Endocrinology 2023-changed.pptx

Endocrinology © 2013-2023, MedSckool Reviews History: Endocrinology Assessment a.Mood b.Energy level c.Unexplainable physical changes d.Skin/Hair Changes e.Sexual Function f. Menstrual Cycle g.Appetite/Weight h.Urination i. Medication list – dopamine, steroids PITUITARY HORMONES Anterior Pituitary P...

Endocrinology © 2013-2023, MedSckool Reviews History: Endocrinology Assessment a.Mood b.Energy level c.Unexplainable physical changes d.Skin/Hair Changes e.Sexual Function f. Menstrual Cycle g.Appetite/Weight h.Urination i. Medication list – dopamine, steroids PITUITARY HORMONES Anterior Pituitary Posterior Pituitary "FLAGTOP” F: Follicle Stimulating Hormone (FSH) Anti-diuretic Hormone (ADH) L: Luteinizing Hormone (LH) Oxytocin A: Adrenocorticotropic hormone (ACTH) G: Growth Hormone (GH) T: Thyroid Stimulating Hormone (TSH) O: melanOcyte stimulating hormone (MSH) P: Prolactin Panhypopituitarism Etiology: Mnemonic: eight “ I ”s Invasive: generally primary tumours (meningioma, craniopharyngioma, lymphomas) Infarction: e.g. Sheehan’s syndrome Infiltrative disease: sarcoidosis, hemochromatosis Iatrogenic: following surgery or radiation Infectious: syphilis, TB Injury: severe head trauma Immunologic: autoimmune destruction Idiopathic: familial forms, congenital midline defects Panhypopituitarism Clinical Features (hormone dependent): 1.↓ GH: clinically not apparent 2.↓ prolactin: may present as decreased lactation 3.↓ GnRH: ↓FSH,LH i. erectile dysfunction in men ii.amenorrhea or infertility in women iii.Decreased libido in both as well as decreased pubic, body, and axillary hair 4.↓ TSH: clinical hypothyroidism 5.↓ ACTH: adrenal insufficiency Panhypopituitarism 1.Dx: Triple Bolus Test a.stimulates release of all anterior pituitary hormones in normal individuals b. rapid sequence IV infusion of – Insulin hypoglycemia  INCR. GH and ACTH – GnRH  INCR. LH and FSH – TRH  INCR. TSH and PRL 2.Tx: Replace hormones Note: Panhypopituitarism timeline varies and can occur over a period of days (ex: apoplexy), months, or even years (radiation). Hyperprolactinemia Dx Due to Initial: Hormone panel Adenoma ↑ Prolactin Anti-dopaminergic medications ↓ FSH/LH Antipsychotics Anti-depressants Triptans Hypothyroidism (TRH stimulation) Sx Pregnancy test! Most accurate: MRI Tx Carbergoline Bromocriptine Females: lactation, galactorrhea, amenorrhea, infertility Euinagolide Males: ED, decreased libido, gynecomastia Transphenoidal surgery Growth Hormone (GH) 1.undetectable much of the day 2.suppressed after meals that are high in glucose content 3.sustained increase during sleep 4.necessary for normal linear growth 5.insulin-like growth factors (IGF) a.IGF shares some insulin-like actions and thus stimulates growth of bone and cartilage Acromegaly Etx Pituitary adenoma Carcinoid Pancreatic islet tutors (ectopic GHrH) Dx Initial: Hormone panel: ↑ IGF-1 (somatomedin) Most accurate: OGTT/glucose suppression test Pituitary lesion: MRI Sx Carpal tunnel (often bilateral) Coarsening facial features Tx Colonic polyps Surgery: transphenoidal resection Arthralgias Medications: Hypertension Carbergoline (DA Cardiac abnormalities antagonist) DM resistant to treatment (GH is anti-insulin) Octreotide (Somatostatin analog) MCC of death: cardiomegaly Pegvisomant (GH receptor antagonist) Anti-Diuretic Hormone (ADH) 1.synthesized in supraoptic nuclei of hypothalamus 2.secreted by posterior pituitary 3.also known as “vasopressin” 4.Acts via cAMP in renal collecting ducts altering permeability of membrane to water 5.allows reabsorption of water thereby increasing urine concentration Diabetes Insipidus (DI) HAI!, YOU’RE PISSING INSANE AMOUNTS OF WATER Etx Neurogenic (Central): ADH-deficient i.stroke ii.lesion iii.trauma Nephrogenic (Peripheral): ADHresistant iv.sickle cell v.amyloidosis vi.chronic pyelonephritis vii.Lithium Dx Hypovolemic hypernatremia SERUM ↑ serum Na URINE ↓ urine osmolality ↓ urine Na ↑ urine volume Diagnose with Vasopressin Urine volume decreased: Central Urine volume unchanged: Peripheral Tx Neurogenic (Central): Desmopressin (DDAVP) Nephrogenic (Peripheral): Sx Polydipsia Polyuria Dehydration Stop offending agents Fix electrolyte imbalances Treat underlying cause Hydrochlorothiazide, Amiloride, Indomethacin SIADH Etx Stress (pain, postsurgical) Malignancy CNS disease Medications Dx euvolemic hyponatremia URINE SERUM ↓ serum Na ↑ osmolality (300-500) ↓ osmolality (280295) ↑ urine Na ↓ urine volume Tx Treat underlying cause Sx Polydipsia Polyuria Over hydrated Fluid restriction (800-1000 ml/day) ADH receptor antagonist (Tolvptan, Conivaptan) Demeclocycline (antibiotic with anti-ADH) Fludrocortisone Furosemide Thyroid Hormone 1.Normal gland size 15-20 g 2.Free T4 (0.03%) and free T3 (0.3%) represent the hormonally active fraction 3.The remainder is hormonally inactive, mainly bound to thyroxine binding globulin (TBG) and albumin 4.T3 is more biologically active than T4 5.Some T4 is converted to T3 in peripheral tissues by 5’-deiodinase 6.Function: Brain Maturation Bone growth Beta-1 adrenergic effects Increase in BMR Total T3 and T4 levels depend on amount of Thyroid Binding Globulin (TBG) TBG ↑ with  pregnancy oral contraceptive (OCP) use acute infectious hepatitis biliary cirrhosis TBG ↓ with  androgens glucocorticoids cirrhosis hyponatremia phenytoin ASA, NSAIDS nephrotic syndrome severe systemic illness Thyroid Diagnostic Tests 1.TSH +/- T4, T3 2.Thyroid U/S to detect - size of gland - solid vs. cystic nodule 3.Fine Needle Aspiration (FNA) for cytology 4.Technetium 99 Thyroid scan (RAIU) a.for hot vs. cold nodules b.Graves’ disease, toxic multi-nodular goitre, solid toxic adenoma Hyperthyroidism 1. Causes: a.Graves disease (TSH ↓) b.Thyroiditis: painful or painless (TSH ↓) c.Exogenous thyroid hormone use (TSH ↓) d.Pituitary adenoma (TSH ↑) What are we looking at? Enlargement of the levator palpebrae superioris Grave’s Disease Etx Dx Autoimmune disorder TSH receptor antibodies (POSITIVE STIM) ↑ T4 ↓ TSH ↑ Diffuse RAIU MCC of thyrotoxicosis Tx Sx Propylthiouracil (PTU) Hyperthyroidism Methimazole Diffuse goitre +/- bruit Radioactive Iodine Exophthalmos Proptosis Diplopia Pretibial Myxedema Onycholysis Propranolol (symptomatic treatment of tremor, palpitations) Pregnancy: PTU in 1st trimester; Methimazole 2nd trimester (1st become Pregnant then become Mom) Ophthalmopathy: prevent drying, high dose prednisone if severe Subacute Thyroiditis Etx Acute inflammatory disorder Hyper→ Hypo → Euthyroidism Two subtypes: Painful (DeQuervain’s) (URTI) Painless (Silent) (post-partem) Giant cells and lymphocytes Dx ↓ TSH ↑ T4 ↓ RAIU + ESR Tx Sx Hyperthyroidism Thyroid gland enlargement Painful: ASA Prednisone (severe pain) Painless: no treatment Guidelines: How do you approach a solitary thyroid nodule? 