HYPERTHYROIDISM

Thyroid Gland Synthesize, Secrete, Store thyroid hormone *ALL cells depend on for metabolism regulation BMR & Temperature Body & Bone Growth Anabolic & Protein Synthesis Glucose Production & Absorption (Gluconeogenesis & Glycogenolysis) Lipid Metabolism HR, CO, Contractibility Nervous System Development (CRETINISM) Composed of spherical FOLLICLES Lumen filled with colloid THYROBLOBIN MOLECULES 80% T4 Prohormone 20% T3 20-100x stronger IODIDETHYROID PEROXIDASEIODINEIODINE+TYROSINE(Amino Acid)HORMONE 75% Bound to THYROXINE BINDING GLOBULIN Carrier Protein = INACTIVE HypothalamusTRHPituitaryTSHThyroidT3/4 Hypothalamus & Pituitary Regulated by NEGATIVE Feedback PHYSIOLOGY Graves Dz *Autoimmune #1 in USA 20-40 Female TSI Antibodies T3/4 & Growth CLINICAL *THYROTOXICOSIS *Diffusely Enlarged Goiter (BRUITS) *Pretibial Myxedema (non-pitting, red/brown) Topical Corticosteroids *PROPTOSIS, Lid Lag, Photophobia, Diplopia Glucocorticoids *THYROTOXICOSIS *ENLARGED Goiter Dysphagia/Dyspnea *ASYMPTOMATIC DIAGNOSIS TSH Free T3/4 +TSI (Pathopneumonic) +/- Anti-TG/TPO RAIU diffuse uptake TSH Free T3/4 TMN/ UPTAKE TREATMENT #1 Radioactive Iodine Thioamines Methimazole PTU (PREGNANT) Iodines Beta Blockers #1 RAI *SURGERY

Toxic Multinodular AUTONOMOUSLY Goiter & functioning nodules ELDERLY >50 Toxic Adenoma #2Iodine areas SINGLE nodule Pituitary Adenomas Secrete TSH *RARE Thyroid Storm *RARE *FATAL Surgery, Trauma, Infection

*Diffuse Goiter *Bitemporal Hemianopsia *Mental Disturbance Metabolic Palpitations, Afib, Tremor, Fever, N&V, Psychosis *Coma & BP

TSH Free T3/4 MRI TSH Free T3/4

Surgery TSS

Methimazole PTU (PREGNANT) Beta Blockers Supportive 1

HYPOTHYROIDISM (#1 WORLD = IODINE)

Hashimotos #1 USA AUTOIMMUNE

PHYSIOLOGY Destruction via: Anti-thyroid peroxidase Antithyroglobulin *p URI *NOT autoimmune

CLINICAL *Enlarged NON-TENDER Goiter *risk of CA

DIAGNOSIS TSH Free T3/4 Anti-TPO Anti-TG ESR Free T3/4 TSH RAI uptake Anti-TPO RAI uptake (GRAVES VS.THYROIDITIS)

TREATMENT #1 LEVOTHYROXINE

Dequervains *5x FEMALES

*Enlarged PAINFUL Goiter *Viral Symptoms

HYPER HYPO NORMAL

Silent Thyroiditis *RARE *2x FEMALES

*AUTOIMMUNE *p AMIODARONE, LITHIUM, XRT INTERFERON *AUTOIMMUNE *1-6 months p partum *Smoking=risk

*Enlarged NON-TENDER Goiter

Supportive Self limiting NSAIDS

Post Partum Thyroiditis

*Enlarged NON-TENDER Goiter

Anti-TPO Anti-TG RAI uptake (GRAVES VS.THYROIDITIS) TSH Free T3/4 ( detectable)

Myxedema Coma *p Infection, CVA, *60% Mortality CHF, Narcotics *#1 ELDERLY Women In WINTER

*HR, BP, RR Na, Glucose Temp, COMA

*IV LEVOTHYROXIN *PASSIVE WARMING

*Subclinical HYPOthyroidism TSH N T3/4 Lipids *Subclinical HYPERthyroidism TSH N T3/4

ADRENAL INSUFFICIENCY

Glucocorticoids (*CORTISOL)STRESS BP & CV function VASOCONSTRICTION ANTI-INFLAMMATORY SERUM GLUCOSE o Gluconeogenesis o Glucose Utilization o Protein Breakdown o Lipolysis Mineralocorticoids (*ALDOSTERONE) BP Na & H2O BALANCE Stimulants K (Most Sensitive) RAAS ACTH (Relatively INDEPENDENT) Physiology *Adrenal Gland DESTRUCTION ACTH CORTISOL &ALDOSTERONE AUTOIMMUNE #1(USA) Industrialized Countries INFECTION (TB, HIV, CMV) #1 World Vascular, Drugs, Mets

