Pathology-Endocrine Pathology Flashcards
1
Q
A 43 year old woman comes to see the neurologist with recurrent headaches and bitemporal hemianopsia. Labs reveal decreased levels of FSH, LH, ACTH, TSH, PRL, and GH. What is causing her condition?
A
She has a benign non function (because it is not producing hormones) anterior pituitary adenoma. She has bitemporal hemianopsia because the lateral visual fields hit the nasal side of the retina and cross over the optic chiasm, which is being compressed by the adenoma.
2
Q
A 43 year old woman comes to see you in clinic with galactorrhea and amenorrhea. What type of pituitary tumor could be causing her condition?
A
She has a prolactinoma, the most common anterior pituitary adenoma. Prolactin inhibits GnRH synthesis and release, which prevents release of FSH and LH, which results in amenorrhea in females. Prolactin also stimulates milk production.
3
Q
A 43 year old male presents with decreased libido and headaches. He is diagnosed with a prolactinoma. Why does he not have galactorrhea?
A
Increased prolactin inhibits production and secretion of GnRH, inhibiting FSH and LH, decreasing his libido. He does not get galactorrhea because males only have a terminal duct and no lobular units in breast tissue. He also has a headache from mass effect.
4
Q
A 43 year old male presents with decreased libido and headaches. He is diagnosed with a prolactinoma. How do you treat him?
A
Surgery or dopamine agonist (dopamine from the hypothalamus inhibits prolactin secretion, bromocriptine)
5
Q
A mother with enlarged hands, feet, tongue and jaw brings in her 8 foot tall 20 year old son. What is the most common cause of death in these patients? What secondary condition is highly associated with their condition?
A
Growth hormone adenomas can cause enlargement of the heart and death from cardiac failure. The mother has acromegaly (adenoma during adulthood) and her son has gigantism (adenoma during childhood). Since GH suppressed insulin release, they often suffer from secondary diabetes.
6
Q
A mother with enlarged hands, feet, tongue and jaw brings in her 8 foot tall 20 year old son. You suspect a growth hormone adenoma. How do you confirm the diagnosis?
A
Elevated GH and IGF-1 (production is increased by increased GH action on hepatocytes) in the serum. Also, giving oral glucose does not suppress GH levels.
7
Q
What is the mediator of tissue growth?
A
IGF-1 from hepatocytes. GH stimulates increased levels of IGF-1.
8
Q
A mother with enlarged hands, feet, tongue and jaw brings in her 8 foot tall 20 year old son. You suspect a growth hormone adenoma. How do you treat them?
A
Octreotide (somatostatin that blocks ant. pit. response to hypothalamic GHRH), surgery or GH receptor antagonists.
9
Q
Pituitary adenoma that causes Cushing’s syndrome?
A
ACTH cell adenomas that secrete ACTH
10
Q
Rare types of functional pituitary adenomas
A
TSH, LH and FSH-producing adenomas.
11
Q
How long does it take for hypopituitarism to manifest?
A
Usually not until 75% of pituitary parenchyma is lost.
12
Q
A 30 year old woman gives birth to a newborn baby. She comes in a few days later complaining that she is having a difficult time producing breast milk for the baby. On physical exam you note decreased pubic hair and when reviewing her history you note that there was significant blood loss on delivery. What is likely causing her condition?
A
Sheehan syndrome. During pregnancy the increased hormone levels cause the pituitary to double in size, with little change in blood supply. If significant blood loss occurs during labor, parts of the pituitary can infarct. She has trouble lactating due to decreased production of prolactin. She has loss of pubic hair because production is dependent on androgens, which is dependent on LH, which comes from the anterior pituitary.
13
Q
A child presents with various symptoms consistent with hypopituitarism. Brain CT shows and empty sella turcica. What can cause this?
A
Damage to the pituitary that causes it to shrink and herniation of arachnoid or dura mater that pushes the pituitary up and out of the sella turcica.
14
Q
2 types of tumors that can cause hypopituitarism
A
Pituitary adenoma and craniopharyngioma (from Rathke’s pouch).
15
Q
A patient comes to the ED after a car accident and is suffering from central diabetes insipidus due to pituitary damage. What symptoms would you expect him to present with?
