ENDOCRINOLOGY

SIGNS AND SYMPTOMS

 Uncontrolled DM  Addison’s Disease  DD:  Cancer (about 30%)  Gastrointestinal disorders (about 15%) and  Dementia or depression (about 15%) 2

        Addison’s Disease Chloasma – ‘Mask of Pregnancy’ Acanthosis nigricans Hemochromatosis- ‘bronze’ diabetes Thiamine/ Niacin deficiency Vitiligo- Addison’s, B12 deficiency Dialysis patients, sprue, HIV Drugs 3

Pigmentation Picture Gallery

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Acanthosis Nigricans

This healthy 16 year old adolescent developed acanthosis nigricans after gaining over 30 pounds during the preceding year

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Drugs causing pigmentation

 amiodarone, arsenic, bleomycin, busulfan, clofazimine, hydroxychloroquine, chlorpromazine, doxorubicin (nail beds), imipramine, methimazole, minocycline, niacin, primaquine, propylthiouracil, topical tretinoin, and zidovudine 7

    Pubertal gynecomastia is common (teenagers who are very tall or overweight) Athletes abusing androgens Klinefelter's syndrome (47,XXY) 8

    

Klinefelter’s Syndrome

Male hypogonadism and infertility Enlarged breasts, sparse facial and body hair, small testes, and inability to produce sperm and psychosocial problems (anxiety, depression, neurosis, and psychosis) 1 in 500-1,000 males is born with an extra sex chromosome; over 3,000 affected males are born yearly. The prevalence is 5-20 times higher in the mentally retarded than in the general newborn population. MVP/ Tall stature/ eunochoid appearance 9

       

Gynecomastia Labworkup

Plasma Prolactin levels increased β HCG levels decreased Low plasma testosterone levels TREATMENT: Pubertal variety resolves within 1-2 years Drug induced –(Spironolactone) stop it Persistent GM treat with SERM drug: Raloxifene (Evista®) ? Liposuction 10

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Muscle Cramps & Tetany

Night cramps Diabetes mellitus Parkinson's disease Central nervous system or spinal cord lesions Peripheral neuropathy Hemodialysis Peripheral vascular disease, and Cisplatin or vincristine 11



A common cause for muscle pain, though not usually with cramping, is

3-hydroxy-3-methylglutaryl coenzyme A

CoA) reductase inhibitor (statin)

therapy for hyperlipidemia

(HMG-

12



Diffuse, recurrent, or severe muscle cramping requires evaluation for hypocalcemia/ Hypomagnesemia

13

     

Mental Changes- Evaluate:

Post partum (15%)/ Premenstrual Anxiety and extreme irritability – Hyperthyroid Cretin-mental slowness-depression-lethargy: Hypothyrodism (‘Myxedema madness’) Hypoglycemic states Altered steroid status B1, B2, B3, B6, B12 deficiencies 14

PITUITARY DISORDERS

WSO 411

Endocrine Control: ‘Negative feedback’

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ANATOMY

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PITUITARY TUMOR

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NORMAL Vs. ABNORMAL

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Relationship Among Hypothalamic, Pituitary, Target Glands, and Feedback Hormones Hypothalamic Regulatory Hormone Pituitary Hormone Target Gland Feedback Hormone TRH TSH Thyroid gland T 4 , T 3 LH-RH LH-RH LH FSH Gonad Gonad E 2 , T Inhibin, E 2 , T GH-RH, SMS GH Multi-organs IGF-1 PIF Prolactin Breast ?

