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General Introduction of Endocrinology Second messenger: cAMP is act as a second messenger by

accepting the information offered by the hormone-receptor
complex and transmitting it to its molecular destination within the
Endocrine: the process of secretion of biologically active

Hormone: is a substance that is secreted by cell and travels Disorder of the endocrine:
through circulation
Hormone Deficiency Hormone excess Multiple endocrine
syndrome syndrome
Receptor: is a molecule to which the hormone binds to elicit its
action. It has two functions: 1.Must be able to distinguish hormone Hypofunction of Hyperfunction of
& bind with its; 2. Must be able to transmit information & trigger a Endocrine Glands Endocrine Glands Multiple endocrine
cellular response deficiencies
Hormone Deficiency Ectopic Hormone
Classification: Secondary to Production Multiple endocrine
Extraglandular neoplasia (MEN)
 Peptides & protein (most of hormone in the body - hormones Disorders Hormone
Administration (for
of the hypothalamus, pituitary gland, parathyroid glands,
Hyporesponsiveness to treatment e.g. cortisol
gastrointestinal tract, and pancreas) hormones treatment)

 Amino acid derivatives (T3,T4) Abnormal Production Tissue
or Administration of Hypersensitivity
 Steroid hormone (Include hormones of the adrenal cortex, Antagonists
gonads (ovary and testes), and placenta and active vitamin D) Autoimmune Disease

Hormone Biosynthetic
Mechanism of hormone action
or metabolic defects
 Through the cell membrane receptor (use cAMP as a “second Secondary Hormone
messenger” to transmit information to its molecular Hypersecretion
destination within the cell)

 Through cytoplasmic or nucleus receptor (diffuse freely
across the cell membrane due to their small size) Ectopic hormone syndrome: Hormone may be produced in
excess by cells of endocrine or non-endocrine origin that are not
Hormone regulation normally the primary source of a hormone. (E.g. small-cell lung
carcinoma can produce the ACTH)
 The relationship between the nervous and endocrinology
(brain & pituitary also produce hormone) Multiple endocrine neoplasia (MEN): is condition in which arise
from at least three syndromes of multiple endocrine hyperfunction
 Hormone release often has rhythmic pattern (Day-night result from hyperplasia, adenomas, or carcinomas of endocrine
rhythms-GH & monthly rhythms-esterogen) tissues. MEN includes 3 types: (1,2a,2b)

 Specific stimuli received by the endocrine cells cause them to Type1 is associated Type2a is associated Type2b is associated
increase their hormone secretion (e.g. glucose induce insulin with Hyperfunction with with medullary thyroid
release from adrenal cortex) of parathyroid, pheochromocytoma, carcinoma,
pancreatic islets medullary carcinoma of pheochromocytoma, and
and pituitary. thyroid, parathyroid other features such as
 Some stimuli decrease hormone (GHIH released by carcinoma. neuromas
hypothalamus decreased the amount of GH released by
anterior pituitary gland)

 The concentration of the secreted hormone in the blood,
and /or the effects produced by the hormone , control
subsequent secretion of the hormone (Negative & positive

Negative feedback (most common regulatory loop): the level of
hormones in circulation or the response produced by the hormone
negates or reverses the original stimulus, decrease the secretion of
their stimulating hormone (ACTH stimulates release of cortisol
which inhibit ACTH release)

Positive feedback: response augments rather than attenuates the
stimulus (in pregnancy feto-placental unit, produces increasing
amounts of the steroid hormones estrogen and progesterone)

reduction in breast size. pubic. a hormone production Gonadotropin decrease in general sense of well-being deficiency and . GH deficiency Obesity (in adult) and fasting Sex Weight loss Low BP Lower bone mineral density hypofunction . apoplexy TSH deficiency Hypothyroidism → fatigue. cold. and body hair genesis & cause pigmentation gradually. and hypotension (Mild Hemochromatosis. carbohydrates & fat  Appear more early in the process of this metabolism disease  PRL (Prolactin) → promote milk production Women:  FSH (Follicle stimulating hormone) & LH (Luteinnizing  Hypogonadism → infertility & decreased hormone) → stimulates testes/ovaries & sex hormone Estradiol secretion synthesize  Estradiol deficiency (after puberty) →  TSH (Thyroid stimulating hormone) → stimulate thyroid Amenorrhea. fatigues. Encephalitis. granulomas. Trauma. Autoimmunity. Stroke. Radiation. muscle growth. Hypopituitarism Specific symptom & sign of hormonal deficiency: Pituitary main hormone production: General: Anterior:  Hypogonadism and infertility  ACTH (Adenocoticotropic hormone) → ↑adrenal steroid  Lose axillary. weight (bleeding). aneurysms. Weakness Easy Axillary 、 Lack of fatigability pubic hair loss resistance to stress. constipation. weakness. postpartum pituitary necrosis (Sheehan’s syndrome). pituitary abscess. not due to ACTH deficiency one. particularly if they are also hypoadrenal  GH → promote bone.  Other: Autoimmune hypophysitis. and men may note diminished beard  Secondary Hypopituitarism is caused by diseases which affect growth hypothalamus  Testosterone deficiency (prior to puberty) Etiology: → incomplete puberty  Mass lesions (common cause): Pituitary tumor. metastatic carcinoma.if the deficiency is severe. Surgery (common). vasomotor instability (hot flashes) and vaginal dryness Posterior: (Loss of LH & FSH) happen  Oxytocin → stimulate uterine & milk ejection  Estradiol deficiency (prior to puberty) → incomplete puberty  ADH → Antideuretic hormone Men: Hypopituitarism definition: Impairment of anterior pituitary or hypothalamus leads to hyposecretion of anterior pituitary hormone. Diminished cortisol secretion → weakness. and hyperlipidemia. dry skin. weight loss. cold intolerance. change (weight gain). Idiopathic disease. cortisol deficiency may asymptomatic) ACTH deficiency General symptoms and signs: Only cortisol deficiency due to primary adrenal disease can cause hyperpigmentation.  Hypogonadism → decreased sperm present itself with related target gland hypofunction production and those of decreased testosterone secretion  Primary Hypopituitarism is caused by anterior pituitary  Testosterone deficiency (after puberty) → hypofunction energy and libido decrease within weeks.

