Flashcards in CH15 - Endocrine Pathology Deck (276):
What is the endocrine system?
Group of glands that maintain body homeostasis
How does the endocrine system function?
by release of hormones that travel via blood to distant organs
In the endocrine system, what controls hormone release?
Feedback mechanisms control hormone release.
What is pituitary adenoma?
Benign tumor of anterior pituitary celts
Is the pituitary adenoma functional or nonfunctional?
May be functional (hormone-producing) or nonfunctional (silent)
What do nonfunctional pituitary adenoma tumors often present with?
mass effect resulting in bitemporal hemianopsia, hypopituitarism, headache
How does bitemporal hemianopsia occur in nonfunctional pituitary adenoma?
Its due to compression of the optic chiasm
How does hypopituitarism occur in nonfunctional pituitary adenoma?
due to compression of normal pituitary tissue
What do functional pituitary adenoma tumors present with?
Features are based on the type of hormone produced.
What does Prolactinoma presents as?
galactorrhea and amenorrhea (females) or as decreased libido and headache (males)
What is the most common type of pituitary adenoma?
What is the treatment of prolactinoma?
Treatment is dopamine agonists (eg bromocriptine or cabergoline) to suppress prolactin production (shrinks tumor) or surgery for larger lesions.
What is seen in growth hormone cell adenoma?
Gigantism in children, acromegaly in adults, diabetes mellitus
What is seen in growth hormone cell adenoma in children?
Gigantism in children; increased linear bone growth (epiphyses are not fused)
What is seen in growth hormone cell adenoma in adults?
Acromegaly in adults;1) Enlarged bones of hands, feet, and jaw 2) Growth of visceral organs leading to dysfunction (e.g., cardiac failure) 3) Enlarged tongue
Why is secondary diabetes mellitus often present in growth hormone cell adenoma?
GH induces liver gluconeogenesis
How is growth hormone cell adenoma diagnosed?
by elevated GH and insulin growth factor-1 (IGF-1) levels along with lack of GH suppression by oral glucose
What is the treatment for growth hormone cell adenoma?
It is octreotide (somatostatin analog that suppresses GH release), GH receptor antagonists, or surgery.
What is seen in ACTH cell pituitary adenomas?
they secrete ACTH leading to Cushing syndrome
What pituitary adenoma tumors occur rarely?
TSH cell, LH-producing, and FSH-producing adenomas occur, but are rare
What is hypopituitarism?
Insufficient production of hormones by the anterior pituitary gland
When do symptoms for hypopituitarism arise?
when > 75% of the pituitary parenchyma is lost
What are the causes for hypopituitarism?
1) Pituitary adenomas (adults) or craniopharyngioma (children) 2) Sheehan syndrome 3) Empty sella syndrome
What is a cause for hypopituitarism in children?
What is a cause for hypopituitarism in adults?
What are pituitary adenomas (adults) or craniopharyngioma (children) resulting in hypopituitarism due to?
mass effect or pituitary apoplexy (bleeding into an adenoma)
In hypopituitarism, what is sheehan syndrome?
pregnancy-related infarction of the pituitary gland
In Sheehan syndrome, what happens?
The gland doubles in size during pregnancy, but blood supply does not increase significantly; blood loss during parturition precipitates infarction.
What does Sheehan syndrome present as?
poor lactation, loss of pubic hair, and fatigue
What is empty sella syndrome?
It?s a congenital defect of the sella where herniation of the arachnoid and CSF into the sella compresses and destroys the pituitary gland, which is absent (empty sella) on imaging.
What hormones are the hormones of the posterior pituitary?
Antidiuretic hormone (ADH) and oxytocin are made in the hypothalamus and then transported via axons to the posterior pituitary for release.
On what does ADH act?
on the distal tubules and collecting ducts of the kidney to promote free water retention
What does oxytocin mediate?
uterine contraction during labor and release of breast milk (let-down) in lactating mothers
What is central diabetes insipidus?
What is central diabetes insipidus due to?
hypothalamic or posterior pituitary pathology (e.g., tumor, trauma, infection, or inflammation)
What are the clinical features for central diabetes insipidus based on?
loss of free water
What are the clinical features for central diabetes insipidus?