CRH, ADH ACTH Adrenal Cortisol ACTH = Adrenocorticotropin hormone; ADH = Antidiuretic hormone; CRH = Corticotropin releasing hormone; E2 = Estradiol; FSH = Follicle-stimulating hormone; GH = Growth hormone; GH-RH = Growth hormone-releasing hormone; IGF = Insulin-like growth factor; LH = Luteinizing hormone; LH-RH = Luteinizing hormone-releasing hormone; PIF = Prolactin release-inhibitory factor; SMS = Somatostatin; T = Testosterone; T 4 = Thyroxine; TRH = Thyrotropin-releasing hormone; TSH = thyroid stimulating hormone

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Pituitary Control

 Only the secretion of prolactin is increased in the absence of hypothalamic influence  It is mainly under tonic suppression through the prolactin inhibitory factor  All anterior pituitary hormones are secreted in a pulsatile fashion and tend to follow a diurnal pattern 21

PITUITARY TUMORS

Prevalence of Pituitary Adenoma Adenoma Type Prevalence (%)

 

Adenomas ; Prevalence 20 cases per 100,000 Incidence of 0.5 to 7.4 per 100,000 population GH cell adenoma PRL cell adenoma GH and PRL cell adenoma ACTH cell adenoma Gonadotroph cell adenoma Nonfunctioning adenoma TSH cell adenoma 15 30 7 10 10 25 1 Unclassified adenoma 2 ACTH=Adrenocorticotropic hormone; GH=Growth hormone; PRL=Prolactin; TSH=Thyroid-stimulating hormone

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Clinical Manifestations of Pituitary Tumors Secondary to Mass Effect

•Headache •Chiasmal syndrome

temperature

•Diabetes insipidus

(SIADH) : visual field defects

•Hypothalamic syndrome:

Disturbances of thirst, appetite, satiety, sleep, and

•Syndrome of inappropriate ADH secretion •Obstructive hydrocephalus •Cranial nerves III, IV, V

1 , V 2 , and VI dysfunction

•Frontal and temporal lobe syndromes •Cerebrospinal fluid rhinorrhea 23

Hyperprolactinemia

 Women: Menstrual cycle disturbances (oligomenorrhea, amenorrhea); galactorrhea; infertility.  Men: Hypogonadism; decreased libido and erectile dysfunction; infertility.  Elevated serum PRL.  CT scan or MRI often demonstrates pituitary adenoma. 24

Hypopituitarism:

 Growth Hormone Deficiency :  Decreased muscle strength and exercise tolerance and  A reduced sense of well-being (eg, diminished libido, social isolation)  Increased body fat 25

Hypopituitarism:

 Gonadotropin Deficiency :  Infertility and oligomenorrhea or amenorrhea  Lack of libido, hot flashes, and dyspareunia 26

Hypopituitarism:

 Adrenocorticotropic Hormone Deficiency :  Chronic malaise, fatigue, anorexia, and hypoglycemia.  Severe hypotension, hyperkalemia, and hyperpigmentation  May lead to hyponatremia 27

Hypopituitarism:

 Thyrotropin (TSH) Deficiency :  Malaise, leg cramps, fatigue, dry skin, and cold intolerance. 28

Pituitary Excess Hormone Secretion:

 Prolactinoma: oligomenorrhea, amenorrhea, galactorrhea, or infertility  Men: impotence and decreased libido 29

ACROMEGALY

Clinical Features in Patients with Acromegaly

• • • • • • • •

Acral enlargement Arthralgias, neuropathic joints Carpal tunnel syndrome Coarsening of facial features Excessive sweating Goiter Hypertension, congestive heart failure Impaired glucose tolerance, diabetes mellitus

• • • • • • • •

Macroglossia Malocclusion and tooth gaps Pituitary mass effect including headache and visual field defects Pituitary insufficiency (partial or complete) Sensory and motor peripheral neuropathy Snoring, sleep apnea Symptoms associated with hyperprolactinemia Thick and course skin, skin tags

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Cushing's Disease

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DIAGNOSIS

 Usually a delay in diagnosis  Pituitary MRI is the preferred diagnostic imaging technique in patients with visual loss or hypopituitarism suggestive of a pituitary tumor  HORMONE ASSAYS 33

THERAPY

      Reduction or complete removal of tumor Elimination of mass effect if present Normalization of hormone hypersecretion, and Restoration of normal pituitary function Medical, surgical, and radiation therapy Availability of a good neurosurgeon 34

