Transcript Document

Diseases of Subcutaneous Fat.
Endocrine Diseases.
Ben Adams
KCOM
5-11-05
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Diseases of Subcutaneous Fat
• Panniculitis
• May appear similar due to depth
• Two broad categories:
– Septal (classically E.N.)
– Lobular (Vascular)
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Erythema Nodosum
Acute Erythema Nodosum
– Crops of bilateral, deep, tender, 1-10 cm diameter, red
nodules, on pretibial area (or other).
– Lesions resolve over several days or weeks, leaving a
bruise like area. (erythema contusiforme) which
resolves without scarring.
– Fever, malaise, leg edema, arthritis and other systemic
symptoms may be present
– Associated states (reactive process)
• W>>M, TB, Streptococcal inf., Mycoplasma,
Coccidioidomycosis, Yersinia, Salmonella, deep fungal
infections, Sarcoidosis, drug (oral contraceptives). Pregnancy.
Many others.
– Idiopathic 35-55% of cases
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Erythema Nodosum
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Erythema Nodosum
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Findings suggestive of a systemic
cause for Erythema Nodosum
•
•
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•
•
Synovitis
Diarrhea
Abnormal chest X-ray
Preceding upper respiratory tract infection
Elevated anti-Dnase B
Positive tuberculin skin test
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Erythema Nodosum
Chronic Erythema Nodosum
• Distinguishing features:
– Older women
– Unilateral, Single lesion which spreads centrifugally to form
annular plaques. Sometimes bilateral.
– No systemic symptoms ( Possibly arthralgia )
– Less tender
– No underlying disease
– Prolonged course of months / years.
• Key to diagnosis: Pretibial, no systemic
complaints. Biopsy seldom required.
• DDX: erythema induratum (post. Calf), syphilitic
gummas (unilateral). Subcutaneous fat necrosis
assoc with pancreatits etc. – systemic.
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Erythema Nodosum
• Histologic Features
– Septal infiltrate of neutrophils (early),
other mononuclear cells. Histiocytes and
Multinucleated Giant cells may
predominate older lesions. Some foamy
histiocytes may be seen.
– Meischer’s radial granulomas:
Aggregates of histiocytes around stellate
clefts is characteristic not diagnostic.
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Erythema Nodosum
Septa are widened and edematous, and infiltrated by
lymphocytes and neutrophils
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Erythema Nodosum
Miescher's microgranulomas within septa.
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Erythema Nodosum
• Treatment:
– Treat underlying causes.
– NSAIDS, bed rest / reduced activity
– Potassium Iodide: Increase to control.
• Watch for hypothyroidism.
• Reports of EN triggered by SSKI
– Intralesional / systemic Steroids
– Refractory cases: anti-malarials, colchicine.
– Most cases resolve in 3-6 wks.
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Nodular Vasculitis
• AKA: Erythema Induratum
• Tender subcutaneous nodules of calves of middle
aged, thick – legged women. Bilateral, often
ulcerate and recur over years.
• Pathology: Arteritis, venulitis of septal vessels
with substantial necrosis of lobular adipocytes
resulting in suppuration and perforation.
Granulomatous inflammation.
• DDX: Erythema induratum. TB testing, PCR of
affected tissue for mycobacterium.
• Treatment: SSKI (50% effective). Other agents
used in E.N.
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Nodular Vasculitis
• Nodular lesions on the lower leg with
evidence of ulceration
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Sclerosing Panniculitis
(Lipodermatosclerosis)
• Presentation: Development of woody induration of lower
calves (esp. left) with appearance of inverted champagne
bottle. Induration begins near ankles and slowly progresses
proximally. Most common W > 40 years. May be painful.
• Pathogenesis: venous insufficiency with hypoxia of center
of fat lobule. May not be apparent venous disease.
• Histopathology: Necrosis of fat lobules with ghost cells
(pale cells no nuclei). Foamy histiocytes, inflammatory
cells and septal thickening with fat microcyst.
• Biopsy should be avoided. Heals poorly. Venous eval.
