General Introduction of Endocrinology Second messenger: cAMP is act as a second messenger by

accepting the information offered by the hormone-receptor

complex and transmitting it to its molecular destination within the
Endocrine: the process of secretion of biologically active
cell
substance

Hormone: is a substance that is secreted by cell and travels Disorder of the endocrine:
through circulation
Hormone Deficiency Hormone excess Multiple endocrine
syndrome syndrome
Receptor: is a molecule to which the hormone binds to elicit its
action. It has two functions: 1.Must be able to distinguish hormone Hypofunction of Hyperfunction of
& bind with its; 2. Must be able to transmit information & trigger a Endocrine Glands Endocrine Glands Multiple endocrine
cellular response deficiencies
Hormone Deficiency Ectopic Hormone
Classification: Secondary to Production Multiple endocrine
Extraglandular neoplasia (MEN)
 Peptides & protein (most of hormone in the body - hormones Disorders Hormone
Administration (for
of the hypothalamus, pituitary gland, parathyroid glands,
Hyporesponsiveness to treatment e.g. cortisol
gastrointestinal tract, and pancreas) hormones treatment)

 Amino acid derivatives (T3,T4) Abnormal Production Tissue

or Administration of Hypersensitivity
 Steroid hormone (Include hormones of the adrenal cortex, Antagonists
gonads (ovary and testes), and placenta and active vitamin D) Autoimmune Disease

Hormone Biosynthetic
Mechanism of hormone action
or metabolic defects
 Through the cell membrane receptor (use cAMP as a “second Secondary Hormone
messenger” to transmit information to its molecular Hypersecretion
destination within the cell)

 Through cytoplasmic or nucleus receptor (diffuse freely

across the cell membrane due to their small size)
Hormone regulation
 The relationship between the nervous and endocrinology
(brain & pituitary also produce hormone)
 Hormone release often has rhythmic pattern (Day-night
rhythms-GH & monthly rhythms-esterogen)
Ectopic hormone syndrome: Hormone may be produced in
excess by cells of endocrine or non-endocrine origin that are not
normally the primary source of a hormone. (E.g. small-cell lung
carcinoma can produce the ACTH)
Multiple endocrine neoplasia (MEN): is condition in which arise
from at least three syndromes of multiple endocrine hyperfunction
result from hyperplasia, adenomas, or carcinomas of endocrine
tissues. MEN includes 3 types: (1,2a,2b)

 Specific stimuli received by the endocrine cells cause them to Type1 is associated Type2a is associated Type2b is associated
increase their hormone secretion (e.g. glucose induce insulin with Hyperfunction with with medullary thyroid
release from adrenal cortex) of parathyroid, pheochromocytoma, carcinoma,
pancreatic islets medullary carcinoma of pheochromocytoma, and
and pituitary. thyroid, parathyroid other features such as
 Some stimuli decrease hormone (GHIH released by carcinoma. neuromas
hypothalamus decreased the amount of GH released by
anterior pituitary gland)

 The concentration of the secreted hormone in the blood,

and /or the effects produced by the hormone , control
subsequent secretion of the hormone (Negative & positive
feedback)

Negative feedback (most common regulatory loop): the level of

hormones in circulation or the response produced by the hormone
negates or reverses the original stimulus, decrease the secretion of
their stimulating hormone (ACTH stimulates release of cortisol
which inhibit ACTH release)

Positive feedback: response augments rather than attenuates the

stimulus (in pregnancy feto-placental unit, produces increasing
amounts of the steroid hormones estrogen and progesterone)
 Hypopituitarism Specific symptom & sign of hormonal deficiency:

Pituitary main hormone production: General:

Anterior:  Hypogonadism and infertility

 ACTH (Adenocoticotropic hormone) → ↑adrenal steroid  Lose axillary, pubic, and body hair
genesis & cause pigmentation gradually, particularly if they are also
hypoadrenal
 GH → promote bone, muscle growth, carbohydrates & fat
 Appear more early in the process of this
metabolism
disease

 PRL (Prolactin) → promote milk production Women:

 FSH (Follicle stimulating hormone) & LH (Luteinnizing  Hypogonadism → infertility & decreased
hormone) → stimulates testes/ovaries & sex hormone Estradiol secretion
synthesize
 Estradiol deficiency (after puberty) →
 TSH (Thyroid stimulating hormone) → stimulate thyroid Amenorrhea, reduction in breast size, a
hormone production Gonadotropin decrease in general sense of well-being
deficiency and ,if the deficiency is severe, vasomotor
instability (hot flashes) and vaginal dryness
Posterior:
(Loss of LH & FSH) happen

 Oxytocin → stimulate uterine & milk ejection  Estradiol deficiency (prior to puberty) →
incomplete puberty
 ADH → Antideuretic hormone
Men:
Hypopituitarism definition: Impairment of anterior pituitary or
hypothalamus leads to hyposecretion of anterior pituitary hormone;  Hypogonadism → decreased sperm
present itself with related target gland hypofunction production and those of decreased
testosterone secretion
 Primary Hypopituitarism is caused by anterior pituitary  Testosterone deficiency (after puberty) →
hypofunction energy and libido decrease within weeks,
and men may note diminished beard
 Secondary Hypopituitarism is caused by diseases which affect growth
hypothalamus
 Testosterone deficiency (prior to puberty)
Etiology: → incomplete puberty

 Mass lesions (common cause): Pituitary tumor, aneurysms,

metastatic carcinoma, granulomas, pituitary abscess, apoplexy TSH deficiency Hypothyroidism → fatigue, weakness, weight
(bleeding). change (weight gain), cold intolerance, dry
skin, constipation, and hyperlipidemia.
 Other: Autoimmune hypophysitis, postpartum pituitary
necrosis (Sheehan’s syndrome), Idiopathic disease, Trauma,
Radiation, Surgery (common), Encephalitis, Diminished cortisol secretion → weakness,
fatigues, weight loss, and hypotension (Mild
Hemochromatosis, Autoimmunity, Stroke. cortisol deficiency may asymptomatic)
ACTH deficiency
General symptoms and signs: Only cortisol deficiency due to primary adrenal
disease can cause hyperpigmentation, not due
to ACTH deficiency one.
Weakness Easy Axillary 、 Lack of
fatigability pubic hair loss resistance to
stress, cold, GH deficiency Obesity (in adult)
and fasting
Sex Weight loss Low BP Lower bone mineral density
hypofunction