A
Damage to either the hypothalamus or posterior pituitary causes decreased ADH release. This results in polyuria, polydipsia, hypernatremia, increased serum osmolality, low urine osmolality and low specific gravity because there is no Na or H2O reabsorption going on in the nephron.
16
Q
A patient comes to the ED after a car accident and is suffering from central diabetes insipidus due to pituitary damage. How do you confirm your diagnosis? How do you treat?
A
Water deprivation test fails to increase urine osmolality. You treat him with desmopressin (an ADH analogue)
17
Q
A patient comes to the ED with polyuria, polydipsia, hypernatremia and decreased urine osmolality. He fails to respond to the water deprivation test and to desmopressin. What could be causing his condition?
A
Since he didn’t respond to desmopressin, you know it is nephrogenic diabetes insipidus. Impaired renal response to ADH can be caused by inherited mutations or drugs (lithium or demeclocycline)
18
Q
A patient presents after a seizure with hyponatremia and low serum osmolality. His condition is improved with free water restriction and demeclocycline. What is causing his condition?
A
SIADH. Increased ADH levels increases Na and H2O retention. He had a seizure because hyponatremia causes swelling of the nerves and cerebral edema. Water restriction will decrease the blood volume and demeclocycline will decrease renal response to ADH
19
Q
A patient presents after a seizure with hyponatremia and low serum osmolality. His condition is improved with free water restriction and demeclocycline. What are common etiologies of this condition?
A
Ectopic ADH production (small cell lung cancer), CNS trauma, pulmonary pathology/infection and drugs (cyclophosphamide) can all cause SIADH.
20
Q
Cysts of thyroid tissue in the anterior midline of the neck
A
Thyroglossal duct cyst
21
Q
Persistence of thyroid tissue at base of tongue
A
Lingual thyroid
22
Q
Why do people with hyperthyroidism lose weight?
A
Increased levels of thyroid hormone increases synthesis of Na/K ATPase and increases energy requirements.
23
Q
Why do people with hyperthyroidism have increased pulse pressure?
A
Increased levels of thyroid hormone increased expression of beta-1 adrenergic receptors, activating the sympathetic nervous system and increasing the systolic blood pressure.
24
Q
Signs and symptoms of hyperthyroidism
A
“Thyroidism” Tremor, HR increase, Yawning (fatigue), Restlessness, Oligomenorrhea, Intolerance to heat, Diarrhea, Irratibility, Sweating, Muscle wasting & weight loss, Exopthalmos
25
What happens to blood calcium, cholesterol and glucose levels in people with hyperthyroidism?
Hypercalcemia from increased bond resorption, hypocholesterolemia and hyperglycemia (from activation of gluconeogenesis and glycogenolysis by thyroid hormone).
26
What is the most common cause of hyperthyroidism, which occurs in women of childbearing age?
Graves disease. IgG autoantibodies stimulate TSH receptors and increases synthesis and release of thyroid hormone.
27
A 30 year old woman presents with a diffuse goiter, exopthalmos and pretibial myxedema. Labs reveal elevated IgG antibodies. What is causing her exopthalmos and pretibial myxedema?
The IgG autoantibodies stimulate TSH receptors on fibroblasts behind the eye and on the shin. This causes them to increase production of glycosaminoglycans, which will give the tissue on the shin a “dough-like” consistency. This will also cause the eyes to be pushed forward.
28
This is a section from a patient who has a diffuse goiter from Graves disease. What would you expect histological examination of this tissue to look like?
TSH stimulation causes enlargement of the follicles due to increased thyroid hormone production. It also causes scalloping around the follicle due to increase thyroid hormone release from the colloid.
29
A 30 year old woman presents with a diffuse goiter, exopthalmos and pretibial myxedema. What labs would you expect to find?
Increased total and free T4, decreased TSH (T4 negative feedback down regulates TRH receptors on anterior pituitary), hypocholesterolemia and increased serum glucose.
30
A 30 year old woman presents with a diffuse goiter, exopthalmos and pretibial myxedema. How do you treat her?
Beta-blockers to decrease sympathetic activation, thioamides (blocks peroxidase conversion of iodide to iodine, addition of DIT/MIT to thyroglobulin and production of T3 & T4 thyroglobulin) and radio iodine ablation.
31
After delivering a baby C-section, the mother has an arrhythmia, hyperthermia, vomiting and hypovolemic shock. No sign of hemorrhage is presents. Labs reveal high levels of T4. What is causing her condition and how do you treat her?
