Endocrine Pathology (Pathoma) Flashcards
Pituitary Adenoma
Benign tumor of anterior pituitary cells
May be functional or nonfuntional
Nonfunctional present w/ mass effect: bitemporal hemionopsia (compression of optic chiasm), hypopituitarism, and headache
Functional tumors: Present w/ features based on hormone produced (MC is prolactinoma). Also GH adenoma, ACTH adenoma, TSH, LH, and FSH are rare
Prolactinoma
MC functional pituitary adenoma
Galactorrhea and amenorrhea (females); decreased libido and headaches (males)
Rx: = dopamine agonists (bromocriptine) or surgery
Growth Hormone Adenoma
Gigantism in children
Acromegaly in adults (cardiac failure is MCC of death
Secondary DM is often present
Dx w/ elevated GH and IGF-1
Lack of GH suppression by oral glucose
Rx: Octreotide, GH receptor antagonists, surgery
Hypopituitarism
Insufficient productions of hormones by Ant. Pit.
Causes: Pituitary Adenoma (adults –> mass affect or bleeding) or craniopharyngioma (children), Sheehan syndrome, Empty sella syndrome
Sheehan syndrome
Pituitary grows great deal during pregnancy, but blood supply doesn’t. –> susceptible to hypoperfusion –> blood loss during pregnancy –> hypopituitarism
Present w/ Poor lactation and loss of pubic hair
Empty Sella Syndrome
Sella is empty and pit. is misisng.
Either due to trauma or congenital malformation allowing herniation of arachnoid CSF into sella
Central Diabetes Insipidus
ADH deficiency
Due to hypothalamic or posterior pit. pathology (i.e. tumor, trauma, infx)
Polyuria and polydipsia
Hypernatremia and high serum osmolarity
low urine osmolarity and specific gravity
Dx: water deprivation fails to increase urine osmolarity. Responds to desmopressin (vs. nephrogenic).
Nephrogenic Diabetes Insipidus
Impaired renal response to ADH
Due to inherited mutations or drugs (lithium or demeclocyline)
Similar to central DI, but there is no response to desmopressin
SIADH
Clinical features: hyponatremia and low serum osmolarity –> mental status changes and seizures.
Causes: ectopic production (small cell carcinoma); CNS trauma; pulmonary infection; drugs (cyclophosphamide)
Rx: Free water restriciton, demeclocycline
Thyroglossal Duct Cyst
Cystic dilitation of thyroglossal duct (develops from base of tongue and descends) remnant
Presents as anterior neck mass
Lingual thyroid
Persistence of thyroid tissue at base of tongue
Presents as base of tongue mass*
Hyperthyroidism
Increased level of circulating thyroid hormone
Increases BMR (increases synthesis of Na/K ATPase)
Increases sympathetic nervous system (increase Beta-1 receptors)
Clinical features:
- Weight loss despite increased appetitite
- Heat intolerance and sweating
- Tachycardia w/ increased cardiac output
- Arrhythmia (esp. A-fib), esp. in elderly
- Tremor, anxiety, insomnia, and heightened emotions
- Staring gaze w/ lid lag
- Diarrhea and malabsorbtion
- Oligomenorrhea
- Bone resorption w/ hypercalcemia
- Decreased muscle mass with weakness
- *Hypocholesterolemia and Hyperglycemia
MCC = Graves Disease
Graves Disease
Autoantibody (IgG) that stimulates TSH receptor –> increased synthesis and release of thyroid hormone
MCC of hyperthyroidism
Occurs in women of childbearing age (like other autoimmune)
Clinical features: Hyperthyroidism, diffuse goiter, and exopthalmos and pretibial myxedema (fibroblasts stimulated by TSH like antibody.
“Scalloped colloid” on histology
Labs: Increased total and free T4; low TSH; Hypocholesteremia and hyperglycemia
Rx: Beta-blockers; Thioamide (blocks peroxidase), and radioiodine ablation.
