorrhagic and shrunken; microscopically, little residual cortical architecture is discernible.