Download Cushing syndrome

Physical signs of most
common endocrine diseases
Dr. Szathmári Miklós
Semmelweis University
First Department of Medicine
05. December 2011.
Subjects of the lecture
• Thyroid diseases
– hyperthyroidism
– hypothyroidism
• Diseases of adrenal cortex
– Cushing’s syndrome
– Addison’s disease
• Gynecomastia
• Acromegaly
Enlargement of thyroid
gland=goiter
nodular
diffuse
Palpation of the thyroid gland
• Place the fingers of both hands on the patient’s
neck so that your index fingers are just below
the cricoid cartilage
• The patient’s neck should be extended, but not
far enough to tighten the muscles
• Ask the patient to sip and swallow water. Feel
for the thyroid gland rising up under your
fingerpads
• Displace the trachea to the right with your left
fingers. With the right hand fingers, palpate
laterally for the right lobe in the space between
the displaced trachea and the relaxed
sternomastoid. Find the lateral margin.
Palpation of the thyroid gland
• Normal size of a lateral lobe is approximately the
size of the distal phalanx of the thumb.
– Enlarged in Graves’ disease (diffuse), malignancy
(nodular), in thyroiditis.
• Normal consistancy: feels somewhat rubbery.
– Soft in Graves’ disease
– Firm in Hashimoto’s thyroiditis, malignancy
• Normally not painful
– Tenderness in thyroiditis
• Localized systolic or continuous bruit (noncardiac
origin) may be heard in hyperthyroidism
Graves’ disease
Stimulatory antibody to the
thyroidal TSH receptors swelling in the neck
Mucinous infiltration of the
dermal and subdermal layers:
pretibial myxedema showing
the coarsened, nodular,
infiltrated, pigmented lesions on
the lower extremities.
Graves’ disease
Ocular involvement is mediated by
one or more distinct but still poorly
characterised orbital-stimulating
immunoglobulins:Proptosis, due to
increased volume and edema of
retrobulbar fat. Shortened
extraocular muscles, because of the
muscle infiltration and fibrosis result
in upper lid retraction. Conjunctival
erythema, and periorbital edema are
evident.
Facial expression
The stare in hyperthyroidism
Hyperthyroidism - clinical features
• Associated directly with thyroid
hormone excess:
– Weight loss, heat intolerance due to
hypermetabolism
– Patients tend to be physically and mentally
hyperactive
– Supraventricular arrhythmias and precipitation
of cardiac failure
– Osteoporosis (increased bone turnover)
– Amenorrhoea (suppressed gonadotrophins)
Hyperthyroidism- clinical features
• Sympathetic potentiation
– Tachycardia
– Sweating
– Tremor
– Intestinal hypermotility
– Anxiety
• Extrathyroid manifestations
Graves’ disease - investigations
Isotopic uptake of tracer
doses of radioactive
iodine or technetium is
increased
Detection of thyroid
antibodies directed
against microsomal
thyroid cell antigens
Measurements TSH and
serum free T4 and T3
Hypothyroidism
• The most common cause
is the Hashimoto’s
thyroiditis, affects appr. 1%
of adult population
This woman demonstrates
the typical hypothyroid
facies. She also had a
slow, hoarse, deep voice
and lassitude (state of
feeling very tired in mind or
body).
• Dull, puffy facies. Edema
does not pit with pressure.
The lateral eyebrows are
thin.
