Repro-Endo: Endocrine Pathology Flashcards Preview

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Flashcards in Repro-Endo: Endocrine Pathology Deck (73):

  • Benign tumor of Anterior Pituitary cells
  • Most commonly Prolactinoma (Benign)
  • Functional (Hormone-producing)
    • Features based on Hormone produced
    • Tx for Prolactinoma: Dopamine agonists (Bromocriptine or Cabergoline)
  • Non-functional (Silent) and present w/ Mass Effect
    • Bitemporal Hemianopsia --> Optic Nerve compression
    • Hypopituitarism --> Pituitary tissue compression
    • Headache

Pituitary Adenoma


  • Most common type of Pituitary Adenoma
  • Galactorrhea and Amenorrhea (Females)
  • Decreased Libido and Headache (Males)
  • Tx: Dopamine agonists (Bromocriptine, Cabergoline) to supress Prolactin production (shrinks tumor) or Surgery for Larger Lesions



  • Gigantism in Children w/ increased Linear Bone Growth (epiphysies not fused)
  • Acromegaly in Adults w/ Enlarged Bones of Hands, Feet, Jaw
    • Growth of Visceral Organs --> Dysfunction (Heart)
    • Enlarged Tongue, Deep furrows, Deep voice, Coarce facial features
    • Impaired glucose tolerance (insulin resistance)
  • Secondary Diabetes Mellitus --> GH induces Liver Gluconeogenesis
  • Dx: Elevated GH and Insulin Growth Factor-1 (IGF-1) lvls along w/ lack of GH suppression by Oral Glucose, Pituitary mass seen on brain MRI
  • Tx: Octreotide (somatostatin analog that suppresses GH release), Pegvisomant (GH receptor agonists), or Surgery

Growth Hormone Cell Adenoma


  • Secrete ACTH --> Cushing Syndrome

ACTH Cell Adenomas


Rare Pituitary Adenomas?

  • TSH cell Adenoma
  • LH-producing Adenoma
  • FSH-producing Adenoma


  • > 75% of the Pituitary Parenchyma is lost
  • Insufficient production of Hormones by Anterior Pituitary gland
  • Nonsecreting Pituitary adenomas (adults)
  • Craniopharyngioma (children)
  • A/w Pituitary Apoplexy (bleeding into the Adenoma)



  • Pregnancy-related infarction of the Pituitary gland
  • Gland doubles in size but Blood supply remains same --> Blood loss during Parturition precipitates Infarction
  • Poor Lactation or Failure to lactate
  • Loss of Pubic Hair
  • Fatigue

Sheehan Syndrome


  • Primary – Congenital defect of the Sella
  • Secondary - Trauma
  • Herniation of the Arachnoid and CSF into the Sella --> Compresses and Destroys the Pituitary Gland
  • Pituitary Gland is “absent” (empty Sella) on imaging

Empty Sella Syndrome


  • ADH deficiency
  • Hypothalamic or Posterior Pituitary Pathology (Tumor, Trauma, Infarction, Ischemic encephalopathy, Idiopathic, or Inflammation)
  • A/w Loss of Free Water --> Intense thirst
  • Polyuria and Polydipsia --> Life-threatening dehydration
  • Hypernatermia
  • Hyperosmotic volume contraction
  • High Serum osmolality (> 290 mOsm/L)
  • Low Urine osmolality and specific gravity (< 1.006)
  • Hyperosmotic volume contraction
  • Water Deprevation test fails to increase Urine osmolality (> 50% Increase)
  • Tx: Desmopressin, Intranasal DDAVP (ADH analog), Hydration

Central Diabetes Insipidus


  • Impaired Renal response to ADH
  • Hereditary (ADH receptor mutation), 2’ to Hypercalcemia
  • Lithium or Demeclocycline (ADH antagonist)
  • A/w Inherited mutations or Drugs (e.g. Lithium and Demeclocycline)
  • Similar to Central Diabetes Insipidus
  • Normal ADH lvls
  • High Serum osmolality (> 290 mOsm/L)
  • Low Urine osmolality and specific gravity (< 1.006)
  • Hyperosmotic volume contraction
  • No response to Desmopressin --> Kidney cannot respond
  • Tx: HCTZ, Indomethacin, Amiloride

