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endocrine diseases
PITUITARY
The normal pituitary. (A) The gland is bean shaped and covered
by a fibrous capsule. It hangs from the hypothalamus by the
pituitary stalk or infundibulum. (B) On horizontal cross-section
the gland is readily seen to have two distinct components, the
anterior lobe representing the larger part (top) and the posterior
lobe, or neurohypophysis, representing the smaller component
(bottom). Between them is the intermediate lobe, which consists
only of vestigial structures that are recognized grossly as tiny
cysts with gelatinous contents
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ADRENAL GLAND
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The cortex, of course, has three "zones": (1) ZONA GLOMERULOSA:
mineralocorticoid
production. Thin and patchy, small cells.
(2) ZONA FASCICULATA: glucocorticoid production (now seems
settled), resting cells (the reserve cells are at the ZG-ZR
interface). Yellow.
(3) ZONA RETICULARIS: glucocorticoid production, androgen and
estrogen production, grossly darker than outer layers. Brown.
(Salt, sugar, and sex: the deeper you go, the sweeter it
gets.)
CUSHINGS SYNDROME (too much glucocorticoids)
Symptoms and signs: truncal obesity with "buffalo hump" ("upper
trunk fat") and "moon
face" increased appetite insomnia and mental changes (Cushing's
psychosis) vascular and connective tissue changes: thinning of the
dermis,
bruisability, striae ("purple stripes"), very poor healing,
purpura high blood pressure glucose intolerance (diabetes, with
complications) osteoporosis loss of normal circadian rhythm of
cortisol secretion other: acne, cellulitis, edema, gastric ulcers,
hirsutism,
oligomenorrhea, hypokalemia, muscle wasting,
CUSHINGS SYNDROME
Etiology (both Cushing's disease and
glucocorticoid-secreting
adenomas are most common in women ages 15 to 45, but can be
diagnosed in anybody and anytime)
Adrenals are: atrophic if glucocorticoids were administered
hyperplastic if ACTH was administered
CUSHINGS SYNDROME. etiology 1. IATROGENIC (the most common).
2. ACTH-PRODUCING PITUITARY LESION, usually a
basophilic microadenoma ("Cushing's disease", "pituitary
Cushingism")
the adrenals usually are diffusely enlarged (but may be
nodular),
"Nelson's syndrome" - rapid enlargement of the pituitary adenoma
leading to hyperpigmentation, blindness and death - followed
adrenalectomy in many of these patients
CUSHINGS SYNDROME. etiology
3. ADRENAL CORTICAL ADENOMA OR CARCINOMA ("adrenal Cushingism")
the tumor may be primary, or an autonomous adrenal tumor may
develop after years of "pituitary Cushingism")
4. ACTH- (OR CRH-) PRODUCING CANCERS OF OTHER ORGANS: small-cell
carcinoma, bronchial and thymic carcinoids, medullary thyroid
carcinoma, islet cell cancer; other APUDomas.
Full-blown Cushingism is rare in oat cell patients, only because
they don't live long enough
CUSHINGS SYNDROME. etiology
5. Really "primary" adrenal hyperplasia (not due to excess
ACTH): "primary pigmented nodular adrenocortical
hyperplasia" (part of the autosomal dominant Carney complex)
circulating antibodies against the ACTH receptor (analogous to
Graves disease) can occasionally stimulate the gland into
hyperactivity
6. Cushingism with a burst of cortisol after eating:
inappropriate expression of GIP receptors on the adrenal
cortex/adrenal adenoma
7. Recurrent cushingism of pregnancy
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PRIMARY HYPERALDOSTERONISM (Conn's syndrome)
"low-renin hyperaldosteronism": too much mineralocorticoid
Etiology: "idiopathic" adrenal hyperplasia, or an adrenal
adenoma. the most familiar cause is an "autonomous" adrenal
cortical adenoma (CONN'S SYNDROME), often very small
a cause of surgically-correctable high blood pressure (0.5% of
hypertensives have primary hyperaldosteronism)
PRIMARY HYPERALDOSTERONISM
clinic: classically, patients exhibit:
hypokalemia (muscle weakness, and even paralysis),
alkalosis, and low rennin, surprisingly, these patients do not
have
edema
SECONDARY HYPERALDOSTERONISM
is much more common then primary part of the picture in:
chronic heart failure, cirrhosis, nephrotic syndrome, and other
problems.
ADRENAL CORTICAL ADENOMAS
round, yellow (like the adrenal cortex) nodules ("nodular
hyperplasia")
adrenal cortical adenomas are found in 2% of autopsies and
abdominal CT scans ("incidentalomas", as far as there is no
evidence of steroid or catecholamine over-production)
may cause: Cushing's syndrome, Conn's syndrome, or virilization,
the vast majority are clinically silent
ADRENAL CORTICAL CARCINOMA
rare tumor, but often lethal many are hormonally active
(Cushing's, Conn's,
and/or virilization), mixed endocrine syndromes usually mean
cancer (Adrenal tumors that feminize, or that produce androgens
without glucocorticoids, are most often malignant)
histology: usually obviously malignant, grossly and
microscopically, with ten or more mitotic figures per high power
field
HYPOADRENOCORTICISM ("Addisonism")
Insufficient glucocorticoid (and usually insufficient
mineralocorticoid) production.
chronic hypoadrenocorticism (ADDISON'S DISEASE, now regardless
of etiology)
troubles start when 80% of the gland tissue is gone, There are
several etiologies of chronic
hypoadrenocorticism:
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HYPOADRENOCORTICISM INFECTIONS most of Dr. Addison's patients
had bovine TB of the
adrenals, worldwide:
fungal infections (histoplasmosis, coccidioidomycosis and South
American blastomycosis)
other important causes: leprosy, now AIDS is too.
