Endocrine - Pathology Flashcards
1
Q
Cushing syndrome (317)
- Etiology
- Findings
- Diagnosis
- Screening tests include:
- Measure/
- Ectopic secretion
A
- Etiology
- Increased cortisol due to a variety of causes:
- Exogenous corticosteroids
- # 1 cause
- Results in decreased ACTH, bilateral adrenal atrophy.
- Primary adrenal adenoma, hyperplasia, or carcinoma
- Results in decreased ACTH, atrophy of uninvolved adrenal gland.
- Can also present as 1° aldosteronism (Conn syndrome).
- ACTH-secreting pituitary adenoma [A] (Cushing disease)
- Paraneoplastic ACTH secretion (e.g., small cell lung cancer, bronchial carcinoids)
- Results in increased ACTH, bilateral adrenal hyperplasia.
- Cushing disease is responsible for the majority of endogenous cases of Cushing syndrome.
- Exogenous corticosteroids
- Increased cortisol due to a variety of causes:
- Findings
- Hypertension, weight gain, moon facies, truncal obesity [B], buffalo hump, hyperglycemia (insulin resistance), skin changes (thinning, striae), osteoporosis, amenorrhea, and immune suppression.
- Diagnosis
- Screening tests include: increased free cortisol on 24-hr urinalysis, midnight salivary cortisol, and overnight low-dose dexamethasone suppression test:
- Measure serum ACTH.
- If decreased, suspect adrenal tumor.
- If increased, distinguish between Cushing disease and ectopic ACTH secretion with a high-dose (8 mg) dexamethasone suppression test and CRH stimulation test.
- Ectopic secretion
- Will not decrease with dexamethasone because the source is resistant to negative feedback
- Will not increase with CRH because pituitary ACTH is suppressed.
2
Q
Hyperaldosteronism
- Primary
- Definition
- Treatment
- Secondary
- Definition
- Treatment
A
- Primary
- Definition
- Caused by adrenal hyperplasia or an aldosterone-secreting adrenal adenoma (Conn syndrome), resulting in hypertension, hypokalemia, metabolic alkalosis, and **low **plasma renin.
- Normal Na+ due to aldosterone escape = no edema due to aldosterone escape mechanism.
- May be bilateral or unilateral.
- Caused by adrenal hyperplasia or an aldosterone-secreting adrenal adenoma (Conn syndrome), resulting in hypertension, hypokalemia, metabolic alkalosis, and **low **plasma renin.
- Treatment:
- Surgery to remove the tumor and/or spironolactone, a K+-sparing diuretic that acts as an aldosterone antagonist.
- Definition
- Secondary
- Definition
- Renal perception of low intravascular volume results in an overactive renin-angiotensin system.
- Due to renal artery stenosis, CHF, cirrhosis, or nephrotic syndrome.
- Associated with high plasma renin.
- Treatment
- Spironolactone.
- Definition
3
Q
Addison disease
- Definition
- Characterized by/
- 1° vs. 2°
A
- Definition
- Chronic 1° adrenal insufficiency due to adrenal atrophy or destruction by disease (e.g., autoimmune, TB, metastasis).
- Deficiency of aldosterone and cortisol, causing hypotension (hyponatremic volume contraction), hyperkalemia, acidosis, and skin and mucosal hyperpigmentation [A] (due to MSH, a by-product of increased ACTH production from pro-opiomelanocortin (POMC).
- Characterized by Adrenal Atrophy and Absence of hormone production
- Involves All 3 cortical divisions (spares medulla).
- Distinguish from 2° adrenal insufficiency (decreased pituitary ACTH production), which has no skin/mucosal hyperpigmentation and no hyperkalemia.
4
Q
Waterhouse- Friderichsen syndrome
A
- Acute 1° adrenal insufficiency due to adrenal hemorrhage
- Associated with Neisseria meningitidis septicemia, DIC, and endotoxic shock.
5
Q
Neuroblastoma
- Definition
- Source
- Most common presentation
- Labs
A
- Definition
- The most common tumor of the adrenal medulla in children, usually < 4 years old.
- Source
- Originates from neural crest cells [A].
- Occurs anywhere along the sympathetic chain.
- Most common presentation
- Abdominal distension
- A firm, irregular mass [B] that can cross the midline (vs. Wilms tumor, which is smooth and unilateral).
- Less likely to develop hypertension.
- Associated with overexpression of N-myc oncogene.
- Labs
- Homovanillic acid (HVA), a breakdown product of dopamine, increased in urine.
- Bombesin (+).
6
Q
Pheochromocytoma (319)
- Etiology
- Symptoms
- Findings
- Treatment
A
- Etiology
- Most common tumor of the adrenal medulla in adults [A] [B].