THERAPY

 For Prolactinoma: tumor shrinkage by medical therapy with Bromocriptine (Parlodel®), and cabergoline (Dostinex®)  Radiosurgery (gamma knife) 35

THYROID DISORDERS

TSH and FT4

 TSH levels : 0.4–5.5 mU/L.  FT4 is a direct measurement of the serum concentration of free (unbound) T4 37

THYROID ‘GOITER’

     Single or multiple thyroid nodules are commonly found with careful thyroid examinations. Thyroid function tests mandatory. Thyroid biopsy for single or dominant nodules or for a history of prior head–neck or chest–shoulder radiation. Ultrasound examination useful for biopsy and follow-up. Clinical follow-up required. 38

‘GOITER’

 4%  Presence of iodine deficiency  Graves’ and Hashimoto’s may have goiter  ?cancer- if prior radiation/ FH of Thyroid cancer/ personal cancer/ presence of lymphnodes and non mobile thyroid nodule is felt.

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Other Tests for nodules

 FNAC  US- irregular margins/ microcalcifications  RAI ( 123 I / 131 I) scans for ‘hot’ vs ‘cold’ nodules 41

Thyroid Cancer

 Painless swelling in region of thyroid.  Thyroid function tests usually normal.  Past history of irradiation to head and neck region may be present.  Positive thyroid needle aspiration. 42

Thyroid Cancer

 F:M 3:1  1/250  Papillary type most common  Solitary nodule  Past exposure of head and neck to radiation  Chernobyl: Age 5 at exposure; 6-7 yrs later had cancer  Spreads to lung 43

Thyroid Cancer Prognosis

 <45-TNM: T1 N1 M0- 98% 10 yr survival  <45-T1 N1 M1 – 5 yr 99% 85% 10 yr >45- T1 N0 M0  >45 T1+ N0 M0- 95% 5 yr 70%10yr  >45 T+ N+ M+- 80% 5 yr 61% 10 yr 44

Hypothyroidism & Myxedema

 Weakness, fatigue, cold intolerance, constipation, weight change, depression, menorrhagia, hoarseness.  Dry skin, bradycardia, delayed return of deep tendon reflexes.  Anemia, hyponatremia.  T4 and RAI uptake usually low.  TSH elevated in primary hypothyroidism. 45

 May affect almost all body functions  Interstitial accumulation of hydrophilic mucopolysaccharides leads to fluid retention (lymphedema)  Hashimoto’s; Drugs- lithium, amiodarone, foods- turnips, cassavas  Chronic HCV patients treated with interferon 46

     TSH increased High cholesterol Thyroid antibodies- Hashimotos Differential Diagnosis: unexplained menstrual disorders, myalgias, constipation, weight change, hyperlipidemia, ascites, heart failure and anemia. 47

Complications

 Cardiac- CAD, CHF  Infection risk  Madness  Infertility/ miscarriage  Coma (rare) 48

Treatment

 Levothyroxine* 50-100 mcg/day  (max 1.6 mcg/kg/day)  Slowly increase the dose every  1-3 weeks (75–250 mcg oral) *Estre™ | Levo-T® | Levothroid® | Levoxyl® | Synthroid® | Thyro-Tabs® | Unithroid® 49

Hyperthyroidism (Thyrotoxicosis)

    Sweating, weight loss or gain, anxiety, loose stools, heat intolerance, irritability, fatigue, weakness, menstrual irregularity. Tachycardia; warm, moist skin; stare; tremor. In Graves' disease: goiter (often with bruit); ophthalmopathy.

Suppressed TSH in primary hyperthyroidism; increased T4, FT4, T3, FT3.