Other symptoms & sign:
 Panhypopituitarism (absence of all anterior pituitary
hormones) → Above manifestation + (long-standing
Hypopituitarism) dry, pale, finely textured skin. The face has
fine wrinkles and an apathetic countenance.
 The patients with pituitary tumors → may have headache,
visual impairment.
Lab findings:
 Biochemical indicator:
 Low fasting blood glucose
 Hyponatremia
 Hyperkalemia does not occurs because aldosterone
production is not affected
 Hormones determine:
 Low plasma sex level (testosterone & estradiol) & low
gonadotropin
 Elevated prolactin levels (in patients with prolactinoma,
acromegaly, and hypothalamic disease), but in most case
the prolactin is low because of lactotroph impairment
 Low Free T4 & TSH is not elevated
 11-deoxycortisol or cortisol concentration level is low
 ACTH level is low or normal in secondary hypoadrenalism
 Stimulating test (Cosyntropin test in secondary
hypoadrenalism)
 Administration of cosyntropin (synthetic ACTH1-24), IM/IV
0.25mg usually causes serum cortisol to rise to less than
20µg/dL by 30-60m after the injection.
 A low-dose cosyntropin test (0.001 mg IV) is slightly more
sensitive in detecting subtle ACTH – cortisol insufficiency
 GH deficiency detecting
 The insulin hypoglycemia test (most accurately but it’s
dangerous for elderly of seizure prone patients)
 IGF-I levels may be low in GH deficiency, but there is
considerable overlap with normal
Other examination → MRI
Differential diagnosis
 Reversible physiologic hypogonadotropic Hypogonadism: The
disease may occur during any serious illness and with
malnutrition. (Normal sex hair, normal adrenal and thyroid
function)
 Primary adrenal or thyroid insufficiency: Serum ACTH and
TSH are not elevated in Hypopituitarism
 Severe illness causes functional suppression of TSH &
thyroxine: Glucocorticoids or megestrol treatment reversibly
suppresses endogenous ACTH and cortisol secretion.
 Multiple endocrine deficiencies: Involve immunologic
destruction of pancreatic islets, thyroid, adrenals, and gonads
(Schimdit Syndrome) → (elevated pituitary hormone →
ACTH, TSH, FSH, LH level are high)
Complication
 Destructive lesions (e.g., tumors) → may develop
complication due to surgery or radiation therapy.
 Untreated hypoadrenalism and a stressful illness → febrile
and die in shock and coma.
 Adults with growth hormone deficiency → ↑cardiovascular
morbidity
 Pituitary acute hemorrhage (occur in large pituitary tumors)
→ rapid loss of vision, headache, and evidence of acute
pituitary failure
Treatment
Lifetime hormone replacement
ACTH replacement
 Oral hydrocortisone 15-25mg/d (devided dose → 15mg in the
morning & 5mg in the late afternoon)
 During states of (e.g. infection, trauma or surgical procedures)
→ Give additional hydrocortisone (50 mg IM/IV every 6
hours and then reduced to normal doses as the stress subsides)
 Mild illness → corticosteroid doses are doubled or tripled
Most common use corticosteroid
Hydrocortisone (20mg) Cortisone (25mg) Prednisone (5mg)
Thyroid replacement
Levothyroxine (0.125 mg/d) → to correct hypothyroidism only
after the patient is assessed for cortisol deficiency or is already
receiving glucocorticoids.
Sex hormone replacement
Adult → subcutaneous somatotropin injection starting at a
dosage of about 0.2 mg (0.6 IU) three times weekly or daily. The
dosage is increased until side effects occur.
Emergency Acute Hypopituitarism
When patient exposed to stress (e.g. infection, surgery or
dehydration and so on) which induce body to need more pituitary
hormone
Clinical finding Adrenal cortex steroid hormone

 Hypotension /shock  Aldosterone: Aldosterone promotes sodium and water

absorption and potassium excretion in the kidney tubules.
 Weakness, apathy, confusion
 Sex hormone (e.g. androgen): growth of hair follicle
 Nausea, vomitting, anorexia
 Cortisol: Cortisol affects the body’s response to stress,
 Dehydraton, hypovolemia,
emotional stability, immune function and carbohydrate,
 Water intoxication (the formation and excretion of urine protein and fat metabolism.
is difficult)
Steroid hormone actions
 Hyperthermia(>40℃) or hypothermia(<30℃)
 Amino acid catabolism (muscle wasting) → gluconeogenesis
 Hypoglycemia in the liver → Hyperglycemia → increased insulin output →
eventual beta cell failure → fat deposition → diabetes
Treatment
 Ca resorption, impairment of Ca absorbtion, ↑ renal Ca
 IV saline & glucose. At first giving 50% glucose to treat excretion → osteoporosis
hypoglycemia; then follow by 10% Glucose & Sodium
Chloride Injection continues.  ↑ gastric acidity → ulcer formation or aggravation

 Hydrocortisol 200-300mg/d if progress is satisfactory
and then taper to oral maintenance dose by day 4 or 5.
 Amelioration Hyperthermia or hypothermia. When T↑ to
350C → levothyroxine.
 K loss and Na retention → edema & hypertension
 Initially increased antibody release → Eventually decreased
antibody production, lymphocytopenia, eosinopenia,
neutrophelia, polycythemia → susceptibility to infections

 Correction of remote causes (e.g. preventing and cure of  Maintenance of arteriolar tone and blood pressure
infection)
Natural & synthetic adrenocorticosteroids
 The patients with water intoxication must be given
cortisol IV infusion or intake water is confined. Glococorticoids Antiinflamation Self retaining

 All drugs about sleeping and calm are inhibited. Short acting hydrocortisone, + +
cortisone

prednisone, ++ ++
prednisolone,
methylprednisolone

Intermediate triamcinolone ++
acting
fluprednisolone ++++

Long acting deoxycorticosterone ++++

Mineralocorticoids + ++++
deoxycorticosterone

Cushing’s syndrome
Adrenal disease
Definition:
Adrenal hormone production
Cushing’s syndrome is hypercortisolism of any etiology, due to
Zona glomerulosa Zona fasciculata Zona reticularis adrenal gland secreting excessive cortisol or by cortisol therapy.

