Physical signs of most common endocrine diseases Dr. Szathmári Miklós Semmelweis University First Department of Medicine 05. December 2011.

Physical signs of most common endocrine diseases

Dr. Szathmári MiklósSemmelweis University

First Department of Medicine05. 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 expressionThe 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 populationThis 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 17-

hydroxylase – cortisol and corticosterone production– The innermost zone – zone reticularis – androgen (preandrogens)

production

Adrenal steroid biosynthesisCholesterol

Pregnenolon 17OH-Pregnenolon DHEA

Progesterone 17OH-Progesterone Androstenedione

DOC 11-desoxycortisol

ALDOSTERONE CORTISOL

P450scc- side chain cleaving

3β-hydroxysteroid dehydrogenase

21-hydroxilase 11β-hydroxilase, 18-hydroxylase and 18-hydroxydehydrogenase

17-hydroxilase and 17,20 liase

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 hypofunctionClinical 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 hyperaldosteronismClinical 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.

GynecomastiaThe 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

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).

Alveolar bone growth causes the teeth to separate

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)