1. Polyuria and polydipsia with risk of life-threatening dehydration 2. Hypernatremia and high serum osmolality 3. Low urine osmolality and specific gravity
What is useful for the diagnosis of central diabetes insipidus?
Water deprivation test fails to increase urine osmolality (useful for diagnosis),
What is the treatment for central diabetes insipidus?
desmopressin (ADH analog)
What is nephrogenic diabetes insipidus?
Impaired renal response to ADH
What is nephrogenis diabetes insipidus due to?
inherited mutations or drugs (e.g lithium and demeclocycline)
What are the clinical features for nephrogenic diabetes insipidus?
They are similar to central diabetes insipidus, but there is no response to desmopressin
What is SIADH?
Syndrome of inappropriate ADH secretion
What is the result of SIADH?
Excessive ADH secretion
What is SIADH most often due to?
ectopic production (e.g., small cell carcinoma of the lung);
What are some other causes (beside ectopic production) for SIADH?
include CNS trauma, pulmonary infection, and drugs (eg cyclophosphamide)
What are the clinical features for SIADH based on?
retention of free water
What are the clinical features for SIADH?
1. Hyponatremia and low serum osmolality 2. Mental status changes and seizures?Hyponatremia leads to neuronal swelling and cerebral edema.
In SIADH, why are there mental status changes and seizures?
Since hyponatremia leads to neuronal swelling and cerebral edema
What is the treatment for SIADH?
it is free water restriction or demeclocycline
What is a thyroglossal duct cyst?
cystic dilation of thyroglossal duct remnant
How does the thyroid develop?
It develops at the base of tongue and then travels along the thyroglossal duct to the anterior neck. Thyroglossal duct normally involutes; a persistent duct, however, may undergo cystic dilation,
How does a thyroglossal duct cyst present?
Presents as an anterior neck mass
What is a lingual thyroid?
Its persistence of thyroid tissue at the base of the tongue
How does a lingual thyroid present?
as a base of tongue mass
What is hyperthyroidism?
It is increased levels of circulating thyroid hormone
What is the effect of hyperthyroidism?
It increases the basal metabolic rate (due to increased synthesis of Na-K ATPase) and Increases sympathetic nervous system activity (due to increased expression of beta-adrenergic receptors
What are the clinical features for hyperthyroidism?
1. Weight loss despite increased appetite 2. Heat intolerance and sweating 3. Tachycardia with increased cardiac output 4. Arrhythmia (e.g., atrial fibrillation), especially in the elderly 5. Tremor, anxiety, insomnia, and heightened emotions 6. Staring gaze with lid lag 7. Diarrhea with malabsorption 8. Oligomenorrhea 9. Bone resorption with hypercalcemia (risk for osteoporosis) 10. Decreased muscle mass with weakness 11. Hypocholesterolemia 12. Hyperglycemia (due to gluconeogenesis and glycogenosis)
What is graves disease?
Autoantibody (IgG) that stimulates TSH receptor (type II hypersensitivity)
What does Graves disease lead to?
increased synthesis and release of thyroid hormone
What is the most common cause of hyperthyroidism?
In whom does Graves disease classically occur?
in women of childbearing age (20-40 years)
What are the clinical features of Graves disease?
1. Hyperthyroidism 2. Diffuse goiter 3. Exophthalmos and pretibial myxedema
In Graves disease why is there diffuse goiter?
constant TSH stimulation leading to thyroid hyperplasia and hypertrophy
In Graves disease, what happens in exophthalmos and pretibial myxedema?
1) fibroblasts behind the orbit and overlying the shin express the TSH receptor. 2) TSH activation results in glycosaminoglycan (chondroitin sulfate and hyaluronic acid) buildup, inflammation, fibrosis, and edema leading to exophthalmos and pretibial myxedema.
In Graves disease, what is seen on histology?
Irregular follicles with scalloped colloid and chronic inflammation are seen on histology
What are the laboratory findings for Graves disease?
1) Increase in total and free T4, decreased TSH 2) Hypocholesterolemia 3) Increased serum glucose
In Graves disease, why is there decreased TSH?
free T4 down regulates TRH receptors in the anterior pituitary to decrease TSH release
What is the treatment for Graves disease?
it involves beta-blockers, thioamide, and radioiodine ablation.