Nephrogenic Diabetes Insipidus


  • Excessive ADH secretion --> Hyponatremia w/ continued urinary Na+ excretion
  • Excessive water retention
  • Urine osmolarity > Serum osmolarity
  • A/w Ectopic production (SCC of the Lung), CNS tumor, Head trauma, Pulmonary infarction/disease, and Drugs (Cyclophosphamide)
  • Clinical features a/w Retention of Free Water --> decreased Aldosterone
    • Hyponatremia --> Neuronal swelling and Cerebral edema
    • Low Serum osmolality
    • Mental status changes (Cerebral edema)
    • Seizures
    • Swelling of Nerves
  • Tx: Free Water Restriction, IV Hypertonic saline, Conivaptan, Tolvaptan, or Demeclocycline (blocks effect of ADH), Correct slowly to prevent Central Pontine Myelinolysis

Syndrome of Inappropriate ADH Secretion (SIADH)


  • Anterior Neck Mass
  • Cystic dilation of Thyroglossal Duct Remnant
  • Thyroid develops at base of Tongue --> along Thyroglossal duct --> Anterior neck
  • Normally involutes
  • Persistant duct --> Cystic dilation

Thyroglossal Duct Cyst


  • Persistence of Thyroid tissue at Base of Tongue --> Did not decent to Anterior Neck
  • Presents as a Base of Tongue Mass

Lingual Thyroid


  • Increased TSH
  • Decreased Free T3 and T4
  • Hypercholesterolemia (due to decreased LDL receptor expression)

Hypothyroidism Lab Findings


  • Decreased TSH
  • Increased T3 and T4
  • Hypocholesterolemia (due to increased LDL receptor expression)

Hyperthyrodisim Lab Findings


  • Increased level of circulating Thyroid Hormone
  • Increased Synthesis of Na+-K+-ATPase --> Increases Basal Metabolic Rate
  • Increased Expression of Beta1-adrenergic receptos --> Increases Sympathetic Nervous System activity



  • Most common cause of Hyperthyroidism
  • Autoantibody (IgG) that stimulates TSH Receptor (Type II) --> Increases release of TSH --> Increased Thyroid Hormone
  • Women of Childbearing age (20 – 40 y.o.)
  • Diffuse goiter – Constant TSH --> Hyperplasia and Hypertrophy
  • Exophthalmos and Pretibial Myxedema (dough like appearance)
    • Retro-orbital Fibroblasts behind the Orbit and Overlying the Shin (during stress and childbirth) express the TSH receptor (Exophthalmos: Proptosis, Extraocular muscle swelling)
    • TSH activation --> Glycosaminoglycan (Chondroitin sulfate and Hyaluronic acid) buildup --> Inflammation, Fibrosis, and Edema
  • Irregular Follicles w/ Scalloped Colloid and Chronic inflammation
  • Increase T4
  • Decrease TSH
  • Hypocholesterolemia
  • Increased Serum glucose
  • Risk of Thyroid Storm
  • Tx: Beta-blockers, Thioamide, and Radioiodine ablation

Graves Disease


  • Potentially Fatal due to Catecholamines and Massive Hormone excess in response to Stress (Childbirth, Surgery) as a Serious complication of Graves Disease and other Hyperthyroid disorders
  • Agitation, Delirium, Fever, Diarrhea, Coma, and Tachyarrhythmia (death)
    • Arrhythmia, Hyperthermia, Vomiting w/ Hypovolemic shock
    • Tx: Treat w/ the 3 P’s
    • Beta-blockers (Propranolol), Propylthiouricil (PTU), and Steroids (Prednisolone)
    • PTU inhibits Peroxidase-mediated Oxidation, Organification, and Coupling --> Thyroid Hormone production

Thyroid Storm


  • Enlarged Thyroid gland w/ Multiple nodules
  • Hyperfunctioning Follicular cells patches working independently of TSH due to a TSH receptor mutation (rarely malignant)
  • Increased T3 and T4
  • Relative Iodine deficiency
  • Usually Nontoxic (Euthroid)
  • Rarely, regions become TSH-independent --> T4 release and Hyperthyroidism (‘Toxic-goiter’) --> Not under the control of TSH
  • Jod-Basedow phenomenon – Thyrotoxicosis if a pt. w/ Iodine def. goiter is made Iodine replete

