Approach in Endocrine Disease Te & Chin

Contents 1. Pathological Fracture 2. Hirsutism 3. Virilization 4. Cushing’s syndrome 5. Hypercalcemia 6. Hypocalcemia 7. Polyuria 8. Ambiguous Genitalia 9. Male Hypogonadism 10. Gynecomastia 11. Galactorrhea 12. Amenorrhea 13. Pituitary disease 14. Acromegaly 15. Short stature 16. Tall stature 17. Pheochromocytoma 18. Hypoglycemia 19. Adrenal Insufficiency 20. Thyroid disease 1. Pathological fracture Local bone disease Infection : Osteomyelitis Tumor Primary : Metastatic AdenoCA : TH / K / PR / LC / BR Lymphoma / MM Metabolic bone disease HyperPTH Hyperthyroidism Vitamin D deficiency Osteoporosis : Dilantin / Heparin / Steroid Osteopetrosis Osteomalacia Paget’s disease RTA

2. Hirsutism Increase Terminal hair in Androgen dependent area female Ferriman Gallwey score > 8 Pathogenesis Local-Systemic factors TH / GH-IGFI / GC / PRL Sex hormone Circulating Androgen excess Increase synthesis Ovary in origin Adrenal in origin + Increae activity 5-α reductase type II Androgen hypersensitivity of hair follicle Causes Ovary / Adrenal / Drugs / Others / Idiopathic Treatment Causes + Mechanical hair removal Medications Laser therapy

3. Virilization Severe Androgen excess in female Clinical manifestations Hirsutism / acne / deep hoarseness voice Cliteromegaly / Temporal balding, Male body contour / increase muscle mass Breast atrophy Confirm Testosterone level Identified origin of androgen : DHEAS Anatomic localization and nature of disease

4. Cushing’s syndrome Clinical Manifestations : Suspected CS easily bruise / weakness / HT / plethora / hirsutism red-purple striae > 1cm abnormal menstruation / truncal obesity Except in recently CS or Cancer relate CS Hypercortisolism without Cushing Morbid obesity / Depression / Alcohol / Pregnancy DM / Stress / Malnutrition / OC / Intensive exercise Lab Screening : UFC / MC Clinical features Adrenal incidentaloma Young onset DM Confirm : Standard LDDST >5 2nd AI-And excess-Hx : Exogenous / Endogenous stop medication 3-5d. then morning cortisol ACTH level <10 / >20 : Dependent / Independent + Hyperpigmentation skin crease / scar / buccal mucosa 10-20 repeat lab + CRH test 20 pg/ml ACTH independent CS DDX

1> Adrenal adenoma 2> Adrenal carcinoma 3> Bilateral adrenal disease : Hyperplasia 4> Ovarian tumor (rare)

Unilateral / Bilateral Synthesis hormone 1 or > 1 Onset / Progression / Clinical setting If no ACTH measurement : HDDST < 50% BL HDDST Suppressible Pituitary CS(CD) Not Huge Pituitary CS (40%) Ectopic ACTH (15%suppress) Adrenal CS ACTH dependent (60%) : MRI Pituitary >6 mm + BIPSS 95% Pituitary / 5% Ectopic ACTH(bilat GL+) MRI negative BIPSS Ectopic Neck : MCT / Thymic CA Chest : SCC / Bronchial carcinoid Abd : Pheo / Islet cell tumor / NET / GI ACTH independent (40%) : CT Adrenal gland 90% Adenoma / 10% Carcinoma

Other : CRH stimulation test / Desmopressin test Treatment Causes Pituitary : Surgery / Radiation Hydrocortisone 300 mg in 24 hr. Morning Cortisol Post-op Day 1st / 2nd < 5 cure !!! > 5 4-6 wk. no 2’ AI Persist dz. Adrenal Long duration of AI steroid 6-12 mo. Complication from hypercortisolism Medical treatment Hypothalamus / Pituitary action 1> DA agonist HD Bromocriptine 40 mg/d Cabergoline 1.5-3.5 mg/wk 2> PPAR-γ agonist Rosiglitazone 3> Somatostatin Octreotide / Pasireotide Adrenal Cortex action 1> Mitotane-direct damage adrenal gland 2> Metyrapone disturb 11-OH 3> Ketoconazole decrease cholesterol 600-800mg/d inhibit 17,21 4> Aminogluthetimide / Mifepristone bind GCR Hormone replacements

