Anterior Pituitary [adenohypophysis]

o Anterior pituitary hyperfunction

Mutation of the GNAS gene constitutive activation of a stimulatory G protein [GsAlpha]
one of the most common genetic alterations
**Prolactinoma with hyperprolactinemia
The most common pituitary tumor
In women galactorrhea amenorrhea
Caused by
o Hypothalamic lesions or medications [methyldopa]interfere with dopamine
Associated with estrogen therapy
Somatotroph adenomawith hypersecretion of GH
2
nd
most common pit tumor
Causes: hepatic secretion of Insulin-like Growth factor [IGF-1 or somatomedin C]
End organ effects are caused by GH and IGF-1
Gigantism
o If adenoma develops in childhoodbefore epiphyseal closure
Acromegaly
o If adenoma develops after epiphyseal closure. Failure to suppress GH
production in response to overload Glucose [most sensitive test]
Local compression effects due to expansion of tumor within sella turcica
Corticotroph adenomahypersectriction of ACTH [Adrenocorticotropic hormone]
Cushing syndrome:
o Excess production of ACTH hypersecretion of cortisol [hypercortisolism]
o Secondary to an adrenal adenoma or carcinoma
Cushing Disease
o Excessive production of ACTH by the pituitary
o Elevated serum cortisol secondary to corticotroph cell pituitary adenoma
o Weight gain, truncal obesity, abdo striae, buffalo hump, etc
Hypercortisolism may be caused by ectopic ACTH production by tumors [small cell
carcinoma of lung]***
o Anterior Pituitary Hypofunction
Hypopituitarism: can result from ANY process that destroys the pituitary
Pituitary tumors
Postpartum pituitary necrosis [Sheehan syndrome]
o Caused by ischemic necrosis [infarction] of the pituitary
o Associated with hemorrhage and shock during childbirth
Selective Deficiency of one or more pituitary hormones
Deficiency of GH
o Pituitary dwarfism: In children results in growth retardation
o In adultsincreased insulin sensitivity with hypoglycemia, decreased muscle
strength, and anemia
Deficiency of gonadotrophins
o In preadolescent children: retarded sexual maturation
o In adults: loss of libido, impotence, loss of macular mass, and decreased facial
hair in men, and amenorrhea and vaginal atrophy in women
Deficiency of TSH secondary hypothyroidism
Deficiency of ACTH secondary adrenal failure
No hyperpigmentation of the skin, because of lack of ACTH and MSH
Primary adrenal failure [ADDISON DISEASE], increased ACTH hyperpigmentation
Posterior Pituitary [Neurohypophysis]
o Hormones are synthesized in the hypothalamaus and store within the axon terminals
Oxytocin: induces uterine contraction during labor and ejection of milk
AntiDiuretic HormoneADH, Vasopression: promotes water retnention through action on the
renal collecting ducts
o Deficiency of ADH Diabetes Insipidus [DI]
Excretion of large volumes of dilute urine with an inappropriately LOW specific gravity
Serum sodium and osmolality are increased as a result of excessive renal loss of free water
thirst and polydipsia
Administration of ADH increases URINE osmolality in central DI, but no change in nephrogenic
DI
o Syndrome of Inappropriate Anti Diuretic Hormone [SIADH] Secretion
Most commonly caused by ECTOPIC production of ADH [small cell carcinoma of the lung]
Retention of water with consequent hyponatremia and reduced serum osmolality
Cerebral edema, and resultant neurologic dysfunctionPeripheral edema DOES NOT develop
Nonfunctioning Pituitary Tumors
o Dysfunction results because of LOACAL MASS EFFECT
Manifestations: hypopituitarism, headache, visual disturbances [bilateral hemianopsia: loss of
peripheral visual fields] due to pressure on optic chiasm]
o Crangiopharyngioma
Benign childhood tumor is derived from remnants of Rathke pouch
Characteristics include:
Bests and cords of squamous cells in a Loose Stroma
Often cystic, the lining epithelium of flat or columnar cells often expands into papillary
projections
Radiographic detection is often possible because of tumor calcification
Other causes of pituitary hypofunction
o Pituitary APOPLEXY
A sudden hemorrhage into the pituitary glandoften into a pituitary adenoma
Can cause the sudden excruciating headache, diplopia, cardiovascular collapse, and loss of
consciousness
o Empty Sella Syndrome
Caused by any condition that destroys the pituitary gland
Primary empty sella syndrome
Defect in diaphragma sella allows the arachnoid and CSF to herniated into the sella