**SECONDARY ADRENAL INSUFFICIENCY MORE COMMON THAN PRIMARY**

*STRESS OVERRIDES NEGATIVE FEEDBACK*

HypothalamusCRHAnterior PituitaryACTHAdrenal CortexCORTISOL

Addisons Dz (Primary)

Secondary

*Pituitary FAILURE to secrete ACTH CORTISOL *ALDOSTERONE intact RAAS #1 EXOGENOUS STEROIDS > 2wks Hypopituitarism (RARE)

Clinical Treatment *PRIMARY ONLY* *PRIMARY ONLY* *HYPERPIGMENTATION (#1) Synthetic Mineralocorticoid FLUDROCORTISONE *ORTHO BP, K, Na *BOTH* *BOTH* *WEAKNESS (#1) Synthetic Glucocorticoids *WT (#2) HYDROCORTISONE *ABD PAIN PREDNISONE *GLUCOSE (SECONDARY) DEXAMETHASONE #1 Emergency *Na effect Testing *ABNORMAL MENSTRATION *During ILLNESS, SURGERY, FEVER Oral Dosage to mimic N cortisol response Imaging Abdominal CT (*PRIMARY ONLY*) Autoimmune Small Atrophied Noncalcified Adrenals TB Calcification Mets/Infection Enlarged Adrenal Gland Pituitary MRI Hypopituitarism Suspected

DIAGNOSIS High Dose ACTH Stimulation Test #1 SCREENING TEST Cortisol = NORMAL Cortisol = ADRENAL INSUFFICIENCY CRH Stimulation Test DIFFERENTIATES ACTH & Cortisol = PRIMARY ACTH = SECONDARY ACTH Delayed/Prolonged/Exaggerated = TERTIARY Low Dose ACTH Test Useful in NEW/RECENT ACTH (SECONDARY)

ADRENAL INSUFFICIENCY

Physiology Addisonian *SUDDEN Worsening of Symptoms due to STRESSFUL EVENT Crisis Aldosterone (Primary Cause) #1 Abrupt Steroid Withdraw ( Taper) #2 Undiagnosed pt. under STRESS #3 Exacerbation of KNOWN Dz (dose under STRESS) #4 Bilateral Adrenal INFARCTION (Hemorrhage)

Clinical #1 SHOCK (Due to ALD) #2 Glucose #3 BP, Hypovolemia #4 Nonspecific

Diagnosis Treatment CBC, SMA IV Fluids NS (BP) Glucose D5NS (Glucose) Na Glucocorticoids K Dexamethasone(Undiagnosed) Hydrocortisone (Known Dz) Mineralocorticoids Fludrocortisone Tx Electrolyte Imbalance SCREENING TESTS 24hr Urine Cortisol* #1* Nocturnal Salivary Cortisol Levels Suppression c Low Dose Dex Supp Test DIFFERENTIATING TESTS High Dose Dexamethasone Suppression Test Suppression = Cushings Dz ACTH Levels N/ =Cushings Dz OR Ectopic ACTH Tumor = Adrenal Tumor

Cushings Syndrome

Cushings Dz (Pituitary Adenoma secretes = ACTH) Ectopic ACTH (SCLCA/Medullary Thyroid CA =ACTH) Adrenal Tumor (Cortisol secreting Adenoma = ACTH) *Factitious* (#1) (Chronic Exogenous Steroid = ACTH) MANAGEMENT Cushings Dz (Pituitary) TSS Ectopic/Adrenal Tumors Surgery

Redistribution of FAT Central Trunk Obesity Moon Face, Buffalo Hump Protein Catabolism Skin Atrophy Bruising, Striae BP, wt, K, Psychosis, Osteoporosis Acanthosis Nigricans

CRH Adrenal (PRIMARY) Pituitary (SECONDARY) Hypothalamus (TERTIARY)

ACTH

CORTISOL

ACTH RESPONSE TO CRH STIMULATION TEST

ALDOSTERONE N

High Dose Dexamethasone Suppression Test SUPPRESSION = CUSHINGS DZ (Pituitary Tumor)