Hypothyroidism –clinical features
• Generalized tiredness and lethargy
• Bradycardy, congestive cardiomyopathy,
occasionally pericardial effusion. ECG: low
voltage
• Muscle weackness, muscle cramps
• Depression, organic psychosis
• Dry and flaky skin, hair loss
• Weight gain
• The voice is deep and husky
Hypothyroidism
The treatment of patient with hypothyroidism is one of the most fruitful task for the
physician. A: before treatment, B: with adequate hormone supplementation
The adrenal cortex
• It secretes steroids which:
– Control either salt and water balance – mineralocorticoids
– Regulate metabolic processes – glucocorticoids
– Androgens and estrogens
• The adult adrenal cortex consists three relatively distinct
bands of cells
– The outermost layer – zone glomerulosa, expresses 18-hydroxylase
and 18-dehydrogenase activity – aldosteron production
– The middle zone – zone fasciculata, expresses the enzyme 17hydroxylase – cortisol and corticosterone production
– The innermost zone – zone reticularis – androgen (preandrogens)
production
Adrenal steroid biosynthesis
Cholesterol
Pregnenolon
17OH-Pregnenolon
DHEA
Progesterone
17OH-Progesterone
Androstenedione
DOC
11-desoxycortisol
ALDOSTERONE
CORTISOL
P450scc- side chain
cleaving
21-hydroxilase
3β-hydroxysteroid
dehydrogenase
17-hydroxilase and
17,20 liase
11β-hydroxilase, 18-hydroxylase and
18-hydroxydehydrogenase
Metabolic effects of glucocorticoids
• Carbohydrate metabolism
– Stimulates hepatic gluconeogenesis
– Increases deposition of glycogen in the liver
– Antagonizes the peripheral action of insulin on glucose uptake
• Protein metabolism
– Inhibits amino acid uptake and protein synthesis in extrahepatic
tissues
– Potent protein catabolic agent in peripheral tissues such as
muscle, skin, and bone
– Stimulates amino acid uptake of the liver which are
gluconeogenesis precursors
• Fat metabolism
– Increases mobilisation of fatty acids
– Stimulates the lypolysis in adipose tissue
– Increases the deposition of fat in the facial and truncal areas
Other effects of glucocorticoids
• Mineralocorticoid activity
– Mostly in case of cortisol excess
• Water metabolism
– Increases glomerular filtration rate, and negative feedback effect
on vasopressin
• Cardiovascular effect
– Potentiating the vasoconstrictor effect of other vasoactive
molecules such as catecholamins and even vasopressin
• Growth
– Inhibitory effect on somatotrophin release and direct inhibitory
action on insulin-like growth factor I production
• Response to stress
– Various stressors are associated with dramatic increase in the
blood concentrations of corticotrophin and cortisol
Cushing’s syndrome, prevalence
Cushing’ syndrome is a rare disease predominantly
affecting women in the age group 30 to 50 years
(The ectopic ACTH production occurs more frequently
in male patients because of the higher prevalence of
lung cancer)
• Incidence: 3.5/million/year
• Prevalence: 39/million
Causes of Cushing’s syndrome
Corticotrophin-dependent Cushing’s syndrome
•
Cushing’s disease
64%
•
Ectopic Cushing’s syndrome
13%
•
Ectopic CRH syndrome
1%
Corticotrophin-independent Cushing’s syndrome
•
Adrenal adenoma
10%
•
Adrenal carcinoma
8%
•
Adrenal hyperplasia
2%
Pseudo-Cushing’s syndrome
•
Depression
1%
•
Alcoholism
1%
Cushing’s syndrome – clinical
features
•
•
•
•
•
•
Proximal muscle weackness (steroid myopathy)
Back pain (osteoporosis)
Gain of weight
Excessive hair growth
Acne
Amenorrhea (suppression by cortisol of the
pitutary-ovarian axis)
• Hypertension (sodium and water retention)
• Hyperglykaemia (steroid induced
gluconeogenesis, peripheral insulin insensitivity)
• Increased proneness to bacterial infections
(immunosuppressive effects of steroids)
Cushing syndrome – purple striae
The purple striae are
found on lower abdomen,
upper arms and thighs,
which reflect the catabolic
effects on protein
structures in the skin.
The thinness and easy
bruising of the skin are
additional manifestations
of this process
Adrenocortical hypofunction
Primary deficiency due to disease of adrenal gland itself →
a decrease in the mineralocorticoid as well as
glucocorticoid hormone concentrations.
Incidence: 5/million/year ; Prevalence: 80/million.
Female/male: 1:0.7; between 30-60 years of age.
