Download Benacka - Endocrinology 2

Academic lectures for general medicine – 3rd year
2005/2006, 2006/2007
Thyroid gland – anatomy and physiology
§ Largest Endocrine organ in the body
§ Involved in production, storage, and
release of thyroid hormone
ENDOCRINOLOGY 2
§ Function influenced by
§ Central axis (TRH)
§ Pituitary function (TSH)
§ Comorbid diseases (Cirrhosis,
Graves, etc.)
§ Environmental factors (iodine
intake)
R. Benacka, MD, PhD
Department of Pathophysiology
Medical faculty, Safarik University, Košice
Figures and tables in this presentation were adopted from various printed and
electronic resorces and serve strictly for educational purposes.
Thyroid gland
§ Physiological review
§ Hyperthyroidism
§ Congenital hypothyreoidism
§ Hyperthyreoidism in adulthood
§ Regulates basal metabolic rate
§ Improves cardiac contractility
§ Increases the gain of catecholamines
§ Increases bowel motility
§ Increases speed of muscle
contraction
§ Decreases cholesterol (LDL)
§ Required for proper fetal neural
growth
Thyroid gland – anatomy and physiology
§ Thyroid gland: follicles formed by
epithelial cells synthetizing,
storing, secreting thyroxine (T4)
and triiodothyronine (T3) in
response to TSH.
§ Thyroid gland actively takes up
iodine, iondinates tyrosine (MIT =
monoiodotyrosine, DIT =
diiodotyrosine), couples these
together to form T4 and T3 and
stores them linked to TG
(thyroglobulin) in the thyroid
follicle.
§ T3 (10% of total amount) and T4
(90%) are released into blood
where these are bound to
Transthyrenin, pre-albumin,
albumin
Physiologic Effects of Thyroid Hormones
Target Tissue Effect
Heart
Etiologic Classification
Mechanism
Chronotropic
Increase number and affinity of adrenergic receptors.
Inotropic
Enhance responses to circulating catecholamines.
Increase proportion of alpha-myosin heavy chain (with
higher ATPase activity).
Adipose
tissue
Catabolic
Stimulate lipolysis.
Muscle
Catabolic
Increase protein breakdown.
Bone
Nervous
system
Developmental and Promote normal growth and skeletal development;
metabolic
accelerate bone turnover.
Developmental
Hyperthyroidism: Causes
Promote normal brain development.
Gut
Metabolic
Increase rate of carbohydrate absorption.
Lipoprotein
Metabolic
Stimulate formation of LDL receptors.
Other
Calorigenic
Stimulate oxygen consumption by metabolically active
tissues (exceptions: adult brain, testes, uterus, lymph
nodes, spleen, anterior pituitary).
Increase metabolic rate.
Pathogenetic Mechanism
Thyroid hormone overproduction
Graves' disease
Thyroid-stimulating hormone receptor-stimulating
antibody (TSH-R [stim] Ab)
Toxic multinodular goiter
Autonomous hyperfunction
Follicular adenoma
Autonomous hyperfunction
Pituitary adenoma
TSH hypersecretion (rare)
Pituitary insensitivity
Resistance to thyroid hormone (rare)
Hypothalamic disease
Excess TRH production
Germ cell tumors: choriocarcinoma,
hydatidiform mole
Human chorionic gonadotropin stimulation
Struma ovarii (ovarian teratoma)
Functioning thyroid elements
Metastatic follicular thyroid carcinoma
Functioning metastases
Thyroid gland destruction
Lymphocytic thyroiditis
Release of stored hormone
Granulomatous (subacute) thyroiditis
Release of stored hormone
Hashimoto's thyroiditis
Transient release of stored hormone
Other
Thyrotoxicosis medicamentosa, factitia Ingestion of excessive exogenous thyroid hormone