5. Hypercalcemia Alteration of conscious / Seizure Polyuria / Recurrent stone / Constipation Band keratopathy / Bone-teeth malformation Brown tumor (Osteitis fibrosa cystica) / Pathological # Suspected and confirm Ca-PO4 / CBC / UA / BUN-Cr / LFT Exclude pseudohypercalcemia (+0.5) Mild 11.5 Moderate 14 Severe Ca-PO4 relation ↑ ↓ PTH effect High PTH level FECa > 2 1’ / 3’ PTH++ 1’ PTH++ R/O MEN I Tc (TH) + MIBI (Both) Surgery in Ca > normal range 1 BMD < 2 SD GFR < 30% U Ca > 400 mg/d Age < 50 yr. Symptom ex. Stone Ectopic PTH (Lithium / Recovery phasr ARF) FECa < 1 : FHH Low PTH level : PTHrP Malignancy-SCC / T cell ↑ ↑/N R/O PTH effect with RF or Vitamin D BUN / Cr Vitamin D related Granulomatous inflammation : TB / F / Sarcoid / Beryllosis Lymphoma mostly B cell Vitamin D intoxication Others Osteolytic bone / Metastasis-MM / Breast Immobilization Milk alkali syndrome Dehydration / Adrenal insufficiency Pheochromocytoma / TH+ / Acromegaly Vitamin A

Treatment Causes and underlying disease Adequate volume Lasix risk for rebound hypercalcemia Expert opinion favor volume only Avoid HCTZ / Lithium / Estrogen Palmidronate / Calcitonin / Steroid

6. Hypocalcemia Muscle cramp / Seizure / weakness / dental hypoplasia Cataract / Papilledema Imaging : Basal ganglia calcification Suspected and confirm Ca-PO4 relation ↓ ↑ HypoPTH except RF BUN/ Cr for R/O Low PTH level 1’ PTH- Congenital DiGeoge’s and others PGA type I Acquired Post surgery : TH / PTH Radiation Infiltrative disease Wilson’s Hemochromatosis TB Sarcoidosis Hypomagnesemia FHH Normal or High PTH level Alkalosis PHP : Albright Hereditary OsteoD End organ resistant to PTH Hypomagnesemia Drugs inhibit Osteoclast Mitomycin C Bisphosphonates ↓ ↓ Vitamin D deficiency Malnutrition or Fat malabsorption 24-OH : Anticonvulsant / Ketoconazole 25-OH : Liver dz. / INH 1-OH : CKD / Osteomalacia(FGF-23) Vitamin D resistant : VDDR2 Others Rhabdomyolysis / Critical illness / Pancreatitis Acute Hyperphosphatemia Chelating agents Increase Ca deposition in bone PPN Post surgery hypocalcemia (TH / PTH)

Low PTH level Parathyroidectomy Transient gland ischemia Normal or high PTH level Hungry bone syndrome Hypomagnesemia Acute Calcitonin release

7. Polyuria Normal maintain SOsm 282-288 SOsm > 288 maximum ADH secretion SOsm > 294 activate thirsty center Definition > 3 L /day or 40 ml/kg/d or 2-4 ml/kg/hr. Glycosuric / Non Glycosuric : BS Osmotic or Water : U/P OSM 0.9 U SpGr. < 1.010 U Na < 20 C OSM < 3 ml/min Osmotic diuresis Organic / Inorganic SL : 2(UNa+K)/UOSM 0.6 Organic : UOG < 200 : Gluc / Urea > 200 : CM Inorganic : U Na+UK < UCl Diuretic / NSS load After RF / Obstruct / KT >> UCl Anion Drugs Ketonuria Bicarbonaturia Water diuresis Water deprivation test : 1’ polydipsia / DI NPO time depend on Urine output Uo < 5 L/d NPO after midnight Uo > 10 L/d NPO after 6.00 Need volume depletion 2 L WL 2 kg Acceptable criteria UOsm change < 30 mOsm/L X 3 (4 value) WL 3-5% SOsm > 288 (290/295) SNa > 145-150 Then DDAVP 1 µg SC or IV or 10 µg IN UOSm 1-2 hr after DDAVP

