Endocrine - Pathology Flashcards
Symptoms of nonfunctional pituitary adenoma (3)
Mass effects
- headache
- bitemporal hemianopsia (compression of optic chiasm)
- hypopituitarism
Most common pituitary adenoma
prolactinoma
Prolactinoma: Presentation
Female: galactorrhea, amenorrhea
Males: decreased libido, headache
Prolactinoma: Treatment
Dopamine agonists (bromocriptine, cabergoline) Surgery for larger lesions
Growth hormone cell adenoma: Presentation
Children: gigantism (increased linear bone growth because epiphyses are not fused)
Adults: acromegaly
Acromegaly: Presentation
Enlarged bones of hands, feet, jaw
Coarse facial features
Growth of visceral organs leading to dysfunction (e.g. cardiac failure)
Enlarged tongue
What is often present with GH adenoma?
Secondary diabetes mellitus (induces liver gluconeogenesis)
Growth hormone cell adenoma: Diagnosis
Elevated GH/IGF-1
Lack of GH suppression by oral glucose
Pituitary mass on brain MRI
Growth hormone cell adenoma: Treatment
Octreotide (somatostatin analog)
GH receptor antagonists
surgery
Common cause of death in acromegaly
Heart failure from cardiomyopathy
ACTH cell adenoma: Presentation
Cushing syndrome
Causes of Hypopituitarism (5)
- Mass effect or pituitary apoplexy (bleeding): pituitary adenoma in adults and craniopharyngioma in children
2 Sheehan syndrome
- Empty sella syndrome
- Brain injury, hemorrhage
- Radiation
Sheehan syndrome: Presentation
Poor lactation, loss of pubic hair, fatigue
Sheehan syndrome: Mechanism
Pregnancy-related infarction of pituitary gland
Gland doubles in size during pregnancy but blood supply does not -> blood loss during parturition precipitates infarction
Empty sella syndrome: Presentation
absent (empty sella) pituitary gland on imaging
Empty sella syndrome: Mechanism
Congenital defect
Herniation of arachnoid and CSF into sella compresses and destroys the pituitary gland
Common in obese women
Central diabetes insipidus: Presentation
Polyuria, Polydipsia with riks of life-threatening dehydration; intense thirst
ab: urine specific gravity < 1.006; serum osmolality > 290 mOsm/L
hypernatremia and high serum osmolality
Central diabetes insipidus: Mechanism
ADH deficiency (pituitary tumor, trauma, infection, inflammation)
Central diabetes insipidus: Diagnosis
Water deprivation test
Urine osmol does not increase, but respond to desmopressin
Central diabetes insipidus: Treatmet
Intranasal desmopressin (ADH analog) Adequate fluid intake
Nephrogenic diabetes insipidus: Treatment
HCTZ, indomethacin, amiloride
Nephrogenic diabetes insipidus: Mechanism
impaired response to ADH
Mutation or drugs (lithium an demeclocycline)
Nephrogenic diabetes insipidus: Presentation
Similar to central diabetes insipidus, but does not respond to desmopressin
SIADH: Presentation
Hyponatremia and low serum osmolality
Mental status changes and seizures (neuronal swelling and cerebral edema)
SIADH: Causes
Ectopic ADH (small cell lung cancer)
CNS disorder/head trauma
Pulmonary disease
Drugs (cyclophosphamide)
SIADH: Treatment
Fluid restriction, IV saline, conivaptan, tolvaptan, demeclocyline
Hyperthyroidism: Presentation (12)
- weight loss despite increased appetite
- heat intolerance/sweating
- tachycardia with increased CO
- arrhythmia (Afib) in elderly
- tremor, anxiety, insomnia, heightened emotions
- staring gaze with lid lag
- diarrhea with malabsorption
- oligomenorrhea
- bone resorption with hypercalcemia (osteoporosis)
- decreased muscle mass with weakness
- hypocholesterolemia
- hyperglycemia
Graves’ disease: Mechanism
Type II hypersensitivity
Autoantibody (IgG) stimulates TSH receptor -> increase syntehsis and release of thyroid hormone
Most common cause of hyperthyroidism
Gaves’ disease
Graves’ disease: Risk group
Women of childbearing age (20-40 years)
Often presents during stress (e.g. childbirth)
Graves’ disease: Presentation
- Hyperthyroidism
- Diffuse goiter (constant TSH stimulation leads to thyroid hyperplasia and hypertrophy)
- Exophthalmos and pretibial myxedema
Mechanism of exopthalmos and pretibial myxedema in Graves’ disease?