1. always check TSH/T4 prior to Bx 2. always perform FNA (U/S guided) 3. DN Bx lesions with INCR. thyroid function 4. If deemed CA  surgery to remove Thyroid Nodule Workup TSH ↓ TSH Normal TSH RAIU COLD U/S +/- FNA or Biopsy HOT Treat Hyperthyroidism U/S +/- FNA or Biopsy ↑ TSH U/S +/- FNA or Biopsy Y NC E G ER M E Thyroid Storm A Pt with diagnosed hyperthyroidism who ‘lost their sh*t’ after a stressor (infection, trauma, surgery)  emergency Etx Dx Precipitated by infection, trauma, or surgery in a patient with hyperthyroidism Undetectable TSH ↑ T3/T4 +/- anemia, leukocytosis, hyperglycemia, hypercalcemia, elevated LFTs Sx Hyperthyroidism Extreme Hyperthermia (>40℃) Tachycardia, CHF, SHOCK Vomiting/Diarrhea Mental status changes: delirium to coma Tx Fluids, Electrolytes, Vasopressor’s Cooling blankets, acetaminophen Propranolol Propylthiouracil Iodide ablation (Lugol’s or Potassium iodide) Dexamethasone Hyperthyroidism (other causes) Exogenous Thyroid Hormone Sx: gland atrophy, non- palpable Dx:↓TSH , ↓RAIU Tx: stop offending meds Pituitary Adenoma Dx: ↑TSH, MRI Tx: Surgery Hypothyroidism 1.2-3% of general population; F:M = 10:1 2.10-20% of women > 50 have subclinical hypothyroidism Sx: Slow Tired Fatigue Weight gain Constipation Cold intolerance Amenorrhea Depression Hypercholesterolemia Hashimoto Thyroiditis Etx MC primary hypothyroidism in North America Chronic autoimmune disease Cell-mediated destruction of thyroid follicles Antibodies against thyroid components: thyroglobulin, thyroid peroxidase, TSH receptor, Na/I symporter Sx Hypothyroidism Dx ↓ T4/T3 ↑ TSH Anti-thyroid peroxidase antibodies Anti-thyroglobulin antibodies INCR ESR & CRP Tx L-Thyroxine E RG E EM MyxEDema Coma Y NC Etx (side column) Severe hypothyoridism as a complication of trauma, sepsis, cold exposure, MI, or stress ↓ T4/T3 ↑ TSH ↓ glucose Tx Decreased mental status Hypothermia Hypotension Bradycardia Hypoventilation Undetectabl e TSH ↑ T3/T4 Dx Sx THYROID STORM Supportive: ABC, ICU admission, mechanical ventilation, vasopressor drugs, passive rewarming, IV dextrose Monitor for arrhythmia L-Thyroxine Hydrocortisone Thyroid Cancers Remember the “ F’s ”: Follicular, Far away mets (blood), Female, FNA biopsy not diagnostic, Favourable prognosis Remember the M’s: Medullary Cancer; Multiple Endocrine Neoplasia, Median Node dissection Remember the “ P ’s”: Papillary, Popular (mc), Psammoma, Palpable nodes, Positive Prognosis, Positive 131 Iodine uptake Parathyroid Hormone (PTH) 1.↑ osteoclast activity  ↑Ca 2+,↑ PO4 in blood 2.↑ renal tubular Ca 2+ (and Mg) reabsorption 3.inhibits renal tubular reabsorption of PO4 4.