This is thyroid storm caused by elevated catecholamines and massive hormone excess due to a stress like childbirth or surgery, which she had both. You would treat her with PTU (inhibits peripheral conversion of T4-\>T3), beta-blockers and steroids.
32
What things do thioamides inhibit?
Oxidation, organification and coupling
33
A patient presents with a multi nodular goiter. What is the most common cause of this and what is the prognosis?
Most common cause is iodine deficiency. Typically it is non-toxic but rarely regions of the goiter can become TSH-independent (toxic goiter)
34
Clinical features of hypothyroidism in neonates and infants
Cretinism: mental retardation, short stature w/skeletal abnormalities, coarse facial features, enlarged tongue and umbilical hernia.
35
A child is born with mental retardation, short stature, skeletal abnormalities, coarse facial features, enlarged tongue and an umbilical hernia. What are possible etiologies of this condition?
This child has cretinism. This can be caused by maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter and iodine deficiency.
36
Most common enzyme disorder that causes cretinism in the neonate?
Thyroid peroxidase enzyme
37
Clinical features of hypothyroidism in older children and adults.
Myxedema, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating.
38
Why do people with hypothyroidism sometimes present with a swollen tongue and deeper voice?
Low thyroid activity causes increased TSH secretion by the anterior pituitary. This also stimulates TSH receptors on fibroblasts in the tongue and larynx, causing tissue to grow.
39
Why do people gain weight w/normal appetite and hypothyroidism?
Decreased sympathetic activity.
40
A patient presents with a deepened voice, swollen tongue, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating. What are possible etiologies of his condition?
This patient has hypothyroidism. Causes include iodine deficiency, Hashimoto thyroiditis (autoimmune destruction of thyroid gland), drugs (lithium), surgical removal of or radio ablation of the thyroid.
41
A patient presents with a deepened voice, swollen tongue, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating. He is in the US, what is the most likely cause of his condition?
Hashimoto thyroiditis, associated with HLA-DR5. This is the most common cause of hypothyroidism where iodine levels are sufficient.
42
A patient presents with a deepened voice, swollen tongue, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating. He is in the US. What labs would you expect to see in this patient?
Initial hyperthyroidism that progresses to hypothyroidism (leakage of already produced thyroid hormone from destruction of thyroid follicles), decreased T4, increased TSH and antithyroglobulin and antimicrosomal antibodies.
43
What causes increased production of TSH by the anterior pituitary when people have Hashimoto’s thyroiditis?
Decreased levels of T4 increases expression of TRH receptors on the anterior pituitary, allowing for increased stimulation from the hypothalamus and increased TSH production by the anterior pituitary.
44
What would you expect to see histologically in a patient with Hashimoto’s thyroiditis?
Abundant chronic inflammatory cells with germinal centers. Also Hurthle cells form (pink cells around follicles)
45
A patient presents with an enlarging thyroid gland who was diagnosed with Hashimoto’s thyroiditis. What cancer is he at increased risk for?
B-cell lymphoma. Germinal centers form in the thyroid, then marginal zones form where lymphoma develops.
46
A 30 year old woman presents with transient heat intolerance, anxiety and tremors after a viral infection. Physical exam reveals a tender thyroid. What is causing her condition?
Subacute (deQuervain) Granulomatous Thyroiditis. Granulomatous inflammation occurs in the thyroid after a viral infection, this condition does not progress to hypothyroidism and is self-limiting.
47
A 30 year old woman presents with wheezing, a 10 pound weight gain, fatigue, cold intolerance and muscle weakness. Physical exam reveals a thyroid gland that is hard as wood and contender. What is causing her condition?
Reidel Fibrosing thyroiditis. Chronic inflammation of the thyroid and extensive fibrosis in the thyroid cause the hard thyroid and hypothyroidism. Remember that fibrosis may extend to local structures (airway wheezing).
48
How do you differentiate anaplastic carcinoma of the thyroid from Reidel Fibrosing thyroiditis?
Carcinoma is a disease of older people that invades local structures like the airway. Reidel is a disease of younger people that invades local structures like the airway. Other than this, history will be similar.
49
When do you decide to biopsy a thyroid nodule?
