Endocrine Pathology

↑ cortisol

Exogenous (iatrogenic) steroids is #1 cause; ↓ ACTH

• Endogenous causes:
• 1. Cushing's disease (70%): ACTH secretion from pituitary adenoma; ↑ ACTH
• 2. Ectopic ACTH (15%): nonpituitary tissue making ACTH (e.g. small cell lung cancer, bronchial carcinoids); ↑ ACTH
• 3. Adrenal (15%): adenoma, carcinoma, nodular adrenal hyperplasia; ↓ ACTH
• 

• Presentation:
• -hypertension
• -weight gain, moon facies, truncal obesisty, buffalo hump
• -hyperglycemia (insulin resistance)
• -skin changes (thinning, striae)
• -osteoporosis
• -amenorrhea
• -immune suppression
• 

• 
• "Dex" is an exogenous steroid that provides negative feedback to the pituitary to ↓ ACTH secretion

• Primary: adrenal hyperplasia or aldo-secreting adrenal adenoma (Conn's syndrome)
• Presentation:
• -hypertension
• -hyhpokalemia
• -metabolic alkalosis
• -low plasma renin
• -bilateral or unilateral

• Treatment:
• -surgery to remove the tumor
• -spironolactone (aldosterone antagonist)

• Secondary: Renal perception of low ECV → overactive renin-angiotensin system
• -high plasma renin
• Causes:
• -Renal artery stenosis
• -chronic renal failure
• -CHF
• -cirrhosis
• -nephrotic syndrome

• Chronic 1° adrenal insufficiency due to adrenal atrophy or destruction by disease (autoimmune, TB, metastasis)
• ·Deficiency of aldosterone and cortisol

• Sx:
• -hypotension (hyponatremic volume contraction)
• -hyperkalemia
• -acidosis
• -skin hyperpigmentation (due to MSH, by-product of ↑ACTH)

*Characterized by Adrenal Atrophy and Absence of hormone production; involves All 3 cortical divisions (spares medulla)

**Distinguish from 2° adrenal insufficiency(↓ pituitary ACTH production), which has no skin hyperpigmentation and no hyperkalemia

• Acute 1° adrenal insufficiency due to adrenal hemorrhage
• Associated with:
• - Neisseria meningitidis septicemia
• - DIC
• - Endotoxic shock

• Most common tumor of adrenal medulla in adults
• -Derived from chromaffin cells (neural crest)
• 

• -Most secrete epinephrine, NE, and dopamine → episodic hypertension
• - ↑ Urinary VMA (breakdown product of NE, EPI)
• - ↑ Plasma catecholamines
• - Associated with neurofibromatosis type 1, MEN types 2A and 2B

• Treatment:
• -Surgical removal only after effective α- and β-blockade:
•     - Irreversible α-antagonist (phenoxybenzamine) given first to avoid hypertensive crisis
•     - β-blockers given to slow heart rate

• *Episodic hyperadrenergic symptoms (5 P's):
• -Pressure (elevated BP)
• -Pain (headache)
• -Perspiration
• -Palpitations (tachycardia)
• -Pallor

• *Rule of 10's:
• -10% malignant
• -10% bilateral
• -10% extra-adrenal
• -10% calcify
• -10% in kids

• Most common tumor of the adrenal medulla in children
• Can occur anywhere along the sympathetic chain
• ↑ Urine homovanillic acid (HVA) (breakdown product of DA)
• Less likely to develop hypertension
• Overexpression of N-myc oncogene is associated with rapid tumor progression

• Cystic dilation of thyroglossal duct remnant
• **thyroid develops at base of tongue and travels along the thyroglossal duct to the anterior neck
• Duct normally involutes
• Presentation: anterior neck mass

• Persistence of thyroid tissue at the base of tongue
• Presentation: base of tongue mass