Calcium Bone Structure Clotting Membrane Potential 99% in Bone 1% Extracellular 50% Free/Active/Ionized 40% Bound to Albumin CALCITROL (Vit D) Blood Ca PTH Blood Ca Activate OSTEOCLASTS/Renal & Intestinal Ca ABSORBTION CALCITONIN Blood Ca Inhibit OSTEOCLASTS *Primary Hyperthyroidism *MEN1 & 2A *Malignancy *Granulomatous Disorders TB, Sarcoid, Histoplasmo *Thiazides, Lithium, Vit D/A Physiology *PTH mediated* *PTH independent* PTH related protein Calcitrol by Macrophages Clinical *ASYMPTOMATIC* #1 N/V/Constipation AMS Kidney Stones Polyuria / Polydipsia

Mild Ca<12 = Tx Moderate Saline, Lasix, Bisphosphonates Severe Ca>14 OR Neuro = ADD Calcitonin

Diagnosis PTH PTH related protein Ionized Ca BUN/Cr Vit D SHORT QT Interval

HYPERCALCEMIA

Treatment IV Saline Dilute & Excrete Lasix Excrete Ca Bisphosphonates Inhibit Osteoclasts Patho Femur Fx & Erosive Esophagis Calcitonin Inhibit Osteoclasts Urine Ca excretion Steroids GRANULOMATOUS DZ Vit D = Ca

HYPOCALCEMIA

Hypoparathyroidism (Sarcoid) Autoimmune Destruction Hypoalbuminemia (Cirrhosis) Binds Ca Vit D False Ionized Ca Hepatorenal Dz Hyperphosphatemia Hypomagnesemia

Tetany SPASMS Chvostek Sign Facial Trousseaus BP Spasm

PTH PTH

Ca Ca Mild ORAL Ca & Vit D Severe IV Ca Gluconate & Mg

PROLONG QT Interval

Physiology

Clinical Stones, Bones, Abd Groans, Psych Moans

Diagnosis Serum Ca 24hr Urine Ca Intact PTH Phosphate

Treatment Parathyroidectomy Ca & Vit D Supplements

HYPERPARATHYROIDISM

Primary Hyperparathyroidism Parathyroid Adenoma #1 Hyperparathyroid Hyperplasia

Excess PTH production

Secondary Hyperparathyroidism Chronic Kidney Failure #1 Ca Vit D

Response to Ca

HYPOPARATHYROIDISM

Accidental #1 Autoimmune

RARE PTH OR Insensitivity

Muscle Spasm Parasthesia

Serum Ca Intact PTH Phosphate

Ca Supplement

*RARE, INHERITED defect in tumor suppressor MENIN gene *90% Parathyroid *60% Pancreas (Gastrinoma, Insulinoma, Glucagonoma) *55% Pituitary *BENIGN *<30yrs will have some gland over activity *SCREENING ANYONE c FAMILY HX or OVERACTIVITY >2 ENDOCRINE GLANDS PTH & Calcium, Prolactin, Gastrin Hyperparathyroidism Physiology #1 Presenting Feature 90% Clinical Stones, Bones, Abd groans, Psych moans *HYPERCALCEMIA *KIDNEY STONES *ILEUS *PSYCHOSIS Pancreatic Tumors #2 **HIGHEST MALIGNANTCY** Diagnosis Ca intact PTH 24hr urine Ca phosphate Treatment *PARATHYROIDECTOMY

MEN 1

Small & Multiple Gastrinomas (ZES) #1 Insulinomas #2 Glucagonomas VIPomas Somatostatinomas 90% Solitary & Benign >6cm ?malignancy MC @ Head of Pancreas

*Multiple PEPTIC ULCERS (GI Bleed) *Epigastric Pain *wt, Reflux, N/V/D *HYPOGLYCEMIA

*REFRACTORY Ulcers Gastrin Insulin C-peptide Pro-insulin *50-80% mets @ Dx

*PPI, Monitor for CA *Surgery #1 Surgery *Octeotride *Small Freq CHO meals *Surgery *Octeotride Hydration Surgery Surgery

*70% Necrolytic Migratory Erythema *Type 2 DM *Watery Diarrhea, K *Achlorhydria *Steatorrhea, Cholelithias Pituitary Adenomas

Prolactinomas (60%) Somatotrophinomas Corticotrophinomas

#1 #2 #3

Amenorrhea, Galactorrhea, Infertility/Impotence Acromegaly Cushings Syndrome (ACTH)