Toxic Multinodular Goiter


  • Hypothyroidism in Neonates and Infants
  • Mental Retardation, Short stature w/ skeletal abnormalities, Course facial features, Enlarged tongue, and Umbilical Hernia
  • 6 P’s of Symptoms
    • Pot-bellied
    • Pale
    • Puffy-faced child
    • Protruding umbilicus
    • Protuberant tongue
    • Poor Brain development
  • Thyroid is req’d for Normal brain and Skeletal development; Thyroxine (T4)
  • A/w Maternal Hypothyroidism during Pregnancy, Thyroid agenesis,  Thyroid dysgenesis, Dyshormonogenetic goiter, and Iodine deficiency (low [I-])
  • Dyshormonogenetic goiter is due to Congenital defect in Thyroid hormone production (a/w Thyroid Peroxidase)



  • Hypothyroidism in Older Children or Adults
  • Decreased Basal Metabolic Rate
  • Decreased Sympathetic Nervous system activity
  • Myxedema – accumulation of Glycosaminoglycans in the skin and soft tissue --> Deepening of Voice and Large Tongue
  • Weight gain w/ normal appetitie
  • Slowing of Mental activity
  • Muscle weakness
  • Cold intolerance /w decreased Sweating
  • Bradycardia w/ decreased Cardiac output --> SOB
  • Oligomenorrhea
  • Hypercholesterolemia
  • Constipation
  • A/w Iodine deficiency, Hashimoto Thyroiditis, Drugs (Lithium), Surgical removal, Radioablation of Thyroid



  • Autoimmune destruction of the Thyroid gland (Anti-thyroid peroxidase, Antithyroglobulin antibodies)
  • Modeeratly enlarged, nontender Thyroid
  • A/w HLA-DR5
  • Increased Risk of non-Hodgkin Lymphoma
  • Most common cause of Hypothyroidism in regions where Iodine lvls are adequate
  • Presents as Hyperthyroidism (Thyrotoxicosis due to Follicle dmg)
  • Progresses to Hypothyroidism; decrease T4 and increase TSH
  • Antithyroglobulin and Antithyroid Peroxidase Antibodies are often present --> sign of Thyroid dmg
  • Chronic inflammation w/ Germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line Follicles, lymphoid aggregate w/ Germinal centers) as seen on Histology
  • Increased Risk of B-cell Lymphoma (marginal zone): presents as an enlarging Thyroid gland Late in the disease course

Hashimoto Thyroiditis


  • Self-limited Hypothyrodism following flu-like illness
  • Increased ESR, Jaw pain, Early inflammation, Very-tender Thyroid
  • Histology: Granulomatous (inflammation) Thyroiditis following Viral infection
  • Tender Thyroid w/ Transient Hyperthyroidism (early)
  • Rarely progresses to Hypothyroidism

Subacute Granulomatous Thyroiditis (De Quervain)


  • Chronic inflammation w/ extensive Fibrosis of the Thyroid gland
  • Hypothyroidism w/ ‘Hard as Wood’ non-tender Thyroid gland
  • Fixed, Rock-hard, Painless goiter
  • Fibrosis may extend to involve Local structures (airway)
  • Considered a manifistation of IgG4-related systemic disease
  • Clinically mimics Anaplastic Carcinoma, but Pts. are Younger (40s) and Malignant cells are absent

Riedel Fibrosing Thyroiditis


  • “Hot Uptake” – Graves Disease and Nodular Goiter
  • “Cold Uptake” – Adenoma and Carcinoma
    • Biopsy is performed by Fine Needle Aspiration

131-I Radioactive Uptake studies


  • Benign Proliferation of Follicles surrounded by a Fibrous Capsule
  • Usually non-functional
  • May secrete Thyroid Hormone (less common)

Follicular Adenoma


  • Thyroidectomy is Tx: for Thyroid cancers and Hyperthyroidism
  • Sx Complications include:
    • Hoarseness (recurrent laryngeal nerve damage)
    • Hypocalcemia (due to removal of Parathyroid glands)
    • Transection of the Inferior Thyroid Artery

Thyroid Cancer


  • Most common type of Thyroid Carcinoma (80%)
  • Ionizing XRT in Childhood (irradiation for severe acne Tx)
  • Pipillae lined by cells with clear, ‘Orphan Annie eye’ nuclei and Nuclear grooves
  • Papillae are often a/w Psammoma bodies
  • Increased Risk w/ RET and BRAF mutations
  • Often spreads to Cervical Lymph nodes (neck)
  • Excellent prognosis (10 year > 95%)