Decreased metabolic rate, decreases SNS activity

• Sx:
• -Myxedema- accumulation of glycosaminoglycans in the skin and soft tissue
• -Cold intolerance (↓ heat production)
• -Weight gain, ↓ appetite
• -Hypoactive, lethargy, fatigue, weakness
• -Constipation
• -↓ reflexes
• -Myxedema (facial/periorbital)
• -Dry, cool skin; coarse, brittle hair
• -Bradycardia, dyspnea on exertion
• -slowing of mental activity
• -Muscle weakness
• -Bradycardia w/decreased CO →SOB and fatigue
• -Oligomenorrhea
• -Hypercholesterolemia
• -Constipation

• Labs:
• -↑ TSH (sensitive for 1° hypothyroidism)
• -↓ free T₄

Increased basal metabolic rate, increased SNS activity

• Sx:
• -Heat intolerance (↑ heat production)
• -Weight loss, ↑ appetite
• -Hyperactivity
• -Tachycardia
• -Diarrhea, malabsorption
• -↑ reflexes
• -Pretibial myxedema (Grave's disease)
• -Warm, moist skin; fine hair
• -Chest pain, palpitations, arrhythmias, ↑ β-adrenergic receptors
• -Oligomenorrhea
• -bone resoprtion with hypercalcemia (risk for osteoporosis)
• -Hypercholesterolemia
• -Hyperglycemia (gluconeogenesis and glycogenolysis)

• Labs:
• -↓ TSH (if 1°)
• -↑ free or total T_⁴
• -↑ free or total T_³

• Hashimoto's thyroiditis
• Cretinism
• Subacute thyroiditis (de Quervain's)
• Riedel's thyroiditis
• Other causes (drugs [lithium], surgical removal or radioablation)

• -Most common cause of hypothyroidism
• -Autoimmune destruction/disorder (thyroid peroxidase, antithyroglobulin antibodies)
• -Associated with HLA-DR5
• -↑ risk of non-Hodgkin's lymphoma

• Histology: Hürthle cells (eosinophilic metaplasia of cells that line follicles), lymphocytic infiltrate with germinal centers
• →increased risk for B-cell (marginal zone) lymphoma

Findings: moderately enlarged, nontender thyroid

*May be hyperthyroid early in course (thyrotoxicosis during follicular rupture)

• Severe fetal hypothyroidism
• -Endemic cretinism where endemic goiter is prevalent (lack of dietary iodine)
• -Sporadic cretinism is caused by defect in T₄ formation or developmental failure in thyroid formation
• -dyshormonogenetic goiter: congenital defect in thyroid hormone production: most commonly involves thyroid peroxidase

• Sx: 
• -mental retardation
• -short stature with skeletal abnormalities
• -coarse facial features
• -enlarged tongue
• -umbilical hernias

• Findings: *5 P's
• -Pot-bellied
• -Pale
• -Puffy-faced child
• -Protruding umbilicus
• -Protuberant tongue

Self-limited hypothyroidism often following a flu-like illness

Histology: granulomatous inflammation

Findings: ↑ ESR, jaw pain, early inflammation, very tender thyroid


*may be hyperthyroid early in course

Chronic inflammation with extensive fibrosis of the thyroid gland (hypothyroid)

Findings: fixed, hard (rock-like), and painless/nontender goiter, often in young females

*Considered a manifestation of IgG₄-related systemic disease

• Congenital hypothyroidism
• iodine deficiency
• goitrogens
• Wolff-Chaikoff effects
• painless thyroiditis

• Toxic multinodular goider
• Graves' disease
• Thyroid storm

• Enlarged thyroid gland with multiple nodules
• Cause: relative iodine deficiency
• Usually nontoxic (euthyroid)

• Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor
• ↑ release of T3 and T4
• Hot nodules are rarely malignant
• 
• Jod-Basedow phenomenon: thyrotoxicosis if a pt with iodine deficiency goiter is made iodine replete