• TX - Treat venous insufficiency.
– Compression stockings (may be painful).
– Stanozolol decreases perivascular fibrin, decreases pain in 3 wks
and induration in 8 wks.
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Sclerosing Panniculitis
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Sclerosing Panniculitis
Lipomembranous change, consisting of cystic
formation with elaborate papillary configurations
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Physical Panniculitis
Sclerema Neonatorium
• Presentation: Gravely ill, premature neonate’s skin
begins to harden on buttocks and LE and rapidly
spreads to involve entire body except palms, soles
and genitalia.
– Mobility affected by induration.
– Rapidly fatal.
– Child is very ill.
• Histopathology: Enlarged adipocytes filled with
needle like clefts in radial array.
• TX: treat underlying disease.
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Sclerema Neonatorium
Needle-shaped clefts within lipocytes,
in the absence of inflammation.
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Subcutaneous Fat
Necrosis of the Newborn.
•
Presentation: Asymptomatic, firm,
rubbery nodules on upper back,
buttocks, cheeks and proximal
extremities. May fuse into plaques
which resolve over several months
without scarring.
– Occurs during first 4 weeks of life.
– Child is otherwise healthy
– Associated with perinatal
hypothermia, asphyxia and
difficult labor and maternal drug
use.
– Rarely, hypercalcemia occurs
during the episode.
•
•
Histopathology: Lobular
panniculitis with radial needle
clefts in adipocytes.
Fine needle aspiration has been
used to DX.
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Subcutaneous Fat
Necrosis of the Newborn.
Indurated plaques on the trunk
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Subcutaneous Fat
Necrosis of the Newborn.
Needle-shaped clefts in radial configuration are
present within giant cells.
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Cold Panniculitis
• Synonyms: Popsicle / equestrian
panniculitis.
• Presentation: Within several
days of cold exposure, affected
skin becomes mildly
erythematous with nontender
firm Sub-Q nodules. Face,
thighs and scrotum.
• Typical patients: (Hx of cold
exposure).
– Infants and young children.
Black > Whites.
– Scrotal disease: prepubertal,
9-14 yr old male who is over
weight. Bilateral, painful, no
transillumination.
• Resolves in several days to
weeks without TX.
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Cold Panniculitis
Erythematous, violaceous plaques on the
thighs in a case of equestrian cold panniculitis.
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Post Steroid Panniculits
• Firm sub-Q nodules form within one month of
rapid withdraw from high dose systemic steroids.
• Predominantly children.
• Most cases resolve. May have to restart steroids
and wean more slowly.
Traumatic Panniculitis
• Trauma, often not recalled, induces a firm mildly
tender lipoma like sub-Q mass.
• Heals with fibrosis of septa.
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Factitial Panniculitis
• Factitial injection of foreign substances into
the skin. Medical personal are common
patients.
• DX:
– Careful HX. Fits no other pattern.
– Healing injection site, biopsy revealing foreign
material, polarized light micro, Mass
spectroscopy in difficult cases is suspicion is
high.
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Sclerosing Lipogranuloma
• Granulomatous and fibrotic reaction from intentional, often
cosmetic, injection of mineral oils, silicon or guayacol
(Mexico).
• Presentation: Up to ten years after implantation, skin
becomes erythematous, hyperpigmented and indurated
with a lumpy quality of sub-q. Due to migration of
material, features may extend beyond the implantation site.
• 66% autoimmune finding (+) ANA, Raynauds, Sjogrens
ect. 10% connective tissue disease usually scleroderma.
• Histologically: Swiss cheese appearance of panniculus.
Histiocytes with ingested material. Fibrosis.
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Sclerosing Lipogranuloma
2nd to Cosmetic Paraffin injections
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Sclerosing Lipogranuloma
Oil granuloma. Numerous vacuolated spaces, in
this case due to grease gun injury.
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Pancreatic Panniculitis
• Fat necrosis 2nd to Pancreatitis or pancreatic
carcinoma. May be first sign of malignancy
(40%). Digestive enzymes cause damage.