Fibroblasts behind orbit and overlying shin express TSH receptors
Glycosamnoglycan (chondroitin sulfate and hyaluronic acid) build up, inflammation, fibrosis, and edema
Graves’ disease: Histology and Lab
Irregular follicles with scalloped colloid and chronic inflammation
Lab: high total and free T4, hypocholesterolemia, increased serum glucose
Graves’ disease: treatment
Beta-blockers, thioamide, radioiodine ablation
Thyroid storm: Mechanism
Elevated catecholamines and massive hormone excess, usually in response to stress (surgery, childbirth)
Thyroid storm: Presentation
Arrhythmia, hyperthermia, and vomiting with hypovolemic shock
May also see increased ALP due to increased bone turnover
Thyroid storm: Treatment
PTU, beta-blockers, steroids
Multinodular goiter: Presentation and Cause
enlarged thyroid gland with multiple nodules, usually nontoxic
Due to relative iodine deficiency
Toxic multinodular goiter: Presentation and Malignancy
Focal patches of follicular cells working independently of TSH due to mutation in TSH receptor
Increased T3, T4
Rarely malignant
Jod-Basedow phenomenon
Thyrotoxicosis if patient with iodine deficiency goiter is made iodine replete
Cretinism: Mechanism and Causes
Hypothyroidism in neonates and infants
Causes: maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter, iodine deficiency
What is dyshormonogenetic goiter?
Congenital defect in thyroid hormone production - thyroid peroxidase
Cretinism: Presentation
Mental retardation, short stature with skeletal abnormalities, coarse facial features (puffy faced-child), enlarged tongue, umbilical hernia (pot bellied, protruding umbilicus), pale
Myxedema: Presentation (9)
Hypothyroidism in older children/adults
- Myxedema (accumulation of glycosaminoglycans in skin and soft tissue - deepening of voice and large tongue)
- weight gain despite normal appetite
- slowing of mental activity
- muscle weakness
- cold intolerance with decreased sweating
- bradycardia with decreased CO; SOB and fatigue
- oligomenorrhea
- hypercholesterolemia
- constipation
Most common causes of hypothyroidism
iodine deficiency and hashimoto thyroiditis
Others: drugs (lithium), surgical removal or radioablation of thyroid
Hashimoto thyroiditis: Mechanism
Autoimmune destruction of thyroid gland
HLA-DR5
Hashimoto thyroiditis: Presentation
Initial hyperthyroidism (follicle damage) Progresses to hypothyroidism (low T4 and high TSH)
Antithyroglobulin and antimicrosomal antibodies often present (signs of damage)
Moderately enlarged, non-tender, firm thyroid
Hashimoto thyroiditis: Histology
Chronic inflammation (lymphocytic infiltrate) with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)
Hashimoto thyroiditis: Complications
Increased risk of B-cell (marginal zone) lymphoma (presents as enlarging thyroid gland late in disease course)
Subacute granulomatous (de quervain) thyroiditis: Presentation
Granulomatous thyroiditis that follows viral infection
Tender thyroid with transient hyperthyroidism; jaw pain, increased ESR
Self-limited
Subacute granulomatous (de quervain) thyroiditis: Histology
multinucleated giant cells, histocytes, and lymphocytes (granulomatous inflammation)
Reidel fibrosing thyroiditis: Mechanism
Chronic inflammation with extensive fibrosis of thyroid gland
IgG4-related systemic disease
Reidel fibrosing thyroiditis: Presentation
Hypothyroidism with “hard as wood”, non-tender thyroid gland
May extend to involve local structures (airways)
Clinically mimic anaplastic carcinoma, but patients are younger (40s) and malignant cells are absent
What are cold and hot nodules? Examples of each.