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Graves' Disease

        Autoimmune, Familial F:M 8:1, Age: 20-40 Exophthalmos Pernicious anemia Myasthenia gravis Risk of Addison’s, Celiac, DM T1, 51

Thyrotoxicosis Factitia

 Eating ground beef containing bovine thyroid gland 52

 Nervousness, restlessness, heat intolerance, increased sweating, fatigue, weakness, muscle cramps, frequent bowel movements, or weight change (usually loss), palpitations or angina pectoris, menstrual irregularities.

 Hypokalemic periodic paralysis (15%) Asians/ Native Americans 53

   stare and lid lag, fine resting finger tremors, moist warm skin, hyperreflexia, fine hair, and onycholysis CVS:forceful heart beat, premature atrial contractions, and sinus tachycardia. Atrial fibrillation or atrial tachycardia occurs in about 8% (older men) 54

Ophthalmopathy

      20-40% Chemosis Conjunctivitis Proptosis Exophthalmos Maximum normal eye protrusion: 22 mm for blacks, 20 mm for whites, and 18 mm for Asians. 55

CT Scan

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Pretibial Myxedema

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  THERAPY: choice of methods  ?Drugs- Symptomatic  Propranolol Inderal® | Inderal® LA | InnoPran XL™ | Pronol™ Effectively relieves the tachycardia, tremor, diaphoresis, and anxiety 58

Thiourea drugs

 Methimazole Tapazole®  Propylthiouracil, PTU  For mild thyrotoxicosis, small goiters, or fear of isotopes  Usually continued for 12–24 months before being discontinued (50% relapse)  Side Effects: BMD- 0.3-0.4%; pruritus, allergic dermatitis, nausea, and dyspepsia 59

Radioactive iodine (

131

I)

 Safe; Should not be given to pregnant women  Thyroid surgery performed les frequently 60

Hashimoto’s Thyroiditis

 Swelling of thyroid gland, sometimes causing pressure symptoms in acute and subacute forms; painless enlargement and rubbery firmness in chronic form.  Thyroid function tests variable.  Serum antithyroperoxidase and antithyroglobulin antibody levels usually elevated in Hashimoto's thyroiditis. 61

Hashimoto’s

 Autoimmune condition and the most common thyroid disorder in the USA  Familial; F:M 6:1  Dietary iodine supplementation.  Certain drugs (amiodarone, interferon, interleukin-2, G-CSF) frequently induce thyroid autoantibodies 

Smokers> Non smokers

(thiocyanates in cigarettes is antithyroid) 62

Hypo parathyroidism

HYPOCALCEMIA

    Tetany, carpopedal spasms, tingling of lips and hands, muscle and abdominal cramps, psychological changes. Positive Chvostek's sign and Trousseau's phenomenon; defective nails and teeth; cataracts. Serum calcium low; serum phosphate high; alkaline phosphatase normal; urine calcium excretion reduced. Serum magnesium may be low.

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HYPOPARATHYROIDISM: Chronic disease

 lethargy,  personality changes,  anxiety state,  blurring of vision due to cataracts,  parkinsonism, and  mental retardation. 65

Chvostek's sign:

 facial muscle contraction on tapping the facial nerve in front of the ear 

Trousseau's phenomenon:

 carpal spasm after application of a cuff 66

CARPOPEDAL SPASM

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Laboratory Findings

 Serum calcium is low,  serum phosphate high,  urinary calcium low, and  alkaline phosphatase normal.  PTH levels are low.

 ? Serum magnesium 68

HYPOCALCEMIA DUE TO DRUGS

 Loop diuretics:Ethacrynic Acid Edecrin® / Furosemide Delone™ | Furocot™ | Furosemide | Lasix®  Phenytoin Di-Phen™ | Dilantin®  Alendronate Fosamax®  Foscarnet Foscavir® 69

Treatment for tetany

 Intravenous calcium gluconate  Calcium gluconate, 10–20 mL of 10% solution intravenously 70

THERAPY

       Oral calcium Calcium salts: 1–2 g of calcium daily.

