Pituitary adenoma:

Basics:
Neoplasm of pituitary gland, mostly benign.
Divided into non-functional tumors, hormone secreting tumors. Microadenomas (<10mm) and
macroadenomas (>10mm).
Excess or insufficient hormone production.
Complications:
Bitemporal hemianopia (if optic chiasm is compressed).
Ophthalmoplegia (if cavernous sinus is compressed).
Diplopia (cranial nerve compressed).
Treatment:
Trans-sphenoidal surgery (via nasal cavity and sphenoid sinus).
Galactorrhea:
Can be caused by dopamine deficiency.
Postpartum hemorrhage:
Heavy bleeding in woman after giving birth.
Causes:
Primary:
Uterine atony (lack of effective uterus contraction).
Genital tract lacerations.
Retained placenta.
Uterine inversion.
Abnormal placentation.
Coagulation disorders.
Secondary:
Retained products of conception.
Infection.
Subinvolution of the placental site.
Inherited coagulation deficits.
Prevention:
Exogenous IV injection of oxytocin.
Prolactinoma:
Most common type of functioning secretory adenoma.
Symptoms:
Asymptomatic until causing hormonal dysfunction, visual changes, hydrocephalus,
hypogonadism.
Cushing disease:
Overproduction of cortisol due to ACTH secreting pituitary adenoma. A type of Cushing’s syndrome.
Symptoms:
Proximal myopathy, psychiatric disturbances, obesity, purple striae over the abdomen, extra fat
around neck (buffalo hump), hypertension.
Treatments:
 Transsphenoidal adenectomy.
Cushing’s syndrome:
Overproduction of glucocorticoids (hypercortisolism). Excess aldosterone and androgen may also
involve.
Causes:
Primary:
Adenoma of adrenal cortex (ACTH-independent).
Bilateral adrenal hyperplasia.
Secondary:
ACTH-dependent.
More ACTH (Cushing’s disease).
Ectopic tumor:
E.g. bronchogenic carcinoma, benign carcinoid tumors.
Others:
Steroid treatment.
Diagnosis:
Single assays:
24-hour urinary free cortisol:
Measure the free cortisol excreted in urine when excess cortisol is presented in blood.
Pitfalls:
Incomplete collections.
Pseudo-Cushing.
Pseudohypercortisoluria (by HPLC/high-performance liquid chromatography):
Carbamazepine.
Increase cortisol level.
Fenofibrate.
Digoxin.
Kidney function and urine volume:
Renal impairment filters and metabolizes less cortisol, so more cortisol in
blood.
Late-night salivary cortisol:
Measure level at ~10pm, which should be extremely low normally.
Cushing’s patients may have high level because diurnal drop is lost.

Dynamic approaches:
Low-dose dexamethasone suppression test:
Sensitivity:
95%.
 Method:
Give 1mg dexamethasone at night and measure blood cortisol level the at 8-9am
the next morning.
Result:
Normal (cortisol <50nmol/l): suppressed cortisol level (because ACTH is
suppressed).
Cushing’s syndrome: cortisol level remains unchanged.
Potential pitfalls:
30% false positive, as in elderly/depressed patients and those taking certain drugs
(oral contraceptives and estrogen) that alter cortisol level.
Others:
Reduced dexamethasone absorption.
Drugs enhancing hepatic dexamethasone metabolism:
Barbiturates, phenytoin, carbamazepine, rifampicin, meprobamate,
aminoglutethimide, methaqualone.
Increased concentration of CBG/capillary blood glucose:
Estrogen treatment, pregnancy.
Pseudo-Cushing states:
Endogenous depression.
Eating disorders.
Chronic alcoholism.
Confirm the cause:
Plasma ACTH level:
Elevated: secondary cause.
Depressed: primary cause.
High-dose dexamethasone suppression test:
Usage:
When there is high ACTH level.
Method:
Give 8mg dexamethasone at night and measure cortisol level the next morning.
Result:
Low cortisol: pituitary-dependent Cushing’s disease.
High cortisol:
Ectopic ACTH source (e.g. lung) if ACTH is high.
Adrenal Cushing’s if ACTH is low.
CRH stimulation test:
Usage:
When there is high ACTH but uncertain cortisol level.
Method:
Give CRH intravenously and measure cortisol response.
Result:
Normal: rise in ACTH and cortisol.
 Cushing’s disease: exaggerated rise in ACTH and cortisol.
Ectopic ACTH syndrome: no response.