• Presentation: Tender or painless, erythematous Sub-q
nodules 1-5 cm. In diameter. Lower leg is affected 90%.
Lesions typically number <10 (may be 100s). Involutes
with scarring.
– Assoc findings: abd pain (sometimes), arthritis (FFA in
synovial fluid), pulm. infiltrates.
• DX: pancreatic workup amylase, lipase.
– Peripheral eosinophila in Pancreatic CA.
• Histology: fat necrosis, Ghost cells. Finely
stippled Basophilic material (Calcium) with rim of
necrotic cells. Inflammatory infiltrate at periphery.
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Pancreatic Panniculitis
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Pancreatic Panniculitis
Neutrophilic inflammation, cellular necrosis, and
deposition of homogeneous basophilic material
due to saponification of fat by calcium salts.
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Alpha-1 Antitrypsin
Deficiency Panniculitis
• 1:2500 of European decent have homozygous deficiency
of enzyme which inhibits neutrophil elastase. The genetic
defect results in a molecule that cannot be released from its
production sites in hepatocytes.
• AAT is 1 of the 3 most common lethal genetic diseases
among whites.
• Presentation: After minor trauma, painful nodules appear
on extremities and trunk. Lesions may form draining
sinuses.
• M=F, 20-40 years.
• Histopathlogy: Dissolution of septae. Islands of normal fat
floating in spaces of destroyed septae.
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Alpha-1 Antitrypsin Deficiency Panniculitis
Purpuric nodules on the ankle
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Alpha-1 Antitrypsin
Deficiency Panniculitis
• DX
– Constellation of Liver dysfunction and
Pulmonary dysfunction with skin lesions
– Serum AAT levels
– AAT function analysis
• TX
– Replace enzyme (prolastin)
– Dapsone, doxycycline
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Cytophagic Histiocytic Panniculitis
• Multi-system disease with widespread, painful sub-q
nodules which may break down and form ulcerations.
– Progressive febrile illness with heptomegaly, pancytopenia, HTG.
• Etiology: Proliferation of histiocytes. Triggered by viral
infection or 2nd to lymphomas.
– Benign: (-) EBV
– Malignant (+) EBV, B or T cell Lymphoma.
– HIV assoc.
• Histopathology: Infiltration of fat lobules with histiocytes
with fat necrosis. Bean bag cell stuffed with RBC.
– Clonal B or T cell proliferation = malignant.
• TX: Benign - cyclosporine induces permanent remissions.
Malignant - Chemo or bone marrow.
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Cytophagic Histiocytic Panniculitis
Subcutaneous
nodules with
purpura
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Cytophagic Histiocytic Panniculitis
Macrophages engaged in cytophagic activity. Some
of them have the appearance of ‘bean bag cells’
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Misc. Panniculitis
• Eosinophilic Panniculitis
– Prominent infiltration with eosinophils assoc
with arthropod bites, parasites, contact derm,
Well’s, bacteria, injections.
• Gouty Panniculitis
– Uric acid in Sub-Q leading to fat necrosis.
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Lipoatrophies
•
•
•
•
•
•
•
Total
Partial
Centrifugal
Semicircular
Lipoatrophia Annularis
Localized
HIV associated
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Total Lipodystrophy
2 types: Congenital vs Acquired.
Both are assoc. with D.M. (lipoatrophic diabetes)
1.) Beradinelli - Seip (congenital)
• Autosomal recessive. Hypermetabolic state.
• General: Paucity of fat at birth with voracious appetite, increased
height velocity, muscular hypertrophy, genital enlargement, mild
MR, protuberant abdomen, HTG. Hypertrophic cardiomyopathy,
pul stenosis. DM resistant to therapy.
•
Cutaneous: AN (often generalized), Hypertrichosis
with abundant curly scalp hair.
•
•
Death in young adulthood from DM, cardiac,
liver dx.
TX: fenfluramine reduces hypermetabolic state.
