ENDOCRINOLOGY SIGNS AND SYMPTOMS UNINTENDED WEIGHT LOSS The

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ENDOCRINOLOGY

• SIGNS AND SYMPTOMS

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UNINTENDED WEIGHT LOSS

• The most common causes
• Uncontrolled DM
• Addisons Disease
• DD
• Cancer (about 30)
• Gastrointestinal disorders (about 15) and
• Dementia or depression (about 15)

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Abnormal 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

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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

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Gynecomastia

• Female appearing male breast
• Pubertal gynecomastia is common (teenagers who
  are very tall or overweight)
• Athletes abusing androgens
• Klinefelter's syndrome (47,XXY)

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Klinefelters 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

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Gynecomastia 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

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Muscle 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

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Remember!

• 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

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

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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

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PITUITARY DISORDERS

• WSO 411

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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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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

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PITUITARY TUMORS

• Adenomas Prevalence 20 cases per 100,000
• Incidence of 0.5 to 7.4 per 100,000 population

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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.

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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

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Hypopituitarism

• Gonadotropin Deficiency
• Infertility and oligomenorrhea or amenorrhea
• Lack of libido, hot flashes, and dyspareunia

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Hypopituitarism

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

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Hypopituitarism

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

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Pituitary Excess Hormone Secretion

• Prolactinoma oligomenorrhea, amenorrhea,
  galactorrhea, or infertility
• Men impotence and decreased libido

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ACROMEGALY
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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

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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

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THERAPY

• For Prolactinoma tumor shrinkage by medical
  therapy with Bromocriptine (Parlodel), and
  cabergoline (Dostinex)
• Radiosurgery (gamma knife)

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THYROID DISORDERS
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TSH and FT4

• TSH levels 0.45.5 mU/L.
• FT4 is a direct measurement of the serum
  concentration of free (unbound) T4

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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 headneck or
  chestshoulder radiation.
• Ultrasound examination useful for biopsy and
  follow-up.
• Clinical follow-up required.

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GOITER

• 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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Other Tests for nodules

• FNAC
• US- irregular margins/ microcalcifications
• RAI (123 I / 131I) scans for hot vs cold
  nodules

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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.

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Thyroid 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

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Thyroid 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

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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.

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• 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

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Lab 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.

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Complications

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

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Treatment

• 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

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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
• FM 81, Age 20-40
• Exophthalmos
• Pernicious anemia
• Myasthenia gravis
• Risk of Addisons,
• Celiac,
• DM T1,

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Thyrotoxicosis Factitia

• Eating ground beef containing bovine thyroid gland

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• 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

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• 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)

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Ophthalmopathy

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

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CT Scan
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Pretibial Myxedema
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Complications

• Atrial fibrillation
• THERAPY choice of methods
• ?Drugs- Symptomatic
• PropranololInderal Inderal LA InnoPran XL
  Pronol
• Effectively relieves the tachycardia, tremor,
  diaphoresis, and anxiety

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Thiourea 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

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Radioactive iodine (131I)

• Safe Should not be given to pregnant women
• Thyroid surgery performed les frequently

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Hashimotos 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.

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Hashimotos

• 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)

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Hypoparathyroidism
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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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HYPOPARATHYROIDISMChronic disease

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

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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

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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

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HYPOCALCEMIA DUE TO DRUGS

• Loop diureticsEthacrynic AcidEdecrin /
  FurosemideDelone Furocot Furosemide
  Lasix
• Phenytoin Di-Phen Dilantin
• Alendronate Fosamax
• Foscarnet Foscavir

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Treatment for tetany

• Intravenous calcium gluconate
• Calcium gluconate, 1020 mL of 10 solution
  intravenously

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THERAPY

• 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

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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.

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• "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.

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• 0.1 incidence
• gt50 FM 31
• Due to adenoma of parathyroid gland
• 5 of renal stones due to this condition

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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

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Other causes for High Calcium

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

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• Bisphosphnates
• Raloxifene

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OSTEOPOROSIS

• FACTS AND FEATURES

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DEFINITION

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

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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 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

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Causes of Secondary OsteoporosisMedications

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

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Conditions Causing Nutritional Deficiencies

• Malabsorption syndromes
• Vitamin D deficiency
• Calcium deficiency
• Gastric and bowel resections
• Alcoholism

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Other Causes

• Athletic amenorrhea
• Tobacco use
• Pregnancy
• Carbonated fizzydrinks

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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 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

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Prevalence

• 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

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?Men

• an important health problem
• 30 of all hip
• 20 of all vertebral

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Pathophysioloy

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

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Nutritional Factors

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

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Calcium

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

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?Diet

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

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?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

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?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)

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?Glucocortiocids (aka. Steroids)

• Most important cause
• vertebrae, ribs, and ends of the long bones
  (20-40)
• Estrogen deficiency

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Risk 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

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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 (Dowagers hump) caused by vertebral
  collapse

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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

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THERAPY

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

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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

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Outcomes

• Raloxifene reduces risk by 0.7
• Bisphosphoantes by 41-49

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ADRENAL DISORDERS
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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 (ACTH124) unable to stimulate a
  normal increase in serum cortisol.

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Pattern of plasma ACTH/Cortisolin patients
recovering from prior long-term daily treatment
with large doses of glucocorticoids
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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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Addisons Images
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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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Addisons Disease
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Causes Etiology

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

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coccidioidomycosis
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• Vitiligo (10)
• Orthostatic hypotension
• Eosinophilia
• Low sodium
• High potassium
• Low plasma cortisol levels

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Complications

• Susceptible to infections
• Leads to crisis precipitation

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THERAPY

• 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

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• medical alert bracelet or medal reading, "Adrenal
  insufficiencytakes hydrocortisone."
• ?Lorenzos oil -Vitiligo

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Prognosis

• With appropriate treatment have normal life
  expectancy.
• Risk of infection/surgery/stress

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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.

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Cushings

• 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

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Cushings Disease
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Cushings Disease
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Adrenal Tumor
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Cushings Syndrome
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Cushings Signs
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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

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Clinical Use of Corticosteroids
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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

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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