Papillary Carcinoma


  • Malignant proliferation of Follicles surrounded by a Fibrous Capsule w/ Invasion through the Capsule
  • Uniform follicles
  • Entire capsule must be examined microscopically
  • FNA only examination
  • Metastasis generally occurs Hematogenously
  • Good prognossis

Follicular Carcinoma


  • Malignant proliferation of Parafollicular “C cells” (5%)
  • C cells are neuroendocrine cells that secrete Calcitonin
  • Calcitonin lowers Serum Calcium by increasing Renal Calcium excretion but is inactive at Normal physiologic levels
  • High lvls of Calcitonin --> Hypocalcemia
  • Calcitonin often deposits w/in Tumor as Amyloid
  • Bpsy --> ‘Malignant cells in an Amyloid Stroma’
  • Familial cases --> Multiple Endocrine Neoplasia (MEN 2A and 2B) a/w RET oncogene mutations
  • MEN 2 results in Medullary Carcinoma, Pheochromocytoma, and Parathyroid adenomas (2A) or Ganglioneuromas of the Oral Mucosa (2B)
  • RET mutations --> Prophylactic Thyroidectomy

Medullary Carcinoma


  • Undifferentiated malignant tumor of the Thyroid
  • A/w Elderly and Older Pts.
  • Invades Local Structures --> Dysphagia or Respiratory Compromise
  • Bpsy --> Highly Malignant Undifferentiated
  • Very Poor Prognossis

Undifferentiated / Anaplastic Carcinoma


  • Chief cells regulate Serum Free (Ionized) Calcium via Parathyroid Hormone (PTH) secretion
  • Increases Bone Osteoblast --> Osteoclast activity --> Releases Calcium and Phosphate
  • Increases Small bowel Absorption of Calcium and Phosphate (indirectly by activating Vit. D)
  • Increases Renal Calcium reabsorption (Distal tubule)
  • Decreases Phosphate reabsorption (proximal tubule)
  • Increased Serum Ionized Calcium lvls provide negative feedback to decrease PTH secretion

Parathyroid Glands


  • Benign neoplasm, usually involving one Gland
  • Often results in Asymptomatic Hypercalcemia  --> Increased PTH and Hypercalcemia
  • Nephrolithiasis (Hypercalciuria - Calcium oxalate stones, large white stone, most common)
  • Nephrocalcinosis – metastatic calcification of Renal Tubules --> Renal Insufficiency and Polyuria
  • Hypophosphatemia, Increased PTH, ALP, cAMP in Urine
  • CNS disturbances (Depression and Seizures)
  • Constipation, Peptic ulcer disease, Acute Pancreatitis
  • Osteitis Fibrosa Cystica – resorption of bone leading to fibrosis and cystic spaces filled w/ Brown Fibrous Tissue
  • “Stones, Bones, Groans, and Psychiatric Overtones”
  • Lab: Increased Serum PTH, Increased Serum Calcium, Increased Urinary cAMP, and Increased Serum Alkaline Phosphatase
  • Lab: Decreased Serum Phosphate
  • Tx: Surgical removal of Affected Gland

Parathyroid Adenoma (Primary)


  • Excess production of PTH due to Extrinsic process
  • Hypovitaminosis D --> Decreased Ca2+ gut-absorption, Increased PO42- absorption
  • Hypocalcemia and Hyperphosphatemia a/w Renal Failure
  • Increased ALP, Increased PTH
  • Renal osteodystrophy (2nd and 3rd Hyperparathyroidism)
  • Most common cause of Chronic Renal Failure
    • Renal insufficiency --> Decreased Phosphate excretion
    • Increased Serum Phosphate binds Free Calcium
    • Decreased Free Calcium stimulates all four Parathyroid glands
    • Increased PTH leads to Bone resorption (Renal Osteodystrophy)
    • Lab: Increased PTH, decreased Serum Calcium, Increased Serum Phosphate, Increased Alkaline Phosphatase

Secondary Hyperparathyroidism


  • Refractory (autonomous) hyperparathyroidism resulting from Chronic Renal Disease
  • Increased Ca2+

