[09.11b] Adrenal Gland Pathology and Multiple Endocrine Neoplasias V2.1

Paired endocrine organs

What are the adrenal glands?

Superior aspect of the kidneys

Where are the adrenal glands located?

Fat or adipose tissue

What covers the adrenal glands?

Cortex and medulla

What are the two distinct parts of the adrenal gland?

Bright yellow

What is the characteristic color of the adrenal cortex?

Dark brown

What is the characteristic color of the adrenal medulla?

Hyperchromatic

How is the staining of the adrenal medulla described?

Pinkish or blander

How is the staining of the adrenal cortex described?

Zona glomerulosa

What is the narrow layer of the cortex located beneath the capsule?

Zona fasciculata

Which thick middle layer makes up 75 percent of the adrenal cortex?

Zona reticularis

Which narrow layer of the cortex is immediately adjacent to the medulla?

Steroids

What broad type of hormones does the adrenal cortex synthesize?

Mineralocorticoids

Which class of hormones, specifically aldosterone, is secreted by the zona glomerulosa?

Glucocorticoids

Which class of hormones, specifically cortisol, is primarily synthesized in the zona fasciculata?

Sex steroids

What class of hormones is synthesized in the zona reticularis?

Estrogen and androgens

Which two types of sex steroids are produced by the adrenal cortex?

DHEA and androstenedione

Which two compounds are secreted by the zona reticularis and converted to testosterone?

ACTH

Which hormone regulates the synthesis of sex steroids in the zona reticularis?

Catecholamines

What type of hormones, primarily epinephrine, are secreted by the adrenal medulla?

Rapid adaptation to environmental changes

What is the primary function of medullary catecholamines?

Hyperfunction and hypofunction

Diseases of the adrenal cortex are divided into which two categories?

Hyperadrenalism

What is the term for adrenocortical hyperfunction?

Adrenocortical insufficiency

What is the term for adrenocortical hypofunction?

Cushing syndrome

What syndrome is characterized by an excess of cortisol?

Women

Cushing syndrome affects which gender four times more frequently?

Young adults

In what age group does Cushing syndrome usually occur?

Exogenous glucocorticoid administration

What is the most common overall cause of Cushing syndrome?

Pituitary microadenoma

What is the majority cause of endogenous ACTH dependent Cushing syndrome?

Macroadenoma and corticotroph cell hyperplasia

What are two rare pituitary causes of Cushing syndrome?

Cushing disease

What is the specific name for Cushing syndrome caused by a pituitary adenoma?

70 percent

What percentage of endogenous Cushing syndrome cases are due to Cushing disease?

Ectopic ACTH

What syndrome accounts for about 10 percent of ACTH dependent Cushing cases?

Small cell carcinoma of the lung

Which tumor is most commonly responsible for ectopic ACTH secretion?

Carcinoid, medullary thyroid carcinoma, and islet cell tumors

What are three other neoplasms associated with ectopic ACTH?

Ectopic CRH

What can neuroendocrine neoplasms occasionally produce to cause hypercortisolism?

Bilateral cortical hyperplasia

What happens to the adrenal glands in pituitary or ectopic ACTH variants of Cushing syndrome?

Men in their 40s and 50s

The ectopic ACTH variant of Cushing occurs more commonly in which demographic?

Diffuse hyperplasia

Which adrenal morphology is found in individuals with ACTH dependent Cushing syndrome?

30 grams

How much can hyperplastic adrenal glands weigh in ACTH dependent Cushing syndrome?

Expanded lipid poor zona reticularis

Microscopically, what zone is expanded in diffuse hyperplasia?

Compact eosinophilic cells

What type of cells comprise the lipid poor zona reticularis in diffuse hyperplasia?

Vacuolated lipid rich cells

What cells surround the eosinophilic cells in diffuse hyperplasia, resembling the zona fasciculata?

Adrenal adenoma and adrenal carcinoma

What are the two most common underlying causes of ACTH independent Cushing syndrome?

10 percent

What percentage of ACTH independent Cushing cases are adrenal adenomas?

5 percent

What percentage of ACTH independent Cushing cases are adrenal carcinomas?

Low

What is the status of ACTH in ACTH independent Cushing syndrome?

Macronodular hyperplasia

Which condition involves prominent 10 to 30 mm nodules almost entirely replacing the adrenals?

McCune Albright syndrome

Which syndrome can produce a special subtype of macronodular hyperplasia?

GNAS gene

Which gene mutation activating stimulatory Gs-alpha is found in McCune Albright?

cAMP

Increased intracellular levels of which second messenger cause hyperplasia in McCune Albright?

G protein coupled receptors

Which receptors are ectopically overexpressed in macronodular hyperplasia?

GIP, LH, and ADH

What three non ACTH hormones can regulate cortisol production in macronodular hyperplasia?