Hot nodule (increased uptake): Graves’ disease or nodular goiter
Cold nodules (decreased uptake): adenoma and carcinoma - warrant biopsy
131I radioactive uptake
Follicular adenoma: Histology
Benign proliferation of follicles surrounded by fibrous capsule
Usually non-functional
Most common type to thyroid carcinoma
Papillary carcinoma
Papillary carcinoma: Risk factors
exposure to ionizing radiation in childhood (severe acne)
Papillary carcinoma: Histology
Papillae lined by cells with clear ‘Orphan Annie eye’ nuclei (empty appearing nuclei) and nuclear grooves
Assocated with psammoma bodies
Papillary carcinoma: Metastasis and Prognosis
Spread to cervical (neck) lymph nodes, but prognosis is excellent
Follicular carcinoma: Histology
Malignant proliferation of follicles surrounded by fibrous capsule with invasion through capsule (FNA cannot make distinction between adenoma and carcinoma)
Follicular carcinoma: Metastasis
Hematogenously
Medullary carcinoma: Mechanism and Presentation
Malignant proliferation of parafollicular C cells (5% of thyroid carcinoma)
Can lead to hypocalcemia
Medullary carcinoma: Histology
Sheets of malignant cells in amyloid stroma (calcitonin deposits within tumor as amyloid)
Which hereditary diseases are associated with medullary carcinoma? And what mutation?
MEN2A and 2B
RET oncogene
Detection of RET mutation warrants prophylactic thyroidectomy
Anaplastic carcinoma: Histology
undifferentiated malignant tumor of thyroid
Anaplastic carcinoma: Presentation
Usually in elderly
Invades local structures, leading to dysphagia or respiratory compromise
Poor prognosis
Most common cause of primary hyperparathyroidism
Parathyroid adenoma (80%) Sporadic parathyroid hyperplasia and carcinoma are less common causes
Parathyroid adenoma: Presentation and Mechanism
Benign neoplasm, usually involving 1 gland
Results in asymptomatic hypercalcemia or symptomatic
What are symptoms of hypercalcemia? (5)
- Nephrolithiasis (calcium oxalate stones)
- nephrocalcinosis: metastatic calcification of renal tubules leading to renal insufficiency and polyuria
- CNS disturbances (depression seizures)
- Constipation, peptic ulcer, acute pancreatitis
- Osteitis fibrosa cystica: resoprtion of bone leading to fibrosis and cystic spaces
Parathyroid adenoma: Laboratory findings
High PTH, High calcium, Low phosphate
High urinary cAMP, High serum alkaline phosphatase
Parathyroid adenoma: Treatment
Surgical removal
Most common secondary hyperparathyroidism
Chronic renal failure
Decreased phosphate excretion -> increase phosphate binding to calcium -> decrease free calcium stimulates all 4 parathyroid glands
Secondary hyperparathyroidism: Laboratory findings
High PTH, Low calcium, High phosphate, High alkaline phosphatase
Hypoparathyroidism: Mechanism and Causes
Low PTH
Autoimmune damage, surgical excision, DiGeorge syndrome
Hypoparathyroidism: Presentation and Lab
Presentation related to low serum calcium
Lab: Low PTH levels and low calcium
Low serum calcium: Presentation
- Numbness and tingling (circumoral)
2. Muscle spasms (tetany) - Troussea sign (blood pressure cuff) and Chvostek sign (tapping on facial nerve)
Pseudohypoparathyroidism: Presentation and Association
Autosomal dominant form: short stature and short 4/5th digits
End-organ resistance to PTH
Hypocalcemia with High PTH level
Type 1 Diabetes mellitus: Mechanism
Insulin deficiency leading to hyperglycemia
Autoimmune destruction of beta ells by T lymphocytes (Type IV hypersensitivity) characterized by inflammation of islets
Type 1 Diabetes mellitus: Genetics
HLA-DR3 and DR-4
Autoantibodies against insulin often present and may be seen years before clinical disease develops