Aldosterone → Cortisol → regulate Androstenedione & Cushing’s disease refers to hypercortisolism resulting from
regulate Na+ and K+ glucose metabolism DHEA → pituitary over-secretion of ACTH.
balance supplement sex
steroids.
  Buffo hump → appears due to accumulation of fat around
the neck (supraclavicular & dorsocervical fat pad)
Etiology:
 Plethoric → thinning and transparent appearance of the skin
1) ACTH-dependent Cushing's syndrome due to atrophy of the epidermis & its underlying connective
tissue (appears in advance stage)
2) ACTH-independent Cushing's syndrome
 Striae → appears due to rapid weight gain
Cause Frequency
 Easy bruisability, slow & poor healing, mucocutaneous
fungal infection → frequently appears
ACTH-dependent (85%) Cushing’s disease 70%
 Hyperpigmentation → rarely presence in Cushing’s
Ectopic ACTH 15%
syndrome
syndrome or adrenal tumor, but common in Ectopic ACTH
syndrome
Adrenal adenoma !5%
 Hirsutism → appear in female due to hypersecretion of
ACTH-independent (15%) Adrenal carcinoma 10% adrenal androgen

Iatrogenic 10%  Hypertension → together with its complication contribute

greatly to morbidity and mortality in spontaneous
Cushing’s syndrome
Clinical manifestation:  Gonadal dysfunction → appears due to elevated levels of
androgens and cortisol
Typical finding:
Diagnosis
 Increase body weight (94%)
General test
 Central obesity with a plethoric moon face (97%)

 Buffalo hump  Glucose tolerance is impaired

 Supraclavicular fat pads  Leukocytosis with relative granulocytosis and

lymphopenia
 Protuberant abdomen
 Hypokalemia particularly in cases of ectopic ACTH
 Thin extremities secretion

Major clinical: Hypercortisolism test

 Muscular weakness, especially proximal (87%)
 Malaise
 Psychological disturbance: Anxiety, emotional lability,
increase irritability decrease concentration, poor memory,
depression and psychosis (66%)
 Hirsuties (80%)
 Striae, acne, skin-thinning, bruising (67%)
 Poluuria, nocturia
 Gonadal dysfunction: Oligomenorrhoea or amenorrhoea
in female (77%); Decreased libido and impotence in males
 The easiest screening test for hypercortisolism: Giving
dexamethasone at 11PM (1 mg orally) follow by collecting
serum for cortisol determination at about 8 AM the next
morning (if cortisol level <5 µg/dL excludes Cushing's
syndrome with 98% certainty)
 A 24-hour urine collection for free cortisol and creatinine:
An abnormally high 24-hour urine free cortisol (or free
cortisol to creatinine ratio of > 95 mg cortisol/g creatinine)
helps confirm hypercortisolism.
 Serum cortisol level is high: especially in midnight serum
cortisol level >7.5 ug/dL is indicative of Cushing's syndrome
and distinguishes it from other conditions associated with a
high urine free cortisol (pseudo-Cushing states)

 Hypertension (75-85%)  Small dose dexamethasone suppression test: Giving

dexamethasone, 0.5 mg orally every 6 hours for 48
 diabetes or impaired glucose tolerance hours,urine is collected on the second day (if Urine free
cortisol > 20ug/d or urine 17-hydroxycorticosteroid > 4.5
mg/d → hypercortisolism)
Notes:

 Central obesity → effecting mainly face, neck, trunk, & Causative test
abdomen with elative spring extremities
  Baseline plasma ACTH: if ↓ than normal range (20pg/mL) =
probable of adrenal tumor; if ↑than normal range = probable  Osteoporosis, Ectopic ACTH hypersecretion
of pituitary or ectopic tumor hypertension, poor wound
healing.  Caused by ACTH hpersecretion
 Big dose dexamethasone suppression test: Giving from nonpituitary tumors.
dexamethasone, 2 mg orally every 6 hours for 48 hours,urine Lab test
is collected on the second day (if Urine free cortisol decrease  Hyperpigmentation in most of
amplitutde >50% indicates secretion of cortisol is suppressed)  Hyperglycemia, cases .
→ Adrenal tumor & ectopic ACTh neoplasm can’t be glycosuria, leukocytosis,
inhibited lymphocytopenia, hypokalemia
 The secretion of cortisol can’t be
inhibited by big dose
 Elevated serum cortisol
 Imaging: CT can localize adrenal tumor in most cases; Ct dexamethasone suppression test
and urinary free cortisol. Lack of
also can localize ectopic source of ACTH (lung, thymus, normal suppression by
pancreas); MRI can demonstratr pituitary adenoma in about dexamethasone.
50% (because some pituitary tumor are very small), PET can Cushing’s syndrome
found concentration of corticol
 There is a hyperscretion of
Notes: cortisol with the hyposecretion of
ACTH.