Interpretation UOsm % Change Diagnosis < 200 > 50% Complete CDI > 300 9-50% Partial CDI < 200 < 9% Complete NDI < 300 9-50 % Partial NDI > 500 < 9% 1’ Polydipsia 1’ Polydipsia Hypothalamic lesion Psychogenic cause Sarcoidosis Craniopharyngioma Nephrogenic DI Lithium most common cause Decrease Aq-2 after 8-12 wk. use Chronic Hypokalemia Hypercalcemia Central DI Congenital Acquired Tumor : Suprasellar DI before panhypopituitarism Trauma / Post-op brain Infection : Meningitis / Encephalitis AI dz. : WG / Sarcoidosis / Hypophysitis Post-op 1 wk. Hyponatremia Cerebral salt wasting 2nd phase DI Adrenal insufficiency Hypothyroidism Minirin overdose Alteration of conscious + meningitis / dilantin overdose Treatment DI DDAVP / Chlopropamide

8. Ambiguous genitalia Sex determination by (2) Menstruation Female / Fertility Male Primary amenorrhea R/O Male karyotype Karyotype and palpable gonad Term Pseudohermaphrodite M / FM depend on Chromosome&Gonad that opposite Genital ext/int sex True Hermaphrodite Gonadal structure 2 sex DDX Female with Virilization Hirsutism / Acne / Baldness / Infertility Androgen excess : External / Synthesis / ↑5-α Enzymatic defect : CAH 11,21 def. 21 common (1% of hirsutism) Hx. of Maternal Androgenemia 17-OHP N : True Hermaphrodite ↑ : CAH / Adrenal-Ovarian tumor Male with hypogonadism or feminization Gynecomastia / ED / Infertility Line approach male hypogonadism T DHT N ↓ 5α reductase N/↑ N/↑ Androgen insensitivity syndrome ↓ ↓ Abnormal T synthesis-Hypogonad

9. Male Hypogonadism 2’ sex characteristic / Tanner staging Muscle strength / Mood-Cognitive / Vasomotor Gynecomastia / loss m. mass / Obesity Low Testosterone level High FSH / LH : 1’ Hypogonadism Testis lesion Normal or Low FSH / LH : 2’ Hypogonadism Pituitary or Hypothalamic lesion Prepubertal or postpubertal onset Eunuchoidism Arm span > Ht. > 5 cm. Upper /Lower segment < 0.9-1

Hypogonadism Pre-pubertal Post-pubertal Primary Klinefelter’s

Cryptorchidism UndescT / Varicocele Other chromosome Myotonic dystrophy FSH/LHr, And syn.

Mumps orchitis RT / Trauma Drugs Bilat. Orchidect Systemic dz. Cirr/CKD/HIV

Secondary Kallman’s Prader-Willi Laurence-Moon Biedl Multiple lentigenes Rud Panhypopituitarism Isolated HG

Sellar-Suprasellar Infiltrative disease Sarcoidosis Hemochromatosis Infection Trauma / Tumor Systemic dz./Drugs

Investigation T < 300 X 2 / SHBG / FSH-LH / Karyotype / Prolactin / Iron / MRI Brain Treatment Testosterone replacement in primary keep LH normal Awareness SE BPH / Prostatic cancer PSA in Age > 50 Dyslipidemia Polycythemia Hct q 3 mo. Liver LFT in Alkylated T CI : PRCA / BRCA / OSA Secondary : GnRH / hCG Treat underlying disease