Short synacthen test:

Usage:
To determine exogenous steroids from endogenous cases.
Method:
Give ACTH analogue (Synacthen) and measure cortisol level.
Result:
If cortisol increases much, then not exogenous steroids.
If cortisol does not increase much, then exogenous steroids. Because the
endogenous production of cortisol is impaired because of exogenous steroid
treatment.
Other tests:
X-ray, MRI (for pituitary), CT (for adrenals, localize active tumor, hyperplasia), inferior
petrosal sinus sampling for ACTH.
Symptoms:
Rapid weight gain/central obesity (buffalo hump, moon face, pendulous abdomen (buildup of fats
in abdomen))
Thin extremities and muscle weakness.
Bruising, edema, hypertension.
Purple striae (tearing of collagen fibers in weakened subcutaneous tissue, causing hemorrhage).
Body hair growth (hirsutism), osteoporosis, skin problem (e.g. parchment skin), adrenal diabetes.
Nephrolithiasis (kidney stones).
 Treatments:
Surgical removal.
Ketoconazole (reduce steroid production).
GH secreting adenoma:
Overproduction of GH.
Symptoms:
Acromegaly (enlarged and thickened fingers), gigantism, carpal tunnel syndrome (pressure on
median nerve that runs from forearm to palm, causing numbness, weakness and pain in hand
and wrist), proximal myopathy, rarely hypertension/DM.