Type 1 Diabetes mellitus: Presentation
Age group: children <30
High serum glocuse
Weight loss, muscle loss, polyphagia
Polyuria, polydipsia, lipolysis, glucosuria
Type 1 Diabetes mellitus: Treatment
lifelong insulin
Diabetic ketoacidosis: Mechanism
Excessive serum ketones
Stress/Infection -> epinephrine stimulates glucagon secretion increasing lipolysis -> increase FFA -> converted to ketones
Diabetic ketoacidosis: Presentation
Hyperglycemia (>300), anion gap metabolic acidosis, hyperkalemia
Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, fruity smelling breath (acetone)
Depleted intracellular K+ due to transcellular shift from decreased insulin
Diabetic ketoacidosis: Treatment
Fluids (correct dehydration), insulin and potassium
Diabetic ketoacidosis: Complications
mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart failure
Type 2 Diabetes mellitus: Mechanism and Prevalence
End-organ insulin resistance
Most common type of diabetes (90%); 5-10% of US population
Type 2 Diabetes mellitus: Risk group
Middle aged, obese adults Family history (strong genetic predisposition)
Progression of Diabetes Mellitus Type 2
Initial rise in insulin early, but later, insulin deficiency due to beta cell exhaustion (amyloid deposits in islets - AIAAP)
Type 2 Diabetes mellitus: Presentation and Lab
Polyuria, polydipsia, hyperglycemia
Lab:
random glucose >200
fasting glucose >126
glucose tolerance test >200 2 hours after glucose loading
Type 2 Diabetes mellitus: Treatment
Weight loss (diet and exercise) Drug therapy or exogenous insulin after exhaustion of beta cells
Hyperosmolar non-ketotic coma
High glucose (>500) leads to life-threatening diuresis with hypotension and coma Ketones absent due to circulating insulin
Type 2 Diabetes mellitus: Complications (Nonenzymati glycosylation)
Nonenzymatic glycosylation of vascular basement membrane
- atherosclerosis (cardiovascular and peripheral vascular disease)
- hyaline arteriolosclerosis of renal (preferentially efferent) progressing to nephrotic syndrome (Kimmelstiel-Wilson nodules)
- glycated hemoglobin (HbA1C) marker of glycemic control
Type 2 Diabetes mellitus: Complications (Osmotic damage)
Glucose enter Schwann cells, pericytes of retinal blood vessels and lens
Aldose reductase converts glucose to sorbitol, leading to osmotic damage
Peripheral neuropathy, impotence, blindness and cataracts
What is the leading cause of death among diabetics?
Cardiovascular disease
What is the leading cause of blindness in the developed world?
Diabetes
Cushing syndrome: Mechanism
Excess cortisol
Cushing syndrome: Presentation (6)
- muscle weakness with thin extremities (break down muscle for gluconeogenesis)
- Moon facies, buffalo hump, truncal obesity
- Abdominal striae (impaired synthesis of collagen)
- Hypertension
- Osteoporosis
- Immune suppression
Cushing syndrome: Diagnosis
Diagnosis by 24-hour urine coritsol levels
Cushing syndrome: Causes (4)
- exogenous corticosteroids (bilateral adrenal atrophy)
- Primary adrenal adenoma, hyperplasia or carcinoma - 15% (unilateral atrophy)
- ACTH-secreting pituitary adenoma -70% (bilateral hyperplasia)
- Paraneoplastic ACTH - 15% (e.g. small cell carcinoma) - bilateral hyperplasia
What is the high-dose dexamethasone test?
Dexamethasone is a cortisol analog that suppresses ACTH production in pituitary adenoma but not in ectopic ACTH (cortisol remains high)
Conn syndrome: Mechanism
Excess aldosterone, most commonly due to adrenal adenoma
Conn syndrome: Presentation
Hypertension with hypernatremia, hypokalemia, metabolic alkalosis
How to distinguish between primary and secondary hyperaldosteronism?