Tertiary Hyperparathyrodism


  • Low PTH
  • Autoimmune DMG to the Parathyroids, Surgical excision, and DiGeorge syndrome (Failure to develop 3rd / 4th Pharyngeal Pouch)
  • Symptoms a/w Low Serum Calcium (Hypocalcemia) and Tetany
  • Numbness and Tingling (peri-oral)
  • Muscle spasms (tetany) – w/ filling blood pressure cuff and carpal spasm --> Trousseau sign or tapping of Facial nerve – Chvostek sign
  • Decreased PTH and decreased Serum Calcium
  • End-organ resistance to PTH
  • Labs reveal Hypocalcemia w/ Increased PTH lvls
  • Autosomal dominant form a/w Short Stature and Short 4th and 5th Digits



  • Albright hereditary osteodystrophy – autosomal dominant unresponsiveness of Kidney to PTH
  • Hypocalcemia
  • Shortened 4th / 5th digits
  • Short stature



  • Insulin is secreted by Beta cells, center of the islets
  • Major anabolic hormone that upregulates insulin-dependent glucose transporter protein (GLUT4) on skeltal muscle and adipose tissue (glucose uptake by GLUT4 --> decreases serum glucose)
  • Increased Glucose uptake by tissues leads to increased Glycogen synthesis, Protein synthesis, and Lipogenesis
  • Glucagon secreted by Alpha cells; opposes insulin in order to increase Blood Glucose lvls (fasting) via Glycogenolysis and Lipolysis

Islets of Langerhans


  • Insulin def. --> metabolic Hyperglycemia due to autoimmune destruction of Beta cells by T lymphocytes (Type IV)
  • Inflammation of Islets
  • A/w HLA-DR3 and HLA-DR4
  • Autoantibodies against insulin – seen years before clinical disease develops
  • Childhood manifests w/ Insulin def.
  • High serum glucose --> decreased  glucose uptake by fat and skeletal muscle
  • Weight loss, Low muscle mass, Polyphagia – Unopposed Glucagon leads to Gluconeogenesis, Glycogenolysis, and Lipolysis --> Hyperglycemia
  • Polyuria, Polydipsia, and Glycosuria – Exceeding Renal ability to reabsorbe --> Osmotic diuresis
  • Hist: Islet leukocytic infiltrate
  • Tx: Lifelong insulin

Type I Diabetes Mellitus


  • Excessive serum Ketones
  • A/w Stress (infection); Epi stimulates Glucagon --> Lipolysis (along w/ Gluconeogenesis and Glycogenolysis)
  • Increased Lipolysis --> Increased Free Fatty Acids (FFAs)
  • Liver converts FFAs --> Ketone bodies (Beta-hydroxybutyric acid > Acetoacetic acid)
  • Hyperglycemia (> 300 mg/dL)
  • Anion gap metabolic acidosis w/ Ketoacids in blood
  • Hyperkalemia
  • Kussmaul respirations --> Blow off the acidosis (Rapid/Deep breathing)
  • Dehydration, Nausea, Vomiting, Abdominal pain, Mental status change, Fruity breath (Acetone), Psychosis/delirium, Dehydration
  • Tx: Fluids, Insulin, Replacement of electrolytes (K+, Potassium), Glucose if necessary to prevent Hypoglycemia

Diabetic Ketoacidosis


  • Hyperglycemia
  • Increased H+
  • Decreased HCO3- (anion gap metabolic acidosis)
  • Increased Blood Ketone lvls
  • Leukocytosis
  • Hyperkalemia
  • Depleted Intracellular K+ due to Transcellular shift from decreased Insulin

Labs: Ketoacidosis


  • End-organ insulin resistance --> Metabolic Hyperglycemia --> Progressive pancreatic B-cell failure
  • Middle-aged, Obese adults
  • NOT related to HLA-DR#s system
  • Obesity --> decreased numbers of Insulin receptors on skeletal muscle and Adipose tissue
  • Strong genetic predisposition
  • Insulin lvls increased early in disease
  • Insulin lvls decreased later in disease due to Beta cell exhaustion
  • Amyloid deposition in the Islets
  • Polyuria, Polydipsia, Hyperglycemia, often clinically silent
  • Hist: Islet amyloid polypeptide (IAPP) deposits
  • Dx:
    • Random Glucose > 200 mg/dL
    • Fasting Glucose > 126 mg/dL
    • GTT w/ Serum Glucose > 200 mg/dL 2 hrs after glucose loading
  • Tx: Weight loss (diet and exercise), Initial drug therapy (Sulfonylureas or Metformin) or exogenous Insulin after Beta cell exhaustion