Gigantism:
Hypersecretion of GH before fusion of epiphysis.
Causes:
Pituitary tumors.
Complications:
Diabetes (GH causes insulin resistance).
Panhypopituitarism (when tumor destroys the pituitary gland later).
Bitemporal hemianopia.
Treatment:
Surgery.
Managements:
Somatostatin analogues:
Octreotide.
Lanreotide.
Irradiation.
Acromegaly:
Overproduction of GH after epiphysis fusion.
Enlargement of extremities.
Causes:
Pituitary tumor.
Features:
Pituitary tumor related:
Headache.
 Bitemporal hemianopia: visual field defects.
Cranial nerve palsies.
GH excess related:
Bone thickening, enlarged hands, feet, and membranous bones, large tongue.
Enlargement of nose, tongue, liver, and kidney.
Prognathism: protrusion of jaw.
Prominent supraorbital ridges.
Thick skin.
Excessive sweating and sebum production.
Carpal tunnel syndrome.
Hypertension, cardiomyopathy.
Glucose intolerance. Diabetes.
Kyphosis, osteoarthritis: forward bending of vertebral column.
Arthropathy.
Goitre.
Sleep apnea. (common with obesity)
Other hormones related:
Hyperprolactinemia.
Hypopituitarism.
Complications:
Cardiovascular:
Hypertension.
Increased left ventricular mass.
Reduced ejection fraction during exercise.
Respiratory:
Sleep apnea (increase risk of MI, HT, stroke, road traffic accidents).
Neoplastic:
Colonic polyps, colon cancer.
Screening:
Glucose tolerance test:
If GH fails to be suppressed to <1mU/l, then likely acromegaly. Glucose can inhibit growth
hormone release.
IGF-1 test:
Active acromegaly unlikely if normal.
GH test:
Acromegaly unlikely for undetectable random GH.
Treatments:
From more to least effective:
Transsphenoidal hypophysectomy:
Medical:
Bromocriptine, cabergoline
Dopamine D2 receptor agonist, dopamine can inhibit growth hormone release.
 Somatostatin analogues:
Octreotide.
Less effect than dopamine agonist.
GH receptor antagonists.
Targeted/stereotactic radiotherapy:
External beam radiotherapy:
Cure after treatment:
Aim:
Restoration of soft tissue overgrowth.
Remission of symptoms.
Return of normal GH secretion.
Preservation of anterior pituitary function.
Mean serum growth hormone level:
2.5ng/ml.
Oral glucose tolerance test:
GH suppression to <2.0ng/ml.
IGF-1 levels.
Dwarfism:
Deficiency of growth hormone.
Causes:
Receptors not sensitive to GH (Laron dwarfism).
Underproduction of IGF-1 even GH is high.
Panhypopituitarism (sexual maturation also impaired).
Treatments:
Hormone replacement by recombinant DNA technology.
Hyperprolactinemia:
Causes:
Prolactin-secreting pituitary tumors:
Secreting prolactin alone or mixed.
Hypothalamic disorders:
Reduced production of prolactin-inhibiting factor.
Functional disorders.
Tumors (e.g. craniopharyngioma).
Stalk compression syndrome:
Presence of sellar/suprasellar mass that compresses stalk, resulting in less inhibition by
dopamine.
Hypothyroidism:
More TSH secretion due to negative feedback. TSH can also stimulate prolactin production.
Renal failure:
Reduced clearance and metabolism by kidney
Increased secretion of PRL due to reduced dopamine secretion.
Ectopic sources:
 Rare.
Drug/hormone administration:
Dopamine receptor-blocking agents:
Phenothiazines, butyrophenones, metoclopramide.
Dopamine-depleting agents:
Reserpine, methyldopa.