• Autoimmune (IgG) hyperthyroidism with thyroid-stimulating immunoglobulins (TSI)
• Opthalmopathy (proptosis, EOM swelling)
• 
• Pretibial myxedema
• ↑ in connective tissue deposition
• Diffuse goiter
• Often presents during stress (childbirth); often in women of child-bearing age
• Histology: irregular follicles with scalloped colloid and chronic inflammation
• Tx:β-blockers, thioamide (blocks peroxidase), and radioiodine ablation

• Stress-induced catecholamine surge leading to death by arrhythmia
• -other sx: hyperthermia, vomiting with hypovolemic shock
• Serious complication of Graves' or other hyperthyroid disorders
• May see ↑ ALP due to ↑ bone turnover
• Tx: propylthiouracil (PTU), β blockers, and steroids

• Propylthiouracil (PTU)
• inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis as well as peripheral conversion of T4 to T3

• Follicular adenoma: benign, usually non-functional
• Papillary carcinoma: most common type of thyroid cancer (80%)
• Follicular carcinoma
• Medullary carcinoma
• Anaplastic carcinoma

• Papillary carcinoma: most common
• -Excellent prognosis
• -Histology: empty-appearing nuclei (Orphan Annie's eyes); psammoma bodies, nuclear grooves
• -
• -↑ risk with childhood irradiation

• Follicular carcinoma: invasion through the fibrous capsule
• -good prognosis
• -uniform follicles
• -Mets generally occur hematogenously

• Medullary carcinoma:
• -from parafollicular "C cells"
• -produce calcitonin → hypocalcemia
• -Histology: calcitonin deposits within tumor as sheets of amyloid in stroma
• -Associated with MEN types 2A and 2B

• Undifferentiated/anaplastic:
• -older patients
• -very poor prognosis

• Lymphoma:
• -associated with Hashimoto's thyroiditis

Disorder of the parathyroid gland itself; usually a parathyroid adeonma; sporadic hyperplasia and parathyroid carcinoma are less common

Parathyroid adenoma: benign neoplasm, most often asymptomatic hypercalcemia

• -Hypercalcemia
• -Hypercalciuria (renal stones)
• -Hypophosphatemia
• -↑ PTH
• -↑ alkaline phosphatase
• -↑ cAMP in urine

• Sx: often asymptomatic, or may present with weakness and constipation ("groans")
• -CNS disturbances
• Osteitis fibrosa cystica - cystic bone spaces filled with brown fibrous tissue (bone pain)

"Stones, bones, and groans"

• 2° hyperplasi due to ↓ gut Ca²⁺ absorption and ↑ phosphate
• -Most often in chronic renal failure (hypo-VitD → decrease Ca absorption; decreased phosphate excretion → decreased free calcium)

• Labs:
• -Hypocalcemia
• -hyperphosphatemia in chronic renal failure (hypophosphatemia in most other causes)
• -↑ alkaline phosphatase
• -↑ PTH

Renal osteodystrophy: bone lesions due to 2° or 3° hyperparathyroidism due, in turn, to renal disease

• Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease
• ↑↑PTH
• ↑Ca²⁺

• Causes:
• -Accidental surgical excision
• -Autoimmune destruction
• -DiGeorge syndrome (failure to develop 3rd, 4th pharyngeal pouch)

• Findings: sx due to low serum calcium
• -hypocalcemia
• -numbness and tingling
• -tetany
• -Chvostek's sign: tapping of facial nerve → contraction of facial muscles
• -Trousseau's sign: occlusion of brachial artery with BP cuff → capal spasm

End-organ ressitance to PTH

• Labs:
• -hypocalcemia
• -Increased PTH

• Autosomal dominant form: kidney unresponsiveness to PTH; defect in Gs leading to increased cAMP
• -Hypocalcemia
• -Shortened 4th/5th digits
• -Short stature

Benign tumor of anterior pituitary cells:

• Functional vs. non-functional:
• -hormone producing
• -mass effect

• Most commonly prolactinoma
• Findings:
• -amenorrhea
• -galactorrhea
• -low libido
• -infertility (↓GnRH)
• -headache

*Can impinge on optic chiasm → bitemporal hemianopia

• Treatment:
• -dopamine agonists (bromocriptine or cabergoline) for prolactinomas
• -surgical resection

• Gigantism in children
• Acromegaly in adults:
• -enlarged bones of hands, feet, and jaw
• -growth of visceral organs → dysfunction (cardiac failure)
• -Enlarged tongue

• Presentation:
• -Secondary diabetes mellitus (GH induces liver gluconeogenesis)

Diagnosed by elevated GH and insulin growth factor-1 (IGF-1), lack of GH suppression by oral glucose

• Tx:
• -octreotide (somatostatin analog)
• -GH receptor antagonists
• -Surgery

Secrete ACTH leading to Cushing syndrome

Excess GH in adults. Typically caused by pituitary adenoma

• Findings:
• -large tongue with deep furrows
• -deep voice
• -large hands and feet
• -coarse facial features
• -impaired glucose tolerance (insulin resistance)

• Diagnosis:
• -↑ serum IGF-1
• -Failure to suppress serum GH following oral glucose tolerance test
• -pituitary mass seen on brain MRI

• Tx:
• -Resection followed by somatostatin analog if not cured

*↑GH in children → gigantism (↑ linear bone growth)

Characterized by intense thirst and polyuria together with an inability to concentrate urine owing to a lack of ADH or lack or renal response to ADH

• Central DI: lack of ADH → hypothalamic or posterior pituitary pathology
• -pituitary tumor
• -trauma
• -surgery
• -histiocytosis X
• Sx:
• -polyuria, polydipsia
• -hypernatremia, high serum osmolality
• -Low urine osmolality
• Dx: fails water deprivation test (fails to increase urine osmolality)

• Nephrogenic DI: lack of renal response to ADH
• -Hereditary
• -2° to hypercalcemia, lithium, demeclocycline [ADH antagonist]
• sx: same as central
• Dx: same
• Tx: does not respond to desmopressin (synthetic ADH)

• Findings:
• -Urine specific gravity <1.006
• -Serum osmolality >290mOsm/L

• Diagnosis:
• -Water deprivation test: U_osm doesn't ↑
• -response to desmopressin (synthetic ADH) distinguishes central DI from nephrogenic DI

• Tx:
• -Adequate fluid intake
• -Central: intranasal desmopressin
• -Nephrogenic: HCTZ, indomethacin, or amiloride

• Sx:
• -Excessive ADH secretion and water retention
• -Hyponatremia with continued urinary Na⁺ excretion → neuronal swelling and cerebral edema
• -Mental status changes, seizures
• -U_osm > P_{osm (low serum osmolality)}
• -Body responds with ↓ aldosterone (hyponatremia) to maintain near-normal volume status
• -Very low sodium levels can lead to seizures
• **Must correct slowly

• Causes:
• -Ectopic ADH (small cell lung cancer)
• -CNS disorders/head trauma
• -Pulmonary disease
• -Drugs (e.g. cyclophosphamide)

• Treatment:
• -fluid restriction
• -IV saline
• -Conivaptan, tolvaptan, demeclocycline

• Undersecretion of pituitary hormones due to:
• -Nonsecreting pituitary adenoma (adults), craniopharyngioma (children)
• -Pituitary apoplexy (bleeding into an adenoma)
• -Sheehan's syndrome (ischemic infarct of pituitary following postpartum bleeding; usually presents with failure to lactate, loss of pubic hair, fatigue)
• -Empty sella syndrome (atrophy or compression of pituitary, often idiopathic, common in obese women)
• -Brain injury, hemorrhage
• -Radiation