Type 2 Diabetes Mellitus


  • High glucose (> 500 mg/dL) leads to life-threatening diuresis w/ Hypotension and Coma
  • Ketones are absent due to Small amounts of Circulating Insulin

Hyperosmolar Non-Ketotic Coma


  • Atherosclerosis
  • Cardiovascular disease (CAD) leading cause of Death (MI) among Diabetics
  • Peripheral vascular disease in Diabetics --> Nontraumatic amputations
  • Cerebrovascular disease

Nonenzymatic Glycosylation (NEG) of
Vascular Basement Membranes (Large)


  • Diffuse thickening of basement membrane --> Retinopathy (Hemorrhage, Exudates, Microaneurysms, Vessel proliferation), Glaucoma
  • Renal arterioles involvement --> Glomerulosclerosis --> Small scarred Kidneys w/ Granular surface--> Nephropathy (nodular sclerosis, progressive proteinuria, Chronic renal failiure) --> HTN
  • Efferent arterioles --> Glomerular Hyperfiltration Injury w/ Microalbuminuria --> Nephrotic syndrome (Kimmelstiel-Wilson nodules in Glomeruli)
  • Hemoglobin produces Glycated Hemoglobine (HbA1C) a marker of Glycemic control

Nonenzymatic Glycosylation (NEG) of
Vascular Basement Membranes (Small)


  • Glucose freely enters Schwann cells (myelinate peripheral nerves), Pericytes of Retinal Blood vessels, and the Lens
  • Aldose reductase converts Glucose --> Sorbitol --> Osmotic damage --> Peripheral Neuropathy, Impotence, Blindness, and Cataracts
  • Diabetes is the leading cause of Blindness in the Developed world

Osmotic Damage


  • Tumors of the Islet cells
  • < 5% of Pancreatic neoplasms
  • A/w MEN 1, Parathyroid Hyperplasia, Pituitary Adenomas

Pancreatic Endocrine Neoplasms


  • Tumor of Beta cells of Pancreas --> Overprodcution of Insulin --> Hypoglycemia
  • Whipple triad of Episodic CNS: Lethargy, Sycope, Diplopia
  • Episodic Hypoglycemia w/ Mental status changes that are relieved by administration of Glucose
  • Increased C-peptide lvls (vs. Exogenous insulin use)
  • Diagnosed by decreased Serum Glucose lvls (usually < 50 mg/dL)
  • Increased Insulin and Increased C-peptide
  • Tx: Surgical resection



  • Present as Treatment-resistant peptic ulcers (Zollinger-Ellison Syndrome)
  • Ulcers can be multiple and can extend into the Jejunum



  • Gastrin secreting tumor of Pancreas or Duodenm
  • Acid Hypersecretion causes recurrent ulcers in Distal Duodenum and Jejunum
  • Abdominal pain (peptic ulcer disease, distal ulcers)
  • Diarrhea (malabsorption)
  • A/w MEN 1

Zollinger-Ellison Syndrome


  • Parathyroid tumors
  • Pituitary tumors (Prolactin or GH)
  • Pancreatic endocrine tumors – Zollinger-Ellison syndrome, Insulinomas, VIPomas, Glucagonomas
  • Presents w/ Kidney stones and Stomach Ulcers
  • 3P’s = “Diamond”
    • Pituitary
    • Parathyroid - Parathyroid
    • Pancreas

Wermer Syndrome (MEN 1)


  • Medullary Thyroid carcinoma (secretes Calcitonin)
  • Pheochromocytoma
  • Parathyroid hyperplasia
  • A/w RET gene
  • Autosomal dominant
  • 2P’s - "Square"
    • Parathyroids – Parathyroids
    • Pheochromocytoma (adrenals) - Pheochromocytoma (adrenals)

Sipple Syndrome (MEN 2A)


  • Medullary thyroid carcinoma (secretes Calcitonin)
  • Pheochromocytoma
  • Oral / Intestinal ganglioneuromatosis (mucosal neuromas)
  • A/w Marfanoid habitus
  • A/w RET gene
  • Autosomal dominant
  • 1P – “Triangle”
    • Oral
    • Pheochromocytoma (adrenals) – Pheochromocytoma (adrenals)



  • Present as Achlorhydria (due to inhibition of Gastrin) and Cholelithiasis w/ Steatorrhea (due to inhibition of Cholecystokinin)