Estrogens:
Inhibit hypothalamic dopamine synthesis and reduced pituitary D2 receptors.
H2 blockers:
Cimetidine.
Dopamine antagonist.
Monoamine oxidase inhibitors:
Dopamine antagonist.
Physiological:
Pregnancy, breastfeeding, stress, physical activity, breast stimulation.
Clinical features:
Related to pituitary tumor:
Headache.
Visual field defects.
Cranial nerve palsies.
Related to excess prolactin:
Females:
Infertility, defective luteal phase.
Oligomenorrhea, amenorrhea.
Galactorrhea.
Hirsutism, acne.
Males:
Loss of libido, impotence.
Gynecomastia (mild).
Galactorrhea.
Decrease in secondary sexual hair.
Others:
Microadenomas:
Normal pituitary function.
Macroadenomas:
Hypopituitarism.
Investigations:
Blood prolactin measurement:
Secretion can be induced by pregnancy and stress, so for minor elevations, several samples
or pooled samples are needed.
Beware of macroprolactin interference.
Macroprolactin: non-bioactive prolactin isoform + IgG molecule with prolonged
 clearance rate.
Blood chemistry/thyroid function test/pregnancy test:
MRI/CT in hypothalamic-pituitary region with contrast:
Mandatory if there is no obvious other causes, even PRL is just increased mildly.
Visual fields.
Test for other hormones:
Co-secretion.
Hypopituitarism.
Gonadal function.
Multiple endocrine neoplasia (MEN).
Treatments:
Medical:
Bromocriptine 泊汀錠/溴隱亭:
MOA:
Ergot derivative that stimulates D2 receptors and decreases prolactin synthesis.
Decrease DNA synthesis, cell multiplication, tumor growth.
Safe in pregnancy.
SE:
Development of perivascular fibrosis with long-term treatment.
Nausea, vomiting, orthostatic hypotension, nasal congestion, depression,
psychotic reaction.
Cabergoline:
About:
Once weekly orally (long T1/2).
Less side effects than bromocriptine.
Quinagolide.
Surgery:
Indications:
Visual impairment (may not need).
Apoplexy.
CSF rhinorrhea.
Tumor enlargement despite treatment.
Intolerance to medical treatment.
Deep x-ray therapy (DXT):
For failed medical or surgery only.
Managements during pregnancy:
Macroprolactinoma/intrasellar macroadenoma:
Stop bromocriptine. This is to prevent hypertensive disorder.
Regular PRL measurements not helpful.
Imaging if there is symptomatic visual problem.
Macroprolactinoma:
Stop bromocriptine and monitor.
 Prepregnancy transphenoidlal debulking.
Continuous bromocriptine.
Treatment skills for having both hypogonadism and prolactinoma:
Prolactin inhibits gonadotropin release:
Treat prolactin (also for most microadenomas).
Stalk effect with macroadenoma:
Medical treatment to shrink the tumor.
Other hypopituitarism:
Gonadal replacement therapy.
Pituitary apoplexy:
Enlarged pituitary adenomas that require more blood, causing hemorrhagic infarction.
Symptoms:
Abrupt onset headache, visual changes (diplopia), panhypopituitarism with low BP, focal
neurological deficitis.
Sheehan syndrome:
Infarction and necrosis of pituitary gland, postpartum hypopituitarism due to pituitary gland
enlargement (lactotropes proliferate a lot to prepare for milk production) that compresses superior
hypophyseal artery. Infarction and necrosis take place if blood pressure drops during childbirth
(massive hemorrhage).
Symptoms:
Failure to lactate during postpartum period.