- Derived from chromaffin cells (arise from neural crest) [C].
-
Rule of 10’s:
- 10% malignant –> 90% benign
- 10% bilateral –> 90% unilateral
- 10% extra-adrenal –> 90% in adrenal medulla
- 10% calcify –> 90% don’t calcify
- 10% kids –> 90% adults
- Symptoms
- Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension.
- Associated with von Hippel-Lindau disease, MEN 2A and 2B.
- Symptoms occur in “spells”—relapse and remit.
- Episodic hyperadrenergic symptoms (5 P’s):
- Pressure (increased BP)
- Pain (headache)
- Perspiration
- Palpitations (tachycardia)
- Pallor
- Findings
- Urinary VMA (a breakdown product of norepinephrine and epinephrine) and plasma catecholamines are increased.
- Treatment
- Irreversible α-antagonists (phenoxybenzamine) and β-blockers followed by tumor resection.
- α-blockade must be achieved before giving β-blockers to avoid a hypertensive crisis.
7
Q
Hypothyroidism vs. hyperthyroidism
- Signs / symptoms
- Heat production
- Weight / appetite
- Activity
- GI
- Reflexes
- Myxedema
- Skin / hair
- Cardio / pulm
- Lab findings
- TSH
- T3 / T4
- Cholesterolemia
A
- Signs / symptoms
- Heat production
- Hypo: Cold intolerance (decreased heat production)
- Hyper: Heat intolerance (increased heat production)
- Weight / appetite
- Hypo: Weight gain, decreased appetite
- Hyper: Weight loss, increased appetite
- Activity
- Hypo: Hypoactivity, lethargy, fatigue, weakness
- Hyper: Hyperactivity
- GI
- Hypo: Constipation
- Hyper: Diarrhea
- Reflexes
- Hypo: decreased reflexes
- Hyper: increased reflexes
- Myxedema
- Hypo: Myxedema (facial/periorbital)
- Hyper: Pretibial myxedema (Graves disease), periorbital edema
- Skin / hair
- Hypo: Dry, cool skin; coarse, brittle hair
- Hyper: Warm, moist skin; fine hair
- Cardio / pulm
- Hypo: Bradycardia, dyspnea on exertion
- Hyper: Chest pain, palpitations, arrhythmias, increased number and sensitivity of β-adrenergic receptors
- Heat production
- Lab findings
- TSH
- Hypo: increased TSH (sensitive test for 1° hypothyroidism)
- Hyper: decreased TSH (if 1°)
- T3 / T4
- Hypo: decreased free T3 and T4
- Hyper: increased free or total T3 and T4
- Cholesterolemia
- Hypo: Hypercholesterolemia (due to decreased LDL receptor expression)
- Hyper: Hypocholesterolemia (due to increased LDL receptor expression)
- TSH
8
Q
Hashimoto thyroiditis
- Definition
- Histologic findings
- Findings
A
- Definition
- Most common cause of hypothyroidism in iodine-sufficient regions
- An autoimmune disorder (anti-thyroid peroxidase, antithyroglobulin antibodies).
- Associated with HLA-DR5.
- Increased risk of non-Hodgkin lymphoma.
- May be hyperthyroid early in course due to thyrotoxicosis during follicular rupture.
- Histologic findings
- Hürthle cells, lymphoid aggregate with germinal centers [A].
- Findings
- Moderately enlarged, nontender thyroid.
9
Q
Congenital hypothyroidism (cretinism)
- Definition
- Findings
A
- Definition
- Severe fetal hypothyroidism due to maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis (most common cause in U.S.), iodine deficiency, dyshormonogenic goiter.
- Findings: 6 P’s [B] [C]
- Pot-bellied
- Pale
- Puffy-faced child with Protruding umbilicus
- Protuberant tongue
- Poor brain development
10
Q
Subacute thyroiditis (de Quervain)
- Definition
- Histology
- Findings
A
- Definition
- Self-limited hypothyroidism often following a flu-like illness.
- May be hyperthyroid early in course.
- Histology
- Granulomatous inflammation.
- Findings
- Increased ESR, jaw pain, early inflammation, very tender thyroid.
- de Quervain** is associated with pain.**
11
Q
Riedel thyroiditis
- Definition
- Findings
A
- Definition
- Form of hypothyroidism
- Thyroid replaced by fibrous tissue (hypothyroid).
- Fibrosis may extend to local structures (e.g., airway), mimicking anaplastic carcinoma.
- Considered a manifestation of IgG4-related systemic disease.
- Findings
- Fixed, hard (rock-like), and painless goiter.