Thyroid storm is feared complication
Thyroid Storm
Feared complication of hyperthyroidism
Elevated catecholamines and massive hormone excess (stress)
Arrhythmia, hyperthermia, and vomiting w/ hypovolemic shock
Treat w/ PTU (inhibits peroxidase and T4–>T3 conversion), Beta blockers, and steroids
Multinodular Goiter
Enlarged thyroid gland with multiple nodules
Due to relative iodine deficiency
Usually nontoxic (euthyroid)
Rarely regions become TSH-independent = toxic goiter –> secretes excess T4
Cretinism
Hypothyroidism in neonates
Clinical features: Mental retadation, short stature w/ skeletal abnormalities, coarse facial features, enlarged tongue, and umbilical hernia
Causes: Maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshomonogenetic disorder (lack of thyroid peroxidase is MC), or lack of Iodine
Myxedema
Hypothryoidism in adults
Clinical features:
- Myxedema (dough like swelling due to fibroblast proliferation due to high TSH. Esp in larynx = deep voice and tongue)
- weight gain despite normal appetite
- Slowing of mental activity
- Muscle weakness
- Cold intolerance w/ decreased sweating
- Bradycardia w/ decreased cardiac output
- Oligomenorrhea
- Hypercholesterolemia
- Constipation
Causes: Iodine deficiency, Hashiomoto’s thyroiditis (MCC), drugs (lithium), or surgical removal/radioablation
Hashiomoto’s Thyroiditis
Commonly associated w/ HLA DR5
MCC of hypothyroidism
Autoimmune attack of thyroid gland
Clinical features: Intially can be hyperthyroidism (destruction of cells) and eventually become hypothyroidism –> low T4 and high TSH.
Antithyroglobulin and anti-microsomal antibodies are often present (markers, not mediators)
Histologically: Inflammation w/ formation of germinal centers. Pink cells around germinal centers (Hurtle cells)
Increased risk of B-cell lymphoma
Subacute (deQuervain) Granulomatous thyroiditis
Granulomatous thyroiditis that follows a viral infection
Presents as *TENDER thryoid with transient hyperthyroidism
Self-limited; does not progress to hypothyroidism
Reidel Fibrosing Thyroidism
Chronic inflammation with extensive fibrosis of thyroid
- Presents as hypothyroidism with “hard as wood” nontender thyroid gland
- Fibrosis may extend to local structures (i.e. airway). –> ddx vs. anaplastic carcinoma (young female vs. older patient)
Thyroid Neoplasia
Present as distinct, solitary nodule
Thyroid nodules are more likely to be benign than malignant
131 I radioactive uptake studies. Increased uptake seen in Graves or nodular goiter. Decreased uptake seen in adenoma and carcinoma and warrants FNA biopsy*
Follicular Adenoma
Benign proliferation of follicles surrounded by fibrous capsule
Usually not functional
Papillary Carcinoma
MC type of thyroid carcinoma (80%)
Exposure to ionizing radiation in childhood is major risk factor.
Histology: Nuclear features (orphan-annie eye and grooves) and possible psammoma bodies are key identifiers.
Often spreads to cervical lymph nodes; rarely metastasizes
Good prognosis (thyroid cancers prevalence and aggressiveness are inverse)
Follicular Carcinoma
Malignant proliferation of follicles
Surrounded by fibrous capsule with invasion through capsule* (ddx vs. follicular adenoma)
FNA cannot distinguish from follicular carcinoma vs adenoma (can’t see capsule invasion on FNA which is key)
Hematogenous metastasis (backwards carcinoma. Others include renal cell, hepatic, follicular, and choriocarcinoma )
2nd MC tumor. Good prognosis (thyroid cancers prevalence and aggressiveness are inverse)
Medullary Carcinoma
Malignant proliferation of parafollicular C cells
High levels of calcitonin produced by tumor may lead to hypocalcemia
Calcitonin often deposits within tumor as amyloid. *
Familial cases associated w/ MEN 2A and 2B. Associated w/ RET mutations. Detection of RET mutation warrants prophylactic thyroidectomy.*
Anaplastic Carcinoma
Undifferentiated malignant tumor of thyroid
Usually seen in elderly (ddx. vs. Ridell’s thyroiditits).