ACTH. IM/IV 0. normal adrenal and thyroid function) When patient exposed to stress (e.g. surgery or dehydration and so on) which induce body to need more pituitary hormone . and gonads  The patients with pituitary tumors → may have headache.  Primary adrenal or thyroid insufficiency: Serum ACTH and TSH are not elevated in Hypopituitarism Other symptoms & sign:  Severe illness causes functional suppression of TSH &  Panhypopituitarism (absence of all anterior pituitary thyroxine: Glucocorticoids or megestrol treatment reversibly hormones) → Above manifestation + (long-standing suppresses endogenous ACTH and cortisol secretion. trauma or surgical procedures) → Give additional hydrocortisone (50 mg IM/IV every 6  Stimulating test (Cosyntropin test in secondary hours and then reduced to normal doses as the stress subsides) hypoadrenalism)  Mild illness → corticosteroid doses are doubled or tripled  Administration of cosyntropin (synthetic ACTH1-24).. (Normal sex hair.g.6 IU) three times weekly or daily. but in most case Lifetime hormone replacement the prolactin is low because of lactotroph impairment ACTH replacement  Low Free T4 & TSH is not elevated  Oral hydrocortisone 15-25mg/d (devided dose → 15mg in the  11-deoxycortisol or cortisol concentration level is low morning & 5mg in the late afternoon)  ACTH level is low or normal in secondary hypoadrenalism  During states of (e.g. adrenals. headache.  Hyperkalemia does not occurs because aldosterone  Adults with growth hormone deficiency → ↑cardiovascular production is not affected morbidity  Hormones determine:  Pituitary acute hemorrhage (occur in large pituitary tumors) → rapid loss of vision. infection. but there is receiving glucocorticoids. The face has fine wrinkles and an apathetic countenance. Most common use corticosteroid  A low-dose cosyntropin test (0. FSH. TSH.25mg usually causes serum cortisol to rise to less than 20µg/dL by 30-60m after the injection. and hypothalamic disease). (Schimdit Syndrome) → (elevated pituitary hormone → visual impairment. The dosage is increased until side effects occur. pale. acromegaly.  Multiple endocrine deficiencies: Involve immunologic destruction of pancreatic islets. Hypopituitarism) dry. tumors) → may develop complication due to surgery or radiation therapy.2 mg (0.  Low fasting blood glucose  Untreated hypoadrenalism and a stressful illness → febrile  Hyponatremia and die in shock and coma. and evidence of acute  Low plasma sex level (testosterone & estradiol) & low pituitary failure gonadotropin Treatment  Elevated prolactin levels (in patients with prolactinoma.125 mg/d) → to correct hypothyroidism only after the patient is assessed for cortisol deficiency or is already  IGF-I levels may be low in GH deficiency. thyroid. considerable overlap with normal Sex hormone replacement Other examination → MRI Adult → subcutaneous somatotropin injection starting at a Differential diagnosis dosage of about 0. LH level are high) Lab findings: Complication  Biochemical indicator:  Destructive lesions (e. finely textured skin.  Reversible physiologic hypogonadotropic Hypogonadism: The disease may occur during any serious illness and with Emergency Acute Hypopituitarism malnutrition.001 mg IV) is slightly more sensitive in detecting subtle ACTH – cortisol insufficiency Hydrocortisone (20mg) Cortisone (25mg) Prednisone (5mg)  GH deficiency detecting Thyroid replacement  The insulin hypoglycemia test (most accurately but it’s dangerous for elderly of seizure prone patients) Levothyroxine (0. infection.

350C → levothyroxine. androgen): growth of hair follicle  Nausea. due to Zona glomerulosa Zona fasciculata Zona reticularis adrenal gland secreting excessive cortisol or by cortisol therapy. neutrophelia. immune function and carbohydrate.g. When T↑ to antibody production. At first giving 50% glucose to treat excretion → osteoporosis hypoglycemia. balance supplement sex steroids. lymphocytopenia. methylprednisolone Intermediate triamcinolone ++ acting fluprednisolone ++++ Long acting deoxycorticosterone ++++ Mineralocorticoids + ++++ deoxycorticosterone Cushing’s syndrome Adrenal disease Definition: Adrenal hormone production Cushing’s syndrome is hypercortisolism of any etiology.  Water intoxication (the formation and excretion of urine protein and fat metabolism. emotional stability. eosinopenia.  Initially increased antibody release → Eventually decreased  Amelioration Hyperthermia or hypothermia. confusion  Sex hormone (e.  Dehydraton. hypovolemia.  ↑ gastric acidity → ulcer formation or aggravation  Hydrocortisol 200-300mg/d if progress is satisfactory  K loss and Na retention → edema & hypertension and then taper to oral maintenance dose by day 4 or 5. anorexia  Cortisol: Cortisol affects the body’s response to stress. ↑ renal Ca  IV saline & glucose. impairment of Ca absorbtion. Short acting hydrocortisone.Clinical finding Adrenal cortex steroid hormone  Hypotension /shock  Aldosterone: Aldosterone promotes sodium and water absorption and potassium excretion in the kidney tubules. ++ ++ prednisolone. polycythemia → susceptibility to infections  Correction of remote causes (e. preventing and cure of  Maintenance of arteriolar tone and blood pressure infection) Natural & synthetic adrenocorticosteroids  The patients with water intoxication must be given cortisol IV infusion or intake water is confined. . vomitting. Glococorticoids Antiinflamation Self retaining  All drugs about sleeping and calm are inhibited. Aldosterone → Cortisol → regulate Androstenedione & Cushing’s disease refers to hypercortisolism resulting from regulate Na+ and K+ glucose metabolism DHEA → pituitary over-secretion of ACTH.  Weakness.g. apathy. then follow by 10% Glucose & Sodium Chloride Injection continues. + + cortisone prednisone. is difficult) Steroid hormone actions  Hyperthermia(>40℃) or hypothermia(<30℃)  Amino acid catabolism (muscle wasting) → gluconeogenesis  Hypoglycemia in the liver → Hyperglycemia → increased insulin output → eventual beta cell failure → fat deposition → diabetes Treatment  Ca resorption.