expansion of sella and compression of pituitary [obese women with multiple
pregnancies]
Secondary empty sella syndrome
Mass enlarges the sella, then ablated by surgery or radiation, or undergoes
SPONTANEOUS necrosis
o Nelson Syndrome
Development of large pituitary adenomas following bilateral adrenalectomy, due to loss of
feedback inhibition on growth of preexisting pituitary microadenomas



Thyroid Gland
o Thyroid Hormones
Include Thyroxine [T4] and triiodothyronine [T3]
Their synthesis depends on sufficient quantities of iodine from dietary sources
Serum T3 and T4 are bound to thyroid-binding globulin [TBG]
The rate of extraction of iodine from the bloodstream and the rate at which T4 and T3 are
synthesized, released, and secreted into the bloodstream are regulated by TSH
Feeback mechanisms regulate pituitary production of TSH
o Hyperthyroidism [thyrotoxicosis]
C/F
Tremor
Restlessness, irritability, fatigability
Heat intolerance; sweating; warm, moist skin [palms]
Tachycardia, arrhythmia, palpitationsometimes high-output cardiac failure
Muscle wasting and weight loss despite increased appeptitie
Fine hair
Diarrhea, menstrual abnormalitiescomonly amenorrhea or oligomenorrhea
Greatly INCREASED free T4 and greatly REDUCED TSH
Total T3 and T4 resin uptake are both Increased
Other causes of hyperthyroidism
Plummer disease is a combination of hyperthyroidism, nodular goiter, and absence of
exophthalmos
o The HOT nodules can be adenomas or non-neoplastic areas of nodular
hyperplasia
Pituitary hyperfunction can cause excess production of TSH and secondary
hyperthyroidism
Struma ovarii is an ovarian teratoma made up of thyroid tissue; can be hyperfunctional
Exogenous administration of thyroid hormone
o Hypothyroidism
Lab abnormalities: decreased serum free T4, increased TSH
Clinical syndromes
Cretinism in children
o Causes: iodine deficiency, deficiency of enzymes necessary for the synthesis of
thyroid hormones, maldevelopment of thyroid gland, placental transfer f
antithyroud antibodies from a mother with autoimmune thyroid disease
o Clinical Features: severe mental retardation, short stature, coarse facial
features, a protruding tongue, and umbilical hernia
Myxedema: hypothyroidism manifestation in adults
o More common in women than in men
o Causes
Iodine deficiency is most important cause in non-iodine deficient regions
Therapy for hyperthroidism with surgery, irradiation, or drugs
Hashimoto thyroiditis
Primary idiopathic myxedmea is a poorly defined form of myxedma ,
which may be of autoimmune origin [TSH receptor blocking antibodies
have been identified]
o Clinical characteristics of myxedema
Insidious onset
Slowing of physical and mental activity: fatugue, apathy, and mental
sluggishness
Cold intolerance and overweigh
Reduced cardiac output, shortness of breath, and decreased exercise
capacity
Accumulation of matrix substances in skin, subcutaneous tissue, and
visceral site: enlargement of tongue and deepening of the voice
o Thyroiditis
Hashimoto thyroiditis
Occurs more often in women than in men
Cause of hypothyroidism: may occasionally have an early transient hyperthyroid phase
Autoimmune disorder: associated with autoantibodies
o Most predominantly: antithyroglobulin, antithyroid peroxidase, anti-TSH
receptor, and anti-iodine receptor antibodies
May also be associated with an increased incidence of other autoimmune disorders
such as pernicious anemia, diabetes mellitus, and Sjogren syndrome; increase is
increased in HLA-DR5 and HLA-B5 + individuals
Clinical characteristics
o A slow, often inapparent course and a modestly enlarged and nontender
thyroid
o Patient is most often eurythroid at first, but transient hyperthyroidism may
occur; hypothroidism develops LATE when the gland has shrunken and scarred
Histo
o Massive infiltrates of lymphocytes with germinal center formation. Thyroid
follicles are atrophic and Hurthle cells are important
Subacute [deQuervain, granulomatous] Thyroiditis
More common in women than in men
**Characteristic**Focal destruction of thyroid tissue and granulomatous inflammation
Causes a variety of viral infectionmumps or coxsackie
Subacute Thyroiditis follows a self-limited course of several weeks duration
consisting of a flu-like illness along with pain and tenderness of the thyroid
sometimes with transient hyperthyroidism
Riedel Thyroiditis
Characterized by thyroid replacement by fibrous tissue [may extend to local