What is a complication of Graves disease?
Thyroid storm is a potentially fatal complication
What is thyroid storm due to?
Due to elevated catecholamines and massive hormone excess, usually in response to stress (e.g., surgery or childbirth)
What dose thyroid storm present as?
arrhythmia, hyperthermia, and vomiting with hypovolemic shock
What is the treatment for thyroid storm?
It is propylthiouracil (PTU), beta-blockers, and steroids
How does PTU treat thyroid storm?
it inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis, as well as peripheral conversion of T4 to T3
What is a multinodular goiter?
Enlarged thyroid gland with multiple nodules
What is a multinodular goiter due to?
relative iodine deficiency
Are multinodular goiters toxic or nontoxic?
Usually nontoxic (euthyroid), rarely, regions become TSH-independent leading to increased release and hyperthyroidism - toxic goiter
What is hypothyroidism?
Cretinism and myxedema
What is cretinism?
Hypothyroidism in neonates and infants
What is cretinism characterized by?
mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, and umbilical hernia
Why does hypothyroidism result in cretinism?
Thyroid hormone is required for normal brain and skeletal development.
What are the causes for cretinism?
Causes include maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter, and iodine deficiency.
What is dyshormonogenetic goiter due to?
its a congenital defect in thyroid hormone production; most commonly involves thyroid peroxidase
What is myxedema?
hypothyroidism in older children or adults
What are the clinical features for myxedema based on?
Its based on decreased basal metabolic rate and decreased sympathetic nervous system activity
What is myxedema?
accumulation of glycosaminoglycans in the skin and soft tissue;
What does myxedema result in?
1) a deepening of voice and large tongue, 2) Weight gain despite normal appetite, 3) slowing of mental activity, 4) Muscle weakness, 5) Cold intolerance with decreased sweating, 6) Bradycardia with decreased cardiac output, 7) leading to shortness of breath and fatigue 8) Oligomenorrhea 9) Hypercholesterolemia 10) Constipation
What are the most common causes for myxedema?
iodine deficiency and Hashimoto thyroiditis;
What are some other causes for myxedema aside from iodine deficiency and Hashimoto thyroiditis?
drugs (e.g., lithium) and surgical removal or radioablation of the thyroid
What is involved in thyroiditis?
Hashimoto thyroiditis, subacute granulomatous (De Quervian) thyroiditis and reidel fibrosing thyroditis
What is hashimoto thyroiditis?
Autoimmune destruction of the thyroid gland; associated with HLA-DR5
What is the frequency of hashimoto thyroiditis as a cause of hypothyroidism?
Its the most common cause of hypothyroidism in regions where iodine levels are adequate
What are the clinical features for hashimoto thyroiditis?
1) Initially may present as hyperthyroidism (due to follicle damage) 2) Progresses to hypothyroidism; decreased T4 and increased TSH
What antibodies may be present in hashimoto thyroiditis, and what is it a sign of?
Antithyroglobulin and antimicrosomal antibodies are often present (sign of thyroid damage)
In hashimoto thyroiditis, what is seen on histology?
Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)
What are Hurthle cells?
eosinophilic metaplasia of cells that line follicles
In Hashimoto thyroiditis, what is there an increased risk for?
B-cell (marginal zone) lymphoma; presents as an enlarging thyroid gland late in disease course
What happens in subacute granulomatous (De Quervian) thyroiditis?
Granulomatous thyroiditis that follows a viral infection
How does subacute granulomatous (De Quervian) thyroiditis present?
as a tender thyroid with transient hyperthyroidism
What does subacute granulomatous (De Quervian) thyroiditis progress to?
Self-limited; does not progress to hypothyroidism
What is reidel fibrosing thyroditis?
chronic inflammation with extensive fibrosis of the thyroid gland
What does reidel fibrosing thyroditis present as?
hypothyroidism with a hard as wood, nontender thyroid gland
In reidel fibrosing thyroditis what might be involved in the fibrosis?
it may extend to involve local structures (eg. airway).
What does reidel fibrosing thyroditis clinically mimic?
anaplastic carcinoma, but patients are younger (40s), and malignant cells are absent
What are the thyroid neoplasias?