↑ hydroxylase activity  vitamin D  increased Ca2+ and PO4 absorption from gut NET ↑ ↑ ↓ EFFECT serum Calcium Vitamin D Phosphate Hyperparathyroidism Dx Etx ↑ Calcium MCC of hypercalcemia Solitary Adenoma ↑ PTH Pituitary adenoma ↓ Phosphate Cancer Tx Symptomatic management Sx Usually asymptomatic “bones, moans, stones, and Hypercalcemia can cause: groans” Short QT syndrome Acute Severe Hypercalcemia: IV fluids Osteoporosis Furosemide Nephrolithiasis Bisphosphonates: Confusion, depression Pamidronate or Hypertension Zoledronic Acid Hypoparathyroidism Etx Neck surgery Dx ↓ Calcium Thyroidectomy ↓ PTH Renal failure (loss of Vit D) ↑ Phosphate Hypomagnesemia Sx Low calcium Chvostek sign Trousseau sign Tx Calcium Vitamin D Prolonged QT syndrome Anyone? What is Pseudohypoparathyroidism? Chvostek Sign Calcium Homeostasis 1. Serum Ca2+ is about 50% protein bound (mostly albumin) and not exchangeable 2. Normal total serum Ca2+ is 2.25-2.62 mmol/L (9.0-10.5 mg/dL) 3. Ionic Ca2+ levels are maintained within narrow limits (1.15-1.31 mmol/L; 4.6-5.25 mg/dL) MCC of hypercalcemia is Primary Hyperparathyroidism Sx: kidney stones, osteoporosis/osteomalacia/fractures, confusion, constipations & abdominal pain Dx: ↑ PTH ↑ Calcium ↓ Phosphate Tx: surgical removal Hypercalcemia 1. Hypervitaminosis D a.Granulomatous Dx (TB or Sarcoid)  ↑ 1,25 Vit D  ↑ Ca and P GI absorption i.↑ Ca ii.↑ P iii.↓ PTH iv.↑ Vit D (differentiate from mets) LET’S PLAY A GAME… Disease PTH Vitamin D Calcium Phosphate Osteoporosis NC NC NC NC Primary Hyperparathyroidism ↑ ↑ ↑ ↓ ↓ NC / ↓ ↑ ↓ ↓ ↓ ↑ ↓ ↓ ↑ ↑ ↓ ↓ ↑ Primary Hypoparathyroidism Vitamin D Deficiency NC / ↑ Chronic Renal Failure Pseudohypoparathyroidism ↓ Adrenal Gland Adrenal Gland Hypercortisolism CUSHINGS Whats the difference between Cushing Syndrome and Cushing Disease? Hypercortisolism Etx Pituitary: ↑ ACTH (Cushing Disease) Adrenal: ↓ ACTH (Cushing Syndrome) Ectopic: ↑ ACTH (Cancer/Carcinoid) Dx Laboratory: hyperglycemia, hyperlipidemia, leukocytosis Tests of Confirmation: 24h urine cortisol low-dose overnight dexamethasone suppression test Sx Moon face Buffalo hump Easy bruising & striae Hypertension Muscle wasting Hirsutism Osteoporosis Sexual dysfunction Polyuria Psychosis Late-night salivary cortisol CT, MRI Petrosal venous sinus sampling (locate disease) Tx Treat underlying cause Adrenal: unilateral adrenalectomy Pituitary: trans-sphenoidal resection Ectopic: Bronchogenic cancer treatment HypoAdrenalism - Addison’s Etx Autoimmune Dx Hyponatremia, Waterhouse Friderichsen Synd (N. meningitidis) Hyperkalemia Hypoglycemia MCC worldwide is TB Sx Hyperpigmentation (in thin Person) Electrolyte imbalance Weakness Fatigue Wt. loss HypoTN Salt Craving Myalgia NVD Cosyntropin Stimulation Test  will not produce Cortisol Tx Replace hormones with hydrocortisone Fludrocortisone for resistant cases PRIMARY (low cortisol) vs SECONDARY (low ACTH) A 24 y/o F with a h/o of T1DM presents to the ED with abdominal pain and wt loss for the past 3 weeks. She has also noticed that her basal insulin requirements have recently DECR. Her mother has a h/o hyperthyroidism. Her vitals include a HR of 100 and BP of 100/60. Initial labs include Na 134; K 5.2, HCO3 22, Cr 1.1 What is the most appropriate step in the management of this pt? a. b. c. d. e. Furosemide Ceftriaxone Spironolactone Fludrocortisone Eplerenone Cushing's Syndrome, exogenous aldost. Liddle’s Syndrome, Licorice!!! Hyperaldosteronism Etx Dx Hypertension Primary: Conn’s Disease ↓ Potassium Secondary: renovascular disease, CHF, cirrhosis, nephrotic syndrome (anywhere the production of aldosterone is dependent upon renin) Sx Persistent hypertension Unresponsive to treatment Hypertension at a young age ↑ Aldosterone ↓ Renin CT adrenal gland