 Certain drugs such as phenytoin, phenobarbital, and

 Adrenal tumor is present in most
primidone accelerate the metabolism of dexamethasone→ of patients
false-positive dexamethasone suppression test.
 The secretion of cortisol can’t be
 Estrogens-during pregnancy or as oral contraceptives or inhibited by big dose
dexamethasone suppression test .
estrogen replacement therapy-may also cause lack of
dexamethasone suppressibility → in pregnancy urine free
cortisol ↑, while 17-hydroxycorticosteroids remain normal
and diurnal variability of serum cortisol is normal
Complication
Differential diagnosis
 Morbidity & mortality → if untreated
 Severe obesity → normal urine free cortisol
 Complication of hypertension or diabetes
 Familial cortisol resistance → have hyperandrogenism,
hypertension, & hypercortisolism  Susceptible to infection

 Alcoholism → mimic to hypercortisolism, will revert to  Compression fracture of osteoporotic spine & aseptic necrosis
normal after cessation of alcohol intake of femoral head

 Depressed patient → no clinical signs of Cushing’s syndrome  Nephrolithiasis & psychosis

 Nelson’s syndrome → Following bilateral adrenalectomy for

Cushing's disease, a pituitary adenoma may enlarge
progressively, causing local destruction (eg, visual field
impairment) and hyperpigmentation

Treatment (Directed at pituitary to control ACTH hypersecretion)

Essential diagnosis
Microsurgery - Radio therapy - ACTH secretion inhibition drugs

Symptom & sign
 Central obesity, muscle
wasting. thin skin, easy
bruisability, psychologic
changes, hirsutism (cancer),
purple striae.
Cushing ’s disease
 hypersecretion of ACTH with
bilateral adrenocortical
hyperplasia and hypersecretion
of cortisol
 absent circadian periodicity of
ACTH and cortisol release
Surgery (to remove causative agent (e.g. tumor)) follow by
hormone replacement post-operatively to avoid adrenal
insufficiency
Addison’s Diseases (Adrenocortical insufficiency)
Definition: is an uncommon disorder caused by destruction or
dysfunction of the adrenal cortices, It is characterized by chronic
deficiency of cortisol, and /or aldosterone, adrenal androgens.
  Primary adrenocortical insufficiency → resulting from  Other → small heart, hyperplasia of lymphoid tissue, scant
destruction or damage to adrenal cortex axillary & pubic hair and amenorrhea

 Secondary adrenocortical insufficiency → resulting secondary Lab finding

to pituitary ACTH secretion
 Ordinary lab features for primary adrenocortical
insufficiency

Etiology Hyponatremia Azotemia Hypoglycemia

(90%)
 Idiopathic/Autoimmune (80%): Addison’s disease + other
autoimmune endocrine disorder (e.g. hypoparathyroidism, Hyperkalemia Lymphocytosis Hypercalcemia
autoimmune thyroid disease, type 1 diabetes) → calls (PGA) (65%)
Polyglandular autoimmune syndrome or Schimdit syndrome
Increased plasma renin activity
 TB
Elevations of BUN & creatinine levels → dehydration and
 Adrenoleukodystrophy → X linked peroxisomal disorder hemoconcentration

 Bilateral adrenal hemorrhage → occurs in patients taking

anticoagulang (clinical: pain, fever, & shock)  Specific lab features for primary adrenocortical insufficiency

 Other (1%) → fungal infection, AIDS, various tumor  Basal levels of Urine or Plasma cortisol (Low or normal)
metastases, Tumor treatment, congenital disease (hereditary
cortisol deficiency)  Basal Plasma ACTH (>55pmol/ml、High)

Physiology  ACTH stimulation test

Rapid ACTH ST Three days ACTH ST

Clinical finding:
Methods Intravenous injection 25u ACTH in Intravenous injection 25u
30min,determin the change of ACTH in 3days,determin the
plasma cortisol after 30 min change of cortisol plasma in
Weakness Hyperpigmentation Loss weight, e,aciation, 1、2 、3day
anorexia, vomiting, diarrhea

normal Increase 276~552nmol/L Gradually increase>2.5 times

Hypotension Salt craving Hypoglycemic episodes
meaning Diagnosis ,combined with ACTH Differentiate primary from
can be used to differentiate diagnosis secondary adrenocortical
 Hyperpigmentation (most common, accentuatuion in sun- insufficiency
exposed areas & pressure points) → vetiligo, pigment
accentuation at nipples & friction area pigment concentration
in skin creases scar

 Gastrointestinal symptom → anorexia (common), nauseam Differential diagnosis

vague abdominal discomfort, vomiting, diarrhea (rare)
 Hypotension (common, not strong enough to suggest
Addison’s) → 90% of patient with systolic pressure
<100mmHg associated with orthostatic dizziness &
occasionally syncope
 Secondary adrenocortical insuffiency →There are other
endocrine gland hypofunction, ACTH is low,
hyperpigmentation of skin isn’t present.
 Chronic liver disease

 Salt craving (20% of cases)  Nelson syndrome

 Hypoglycemia (unusual) → provoked fasting, fever,  Other chronic disease

infection, or nausea which may lead to coma
Treatment
 Weakness → accompanied by fatigue & malaise
Lifetime therapy with glucocorticoids & mineralocorticoids
 Weight loss → due to tissue loss resulting from anorexia;
dehydration also contribute Chronic:
  Hydrocortisone 15-25 mg/d → two divided doses: 2/3 in the  Distinguished from an acute abdomen → neutrophilia is the
morning and 1/3 in the late afternoon or early evening. rule (eosinophilia & lymphocytosis → of adrenal insufficiency)

 Some patients respond better to prednisone in a dosage of

about 3 mg in the morning and 2 mg in the evening.
Treatment
 Fludrocortisone supplementation or extra dietary salt → if
sufficient salt-retaining effect and require do not obtain. Acute phase

 Increased cortisol dosage during “stress”
Adrenal crisis (emergency)
Etiology:
 Following stress, e.g. trauma, surgery, infection, or prolonged
fasting in a patient with latent insufficiency.
 Following sudden withdrawal of adrenocortical hormone in a
patient with chronic insufficiency or in a patient with chronic
insufficiency due to suppression by exogenous
glucocorticoids.
 If the diagnosis is suspected, draw a blood sample for cortisol
determination.
 Treat with hydrocortisone, 100-300mg IV, & saline
immediately, without waiting for the results. Followed by
continue IV infusions of 50-100mg every 6 hours for the first
day. Give the same amount every 8 hours on the second day
and then adjust the dosage in view of the clinical picture.
 Correcton of precipiating factors (e.g. broad spectrum
antibiotic)
 IV saline & glucose → to treat dehydration, hypovolemia,
hyponatremia, hypoglacemia