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Beradinelli - Seip (congenital)
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Congenital
Total
Lipodystrophy
AN and Loss of Bichat’s fat pad
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Total Lipodystrophy
2.) Seip
- Lawrence (acquired)
• Begins <15 yrs old, often <5yrs (not at birth)
• Well defined illness precedes 30 % of cases.
• Presentation: As in congenital, but less striking.
AN with DM is common. Severe liver
involvement is more common (death). Loss of fat
may begin local and generalize or start
generalized.
• TX: etretinate has helped AN in some.
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Seip - Lawrence (acquired)
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Partial Lipodystrophy
(Inherited Forms)
Kobberling-Dunnigan syndrome
• Autosomal dominate.
• At puberty adipose tissue is lost from extremities, gluteal
and truncal areas with fat accumulation on the neck and
face.
• DM with AN, HTG, hirsutism, PCOS after age of 20 years.
Other inherited forms:
• Onset early infancy with adipose tissue loss localized to
the face and buttocks. Rieger anomaly: tooth and eye
abnormalities: hypoplasia of the iris and iris strands to the
peripheral cornea.
• Bone age and dentition are retarded.
• DM late. No AN.
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Partial Lipodystrophy
(Acquired Forms)
Progressive Partial Lipo. (Barraquer-Simons)
• W > M, Present first or second decade.
• After a febrile illness, diffuse and progressive loss
of fat beginning on face and scalp and progressing
downward to iliac crest. Sparing of LE.
• No discomfort or inflammation.
• Low C3 levels are assoc. and proteinuria occurs in
in 50% of these cases.
• 3rd trimester intrauterine death may occur.
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Progressive Partial Lipo.
Loss of buccal fat and AN.
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Lipoatrophies
• Centrifugal
– One type is seen primarily in infants from Japan. 90 %
are under 5 years.
• Centrifugally spreading loss of abdominal fat over 3- 8 years
with regional lymphadenopathy.
• Resolves completely after progression stops.
• Semicircular
– Adult women affected with single or multiple,
asymptomatic, symmetric depressions of anterolateral
thigh.
– Often after trauma. Resolves in several years.
• Annular Atrophic panniculitis
– 10cm band of atrophy, bilaterally, around the ankles of
children and young adults. Rare.
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Lipoatrophies
Lipoatrophia Annularis
– Bracelet like constrictions of upper extremities 1-2 cm
wide on women following a period of swelling and
erythema of extremity.
– Arthralgias and Pain of affected extremity
– Persist up to 20 years.
Localized lipodystrophy
– 2nd to injection of medications esp. insulin.
HIV assoc. Lipodystrophy.
– Occurs in effectively Treated Aids Patients with reverse
transcriptase inhibitors and protease inhibitors.
– Fat redistribution from face, buccal, buttocks and limbs
is lost to neck , upper back and inter abdominal areas.
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Localized lipodystrophy
Insulin injection lipodystrophy
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HIV assoc. Lipodystrophy
Loss
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Endocrine diseases
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Acromegaly
• Hypersecretion of growth hormone.
– 2nd to adenoma
• Changes:
• Diffuse hypertrophy of skin. Reddening and wrinkling of
forehead.
• Cutis verticis gyryata in 30%
• Enlargement of hands and feet and tongue. Drum-stick
fingers.
• Hypertrichosis, hyperpigmentation, hyperhydrosis.
• TX: transpenoidal microsurgery. Irradiation.
Octreotide inhibits GH if surgery is not an option.
– 50% of patients completely normalize with TX.
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Acromegaly
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Cushing’s Syndrome
•
•
•
Hyperfunctioning of adrenocortical
tissue
1.
Cushing disease : microadenoma
of pituitary. 10%
2.
Hyperfunctioning
adrenals/adenomas or other
tumors account for remainder.
Non – Iatrogenic: W > M. Peak age
20-30s.
Features:
–
Obesity of face, neck and trunk.
Buffalo trunk. Moon face
–
Cutaneous: hypertrichosis,
dryness, fragility, acne,
dermatphyte/pityrosporum
infections, flushing, striae of
abdomen and thighs. Thinning
of skin.
