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ENDOCRINOLOGY
SIGNS AND SYMPTOMS
UNINTENDED
LOSS
 The most commonWEIGHT
causes:
 Uncontrolled DM
 Addison’s Disease
 DD:
 Cancer (about 30%)
 Gastrointestinal disorders (about 15%) and
 Dementia or depression (about 15%)
2
Abnormal Skin Pigmentation
 Excessive ACTH secretionAddison’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
4
Acanthosis Nigricans
This healthy 16 year old adolescent
developed acanthosis nigricans after
gaining over 30 pounds during the
preceding year
5
6
Drugs causing pigmentation
 amiodarone, arsenic, bleomycin, busulfan,
clofazimine, hydroxychloroquine,
chlorpromazine, doxorubicin (nail beds),
imipramine, methimazole, minocycline, niacin,
primaquine, propylthiouracil, topical tretinoin,
and zidovudine
7
 ‘Female
appearing male breast’
Gynecomastia
 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


1.
2.
3.
4.
5.
6.
7.
Muscle Cramps & Tetany
Occupational
Night crampsDiabetes mellitus
Parkinson's disease
Central nervous system or spinal cord lesions
Peripheral neuropathy
Hemodialysis
Peripheral vascular disease, and
Cisplatin or vincristine
11
Remember!
A common cause for muscle pain,
though not usually with cramping, is
3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitor (statin)
therapy for hyperlipidemia
12
Diffuse, recurrent, or severe
muscle cramping requires
evaluation for hypocalcemia/
Hypomagnesemia
13
Mental Changes- Evaluate:
 Nervousness, irritability, apathy, and depression – Hypogonadic states/
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’
16
ANATOMY
17
PITUITARY TUMOR
18
NORMAL Vs. ABNORMAL
19
Relationship Among Hypothalamic, Pituitary, Target Glands, and Feedback Hormones
Hypothalamic
Regulatory
Hormone
Pituitary
Hormone
Target
Gland
Feedback
Hormone
TRH
TSH
Thyroid gland
T4, T3
LH-RH
LH
Gonad
E2, T
LH-RH
FSH
Gonad
Inhibin, E2, T
GH-RH, SMS
GH
Multi-organs
IGF-1
PIF
Prolactin
Breast
?
CRH, ADH
ACTH
Adrenal
Cortisol
ACTH = Adrenocorticotropin hormone; ADH = Antidiuretic hormone; CRH = Corticotropinreleasing 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; T4 = Thyroxine; TRH = Thyrotropin-releasing hormone; TSH = thyroidstimulating hormone
20
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
GH cell adenoma
15
PRL cell adenoma
30
GH and PRL cell adenoma
 Adenomas ; Prevalence
20 cases per 100,000
 Incidence of 0.5 to 7.4
per 100,000 population
Prevalence (%)
7
ACTH cell adenoma
10
Gonadotroph cell
adenoma
10
Nonfunctioning adenoma
25
TSH cell adenoma
1
Unclassified adenoma
2
ACTH=Adrenocorticotropic hormone;
GH=Growth hormone; PRL=Prolactin;
TSH=Thyroid-stimulating hormone
22
Clinical Manifestations of
Pituitary Tumors Secondary to Mass Effect
•Headache
•Chiasmal syndrome: visual field defects
•Hypothalamic syndrome:
Disturbances of thirst, appetite, satiety, sleep, and
temperature
•Diabetes insipidus
•Syndrome of inappropriate ADH secretion
(SIADH)
•Obstructive hydrocephalus
•Cranial nerves III, IV, V1, V2, 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
30
31
Cushing's Disease
32
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

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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.
39
40
Other Tests for nodules
 FNAC
 US- irregular margins/ microcalcifications
 RAI (123 I / 131I) 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
Lab
 FT4
low/workup
normal
 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.
50
Graves' Disease
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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

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



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
56
Pretibial Myxedema
57
Complications
 Atrial
fibrillation
 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 (131I)
 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.
64
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
67
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."
73
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
76
Reduction of
plasma
phosphate
with
aluminum
hydroxide gel
/ Aloh-Gel® |
Alternagel® |
Alu-Cap® |
77
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
gonadal
function in females and
 3
The aging process in males.
 Secondary osteoporosis: results from1
a variety of chronic conditions
leads to bone
mineral loss
2
effects of medications and nutritional
deficiencies
83
Causes of Secondary Osteoporosis :
Chronic Diseases

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




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
87
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 (2040%)
 Estrogen deficiency
97
Risk Factors seen in Osteoporosis



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
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


Non-ModifiableAge
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
 AT ALL AGES- CALCIUM INTAKE
 Diet or calcium supplements
 Vit D 800 IU/day if needed
Children
Adolescents
Adults
Elderly
US RDA Ca
800 mg/d
1200 mg/d
800
mg/d
800 mg/d
Consensus
Development
Conference
Ca
None
provided
1200 mg/d
1000
mg/d
1500 mg/d
NIH
Consensus
Development
Conference
800-1200
mg/d
1200-1500
mg/d
1000
mg/d
< 65 on HRT
1000 mg,
all others
1500 mg/d
101
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
Bisphosphonate Medications
Generic Name
Trade Name
Alendronate
Fosamax
Risedronate
Actonel
Etidronate
Didronel
Tiludronate
Skelid
Pamidronate
Aredia
Ibandronate
Clodronate
Zoledronate
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
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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.
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Addison’s Images
111
112
Thomas Addison (17931860). On the
constitutional and local
effects of disease of the
supra-renal capsules.
London, Samuel
Highley, 1855.
113
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
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




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
Complications
 Untreated
causes morbidity and death
 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
4–5
1–2
Fluprednisolone
8–10
10
Triamcinolone
5
1
Triamcinolone
5
40
Dexamethasone
30–120
10
Betamethasone
30
5–10
Betamethasone
—
50–150
Methylprednisolone
5
5
Fluocinolone
—
40–100
Flurandrenolone
—
20–50
Fluorometholone
1–2
40
Deflazacart
3–4
—
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