 Following bilateral adrenalectomy or removal of a functioning Convalescent phase

adrenal tumor that had suppressed the other adrenal.
 When the patient is able to take food by mouth, give oral
 Following sudden destruction of the pituitary gland (pituitary hydrocortisone, 10-20 mg every 6 hours, and reduce dosage to
necrosis), or when thyroid hormone is given to a patient with maintenance levels as needed.
hypoadrenalism.
 Mineralocorticoid therapy is not needed when large amounts
of hydrocortisone are being given, but as the dose is reduced it
 Following injury to both adrenals by trauma, hemorrhage,
is usually necessary to add fludrocortisone acetate, 0.05-0.2
anticoagulant therapy, thrombosis, infection, or rarely
mg daily
metastatic carcinoma.

Clinical finding

 Hypotension /shock, confusion or coma may be present

 Weakness, apathy, headache, lassitude

 Nausea, vomitting, anorexia, diarrhea, abdominal or flank

pain
Hperthyroidsm
 Dehydration, hypovolemia, hyponatremia,
Thyrotoxicosis: refers to clinical manifestation associated with
 Hyperkalemia, Hypoglycemia serum level of thyroxine (T4) or triodothyroine (T3) that are
excessive for individual.
 Hyperthermia (40.6℃ or more), Blood,sputum, or urine
culture may be positive if bacterial infection is the
Hyperthyroidism: term for overactive tissue within the thyroid
precipitating cause of the crisis.
gland causing an overproduction of thyroid hormones.
Hyperthyroidism causes thyrotoxicosis, but hyperthyroidism &
 Other signs: cyanosis, dehydration, skin hyperpigmentation,
thyrotoxicosis are not synonymous
and sparse axillary hair (if hypogonadism is also present).
Cause of thyrotoxicosis
Differential diagnosis
Dependent Independent
 Differentiate of shock → e.g. septic, hemorrhagic, cardiogenic
Increased occupancy of the Increased thyroid hormone
 Differentiate of Hyperkalemia → GI bleeding, rhabdomyolysis,
TSH receptor by: release
hyperkalemic paralysism, & under the effect of certain drugs
(e.g. ACE inhibitor, sprinolactone)
o Thyroid-stimulating o Subacute granulomatous
immunoglobulin (TSI) thyroiditis (painful)
 Differentiate of hyponatremia → e.g. hypothyroidism, diuretic
use, heart failure, cirrhosis, vomiting, diarrhea, severe illness,
o Subacute lymphocytic
or major surgery
o Graves' disease
o Hashitoxicosis
o Human chorionic
gonadotropin (hCG)
o Hydatiform mole
o Choriocarcinoma
o Thyroid-stimulating hormone
(TSH)
o TSH-producing pituitary
tumor
Autonomous overproduction
of thyroid hormone
(independent of TSH)
thyroiditis (painless) o Tumors: Metastatic thyroid cancer, Ovarian tumor that
produces thyriod hormone (struma ovarii), Trophoblastic
Nonthyroidal source of tumor, TSH secreting tumor
thyroid hormone
o Greves disease (50-60%) → clinical exophthalmos,
o Thyrotoxicosis factitia dermopathy (especially pretibial myxedema), and rarely
thyroid acropachy
o "Hamburger" thyrotoxicosis
Clinical manifestation (depend on age, amount of hormone)
o Ectopic production by:
 Older patient presents with lack of clinical signs and
o Ovarian teratoma (struma symptoms, which makes diagnosis more difficult
ovarii)
 Thyroid storm is a rare presentation, occurs after
o Metastasis of follicular stressful illness in under treated or untreated patient.
cancer Characteristics: Delirium, Dehydration, Severe tachycardia,
Vomiting, Fever, Diarrhea
Common symptoms:

o Toxic adenoma (TSH

receptor mutant) Nervousness Anxiety Increased perspiration

o Toxic multinodular goiter

Heat Tremor Hyperactivity
o Follicular cancer (rare) intolerance

Jod-Basedow effect (excess

iodine-induced Palpitations Weight loss Reduction in menstrual
hyperthyroidism) despite increased flow or oligo-
appetite menorrhea

Etiology

 Grave’s disease → Autoimmune disease caused by antibodies

to TSH receptors
Common sign:

 Toxic multi-nodular goiter (5%) → 10x more common in Hyperactivity, Hyper kinesis Sinus tachycardia or atrial
iodine deficient area; typically occurs in >40y old with long arrhythmia, AF, CHF
standing goiter
Systolic hypertension, wide Warm, moist, soft and smooth
 Toxic adenoma → More common in young patients pulse pressure skin- warm handshake

 Thyroiditis Excessive perspiration, Lid lag and stare (sympathetic

palmar erythema, Onycholysis over activity)
 Subacute: Abrupt onset due to leakage of hormones,
Follows viral infection, Resolves within eight months, Can Fine tremor of out stretched Large muscle weakness,
re-occur. hands – format's sign Diarrhea, Gynecomastia
 Lymphatic and postpartum: Transient inflammation,
Postpartum can occur in 5-10% cases in the first 3-6
months, Transient hypothyroidism occurs before resolution Nervous & psychiatric:

Psychiatric Neuromascular
 Treatment Induced Hyperthyroidism

 Iodine Induced: Excess iodine indirect, Exposure to Hyperactivity Tremors-outstretched hand and
radiographic contrast media, Medication tongue
Emotional lability
 Amiodarone Induced Thyroiditis Hyperactive tendon reflexes
Anxiety
 Thyroid Hormone Induced:
Decreased
o Factitious hyperthyroidism in accidental or intentional concentration
ingestion to lose weight
 Insomnia  Frequent blinking

