Title: ENDOCRINOLOGY SIGNS AND SYMPTOMS UNINTENDED WEIGHT LOSS The
1ENDOCRINOLOGY
2UNINTENDED WEIGHT LOSS
- The most common causes
- Uncontrolled DM
- Addisons Disease
- DD
- Cancer (about 30)
- Gastrointestinal disorders (about 15) and
- Dementia or depression (about 15)
-
3Abnormal Skin Pigmentation
- Excessive ACTH secretion-
- Addisons Disease
- Chloasma Mask of Pregnancy
- Acanthosis nigricans
- Hemochromatosis- bronze diabetes
- Thiamine/ Niacin deficiency
- Vitiligo- Addisons, B12 deficiency
- Dialysis patients, sprue, HIV
- Drugs
4Pigmentation Picture Gallery
5Acanthosis Nigricans
This healthy 16 year old adolescent developed
acanthosis nigricans after gaining over 30 pounds
during the preceding year
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7Drugs causing pigmentation
- amiodarone, arsenic, bleomycin, busulfan,
clofazimine, hydroxychloroquine, chlorpromazine,
doxorubicin (nail beds), imipramine, methimazole,
minocycline, niacin, primaquine,
propylthiouracil, topical tretinoin, and
zidovudine
8Gynecomastia
- Female appearing male breast
- Pubertal gynecomastia is common (teenagers who
are very tall or overweight) - Athletes abusing androgens
- Klinefelter's syndrome (47,XXY)
9Klinefelters 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
10Gynecomastia Labworkup
- Plasma Prolactin levels increased
- ß 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
11Muscle Cramps Tetany
- Occupational
- Night cramps-
- Diabetes mellitus
- Parkinson's disease
- Central nervous system or spinal cord lesions
- Peripheral neuropathy
- Hemodialysis
- Peripheral vascular disease, and
- Cisplatin or vincristine
12Remember!
- A common cause for muscle pain, though not
usually with cramping, is 3-hydroxy-3-methylglutar
yl coenzyme A (HMG-CoA) reductase inhibitor
(statin) therapy for hyperlipidemia
13- Diffuse, recurrent, or severe muscle cramping
requires evaluation for hypocalcemia/
Hypomagnesemia
14Mental 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
15PITUITARY DISORDERS
16Endocrine Control Negative feedback
17ANATOMY
18PITUITARY TUMOR
19NORMAL Vs. ABNORMAL
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21Pituitary 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
22PITUITARY TUMORS
- Adenomas Prevalence 20 cases per 100,000
- Incidence of 0.5 to 7.4 per 100,000 population
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24Hyperprolactinemia
- 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.
25Hypopituitarism
- Growth Hormone Deficiency
- Decreased muscle strength and exercise tolerance
and - A reduced sense of well-being (eg, diminished
libido, social isolation) - Increased body fat
26Hypopituitarism
- Gonadotropin Deficiency
- Infertility and oligomenorrhea or amenorrhea
- Lack of libido, hot flashes, and dyspareunia
27Hypopituitarism
- Adrenocorticotropic Hormone Deficiency
- Chronic malaise, fatigue, anorexia, and
hypoglycemia. - Severe hypotension, hyperkalemia, and
hyperpigmentation - May lead to hyponatremia
28Hypopituitarism
- Thyrotropin (TSH) Deficiency
- Malaise, leg cramps, fatigue, dry skin, and cold
intolerance.
29Pituitary Excess Hormone Secretion
- Prolactinoma oligomenorrhea, amenorrhea,
galactorrhea, or infertility - Men impotence and decreased libido
30ACROMEGALY
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32Cushing's Disease
33DIAGNOSIS
- 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
34THERAPY
- 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
35THERAPY
- For Prolactinoma tumor shrinkage by medical
therapy with Bromocriptine (Parlodel), and
cabergoline (Dostinex) - Radiosurgery (gamma knife)
36THYROID DISORDERS
37TSH and FT4
- TSH levels 0.45.5 mU/L.
- FT4 is a direct measurement of the serum
concentration of free (unbound) T4
38THYROID 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 headneck or
chestshoulder radiation. - Ultrasound examination useful for biopsy and
follow-up. - Clinical follow-up required.
39GOITER
- 4
- Presence of iodine deficiency
- Graves and Hashimotos 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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41Other Tests for nodules
- FNAC
- US- irregular margins/ microcalcifications
- RAI (123 I / 131I) scans for hot vs cold
nodules
42Thyroid 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.
43Thyroid Cancer
- FM 31
- 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
44Thyroid Cancer Prognosis
- lt45-TNM T1 N1 M0- 98 10 yr survival
- lt45-T1 N1 M1 5 yr 99 85 10 yr
- gt45- T1 N0 M0
- gt45 T1 N0 M0- 95 5 yr 7010yr
- gt45 T N M- 80 5 yr 61 10 yr
45Hypothyroidism 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.