HYPOADRENOCORTICISM AUTOIMMUNE the most prevalent non-iatrogenic
cause of Addison's
disease in the US the adrenals are typically loaded with
lymphocytes. most of patients have autoantibodies against 21-
hydroxylase ("adrenal cortex antibodies) autoimmune adrenalitis
often occurs jointly with Hashimoto's
thyroiditis, type I diabetes mellitus, vitiligo, gluten
enteropathy, and/or pernicious anemia ("autoimmune polyendocrine
deficiency syndrome II", "Schmidt's syndrome", etc.)
HYPOADRENOCORTICISM IATROGENIC results from too-rapid withdrawal
of glucocorticoid
medication, post-adrenalectomy for breast cancer or
Cushingism,
etc., ketoconazole or fluconazole (antifungal drug therapy),
removal of a "non-functioning adenoma" (rare). CORTICOSTEROID
INSUFFICIENCY OF CRITICAL
ILLNESS a newly-characterized entity, seen especially in
severe
systemic infections, in which the body does not put out enough
glucorticoid to handle the extra stress
HYPOADRENOCORTICISM OTHERS: amyloidosis congenital hypoplasia
hemochromatosis (a common disease still under-
diagnosed in the U.S.) sarcoidosis DAX1 mutations metastatic
cancer to adrenal glands anticoagulant therapy CMV infection (in
AIDS, it's almost the rule) adrenal leukodystrophy (one male in
17,000)
SECONDARY HYPOADRENOCORTICISM (ACTH deficiency)
patients almost always with lost of adenohypophysis and
"panhypopituitarism".
less often, selective, presumably autoimmune, loss of the
ACTH-producing cells.
SECONDARY HYPOADRENOCORTICISM (ACTH deficiency)
Clinical picture ("Addisonian" patients): weakness, nausea, and
weight loss, and are usually
hypotensive and other complaints (like in most endocrine
patients, the problems are likely to appear "emotional")
In primary hypoadrenocorticism, the skin and buccal mucosa will
usually be hyperpigmented, due to increased ACTH (MSH?)
Lab studies typically show hyponatremia, hyperkalemia, metabolic
acidosis, hypoglycemia, low serum cortisol, low urinary
17-OH-steroids, and (most important) failure to respond to various
"stimulation tests" by increasing cortisol output.
commonly patients die suddenly and unexpectedly before anyone
thinks of adrenocortical insufficiency
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ACUTE HYPOADRENOCORTICISM
"adrenal apoplexy", "Addisonian crisis
Sudden collapse, often fatal (opening of the peripheral
vasculature and shock with high
cardiac output)
It may result from undiagnosed adrenal insufficiency iatrogenic,
infection, surgery, or treatment
WATERHOUSE-FRIDERICHSEN SYNDROME
"adrenal apoplexy" features hemorrhage, fibrin thrombi, and
sometimes
necrosis in the adrenals in a setting of sepsis is not rare
(often overlooked (patients in shock
WITHOUT elevated serum cortisol) occurs when there is
overwhelming sepsis with
hemorrhage into, and destruction of, the adrenals, patients
develop: purpura, shock, and die in a few hours. etiology:
classically the meningococcus, staphylococci pneumococci, and H.
influenza
ADRENAL MEDULLA
around 10% of the normal adrenal by weight
produce "adrenalin" (epinephrine, also norepinephrine)
"Adrenal medullary hyperplasia" is a marker for MEN II and a few
rarities
any nodule bigger than 1 cm is a pheochromocytoma. -
pheochromocytoma (well-differentiated, adults) - neuroblastoma
(poorly-differentiated, children)
PHEOCHROMOCYTOMA
"paraganglioma", formerly "10% tumor":
in young patients (10-20 yrs) cases involve both adrenals, are
familial, and 10% metastasize
- is named for its colorful reaction in fixatives containing
chromic acid salts
- secrete norepinephrine (most common) and/or epinephrine
(usually less, and often others: dopamine, serotonin, ACTH,
somatostatin, neuropeptide Y, and/or VIP)
- IHC: chromogranin+ and/or synaptophysin+
PHEOCHROMOCYTOMA
Clinic: The infamous paroxysms of extreme hypertension,
accompanied by sweating, headache, and other autonomic
disturbances, probably result from physical compression and/or
ischemia
Even a tiny (1 gm) benign pheochromocytoma can make a person
very sick and will eventually cause death
Regardless of location and appearance, the patients will report
anxiety, headache, palpitations, "panic attacks", sweating,
dizziness, etc. (the basic problem is emotional. "Pheo is a great
imitator.")
PHEOCHROMOCYTOMA
"pheochromocytoma" is defined to arise in the adrenal medulla,
however similar tumors (less common) arise elsewhere are called
"extra-adrenal paragangliomas."
Macro: - are very bloody (because they are very vascular),
and
often show fibrosis, calcification, cystic change, or even fatty
change
Microscopically: resemble adrenal medulla, there are no
histologic criteria
for malignancy, not even vascular invasion. 5-year survival rate
with malignant pheo is around 50%