12
Q
Causes of hypothyroidism
- Most important
- Other
A
- Most important
- Hashimoto thyroiditis
- Congenital hypothyroidism (cretinism)
- Subacute thyroiditis (de Quervain)
- Riedel thyroiditis
- Other
- Iodine deficiency [D]
- Goitrogens
- Wolff-Chaikoff effect
- Painless thyroiditis.
13
Q
Toxic multinodular goiter
- Definition
- Jod-Basedow phenomenon
A
- Definition
- Hyperthyroid condition
- Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor [A].
- Increased release of T3 and T4.
- Hot nodules are rarely malignant.
-
Jod-Basedow phenomenon
- Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete.
14
Q
Graves disease
- Definition
- Findings
A
- Definition
- Most common cause of hyperthyroidism.
- Often presents during stress (e.g., childbirth).
- Findings
- Autoantibodies (IgG) stimulate TSH receptors on thyroid (hyperthyroidism, diffuse goiter)
- Retro-orbital fibroblasts (exophthalmos: proptosis, extraocular muscle swelling [B])
- Dermal fibroblasts (pretibial myxedema).
15
Q
Thyroid storm
- Definition
- Findings
- Treatment
A
- Definition
- Stress-induced catecholamine surge seen as a serious complication of Graves disease and other hyperthyroid disorders.
- Findings
- Presents with agitation, delirium, fever, diarrhea, coma, and tachyarrhythmia (cause of death).
- May see increased ALP due to increased bone turnover.
- Treatment: 3 P’s
- β-blockers (e.g., Propranolol)
- Propylthiouracil
- Corticosteroids (e.g., Prednisolone).
16
Q
Thyroid cancer (323)
- Treatment
- Complications of surgery
- Papillary carcinoma
- Follicular carcinoma
- Medullary carcinoma
- Undifferentiated / anaplastic carcinoma
- Lymphoma
A
- Treatment
- Thyroidectomy is treatment option for thyroid cancers and hyperthyroidism.
- Complications of surgery
- Hoarseness (due to recurrent laryngeal nerve damage)
- Hypocalcemia (due to removal of parathyroid glands)
- Transection of inferior thyroid artery.
- Papillary carcinoma
- Most common, excellent prognosis.
- Empty-appearing nuclei (“Orphan Annie” eyes) [A], psammoma bodies, nuclear grooves.
- Increased risk with RET and BRAF mutations, childhood irradiation.
- Follicular carcinoma
- Good prognosis
- Invades thyroid capsule (unlike follicular adenoma)
- Uniform follicles.
- Medullary carcinoma
- From parafollicular “C cells”
- Produces calcitonin, sheets of cells in an amyloid stroma [B].
- Associated with MEN 2A and 2B (RET mutations).
- Undifferentiated / anaplastic carcinoma
- Older patients
- Invades local structures, very poor prognosis.
- Lymphoma
- Associated with Hashimoto thyroiditis.
17
Q
Primary hyperparathyroidism
- Definition
- Osteitis fibrosa cystica
A
- Definition
- Usually an adenoma.
- Hypercalcemia, hypercalciuria (renal stones), hypophosphatemia, increased PTH, increased ALP, increased cAMP in urine.
- Most often asymptomatic.
- May present with weakness and constipation (“groans”), abdominal/flank pain (kidney stones, acute pancreatitis), depression (“psychiatric overtones”).
-
Osteitis fibrosa cystica
- Cystic bone spaces filled with brown fibrous tissue [A] (bone pain).
- “Stones, bones, groans, and psychiatric overtones.”
18
Q
Hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
- Renal osteodystrophy
A
- Secondary
- 2° hyperplasia due to decreased gut Ca2+ absorption and increased PO43-, most often in chronic renal disease (causes hypovitaminosis D –> decreased Ca2+ absorption).
- Hypocalcemia, hyperphosphatemia in chronic renal failure (vs. hypophosphatemia with most other causes), increased ALP, increased PTH.
- Tertiary
- Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease.
- Really increased PTH, increased Ca2+.
-
Renal osteodystrophy
- Bone lesions due to 2° or 3° hyperparathyroidism due in turn to renal disease.
19
Q
Hypoparathyroidism
- Due to:
- Findings
- Chvostek sign
- Trousseau sign
- Pseudohypoparathyroidism (Albright hereditary osteodystrophy)
A
- Due to:
- Accidental surgical excision of parathyroid glands
- Autoimmune destruction
- DiGeorge syndrome.
- Findings
- Hypocalcemia, tetany.
-
Chvostek sign
- Tapping of facial nerve (tap the Cheek) –> contraction of facial muscles.
-
Trousseau sign
- Occlusion of brachial artery with BP cuff (cuff the Triceps) –> carpal spasm.