Sx don't arise till >75% of pituitary parenchyma is lost

• Treatment:
• -Substitution therapy (corticosteroids, thyroxine, sex steroids, human growth hormone)

• Nonenzymatic glycosylation:
• 1. Small vessel disease (diffuse thickening of basement membrane)
• -retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation)
• 
• -glaucoma
• -nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to HTN, Kimmelstiel-Wilson nodules)

• 2. Large vessel atherosclerosis
• -CAD
• -Peripheral vascular occlusive disease
• -Gangrene → limb loss
• -Cerebrovascular disease

• Osmotic damage (sorbitol accumulation in organs with aldose reductase):
• -Neuropathy (motor, sensory, and autonomic degeneration)
• -Cataracts

• Polydipsia, polyuria, polyphagia, weight loss, DKA (type 1), hyperosmoalr coma (type 2), unopposed secretion of GH and epinephrine (exacerbating hyperglycemia)
• 

• Fasting serum glucose >126
• Random blood glucose >200
• Oral glucose tolerance test (OGTT): 2hr>200
• HbA_1C (reflects average blood glucose over prior 3 months)

• 1° defect: Autoimmune destruction of β cells
• Insulin always needed
• Presents: <30 years of age
• NOT associated with obesity
• Relatively weak genetic predisposition (50% concordance in twins)
• Polygenic
• HLA associations: HLA-DR3 and 4
• Severe glucose inolerance
• High sensitivity to insulin
• Ketoacidosis: common
• β cell number ↓
• Serum insulin level ↓
• Classic sx (poyluria, polydipsia, polyphagia, weight loss): common
• Histology: Islet leukocytic infiltarte

• 1° defect: ↑ resistance to insulin, progressive pancreatic β cell failure
• Insulin needed sometimes
• Presents: >40 years of age
• Associated with obesity
• Strong genetic predisposition (90% concordance in twins)
• Polygenic
• No HLA associations
• Mild to moderate glucose inolerance
• Low sensitivity to insulin
• Ketoacidosis: rare
• β cell number is variable (with amyloid deposits)
• Serum insulin level is variable
• Classic sx (poyluria, polydipsia, polyphagia, weight loss): Sometimes
• Histology: Islet amyloid (AIAPP) deposits)

• Significant complication of diabetes (usually type 1)
• -Usually due to ↑ insulin requirement from ↑ stress (e.g. infection)
• -Excess fat breakdown and ↑ ketogenesis from ↑ free fatty acids, which are then made into ketone bodies (β-hydroxybutryate > acetoacetate)

Labs: hyperglycemia, anion gap metabolic acidosis, hyperkalemia

Presents: Kussmaul respirations, dehydration, nauseea, vomiting, mental status change, fruity smelling breath (acetone)

• Signs/Sx:
• -Kussmaul respirations
• -Naus/vom, abdominal pain
• -psychosis/delirium
• -dehydration
• -Fruity breath odor (exhaled acetone)

• Labs:
• -Hyperglycemia
• -↑ H⁺, ↓ HCO₃^- (anion gap metabolic acidosis), ↑ blood ketone levels
• -leukocytosis
• -Hyperkalemia, but depleted intracellular K⁺ due to transcellular shift from ↓ insulin

• Complications: Life-threatening mucormycosis, 
• -Rhizopus infection,
• -cerebral edema,
• -cardiac arrhythmias,
• -heart failure

• Treatment:
• -IV fluids, IV insulin and K⁺ (to replete intracellular stores)
• -glucose if necessary to prevent hypoglycemia

• 1. Tumor of islet cells - MEN1
• 2. Insulinomas: increased insulin, increased C-peptide
• 3. Gastrinomas (zollinger-Ellison)
• 4. Somatostatinomas: achlorhydria and cholelithiasis with steatorrhea
• 5. VIPomas: watery diarrhea, hypokalemia, achlorhydria