10. Gynecomastia Only in male with breast tissue diameter > 2 cm Gynecomastia / Pseudogynecomastia (Lipomastia) Physiologic / Pathologic (>18 wk. / > 4cm. Physiologic Newborn : maternal estrogen Puberty age < 17 yr. regression in 18 wk.!!! Elderly : decrease testosterone level Pathologic always exclude germ cell β-hCG producing Local factors TH / Cortisol / Prolactin / GH / Insulin High Estrogen (History Growth spurt ) Normal or Low LH External Estrogen use Estrogen producing tumor Leydig or Sertoli cell tumor Adrenal mass Increase Aromatization Normal Estrogen-Low Testosterone : Line approach hypogonadism + Antiandrogen / Increase T met-clearance / Favor 2’ > 1’ + TH+ + increase metabolite Testosterone Prolactinoma (High LH) Normal Estrogen –Normal Testosterone Androgen insensitivity syndrome Drugs Hormone : Androgen Antibiotic : INH / Metronidazole / Ketoconazole Anti-peptic : Cimetidine CMT : Alkylating agents-Vinca alkaloid / MTX Heart : Amiodarone / Captopril / Digoxin Metoclopramide (Plasil) / Psychiatric drugs Substance uses : Alcohol / Heroin / Amphetamine

11. Galactorrhea Postpartum > 1 yr. / Non pregnant / Male Clinical features FM : galactorrhea / amenorrhea / infertility / osteoporosis mostly microadenoma M : decrease libido / impotence / infertility galactorrhea late and mostly macroadenoma Pressure effect from pituitary mass Lactogenesis EST / Prog / GH / Insulin / TH / GC + Prolactin / Oxytocin Sucking + T4-6 Supra-optic / Paravent N ↓DA + PRL / Oxytocin Pituitary Stimulating factors TRH Sucking / Stress / Dehydration / Exercise / SI / Sleep EST / 5HT Pituitary Inhibiting factors Only Dopamine signal from Stalk Approach Confirm milk or nipple discharge : fat globle Physiologic or pathologic Witch milk from maternal Estrogen Pregnancy-Lactation Nipple stimulation Pathologic Prolactinoma / Stalk effect Cushing’s / Acromegaly / MS Systemic disease : 1’HypoTH / CKD / PCOS / cirrhosis Medication : DA-Ant / Psych / HZ / Hormone Chest wall irritation Idiopathic Diagnosis Prolactin level in the morning Level always relate with mass size Macroadenoma with low PRL Hook effect : Dilute Non functioning Microadenoma with high PRL Macroprolactinemia large mol. Low aff. bind R

Normal < 20 ng/ml if µIU X 0.03 ng/ml > 150 likely prolactinoma Stalk effect prolactin level always < 150-200 Near P effect and amenoorhea period Prolactinoma amenorrhea long then P Treatment DA agonist : Bromocriptine Micro well response 80-90% Macro 70% Normal PRL level Decrease size Restore gonadal function No teratogenic effect in pregnancy Microadenoma can stop and F/U ↑ size but rare to develop macroadenoma Macroadenoma continue drug Symptom can F/U only VF defect Titrate drugs q 1 mo. start ½ tab Surgery recurrent 20% Apoplexy with neuroSS Cystic Macroprolactinoma Intolerate DA agonist Macroprolactinoma FM with pregnancy desire Symptom from mass Enlargement During pregnancy not reponse DA agonist Radiation low efficacy

12. Amenorrhea Primary Delay puberty ↑ FSH / LH : Turner / AIS / Gonadal failure ↓ FSH / LH : CD / AN / illness / GnRH def. Normal puberty U/S : Outflow obstruction Normal : Approach as secondary amenorrhea Secondary Positive hCG Pregnancy Negative hCG ↑TSH Thyroid dysfunction None ↑ PRL Hyperprolactinemia None ↑ FSH Ovarian failure N / ↓ Progesterone challenge test Bleeding : Anovulation PCOS / Idiopathic No EST + Progesterone Bleeding : Hypothalamic None : Uterine factor