Addison’s disease with
hyperpigmentation
Courtesy of David N Orth MD. www. uptodate
Adrenocortical hypofunction
Clinical features
• Extreme muscular weakness and fatigue (characteristically at the night) due to
electrolyte abnormalities and hypoglykaemia
• Weight loss (anorexia, dehydration)
• Gastrointestinal symptoms: diarrhea, vomiting, abdominal pain
• Increased pigmentation (points of friction, palmar creases, buccal mucosa)
• Depigmentation reflecting an associated immunological abnormality
• Diziness (because of the orthostatic hypotension and hypoglykaemia)
• Depression, confusion even coma
• Salt-hunger
• Amenorrhea, decreased libido, impotency
• Anaemia
• Loss of body hair (because of androgen deficiency)
• Severe hyponatraemia – rhabdomyolysis, severe hyperkalaemia – tetraparesis
• Additional symptoms according to the underlying disease
Primary hyperaldosteronism
Clinical symptoms of classical aldosterone-producing
adenoma
• Hypertension (sodium and water retention and increased vascular
resistance).
• The treatments generally used in hypertensive patients are ineffective.
• Serious hypertensive complications.
• Headache (due to the hypervolaemia)
• Hypokalaemia is usually but not obligatory dominant feature of the clinical
presentation, giving rise to symptoms such as muscle weakness and polyuria,
psychiatric changes and cardiac arrythmias.
• Metabolic alkalosis
• Impaired glucose tolerance (direct effect of hypokalaemia on insulin secretion
or/and increased glucocorticoid effect)
• Mild hypernatraemia
• Oedema is characteristically rare due to the renal escape phenomenon
Polycystic ovary syndrome
• Approximately 10% of women
have polycystic ovary
syndrome (PCOS). Women
with PCOS experience
increased body hair
(hirsutism), increased weight
and infertility due to both lack
of ovulation and recurrent
miscarriage. In addition,
women with PCOS are subject
to a markedly increased risk of
heart disease, endometrial
cancer and possibly breast
cancer. If you have menstrual
irregularities, you may have
PCOS.
Hirsutism- acanthosis nigricans PCOS
Young woman with PCOS showing facial hirsutism (A) and axillary
acanthosis nigricans (B). The latter is associated with severe insulin
resistance and hyperinsulinaemia and is an occasional finding in PCOS
Gynecomastia
Excessive development of the mammary glands, even to
the functional state, in children or males.
Gynecomastia
The feminine type enlargement of male breast
The mean reason is higher estrogen/androgen ratio.
Physiological gynecomastia
1. in newborns
2. during the puberty
3. in elderly men (prevalence is more than 40%)
Pathological gynecomastia
1. Estrogen-producing adrenal and testis tumor
2. Increased aromatase activity (obesity, congenital)
3. hCG-producing testis, lung or liver tumor
4. Exogenous estrogen (prostatic carcinoma)
5. Hypogonadism (Klinefelter’s syndrome)
6. Systemic diseases: renal and,hepatic disorders, hyperthyroidism
7. Drugs (hormones, drugs with antiandrogen effect, sedativs,
8. Idiopathic (15%)
Inspection of the breast
• Examination of the breast includes careful
inspection for skin changes, symmetry, contours,
and retraction in four views:
– Arm at sides (skin color, symmetry, contour)
– Arm over head (dimpling or retraction of the breast in
this position suggest an underlying cancer)
– Arm pressed against hips (to contract the pectoral
muscles)
– Leaning forward (provocation of retraction nipple and
areola that suggest underlying cancer)
Acromegaly
Characteristic clinical appearance manifest by coarsening of facial
features due to an increase of connective tissue
Acromegaly
Alveolar bone
growth causes the
teeth to separate
The enlargement of the
frontal and maxillary
sinuses results in an
prominent brow and long
face
Growth of
mandible leads to a
jutting jaw
(prognathism).
Acromegaly
Macroglossia. There is
also generalized visceral
enlargement
Broadening and enlargement
of the hands and feet due to
increased periosteal growth as
well as thickening of the skin
Acromegaly- clinical features
• Hypertension (related to sodium and water
retention)
• Anatomical effects of the pituitary tumor on
neighbouring structures
• Joint pain (due to associated synovial
hypertrophy and degenerative arthritis)
• Excessive sweating (direct effect of growth
hormone)
• Paraesthesiae of hands and feet because of the
nerve entrapment by thickened bone and
subcutaneous tissue
• Headache (sensory nerve entrapment)