Do an I-131 uptake scan. If there is uptake then it is a nodular goiter and does not need biopsy. If it is a “cold spot”, then it could be an adenoma (most likely) or a carcinoma and warrants a fine-needle aspiration (FNA) biopsy.
50
A patient presents with a thyroid nodule. I-131 uptake scan shows a cold spot. FNA is shown below. What is your diagnosis?
Follicular adenoma. Note the lower area with a dense pink capsule and proliferation follicle-like spaces.
51
4 types of thyroid carcinoma
Papillary (most common type), follicular, medullary and anaplastic.
52
Exposure to ionizing radiation in childhood puts you at risk for which type of thyroid carcinoma? What is the prognosis?
Papillary. Although this thyme often spreads to the cervical lymph nodes, prognosis is excellent.
53
Histologic features of papillary carcinoma
Orphan Annie eye nuclei, presence of nuclear grooves, formation of papilla and sometimes circular calcifications in papillae (psammoma bodies)
54
What differentiates a follicular adenoma from a follicular carcinoma? How do we obtain this differentiation?
Follicular carcinoma as a malignant proliferation of follicles surrounded by a fibrous capsule through which the malignant cells have invaded. You cannot see this through FNA, you must do an actual biopsy where you can analyze the tumor capsule.
55
What is the prognosis for a patient with a follicular carcinoma?
The malignant cells tend to metastasize hematogenously.
56
4 carcinomas that like to metastasize to blood instead of lymph nodes?
RCC via renal vein, hepatocellular carcinoma via hepatic vein, follicular carcinoma and choriocarcinoma.
57
A patient presents with hypocalcemia and a lump in her thyroid. What is most likely causing her condition and what would you expect to see histologically?
Medullary carcinoma, a malignant proliferation of parafollicular C cells that secrete high levels of calcitonin, causing hypocalcemia. On FNA you would see malignant cells in an amyloid stroma (high levels of calcitonin deposit as amyloid).
58
A patient presents with hypocalcemia and a lump in her thyroid. After FNA you diagnose him with medullary carcinoma of the thyroid. What are etiologies of this condition?
MEN 2A (medullary thyroid carcinoma, pheochromocytoma and parathyroid adenoma) MEN 2B (medullary thyroid carcinoma, pheochromocytoma and ganglioneuromas of the oral mucosa) and mutations in RET oncogene.
59
What do you do if a patient comes to see you and says her brother was just diagnosed with medullary carcinoma of the thyroid?
Test for mutation of the RET oncogene. If it is positive, then she should have her thyroid removed prophylactically to prevent complications.
60
An 80 year old man presents with dysphagia and dyspnea. Physical exam reveals a lump on his thyroid. What is likely causing his condition?
Anaplastic carcinoma of the thyroid commonly occurs in the elderly. It is an undifferentiated malignant tumor that often invades local structures and has a poor prognosis.
61
What would you expect to see on FNA in a patient with anaplastic carcinoma of the thyroid?
Highly malignant cells from FNA of the thyroid.
62
3 forms of serum Ca
Ionized, protein-bound and phosphate-bound
63
Actions of PTH in response to low serum free Ca
Increased osteoclast activity via osteoblast activation and release of RANKL, increased gut absorption of Ca and PO4 via Vitamin D activation and increased renal absorption of Ca and secretion of PO4.
64
Why is it imperative that PTH increases renal excretion of PO4?
If it didn’t the level of ionized Ca would not increase and the level of phosphate-bound Ca would increase
65
Most common cause of primary hyperparathyroidism? Other causes?
Most common = parathyroid adenoma. Other causes = sporadic hyperplasia and parathyroid carcinoma.
66
A 37 year old man is found to have asymptomatic hypercalcemia. Further testing reveals elevated serum PTH and a benign parathyroid adenoma. What symptoms might this patient develop as PTH levels continue to increase?
Nephrolithiasis (Ca-oxalate stone), nephrocalcinosis (Ca deposition in renal tubules causes renal insufficiency and polyuria), CNS disturbances (depression & seizures), constipation, peptic ulcer disease, acute pancreatitis (hypercalcemia activates pancreatic enzymes) and osteitis fibrosa cystica.
67
What causes this condition in the renal biopsy shown below from a patient with primary hyperparathyroidism?
Metastatic calcification from hypercalcemia causing nephrocalcinosis.