5 mg orally every 6 hours for 48  diabetes or impaired glucose tolerance hours. Decreased libido and impotence in males  Hypertension (75-85%)  Small dose dexamethasone suppression test: Giving dexamethasone. especially proximal (87%)  The easiest screening test for hypercortisolism: Giving dexamethasone at 11PM (1 mg orally) follow by collecting  Malaise serum for cortisol determination at about 8 AM the next morning (if cortisol level <5 µg/dL excludes Cushing's  Psychological disturbance: Anxiety.5 mg/d → hypercortisolism) Notes:  Central obesity → effecting mainly face.  Buffo hump → appears due to accumulation of fat around the neck (supraclavicular & dorsocervical fat pad) Etiology:  Plethoric → thinning and transparent appearance of the skin 1) ACTH-dependent Cushing's syndrome due to atrophy of the epidermis & its underlying connective tissue (appears in advance stage) 2) ACTH-independent Cushing's syndrome  Striae → appears due to rapid weight gain Cause Frequency  Easy bruisability. 0. emotional lability. acne. depression and psychosis (66%)  A 24-hour urine collection for free cortisol and creatinine: An abnormally high 24-hour urine free cortisol (or free  Hirsuties (80%) cortisol to creatinine ratio of > 95 mg cortisol/g creatinine) helps confirm hypercortisolism. skin-thinning. mucocutaneous fungal infection → frequently appears ACTH-dependent (85%) Cushing’s disease 70%  Hyperpigmentation → rarely presence in Cushing’s Ectopic ACTH 15% syndrome syndrome or adrenal tumor. syndrome with 98% certainty) increase irritability decrease concentration. bruising (67%)  Serum cortisol level is high: especially in midnight serum  Poluuria. trunk. neck. poor memory.urine is collected on the second day (if Urine free cortisol > 20ug/d or urine 17-hydroxycorticosteroid > 4. nocturia cortisol level >7.  Striae.5 ug/dL is indicative of Cushing's syndrome and distinguishes it from other conditions associated with a  Gonadal dysfunction: Oligomenorrhoea or amenorrhoea high urine free cortisol (pseudo-Cushing states) in female (77%). but common in Ectopic ACTH syndrome Adrenal adenoma !5%  Hirsutism → appear in female due to hypersecretion of ACTH-independent (15%) Adrenal carcinoma 10% adrenal androgen Iatrogenic 10%  Hypertension → together with its complication contribute greatly to morbidity and mortality in spontaneous Cushing’s syndrome Clinical manifestation:  Gonadal dysfunction → appears due to elevated levels of androgens and cortisol Typical finding: Diagnosis  Increase body weight (94%) General test  Central obesity with a plethoric moon face (97%)  Buffalo hump  Glucose tolerance is impaired  Supraclavicular fat pads  Leukocytosis with relative granulocytosis and lymphopenia  Protuberant abdomen  Hypokalemia particularly in cases of ectopic ACTH  Thin extremities secretion Major clinical: Hypercortisolism test  Muscular weakness. slow & poor healing. & Causative test abdomen with elative spring extremities .

 Caused by ACTH hpersecretion  Big dose dexamethasone suppression test: Giving from nonpituitary tumors. while 17-hydroxycorticosteroids remain normal and diurnal variability of serum cortisol is normal Complication Differential diagnosis  Morbidity & mortality → if untreated  Severe obesity → normal urine free cortisol  Complication of hypertension or diabetes  Familial cortisol resistance → have hyperandrogenism. Ct dexamethasone suppression test and urinary free cortisol. It is characterized by chronic deficiency of cortisol. 2 mg orally every 6 hours for 48 hours. poor wound healing. Lack of also can localize ectopic source of ACTH (lung. cases . psychologic hyperplasia and hypersecretion changes. thin skin. . and  Adrenal tumor is present in most primidone accelerate the metabolism of dexamethasone→ of patients false-positive dexamethasone suppression test. MRI can demonstratr pituitary adenoma in about dexamethasone. Ectopic ACTH hypersecretion of pituitary or ectopic tumor hypertension. dexamethasone. a pituitary adenoma may enlarge progressively. 50% (because some pituitary tumor are very small). hypokalemia  The secretion of cortisol can’t be inhibited by big dose  Elevated serum cortisol  Imaging: CT can localize adrenal tumor in most cases.  The secretion of cortisol can’t be  Estrogens-during pregnancy or as oral contraceptives or inhibited by big dose dexamethasone suppression test . normal suppression by pancreas). hirsutism (cancer). → Adrenal tumor & ectopic ACTh neoplasm can’t be glycosuria. easy bilateral adrenocortical bruisability. muscle  hypersecretion of ACTH with insufficiency wasting.  absent circadian periodicity of Addison’s Diseases (Adrenocortical insufficiency) ACTH and cortisol release Definition: is an uncommon disorder caused by destruction or dysfunction of the adrenal cortices. will revert to  Compression fracture of osteoporotic spine & aseptic necrosis normal after cessation of alcohol intake of femoral head  Depressed patient → no clinical signs of Cushing’s syndrome  Nephrolithiasis & psychosis  Nelson’s syndrome → Following bilateral adrenalectomy for Cushing's disease. visual field impairment) and hyperpigmentation Treatment (Directed at pituitary to control ACTH hypersecretion) Essential diagnosis Microsurgery . & hypercortisolism  Susceptible to infection  Alcoholism → mimic to hypercortisolism. if ↑than normal range = probable  Osteoporosis. thymus.ACTH secretion inhibition drugs Symptom & sign Cushing ’s disease Surgery (to remove causative agent (e.  Baseline plasma ACTH: if ↓ than normal range (20pg/mL) = probable of adrenal tumor. estrogen replacement therapy-may also cause lack of dexamethasone suppressibility → in pregnancy urine free cortisol ↑. adrenal androgens. leukocytosis. and /or aldosterone. PET can Cushing’s syndrome found concentration of corticol  There is a hyperscretion of Notes: cortisol with the hyposecretion of ACTH. phenobarbital.  Certain drugs such as phenytoin.g. inhibited lymphocytopenia. tumor)) follow by hormone replacement post-operatively to avoid adrenal  Central obesity. causing local destruction (eg. of cortisol purple striae.urine Lab test is collected on the second day (if Urine free cortisol decrease  Hyperpigmentation in most of amplitutde >50% indicates secretion of cortisol is suppressed)  Hyperglycemia. hypertension.Radio therapy .