–
Systemic: HTN, weakness,
reduced bone density, DM,
atherosclerosis, osteoporosis.
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Cushing’s Syndrome
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Cushing’s Syndrome
Stria rubra
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Addison’s Disease
• Adrenal insufficiency
• Increased Pituitary POMC
leads to increased ACTH
and melanocyte stim.
hormone.
• Cutaneous signs:
– Diffuse hyperpigmentation
• Most prominent in sun
exposed areas and sites of
recent trauma
• Axillae, perineum and
nipples.
• Darkening of palmar,
scars, hair and nails.
•
Diffuse hyperpigmentation, which
persisted into autumn months, in a 11year old boy with Addison’s disease.
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Addison’s Disease
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Panhypopituitarism
•Loss of pituitary hormones 2nd
to infections (syphilis and TB),
tumor, postpartum hemorrhage.
•Loss of melanin 2nd to
decreased ACTH/MSH.
Fine facial wrinkles and light skin
•Cutaneous signs: Thin dry
skin. Diffuse loss of body hair.
Thin, opaque, slow growing
nails. Light skin susceptible to
sunburn. Decrease in facial
folds.
Diminished axillary hair is an early sign
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Hypothyroidism
•
Cretinism
– Insufficient thyroid hormone in
fetal life
– Cool, dry, white to yellow skin.
Patchy alopecia.
Hypohydrosis. Brittle nails.
Thick protuberant lips.
Enlarged tongue. Wide face.
•
Myxedema
– Systemic mucinosis
– Rough, dry, dull skin over
areas of swelling, esp the face.
(lips, tongue and nose)
– Diffuse hair loss and shedding
of outer third of eyelashes
occurs
– Brittle, coarse nails.
– Generalized myxedema in adult
hypothyroidism. Face is puffy
with a dull expression and the hair
is dry.
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Hypothyroidism
Pretibial Myxedema with
peau d’ orange of mucin
deposition
Cretinism
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Hypothyroidism
• Mild Hypothyroidism
– Harder to detect
– Coldness of hands and
feet in absence of
vascular disease, cool
intolerance,
hypohydrosis, weight
gain, excessive
sleeping, constipation.
– Palmoplantar
keratoderma may occur
and resolves with TX.
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Hypothyroidism
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Hypothyroidism
Palmoplantar keratoderma
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Hyperthyroidism
• Cutaneous changes:
– Warm, moist, smooth textured skin.
– Thin, downy hair with possible non-scarring alopecia.
– Diffuse pigmentary changes - ‘melanoderma’. may
result in melasma.
– Plummers’s nails – concave with distal onycholysis.
• Graves disease (F>M, onset 20-30 years.)
– Thyroid Acropachy ( 1% of graves patients)
• Digital clubbing, diaphyseal proliferation in acral and distal
bones.
• Frequently accompanies exophthalmos and pretib. myxedema
• May be seen in euthyroid and hypothyroid pt on occasion.
Acromegally, Pul. osteoperiostitis.
• Radiographic findings are pathognomonic.
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Thyroid Acropachy
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Hyperthyroidism
•
•
Pretibial Myxedema
– 4% of graves patients. Also,
during Hashimoto’s thyroiditis
and primary hypothyroidism.
– Bilateral, localized
accumulations of
glycosaminoglycans assoc with
thyroid stimulating antibodies.
– Exophthalamous and
acropachy assoc.
– TX:
• intralesional steroids,
clobetasol under
occlusion. (not systemic)
• IVIG
Vitiligo – 7 % assoc with graves.
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Hyperthyroidism
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Hypo-parathyroidism
• Cutaneous:
–
–
–
–
–
–
Poor dentition if during development.
Dry scaly skin.
Scanty hair. Absence of axillary and pubic hair.
Brittle malformed nails with onycholysis.
15 % of idiopathic cases develop candidisis.
APECED syndrome:
• Autoimmune PolyEndocrinopathy, Candidasis,
External Dystrophy - syndrome.
• Hypoparathroidism most common endo.
Dysfunction with this syndrome.
