Repro-Endo: Endocrine Pathology Flashcards by James Wren

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

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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

Prolactinoma

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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

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Secrete ACTH –> Cushing Syndrome

ACTH Cell Adenomas

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Rare Pituitary Adenomas?

TSH cell Adenoma
LH-producing Adenoma
FSH-producing Adenoma

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> 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)

Hypopituitarism

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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

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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

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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

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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

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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)

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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

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

Lingual Thyroid

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

Hypothyroidism Lab Findings

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

Hyperthyrodisim Lab Findings

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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

Hyperthyroidism

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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

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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

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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

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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)

Cretinism

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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

Myxedema

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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

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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)

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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

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* “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** (2^nd and 3^rd 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* PTH * *Increased* Ca2+

Tertiary Hyperparathyrodism

* Low PTH * **Autoimmune DMG** to the **Parathyroids**, **Surgical excision**, and **DiGeorge syndrome** (Failure to develop **3^rd / 4^th 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 4^th and 5^th Digits

Hypoparathyroidism

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

Pseudohypoparathyroidism

* 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 (HbA_1C) 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

Insulinomas

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

Gastrinomas

* 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)

MEN 2B

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

Somatostatinomas

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

VIPomas

* 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

Hyperaldosteronism

* 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**

Neuroblastoma

* 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!**

Pheochromocytoma

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/ 2^nd 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

Repro-Endo: Endocrine Pathology Flashcards

(73 cards)