<100mmHg associated with orthostatic dizziness & occasionally syncope  Chronic liver disease  Salt craving (20% of cases)  Nelson syndrome  Hypoglycemia (unusual) → provoked fasting. Addison’s) → 90% of patient with systolic pressure hyperpigmentation of skin isn’t present. not strong enough to suggest endocrine gland hypofunction. vomiting. Tumor treatment.aciation. fever. e. or nausea which may lead to coma Treatment  Weakness → accompanied by fatigue & malaise Lifetime therapy with glucocorticoids & mineralocorticoids  Weight loss → due to tissue loss resulting from anorexia. diarrhea (rare)  Secondary adrenocortical insuffiency →There are other  Hypotension (common. various tumor  Basal levels of Urine or Plasma cortisol (Low or normal) metastases.5 times Hypotension Salt craving Hypoglycemic episodes meaning Diagnosis . AIDS.  Other chronic disease infection. pigment accentuation at nipples & friction area pigment concentration in skin creases scar  Gastrointestinal symptom → anorexia (common). dehydration also contribute Chronic: . hyperplasia of lymphoid tissue. insufficiency exposed areas & pressure points) → vetiligo.determin the plasma cortisol after 30 min change of cortisol plasma in Weakness Hyperpigmentation Loss weight. nauseam Differential diagnosis vague abdominal discomfort. diarrhea normal Increase 276~552nmol/L Gradually increase>2.combined with ACTH Differentiate primary from can be used to differentiate diagnosis secondary adrenocortical  Hyperpigmentation (most common.g.determin the change of ACTH in 3days. hypoparathyroidism. accentuatuion in sun. & shock)  Specific lab features for primary adrenocortical insufficiency  Other (1%) → fungal infection. ACTH is low. Hyperkalemia Lymphocytosis Hypercalcemia autoimmune thyroid disease. type 1 diabetes) → calls (PGA) (65%) Polyglandular autoimmune syndrome or Schimdit syndrome Increased plasma renin activity  TB Elevations of BUN & creatinine levels → dehydration and  Adrenoleukodystrophy → X linked peroxisomal disorder hemoconcentration  Bilateral adrenal hemorrhage → occurs in patients taking anticoagulang (clinical: pain. 1、2 、3day anorexia.  Primary adrenocortical insufficiency → resulting from  Other → small heart. congenital disease (hereditary cortisol deficiency)  Basal Plasma ACTH (>55pmol/ml、High) Physiology  ACTH stimulation test Rapid ACTH ST Three days ACTH ST Clinical finding: Methods Intravenous injection 25u ACTH in Intravenous injection 25u 30min. fever. vomiting. scant destruction or damage to adrenal cortex axillary & pubic hair and amenorrhea  Secondary adrenocortical insufficiency → resulting secondary Lab finding to pituitary ACTH secretion  Ordinary lab features for primary adrenocortical insufficiency Etiology Hyponatremia Azotemia Hypoglycemia (90%)  Idiopathic/Autoimmune (80%): Addison’s disease + other autoimmune endocrine disorder (e.