68
What causes this condition in the bone biopsy shown below in a patient with primary hyperparathyroidism?
Increased activation of osteoclasts causes fibrosis of the bone and osteitis fibrosa cystica.
69
Lab findings in patients with primary hyperparathyroidism?
Increased serum PTH, serum Ca, urinary cAMP and serum Alk Phos. Decreased serum phosphate.
70
Why do people with primary hyperparathyroidism have an increased urinary cAMP?
In the kidney, PTH binds a Gs-protein receptor on tubular cells. Adenylyl cyclase is activated -\> cAMP is produced to increase Ca uptake and PO4 excretion. This cAMP is then excreted in high levels in the urine from high PTH stimulation.
71
Why do people with primary hyperparathyroidism have an increased serum alkaline phosphatase?
PTH activates osteoblasts 1st. Osteoblasts use the enzyme alkaline phosphatase to make an alkaline environment in which calcium can be deposited.
72
How do you treat primary hyperparathyroidism?
Surgical removal of the affected gland.
73
Most common cause for secondary hyperparathyroidism?
Chronic renal failure. PO4 excretion decreases, serum PO4 levels rise and bind up free calcium. This decreases ionized Ca stimulation to the parathyroid glands and increases PTH and bone resorption.
74
Lab findings in patients with secondary hyperparathyroidism?
Increased serum PTH, serum phosphate and alkaline phosphate. Decreased serum calcium.
75
3 main causes of hypoparathyroidism
Autoimmune destruction, surgical removal and DiGeorge syndrome (failure of 3rd and 4th pharyngeal pouches to develop)
76
A patient presents with numbness and tingling around the lips. Physical exam reveals Trousseau’s sign (hand spasms w/BP cuff) and Chvostek sign (facial spasm when tapping facial nerve). What is likely causing his condition?
Hypoparathyroidism with decreased serum PTH and serum Ca.
77
Causes of pseudohypoparathyroidism
End-organ resistance of Gs protein to PTH causes hypocalcemia with increased PTH levels. There is an autosomal dominant form associated with short stature and short 4th and 5th digits.
78
What is the basic composition of the endocrine pancreas?
Clusters of cells (islets of Langerhans) with multiple cell types in each islet that produce one type of hormone
79
Where are the insulin secreting cells located in the islets of Langerhans?
Beta cells are located in the center of the islets
80
What does insulin do?
Upregulates GLUT4 on skeletal and adipose tissue. Glucose enters these tissues, lowers serum glucose and insulin increases glycogen synthesis, protein synthesis and increased lipogenesis.
81
What does glucagon secreted by the alpha cells in the islets of Langerhans do?
Increases blood sugar by breaking down glycogen, it also induces lipolysis.
82
Pathophysiology of type I diabetes mellitus
Type IV hypersensitivity reaction. HLA-DR3 & 4 increase risk for autoimmune destruction of beta cells by T-cells. Antibodies against insulin may be found in the blood and inflammation of the islets may be seen on histology.
83
Childhood manifestations of insulin deficiency. How do you treat?
High serum glucose, weight loss (unopposed glucagon action), low muscle mass (from unopposed glucagon), polyphagia, polyuria (overflow of sugar into urine draws water with it), polydipsia and glycosuria. Treated with lifelong insulin supplementation.
84
A 12 year old girl presents with Kussmaul respirations, nausea, vomiting, mental status change and a fruity smelling breath associated with a recent infection. Labs show hyperkalemia, hyperglycemia (\>300mg/dL) and anion gap metabolic acidosis. What is causing her condition?
Inability to uptake sugar already puts the child in ketosis. With stress of an infection epinephrine increases glucagon levels and exacerbates lipolysis, gluconeogenesis and glycogenolysis. The liver converts the FFAs to ketone bodies. These ketone bodies (beta-hydroxybutyrate and acetoacetate) are acidic and cause diabetic ketoacidosis.
85
What causes the anion gap metabolic acidosis in a child in diabetic ketoacidosis?
+ charged ketoacids produced by the liver are not accounted for in the equation and are elevated.
86
What is deceptive about the hyperkalemia that is present in kids with diabetic ketoacidosis?
1) Insulin drives K+ into cells and insulin is absent 2) To compensate for acidosis, the cells take in H+ in exchange for K+, so even though serum K+ is high, you are depleting the body of potassium.