Prolactin CT/MRI Pituitary

Surgery TSS

*RARE, INHERITED, AUTOSOMAL DOMINANT *Defect in RET proto-oncogene MEN 2A Medullary Thyroid Carcinoma, Pheochromocytoma, HYPERPARATHYROIDISM Parathyroid Hyperplasia MEN 2B Medullary Thyroid Carcinoma, Pheochromocytoma, NEUROMAS More Aggressive MTC & Marfanoid Habitus Familial MTC Medullary Thyroid Carcinoma ALL will eventually develop *Screening PTH & Calcium, Epinephrine, Calcitonin Physiology Parafollicular C cells Secrete Calcitonin Clinical *#1 Presenting Feature *Palpable Neck Mass *Hoarseness, Dysphagia Diagnosis Thyroid Ultrasound FNA Treatment Total Thyroidectomy Parathyroids transplanted Prophylactic Thyroidectomy 2B=1st 6months of life 2A= <5-6yrs old Complete Adrenalectomy Blockades 2wks pre-op

Medullary Thyroid Carcinoma

MEN 2

Pheochromocytoma

Adrenal Medullary Tumor Palpitations, Headache, Sweating, that secretes catecholamines Refractory BP ITERMITTENTLY INTERMITTENTLY

*24HR Urine Methamphetamines & Catecholamines *CT/MRIAdrenal Ca intact PTH 24hr urine Ca phosphate

Hyperparathyroidism

MEN 2A ONLY

Stones, Bones, Abd groans, Psych moans *HYPERCALCEMIA *KIDNEY STONES *ILEUS *PSYCHOSIS Eyelids, Conjunctiva, Tongue, Lips, Nasal & Laryngeal Conjunctiva *Prominent Hypertrophied Lips *Marfanoid Body Habitus

PARATHYROIDECTOMY

Neuromas

MEN 2B ONLY BENIGN

Insulin blood Glucose Glucose Uptake Allowing Liver/Muscles to store as Glycogen Inhibit Gluconeogenesis *Hgb A1c > 6.5% *FPG > 126 *Oral Glucose Test > 200 *Plasma Glucose > 220

Counter regulatory Hormones Protect against HYPOGLYCEMIA Cortisol GH Glucagon Catecholamines

Dawn Phenomenon Glucose in AM due to surge of counter regulatory hormones Bedtime NPH OR Bedtime snack Somogyi Effect Nocturnal Glucose followed by Rebound Glucose Prevent Glucose by Noc NPH OR Bedtime snack Insulin Waning Progressive rise in Glucose from Bedtime till morning Move insulin dose to bedtime Rapid Lispro, Aspart Short Regular Intermediate NPH, Lente Long Ultralente, Glargine Sulfonylureas Meglitinides Biguanides -Glucosidase Inhibitors Thiazolidinediones 1 day coverage Lantus = Hypoglycemic episode MIX Secretagages Secretagages Live glucose production peripheral glucose utilization Delay absorption of glucose Insulin sensitivity Hypoglycemia Hypoglycemia Lactic Acidosis Hepatitis, Flatulence, Diarrhea CHF, Bladder CA, Fx Overnight coverage 30-60min before meal Give w/meal

Physiology *Younger, Type 1 DM* 1) Hyperglycemia Insulin Counter Regulatory Hormones 2) Dehydration/Osmolarity Major factor in AMS 3) Ketonemia/Metabolic Acidosis Lipolysis Ketoacids 4) Total Body K+ Osmotic Diuresis Insulin shifts K+ extracellular HypovolemiaAldosteroneK+ Acidosis shifts K+ extracellular *May be masked by N/ Serum Levels *Serum K+ once Insulin Tx started

Clinical *Infection (UTI) 40% *Missed Insulin Dose 25% *Newly Dx/Unknown 15% CVA, Trauma, Stress, MI *Abd PAIN* *Kussmauls Breathing *Ketotic Breath

Diagnosis *PG > 250* *Anion Gap > 12*

Treatment *RESOLVED Normal Anion Gap

1) IV Fluids NS until Hypotension Resolves NS when Na Resolves NS D5 when glucose = 250 2) Insulin Bolus 0.1u/kg Drip 0.1u/kg/Hr SQ Anion Gap Resolves 3) K+ 1st Verify Renal Output <5.5 20-40 mEq/L 4) HCO3 risk of Cerebral Edema (Kids)

DKA

BMP Anion Gap/Glucose UA Ketones EKG ABG

*Older, Type 2 DM *Mortality *Fluid Intake * Hyperglycemia *NO Ketones 1) Dehydration/Osmolarity/ Hyperglycemia More SEVERE Present Later, Older (GFR) 2) K+ & Na Osmotic Diuresis

*PG > 600* *Anion Gap < 12*

*RESOLVED pOsm <315 / A&O x3

HHS

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