Autoimmune Disorders Associated with Graves' Disease and
Hashimoto's Thyroiditis
Hypertyroidism
§ Endocrine disorders
§ Diabetes mellitus
§ Hypoadrenalism, autoimmune (Addison's disease)
§ Orchitis or oophoritis, autoimmune
§ Hypoparathyroidism, idiopathic
§ Nonendocrine disorders
§ Pernicious anemia
§ Vitiligo
§ Systemic lupus erythematosus
§ Rheumatoid arthritis
§ Immune thrombocytopenic purpura
§ Myasthenia gravis
§ Sjögren's syndrome
§ Primary biliary cirrhosis
§ Chronic active hepatitis
Graves disease
Clinical findings in hyperthyroidism
§ Symptoms
§ Alertness, emotional lability, nervousness, irritability, poor concentration
§ Proximal muscle weakness (quadriceps), fatigability
§ Hyperkinesia, fine tremor, rapid speech,
§ Palpitations, tachycardia, atrial fibrillation (resistant to digitalis), widened
§ Most common cause of hyperthyroidism
§ Result of anti-TSH receptor antibodies
§ Diagnosis
§ Symptoms of hyperthyroidism
§ Clinical exopthalmos and goiter
§ Low TSH, normal/high FT4, anti-TSH
pulse pressure, accentuated first heart sound; Dyspnea
§ Voracious appetite, weight loss,
§ Hyperdefecation (increased frequency of bowel movements)
§ Sweating, skin is fine, moist, warm; heat intolerance; fine & abundant
Ab (Optional)
§ If no clinical findings I123 may demonstrate
hair; onycholysis
increased uptake.
§ Periorbital edema, lid lag, proptosis, stare, chemosis
§ Treatments
§ Medical – Propothyouracil,
§ Laboratory findings
§ Suppressed serum TSH level
§ Elevated serum free thyroxine, elevated serum total T4, elevated resin T3
Methimazole, Propranolol
§ Surgical – Subtotal Thyroidectomy
§ Radiation – RAI ablation [I131(µCi/g) x
or T4 uptake, elevated free thyroxine index
§ Increased radioiodine uptake by thyroid gland (some causes)
§ Increased basal metabolic rate (BMR)
§ Decreased serum cholesterol level
weight / %RAIU]
Graves disease
Hypertyroidism - symptoms
§ Alertness, emotional lability, nervousness,
irritability, poor concentration
§ Proximal muscle weakness (quadriceps,
biceps), fatigability
§ Hyperkinesia; rapid speech; fine tremor,
§ Tachycardia, palpitations, widened pulse
pressure, accentuated first heart sound;
Graves' dermopathy lumpy, reddish thickening
of the skin (accumulation
of proteins).
§ Dyspnea
§ Voracious appetite, weight loss
§ Hyperdefecation (increased frequency of
bowel movements)
§ Sweating, skin is fine, moist, warm;;
Graves' acropachy (watch glass
nail shape
Exopthalmic goiter in 5y - old girl.
Common in adults very rare in kids.
Symptoms: nervousness, bulging of the eyes
tachycardia, underweight, enlarged thyroid
onycholysis; Fine & abundant hair;
§ Exopthlamos; periorbital edema, lid lag,
proptosis, staring
§ Heat intolerance
Histological comparison
Hypotyroidism
Etiological comparison
Congenital hypopituitarism
§ Retardation, short stature,
swelling of face/hands,
possible deafness
§ Cool skin, dry skin, swelling of
face/hands/legs, slow reflexes
Types of Hypothyroidism
Primary – Thyroid gland
failure
Secondary – Pituitary
failure
Tertiary – Hypothalamic
failure
Peripheral resistance
Congenital cretinism
Endemic goitre and cretinism in Bolivia. The
mother is goitrous but otherwise normal. The
daughter is goitrous, mentally retarded, deaf mute,
but of normal stature and clinically euthyroid.