structureairways]; unknown origin. It can clinically mimic aplastic carcinoma
Hard as wood tender thyroid gland
Young women
o Graves Disease
General
Occurs more frequently in women than in men
Incidence is increased in HLA-DR3 and HLA B8 + individuals
Exophthalmos, possibly due to autoimmune mechanisms and independent of thyroid
hyperfunctioncharacteristic
Manifestations: signs and symptoms of hyperthyroidism
Mechanism
Thyroid-Stimulating Immunoglobulin, an IgG antibody, reacts with thyroid follicle TSH
recepetors and stimulates thyroid hormone production
Thyroid growth-stimulating immunoglobulins: proliferation of thyroid follicular
epithelium [hyperplasia and enlargement]
TSH-binding inhibitor immunoglobulinsprevent TSH from binding normally to its
receptor
o Goiter general term for enlargement of the thyroid
Causes:
Physiologic enlargement is not uncommon in puberty and pregnancy
Iodine deficiency occurs in geographic areas in which the diet is deficient in iodine
Hashimoto Thyroiditis
Gointrogens [food and drugs] suppress synthesis of thyroid hormones
Dyshormonogenesis, or partial or complete failure of thyroid hormone synthesiscan
be aused by various enzyme deficiencies
Terminology
Diffuse nontoxic [simple] goiter
o Is without thyroid hormone dysfunction
o Patients are euthryoid or hypothroid
Toxic goiter
o Associated with hyperthyroidism
Endemic goiter is occurring with high frequency in iodine-deficient geographic areas.
o Term: sporadic goiter is used for goiter caused by similar mechanisms in non-
iodine deficient areas
Colloid goiter:
o If dietary iodine increases or if the demand for thyroid hormone decreases, the
goiter invilutes to form an enlargem colloid-rich gland
Nodular goiter
o Irregular enlargement of the thyroid resulting in nodule formation
o Nodules may be single or multiplemultinodular goiter
o Most nodules are hypoplastic and do not take up radioactive iodine [cold
nodules]
o Occasionally nodules are hyperplastic and actively produce thyroid hormone
and take up radioactive iodine [hot nodules]
o Benign tumors [adenomas] of the thyroid
Typically discrete, solitary masses, derived from follicular epithelium, and are also know as
folllicular adenomas
Follicular adenoma
Encapsulated lesion that is well demarcated from surround thyroid parenchyma.
Neoplastic cells are demarcated by a well-defined,intact CAPSULE
Most oftennonfunctional, but they can occasionally cause hyperthyroidism
o Malignant tumors of the thyroid
Papillary carcinoma
Most common thyroid cancer
Histo
o Papillary projections into gland-like spaces; nuclei of papilarry carcinoma have
optically clear or empty appearance: ground glass//Orphan Annie nuclei
o Concentrically calcified structurespsammoma bodies may be present
Have better prognosis than other forms of thyroid cancer; even when adjacent LN are
involved
Can be associated with changes in chromosomeparacentric inversion of chrom 10 or
reciprocal translocation between chroms 10 and 17] constitutively activate tyrosine
kinase domain of RET [novel fusion genes formed are RET/PTC]
Can be long-term consequence of prior radiotherapy to the neck
Follicular Carcinoma
Characterized histo: relatively uniform follicles
Deficiency of dietary iodine [assc with goiter] is linked with a higher freq of follicular
carcinoma. Poorer prognosis than papillary carcinoma
Gain of function POINT mutation: RAS, PIK3CA
Loss of function of PTEN
Unique (2;3)(q13;p25) translocated fusion of PAX 8 with PPARG 1/3 to of
follicular carcinomas [PAX8-PPARG fusion genes]
Distinction from follicular adenoma requiresextensive histo sampling of tumor
capsule thyroid interfaceto exclued CAPSULAR AND/OR VASCULAR INVASION
Medullary carcinomas
Originates from parafollicular cells [C cells] of the thyroidproduces CALCITONIN
Histologic characteristics include sheets of tumor cells in an amyloid stroma
Familial medullary thyroid carcinomas occur in MEN2 and are associated with RET
proto-oncogene mutations lead to constitutive activation of the receptor
RET mutations are also seen in approximately of nonfamilial [sporadic] medullary
thyroid cancers
Undifferentiated carcinoma
Tends to occur in older patients and has a very poor prognosis
RAS or PIK3CA mutations are at a significantly higher rate
Inactivation of p52 or activating mutations of beta-cateninrestricted to ANAPLASTIC
carcinoma
o Congenital anomalies
Thyroglossal duct cystmost common thyroid anomaly!!