Liquid calcium carbonate (Titralac Plus), 500 mg/5 mL, may be especially useful. The dosage is 1–3 g calcium daily. Calcium citrate contains 21% calcium, but a higher proportion is absorbed with less gastrointestinal intolerance.

Active metabolite of vitamin D: 1,25-dihydroxycholecalciferol (calcitriol), Calcifediol: Calderol® (D3) rapid onset of action Ergocalciferol:(D2)Calciferol® | Deltalin™ | Drisdol® | Ergo D™ | Vitamin D for chronic cases –slow acting 71

    

Hyperparathyroidism

Frequently asymptomatic, detected by screening. Renal stones, polyuria, hypertension, constipation, fatigue, mental changes. Bone pain; rarely, cystic lesions and pathologic fractures. Serum and urine calcium elevated; urine phosphate high with low to normal serum phosphate; alkaline phosphatase normal to elevated. Elevated PTH. 72



"bones, stones, abdominal groans, psychic moans, with fatigue overtones."

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Signs of Hypercalcemia

 thirst,  anorexia,  nausea, and vomiting  Constipation,  fatigue, anemia, weight loss, and hypertension  Pancreatitis occurs in 3%. 74

 0.1% incidence  >50 F:M 3:1  Due to adenoma of parathyroid gland  5% of renal stones due to this condition 75

X-Rays

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Reduction of plasma phosphate with aluminum hydroxide gel / Aloh-Gel® | Alternagel® | Alu-Cap® |

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Complications

   Pathologic fractures Renal failure and uremia Peptic ulcer and pancreatitis 78

Other causes for High Calcium

 Calcium or Vitamin D Ingestion  Cancer: breast, lung, pancreas, uterus, hypernephroma  Sarcoidosis  Multiple myeloma  Thiazides/Lithium 79

 Bisphosphnates  Raloxifene 80

OSTEOPOROSIS

FACTS AND FEATURES

DEFINITION

 A metabolic bone disease  Low bone mass and microarchitectural deterioration of bone tissue  Leads to enhanced bone fragility and increased fracture risk 82

Osteoporosis types

    

Primary osteoporosis: bone mass loss 1 Unassociated with any other chronic illness 2 Related to aging and loss of the function in females and 3 The aging process in males. gonadal Secondary osteoporosis: results from 1 a variety of chronic conditions leads to bone mineral loss 2 effects of medications and nutritional deficiencies

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Causes of Secondary Osteoporosis : Chronic Diseases        Cushing syndrome Anorexia nervosa Hyperthyroidism Hyperparathyroidism Hypophosphatasia Marfan syndrome Osteogenesis imperfecta       Chronic renal insufficiency Chronic liver disease Hemochromatosis Hyperprolactinemia Multiple myeloma Disseminated carcinomatosis 84

Causes of Secondary Osteoporosis: Medications

         Steroids Excess thyroid hormones GnRH agonists Cyclosporine Methotrexate Phenobarbital Phenytoin Phenothiazines Heparin 85

Conditions Causing Nutritional Deficiencies

 Malabsorption syndromes  Vitamin D deficiency  Calcium deficiency  Gastric and bowel resections  Alcoholism 86

Other Causes



Athletic amenorrhea



Tobacco use



Pregnancy



Carbonated ‘fizzy’drinks

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WHO definition

   Bone density (BD) that is 2.5 standard deviation (SD) or more below the young adult mean value (T-score < -2.5) BD between 1 and 2.5 SD below average (T-score = -1 to -2.5) = ‘Osteopenia’ Lead to increased risk for bone fracture 88

Prevalence

       Primarily white women: 54% of postmenopausal –Osteopenia 30% have osteoporosis 1.3 million osteoporotic fractures annually – 50% Vertebral 60+ 25% Hip 70+ 25% Colles’s (wrist) 50+ 89

?Men

 an important health problem  30% of all hip #  20% of all vertebral # 90

Pathophysioloy

 Poor bone mass acquisition during growth in early years  Accelerated bone loss post menopausal  ?Environmental (nutritional, behavioral, and medications)  ?Genetic (40-80%) 91