Often invades local structures leading to dysphagia or respiratory compromise
Poor prognosis, but rare
Primary Hyperparathyroidism
Excess PTH due to disorder of parathyroid gland
Can be from parathyroid adenoma, hyperplasia, or carcinoma. Adenoma is MCC
Parathyroid Adenoma
Benign neoplasm, usually involving one gland
Usually asx
Features:
- Nephrolithiasis
- Nephrocalcinosis
- CNS disturbances (depression and seizures)
- Constipation, peptic ulcer disease, and acute pancreatitis* (Ca++ is enzyme activator)
- Osteitis fibrosis cystica
Lab findings:
- High PTH
- High Ca; Low phosphate
- Increased urinary cAMP (PTH works through Gs on tubular cells)
- Increased serum Alk Phos (due to activation of Osteoblast stimulation (which bind PTH and then release RANKL –> osteoclasts)
Rx: Surgery
Secondary Hyperparathyroidism
Excess production of PTH due to disease process extrinsic to parathyroid gland
MCC is CKD (chronic hyperphosphatemia and subsequent low free Ca++ stimulates PTH release)
Lab findings:
- Increased PTH
- Low serum Ca++
- High serum phosphate
- High Alk Phos
Hypoparathyroidism
Low PTH
Causes include AI, surgery, and Digeorge
Presents w/ perioral numbness and tingling. Muscle spasms (Chovestk’s sign and Trousseau’s sign), low PTH and low Ca
Pseudohypoparathyroidism
Due to end-organ resistance to PTH (mutation in Gs)
Hypocalcemia with high PTH
Autosomal dominant form is associated w/ short stature and short 4th and 5th digits.
Type I DM
Insulin defiency due to AI destruction of B cells
Inflammation of islets
Association w/ DR3 and DR4
Autoantibodies vs. Insulin often present
Presents in childhood w/ features of insulin deficiency:
- high serum glucose
- Weight loss, low muscle mass, and polyphagia
- Polyuria, polydipsia, and glycosuria
Treatment is lifelong insulin
Risk for DKA
DKA
Excess serum ketoacids
Often arises with stress (infection) –> epi is synergistic w/ glucagon raises blood sugar, exacerbates lipolysis (become ketones)
Clinical features:
- Hyperglycemia
- Anion gap acidosis
- Hyperkalemia (low stores however). Due to lack of insulin which normally drives in K+ and H+/K+ buffering
- Kussmaul breathing, dehydration, nausea, vomiting, mental status chages, fruity smelling breath
Rx: Fluids, Insulin, Replace electrolytes (K+)
Type 2 DM
End-organ isulin resistance leading to metabolic disorder characterized by hyperglycemia
MC type of DM; incidence is rising.
Arises in middle-aged, obese adults –> obesity leads to decreased number of insulin receptors
Strong genetic predisposition (higher than DM I)
Insulin levels are high early, low due to exhausion.
Histology reveals amyloid deposition in islets
Clinical features:
- Polyuria
- Polydyspsia
- Often silent
Dx by: Random glucose >200; fasting >126; Glucose tolerance test >200
Rx; Weight loss. Drug therapy, Insulin
Risk for hyperosmolar non-ketotic coma
NEG of vascular BM:
- Large and medium sized vessels –> atherosclerosis
- NEG of small vessels leads to hyaline arteriolocslerosis
- NEG of hemoglobin –> HbA1C
Osmotic damage (esp. cells that take up sugar w/o insulin and w/ aldose reductase)
- Schwann cells (neuropathy)
- Pericytes of retinal blood vessels
- Lens (cataracts)
Hyperosmolar non-ketotic coma
High glucose levels (>500) leads to life threatening diuresis.