Both have high aldosterone, but primary hyperaldosteronism has low renin (high blood pressure downregulates renin)
Examples of Secondary Hyperaldosteronism
Activation of renin-angiotensin
Renovascular hypertension, CHF, renal artery stenosis, nephrotic syndrome
Primary Hyperaldosteronism: Treatment
Surgery to remove tumor
Spironolactone as aldosterone antagonist
Secondary Hyperaldosteronism: Treatment
Spironolactone
Adrenal insufficiency: Acute and Chronic Causes
Acute: Waterhouse-Friderichsen syndrome
Chronic: autoimmune, TB, metastitic carcinoma (lung)
Addison’s disease: Presentation
Hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (increased ACTH by-products stimulate melanocytic production of pigment), vomiting, diarrhea
Waterhouse-Friderichsen syndrome: Mechanism
Hemorrhagic necrosis of adrenal glands, classically due to DIC in young children with N. meningitidis
Lack of cortisol exacerbates hypotension, often leading to death
Addison’s disease: Mechanism
Primary adrenal insufficiency
Adrenal atrophy and absence of hormone production (all 3 cortical divisions)
How is primary and secondary adrenal insufficiency differentiated?
Secondary adrenal insufficiency: low pituitary ACTH - no skin hyperpigmentation and no hyperkalemia
Pheochromocytoma: Mechanism
Tumor of chromaffin cells
Increased serum catecholamines
Pheochromocytoma: Presentation
Episodic hypertension, headache, palpitations, tachycardia, sweating
Pheochromocytoma: Diagnosis
Increased serum metanephrines and increased 24-hour urine metanephrines and vanillymandelic acid
Pheochromocytoma: Treatment
Surgical excision
Phenoxybenzamine (irreversible alpha-blocker) administered perioperatively to prevent hypertensive crisis
What is Pheochromocytoma’s rule of 10?
10% bilateral
10% familial
10% malignant
10% outside of adrenal medulla (bladder wall or organ of Zuckerkandl at inferior mesenteric artery root)
What hereditary conditions are associated with pheochromocytoma?
MEN 2A, 2B
Von hippel-lindau
Neurofibromatosis 1
Neuroblastoma: Presentation
Occur anywhere along sympathetic chain
Elevated homovanillic acid in urine (breakdown product of dopamine)
What gene is associated with neuroblastoma and tumor progression?
N-myc
Carcinoid tumor: Mechanism
Carcinoid tumors (neuroendocrine cells), especially in small bowel which secretes high levels of serotonin.
No carcinoid syndrome if within GI tract (first-pass metabolism in liver)
Carcinoid syndrome: Presentation
Recurrent diarrhea, cutaneous flushing, asthmatic wheezing, R sided valvular disease
Increased 5-HIAA in urine, niacin deficiency
Carcinoid syndrome: Treatment
Somatostatin analog (Octreotide)
What is the most common tumor fo the appendix?
Carcinoid tumor
What is carcinoid tumor/s rule of 1/3
1/3 metastasize
1/3 present with 2nd malignancy
1/3 multiple
Zollinger-Ellison syndrome: Mechanism
Gastrin-secreting tumor of pancreas or duodenum
Zollinger-Ellison syndrome: Histology
Stomach shows rugal thickening with acid hypersecretion
Can cause recurrent ulcers
What hereditary disorder is associated with Zollinger-Ellison syndrome?
MEN 1
MEN 1 (Wermer’s syndrome): Presentations
Pituitary tumor (prolactin/GH) Parathyroid tumor Pancreatic tumor (ZE, insulinoma, VIPoma, glucagonoma)
Kidney stones and stomach ulcers
MEN 2A (Sipple’s syndrome: Presentations
Medullary thyroid carcinoma
Pheochromocytoma
Parathyroid tumors
MEN 2B: Presentations
Medullary thyroid carcinoma
Pheochromocytoma
Oral/intestinal ganglioneuromatosis
(associated with marfanoid habitus)