Nutritional Factors

 Dietary calcium intake, Vitamin D status, protein and calorie intake  Trace elements:  Phosphorus  Vitamins C and K,  Copper, zinc, and manganese 92

Calcium

 Got milk?- during adolescence helps  Low calcium intake in childhood increases later life fractures  Supplementation reduces fractures in elderly 93

?Diet

 Typical U.S. diet is sodium and protein rich, both of which increase urinary calcium excretion, thus increasing dietary calcium requirements 94

?Protein

   malnutrition predisposes to falls and diminishes soft tissue cover.

serum albumin level is the single best predictor of survival body weight history of females with anorexia nervosa predicts osteoporosis risk 95

?Behavior

   physical activity, smoking, and alcohol consumption athletes engaging in strength training increase bone mass Chronic alcohol abuse has been associated with decreased BMD in the femoral neck and lumbar spine and is commonly listed as a risk factor for osteoporosis (28-52%) 96

?Glucocortiocids (aka. Steroids)

 Most important cause  vertebrae, ribs, and ends of the long bones (20 40%)  Estrogen deficiency 97

Risk Factors seen in Osteoporosis

         Non-Modifiable Age Caucasian or Asian race Low body weight Family history of osteoporosis Nulliparity Calcium deficient diet Use of medications      Modifiable – Sedentary lifestyle Smoking Excessive alcohol intake Estrogen-deficient states 98

SIGNS AND SYMPTOMS

 Skeletal fracture- vertebral most common- usually lower thoraic(T8)  or lumbar  Acute pain can get chronic  Multiple fractures on x-ray  Kyphosis (Dowager’s hump) caused by vertebral collapse 99

SIGNS AND SYMPTOMS

   Hip fractures 80+ trivial falls lead to it Colles’ fracture Tests: Urine/Serum Bone Density Measurements: ?US (evaluated)/ DEXA- Spine and hip (measures apparent bone density) or Quantitative CT (QCT) measures true bone density 100

THERAPY

  

US RDA Ca Consensus Development Conference Ca NIH Consensus Development Conference

AT ALL AGES- CALCIUM INTAKE Diet or calcium supplements Vit D 800 IU/day if needed

Children Adolescents Elderly 800 mg/d None provided 800-1200 mg/d 1200 mg/d 1200 mg/d 1200-1500 mg/d Adults 800 mg/d 1000 mg/d 1000 mg/d 800 mg/d 1500 mg/d < 65 on HRT 1000 mg, all others 1500 mg/d

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THERAPY

       Good general nutrition Stop tobacco Limit alcohol intake Exercise helps HRT does not reduce fractures occurrence Raloxifene (Evista®) SERM preserves bone density, decreases total cholesterol Bisphosphonates 102

Generic Name Alendronate Risedronate Etidronate Tiludronate Pamidronate Ibandronate Clodronate Zoledronate Bisphosphonate Medications Trade Name Fosamax Actonel Didronel Skelid Aredia Zometa / Reclast 103

Outcomes

  Raloxifene reduces risk by 0.7% Bisphosphoantes by 41-49% 104

ADRENAL DISORDERS

Adrenal Crisis

    Weakness, abdominal pain, fever, confusion, nausea, vomiting, and diarrhea. Low blood pressure, dehydration; skin pigmentation may be increased. Serum potassium high, sodium low, BUN high. Cosyntropin (ACTH1–24) unable to stimulate a normal increase in serum cortisol. 106

Pattern of plasma ACTH/Cortisol in patients recovering from prior long-term daily treatment with large doses of glucocorticoids 107

Adrenal Isufficiency

 following stress, eg, trauma, surgery, infection, or prolonged fasting in a patient with latent insufficiency  following sudden withdrawal of adrenocortical hormone in a patient with chronic insufficiency  Following pituitary/ adrenal destruction 108

     