  • Secrete excessive vasoactive interstinal peptide leading to watery diarrhea, Hypokalemia, and Achlorhydria



  • Excess Aldosterone
  • HTN, Hypokalemia, and Metabolic Alkalosis
  • Aldosterone increases absorption of Sodium and Secretion of Potassium and Hydrogen Ions in the Distal Tubule and Collecting duct
  • Increased Sodium expands Plasma Volume leading to HTN
  • Edema often absent, due to Aldosterone escape



  • Bilateral Adrenal Hyperplasia – or -
  • Adrenal Adenoma (Conn syndrome)
  • Adrenal Carcinoma (rare)
  • HTN, 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
  • High Aldosterone and Low Renin --> Increased Renal Perfusion pressure, downregulation of Renin
  • Tx: Mineralocorticoid receptor Antagonist (Spironolactone or Eplerenone), Adenomas are usually surgically resected

Primary Hyperaldosteronism


  • Renal perception of Low Intravascular Volume
    --> Overactive Renin-Angiotensin system
  • A/w Renal artery stenosis, CHF, Cirrhosis, or Nephrotic syndrome
  • Seen w/ Activation of the Renin-angiotensin system (e.g. Renovascular HTN or CHF)
  • High Aldosterone
  • High Renin
  • Tx: Spironolactone

Secondary Hyperaldosteronism


  • Rarely due to Glucocorticoid-remediable aldosteronism (GRA)
  • Aberrant expression (AD) of Aldosterone synthase in the Fasciculata
  • Presents in children as HTN, Hypokalemia, High Aldosterone and Low Renin
  • Responds to Dexamethasone, Confirmed w/ Genetic testing

Familial Hyperaldosteronism


  • Mimics Hyperaldosteronism
  • Decreased degradation of Sodium Channels (AD) in Collecting Tubules
  • HTN, Hypokalemia, and Metabolic Alkalosis in a Young Pt.
  • Low Aldosterone and Low Renin
  • Tx: Potassium-sparing diuretics (e.g. Amiloride or Triamterene), blocks Tubular Sodium Channels, Spironolactone is not effective

Liddle Syndrome


  • Excess Cortisol
  • Muscle weakness w/ Thin Extremeties – Cortisol breaks down muscle to produce Amino acis for Gluconeogenesis
  • Moon Facies, Buffalo hump, and Truncal obesity – High Insulin (due to High Glucose) Increases storage of Fat Centrally
  • Abdominal Striae – due to impaired collagen synthesis resulting in thinning of skin --> Ruptured blood vessels on abdomen
  • Hypertension often w/ Hypokalemia and Metabolic acidosis
  • High cortisol increases sensitivity of Peripheral vessels to Catecholamines
  • At very high levels, Cortisol cross-reacts w/ Mineralocorticoid receptors (aldosterone is not increased)
  • Osteoporosis
  • Immune Suppression
  • Dx: 24-hour Urine Cortisol lvl, Late night salivary cortisol lvl, low-dose Dexamethasone suppression test
  • Plasma ACTH distinguishes ACTH-dependent causes Cushing syndrome from ACTH-independent causes

Hypercortisolism (Cushing Syndrome)


  • ACTH-secreting Pituitary Adenoma
  • Paraneoplastic ACTH secretion (SC Lung cancer, Bronchial carcinoids)
  • Increased ACTH --> Bilateral Adrenal Hyperplasia
  • Responsible for the majority of Enogenous cases of Cushing syndrome

Cushing Disease


  • Most common cause of Congenital Adrenal Hyperplasia (90%)
  • Decreased Aldosterone
  • Decreased Cortisol
  • Steroidogenesis is shunted towards Androgens
  • Neonates: Hyponatremia, Hyperkalemia, and Hypovolemia w/ Life-threatening HTN (Salt wasting)
  • Females: Clitoral enlargement (genital ambiguity due to increased Androgens)
  • Non-classic form presents later in life w/ Androgen excess --> Precocious puberty (males) or Hirsutism w/ Mentrual Irregularities (Females)

21-hydroxylase deficiency


  • Similar to 21-hydroxylase def. but weak Mineralocorticoids (DOC) are Increased
  • HTN (sodium retention)
  • Mild Hypokalemia (no salt wasting)
  • Renin and Aldosterone are low

11-hydroxylase deficiency


  • Decreased Cortisol
  • Decreased Androgens
  • Weak Mineralocorticoids (DOC) are increased leading to HTN and mild Hypokalemia
  • Renin and Aldosterone are low
  • Decreased Androgens (Adrenal and Gonads) lead to Primary Amenorrhea and Lack of Pubic Hair in Females or Pseudohermaphroiditism in Males

17-hydroxylase deficiency


  • Dx: Screening w/ serum 17-hydroxyprogesterone lvls
    • Increased in 21- and 11-hydroxylase def.
    • Decreased in 17-hydroxylase def.