13. Pituitary disease !!! Boundaries Upper : Stalk / Hypothalamus / 3rd ventricle Optic chiasma (80% above sellar 20% antr or postr) Lower : Sphenoid sinus Lateral : Carvernous sinus / CN Vessels Superior : Anterior and Posterior Inferior : Posterior Anterior tendency to ischemia > Posterior Neuron that secrete ADH at Posterior bright spot Sellar mass upward and posterior rarely DI Suprasellar mass direct compression Commonly present with DI / P effect Normal size Pituitary gland < 1 cm. and Stalk < 1 cm.(0.6) (Cut Cerebellum) Sellar lesion Functioning PRL / GH / GC TSHoma ↑T3 / T4 N / ↑ TSH 2’ TH++ / Peripheral TSH resistant Most common Macroadenoma VF defect / Goiter / Thyrotoxicosis Treatment Surgery Somatostatin analogue Can mixed commonly PRL + GH Non functioning Metastasis : Breast / Lung / GI Hematogenous spread predominate DI Hypophysitis Craniopharyngioma Rathke’s cleft cyst Trauma / Radiation

Infiltrative disease Sarcoidosis / Hemochromatosis / Infection

Parameter Sellar mass Suprasellar DI Symptom Figure of 8 Sellar floor Ballooning S Epicenter Mass size Pineal mass

Rare or late Hormone / None Absent Destruction Present Within Sellar Small to medium Absent

Common Pressure effect Present Intact Absent Out of Sellar Huge mass Present

Treatment common functioning PRL : Medication GH : Surgery RT CS : Surgery Panhypopituitarism 2’AI / TH- / Hypogonad / Dwafism / DI MC : Sheehan’s syndrome Necrosis anterior pituitary No DI Other causes Pituitary tumor Histiocytosis Empty sellar syndrome Infection : Hypophysitis Trauma / Radiation

Infiltrative disease Sarcoidosis Hemochromatosis Infection Treatment Prednisolone / L-T4 / EST-PG / GH / DDAVP

14. Acromegaly Variation 5-6 peak can’t direct measure GH IGF-I stable all day GH + Liver synthesis IGF-I SS + Stroke / CAD / Sleep apnea Diagnosis Screening IGF-I Confirm Glucose loading test Fasting 8 hr. 75-100 g Glucose GH level after Glucose 1,2 hr. Normal < 2 ng/ml RIA < 1 ng/ml 2-site IRMA + MRI pituitary + GHRH level Causes Pituitary tumor Ectopic GH ( MRI no mass ) GHRH level and CT chest + abdomen Lymphoma Pancreatic Islet tumor Exogenous GH GRH : Hypothalamic tumor Bronchial carcinoid Medullary CA Thyroid / Pheochromocytoma Adrenal adenoma Treatment aim GH < 1 Drugs ↓ Secretion : Somatostatin analogue ↓GH F/U GH and IGF-I Anti-GH : Pegvisomant (GHr) not ↓GH F/U IGF-I only Transphenoidal Surgery : treatment of choice Macroadenoma cure < 50% Microadenoma cure 80% Dz. persistence 3 modality Radiation : treatment of choice Acromegaly mostly macroadenoma : Surgery then RT

15. Short Stature Diagnosis R/O Scoliosis / Bone deformities / ����� Growth curve limit at Age 19 yr. stable Ht. Age > 19 yr. use at Age 19 Ht. < 3 percentile FM <145 or 148 cm. M < 155 or 160 cm. Proportionate / Disproportionate US/LS 0.9-1.1 Arm span-Ht. FM 1cm. M 4 cm. Disproportionate Short limb OIs / Achondroplasia Short trunk Morquio Proportionate Physiologic (MPH D+M +13/2) FSS / CDGD / GSS

Parameter FSS CDGD SS Height Parent / FH Growth rate Bone age 2’ sex Treatment

Proportionate Within MPH SS / Negative Normal In 2SD CA Present Reassure

Proportionate Out of MPH Tall / Positive Normal < 2SD CA=Ht. Absent Reassure

Pathologic Most common FM 80-90% Turner Most common M CDGD / GH def. Perinatal Prenatal IUGR Maternal / Placental Postnatal Malnutrition Genetic / Chromosome dz.