Treatment:
Hormone replacement.
Lymphocytic hypophysitis:
Autoimmune condition where diffuse lymphocytic infiltration in pituitary glands destroy normal tissue
with scarring.
 Associated with pregnancy.
Granulomatous hypophysitis:
Non-caseating granuloma with Langerhans type giant cells.
May present in posterior lobe of pituitary gland due to neurosarcoidosis.
Empty sella syndrome:
Primary:
Defect in diaphragma sellae that allows contents above to herniate into the sella, compressing
the pituitary gland.
Secondary:
Due to tumors, surgery that compress the gland, may also link with multiparous women, obesity
and benign intracranial hypertension.
Syndrome of inappropriate antidiuretic hormone (SIADH):
Overproduction of ADH.
Causes:
Nervous system disorders, neoplastic, ectopic sources like paraneoplastic syndromes, head
trauma, drugs.
Symptoms:
Altered mental status, seizures, coma, hyponatremia.
Craniopharyngiomas:
Adamantinomatous craniopharyngioma (aCP):
In children.
Papillary craniopharyngioma (pCP):
In adults.
Causes:
Ectopic embryonic remnants of Rathke’s pouch.
Squamous epithelial in the gland undergoes metaplasia and transforms.
Rathke’s cleft cyst:
Remnant of Rathke’s pouch that forms cyst that contains pink eosinophilic substance.
Complications:
May develop xanthogranulomas or cholesterol crystals (during chronic inflammation).
Multiple endocrine neoplasia-1 (MEN-1):
Abnormal growth in pituitary gland, parathyroid gland and pancreas.
Goitre:
Causes:
Iodine deficiency:
Stimulate TSH release via negative feedback and hyperplasia (toxic multinodular goitre).
Iodine excess.
Goitrogenic agents:
Drugs:
Thionamides:
Propylthiouracil:
Treat thyrotoxicosis.
 Amino heterocyclic compounds:
P-aminosalicylic acid (PAS):
Treat tuberculosis.
Resorcinol:
Cutaneous anesthetic.
Substituted phends:
Salicylamide:
Antipyretic.
Iodine:
Antithyroid, expectorant.
Other drugs:
Lithium:
Treat manic depressive illness.
Aminoglutethimide:
Anti-adrenal agent.
Phenylbutazone:
Anti-inflammatory agent.
Nitroprusside:
Hypotensive agent.
6-mercaplopurine:
Cancer chemotherapy.
Food stuffs:
Brassica family.
Cabbage, turnips.
Plants used in animal fodder.
Soybean (infant formulas).
Cassava (staple diet in certain regions).
Dyshormonogenesis:
Inherited enzyme deficiencies.
Autoimmunizing thyroiditis:
Grave’s disease, Hashimoto’s thyroiditis.
Ionizing radiation.
Cretinism:
Causes:
Congenital hypothyroidism:
Genetic defects.
Endemic cretinism:
Iodine deficiency in diet.
Features:
Pot belly, protruding umbilicus.
Short, obese, and stocky (compact) appearance.
Physical and mental retardation.
 Treatments:
Iodine.
Thyroxine hormone.
Pituitary agenesis:
Complete absence of pituitary gland.
Absence of anterior lobe:
Failure of development of Rathke’s pouch.
Pharyngeal hypophysis:
Pituitary at the roof of nasopharynx, maybe due to remnant of Rathke’s pouch.
Ectopic thyroid gland:
Usually along the route of decent of thyroid gland.
e.g. lingual thyroid.
Accessory thyroid:
Arise from remnants of thyroglossal duct.
Thyroglossal duct cyst:
Cyst with mucous filled sac along the path of thyroglossal duct, causing build-up of secretions within
duct.
Hypoadrenalism:
Primary causes:
Addison’s disease:
About:
Hypoadrenalism when too little mineralocorticoids and glucocorticoids are made.
Insufficient androgen in extreme cases.
Causes:
Mostly autoimmunity against cortices (female predominance).
Infections:
Tuberculosis.
Fungal: histoplasmosis.
AIDS.
Congenital:
Congenital adrenal hyperplasia (CAH).
DAX1, ACTH-R mutations.
Adrenoleukodystrophy/adrenomyeloneuropathy.
Drugs:
Inhibit cortisol synthesis:
Aminogluthimide.
Metyrapone.
opDDD/mitotane.
Ketoconazole.
Increase cortisol clearance:
Barbituates.
Phenytoin.
 Hemorrhage:
Anti-coagulants.
Waterhouse-Friderichsen syndrome:
Bilateral adrenal hemorrhage, mostly due to fulminant meningococcemia.
Metastases.
Bilateral adrenalectomy.
Sarcoid.
Hemochromatosis.
Amyloidosis.
Injury, surgery.
During major stressors:
Acute primary adrenal insufficiency (adrenal crisis).
There is a sudden need for aldosterone and cortisol.
Secondary causes:
Decreased ACTH production.
Features:
No pigmentation.
Visual field defect, other hormone deficiencies/abnormalities (e.g. hypogonadism,
hypothyroidism).
Mineralocorticoid not affected (mainly stimulated by RAAS).
Dilutional hyponatremia, hypoglycemia.
Underlying illness precipitating crisis:
Gastroenteritis.
Pneumonia.
Features:
General:
Tiredness, malaise, vomiting, abdominal pain, dizziness.
Due to lack of mineralocorticoids:
Low BP & blood volume & cardiac output, hyponatremia, hyperkalemia, metabolic acidosis
(high anion gap), shock.
Due to lack of glucocorticoids:
Muscle weakness, hypoglycemia, adrenal crisis (low BP, low sugar, high potassium), weight
loss, emaciation (extreme weight loss).
Due to lack of androgens:
Male:
No signs because testes produce most androgens.
Female:
Decreased body hairs, loss of libido, hot flushes (uncomfortable hot feeling and
swelling, like during menopause).
Due to high ACTH production:
Skin pigmentation:
About:
 Only for primary adrenal insufficiency.
Areas:
Non-sun-exposed and pressured areas (knuckles, elbow, knees, palmar creases,
recent scares).
Causes:
Both ACTH and MSH derive from proopiomelanocortin (POMC).
ACTH contains alpha-MSH, it has melanocyte-stimulating hormone (MSH) like
effect by stimulating melanocytes to produce melanin.
ACTH binds to melanocortin 1 receptor on dermal melanocytes.
Diagnosis:
Single assays:
Measure cortisol level at 8am – 9am (highest level due to circadian rhythm, most sensitive).