Followed by Etiology: continue IV infusions of 50-100mg every 6 hours for the first day. hyponatremia. lassitude  Nausea. is usually necessary to add fludrocortisone acetate. hemorrhage. dehydration. hyponatremia. headache. confusion or coma may be present  Weakness. ACE inhibitor. rule (eosinophilia & lymphocytosis → of adrenal insufficiency)  Some patients respond better to prednisone in a dosage of about 3 mg in the morning and 2 mg in the evening. Cause of thyrotoxicosis Differential diagnosis Dependent Independent  Differentiate of shock → e. hypothyroidism. heart failure. and reduce dosage to necrosis). sprinolactone) o Thyroid-stimulating o Subacute granulomatous immunoglobulin (TSI) thyroiditis (painful)  Differentiate of hyponatremia → e. e. or prolonged and then adjust the dosage in view of the clinical picture.  Mineralocorticoid therapy is not needed when large amounts of hydrocortisone are being given. diarrhea. without waiting for the results. or urine culture may be positive if bacterial infection is the Hyperthyroidism: term for overactive tissue within the thyroid precipitating cause of the crisis. & saline immediately. skin hyperpigmentation.g. hemorrhagic. apathy. Thyrotoxicosis: refers to clinical manifestation associated with  Hyperkalemia. Acute phase  Increased cortisol dosage during “stress”  If the diagnosis is suspected. infection. diarrhea. hypovolemia. abdominal or flank pain Hperthyroidsm  Dehydration. TSH receptor by: release hyperkalemic paralysism. trauma.6℃ or more). Blood.  Correcton of precipiating factors (e. vomitting. 10-20 mg every 6 hours. cirrhosis. Clinical finding  Hypotension /shock. cardiogenic Increased occupancy of the Increased thyroid hormone  Differentiate of Hyperkalemia → GI bleeding. but hyperthyroidism &  Other signs: cyanosis.g. Give the same amount every 8 hours on the second day  Following stress. infection.  Hyperthermia (40.sputum.g. Hyperthyroidism causes thyrotoxicosis.  Hydrocortisone 15-25 mg/d → two divided doses: 2/3 in the  Distinguished from an acute abdomen → neutrophilia is the morning and 1/3 in the late afternoon or early evening. surgery. Hypoglycemia serum level of thyroxine (T4) or triodothyroine (T3) that are excessive for individual.2 anticoagulant therapy. give oral  Following sudden destruction of the pituitary gland (pituitary hydrocortisone.  When the patient is able to take food by mouth. hypovolemia. & under the effect of certain drugs (e. glucocorticoids. or when thyroid hormone is given to a patient with maintenance levels as needed. broad spectrum  Following sudden withdrawal of adrenocortical hormone in a antibiotic) patient with chronic insufficiency or in a patient with chronic insufficiency due to suppression by exogenous  IV saline & glucose → to treat dehydration. gland causing an overproduction of thyroid hormones. hypoglacemia  Following bilateral adrenalectomy or removal of a functioning Convalescent phase adrenal tumor that had suppressed the other adrenal.05-0. vomiting. Treatment  Fludrocortisone supplementation or extra dietary salt → if sufficient salt-retaining effect and require do not obtain.g. fasting in a patient with latent insufficiency.g. thyrotoxicosis are not synonymous and sparse axillary hair (if hypogonadism is also present). diuretic use. or rarely mg daily metastatic carcinoma. o Subacute lymphocytic or major surgery . 100-300mg IV. 0. severe illness. thrombosis. draw a blood sample for cortisol determination. Adrenal crisis (emergency)  Treat with hydrocortisone. rhabdomyolysis. hypoadrenalism. but as the dose is reduced it  Following injury to both adrenals by trauma. anorexia. septic.

o Graves' disease thyroiditis (painless) o Tumors: Metastatic thyroid cancer. re-occur. occurs after o TSH-producing pituitary o Metastasis of follicular stressful illness in under treated or untreated patient. Trophoblastic o Hashitoxicosis Nonthyroidal source of tumor. Can Fine tremor of out stretched Large muscle weakness. Hyper kinesis Sinus tachycardia or atrial iodine deficient area. TSH secreting tumor thyroid hormone o Human chorionic o Greves disease (50-60%) → clinical exophthalmos. CHF standing goiter Systolic hypertension. Resolves within eight months. moist. which makes diagnosis more difficult (TSH) ovarii)  Thyroid storm is a rare presentation. and rarely thyroid acropachy o Hydatiform mole o "Hamburger" thyrotoxicosis Clinical manifestation (depend on age. Follows viral infection. Dehydration. Postpartum can occur in 5-10% cases in the first 3-6 months. Medication tongue Emotional lability  Amiodarone Induced Thyroiditis Hyperactive tendon reflexes Anxiety  Thyroid Hormone Induced: Decreased o Factitious hyperthyroidism in accidental or intentional concentration ingestion to lose weight . Gynecomastia  Lymphatic and postpartum: Transient inflammation. Exposure to Hyperactivity Tremors-outstretched hand and radiographic contrast media. Severe tachycardia. AF.warm handshake  Thyroiditis Excessive perspiration. tumor cancer Characteristics: Delirium. Ovarian tumor that produces thyriod hormone (struma ovarii). soft and smooth  Toxic adenoma → More common in young patients pulse pressure skin. Onycholysis over activity)  Subacute: Abrupt onset due to leakage of hormones. Fever. hands – format's sign Diarrhea. wide Warm. typically occurs in >40y old with long arrhythmia. gonadotropin (hCG) o Thyrotoxicosis factitia dermopathy (especially pretibial myxedema). Diarrhea Autonomous overproduction of thyroid hormone Common symptoms: (independent of TSH) o Toxic adenoma (TSH receptor mutant) Nervousness Anxiety Increased perspiration o Toxic multinodular goiter Heat Tremor Hyperactivity o Follicular cancer (rare) intolerance Jod-Basedow effect (excess iodine-induced Palpitations Weight loss Reduction in menstrual hyperthyroidism) despite increased flow or oligo- appetite menorrhea Etiology  Grave’s disease → Autoimmune disease caused by antibodies to TSH receptors Common sign:  Toxic multi-nodular goiter (5%) → 10x more common in Hyperactivity. Vomiting. Transient hypothyroidism occurs before resolution Nervous & psychiatric: Psychiatric Neuromascular  Treatment Induced Hyperthyroidism  Iodine Induced: Excess iodine indirect. amount of hormone) o Choriocarcinoma o Ectopic production by:  Older patient presents with lack of clinical signs and o Thyroid-stimulating hormone o Ovarian teratoma (struma symptoms. Lid lag and stare (sympathetic palmar erythema.