S&S Turner Noonan Sex 2’sex IQ Heart dz. Web neck Cubitus vg Other ass.

FM Absent Intact Coarc-BicuspAV Posterior Present DM/TH-/IBD/CA

Both Present Impair PS Anterior Absent HemophilC

Prader-Willi

SS + HypoGd + Obesity + LD Almond shaped Eyes Wiliam SS + MR + Supravalvular AS + HT HyperCa + Hypercussis Elfin face Laurence-Moon-Biedl Down’s syndrome McCune Albright Chronic dz. Endocrine dz. / Metabolic dz. Cretinism Hypothyroidism Panhypopituitarism Bone dz. Deprivation Drugs 16. Tall stature Diagnosis Ht. > 3 percentile FM > 166 cm. M > 180 cm. Male Hypogonadism : previous line approach CNT : Marfan syndrome / Ehler-Danlos Gigantism 17. Pheochromocytoma

Tumor of chromaffin cell secrete cathecholamine Most common Neuroendocrine tumor Extraadrenal sympathetic gg. : Paraganglioma Clinical feature depend on main secrete cathecholamine Highly activate β2 profound hypotension Headache + Diaphoresis + Tachycardia-Palpitation HT + Orthostatic hypotension-Shock + Hypercalcemia 10% associated inherited disorders MEN2(10q11) / VHL(3p25) / NFI(17q11) / Familial Paraganglioma(11q22-23) Screening U24 hr. for cathecholamine / VMA / Metanephrine Repeat especially after paroxysmal attack Drugs interfere : TCA / Sympathomimetic / BB / Alc Plasma Chromogranin A level CT-MRI or I131 MIBG Stepwise U 24 hr. negative X 2 after attack F/U positive : adrenal-abdominal MRI I131 MIBG when Suspected bilateral disease Hereditary syndrome Suspected paraganglioma Positive Pre-op + AntiHT/Fluid Surgery Negatvie : false positive hormone Pre-operative treatment AntiHT Selective α-blocker : Prazosin / Doxasozin CCB / BB after adequate α-blocker Hypoglycemia from rebound hyperinsulinemia Awareness Cath. withdrawal synd. Post-op 75% normal BP 25 % persistent HT with easy control F/U Cath. At 6 wk. and 6 mo. then q 1 yr. X 5 yr. Familial : Life long 18. Hypoglycemia

R/O Pseudohypoglycemia : PV / Leukemia Whipple triad BS < 50 or < 60 with symptom Clinical Hypoglycemia Improve by correct BS Clinical features : Non specific Sympathetic overactivity Neuroglycopenic symptom Counter regulatory hormone response to hypoglycemia Inhibit I secretion Glucagon E Cortisol / GH Others Stepwise 72 hr. fasting induced hypoglycemia Lab W/U BS / BUN / Cr / LFT / Sulfonylurea level I / C-peptide / serum ketone / Cortisol / GH + ACTH stimulation test Fasting / Postprandrial After diet within 6 hr. Past history compatible Mild Hypoglycemia No neuroglycopenic symptoms Diabetic / Non diabetic Postprandrial Congenital enz. def of CBH metabolism Alimentary Hypoglycemia : Dumping Rapid transit time-glucose absorption Idiopathic / Functional + Insulinoma / Early onset DM Fasting Underproduction / Overutilization Need Glucose maintain > 10 g/hr. Underproduction GH def. / AI Liver disease Kidney disease MOF : Severe sepsis Overutilization Severe sepsis Cut point I > 6uIU/ml C-peptide > 0.2 I C-peptide