Follicular adenoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, anaplastic carcinoma
What does thyroid neoplasia usually present as?
a distinct, solitary nodule
Are thyroid nodules benign or malignant?
Thyroid nodules are more likely to be benign than malignant,
In thyroid neoplasia what studies are conducted?
I-131 radioactive uptake studies are useful to further characterize the nodules of thyroid neoplasia
What happens as a result of I-131 radioactive uptake studies?
Either increased or decreased uptake
In I-131 studies, what does an increased uptake indicate?
(hot nodule) which is seen in Graves disease or nodular goiter
In I-131 studies, what does decreased uptake indicate?
(cold nodule) which is seen in adenoma and carcinoma; often warrants biopsy
How is a biopsy of a cold nodule (thyroid) performed?
Biopsy is performed by line needle aspiration (FNA).
What is follicular adenoma?
Benign proliferation of follicles surrounded by a fibrous capsule
Is follicular adenoma functional or nonfunctional?
Usually nonfunctional; less commonly, may secrete thyroid hormone
What is papillary carcinoma?
Most common type of thyroid carcinoma (80% of cases)
What is a major risk factor for papillary carcinoma?
Exposure to ionizing radiation in childhood is a major risk factor.
What is papillary carcinoma comprised of?
papillae lined by cells with clear, Orphan Annie eye nuclei and nuclear grooves; papillae are often associated with psammoma bodies
What does papillary carcinoma often spread to?
cervical (neck) lymph nodes
What is the prognosis for papillary carcinoma?
It is excellent (10-year survival > 95%)
What is follicular carcinoma?
Malignant proliferation of follicles surrounded by a fibrous capsule with invasion through the capsule
How do you distinguish follicular carcinoma from follicular adenoma?
Invasion (follicular carcinoma) through the capsule helps do this
For follicular carcinoma, what must be examined?
The entire capsule must be examined microscopically, FNA only examines cells and not the capsule; hence, a distinction between follicular adenoma and follicular carcinoma cannot be made by FNA.
Does metastasis occur in follicular carcinoma?
Metastasis generally occurs hematogenously.
What is medullary carcinoma?
Malignant proliferation of parafollicular ? cells; comprises 5% of thyroid carcinomas
What are ? cells?
neuroendocrine cells that secrete calcitonin.
What does calcitonin do?
lowers serum calcium by increasing renal calcium excretion but is inactive at normal physiologic levels.
How might medullary carcinoma affect calcium levels?
High levels of calcitonin produced by tumor may lead to hypocalcemia.
What is the relation between calcitonin and tumor in medullary carcinoma?
Calcitonin often deposits within the tumor as amyloid
What does biopsy of the tumor in medullary carcinoma reveal?
sheets of malignant cells in an amyloid stroma
What are familial cases of medullary carcinoma often due to?
multiple endocrine neoplasia (MEN) 2A and 2B, which are associated with mutations in the RET oncogene
What does MEN 2 result in?
medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral mucosa (2B).
What does the detection of the R?? mutation mean?
it warrants prophylactic thyroidectomy
What is anaplastic carcinoma?
Its undifferentiated malignant tumor of the thyroid usually seen in elderly
What does anaplastic carcinoma lead to?
It often invades local structures, leading to dysphagia or respiratory compromise
What is the prognosis for anaplastic carcinoma?
What do the parathyroid glands do?
Chief cells regulate serum free (ionized) calcium via parathyroid hormone (PTH) secretion
What are the effects of PTH?
1. Increases bone osteoclast activity, releasing calcium and phosphate 2. Increases small bowel absorption of calcium and phosphate (indirectly by activating vitamin D) 3. Increases renal calcium reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule)
How does PTH increase small bowel absorption of calcium and phosphate?
It does it indirectly by activating vitamin D
How is PTH secretion limited?
Increased serum ionized calcium levels provide negative feedback to decrease PTH secretion.
What is primary hyperparathyroidism?