tremor. weakness. ophthalmopathy)  Enlargement of nodule  Free T4. keratitis and corneal ulceration Cardiac: Skin: ↑CO (cardiac output) Sinus tachycardia  Warm moist smooth skin Atrial fibrillation: 10-20%. T3. more High output – heart failure  Onycholysis common elderly output  fine hair. Insomnia  Frequent blinking  Graves ophthalmopathy: Proptosis. widened LV hypertrophy & pulse pressure cardiomyopathy  excessive perspiration Mitral valve problem  Graves’ skin change (rare): orange-peel thickening of the pretibial areas Muskuloskeletal system: Graves’ disease  Atopic & weak Enlargement of the thyroid gland  Myesthenia gravis (especially in Grave’s disease) Infiltrative ophthalmopathy  Hypokalemic periodic paralysis Dermopathy  Thyroid acropathy (clubbing of nails) Acropachy  Bone resorption exceeds bone formation → hypercalciuria & sometime hypercalcemia Diagnosis  Osteopenia (long-standing hyperthyroidism)  Thyroid function test (establish hyperthyroidism & the cause)  ↑ (Serum T4 & free T4 concentration) GI:  ↑ (Serum T3 and free T3 concentration)  ↑food intake & unstable appetite  Serum TSH → A normal or elevated TSH in a hyperthyroid  Hyperphagia (weight gain younger patient) patient indicates TSH-induced hyperthyroidism  Anorexia-weght loss elderly  Etiological test  Weight loss is common  TSI (Grave’s disease marker)  Hyoerdefication or diarrhea because of GI hypermotility  Antiperoxidase antibody in Hasimoto’s thyroiditis → common cause oh HYPO thyroidism  Abnormal liver function test Reproductive:  Radioactive iodine uptake scan  Oligoenorrhea & amenorrhea Differential diagnosis  Gynecomastia occurs in men 1) Grave’s disease Thyroid gland:  Typical sign of thyrotoxicosis & autoimmune-mediated manifestation (e. lid retraction (prevent complete closure of the eyes). and weight loss . tachycardia.g. hair loss Systolic hypertension. & TSH test: In all patient T3↑ & most such Eye: patient ↑Free T4 levels  Increased sympathetic tone & include a widened distance 2) Anxiety state between the upper and lower lid  Lid lag on upward gaze  Irritability.

 There is no thyroid tenderness.(solution of PO potassium iodide )  Inhibit the biosynthesis of thyroid hormones : . or emergency surgery. considerations Propylthiouracil (PTU) (MMI)  Compilcation: Hypothyroidism. Usually a small firm goiter is  Should stop antithyroid administration before starting therapy present. followed by a transition to a hypothyroid phase of several weeks  Contraindication: asthma & congestive heart failure and then recovery. not candidates for Antithyroid drug therapy antithyroid drugs and refuse radioactive iodine  Euthyroid must be achieved before surgery: using antithyroid Methimazole drugs Imp. hypoparathyroidism. ↑Neutropenia Nausea Vomiting and/or diarrhea Neutropenia Treatment: 20 to 40 mg/ OD Dosage 100 to 150mg qid PO  Inhibit the release of hormone from the hyperthyroidism (thyroidectomy during the second trimester).  Thyroid hormone → normal For severe Notes thyrotoxicosis Supportive therapy (ß-Adrenergic blocking agents) 3) Subacute tyroiditis  Rrelief symptoms (tachcardiam tremor. such as gastroenteritis or pneumonia. Surgical (Subtotal thyroidectomy)  Low thyroid uptake of 121I  Indication: large obstructing glands. wound Efficacy Very potent Potent infections. Iodination. the thyroid uptake of radioiodine is very low. Adverse reactions Rashes. pregnant women with severe Antithyroid drugs – radioactive iodine . but the thyroid may not be enlarged or may be up to three times the normal size.  for older patients with moderate hyperthyroidism and thyroid  Low thyroid uptake of 121I enlargement 4) Lymphotic thyroiditis  for patients with a prior allergic or toxic reaction to the antithyroid medication  This disorder is responsible for a small percentage of new cases currently. Antithyroid antibodies are usually negative. resulting In pregnancy Contraindicated Safely can be given from long-neglected severe hyperthyroidism to which there is added a complicating intercurrent illness. recurrent laryngeal nerve paralysis. anxiety. A  Small inhibitory effect T4 to T3 hyperthyroid phase lasts for several weeks. and keloids. 50% of Grave’s ophthalmology can develop or worsen Long acting Duration of action Short acting QID/TID Thyroid strom BID/OD Dangerous condition of decompensated thyrotoxicosis. Coupling Coupling Clinical: Tachycardia Fever Conversion of T4 to T3 No action Inhibits conversion Agitation Restlessness or psychosis Rashes. & heat intolerance  ↑sedimentation rate. hemorrhage. toxic reactions to antithyroid drugs. glands containing Treatment (Decreasing thyroid hormone formation & secretion) nodules that are identified as malignant or equivocal on fine- needle aspiration. Radioactive iodine  Thyroid tenderness is the hallmark of the disorder. Mechanism of action Iodination.