46- May affect almost all body functions
- Interstitial accumulation of hydrophilic
mucopolysaccharides leads to fluid retention
(lymphedema) - Hashimotos Drugs- lithium, amiodarone,
- foods- turnips, cassavas
- Chronic HCV patients treated with interferon
47Lab workup
- FT4 low/ normal
- TSH increased
- High cholesterol
- Thyroid antibodies- Hashimotos
- Differential Diagnosis unexplained menstrual
disorders, myalgias, constipation, weight change,
hyperlipidemia, ascites, heart failure and
anemia.
48Complications
- Cardiac- CAD, CHF
- Infection risk
- Madness
- Infertility/ miscarriage
- Coma (rare)
49Treatment
- Levothyroxine 50-100 mcg/day
- (max 1.6 mcg/kg/day)
- Slowly increase the dose every
- 1-3 weeks (75250 mcg oral)
- Estre Levo-T Levothroid Levoxyl
Synthroid Thyro-Tabs Unithroid
50Hyperthyroidism (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.
51Graves' Disease
- Autoimmune, Familial
- FM 81, Age 20-40
- Exophthalmos
- Pernicious anemia
- Myasthenia gravis
- Risk of Addisons,
- Celiac,
- DM T1,
52Thyrotoxicosis Factitia
- Eating ground beef containing bovine thyroid gland
53- 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
54- stare and lid lag, fine resting finger tremors,
moist warm skin, hyperreflexia, fine hair, and
onycholysis - CVSforceful heart beat,
- premature atrial
- contractions, and sinus
- tachycardia.
- Atrial fibrillation or
- atrial tachycardia occurs
- in about 8 (older men)
55Ophthalmopathy
- 20-40
- Chemosis
- Conjunctivitis
- Proptosis
- Exophthalmos
- Maximum normal
- eye protrusion
- 22 mm for blacks,
- 20 mm for whites, and
- 18 mm for Asians.
56CT Scan
57Pretibial Myxedema
58Complications
- Atrial fibrillation
- THERAPY choice of methods
- ?Drugs- Symptomatic
- PropranololInderal Inderal LA InnoPran XL
Pronol - Effectively relieves the tachycardia, tremor,
diaphoresis, and anxiety
59Thiourea drugs
- Methimazole Tapazole
- Propylthiouracil, PTU
- For mild thyrotoxicosis, small goiters, or fear
of isotopes - Usually continued for 1224 months before being
discontinued (50 relapse) - Side Effects BMD- 0.3-0.4 pruritus, allergic
dermatitis, nausea, and dyspepsia
60Radioactive iodine (131I)
- Safe Should not be given to pregnant women
- Thyroid surgery performed les frequently
61Hashimotos 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.
62Hashimotos
- Autoimmune condition and the
- most common thyroid disorder in the USA
- Familial FM 61
- Dietary iodine supplementation.
- Certain drugs (amiodarone, interferon,
interleukin-2, G-CSF) frequently - induce thyroid autoantibodies
- Smokersgt Non smokers
- (thiocyanates in cigarettes is antithyroid)
63Hypoparathyroidism
64HYPOCALCEMIA
- 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.
65HYPOPARATHYROIDISMChronic disease
- lethargy,
- personality changes,
- anxiety state,
- blurring of vision due to cataracts,
- parkinsonism, and
- mental retardation.
66Chvostek'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
67CARPOPEDAL SPASM
68Laboratory Findings
- Serum calcium is low,
- serum phosphate high,
- urinary calcium low, and
- alkaline phosphatase normal.
- PTH levels are low.
- ? Serum magnesium
69HYPOCALCEMIA DUE TO DRUGS
- Loop diureticsEthacrynic AcidEdecrin /
FurosemideDelone Furocot Furosemide
Lasix - Phenytoin Di-Phen Dilantin
- Alendronate Fosamax
- Foscarnet Foscavir
70Treatment for tetany
- Intravenous calcium gluconate
- Calcium gluconate, 1020 mL of 10 solution
intravenously
71THERAPY
- Oral calcium
- Calcium salts 12 g of calcium daily.
- Liquid calcium carbonate (Titralac Plus), 500
mg/5 mL, may be especially useful. The dosage is
13 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
72Hyperparathyroidism
- 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.
73- "bones, stones, abdominal groans, psychic moans,
with fatigue overtones."
74Signs of Hypercalcemia
- thirst,
- anorexia,
- nausea, and vomiting
- Constipation,
- fatigue, anemia, weight loss, and hypertension
- Pancreatitis occurs in 3.