• Rare syndrome caused by carcinoid tumors (neuroendocrine cells), especially metastatic small bowel tumors (secrete high levels of 5-HT)
• -NOT seen in tumors limited to GI tract (first past metabolism of 5-HT in liver)
• Sx:
• -recurrent diarrhea,
• -cutaneous flushing,
• -asthmatic wheezing,
• -right sided valvular disease
• -↑ 5-HIAA in urine
• -niacin deficiency

Tx: somatostatin analog (e.g. octreotide)

• Rule of 1/3s:
• -1/3 metastasize
• -1/3 present with 2nd malignancy
• -1/3 multiple

*most common tumor of appendix

• Gastrin-secreting tumor of pancreas or duodenum
• Stomach shows rugal thickening with acid hypersecretion
• Causes recurrent ulcers
• May be assocaited with MEN type 1

• MEN 1 (Wermer's syndrome) - 3P's (Pituitary, Parathyroid, Pancreas)
• MEN 2A (Sipple's syndrome) - 2P's (Parathyroid, Pheochromocytoma)
• MEN 2B - 1P (Pheochrommocytoma)
• **All MEN syndromes have autosomal dominant inheritance

• Parathyroid tumors
• Pituitary tumors (prolactin or GH)
• Pancreatic endocrine tumors: ZE syndrome, insulinomas, VIPomas, glucagonomas (rare)
• Commonly present with kidney stones and stomach ulcers
• 

• Medullary thyroid carcinoma (secretes calcitonin)
• Pheochromocytoma
• Parathyroid tumors
• 
• *Associated with ret gene mutation

• Medullary thyroid carcinoma (secretes calcitonin)
• Pheochromocytoma
• Oral/intestinal ganglioneuromatosis (associated with marfanoid habitus)
• 
• *Associated with ret gene mutation

Excessive sex steroids with hyperplasia of both adrenal galnds

• 21-hydroxylase deficiency is the most common
• Sx:
• -Salt wasting with hyponatremia, hyperkalemia, and hypovolemia (lack of aldosterone)
• -Life-threatening hypotension due to lack of cortisol (vascular tone)
• -Clitoral enlargement or precocious puberty (excess androgens)

• 11-hydroxylase deficiency:
• -Increased sex steroids
• -Decreased cortisol
• -Increased mineralocorticoid (weak)
• -Same as 21hydroxylase deficiency without salt wasting

• 17-hydroxylase deficiency:
• -Increased Mineralocorticoid
• -Decreased Cortisol
• -Decreased sex steroids

• -DM 1: low-sugar diet, insulin replacement
• -DM 2: dietary modification and exercise for wieght loss; oral hypoglycemics and insulin replacements

• Drug classes:
• -Insulin: short/rapid-acting, long acting
• -Biguanides: Metformin (mechanism unknown; ↓gluconeogenesis, ↑ glycolysis, ↑ peripheral glucose uptake)
• -Sulfonylureas: Glipizide (mechanism: close K+ channels in β-cell membrane → depolarizes cell membrane → triggering insulin release via ↑ Ca²⁺ influx)
• -Glitazones/thiazolidinediones: "-glitazones" (↑ insulin sensitivity)
• -α-glucoside inhibitors: Acarbose (inhibit intestinal brush-border α-glucosidases)
• -Amylin analogs: Pramlintide (↓ glucagon)
• -GLP-1 analogs: Exenatide (↑ insulin, ↓ glucagon release)
• -DPP-4 inhibitors: linagliptin (↑ insulin, ↓ glucagon release)

• Lispro (rapid-acting)
• Aspart (rapid-acting)
• Glulisine (rapid-acting)
• Regular (short-acting)
• NPH (intermediate)
• Glargine (long-acting)
• Detemir (long acting)

• Action: bind insulin receptor (tyrosine kinase activity)
• -Liver: ↑ glucose stored as glycogen
• -Muscle: ↑ glycogen and protein synthesis, K⁺ uptake
• -Fat: aids TG storage