life style  Symptomatic and supportive treatment: 2) Insulin resistance & B cell function defection  Fluid replacement (IV fluids) 3) Glucotoxicity & lipotoxicity  O2  Temperature control (acitaminopen. acanthosis nigricans  Sodium Iodine 1g IV in 24h  Inhibit the sympathetic blockade: Propranolol in large oral Risk factors doses (20-40mg q4-6h / 1mg IV slowly)  Antagonism to stress: hydrocortisone (50-100mg IV q6h) 1) Genetic & Environemtntal factor → aging.  Antithyroid drugs in large doses (600 mg propylthiouracil  Uncommon immune-mediated diabetes → insulin or 60 mg methimazole stat and half this dose q6h) autoimmune syndrome.  Lethargy  Abdominal pain Complication: involvine eyes (blindness). ketoacidosis Systemic: weight loss Eyes: blurred vision Classification: 1) Type 1 DM: Breath: smell of acetone Respiratory: Kussmaul breathing (hyperventilation)  Immune-mediated type 1 DM  Idiopathic Type 1 DM Urinary: Polyuria.  Stupor nerves (stroke). myocardial infarction). surgery. cytomegalovirus Type 1 Type 2  Other inherited disease → syndrome Age of onset Young Adult . trauma. cooling blankets) 4) Clinical DM  Anti-infection Main symptom & sign CNS: Gastric: Diabetes  Polydipsia  Nausea Definition: is a syndrome with disordered metabolism and inappropriate hyperglycemia due to either a deficiency of insulin  Polyphagia  Vomiting secretion or insulin resistance & inadequate insulin secretion to compensate. an absolute deficiency of insulin 4) Other specific types: → accumulation os circulation glucose & fatty acids → hyperketonemia  Hereditary defect of B cell function → associated with mutation of mitochondrial DNA  Latent autoimmune diabetes in adult (LADA) occurs in non- obese people with absolute deficiency of insulin & insulin  Heriditary defect of insulin action → lipoatrophia DM autoimmune antibody (+)  Endocrine disease → Cushing’s syndrome. obesity. hyperthyroidism Type 2:  Disease of pancreas → pancreatitis. thyroid hormones. Glycosuria 2) Type 2 DM → genetic and environmental factors Type 1: 3) Gestational DM  Common in thin & young. kidney (renal failure). cancer  Tend to occur in overweight & elderly  Diabetes due to drug → glucocorticoid.  Asymptomatic → detect by its complication or thiazide diuretic routine health exam  Infection → congenital rubella . diet. blood vessels (gangrene.

0mmol/L. drink it over in 5 minutes and measure the plasma  Third period: microalbuminuria period persistent glucose level after 2 hours-normal range is 5.9-  First period: enlarge kidneys.1mmol/L . hemorrhage. postprandial <7. and kidney function decline is 3-6%  Fifth period: uremic period. Ketosis prone Frequently Rare urinary retention and sexual dysfunction Complication A. type2-20%)  Occlusive vascular disease involves both microangiopathy and atherosclerosis of large and medium-sized arteries  Pathological: Diffuse glomerular sclerosis (70%). TB & membrane & endothelial proliferation) moniliasis are also common 1) Diabetic retinopathy (microaneurysms. C.  Single nerve paralysis (commonly involve femoral & cranial nerve) → vascular ischemia or traumatic Weight Lean Obese damage Onset More abrupt May be very insidious Symptom Characteristic Asymptomatic features  Autonomic neuropathy Insulin Absolute deficiency Relative/resistence  Symptoms: anhidrosis of the lower limbs or Treatment Insulin Oral drug hyperhidrosis of the upper half of the body. Acute complication  Large vessel disease: Atherosclerosis → coronary heart  Diabetic ketoacidosis disease.8mmol) normoalbuminuria. hyperfiltration. Normal range hypertension. orthostatic hypotension. Proliferative retinopathy (newly formed vessels. blindness). nodular glomerular sclerosis Lab findings  Manifestation: Proteinuria.7mmol/L) ( UAE 20-200ug/min)  Glycosylated hemoglobin (HbA1C): reflect the state of  Fourth period: increasted microalbuminuria (UAE > glycemia over the preceding 8-12 weeks.9 mmol/L <7.0mmol/L ≥11. Declines kidney function  Glucosuria  Staging:  Plasma glucose: Fasting plasma glucose level (Normal: 3. diarrhoea.  Diabetic foot is syndrome which includes ischemia.  Oral glucose tolerance test (OGTT): if plasma glucose is less  Second period: thickening of glomerular basement than diagnostic value (75g oral glucose put into 250-300ml membrane. glaucoma. peripheral Diabetic cataracts. neuropathy. and secondary infection 2) Diabetic nephropathy: (Type 1-40%. vitreous hemorrhage scaring retinal detachment.  Hyperglycemic hyperosmolar status  Small vessel disease: Diabetic microangiopathy (associated with homogeneous thickening of vascular basement  Infection: Urinary tract & skin infection are common. and provide an 200ug/min). patients may be present with edema.1mmol/L <7. hypertension. constipation. & stroke.8~11.1~ 6. creatinine & urea nitrogen accumulate in the blood Diagnosis 3) Diabetic neuropathy Subject PPG FPG  Paripheral neuropathy: Normal < 6. burning.6-7. 6. microalbuminuria period intermittent water.Chronic complication B. lightning pain (worse at night) IGT < 7.8mmol/L (common) + numbness. Diabetic foot exudates).0mmol/L Diabetes ≥7.8mmol/L  Symmetrical sensory loss in the distal lower limbs IFG 6.0mmol/L 7. improved method of assessing diabetic control.