Hypotension and coma
Ketones are absent (some insulin)
Pancreatic Endocrine Tumors
Tumor of islets cells
Often a component of MEN1 (along w/ parathyroid hyperplasia and pituitary adenoma)
Insulinoma
Episodic hypoglycemia w/ mental status changes that are relieved by glucose
Low glucose, high insulin and *** high C-peptide
Gastrinoma
Treatment-resistant peptic ulcers (ZE syndrome)
May be multiple and extend into jejunum
Somatistatinoma
Achlorhydria (inhibition of gastrin)
Cholelithiasis and steatorrhea (inhibition of CCK)
VIPoma
Excessive VIP
Water diarrhea, hypokalemia and achlorhydria (WDKA syndrome)
Cushing Syndrome
Excess cortisol
Sx:
- Muscle weakness w/ thin extremities
- Moon facies, buffalo hump, and truncal obesity
- Abdominal striae
- HTN (increased alpha-1 receptors)
- Osteoporosis
- Immune suppression (1. inhibits phospholipase A2 2.) inhibits IL-2, and 3.) inhibits histamine)
Dx: Increased 24-hr. cortisol syndrome
4 Major causes:
- Exogenous corticosteroids (bilateral adrenal atorphy)
- Adrenal probs (Adrenal adenoma, hyperplasia, or carcinoma –> unilateral large adrenals)
- ACTH-secreting pituitary adenoma (both adrenals big = cushing’s disease)
- Paraneoplastic ACTH secretion (Both adrenals are big, most commonly due to Small cell lung cancer)
DDX between Cushing’s disease and paraneoplastic is by high-dose dexamethasone suppression test. Ectopic doesn’t suppress.
Primary Hyperaldosteronism
Principal cell will increase Na resorption in exchange for K+ (hypernatremia and hypokalemia)
Alpha-intercalated cells will dump H+ (Metbaolic alkalosis)
MC due to adrenal adenoma (rarely sporadic hyperplasia or carcinoma)
Characterized by high aldosterone and low renin
Secondary Hyperaldosteronism
Activation of RAAS due to fibromuscular dysplasia or renal-artery atherosclerosis.
Characterized by high aldosterone and high renin.
Congenital Adrenal Hyperplasia
Excess sex steroids w/ hyperplasia of both adrenal glands
21-a hydroxylase def. is MCC
All subtypes lack cortisol which results in lack of negative feedback on ACTH resulting in hyperplasia.
21-a hydroxylase deficiency
MCC of congenital adrenal hyperplasia (continuous ACTH secretion in response to low cortisol)
Inability to convert pregnilone into cortisole or aldo. Excess shunted to sex steroids
Causes clitoral enlargement in females and precocious puberty in males.
Also results in life threatening hypotension and bilateral adrenal enlargement and salt wasting (hyponatremia and hyperkalemia w/ hypovolemia)
11-a hydroxylase defiency
Same as 21-a hydroxylase def. without salt wasting becasue you are able to make a somewhat active form of mineralocorticoids.
17-a hydroxylase deficiency
Inability to change pregnilone into cortisol or sex steroid precursors.
Excess mineralocorticoids and lack of sex steroids and cortisol.
Adrenal Insufficiency
Lack of adrenal hormones
Acute insuffiency may arise w/ Waterhous-Friedrichsen syndrome
Chronic insufficiency is due to progressive destruction of glands
AI destruction (MCC in West), TB (MCC in developing world), or metastatic carcinoma (lung cancer)
Features:
- Hypotension
- Hyponatremia, hypovolemia, and hyperkalemia
- Weakness
- Hyperpigmentation (Excess ACTH demand –> excess POMC precursor –> also produces Melanocyte Stimulating Hormone
- Vomiting and diarrhea
Waterhouse-Friedrichsen Syndrome
Young child w/ Neisseria meningitidis infection w/ DIC leading to hemorrhage in both adrenals –> lack of cortisol –> worsened hypotension
Adrenals that look like a sac of bleed.
Pheochromocytoma
Tumor of Adrenal Medulla of enterochromaffin cells (brown)
Features:
-Epidsodic hypertension, headaches, palpitations, tachycardia, and sweating
Dx: w/ increased serum metanephrines and increase 24hr. urine metanephrines and VMA
Rx: surgical excision and phenoxybenzamine (alpha-blockers)
10% disease (bilateral, malignant, familial, located outside adrenal medulla, esp. bladder walls).
Associations of MEN2A and 2B. VHL disease. NF type 1.