Addison's Disease

Weakness, easy fatigability, anorexia, weight loss; nausea and vomiting, diarrhea; abdominal pain, muscle and joint pains; amenorrhea. Sparse axillary hair; increased skin pigmentation, especially of creases, pressure areas, and nipples. Hypotension, small heart. Serum sodium may be low; potassium, calcium, and BUN may be elevated; neutropenia, mild anemia, eosinophilia, and relative lymphocytosis may be present. Plasma cortisol levels are low or fail to rise after administration of corticotrophin. Plasma ACTH level is elevated. 109

Addison’s Images

111

112

Thomas Addison (1793 1860). On the constitutional and local effects of disease of the supra-renal capsules. London, Samuel Highley, 1855.

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Addison’s Disease

114

Causes: Etiology

 Autoimmune destruction (80%)  Tuberculosis  Hemorrhage into adrenals due to meningococcal meningitis (Waterhouse-Friderichsen syndrome)  Fungal adrenal destruction in AIDS/HIV 115

coccidioidomycosis

116

 Vitiligo (10%)  Orthostatic hypotension  Eosinophilia  Low sodium  High potassium  Low plasma cortisol levels 117

Complications

 Susceptible to infections  Leads to crisis precipitation 118

     

THERAPY

Corticosteroid replacement Mineralocorticoid replacement Hydrocrotisone (Cortisone acetate) Prednisone Deltasone® | Predone™ | Sterapred® | Fludrocortisone Florinef® for salt (sodium) retention Prasterone, Dehydroepiandrosterone, DHEA Prestara™ | Vitamist® DHEA-M for Men | Vitamist® DHEA-W for Women 119

 medical alert bracelet or medal reading, "Adrenal insufficiency—takes hydrocortisone."  ?Lorenzo’s oil -Vitiligo 120

Prognosis

 With appropriate treatment have normal life expectancy.

 Risk of infection/surgery/stress 121

Cushing's Syndrome (Hypercortisolism)

    Central obesity, muscle wasting, thin skin, easy bruisability, psychological changes, hirsutism, purple striae. Osteoporosis, hypertension, poor wound healing. Hyperglycemia, glycosuria, leukocytosis, lymphocytopenia, hypokalemia. Elevated serum cortisol and urinary free cortisol. Lack of normal suppression by dexamethasone. 122

Cushing’s

   Syndrome- manifestations of excessive corticosteroids, commonly due to supraphysiologic doses of corticosteroid drugs / rarely over production(15%) Disease- 50% Pituitary tumor related A midnight serum cortisol level > 7.5 mcg/dL is indicative of Cushing's syndrome 123

Cushing’s Disease

124

Cushing’s Disease

125

Adrenal Tumor

126

Cushing’s Syndrome

127

Cushing’s Signs

128

  Hypertension or of diabetes  Compression fractures of the osteoporotic spine and aseptic necrosis of the femoral head  Nephrolithiasis and psychosis  5-year survival of 95% and a 10-year survival of 90% 129

Clinical Use of Corticosteroids

Systemic Activity Topical Activity Prednisone Fluprednisolone Triamcinolone Triamcinolone Dexamethasone Betamethasone Betamethasone Methylprednisolone Fluocinolone Flurandrenolone Fluorometholone Deflazacart 5 5 4–5 8–10 30–120 30 — 5 — — 1–2 3–4 1–2 10 1 40 10 5–10 50–150 5 40–100 20–50 40 — 130

adverse effects

       insomnia personality change weight gain muscle weakness polyuria kidney stones diabetes mellitus     sex hormone suppression occasional amenorrhea candidiasis and opportunistic infections osteoporosis with fractures, or aseptic necrosis of bones 131



Therapy for Osteoporosis

Alendronate Fosamax® 5-10 mg/daily  Risedronate Actonel® 35 mg/ weekly  Ibandronate Boniva® 150 mg/ monthly  Pamidronate Aredia® infusion  Zoledronic Acid Zometa® infusion/ monthly 132