Vestigial remnant of the Tubular development of the thyroid gland

Parathyroidism [PTH]
o Parathyroid Homrone [PTH]
The parathyroid glands are responsive to the plasma concentration of ionized calcium;
decreased calcium concentration stimulates PTH production
Hypercalcemia is induced by elevated levels of PTH.
Malignancy is MOST common cause of clinically apparent hypercalcemia
o Hyperparathyroidism
Primary hyperparathyroidism
Most often, the cause is parathyroid adenoma; a few cases are caused by primary
parathyroid hyperplasia; carcinoma is RARELY a cause
Less often, the cause is production of PTH-like hormone by nonparathyroid malignant
tumors such as bronchogenic squamous cell carcinoma or renal cell carcinoma
Primary parathyroidism can occur as part of MEN-1 and MEN-2A
Primary hyperparathyroidism is a more common cause of asymptomatic elevated blood
calcium
Lab Findings:
o Hypercalcemia and hypercalciuria
o Decreased serum phosphorus, decreased tubular reabsorption of phosphorus,
and increased urinary phosphorus
o Increased serum alkaline phosphatase
o Increased Serum PTH
Clinical characteristics
o Osteitis fibrosa cystica, cystic changes in bone due to osteoclastic resorption;
fibrous replacement of resorbed bone formation of non-neoplastic tumor-like
masses brown tumor
o Metastatic calcification affecting various tissueskidneys [nephrocalcinosis]
o Renal calculi, frequent complication
o Peptic duodenal ulcer; hypercalcemia predisposes to peptic ulcer
Secondary hyperparathyroidism
Compensatory parathyroid hyperplasia occurs in response to decreased concentration
of serum ionized calcium
The most common cause is hypocalcemia of chronic renal disease
o Reduced alpha-1hydroxylase necessary for the synthesis of active form of
Vitamin Dwhich reduced intestinal absorption of calcium
o The increased serum phosphorus of renal disease induces a reciprocal decrease
in serum calcium
Characteristics:
o Decreased serum calcium, increased serum phosphorus, and increased serum
alkalin phosphatase
o Diffuse osteoclastic bone disease
o Metastatic calcification
o PTH increased
Teritiary hyperparathyroidism
Persistent parathyroid hyperfunction occurs inspite of correction of hypocalcemia and
preexisting secondary hyperparathyroidism
Often, the cause is development of an adenoma in previous hyperplastic gland
o Hypoparathyroidism
The most common cause is accidental surgical excision during thyroidectomy
In rare instances, this disorder is associated with congenital thymic hypoplasia [DiGeorge
syndrome]
Severe hypocalcemia manifest clinically by increased neuromuscular excitability and
tetany**characteristic**
o Pseudohypoparathyroidism
Decreased calcium, increased phosphate, and increased PTH
Characterized: multihormone resistance involving PTH and pituitary hormones: TSH, LH, and
FSH
Additional characteristics include
End organ unresponsiveness of the kidney to PTH, as well as shortened 4
th
and 5
th

metacarpals and metatarsals, short stature, and other skeletal abnormalities
Endocrine Pancreas
o Type I DIABETES MELLITUS
Epidemiologic and etiologic factor
Often begins early in life, usually before 30 years of age
Less common than type 2 disease
Type 1 diabetes is due to failure of insulin synthesis by BETA cells of the Islets of
Langerhans in the Pancreas
The cause maybegenetic predisposition complicated by autoimmune inflammation
of islets [insulitis] triggered by viral infection or environmental factors
Incidence is greatly increased in individuals with a specific point mutation in HLA-DQ
gene
Incidence is markedly increased in HLA-DR3 and HLA-DR4 + individuals
Characteristics
Unless insulin is replaced, type 1 diabetes marked carbhohydrate intolerance with
hyperglycemia LEADING to Polyuria, polydipsia, weight loss despite increased
appeitie, ketoacidosis, coma and death
Diabetic Ketoacidosis from increased catabolism of fat, with production of ketone
bodies
o Type 2 Diabetes
Epidemiologic and etiologic factors
Type 2 diabetes is much more common. A + family history is more frequent than in
type 1.