Postpubertal hypothyroidism - myxedema
§ Symptoms
§ Decreased vigor, lethargy, slow thinking, mental
clouding, depression
§ Round puffy face; periorbital edema,
§ Enlarged tongue, slow speech; hoarseness,
§ Cold, dry, thick, scaling skin; dry, coarse,
brittle thickened hair; hair loss; longitudinally
ridged nails; feeling cold, cold intolerance
§ Cause is determined by geography
§ Diagnosis
§ Low FT4, High TSH (Primary,
check for antibodies)
§ Low FT4, Low TSH (Secondary
or Tertiary, TRH stimulation test,
MRI)
§ Loss of appetite; weight gain, constipation
§ Ascites; pericardial effusion; ankle edema
§ Menorrhagia; diminished libido
§ Hypokinesia; generalized muscle weakness;
§ Treatment
§ Levothyroxine (T4) due to longer
delayed relaxation of deep tendon reflexes
cardiomyopathy, myxedema
§ Cardiac enlargement; bradycardia, indistinct
half life
§ Treatment prevents bone loss,
heart sounds
Post-operative myxedema.
Basal metabolic rate 40%
§ Laboratory findings
§ Increased serum TSH level
§ Decreased serum free thyroxine, decreased
serum total T4 and T3 decreased T3 or T4
uptake; decreased free thyroxine index
Symptomatology
§ Decreased vigor, lethargy, slow thinking,
mental clouding, depression
§ Fatigability, coldness, weight gain,
constipation, low voice
§ Round puffy face; periorbital edema,
§
§
§
§
§
§
§
§
swelling of face/hands/legs, slow reflexes,
myxedema
Enlarged tongue, slow speech; hoarseness,
Cold, dry, thick, scaling skin; Feeling cold,
cold intolerance
Dry, coarse, brittle thickened hair; hair loss;
longitudinally ridged nails;
Loss of appetite; weight gain, constipation
Ascites; pericardial effusion; ankle edema
Menorrhagia; diminished libido
Hypokinesia; generalized muscle weakness;
delayed relaxation of deep tendon reflexes
Cardiac enlargement; bradycardia, indistinct
heart sounds
Goiter
Goiter
§ Endemic goiter
§ Caused by dietary deficiency of Iodide
§ Increased TSH stimulates gland
growth
§ Also results in cretinism
§ Goiter in developed countries
§ Hashimoto’s thryoiditis
§ Subacute thyroiditis
§ Other causes
§ Excess Iodide (Amiodarone, Kelp,
Lithium)
§ Adenoma, Malignancy
§ Genetic / Familial hormone synthesis
defects
Etiology of goiter
I. Goiter associated with hypothyroidism & euthyroidism
§ Iodine turnover
§ Iodine deficiency; defective transport of iodide (hormone biosynthesis);
§ Iodine excess (secretion of hormone)
§ Hormone biosynthesis
§ Defective organification of iodide : absence or reduction of peroxidase or
production of an abnormal peroxidase
§ Thyroglobulin (TG): synthesis of an abnormal TG; impaired proteolysis of TG
§ Iodotyrosine : abnormal interrelationships; defective deiodination
§ Congenital disorders
§ Exogenous substances and drugs (hormone biosynthesis)
§ Goitrogen in diet , drinking water or medication
§ Thioamides (propylthiouracil, methimazole, carbimazole), Thiocyanates
(nitroprusside), Aniline derivatives (sulfonylureas, sulfonamides, aminosalicylic
acid, phenylbutazone, aminoglutethimide)
§ Lithium (secretion of hormone)
§ Resistance
§ Pituitary and peripheral resistance to thyroid hormone (receptor defects)
II. Goiter associated with hyperthyroidism
§ Graves' disease
§ Toxic multinodular goiter
§ Germ cell tumor
§ Pituitary adenoma
§ Thyroiditis
(TSH-R [stim] Ab stimulation of gland)
(Autonomous hyperfunction)
(hCG stimulation of gland)
(TSH overproduction)
("injury" due to infiltration, and edema)
Thyroid storm
§ Causes
§ Surgery, Radioactive Iodine, Therapy, Severe Illness
§ Diagnosis
§ Clinical – tachycardia, hyperpyrexia, thyrotoxicosis symptoms
§ Labs (Low TSH, High T4, FT4)
§ Treatment
§ Propranolol IV vs. Verapamil IV, Propylthiouracil, Methimazole
§ Sodium Iodide, Acetamenophen, cooling blankets
§ Plasmapheresis (rare), Surgical (rare)
Euthyroid Sickness
§ Cause is an inactivation of 5’-deiodinase,
resulting in conversion of FT4 to rT3.