Excess PTH due to a disorder of the parathyroid gland itself
What is the most common cause of primary hyperthyroidism?
parathyroid adenoma (>80% of cases);
What are some other causes of primary hyperthyroidism?
sporadic parathyroid hyperplasia and parathyroid carcinoma
What is parathyroid adenoma?
it is a benign neoplasm, usually involving one gland,
What does parathyroid adenoma most often result in? How does it present?
asymptomatic hypercalcemia; however, may present with consequences of increased PTH and hypercalcemia such as; 1) nephrolithiasis 2) nephrocalcinosis 3) CNS disturbances (eg depression and seizures) 4) constipation, peptic ulcer disease, and acute pancreatitis 5) Osteitis fibrosa cystica
What is nephrolithiasis?
calcium oxalate stones
What is nephrocalcinosis?
metastatic calcification of renal tubules potentially leading to renal insufficiency and polyuria
What is Osteitis fibrosa cystica?
resorption of bone leading to fibrosis and cystic spaces
What are the laboratory findings for primary hyperparathyroidism?
include inc serum PTH, inc serum calcium, dec serum phosphate, inc urinary cAMP, and inc serum alkaline phosphatase.
What is the treatment for primary hyperparathyroidism?
it involves surgical removal of the affected gland
What is secondary hyperparathyroidism?
Excess production of PTH due to a disease process extrinsic to the parathyroid gland
What is the most common cause of secondary hyperparathyroidism?
Most common cause is chronic renal failure
How does chronic renal failure lead to secondary hyperparathyroidism?
1) decreased phosphate excretion 2) inc serum phosphate binds free calcium 3) dec free calcium stimulates all four parathyroid glands 4) inc PTH leads to bone resorption (contributing to renal osteodystrophy)
What are the lab findings for secondary hyperparathyroidism?
they include inc PTH, dec serum calcium, inc serum phosphate, and inc alkaline phosphatase.
What are the causes for hypoparathyroidism?
autoimmune damage to the parathyroids, surgical excision, and DiGeorge syndrome
How does hypoparathyroidism present?
It presents with symptoms related to low serum calcium such as; 1. Numbness and tingling (particularly circumorai) 2. Muscle spasms (tetany) may be elicited with filling of a blood pressure cuff (Trousseau sign) or tapping on the facial nerve (Chvostek sign)
What do the labs for hypoparathyroidism reveal?
dec PTH levels and dec serum calcium.
What is pseudohypoparathyroidism due to?
end-organ resistance to PTH
What do the labs for pseudohypoparathyroidism reveal?
hypocalcemia with inc PTH levels
What is the autosomal dominant form of pseudohypoparathyroidism associated with?
short stature and short 4th and 5th digits.
What iss the endocrine pancreas composed of?
It is composed of clusters of cells termed islets of Langerhans
In the islet of Langerhans what does a single islet consist of?
multiple cell types, each producing one type of hormone
What secretes insulin?
Insulin is secreted by beta cells
Where are beta cells located?
They lie in the center of the islets
What is insulin?
Major anabolic hormone
What does insulin do?
It up regulates insulin-dependent glucose transporter protein (GLUT4)
Where are the GLUT4 transporters that are up regulated by insulin?
Its on skeletal muscle and adipose tissue - glucose uptake by GLUT4 decreases serum glucose
What does increased glucose uptake by tissues lead to?
Increased glucose uptake by tissues leads to increased glycogen synthesis, protein synthesis, and lipogenesis,
What is glucagon secreted by?
What does glucagon do and how does it do this?
it opposes insulin in order to increase blood glucose levels (e.g., in states of fasting) via glycogenolysis and lipolysis.
What is type 1 diabetes mellitus?
Insulin deficiency leading to a metabolic disorder
What is type 1 diabetes mellitus characterized by?
What is type 1 diabetes mellitus due to?
autoimmune destruction of beta cells by T lymphocytes
What is the destruction of beta cells by T lymphocytes characterized by?
inflammation of islets
What is the destruction of beta cells by T lymphocytes associated with?
HLA-DR3 and HLA-DR4
In type 1 diabetes mellitus what may be seen years before clinical disease develops?
Autoantibodies against insulin are often present and are a sign of damage
When does Type 1 diabetes mellitus manifest?
in childhood with clinical features of insulin deficiency
What are the clinical features of type 1 diabetes mellitus?
1) High serum glucose 2) Weight loss, low muscle mass, and polyphagia 3) Polyuria, polydipsia, and glycosuria
Why is there hig serum glucose in type 1 diabetes mellitus?