Micronodular hyperplasia

What is another name for primary pigmented nodular adrenal disease?

1 to 3 mm darkly pigmented nodules

How is the histology of micronodular hyperplasia described?

Lipofuscin

What pigment, known as wear and tear pigment, causes the color in micronodular hyperplasia?

PRKAR1A and PDE11

Mutations in which two genes are associated with primary cortical hyperplasia?

Functional adenomas and carcinomas

Which adrenal cortex neoplasms are not morphologically distinct from non functioning counterparts?

Bright yellow

What is the characteristic color of an adrenocortical adenoma?

Less than 30 grams

How much does a typical adrenocortical adenoma weigh?

Zona fasciculata

Which cortex layer does an adrenocortical adenoma microscopically resemble?

Cortical carcinoma

Which adrenal neoplasm is more strongly associated with Cushing syndrome and weighs over 200 grams?

Unencapsulated

Are adrenocortical carcinomas typically encapsulated or unencapsulated?

Unilateral

Is adrenocortical carcinoma usually unilateral or bilateral?

Atrophy of the opposite gland

What happens to the contralateral adrenal gland in functional unilateral cortical neoplasms?

Bilateral cortical atrophy

What adrenal morphology results from chronic exogenous glucocorticoid intake?

Zona glomerulosa

Which layer of the cortex remains of normal thickness during bilateral cortical atrophy from exogenous steroids?

Functions independently of ACTH

Why is the zona glomerulosa spared in steroid induced atrophy?

Iatrogenic

What is the term for Cushing syndrome caused by medical treatment?

Secondary diabetes

Iatrogenic Cushing syndrome is a possible etiology for which metabolic disease?

Hyperglycemia, glucosuria, and polydipsia

What are three diabetic symptoms caused by excess glucocorticoids?

Hypertension and weight gain

What are two early manifestations of Cushing syndrome?

Truncal obesity, moon facies, and buffalo hump

What are the three components of the central pattern of adipose deposition in Cushing?

Posterior neck and back

Where does fat accumulate to form a buffalo hump?

Fast twitch or type 2 myofibers

The selective atrophy of which muscle fibers leads to proximal limb weakness in Cushing?

Skin that is thin, fragile, and easily bruised

What is a consequence of collagen loss in Cushing syndrome?

Cutaneous striae

Which skin finding is particularly common on the abdomen in Cushing?

Osteoporosis

Bone resorption from hypercortisolism results in what condition?

Increased risk for infections

What is the effect of glucocorticoids on the immune response?

Mental disturbances

Mood swings, depression, and psychosis in Cushing are classified as what?

Hirsutism and menstrual abnormalities

What are two reproductive/androgenic manifestations of Cushing in women?

Increased 24 hour urine free cortisol

What is a primary laboratory finding for diagnosing Cushing syndrome?

Loss of diurnal pattern of secretion

What happens to the normal daily cycle of cortisol in Cushing?

Serum ACTH and Dexamethasone suppression test

The cause of Cushing is determined by evaluating which two parameters?

High dose dexamethasone

Which test causes a reduction in urinary 17-hydroxycorticosteroids in pituitary Cushing but not ectopic?

Low ACTH

What distinguishes adrenal tumors from pituitary Cushing regarding hormone levels?

Adrenal tumor and ectopic ACTH secretion

Which two forms of Cushing are completely insensitive to dexamethasone suppression?

Hyperaldosteronism

What condition results from excessive aldosterone?

Primary hyperaldosteronism

Which condition is characterized by autonomous aldosterone production and suppressed renin?

Hypertension

What is the most common clinical manifestation of primary hyperaldosteronism?

Sodium reabsorption

Why does blood pressure rise in hyperaldosteronism?

Idiopathic hyperaldosteronism

What is the most common cause of primary hyperaldosteronism?

Bilateral nodular hyperplasia

What is the underlying pathology of idiopathic hyperaldosteronism?

Older

Are patients with idiopathic hyperaldosteronism usually younger or older?

KCNJ5 mutations

Recent studies suggest familial idiopathic hyperaldosteronism may harbor which germline mutation?

Conn syndrome

What is the name for primary hyperaldosteronism caused by an aldosterone secreting adenoma?

Adrenal adenoma

What is the second most common cause of primary hyperaldosteronism?

Glucocorticoid suppressible hyperaldosteronism

Which rare familial cause involves a chromosome 8 rearrangement?

CYP11B2 under the control of CYP11B1 promoter

What is the specific genetic rearrangement in glucocorticoid suppressible hyperaldosteronism?

Aldosterone synthase

What enzyme is encoded by the CYP11B2 gene?

Dexamethasone

In the rare suppressible familial form, aldosterone production can be stopped by which drug?