Dynamic approach:
ACTH stimulation test:
Method:
Give synthetic ACTH (cosyntropin)/Synacthen (ACTH analogue) and measure
cortisol level.
Done at any time of the day.
Result:
If cortisol level increases, normal adrenal gland can be confirmed, further
verification of secondary or tertiary causes is required.
Disease: cannot response to ACTH.
CRH stimulation test:
Method:
Give ovine/human CRH and measure cortisol.
Result:
No/little increase in cortisol if pituitary disease.
2x to 4x increase within 30-60mins if hypothalamic disease.
Confirm:
Metyrapone stimulation test:
Usage:
Indeterminate cortisol result/suspected pituitary diseases.
Method:
Give metyrapone that inhibits 11-beta hydroxylase which produce cortisol from
11-deoxycortisol.
 Result:
Normal cortisol response:
More ACTH is secreted (pituitary function), less cortisol synthesis, buildup of
11-deoxycortisol.
No adrenal insufficiency.
Absent/subnormal response:
Adrenal insufficiency.

Other tests:
Serum level of sodium and potassium.
Fasting blood glucose level.
Raised plasma renin/low aldosterone.
Blood count and autoantibodies against adrenal gland.
Treatments:
Glucocorticoid replacement:
IV fluids for Addisonian crisis.
IV hydrocortisone 100mg Q6-8H (after blood taking)
IV dexamethasone 4mg.
1mg hydrocortisone = 1.6mg cortisone acetate = 0.2mg prednisolone = 0.05mg
dexamethasone.
Increase dose for stress cover during acute illness/fever/surgery.
Mineralocorticoid replacement:
Fludrocortisone 0.1mg/day.
Low dose hydrocortisone: some mineralocorticoid activity.
Monitor plasma renin activity.
Treatment of secondary adrenal failure:
Only replace glucocorticoid.
Treat other hormone deficiencies as required, such as thyroid hormone.
If both hypoadrenalism & hypothyroidism present, treat hypoadrenalism first (adrenal crisis
 may precipitate).
Glucocorticoid replacement can unmask diabetes insipidus.
Conn’s syndrome/hyperaldosteronism:
About:
Overproduction of aldosterone.
Causes:
Primary:
Aldosterone producing adenoma (APA).
Bilateral idiopathic hyperaldosteronism (IHA).
Primary adrenal hyperplasia (unilateral).
Aldosterone-producing adrenal carcinoma.
Familial hyperaldosteronism (FH):
Type 1: glucocorticoid-suppressive hyperaldosteronism.
Type 2: early-onset primary aldosteronism.

Diseases with hypertension not related to aldosterone (pseudo primary hyperaldosteronism):

Low renin and aldosterone.
Deoxycorticosterone-secreting tumors:
Deoxycorticosterone is a precursor of aldosterone and has mineralocorticoid-like
action.
So deficiency/mutation of 11beta-hydroxylase could cause accumulation of
deoxycorticosterone, so hypertension.

Congenital adrenal hyperplasia.

Liddle’s syndrome:
Mutations of subunits of epithelial sodium channel (ENaC), reducing its internalization
from membrane, so more absorption of sodium.
 Syndrome of apparent mineralocorticoid excess:
Features:
Hypertension, hypokalemia, low renin, hypoaldosteronism.
Causes:
Deficiency of 11beta-hydroxysteroid dehydrogenase, so cortisol cannot be
metabolized to cortisone.
High cortisol can cross-react with mineralocorticoid receptor, leading to
aldosterone-like effects, causing hypertension.

Secondary:
Excessive activation of RAAS:
Renin-producing tumor.
Renal artery stenosis.
Edematous disorders:
LVHF, pregnancy, cor pulmonale, cirrhosis with ascites.
Features:
Low renin. Increased aldosterone excretion.
Hypokalemia & metabolic alkalosis (more hydrogen removal).
Symptoms:
High BP, headache, muscle cramps/paralysis, weakness. Due to less potassium in blood.
Screening & diagnosis:
For:
Young/resistant hypertension.
HT that requires multiple medications/with hypokalemia.
Tests:
Aldosterone to Renin Ratio (ARR):
If abnormal, go for further tests:
Postural test: supine and erect renin, aldosterone.
 Suppression test: after oral salt loading (24-hour urine aldosterone).
Postural test:
Salt loading:
Potassium supplements to normalize K.
Recumbency:
Leaning down.
Ambulation:
Stand up and walk for 4hours.
Measure renin and aldosterone before and after ambulation.