The lack of insulin leads to decreased glucose uptake by fat and skeletal muscle
In type 1 diabetes mellitus why is there weight loss, low muscle mass, and polyphagia?
Unopposed glucagon leads to gluconeogenesis, glycogenosis and lipolysis, which further exacerbates hyperglycemia
In type 1 diabetes mellitus why is there polyuria, polydipsia, and glycosuria?
Hyperglycemia exceeds renal ability to resorb glucose; excess filtered glucose leads to osmotic diuresis
What is the treatment for type 1 diabetes mellitus?
It involves lifelong insulin
What is there a risk for in type 1 diabetes mellitus?
What is diabetic ketoacidosis characterized by?
excessive serum ketoacids
In type 1 diabetes mellitus, what does diabetic ketoacidosis often arises with?
stress (e.g., infection) where epinephrine stimulates glucagon secretion increasing lipolysis (along with gluconeogenesis and glycogenolysis),
How are ketones related to type 1 diabetes mellitus?
increased lipolysis leads to increased free fatty acids (FFAs) and the liver converts FFAs to ketone bodies (beta-hydroxybutyric acid and acetoacetic acid)
What are the clinical features for diabetic ketoacidosis?
It results in hyperglycemia (> 300 mg/dl.), anion gap metabolic acidosis, and hyperkalemia
What does diabetic ketoacidosis present with?
Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, and fruity smelling breath (due to acetone)
What is the treatment for diabetic ketoacidosis?
fluids (corrects dehydration from polyuria), insulin, and replacement of electrolytes (e.g., potassium)
What is type 2 diabetes mellitus?
End-organ insulin resistance leading to a metabolic disorder characterized by hyperglycemia
What is the most common type of diabetes?
Type 2 diabetes mellitus (90% of cases)
What is the frequency of type 2 diabetes mellitus?
It affects 5-10% of the US population and the incidence is rising
In whom does diabetes mellitus arise?
in middle-aged, obese adults
What does obesity lead to?
decreased numbers of insulin receptors
Is there a genetic component to type 2 diabetes mellitus?
Strong genetic predisposition exists.
What is the progression of type 2 diabetes mellitus?
The insulin levels are increased early in disease, but later, insulin deficiency develops due to beta cell exhaustion
For type 2 diabetes mellitus what does histology reveal?
amyloid deposition in the islets
What are the clinical features for type 2 diabetes mellitus?
it includes polyuria, polydipsia, and hyperglycemia, but disease is often clinically silent.
How is type 2 diabetes mellitus diagnosed?
It is made by measuring glucose levels (normal is 70-120 mg/dL) (1) Random glucose > 200 mg/dL (2) Fasting glucose > 126 mg/dL (3) Glucose tolerance test with a serum glucose level > 200 mg/dL two hours after glucose loading
What is the treatment for type 2 diabetes mellitus?
it involves weight loss (diet and exercise) initially; may require drug therapy to counter insulin resistance (e.g., sulfonylureas or metformin) or exogenous insulin after exhaustion of beta cells
In type 2 diabetes mellitus what is there a risk for?
Risk for hyperosmolar non-ketotic coma
What happens in a non-ketotic coma?
1. High glucose (> 500 mg/dL) leads to life-threatening diuresis with hypotension and coma. 2. Ketones are absent due to small amounts of circulating insulin.
What are the long term consequences of diabetes?
Nonenzymatic glycosylation (NEG) of the vascular basement membrane (BM)
As a consequence of diabetes what is the effect of NEG of large- and medium-sized vessels?
It leads to atherosclerosis and its resultant complications cardiovascular disease and peripheral vascular disease
What is the leading cause of death among diabetics?
What is the leading cause of nontraumatic amputations among diabetics?
Peripheral vascular disease in diabetics is the leading cause of nontraumatic amputations
As a consequence of diabetes what does NEG of small vessels (arterioles) lead to?
In NEG of the arterioles, what does involvement of renal arterioles lead to?
glomerulosclerosis, resulting in small, scarred kidneys with agranular surface
In NEG of the arterioles, what does preferential involvement of efferent arterioles lead to?
glomerular hyperfiltration injury with microalbuminuria that eventually progresses to nephrotic syndrome
What is the nephrotic syndrome characterized by resulting from NEG of the efferent arterioles?