 Graves ophthalmopathy: Proptosis, lid retraction (prevent

complete closure of the eyes), keratitis and corneal
ulceration
Cardiac:
Skin:
↑CO (cardiac output) Sinus tachycardia  Warm moist smooth skin
Atrial fibrillation: 10-20%, more High output – heart failure  Onycholysis
common elderly output
 fine hair, hair loss
Systolic hypertension, widened LV hypertrophy &
pulse pressure cardiomyopathy  excessive perspiration

Mitral valve problem  Graves’ skin change (rare): orange-peel thickening of

the pretibial areas

Muskuloskeletal system: Graves’ disease

 Atopic & weak Enlargement of the thyroid gland

 Myesthenia gravis (especially in Grave’s disease) Infiltrative ophthalmopathy

 Hypokalemic periodic paralysis Dermopathy

 Thyroid acropathy (clubbing of nails) Acropachy

 Bone resorption exceeds bone formation → hypercalciuria

& sometime hypercalcemia Diagnosis

 Osteopenia (long-standing hyperthyroidism)

 Thyroid function test (establish hyperthyroidism & the cause)

 ↑ (Serum T4 & free T4 concentration)

GI:
 ↑ (Serum T3 and free T3 concentration)
 ↑food intake & unstable appetite
 Serum TSH → A normal or elevated TSH in a hyperthyroid
 Hyperphagia (weight gain younger patient) patient indicates TSH-induced hyperthyroidism

 Anorexia-weght loss elderly  Etiological test

 Weight loss is common  TSI (Grave’s disease marker)

 Hyoerdefication or diarrhea because of GI hypermotility  Antiperoxidase antibody in Hasimoto’s thyroiditis →

common cause oh HYPO thyroidism
 Abnormal liver function test

Reproductive:  Radioactive iodine uptake scan

 Oligoenorrhea & amenorrhea Differential diagnosis

 Gynecomastia occurs in men 1) Grave’s disease

Thyroid gland:  Typical sign of thyrotoxicosis & autoimmune-mediated

manifestation (e.g. ophthalmopathy)
 Enlargement of nodule
 Free T4, T3, & TSH test: In all patient T3↑ & most such
Eye: patient ↑Free T4 levels

 Increased sympathetic tone & include a widened distance 2) Anxiety state

between the upper and lower lid

 Lid lag on upward gaze  Irritability, tremor, weakness, tachycardia, and weight
loss
  Thyroid hormone → normal
For severe
Notes
thyrotoxicosis

Supportive therapy (ß-Adrenergic blocking agents)

3) Subacute tyroiditis
 Rrelief symptoms (tachcardiam tremor, anxiety, & heat
intolerance
 ↑sedimentation rate, Antithyroid antibodies are usually
negative, the thyroid uptake of radioiodine is very low. A  Small inhibitory effect T4 to T3
hyperthyroid phase lasts for several weeks, followed by
a transition to a hypothyroid phase of several weeks  Contraindication: asthma & congestive heart failure
and then recovery.
Radioactive iodine
 Thyroid tenderness is the hallmark of the disorder.
 for older patients with moderate hyperthyroidism and thyroid
 Low thyroid uptake of 121I enlargement

4) Lymphotic thyroiditis  for patients with a prior allergic or toxic reaction to the
antithyroid medication
 This disorder is responsible for a small percentage of
new cases currently. Usually a small firm goiter is  Should stop antithyroid administration before starting therapy
present, but the thyroid may not be enlarged or may be
up to three times the normal size.

 There is no thyroid tenderness.

Surgical (Subtotal thyroidectomy)
 Low thyroid uptake of 121I
 Indication: large obstructing glands; glands containing
Treatment (Decreasing thyroid hormone formation & secretion) nodules that are identified as malignant or equivocal on fine-
needle aspiration; pregnant women with severe
Antithyroid drugs – radioactive iodine - surgery hyperthyroidism (thyroidectomy during the second trimester);
toxic reactions to antithyroid drugs; not candidates for
Antithyroid drug therapy antithyroid drugs and refuse radioactive iodine

 Euthyroid must be achieved before surgery: using antithyroid

Methimazole drugs
Imp. considerations Propylthiouracil (PTU)
(MMI)
 Compilcation: Hypothyroidism, hypoparathyroidism,
recurrent laryngeal nerve paralysis, hemorrhage, wound
Efficacy Very potent Potent
infections, and keloids, 50% of Grave’s ophthalmology can
develop or worsen
Long acting
Duration of action Short acting QID/TID Thyroid strom
BID/OD

Dangerous condition of decompensated thyrotoxicosis, resulting

In pregnancy Contraindicated Safely can be given from long-neglected severe hyperthyroidism to which there is
added a complicating intercurrent illness, such as gastroenteritis or
pneumonia, or emergency surgery.
Iodination,
Mechanism of action Iodination, Coupling
Coupling Clinical:

Tachycardia Fever
Conversion of T4 to T3 No action Inhibits conversion
Agitation Restlessness or psychosis
Rashes,
Adverse reactions Rashes, ↑Neutropenia Nausea Vomiting and/or diarrhea
Neutropenia
Treatment:
20 to 40 mg/ OD
Dosage 100 to 150mg qid PO  Inhibit the release of hormone from the gland.(solution of
PO
potassium iodide )

 Inhibit the biosynthesis of thyroid hormones :

  Antithyroid drugs in large doses (600 mg propylthiouracil  Uncommon immune-mediated diabetes → insulin
or 60 mg methimazole stat and half this dose q6h) autoimmune syndrome, acanthosis nigricans

 Sodium Iodine 1g IV in 24h

 Inhibit the sympathetic blockade: Propranolol in large oral

Risk factors
doses (20-40mg q4-6h / 1mg IV slowly)

 Antagonism to stress: hydrocortisone (50-100mg IV q6h) 1) Genetic & Environemtntal factor → aging, obesity, diet, life
style
 Symptomatic and supportive treatment:
2) Insulin resistance & B cell function defection
 Fluid replacement (IV fluids)
3) Glucotoxicity & lipotoxicity
 O2