neutral protamine hagedorn. can induce hypoglycemia in type 1  Thiazolidinediones 3)Oral drugs o Mechanism not clear Oral drugs o Indication: type 2 with insulin resistance Sulfonylureas o Adverse reaction: Edema Meglitinide analogs o Contraindication: Heart failure. During the course of o Pregnancy surgery. Acute complication o Adverse reaction: Lactic acidosis. Rosiglitazone Thiazolidinediones Alpha-glucosidase inhibitors 4) Insulin therapy  Indication:  Sulfonylureas o Type 1 DM o Stmulate insulin secretion . Hepatic or renal impairment o Pancreatic excision o Adverse reaction: Hypoglycemia. Glimeperide response (pruritus . Glipizide. o Type 2 diabetic patients whose hyperglycemia does not Leukopenia . Skin rashes. Gestational DM. Lactic acidosis o Indication: nonobese type 2 that can’t control glucose o With infection.  Adverse reaction: Hypoglycemia. Type 2 DM with severe complication. insulin aspart o ↓ blood glucose by diminished hepatic gluconeogenesis (2) long-acting: insulin glargin .by bind with receptor in o Diabetic ketoacidosis . exercise. o Indication: obese type 2 (either alone or in conjunction with sulfonylureas) o Contraindication: Hepatic or renal impairment. hepatic/renal impairment Biguanides o Classic drugs: Pioglitazone. hyperglycemia hyperosmolar Bcell status . thrombopenia. Hypersensitive Gliquidone. Nausea . skin rashes)  Meglitinide analogs  Classic drugs: regular insulin. Pregnancy. vomiting o Classic drugs: Metformin Treatment  Alpha-glucosidase inhibitors 1) Diet o Inhibit digest dietary starch & sucrose Breakfast Lunch Dinner Bedtime o Indication: type 2 with postprandial hyperglycemia 3 meals 20% 40% 28% Calories o Containdication: GI diseases. & without complication o Trauma or surgery o Contraindication: Type 1 DM. vomiting respond to diet therapy combined with oral drugs o Classic drugs: Glyburide. severe chronic complication level by diet. pregnancy 4 meals 28% 28% 28% 16% o Adverse reaction: Abdominal distention. Pancreatic excision. o Stmulate insulin secretion with less hypoglycemia protamine zinc insulin complication than sulfonlyureas  Insulin analogue:  Biguanides (1) rapid-acting: insulin lispro. Gliclazide. diarrhea o Classic drugs: Acarbose 2) Exercise: for type 2. Nausea. Edema.

myocardial infarction. plasma glucose. Diabetic ketoacidosis bicarbonate.9% saline is infused at rate of 300-500ml/h with careful monitoring serum potasium .9% saline solution should be started in emergency after disease esteblisment  Serum potassium is normal or high despite total body potassium depletion resulting from polyuria or vomiting  First hour: at least 1L of 0. Emergancy measures: insulin hormone increases. serum nitrogen.35  Fluid replacement  Serum bicarbonate<18mmol/L  Most patient loss 4-5L of fluid  Urine positive for ketones  0. & electrolytes per 2h  Abdominal pain & tenderness (present in the absence of  When plasma glucose falls to 13.1 unit/kg/h). gestation  Fluid intake & output should be recorded Symptom n sign:  Patient should not receive sedative or narcotics  Polyuria  Insulin replacement  Polydipsia associated with marked fatigue  Only use regular insulin  Should be given immediately after the diagnosis is establish  Nausea & vomiting  Continuous low-dose insulin infuse (0. acetone. consider:  Urine ketons measurement for patients with signs of infection or blood glucose is high  The insulin or oral drug of night is not enough  Dawn phenomenon: blood glucose in night is normal. trauma.9mmol/L be given in hypo  Acidosis with blood PH<7.Treatment principle  Serum creatinine and urea nitrogen may be mild high  Should start from minimum dosage & slowly raise according  Leukocytosis may occur with or without associated infection to the level of plasma glucose Treatment  Combination drugs insulin/sulfonylureas & meglitinide analogs + biguanides/alpha-glucosidase Prevention: inhibitor/thiozolidinediones → not only can increase to treat hyperglycemia but also may increase risk of hypoglycemia  Education of early symptom & sign  If fasting plasma glucose always high. if  Mental stupor that can progress to coma plasma glucose level fails to fall (at least 10%) in first hour → required doubling dose  Rapid deep breathing & fruity breath odor of acetone  Measure plasma glucose. and secondary hyperglycemia (monitoring blood glucose help  Vital sign to detect the cause of morning hyperglycemia)  Lab exam: Urine ketones. give 5% abdominal disease) glucose while insulin therapy still continue (to clear ketonemia) Lab finding:  When urine ketones has been cleared. arterial pH. electrolytes & serum osmolality General consideration:  Avoid urinary catheter & gastric intubation in needed in  The initial manifestation of type 1 diabetes comatose patient when diabetic present due to high risk of bladder infection  During the course of infection . or surgery.9mmol/L or less. serum urea  Dehydration & hypotension nitrogen. bicarbonate. regular insulin should  Hyperglycemia >13.  Therapeutic flow sheet  Somogyi phenomenon: there is hypoglycemia in night. but hyperglycemia appears in dawn (subuh) because of the anti.

trauma Symptom Nausea. cholecystitis & pyelonephritis): antibiotic  Cardiac failure (in aged with coronary heart disease): Diuretics & digitalis glycosides  Renal failure (serious prognostic sign): prevention is important  Cerebral edema (rare): maintain blood glucose between 11.3mmol/L Serum natrium Normal or low High PH.1~16. polydipsia. bicarbonate low Normal or low Serum Normal or mild high >320mosm/L osmolality . It should be deferred when serum potassium fail to response (remain above 5mmol/L) in order to avoid renal insufficiency  Treatment of complication  Infection (e. Mental confusion. diabetes Agedm undiagnosed diabetes Cause infection Stroke. Dehydration (5-8L). mental stupor coma.  Electrolyte replacement Sodium bicarbonate: used when blood pH <7. hypotension palsy (paralysis) Ketonuria (+) to (+++) (-) to (+) Glycemia >13.7mmol/L for initial 24h after correction of severe hyperglycemia to reduce risk DKA HHS History Young. infection. hallucination Sign Dehydration (4-5L).9mmo/L >33.1 bicarbonate treatment should be stopped (to avoid cerebral edema) Potassium replacement: (30-30mmol/h) for 2-3h after start treatment or sooner when serum potassium is low.7mmol/L.g.1 or blood bicarbonate < 6. when pH reach 7. tic.