Kimmelstiel-Wilson nodules in glomeruli
What does NEG of hemoglobin produce?
glycated hemoglobin (HbA1C), a marker of glycemic control.
What is osmotic damage as a consequence of diabetes?
1. Glucose freely enters into Schwann cells (which myelinate peripheral nerves), pericytes of retinal blood vessels, and the lens. 2. Aldose reductase converts glucose to sorbitol, resulting in osmotic damage.
What does osmotic damage lead to?
peripheral neuropathy, impotence, blindness, and cataracts; diabetes is the leading cause of blindness in the developed world.
What is the leading cause of blindness in the developed world?
What are pancreatic endocrine neoplasms?
Tumors of islet cells, insulinomas, gastrinomas, somatostatinomas and lipomas
What percentage of pancreatic endocrine neplasms are tumors of islet cells?
They account for < 5% of pancreatic neoplasms
Tumors of islet cells are often a component of what?
MEN 1 along with parathyroid hyperplasia and pituitary adenomas
What do insulinomas present as?
episodic hypoglycemia with mental status changes that are relieved by administration of glucose
How are insulinomas diagnosed?
Its diagnosed by decreased serum glucose levels (usually < 50 mg/dL), increased insulin, and increased C-peptide
What do gastrinomas present as?
treatment-resistant peptic ulcers (Zollingcr-Ellison syndrome); ulcers may be multiple and can extend into the jejunum.
What do somatostatinomas present as?
achlorhydria (due to inhibition of gastrin) and cholelithiasis with steatorrhea (due to inhibition of cholecystokinin).
In somatostatinomas what is achlorhydria due to?
inhibition of gastrin
In somatostatinomas what is steatorrhea due to?
Inhibition of cholecystokinin
What happens with vipomas?
they secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria.
What is the adrenal cortex composed of?
three layers that each secrete distinct hormones
What are the three layers of the adrenal cortex?
1) glomerulosa 2) Fasciculata 3) Reticularis
What does the glomerulosa of the adrenal cortex produce?
mineralocorticoids (e.g., aldosterone).
What does the fasciculate of the adrenal cortex produce?
glucocorticoids (e.g., Cortisol).
What does the reticularis of the adrenal gland produce?
sex steroids (e.g., testosterone).
What is hypercortisolism (cushing syndrome)?
What are the clinical features for hypercortisolism (cushing syndrome)?
1) Muscle weakness with thin extremities 2) Moon facies, buffalo bump, and truncal obesity 3) Abdominal striae 4) Hypertension 5) Osteoporosis 6) Immune suppression
In Cushing syndrome, why is there abdominal striae?
due to impaired synthesis of collagen with thinning of skin
What is abdominal straie?
Streaks or stripes on the skin
In Cushing syndrome why is there moon facies, buffalo hump and truncal obesity?
There is high insulin due to high glucose which increases storage of fat
In hypercortisolism (cushing syndrome) why is there muscle weakness with thin extremities?
cortisol breaks down muscle for gluconeogenesis
How is the diagnosis for Cushing Syndrome made?
by increased 24-hour urine cortisol levels
What are the causes for Cushing Syndrome?
1) exogenous corticosteroids 2) Primary adrenal adenoma, hyperplasia, or carcinoma 3) ACTH-secreting pituitary adenoma 4) Paraneoplastic ACTH secretion
How does exogenous corticosteroids lead to Cushing syndrome?
It leads to bilateral adrenal atrophy; steroids suppress ACTH secretion (negative feedback)
How does primary adrenal adenoma, hyperplasia, or carcinoma lead to Cushing syndrome?
It leads to atrophy of the uninvolved adrenal gland
How does ACTH-secreting pituitary adenoma lead to Cushings?
It leads to bilateral adrenal hyperplasia
How does paraneoplastic ACTH secretion (eg small cell carcinoma of the lung) leads to Cushings?
leads to bilateral adrenal hyperplasia
What is the effect of high-dose dexamethasone in Cushings?
(Cortisol analog) suppresses ACTH production by a pituitary adenoma (Cortisol levels decrease), but fails to suppress ectopic ACTH production by a small cell lung carcinoma (Cortisol levels remain high).