 Temperature control (acitaminopen, cooling blankets) 4) Clinical DM

 Anti-infection

Main symptom & sign

CNS: Gastric:
Diabetes
 Polydipsia  Nausea
Definition: is a syndrome with disordered metabolism and
inappropriate hyperglycemia due to either a deficiency of insulin  Polyphagia  Vomiting
secretion or insulin resistance & inadequate insulin secretion to
compensate.  Lethargy  Abdominal pain

Complication: involvine eyes (blindness), kidney (renal failure),  Stupor

nerves (stroke), blood vessels (gangrene, myocardial infarction),
ketoacidosis
Systemic: weight loss Eyes: blurred vision
Classification:

1) Type 1 DM: Breath: smell of acetone Respiratory: Kussmaul breathing

(hyperventilation)
 Immune-mediated type 1 DM

 Idiopathic Type 1 DM Urinary: Polyuria, Glycosuria

2) Type 2 DM → genetic and environmental factors

Type 1:
3) Gestational DM
 Common in thin & young, an absolute deficiency of insulin
4) Other specific types: → accumulation os circulation glucose & fatty acids →
hyperketonemia
 Hereditary defect of B cell function → associated with
mutation of mitochondrial DNA  Latent autoimmune diabetes in adult (LADA) occurs in non-
obese people with absolute deficiency of insulin & insulin
 Heriditary defect of insulin action → lipoatrophia DM autoimmune antibody (+)

 Endocrine disease → Cushing’s syndrome, hyperthyroidism Type 2:

 Disease of pancreas → pancreatitis, surgery, trauma, cancer  Tend to occur in overweight & elderly

 Diabetes due to drug → glucocorticoid, thyroid hormones,  Asymptomatic → detect by its complication or
thiazide diuretic
routine health exam
 Infection → congenital rubella , cytomegalovirus
Type 1 Type 2

 Other inherited disease → syndrome Age of onset Young Adult

  Single nerve paralysis (commonly involve femoral &
cranial nerve) → vascular ischemia or traumatic
Weight Lean Obese damage

Onset More abrupt May be very insidious

Symptom Characteristic Asymptomatic

features
 Autonomic neuropathy
Insulin Absolute deficiency Relative/resistence
 Symptoms: anhidrosis of the lower limbs or
Treatment Insulin Oral drug
hyperhidrosis of the upper half of the body,
orthostatic hypotension, diarrhoea, constipation,
Ketosis prone Frequently Rare
urinary retention and sexual dysfunction

Complication

A.Chronic complication B. Acute complication

 Large vessel disease: Atherosclerosis → coronary heart
disease, hypertension, & stroke.
 Small vessel disease: Diabetic microangiopathy (associated
with homogeneous thickening of vascular basement
membrane & endothelial proliferation)
1) Diabetic retinopathy (microaneurysms, hemorrhage,
exudates), Proliferative retinopathy (newly formed vessels,
vitreous hemorrhage scaring retinal detachment, blindness),
Diabetic cataracts, glaucoma.
2) Diabetic nephropathy: (Type 1-40%, type2-20%)
 Pathological: Diffuse glomerular sclerosis (70%),
nodular glomerular sclerosis
 Manifestation: Proteinuria, Declines kidney function
 Staging:
 First period: enlarge kidneys, hyperfiltration,
normoalbuminuria.
 Second period: thickening of glomerular basement
membrane, microalbuminuria period intermittent
 Third period: microalbuminuria period persistent
( UAE 20-200ug/min)
 Fourth period: increasted microalbuminuria (UAE >
200ug/min), patients may be present with edema,
hypertension, and kidney function decline
 Diabetic ketoacidosis
 Hyperglycemic hyperosmolar status
 Infection: Urinary tract & skin infection are common. TB &
moniliasis are also common
C. Diabetic foot
 Diabetic foot is syndrome which includes ischemia, peripheral
neuropathy, and secondary infection
 Occlusive vascular disease involves both microangiopathy
and atherosclerosis of large and medium-sized arteries
Lab findings
 Glucosuria
 Plasma glucose: Fasting plasma glucose level (Normal: 3.9-
6.0mmol/L, postprandial <7.8mmol)
 Oral glucose tolerance test (OGTT): if plasma glucose is less
than diagnostic value (75g oral glucose put into 250-300ml
water, drink it over in 5 minutes and measure the plasma
glucose level after 2 hours-normal range is 5.6-7.7mmol/L)
 Glycosylated hemoglobin (HbA1C): reflect the state of
glycemia over the preceding 8-12 weeks, and provide an
improved method of assessing diabetic control. Normal range
is 3-6%

 Fifth period: uremic period, creatinine & urea

nitrogen accumulate in the blood Diagnosis

3) Diabetic neuropathy Subject PPG FPG

 Paripheral neuropathy: Normal < 6.1mmol/L <7.8mmol/L

 Symmetrical sensory loss in the distal lower limbs IFG 6.1~ 6.9 mmol/L <7.8mmol/L
(common) + numbness, burning, lightning pain (worse
at night) IGT < 7.0mmol/L 7.8~11.0mmol/L

Diabetes ≥7.0mmol/L ≥11.1mmol/L

 o Indication: obese type 2 (either alone or in conjunction
with sulfonylureas)

o Contraindication: Hepatic or renal impairment,

Pregnancy, Acute complication

o Adverse reaction: Lactic acidosis, Nausea, vomiting

o Classic drugs: Metformin

Treatment  Alpha-glucosidase inhibitors

1) Diet o Inhibit digest dietary starch & sucrose

Breakfast Lunch Dinner Bedtime o Indication: type 2 with postprandial hyperglycemia

3 meals 20% 40% 28% Calories o Containdication: GI diseases, pregnancy

4 meals 28% 28% 28% 16% o Adverse reaction: Abdominal distention, diarrhea

o Classic drugs: Acarbose

2) Exercise: for type 2, can induce hypoglycemia in type 1
 Thiazolidinediones
3)Oral drugs o Mechanism not clear