↑ ↓ Exogenous I AutoAb to Ir ↑ ↑ I secretagogue IPIT Β cell hyperplasia (Nesidioblastosis) AutoAb to I ↓ ↓ IGF Insulinoma 80% single 10% multiple 10% malignant mean size 2 cm. 5% associated MENI 99% in pancreas and 1 % duodenal wall CT abdomen + 50% no need pre-op localization The best intra-op palpation and U/S Treatment Enucleation except Hard consistency Distal pancreatic duct dilate Multiple mass Diatal pancreatectomy to 70% Ass. MENI surgery head Recurrent 20% Drugs Diazoxide / Dilantin / GC Verapamil / Sandostatin / Propanolol / HCTZ Recurrent 5% in 10 yr. 7% in 20 yr. 19. Adrenal insufficiency

Non specific symptom Fatigue / Dizziness / Postural hypotension / Hyponatremia / Hypoglycemia Classification

Onset Primary (Adrenal) Secondary (Pituitary) Slow Abrupt

AI adrenalitis Disseminated infection TB-F Metastatic CA AIDS Adrenomyeloneuropathy Hemorrhage : Sepsis- Meningococcemia Necrosis Thrombosis : APS

Tumor : 1’ / Metast Craniopharyngioma Surgery / Radiation LO hypophysitis Hypothalamic tumor Histiocytosis X Empty sellar synd. Long term steroid Sheehan’s syndrome Apoplexy Trauma-Stalk lesion Surgery

Screening Stop GC > 48 hr. Awareness CBG effect Basal morning cortisol (Non fasting 8.00-9.00) < 3.5 µg/dl Diagnosis 3.5-18 µg/dl Further test > 18 µg/dl Exclude then ½ of test R/O 1’ ACTH stim / 2’ ITT Insulin induce hypoglycemia Gold standard !!! But C/I : Sz. / Stroke / 1’ Fasting then RI 0.1U/kg IV PG + Cortisol 0 / 30 / 45 / 60 min < 18 µg/dl with PG < 40 diagnosis > 18 µg/dl Normal HPA axis ACTH stimulation test ACTH 20 µg/dl IV Cortisol 0 / 30 / 60 min < 18 µg/dl both Diagnosis > 18 only one Adrenal preserve-Exclude High dose ACTH can’t use for Mild 1’ AI Recent onset 2’ AI Primary or Secondary

ACTH 8.00-9.00 > 10 pg/ml Primary : HyperK Hyperpigmentation skin crease / scar / buccal mucosa N / ↓ Secondary Causes Primary CT Adrenal + 21OHAb / ACA / VLCFA /CAH Adrenal++ / calcification TB / F / Bleeding / Tumor Normal imaging Autoimmune Addison’s Adrenomyeloneuropathy Secondary Non Exogenous MRI Pituitary Pituitary-Hypothalamus lesn Normal imaging Sheehan Isolated ACTH def. Treatment Hormone replacement depend on stress + F/U Treat causes 20. Thyroid disease

Clinical Solitary nodule Diffuse goiter Multinodular Goiter Thyrotoxicosis Hypothyroidism Clinical Solitary Thyroid Nodule (CSTN) TFT confirm EUTH Most common Benign : Cyst Adequate FNA X 3 negative-colloid : Cancer < 5% Awareness in Age < 20 / > 60 yr. Male LN + Rapid increase in size Compressive or invasive symptom Solid or Mixed FH Medullary Thyroid cancer Previouos radiation Diffuse Goiter (prone TH-) Causes (Euthyroid / HypoTH) Iodine deficiency (habitat) Goitrogen (mild size + soft ) Physiologic goiter : Puberty / Pregnancy Enzymatic defect : PENDRED synd. (Perioxidase deficiency) SNHL + FH Perchlorate discharge test Hashimoto’s thyroiditis Idiopathic Toxic / Non toxic Non Toxic FT4 / TSH EuTH / Subclinal hypoTH / HypoTH HypoTH diffuse goiter Approach by setting Non Ab Tg / Microsomal Positive Hashimoto’s / Negative Idiopathic Treatment