Tx Adenoma: Surgery Bilateral hyperplasia: Eplerenone Spironolactone Hypoaldosteronism Etx Dx Electrolyte imbalances: metabolic acidosis, hypoglycemia Autoimmune Destruction of gland ↑ Potassium (hyperkalemia) Waterhouse Friderichsen syndrome ↓ Sodium (hyponatremia) CT adrenal gland Sx Hypotension Hyperpigmentation Fatigue Weight loss Myalgia N/V/D Check Renin levels Tx Acute Crisis IV NS + D5W and hydrocortisone Stable patient Prednisone or fludrocortisone CAH made easy cholesterol 17 21 11 deoxycorticosterone (like aldosterone) 11 Androgens (Testosterone) Glucocorticoids (Cortisol) Mineralcorticoids (Aldosterone) 17-OH Deficiency: ↓ androgens & Hypertension 21-OH Deficiency: ↑ androgens & Hypotension 11-OH Deficiency: ↑ androgens & Hypertension Congenital Adrenal Hyperplasia (CAH) Sx: HIGH ACTH, LOW aldosterone, LOW cortisol Tx: prednisone to inhibit pituitary Different Kinds of CAH 17-OH Deficiency: low androgens & Hypertension 21-OH Deficiency: MC type; hirsutism (high androgens), Hypotension 11-OH Deficiency: hirsutism (high androgens) & Hypertension Pheochromocytoma Etx Rare tumor from chromatin cells of medulla Dx ↑ plasma/urine catecholamines Synthesize and release catecholamines ↑ plasma/urine free metanephrines 10% extra adrenal 10% multiple tutors CT/MRI of adrenals 10% malignant MIBG scan (metastatic disease) 10% Familial MEN IIA/IIB association Sx Paroxysmal hypertension Sustained hypertension Triad: pounding headache, palpitations, diaphoresis Tremor Anxiety N/V Tx Volume restoration Alpha blockade: Phenoxybenzamine IV phentolamine Beta blockade Propranolol Surgical removal of tumour Multiple Endocrine Neoplasia PPP PPM PMM Multiple Endocrine Neoplasia Multiple Endocrine Neoplasia Diabetes Mellitus Sx Normal Glucose Levels Dx polyuria RPG ≥ 11.1 mmol/L polydipsia FBS ≥ 7.0 mmol/L FBS: 4-7 mmol/L weight loss 2hrs after meal: 5-10 mmol/L 2h OGTT ≥ 11.1 mmol/L nocturia HbA1C ≥ 6.5% polyphagia blurry vision Cx Cardiovascular: HTN, stroke, CHF Nephropathy Gastroparesis Retinopathy Neuropathy Note: In the presence of hyperglycemia symptoms (polyuria, polydipsia, polyphagia, weight loss, blurry vision), confirmatory test is not required Health prevention Pneumococcal vaccination Yearly eye examination Statins for hyperlipidemia ACEi/ARBs for BP Yearly urine tests for microalbuminuria Regular foot examinations Metformin Blockage of gluconeogenesis Causes Lactic Acidosis – c/i in renal insufficiency No risk of hypoglycemic attack No risk of obesity Glyburide/Glipizide (Add if metformin is not working) Increase insulin release however side effects hypoglycemic attack and SIADH Contraindicated in renal insufficiency (Cr >1.5) Thiazolidinedienes (Add if above is not working) Increase peripheral insulin sensitivity Resiglitazone is contraindicated in CHF patients Glucagon-like Peptide Analog (Add if above is not working) Promotes weight loss and decrease glucose levels Think: Exenatide, Liraglutide Insulin Types Fast Acting Regular: acts in 30mins, peaks at 2-4hrs and lasts 8hrs Humalog/Lispro: acts in 5mins, peaks at 1.5hrs and lasts 8hrs Long Acting NPH: acts in 2-4hrs, peaks at 6-10hrs and lasts 28hrs (usually given twice a day) Lantus: acts in 1-4hrs and lasts 24hrs (usually give once per day) Dosage: NPH/Regular = 70/30 ratio DKA vs HHS