Characteristically begins later in life [middle age]
2 metabolic defects characterize Type 2 Diabtetes
o Insulin resistance: a decreased response of peripheral tissues to insulin
o Beta-Cell Dysfunction: manifested as inadequate insulin secretion
Obesity has an important relationship with insulin resistance
Risk factors for diabetes increases as BMI increases
Other players include
o Nonesterfied Fatty Acids [NFAs, lipotoxicity] and the PPAR-gamma receptor,
which promotes secretion of anti-hyperglycemic adipokines and shifts
deposition of NEFAs toward adipose tissue
Characteristics
The plasma insulin concentration is NORMAL and often INCREASED
Mild carbohydrate tolerance can be managed by diet and oral antidiabetic agents
In decompensated state, type 2 diabetics may develop hyperosmolar ketotic coma.
Ketoacidosis is unusual but does occur, precipitated by stress such as infection or
surgery
o Maturity-onset Diabetes Mellitus of the young [MODY]
This AUTOSOMAL dominant syndrome is characterized by:
Mild hyperglycemia and hyposecretion of insulin
NO loss of beta-cells
Earlier onset than dibatetes mellitus type 2
Caused by a diverse group of single gene defects
o Secondary diabetes mellitus occurs as a secondary phenomenon
Pancreatic disease
Hereditary hemochromatosis [bronze diabetes]
Characteristics: excess iron absorption and parenchymal deposition of hemosiderin,
with reactive fibrosis in various organspancreas, liver, and heart
Pancreatitis:
o Acute pancreatitis: hyperglycemia
o Chronic pancreatitis: result in islet cell destruction and secondary diabetes
mellitus
Carcinoma of pancreasDiabetes Mellitus maybe presenting sign
Other endocrine diseases
Cushing syndrome:
o Produces hyperglycemia as a result of increased gluconeogenesis and impaired
peripheral utilization of glucose
Acromegaly
o Produces hyperglycemia due to the anti-insulin-like effect of GH
Glucagon hypersecretion
o Promotes: Glycogenolysis
o Characteristically caused by: islet alpha cell tumor [glucagonoma]
Other endocrine disorders
o Pheochromocytoma and hyperthyroidism sometimes associated with
hyperglycemia
Pregnancy
Pregnancy may be associated with transient diabetes mellitus [gestational diabetes];
over nongestational diabetes sometimes develops later
DM is characteristically associated with increased fetal birth weight and increased fetal
mortality; notably from neonatal Respiratory Distress Syndrome [hyaline membrane
disease]
When a mother has hyperglycemia, her infant may be born with hyperplasia of
pancreatic islets and hypoglycemia!