Causes EUTH F/U GL > 30g Supressive L-T4 1-2 tab/d Keep TSH 0.1-0.3 6 mo. not decrease off response 2 yr. C/I Age > 60 yr. Heart disease Postmenopausal Osteoporosis Surgery for cosmetic HypoTH Replacement ¾-1½ F/U TSH only keep normal Multinodular Goiter (prone TH+) Toxic : Line management Thyrotoxicosis I131 GL>5X / R/O Cancer Surgery Subclinical TH+ : F/U EUTH : as Non Toxic Diffuse Goiter FNA in Suspicious cancer rapid increase size of nodule Low yield thyroid scan / ultrasound / Thyrotoxicosis Most common GD Thyroid bruit + : GD no DDX Diffuse enlargement TH Opthalmopathy : Exopthalmos / EOM Dermopathy Duration > 3 mo. Can be lymphopenia PMN < 1500 off ATD Gland Multinodular : TMNG Solitary nodule Thyroid scan Toxic Adenoma GD with Cold nodule Diffuse : GD

Non obvious GD I131 uptake N / ↑ hCG : GD / Hydratid mole ↓ ThAb : Hashimoto’s ↓↓↓(6)Exogenous TH Transient painless thyroiditis Struma ovarii Subacute painful thyroiditis Functional metastatic TH Carcinoma Treatment GD : ATD / I131 / Surgery TMNG : ATD EUTH RT Surgery in GL>5X, Or R/O CA TA : ATD EUTH RT Surgery in GL>5X, Or R/O CA Thyroiditis : BB + Supportive recovery in 2 mo. Hypothyroidism Clinical manifestation Husky voice / Macroglossia / Myoedema / Weakness / CTS / Conscious Delayed relaxation : SS 77% / SP 94% Constipation / Psychiatric disease HT / Bradycardia synd. / Pericardial effusion Myxedema (in 1’ TH-) Lab confirm 1’/2’ : Myxedema / TSH Goitrous / Non Goitrous Non Goitrous Central TH- : Pituitary /Hypothalamus Post surgery or RT-I131 Thyroid External RT Head&Neck Thyroid agenesis / hypoplasia Drugs Goitrous GD during or post treatment Hashimoto’s thyroiditis Dyshormogenesis : PENDRED (AR/SNHL) Iodine deficiency / Drugs Lab

FT4 / TSH + TPOAb / TgAb + RAIU / Urine I + Perchlorate Discharge test

Causes T4 TSH TRH response Primary Secondary Tertiary NTI

↓ ↓ ↓

↓ rare

↑ N / ↓ N / ↓

N

Exaggertated Absent ,↑<10 Normal-Delay Normal

R/O Transient causes of TH- After I131 / Surgery Thyroiditis : Postpartum / Subacute / Painless Withdrawal TH Untreatment Addison’s disease Treatment TH Replacement Optimal Dose 1.6-1.8 µg/kg/d GD 1.6 (risk for relapse) HMT 1.76 Initial Dose < 60 yr. FM ¾ -1 M 1-1½ > 60 yr. HD ¼ - ½ NO 1/8 - ¼ Increase dose ¼ tab q 4 wk. F/U TSH after stable dose at least 6-8 wk. Can wait for 3-6 mo. T4 t½ 6.5 d. Duration 6 wk. FT4 TSH N ↑ Not reach equilibrium state Inadequate dose Non compliance Drugs / Condition require higher dose N ↓ Over replacement Relapse GD Pregnancy

Keep TSH near 2 before 1st T increase dose 25-50% Adjust dose by FT4 weekly Keep FT4 normal TSH 1-2X UL Initial < 800 µg/wk. ↑ 100 µg/wk. Initial 900-1050 ↑ 150 µg/wk. FT4 N TSH < 0.1 Total < 900 ↓100 µg/wk. Total 1050-1200 ↑150 µg/wk. Drugs decrease absorption Cholestyramine / Sucralfate / Al(OH)3 FeSO4 / Kayexalate / CaCO3 NPO > 1 wk. start L-T4 injection or oral Subclinical HypoTH- Replacement in high risk overt TH- Or risk to MM from TH- Pregnancy or plan for pregnant TSH > 10 benefit >20 definite Age > 65 Microsomal Ab > 1:1600 Post I131