Oral drugs o Indication: type 2 with insulin resistance

Sulfonylureas o Adverse reaction: Edema

Meglitinide analogs o Contraindication: Heart failure, hepatic/renal

impairment
Biguanides
o Classic drugs: Pioglitazone, Rosiglitazone
Thiazolidinediones

Alpha-glucosidase inhibitors 4) Insulin therapy

 Indication:
 Sulfonylureas o Type 1 DM
o Stmulate insulin secretion - by bind with receptor in o Diabetic ketoacidosis , hyperglycemia hyperosmolar
Bcell status , Lactic acidosis
o Indication: nonobese type 2 that can’t control glucose o With infection, severe chronic complication
level by diet, exercise, & without complication
o Trauma or surgery
o Contraindication: Type 1 DM, Gestational DM, Type 2
DM with severe complication, During the course of o Pregnancy
surgery, Pancreatic excision, Hepatic or renal
impairment o Pancreatic excision
o Adverse reaction: Hypoglycemia, Skin rashes,
o Type 2 diabetic patients whose hyperglycemia does not
Leukopenia , thrombopenia, Nausea , vomiting
respond to diet therapy combined with oral drugs
o Classic drugs: Glyburide, Glipizide, Gliclazide,
 Adverse reaction: Hypoglycemia, Edema, Hypersensitive
Gliquidone, Glimeperide
response (pruritus , skin rashes)
 Meglitinide analogs
 Classic drugs: regular insulin, neutral protamine hagedorn,
o Stmulate insulin secretion with less hypoglycemia protamine zinc insulin
complication than sulfonlyureas
 Insulin analogue:
 Biguanides
(1) rapid-acting: insulin lispro, insulin aspart
o ↓ blood glucose by diminished hepatic gluconeogenesis
(2) long-acting: insulin glargin
Treatment principle
 Should start from minimum dosage & slowly raise according
to the level of plasma glucose
 Combination drugs insulin/sulfonylureas & meglitinide
analogs + biguanides/alpha-glucosidase
inhibitor/thiozolidinediones → not only can increase to treat
hyperglycemia but also may increase risk of hypoglycemia
 If fasting plasma glucose always high, consider:
 The insulin or oral drug of night is not enough
 Dawn phenomenon: blood glucose in night is normal, but
hyperglycemia appears in dawn (subuh) because of the anti-
insulin hormone increases.
 Somogyi phenomenon: there is hypoglycemia in night, and
secondary hyperglycemia (monitoring blood glucose help
to detect the cause of morning hyperglycemia)
Diabetic ketoacidosis
General consideration:
 The initial manifestation of type 1 diabetes
 During the course of infection , trauma, myocardial infarction,
or surgery, gestation
Symptom n sign:
 Polyuria
 Polydipsia associated with marked fatigue
 Nausea & vomiting
 Mental stupor that can progress to coma
 Rapid deep breathing & fruity breath odor of acetone
 Dehydration & hypotension
 Abdominal pain & tenderness (present in the absence of
abdominal disease)
Lab finding:
 Hyperglycemia >13.9mmol/L
 Acidosis with blood PH<7.35
 Serum bicarbonate<18mmol/L
 Urine positive for ketones
 Serum potassium is normal or high despite total body
potassium depletion resulting from polyuria or vomiting
 Serum creatinine and urea nitrogen may be mild high
 Leukocytosis may occur with or without associated infection
Treatment
Prevention:
 Education of early symptom & sign
 Urine ketons measurement for patients with signs of infection
or blood glucose is high
Emergancy measures:
 Therapeutic flow sheet
 Vital sign
 Lab exam: Urine ketones, arterial pH, plasma glucose,
bicarbonate, serum nitrogen, electrolytes & serum
osmolality
 Avoid urinary catheter & gastric intubation in needed in
comatose patient when diabetic present due to high risk of
bladder infection
 Fluid intake & output should be recorded
 Patient should not receive sedative or narcotics
 Insulin replacement
 Only use regular insulin
 Should be given immediately after the diagnosis is establish
 Continuous low-dose insulin infuse (0.1 unit/kg/h), if
plasma glucose level fails to fall (at least 10%) in first hour
→ required doubling dose
 Measure plasma glucose, acetone, bicarbonate, serum urea
nitrogen, & electrolytes per 2h
 When plasma glucose falls to 13.9mmol/L or less, give 5%
glucose while insulin therapy still continue (to clear
ketonemia)
 When urine ketones has been cleared, regular insulin should
be given in hypo
 Fluid replacement
 Most patient loss 4-5L of fluid
 0.9% saline solution should be started in emergency after
disease esteblisment
 First hour: at least 1L of 0.9% saline is infused at rate of
300-500ml/h with careful monitoring serum potasium
  Electrolyte replacement

Sodium bicarbonate: used when blood pH <7.1 or blood

bicarbonate < 6.7mmol/L. when pH reach 7.1 bicarbonate
treatment should be stopped (to avoid cerebral edema)

Potassium replacement: (30-30mmol/h) for 2-3h after start

treatment or sooner when serum potassium is low. It should be
deferred when serum potassium fail to response (remain
above 5mmol/L) in order to avoid renal insufficiency

 Treatment of complication

 Infection (e.g. cholecystitis & pyelonephritis): antibiotic

 Cardiac failure (in aged with coronary heart disease):

Diuretics & digitalis glycosides

 Renal failure (serious prognostic sign): prevention is

important

 Cerebral edema (rare): maintain blood glucose between

11.1~16.7mmol/L for initial 24h after correction of severe
hyperglycemia to reduce risk

DKA HHS

History Young, diabetes Agedm undiagnosed

diabetes

Cause infection Stroke, infection,

trauma

Symptom Nausea, polydipsia, Mental confusion, tic,

mental stupor coma, hallucination

Sign Dehydration (4-5L), Dehydration (5-8L),

hypotension palsy (paralysis)

Ketonuria (+) to (+++) (-) to (+)

Glycemia >13.9mmo/L >33.3mmol/L

Serum natrium Normal or low High

PH, bicarbonate low Normal or low

Serum Normal or mild high >320mosm/L

osmolality