Screening for CAH


  • Classic cause of Acute Adrenal Insufficiency w/ the Adrenal Hemorrhage (gland converted to a sac of blood)
  • A/w Hemorrhagic Necrosis of Adrenal glands
  • Classically due to DIC, in young Children w/ Neisseria meningitidis infection, and Endotoxic shock
  • Lack of Cortisol exacerbate HTN --> Death

Waterhouse-Friderichsen Syndrome


  • Most common Adrenal Medulla in Children
  • < 4 y.o.
  • Originates from Neural Crest Cells
  • Occurs anywhere along the Sympathetic chain
  • A/w Abdominal distention and a Firm, Irregular mass that can Cross the Midline (vs. Wilms tumor: smooth and unilateral)
  • Homovanillic acid (HVA) a breakdown product of Dopamine in Urine
  • Bombesin +
  • Low liklihood of HTN
  • A/w N-myc oncogene



  • Due to Atrophy or Progressive destruction of the Adrenal glands
  • Def. of Aldosterone and Cortisol
  • All 3 Corticol divisions and Spares the Medulla
  • (3) Main causes of Adrenal Destruction:
  1. Autoimmune destruction (in the West)
  2. TB (developing world)
  3. Metastatic carcinoma (lung)
  • HTN
  • Hyponatremia
  • Hypovolemia
  • Hyperkalemia
  • Metabolic acidosis
  • Weakness
  • Hyperpigmentation (ACTH stimulates melanocytes. POMC --> MSH)
  • Vomiting
  • Diarrhea
  • Hyperpigimentation + Hyperkalemia --> Dx Primary vs. Secondary Insuff.

Addison Disease
(Chronic Adrenal Insufficiency)


  • Decreased Pituitary ACTH
  • No Skin / Mucosal Hyperpigmentation and no Hyperkalemia

Secondary Adrenal Insufficiency


  • Tumor of Chromaffin Cells
  • Increased Serum Catecholamines: Epi, NorEpi, Dopamine
  • Symptoms occur in “spells” – relapse and remit
  • Episodic Hyperadrenergic Symptoms (5 P’s)
  • Pressure: BP --> Episodic HTN
  • Pain - Headache
  • Palpitations - Tachycardia
  • Perspiration – Sweating
  • Pallor
  • Increased Serum Metanephrines / Catecholamines and Increased 24-hour Urine Metanephrines and Vanillylmandelic acid (VMA)
  • A/w MEN 2A and 2B (RET gene test), vonHippel-lindaue disease (loss of tumor supressor), Neurofibromatosis Type I
  • Tx: Beta-blockers followed by Surgical Excision w/ Phenoxybenzamine (irreversible alpha-blocker, alpha-antagonist)
  • Very Important: “A’s before B’s” to avoid Hypertensive Crisis!



Rule of 10’s of Pheochromocytoma?

  • Most common tumor of the Adrenal Medulla in Adults
  • Derived from Chromaffin cells (from Neural crest)
  • Rule of the 5x 10’s
    • 10% Malignant
    • 10% Bilateral
    • 10% Extra-Adrenal
    • 10% Calcify
    • 10% Kids


  • Carcinoid tumors (rare, neuroendocrine cells)
    • 1/3 Metastasize
    • 1/3 present w/ 2nd malignancy
    • 1/3 are multiple
  • Small bowel tumors (most common)
    --> secrete High levels of Serotonin (5-HT)
  • Not seen if tumor is limited to GI tract (5-HT first pass metabolism)
  • Recurrent diarrhea
  • Cutaneous flushing
  • Asthmatic wheezing
  • Right-sided valvular disease
  • Increased 5-hydroxyindoleacetic acid (5-HIAA) in urine
  • Niacin def. (Vit. B3) --> Pellagra

Carcinoid Syndrome