o Long term complications of DM
Pathogenesis of the long-term complications of DM is similar in both types
Persistent hyperglycemia is key mediator
Assessment of glycemic control has been based on glycosylated hemoglobin [Hb1AC]
HB1AC provides a measure of glycemic control over the lifespan of a red cell [120 days, little
affected by day-day variations]
Three underyling mechanisms
Formation of advanced glycation end products [AGEs] through nonenzymatic
glycosylation
Activation of intracellular protein kinase C [PKC]
Accumulation of intracellular sorbitol
Pancreatic islets
Type 1 diabetes
o Islets are small and beta cells are greatly decreased in number or are absent
o Insulitis marked by lymphocytic infiltration is a highly specific early change
Type 1 Diabetes
o Amyloid replacement of islets is a characteristic finding with long-standing
type 2 DM islet amyloid deposition
Is thought to interfere either with the conversion of proinsulin to insulin
or with the sensing of insulin by beta-cells
Kidney
Thickening of glomerular basement membrane: is the earliest and most common renal
manifestation
Diffuse glomerulosclerosis, nodular glomerulosclerosis [Kimmelstiel-Wilson disease],
arteriolar lesions, and exudative lesions fibrin cap or capsular drop
Pyelonephritis is a frequent complication that may be compounded by renal papillary
necrosis
CVS
Incidence of atherosclerosis is greatly increased
Clinically significant atherosclerotic complications occur at a MUCH earlier age than in
nondiabetics
The incidence in women, both premenopausal and postmenopausal, is GREATLY
increased
Myocardial infarction and Peripheral Vascular Insufficiency [gangrene of lower
extremities]
Capillary Basement Membrane THICKENING occurs in multiple organs and is due to
nonenzymatic glycosylation of membrane protein
Eye
Cataract formation is common
Proliferative retinopathy [retinal exudates, edema, hemorrhages, and micro-aneurysms
of small vessels] can lead to blindness
Nervous System
Peripher Neuropathy and changes in brain and spinal cord
Liver
Fatty change is seen
Skin
XANTHOMAS: collection of lipid-laden macrophages in the dermis
Furnuncles and abscesses because of increased propensity to infection
Frequent fungal infectionespecially Candida
o Endocrine tumors [islet cell tumors]
Insulinomabeta cell tumor: most COMMON islet cell tumor
Characterized by greatly increased secretion of insulin
Can be benign or malignant
Circulating C-Peptide is increased in patients with insulinoma
In contrast C-peptide is NOT increased by exogenous insulin adminstration
Clinical characteristics= TRIAD
o 1. Episodic hyperinsulinemia and hypoglycemia
o 2. CNS dysfunction related to hypoglycemia [confusion, anxiety, stupor,
convulsions, coma]
o 3. Dramatic reversal of CNS abnormalities by glucose administration
Gastrinoma is often malignant and sometimes occurs in extrapancreatic sites
It results in gastrin HYPERSECRETION and HYPERGASTRINEMIA
Associated with Zollinger-Ellison syndromemarked gastric hypersecretion of HCl,
recurrent peptic ulcer disease and hypergastrinemia
Glucagonoma [Alpha cell tumor] rare
Results in secondary diabetes mellitus
Causes a characteristic skin lesion: necrolytic migratory erythema
VIPoma is rare
Marked by secretion of vasoactive intestinal peptide [VIP]
Associated with Water Diarrhea, Hypokalemia, and Achlorhydria [WHDA] Syndrome
Adrenal Glands
Cushing Syndrome [HYPERCORTISOLISM]
o Causes: increased circulating glucocorticoidsprimarily cortisol
Exogenous corticosteroid medication [most common]
Hyperproduction of ACTH by corticotrophs of the pituitary
Adrenal cortical adenoma or adrenal carcinoma [less common than adenoma]
Ectopic production of ACTH by nonpituitary tumors
Especially small cell carcinoma of lung****
Hypercortisolism is autonomous and cannot be suppressed by exogenous adrenal steroids
[dexamethasone suppression test]
The autonomous ACTH stimulation elimates the normal circadian rhythm of cortisol
production
o Clinical characteristics of CUSHING Syndrome
Central pattern of adipose tissue deposition becomes apparent: truncal obesity, moon facies,
and buffalo hump; often with relatively thin extremities caused by muscle wasting
Skin atrophy with easy bruising and purplish striae, especially over abdomen; Hirsutism
Muscle weakness, osteoporosis, amenorrhea, HTN, Hyperglycemia, and psychiatric dysfunction
o Morphological changes of Cushing syndrome in adrenal gland
Bilateral hyperplasia of adrenal Zona Fasciculata occurs when results from ACTH stimulation
Adrenal cortical atrophyseen when exogenous glucocorticoid medication is the cause
Adrenal cortical adenoma** or carcinoma
o ACTH determinations are useful diagnostic measures in determining the cause of hypercorticism
ACTH is
Increased in pituitary hypercorticism and in ectopic ACTH production [S.C.C of lung]
Low when hypercorticolism is of ADRENAL origin
Determing the cause depends on SERUM ACTH and measurement of urinary steroid excretion
after administration of Dexamethasone {Dexamethasone suppression test}
ACTH Cortisol Interpretation
Elevated Elevated; not suppressed by LOW
doeses, but suppressed by HIGH
doses [suppression of urinary steroid
secretion]
Pituitary Cushing Syndrome
[Cushing Disease]
Elevated Elevated; not suppressed by HIGH or
LOW doses [insensitive to exogenous
dexamethasone]
Ectopic ACTH secretion: ACTH-
secreting tumors [S.C.C of lung]
Low Elevated; not suppressed by HIGH or
LOW doses
Primary Cushing Syndrome
problem with adrenal gland itself

Hyperaldosteronism
o Primary Aldosteronism
The cause is primary hyperproduction of adrenal MINERALCORTICOIDS
Usually results from an aldosterone producing adrenocortical adenoma [Conn Syndrome]
It can also result from hyperplasia of Zonal glomerulosararely may be caused by
adrenocortical carcinoma
Clinical Characteristics:
Hypertension, sodium and water retention, and hypokalemiaoften with
hypokalemic alkalosis
Decreased serum RENIN occurs due to FEEDBACK inhibition of increased blood
pressure of rennin secretion.