87
How do you treat someone with diabetic ketoacidosis?
Replace fluids (from glucose diuretic effect), supplement insulin (to counteract glucagon) and replace electrolytes (will be K+ depleted)
88
What is the cause of the most common form of diabetes?
Type II diabetes mellitus is caused by end-organ insulin resistance leading to hyperglycemia.
89
What are two factors that may predispose someone to type II diabetes?
Obesity (decreases insulin receptors on target cells) and genetics (type II genetic predisposition is stronger than type I)
90
How does early type II diabetes differ from late type II diabetes?
Early on insulin levels are increased. Later on beta-cell exhaustion leads to insulin deficiency (note islets full of amyloid).
91
Clinical features of type II diabetes
Polyuria, polydipsia, hyperglycemia, otherwise clinically silent.
92
How do you diagnose someone with type II diabetes?
Random glucose \>200mg/dL, fasting glucose \>126mg/dL or glucose tolerance test \>200mg/dL 2 hours after you administer the glucose load.
93
How do you treat type II diabetes?
Lose weight, drug therapy to counter insulin resistance and final stage insulin supplementation.
94
A patient is brought to the ED in a coma. His blood pressure is 70/40. Labs reveal a serum glucose \>500mg/dL and ketones are absent. What is causing his condition?
Hyperosmolar Non-Ketotic Coma. High glucose levels lead to a life-threatening diuresis. In these patients, there is sufficient amount of circulating insulin to suppress ketogenesis.
95
What are the major complications associated with diabetes?
#1) Non-enzymatic glycosylation (NEG) of vascular basement membranes. NEG of large & medium vessels = atherosclerosis -\> CV disease -\> amputations. NEG of small vessels = hyaline arteriolosclerosis -\> glomerulosclerosis. NEG of Hgb = HbA1c (marker of glycemic control because RBCs last 120 days). #2) Osmotic damage. Schwann cell (takes up sugar w/o insulin: glucose -\> sorbitol by aldose reductase) damage = diabetic neuropathy. Pericytes of retinal blood vessels (take up glucose -\> sorbitol by aldose reductase) get damaged and die -\> weakened blood vessels = retinal aneurism, hemorrhage & blindness. Lens (takes up glucose -\> sorbitol by aldose reductase) = cataracts.
96
How does diabetes injure the kidney?
Preferential hyaline atherosclerosis of the efferent arteriole increases the glomerular filtration pressure and you get hyper filtration injury. Initially you will get microalbuminuria, then you get glomerular sclerosis in the mesangium (Kimmelstein-Wilson nodules) and nephrotic syndrome. As hyaline arteriolosclerosis progresses to the afferent arteriole you get decreased glomerular filtration and progression to diffuse sclerosis of the glomerulus and chronic renal failure.
97
When do you often see pancreatic endocrine tumors (tumors of the islet cells)?
MEN1 (pancreatic endocrine tumor, parathyroid hyperplasia and pituitary adenoma)
98
How do you differentiate an insulinoma from someone injecting themselves to seek medical attention?
They will both suffer from hypoglycemia with mental status changes relieved by glucose. Labs will show decreased glucose levels and increased insulin levels. However, the person will have the protein release with insulin, C-peptide, increased because their body is actually making the excess insulin, not injecting it.
99
A patient presents with treatment-resistant peptic ulcers. Where would you look on imaging if you suspected an endocrine tumor?
This condition is called Zollinger-Ellison (ZE) syndrome. The tumor secretes lots of gastrin and continually stimulates secretion of acid from the gastric parietal cells. It can be found in the pancreas, but can also extend into the duodenum and jejunum and be found in multiples.
100
A patient presents with refractory cholelithiasis and steatorrhea. He also has lots of GI infections. What type of endocrine tumor could cause this?
Somatostatinoma. Somatostatin inhibits gastrin, thus inhibiting parietal cell acid release and causes achlorhydria which can lead to infections. It also inhibits release of CCK, which normally promotes release of bile from the gallbladder. Inhibition of CCK can lead to cholelithiasis and steatorrhea.
101
A patient presents with watery diarrhea, hypokalemia and achlorhydria. What endocrine tumor is likely causing this condition?