Clinical use: Type 1 DM, type 2 DM, gestational diabetes, life-threatening hyperkalemia, and stress-induced hyperglycemia

Toxicity: hypoglycemia, very rarely hypersensitivity reaction

Metformine

• Action: Exact mechanism unknown
• -↓ gluconeogenesis
• -↑ glycolysis
• -↑ peripheral glucose uptake (insulin sensitivity)

• Clinical use: oral
• -First line therapy in DM2
• -Can be used in pts without islet function

• Toxicities: GI upset
• -Lactic acidosis (*contraindicated in renal failure)

• Fist generation: Tolbutamide, chlorpropamide
• Second generation: Glyburide, glimepiride, glipizide

• Mechanism:
• -Close K⁺ channel in β-cell membrane, so cell depolarizes
• -leads to ↑Ca²⁺influx which triggers release of insulin

• Clinical use: stimulates release of endogenous insulin in type 2 DM
• -Require some islet cell function, useless in DM1

• Toxicities:
• -First gen: disulfiram-like effects
• -Second gen: hypoglycemia

Pioglitazone, Rosiglitazone

• Mechanism:
• -↑ insulin sensitivity in peripheral tissue
• -binds to PPAR-γ nuclear transcription regulator

• Clinical use: 
• -Used as monotherapy in type 2 DM, or in combination

• Toxicities:
• -Weight gain
• -Edema
• -Hepatotoxicity
• -Heart failure

Acarbose, Miglitol

• Mechanism:
• -Inhibit intestinal brush-border α-glucosidases
• -Delayed sugar hydrolysis and glucose absorption → ↓ postprandial hyperglycemia

Clinical use: Monotherapy in type 2 DM, or combination

Toxicities: GI disturbances

Pramlintide

Mechanism:↓ glucagon

Clinical use: type 1 or 2 DM

• Toxicities:
• -Hypoglycemia
• -Nausea
• -Diarrhea

Exenatide, Liraglutide

• Mechanism:
• ↑ insulin, ↓ glucagon release

Clinical use: Type 2 DM

Toxicities:

• -Naus/Vom
• -pancreatitis

Linagliptin, saxagliptin, sitagliptin

• Mechanism:
• -↑ insulin, ↓ glucagon release

Clinical use: Type 2 DM

Toxicities: mild urinary or respiratory infections

• Mechanism:
• -Block peroxidase, inhibiting organification of iodide and coupling of thyroid hormone synthesis
• -Propylthiouracil also blocks 5'-deiodinase, decreasing peripheral conversion of T₄ to T₃

Clinical use: Hyperthyroidism

• Toxicity:
• -Skin rash
• -agranulocytosis (rare)
• -aplastic anemia
• -hepatotoxicity (propylthiouracil)
• -Methimazole is a possible teratogen

• Mechanism: Thyroxine replacement
• Clinical use: hypothyroidism, myxedema
• Toxicity: Tachycardia, heat intolerance, tremors, arrhythmias

• GH → GH deficiency, Turner syndrome
• Somatostatin (octreotide) → Acromegaly, carcinoid, gastrinoma, glucagonoma, esophageal varices
• Oxytocin → Stimulates labor, uterine contraction, milk let-down; controls uterine hemorrhage
• ADH (desmporessin) → Pituitary (central) DI

• Mechanism: ADH antagonist (member of the tetracycline family)
• Clinical use: SIADH
• Toxicity: Nephrogenic DI, photosensitivity, abnormalities of bone and teeth

• Mechanism: ↓ production of leukotrienes and PGs by inhibiting phospholipase A2 and expression of COX-2
• Clinical use: Addison's disease, inflammation, immune suppression, asthma
• Toxicity: Iatrogenic Cushing's syndrome → buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruising, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic). Adrenal insufficiency when stopping drug abruptly after chronic use