o Secondary Aldosteronism
This condition is secondary to renal ischemia, renal tumors, and edema [cirrhosis, nephritic
syndrome, and cardiac failure]
The cause is stimulation of RAAS
Serum Renin is increased; in contrast to primary aldosteronism
Adrenal VIrilism [Adrenogenital System]
o Congenital ENZYME defects diminished cortisol production and compensatory increased ACTH with
resultant adrenal hyperplasia with androgenic steroid produ ction
21-HYDROXYLASE DEFICIENCY!!!
Most common, in its most severe salt-wasting form results in SALT losss and
HYPOTENSION
11-Hydroxylase Deficiencymuch less common
results in SALT retention and hypertension
o Can also be caused by tumors of the adrenal cortex
o Clinical charcateristics: Virilism in females and precocious puberty in males
Adrenocortical InsufficiencyHypofunction
o Primary adrenal disease [primary hypoadrenalism]
o Decreased stimulation of adrenal glands due to deficiency of ACTH secondary to hypothalamic or
pituitary dysfunction [secondary hypoadrenalism]
o Deficiency of glucocorticoids [primary cortisol], often with associated mineralcorticoid deficiency
characteristic
Chronic Adrenocortical InsufficiencyAddison Disease
o The most commonly due to idiopathic adrenal atrophyautoimmune adrenalitis
o It can also be caused by TB, AIDS, and metastatic cancers
o Characteristics
Hypotension
Increased pigmentation of skin
Decreased serum sodium, chloride, glucose, and bicarbonae
Increased Potassium
Waterhouse-Friderischen Syndrome
o Massive bilateral adrenal hemorrhage with rapidly developing adrenocortical insufficiency due to
hemorrhagic necrosis of the adrenal cortex
o Often associated with Disseminated Intravascular Coagulation
o Overwhelming bacterial infectionespecially Neisseria meningitides septicemia [meningococcemia]
Tumors of Adrenal Medulla
o Pheochromocytoma
Derived from chromaffin cells of the adrenal medulla; paragangliomaif it is derived from
extra-adrenal chromaffin cells
Most often benign
10% malignant
HTN results from hyperproduction of catecholamines [epinephrine and norepinephrine]
HTN= paroxysmal and surgically correctable
Increased urinary excretion of catecholamines and their metabolites [metanephrine and
vanillymandelic acid]**Characteristic**
Can be part of MEN-2
Can be associated with Neurofribomatosis or with von Hippel-Lindau
Multiple Endocrine Neoplasia [MEN] Syndromes
o MEN-1 [Wermer Syndrome]
Includes hyperplasias or tumors of the pituitary, parathyroid, or pancreatic islets [3 Ps]
In addition may include hyperplasia/tumors of thyroid or adrenal cortex
It is linked to mutations in the MEN 1 gene
May manifest its pancreatic component by Zollinger-Ellison syndrome, hyperinsulinism, or
pancreatic cholera
o MEN 2A- Sipple Syndrome
Includes pheochromocytoma, medullary carcinoma of the thyroid, and hyperparathyroidism
due to hyperplasia/tumor
Linked to mutations in the RET oncogene.
When a diagnosis of pheochromocytoma is madethe finding CHARACTERISTIC RET mutations
would justify prophylactic thyroidectomy
o MEN 2B
Includes pheochromocytoma, medullary carcinoma, and multiple mucocutaneous neurons or
ganglioneuromas
No hyperparathyroidism
A single amino acid change in RET-!!