§ Occurs in critically ill patients; may occur
with DM, malnutrition, iodine loads, or
medications (Amiodarone, PTU,
glucocorticoids)
§ Treatment
§ Avoid above medications
§ Treat primary illness
§ T3, T4 not helpful
Anatomical overview
Suprarenal cortex
§ Physiological overview
§ Hypercortisolism- Cushing syndrome
§ Hypocortisolism – Addison disease
§ zona glomerulosa - 15% of the
cortex aldosterone production is
stimulated by angiotensin and
potassium, and inhibited by atrial
natriuretic peptide and somatostatin.
§ zona fasciculata - 75% of the cortex.
glucocorticoids under the control of
ACTH
§ zona reticularis –
glucocorticosteroids, weak androgen
– S- DHEA
§ Ectopic adrenal tissue retroperitoneum, broad ligament near
the ovary, near the epididymis, lung,
and liver. Ectopic adrenal tissue does
not contain medullary cells.
Hormone synthesis
§ pyramidal organs found
anteriorly above each kidney.
§ each gland is 4 to 6 cm in
greatest dimension and
weighs about 4 g
Cortisol effects
Hypercorticism - Cushing syndrome
Note the wide (> 1 cm) purplish abdominal striae in
Cushing's syndrome
Cushing syndrome - symptoms
§ Obesity of the face (moon face), neck (buffalo
hump), trunk, and abdomen; extremities are even
wasted (spider); skin is atrophic; fat decreased.
§ Enlargement of the abdomen fat deposition
stretches the thin skin and produces purplish
striae,
§ Skin - atrophic; hyperpigmentation (POMC).
Acanthosis nigricans
§ Bone resorption – osteoporosis, fractures of ribs,
occ. long bones, vertebral fractures + back pain.
§ Proximal muscle wasting (steroid myopathy) weakness (severe)
Hypercortisolism
§ Hypertension (excessive mineralocorticoid
activity), congestive heart failureincreased
intraocular pressure (1/4)
§ Sex: women (virilism) - increased facial hair,
thinning of scalp hair, acne, and oligomenorrhea.
men - erectile dysfunction, decreased libido.
§ Hyperglycaemia + hyperinsulinemia. (steroid
diabetes in 15% of patients)
§ Personality changes (irritability, emotional lability,
depression, and paranoia, suicide.
Hypercortisolism
Hypocorticism – Addison disease
§ Laboratory - absolute lymphopenia (2/3),
abnormally low eosinophils (1/3). Hypercalciuria is
common, although serum calcium levels remain
unchanged. Serum cholesterol and triglyceride
levels are frequently elevated.
§ Increased glucocorticoid levels + dexamethasone
suppression test distinguishes ACTH-dependent
and ACTH-independent forms of Cushing sy.
Dexamethasone suppresses pituitary ACTH
secretion, and hence hypercortisolism, whereas it
is without effect on adrenal tumors.
Woman with ACTH - adenoma
§ Cushing syndrome is treated by (1) extirpation
(surgery or irradiation) of pituitary, adrenal, or
ectopic ACTH-producing tumors; (2)
discontinuation of corticosteroid therapy; or (3)
administration of adrenal enzyme inhibitors (e.g.,
aminoglutethimide, ketoconazole, metapyrone).
With the exception of ectopic ACTH syndrome
and adrenal carcinoma, in which patients die of
cancer rather than of hypercortisolism, Cushing
syndrome is highly curable.
Nelson’s syndrome after treatment of
Cushing’s disease by bilateral adrenalectomy.
Hypocorticism
Aldosteron
effects