-
Pseudohypoparathyroidism (Albright hereditary osteodystrophy)
- Autosomal dominant unresponsiveness of kidney to PTH.
- Hypocalcemia, shortened 4th/5th digits, short stature.
20
Q
Pituitary adenoma
- Definition
- Nonfunctional vs. functional tumors
- Treatment for prolactinoma
A
- Definition
- Most commonly prolactinoma (benign).
- Adenoma [A] may be functional (hormone producing) or nonfunctional (silent).
- Nonfunctional vs. functional tumors
- Nonfunctional tumors present with mass effect (bitemporal hemianopia, hypopituitarism, headache).
- Functional tumor presentation is based on the hormone produced (e.g., prolactinoma: amenorrhea, galactorrhea, low libido, infertility; somatotropic adenoma: acromegaly).
- Treatment for prolactinoma
- Dopamine agonists (bromocriptine or cabergoline). .
21
Q
Acromegaly
- Definition
- Findings
- Diagnosis
- Treatment
A
- Definition
- Excess GH in adults.
- Typically caused by pituitary adenoma.
- Findings
- Large tongue with deep furrows, deep voice, large hands and feet, coarse facial features [A], impaired glucose tolerance (insulin resistance).
- Increased GH in children –> gigantism (increased linear bone growth).
- Cardiac failure most common cause of death.
- Diagnosis
- Increased serum IGF-1
- Failure to suppress serum GH following oral glucose tolerance test
- Pituitary mass seen on brain MRI.
- Treatment
- Pituitary adenoma resection.
- If not cured, treat with octreotide (somatostatin analog) or pegvisomant (growth hormone receptor antagonist).
26
Q
Diabetes mellitus
- Acute manifestations
- Chronic manifestations
- Nonenzymatic glycosylation
- Small vessel
- Large vessel
- Osmotic damage
- Nonenzymatic glycosylation
- Tests
A
- Acute manifestations
- Polydipsia, polyuria, polyphagia, weight loss, DKA (type 1), hyperosmolar coma (type 2).
- Rarely, can be caused by unopposed secretion of GH and epinephrine.
- Chronic manifestations
- Nonenzymatic glycosylation:
- Small vessel disease (diffuse thickening of basement membrane)
- –> retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation) [A], glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriolosclerosis leading to hypertension, Kimmelstiel-Wilson nodules)
- Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, and gangrene
- –> limb loss, cerebrovascular disease.
- MI most common cause of death.
- Small vessel disease (diffuse thickening of basement membrane)
- Osmotic damage
- Sorbitol accumulation in organs with aldose reductase and decreased or absent sorbitol dehydrogenase
- Neuropathy (motor, sensory, and autonomic degeneration)
- Cataracts
- Nonenzymatic glycosylation:
- Tests
- Fasting serum glucose, oral glucose tolerance test, HbA1c (reflects average blood glucose over prior 3 months).
32
Q
Multiple endocrine neoplasias: MEN 1 (Wermer syndrome)
- Characteristics
- Comments
A
- Characteristics
- Parathyroid tumors
- Pituitary tumors (prolactin or GH)
- Pancreatic endocrine tumors—Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas (rare)
- Commonly presents with kidney stones and stomach ulcers
- Comments
- All MEN syndromes have autosomal dominant inheritance.
- “All MEN are dominant” (or so they think).
-
MEN 1 = 3 P’s
- From cephalad to caudad: Pituitary, Parathyroid, and Pancreas
- Remember by drawing a diamond
- All MEN syndromes have autosomal dominant inheritance.
33
Q
Multiple endocrine neoplasias: MEN 2A (Sipple syndrome)
- Characteristics
- Comments
A
- Characteristics
- Medullary thyroid carcinoma (secretes calcitonin)
- Pheochromocytoma
- Parathyroid hyperplasia
- Associated with ret gene mutation
- Comments
- All MEN syndromes have autosomal dominant inheritance.
- “All MEN are dominant” (or so they think).
-
MEN 2A = 2 P’s
- Parathyroids and Pheochromocytoma
- Remember by drawing a square
- All MEN syndromes have autosomal dominant inheritance.
34
Q
Multiple endocrine neoplasias:
MEN 2B
- Characteristics
- Comments
A
- Characteristics
- Medullary thyroid carcinoma (secretes calcitonin)
- Pheochromocytoma
- Oral/intestinal ganglioneuromatosis (mucosal neuromas).
- Associated with marfanoid habitus.
- Associated with ret gene mutation
- Comments
- All MEN syndromes have autosomal dominant inheritance.
- “All MEN are dominant” (or so they think).
-
MEN 2B = 1 P
- Pheochromocytoma
- Remember by drawing a triangle
- All MEN syndromes have autosomal dominant inheritance.