What does it mean if after high-dose dexamethasone there is a decrease in cortisol levels?
The dexamethasone suppressed ACTH production by a pituitary adenoma
What does it mean if after high-dose dexamethasone the cortisol levels remain high?
The dexamethasone failed to suppress ectopic ACTH production by a small cell lung carcinoma (Cortisol levels remain high)
What is Conn Syndrome?
Its hyperaldosteronism - excess aldosterone
How does Conn Syndrome present?
It presents as hypertension with hypernatremia, hypokalemia, and metabolic alkalosis
What is the effect of aldosterone?
it increases sodium absorption with secretion of potassium and hydrogen ions (distal tubules and collecting duct)
What does increased absorption of sodium lead to?
it expands plasma volume leading to hypertension
What is primary hyperaldosteronism due to?
it is most commonly due to an adrenal adenoma; sporadic adrenal hyperplasia and adrenal carcinoma are less common causes.
What is primary hyperaldosteronism characterized by?
high aldosterone and low renin (high blood pressure downregulates renin via negative feedback)
What is secondary hyperaldosteronism seen with?
activation of the renin-angiotensin system (e.g., renovascular hypertension or CHE).
What is secondary hyperaldosteronism characterized by?
high aldosterone and high renin
What is congenital adrenal hyperplasia?
excess sex steroids with hyperplasia of both adrenal glands
What is the most common cause of congenital adrenal hyperplasia?
Inherited 21-hydroxylase deficiency
What is 21-hydroxylase required for?
production of aldosterone and corticosteroids.
In congenital adrenal hyperplasia what is seen in enzyme deficiency?
steroidogenesis is predominantly shunted toward sex steroid production (which does not require 21 -hydroxylase)
In congenital adrenal hyperplasia, what is seen in a deficiency of cortisol?
it leads to increased ACTH secretion (lack of negative feedback), which results in bilateral adrenal hyperplasia.
What are the clinical features for congenital adrenal hyperplasia?
1) Salt wasting with hyponatremia, hyperkalemia, and hypovolemia due to lack of aldosterone. 2) Life-threatening hypotension due to lack of Cortisol. 3) Clitoral enlargement (females) or precocious puberty (males) due to excess androgens
What is adrenal insufficiency?
Lack of adrenal hormones
What might Acute adrenal insufficiency arise with?
What is acute adrenal insufficiency characterized by?
hemorrhagic necrosis of the adrenal glands classically due to DIC in young children with N meningitidis infection
How might acute adrenal insufficiency lead to death?
Lack of cortisol exacerbates hypotension, often leading to death
What is chronic insufficiency due to?
Addison disease which is due to progressive destruction of the adrenal glands.
What are the common causes for acute adrenal insufficiency?
It includes autoimmune destruction (most common cause in the West), TB (most common cause in the developing world), and metastatic carcinoma (e.g., arising from lung)
What are the clinical features for acute adrenal insufficiency?
include hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (increased ACTH by-products stimulate melanocytic production of pigment), vomiting, and diarrhea.
What is adrenal medulla composed of?
neural crest-derived chromaffin cells
What is the main physiologic source of catecholamines?
(epinephrine and norepinephrine) mainly are from the adrenal medulla
What is pheochromocytoma?
Tumor of chromaffin cells
What are the clinical features for pheochromocytoma due to?
increased serum catecholamines.
What are the clinical features for pheochromocytoma?
Episodic hypertension, headache, palpitations, tachycardia, and sweating
How is pheochromocytoma diagnosed?
by increased serum metanephrines and increased 24-hour urine metanephrines and vanillylmandelic acid
What is the treatment for pheochromocytoma?
it is surgical excision.
In pheochromocytoma what happens with manipulation of the tumor?
Catecholamines may leak into the bloodstream upon manipulation of the tumor.
What is used to treat pheochromocytoma?
Phenoxybenzamine (irreversible a-blocker) is administered perioperatively to prevent a hypertensive crisis.
What rule does pheochromocytoma often follow?
Often follows the rule of 10s: 10% bilateral, 10% familial, 10% malignant, and 10% located outside of the adrenal medulla (e.g., bladder wall or organ of Zuckerkand at the inferior mesenteric artery root)