VIPoma. VIP stimulates smooth muscle relaxation of the GI tract (watery diarrhea and loss of electrolytes) and inhibits gastric acid secretion (achlorhydria).
102
3 layers of the adrenal cortex. What hormones do they produce?
Glomerulosa (mineralocorticoids), fasciculata (glucocorticoids) and reticularis (androgens). All of the hormones produced in the cortex come from cortisol.
103
What are the clinical features of Cushing’s syndrome and why?
Muscle weakness w/thin extremities (cortisol turns on gluconeogenesis and muscle breakdown to generate precursors), centripetal fat distribution (high glucose = excess insulin = fat storage), abdominal stria (cortisol impairs collagen synthesis and blood vessels can rupture easily), HTN (cortisol upregulates alpha-1 receptors on arterioles and increases vasoconstrictive effects of NE), osteoporosis and immune suppression.
104
3 mechanisms by which cortisol mediates immunosuppression.
1) Inhibits phospholipase A2, preventing release of arachadonic acid and generation of inflammatory mediators 2) Inhibits IL-2 preventing T-cell growth 3) Inhibits release of histamine from mast cells, limiting vasodilation and vascular permeability.
105
How do you diagnose someone with Cushing’s syndrome?
Increased 24-hour urine cortisol level
106
What are 4 main causes of Cushing’s syndrome?
1) Exogenous corticosteroid use (most common cause) 2) Primary adrenal adenoma, hyperplasia or carcinoma 3) ACTH-secreting pituitary adenoma 4) Paraneoplastic ACTH secretion
107
What happens to the adrenal glands with Cushing’s syndrome from exogenous corticosteroids?
Corticosteroids inhibit ACTH and CRH release from the anterior pituitary and hypothalamus. This will cause atrophy of bilateral adrenal glands.
108
What happens to the adrenal glands with Cushing’s syndrome from primary adrenal adenoma, hyperplasia or carcinoma?
The adrenal gland secreting the cortisol is large, but the cortisol feedback inhibits ACTH and CRH release from the anterior pituitary and hypothalamus. This causes atrophy of the adrenal gland without the adenoma, carcinoma or hyperplasia.
109
What happens to the adrenal glands with Cushing’s syndrome from an ACTH-secreting pituitary adenoma? How do you differentiate this from paraneoplastic ACTH secretion?
ACTH causes hypertrophy of both glands. High dose dexamethasone will inhibit ACTH secretion from the pituitary adenoma and cortisol levels will fall, but ACTH levels will still be high if it is paraneoplastic and cortisol levels will still be high.
110
What happens to the adrenal glands with Cushing’s syndrome from paraneoplastic ACTH secretion from small cell lung carcinoma? How do you differentiate this from an ACTH secreting pituitary adenoma?
ACTH causes hypertrophy of both glands. High dose dexamethasone will inhibit ACTH secretion from the pituitary adenoma and cortisol levels will fall, but ACTH levels will still be high if it is paraneoplastic and cortisol levels will still be high.
111
How do patient’s with hyperaldosteronism present? Why?
In response to aldosterone, the principle cell of the collecting duct and distal nephron will collect Na and dump K. The alpha-intercalated cell will dump H+. Consequently, if someone has hyperaldosteronism they will get hypernatremia, hypokalemia, metabolic alkalosis and hypertension.
112
What are causes of primary hyperaldosteronism?
Most common is an adrenal adenoma. Sporadic adrenal hyperplasia and adrenal carcinoma are less common.
113
What lab values characterize primary hyperaldosteronism?
High aldosterone levels and low renin levels. This is because the kidney responds to the high blood pressure from increased aldosterone release.
114
What are causes of secondary hyperaldosteronism?
Activation of the renin-angiotensin system (renovascular hypertension)
115
What lab values characterize secondary hyperaldosteronism?
High levels of aldosterone and high levels of renin because the kidney is sensing low blood pressure/volume.
116
Common cause of secondary hyperaldosteronism in a young woman?
Fibromuscular dysplasia of the renal artery (thickening of blood vessel wall decreases blood flow to juxtaglomerular apparatus)
117
Common cause of secondary hyperaldosteronism in an old man?
Atherosclerosis that decreases blood flow to the kidney and juxtaglomerular apparatus.