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Pseudo - hypoparathyroidism
•
•
•
•
Autosomal dominate or X-linked.
End organ unresponsiveness to PTH.
Elevated PTH and phosphorus. Low calcium.
Clinical findings:
– Short stature, obesity, round face, prominent forehead, low
nasal bridge, attached ear lobes, short neck, short wide nails,
delayed dentition, mental deficiency, blue sclera and
cataracts. Sub-Q calcifications
– Shortened long bones 2nd to premature epiphyseal closure.
• Short stubby toes with metacarpophalangeal dimpling (Albright’s
sign).
– Albright’s hereditary osteodystrophy
• Includes Pseudo-hypoparathyroidism and Pseudo-pseudo PH.
• Defect in G protein pathway leads to resistance to agents acting
through adenylate cyclase pathway.
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Albright’s Hereditary Osteodystrophy
Features of Albright Hereditary
Osteodystrophy (AHO). [A] Young
woman with short stature (~ 3rd
centile), disproportionate
shortening of the limbs,
generalized obesity, and round,
flattened face. [B] Radiograph of
the hand showing the shortened
4th and 5th metacarpals. [C] Fist
with the characteristic 'dimples'
over the 3rd, 4th, and 5th digits
replacing the knuckles formed by
the distal head of normally sized
metacarpal bones (Archibald
sign). [D] Brachydactyly of the
hand, with the short 4th and 5th
digits, the greatly foreshortened
terminal 1st digit, and very short,
wide thumbnail (potter's thumb).
(Reproduced from Levine, 2000,
with permission).
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Hyper-Parathyroidism
• Multiple endocrine neoplasia (MEN-I)
– Tumors of Parathyroid, pancreas, pituitary,
thyroid and adrenal glands.
– Most common abnormality is hypercalcemia
from the tumors of the parathyroids.
– Autosomal dominate. Presents in 4th decade.
– Assoc. with multiple angiofibromas,
collaganomas, café au lait macules, lipomas,
confetti like hypopigmentation and gingival
macules.
– Tumors arise 2nd to abnormal tummor suppresor
genes
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Hyper-Parathyroidism and MEN-I
Angiofibromas
Collagenomas
Gingival papules
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Acanthosis Nigricans
• Hyperpigmentation and
papillary hypertrophy in a
symmetrical distribution.
• Any area of the body may
be involved including
conjunctiva, lips and
buccal mucosa. Palms
may show hyperkeratosis.
• Type I : Malignancy
associated.
– Preceeds(18%),
accompanies(60%),
follow(22%) malignancy
– Adenocarcinoma most
associated. Esp G.I.
• Nonobese male >40 yrs
old.
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Malignant Acanthosis Nigricans
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Acanthosis Nigricans
– Tripe Palms – thickened velvety palms with
demoglyphics.
• 95 % assoc with cancer.
• 77% occurs with AN.
• If only palms were only presenting sign then lung
CA most common.
• If palms and AN then gastric cancer most common.
• Type II : Familial Acanthosis Nigricans.
– Present at birth or early childhood.
– No cancer assoc.
– Accentuated at Puberty.
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Tripe Palms
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Acanthosis Nigricans
• Type III: DM assoc.
– Most common
– Grayish, velvety thickening of neck, axillae and
groin.
– Occurs in obesity and with endocrine disorders
such as DM, acromegaly, Stein – Leventhal,
Cushing, Addisons, thyroid d/o. Renal
transplant pts. Many others.
– Insulin resistance either clinical or subclincal.
– Drugs: nicotinic acid, glucocorticoids,
diethylstilbestrol, trizineate, BCP.
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Acanthosis Nigricans
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Acanthosis Nigricans
• Histopathology: papillomatosis,
hyperkeratosis and slight
hyperpigmentation. Without
thickening of the Malpighian
layer.
– Darkening of skin 2nd to
hyperkeratosis.
Treatment
– Address malignancy,
endocrinopathy
– Weight Loss
– Lipodystrophic DM
improves with fish oil.
– Etretinate and tretinoin.
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The End
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