75- 0.1 incidence
- gt50 FM 31
- Due to adenoma of parathyroid gland
- 5 of renal stones due to this condition
76X-Rays
77Reduction of plasma phosphate with aluminum
hydroxide gel / Aloh-Gel Alternagel
Alu-Cap
78Complications
- Pathologic fractures
- Renal failure and uremia
- Peptic ulcer and pancreatitis
79Other causes for High Calcium
- Calcium or Vitamin D Ingestion
- Cancer breast, lung, pancreas, uterus,
hypernephroma - Sarcoidosis
- Multiple myeloma
- Thiazides/Lithium
80- Bisphosphnates
- Raloxifene
81OSTEOPOROSIS
82DEFINITION
- A metabolic bone disease
- Low bone mass and microarchitectural
deterioration of bone tissue - Leads to enhanced bone fragility and increased
fracture risk
83Osteoporosis 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 from-
- 1 a variety of chronic conditions leads to
bone mineral loss - 2 effects of medications and nutritional
deficiencies
84Causes 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
85Causes of Secondary OsteoporosisMedications
- Steroids
- Excess thyroid hormones
- GnRH agonists
- Cyclosporine
- Methotrexate
- Phenobarbital
- Phenytoin
- Phenothiazines
- Heparin
86Conditions Causing Nutritional Deficiencies
- Malabsorption syndromes
- Vitamin D deficiency
- Calcium deficiency
- Gastric and bowel resections
- Alcoholism
87Other Causes
- Athletic amenorrhea
- Tobacco use
- Pregnancy
- Carbonated fizzydrinks
88WHO definition
- Bone density (BD) that is 2.5 standard deviation
(SD) or more below the young adult mean value
(T-score lt -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
89Prevalence
- Primarily white women
- 54 of postmenopausal Osteopenia
- 30 have osteoporosis
- 1.3 million osteoporotic fractures annually
- 50 Vertebral 60
- 25 Hip 70
- 25 Colless (wrist) 50
90?Men
- an important health problem
- 30 of all hip
- 20 of all vertebral
91Pathophysioloy
- Poor bone mass acquisition during growth in early
years - Accelerated bone loss post menopausal
- ?Environmental (nutritional, behavioral, and
medications) - ?Genetic (40-80)
92Nutritional Factors
- Dietary calcium intake, Vitamin D status, protein
and calorie intake - Trace elements
- Phosphorus
- Vitamins C and K,
- Copper, zinc, and manganese
93Calcium
- Got milk?- during adolescence helps
- Low calcium intake in childhood increases later
life fractures - Supplementation reduces fractures in elderly
94?Diet
- Typical U.S. diet is sodium and protein rich,
both of which increase urinary calcium excretion,
thus increasing dietary calcium requirements
95?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
96?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)
97?Glucocortiocids (aka. Steroids)
- Most important cause
- vertebrae, ribs, and ends of the long bones
(20-40) - Estrogen deficiency
98Risk Factors seen in Osteoporosis
- Modifiable
- Sedentary lifestyle
- Smoking
- Excessive alcohol intake
- Estrogen-deficient states
- Non-Modifiable-
- Age
- Caucasian or
- Asian race
- Low body weight
- Family history of osteoporosis
- Nulliparity
- Calcium deficient diet
- Use of medications
-
99SIGNS AND SYMPTOMS
- Skeletal fracture- vertebral most common- usually
lower thoraic(T8) - or lumbar
- Acute pain can get chronic
- Multiple fractures on x-ray
- Kyphosis (Dowagers hump) caused by vertebral
collapse
100SIGNS 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
101THERAPY
- AT ALL AGES- CALCIUM INTAKE
- Diet or calcium supplements
- Vit D 800 IU/day if needed
102THERAPY
- 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
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104Outcomes
- Raloxifene reduces risk by 0.7
- Bisphosphoantes by 41-49
105ADRENAL DISORDERS
106Adrenal 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 (ACTH124) unable to stimulate a
normal increase in serum cortisol.
107Pattern of plasma ACTH/Cortisolin patients
recovering from prior long-term daily treatment
with large doses of glucocorticoids
108Adrenal 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
109Addison'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.
110Addisons Images
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113Thomas Addison (1793-1860). On the constitutional
and local effects of disease of the supra-renal
capsules. London, Samuel Highley, 1855.
114Addisons Disease
115Causes Etiology
- Autoimmune destruction (80)
- Tuberculosis
- Hemorrhage into adrenals due to meningococcal
meningitis (Waterhouse-Friderichsen syndrome) - Fungal adrenal destruction in AIDS/HIV
116coccidioidomycosis
117- Vitiligo (10)
- Orthostatic hypotension
- Eosinophilia
- Low sodium
- High potassium
- Low plasma cortisol levels
118Complications
- Susceptible to infections
- Leads to crisis precipitation
119THERAPY
- Corticosteroid replacement
- Mineralocorticoid replacement
- Hydrocrotisone (Cortisone acetate)
- Prednisone Deltasone Predone Sterapred
- Fludrocortisone Florinef for salt (sodium)
retention - Prasterone, Dehydroepiandrosterone,
DHEAPrestara Vitamist DHEA-M for Men
Vitamist DHEA-W for Women
120- medical alert bracelet or medal reading, "Adrenal
insufficiencytakes hydrocortisone." - ?Lorenzos oil -Vitiligo
121Prognosis
- With appropriate treatment have normal life
expectancy. - Risk of infection/surgery/stress
122Cushing'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.
123Cushings
- 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 gt 7.5 mcg/dL is
indicative of Cushing's syndrome
124Cushings Disease
125Cushings Disease
126Adrenal Tumor
127Cushings Syndrome
128Cushings Signs
129Complications
- 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
130Clinical Use of Corticosteroids
131adverse 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
132Therapy 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