118
A mother gives birth to a set of twins. Early on the boy has precocious puberty and the girl has clitoral enlargement. They are brought to the ED because of life-threatening hypotension. Labs reveal a decreased level of cortisol in the blood, hyponatremia and hyperkalemia. What is causing their condition?
They have Congenital Adrenal Hyperplasia (CAH) from deficiency in the enzyme 21-hydroxylase. This causes increased synthesis of androgens (clitoral enlargement and precocious puberty), cortisol deficiency (life-threatening hypotension and bilateral enlarged adrenal glands from ACTH stimulation) and mineralocorticoid deficiency (lack of aldosterone causes hyponatremia and hyperkalemia)
119
A mother gives birth to a set of twins. Early on the boy has precocious puberty and the girl has clitoral enlargement. They are brought to the doctor because of enlarged adrenal glands on incidental imaging. Labs reveal a decreased level of cortisol. What is causing their condition?
The have an 11-hydroxylase deficiency. This causes cortisol deficiency (hypotension and bilaterally enlarged adrenal glands) and increased androgens (precocious puberty and clitoral enlargement). Since 21-hydroxylase is still active and produce weakly active mineralocorticoids you don’t have the hyponatremia and hyperkalemia seen with 21-hydroxylase deficiency.
120
A mother brings in her kid because he had enlarged bilateral adrenal glands as an incidental finding on abdominal imaging. He is actually 16 but never hit puberty. Labs reveal hypernatremia and hypokalemia. What is causing his condition?
They have 17-hydroxylase deficiency. This causes cortisol deficiency (bilaterally enlarged adrenal glands) and androgen deficiency (late puberty). It also causes excess mineralocorticoids (hypernatremia and hypokalemia).
121
A young child presents with N. meningitis infection that progressed to DIC. What could exacerbate his condition?
Waterhouse-Friderichsen syndrome. This is central necrosis of the adrenal gland producing a “sac of blood” on biopsy. Adrenal insufficiency leads to hypotension on top of meningitis and DIC, complicating the condition.
122
3 main causes of chronic adrenal insufficiency
Autoimmune destruction (most common cause in west), Tb (most common cause in developing world) or metastatic carcinoma (LUNG LOVES TO GO TO THE ADRENAL)
123
Clinical features of chronic adrenal insufficiency?
Hypotension (lack of cortisol). Hyponatremia, hypovolemia, hyperkalemia (lack of aldosterone). Hyperpigmentation (lack of cortisol -\> excess ACTH production -\> MSH is also a derivative of POMC as ACTH is -\> MSH stimulates melanocytes -\> hyper pigmentation around oral mucosa). Weakness. Vomiting and diarrhea.
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What embryonic origin is the main source of catecholamines?
Neural crest, this is what produces the chromaffin cells in the adrenal medulla.
125
A female presents complaining of episodic HTN, headaches, palpitations, tachycardia and sweating. She later dies of a heart attack and biopsy is shown below. What is your diagnosis?
Note that all of her symptoms are a result of increased EPI and NE. Note the brown tumor that is the same color as the medulla, classic of a medullary pheochromocytoma.
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A female presents complaining of episodic HTN, headaches, palpitations, tachycardia and sweating. How do you diagnose and treat this woman if she has a pheochromocytoma?
Diagnose by looking for increased serum metanephrines (breakdown products of EPI and NE), increased 24-hour urine metanephrines and VMA (breakdown product of MAO) because the tumor will be producing lots of EPI and NE and there will be lots of breakdown products. Treat by surgical excision.
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What drug do you give a patient before surgically removing a pheochromocytoma
Phenoxybenzanine (irreversible blocker of alpha adrenergic receptors)
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Pheochromocytoma rule of 10’s.
10% bilateral, 10% familial, 10% malignant, 10% located outside of adrenal medulla
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Classic location of pheochromocytoma outside of adrenal medulla?
Bladder wall (patient develops episodic hypertension when they urinate)
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Genetic associations with pheochromocytoma
MEN2A (medullary carcinoma of thyroid, pheochromocytoma and parathyroid hyperplasia). MEN2B (medullary carcinoma of thyroid, pheochromocytoma and oral mucosal ganglioneuromas). VHL disease (AD loss of tumor suppressor gene increases risk of hemangioblastoma of cerebellum, increased risk for RCC and increased risk of pheochromocytoma). NF type 1 (neurofibromas).