Result of aldosterone changes after ambulation:

Adenomas (APA): aldosterone concentration decreases.
Hyperplasia (IHA): aldosterone concentration increases.
Suppression test:
Saline suppression test:
Method:
600ml/hr for 4-6hrs.
Result:
Normal: aldosterone <6ng/dl.
Problem: aldosterone >10ng/dl.
Oral salt loading:
Method:
200mmol sodium for 3days/two 1g NaCl tablet TDS (3 times per day) 3days.
Result:
Normal:
24hr urine Na >200mmol/d.
24hr urine aldosterone <12mcg/24hr.
Fludrocortisone suppression:
About:
 Fludrocortisone is a mineralocorticoid.
Method:
0.1mg orally Q6H with Na supplement (20-30mol Na TID) 4 days.
Result:
Normal:
Plasma aldosterone <6ng/dl.
Treatments:
Medical:
Indications:
Idiopathic aldosteronism.
Unilateral adrenal hyperplasia.
Primary adrenal hyperplasia.
Aldosterone-producing adenoma not for surgery.
Drugs:
Mineralocorticoid receptor antagonists:
Spironolactone.
Eplerenone.
Potassium-sparing diuretics:
Amiloride.
Others:
Thiazide diuretics.
Calcium channel blockers.
ACEi.
Surgical removal:
Indications:
Aldosterone-producing adenoma.
Adrenocorticoid carcinoma.
Unilateral adrenalectomy:
Can reduce aldosterone secretion, BP and corrects hypokalemia.
Persistent hypertension:
Nephrosclerosis after prolonged uncontrolled hypertension.
Essential hypertension.
Can be predicted to BP response to spironolactone.
Laparoscopic adrenal resection:
Complications: right diaphragm injury, incisional hernia, pneumothorax, conversion to
open surgery, general anesthesia.
Ablative procedures:
Super-selective adrenal arterial embolization.
Transcatheter arterial ablation with acetic acid injection.
Radiofrequency ablation (RFA).
Adrenogenital syndrome:
About:
 Excess androgen production.
Features:
Female:
Growth of beard and body hair, deep voice, baldness.
Enlargement of clitoris that resembles penis.
Prepubertal male:
Penis enlargement, increased muscle mass.
Urine:
More excretion of 17 ketosteroid (breakdown product of androgens).
Pheochromocytoma:
Causes:
Tumor of adrenal medulla, so overproduction of catecholamines.
Features:
Tachycardia, palpitation, atrial fibrillation, hypertension, headache, anxiety, panic attacks, tremor,
sweating, pale face (cutaneous vasoconstriction).
Paroxysms (sudden attack of symptoms), diaphoresis (excessive sweating), orthostatic
hypotension.
Tests:
More urinary excretion of catecholamines and metanephrines (breakdowns of catecholamines).
Treatments:
Medical:
Need adequate alpha-blockade before beta-blockade. This is because in the absence of beta-
2-mediated vasodilation, profound unopposed alpha-mediated vasoconstriction may lead to
hypertensive crisis/pulmonary edema.
Control BP:
Alpha-blockers:
Phenoxybenzamine.
Terazosin.
Calcium channel blockers.
Treat HT crisis:
Phentolamine.
Sodium nitroprusside.
Arrhythmias:
Beta-blockers:
Propranolol.
Esmolol.
Prevent post-surgical hypotension:
Adequately long pre-operative alpha- & beta-blockades.
Volume replacement.
Pressor agents (noradrenaline).
Surgical removal:
Laparascopic adrenalectomy.
 Open adrenalectomy.
Need careful pre-operative preparation and anaesthetic assessment. Monitor hematocrit
after alpha-blockade.

Congenital adrenal hyperplasia:

Causes:
Lack of 21-hydroxylase. Inability/reduced ability to produce cortisol, sometimes aldosterone
deficiency also presents. Excessive steroid precursors are released.
The blockage causes shift to androgen production, so more androgen.
Since cortisol can suppress ADH release, glucocorticoid replacement causes less ADH, so diabetes
insipidus.
Low cortisol stimulates negative feedback that overproductions of CRH and ACTH occur. High
ACTH stimulates adrenal cortex to undergo hyperplasia.
Complications:
Less aldosterone and DOC/deoxycorticosterone:
Salt wasting.
Hypovolemia.
Less cortisol:
Metabolic syndrome.
More androgens:
Virilization 男性化.
Precocious puberty.
Atypical hirsutism.
Ambiguous genitalia.
Less adrenaline (developmental defects in formation of adrenal medulla):
Hypoglycemia.
Cardiovascular instability.
High ACTH:
Hyperplastic glands.
Psychological effects.
Skin pigmentation.
Markers:
 17-hydroxyprogesterone level.
ACTH concentration.
Bone-age (for children).
Other forms of CAH:

11beta-hydroxylase deficiency:
Features:
Virilization.
Hypertension (elevated DOC which also has some mineralocorticoid effect).
3beta-hydroxysteroid dehydrogenase deficiency:
Features:
Gonadal ambiguity in both sexes.
17alpha-hydroxylase deficiency:
Features:
No androgen & estrogen formation.
Excess DOC & corticosterone.
Causing hypertension, hypokalemia, infantile female genitalia (male & female), failure
of puberty.
17,20-lyase deficiency:
Does not affect glucocorticoid/mineralocorticoid that much.
 Not causing adrenal hyperplasia:
High cortisol at the beginning decreases ACTH secretion by negative feedback.
Not causing hypertension:
Normal aldosterone level so no hypertension.
Panhypopituitarism:
Decreased secretion of all anterior pituitary hormones.
Causes:
Congenital.
Acquired:
Tumors:
Pituitary, primary or secondary.
Suprasellar:
Craniopharyngioma, meningiomas, gliomas.
Granulomas:
Sarcoidosis.
Tuberculosis.
Histiocytosis.
Syphilis.
Infarction:
Postpartum necrosis (Sheehan’s syndrome).
Pituitary apoplexy.
Developmental causes:
With anosmia 嗅覺喪失症 (Kallmann’s syndrome).
With cerebellar ataxia, retinitis pigmentosa.
With congenital rubella.
Miscellaneous causes:
Trauma (e.g. surgery).
Previous radiotherapy to hypothalamus or nasopharynx.
Clinical features:
Hypogonadism: loss of sexual functions.
Hypothyroidism: without goitre, with lethargy.
Growth hormone deficiency: fine wrinkling of skin, mood disorder, obesity, muscle weakness.
Hypoadrenalism: no pigmentation and no mineralocorticoid deficiency.
Diabetes insipidus: thirst, polyuria.
Visual field defects: compressed optic nerves.
Investigations:
Visual fields:
Formal perimetry test.
Pituitary radiology:
MRI, CT.
Pituitary function tests:
LH, FSH, prolactin, testosterone (for men), oestradiol in all patients.
 fT4, TSH (not accurate).
IGF1 if possible.
Stimulation tests:
Synacthen test:
Synacthen (synthetic ACTH) is given and measure if adrenal gland can produce cortisol
normally.
Insulin/glucagon stimulation test for cortisol and GH.
Treatment:
Hormone replacement:
Need to make sure cortisol is normal before starting thyroxine. This is to prevent adrenal
crisis because thyroxine can inhibit TSH via negative feedback. TSH can stimulate cortisol
release as well.
Thyroxine:
Circa 2ucg/kg/day.
Cortisol:
Hydrocortisone 20-30mg/day.
May use prednisolone/dexamethasone, but longer acting so harder to control.
No need mineralocorticoid.
Sex steroids replacement:
For male:
Testosterone:
Intramuscular, patch, oral.
Give gonadotrophins/LHRH instead if fertility required because testosterone
can suppress FSH and LH secretion via negative feedback, causing AAS-
induced hypogonadotropic hypogonadism.
Infertility: oligozoospermia/azoospermia.
HCG (human chorionic gonadotropin) with/without FSH/LHRH:
Mimic puberty in adolescents.
Allow spermatogenesis.
hGH (human growth hormone):
Symptomatic despite other replacement, IGF1 low, GH low on stimulating test.
DDAVP:
For diabetes insipidus.
Oral, intranasal, sublingual.
Q8H or Q12H dosing.
Diabetes insipidus:
ADH deficiency causing large volume dilute urine, even with water deprivation.
Central:
Secretion from hypothalamus decreases.
Causes:
Congenital:
Isolated defect.
 DIDMOAD syndrome:
Diabetes insipidus, diabetes mellitus, optic atrophy, deafness.
Acquired:
Idiopathic.
Trauma:
Head injury, fracture, surgery.
Tumor:
Pituitary adenoma, craniopharyngioma, metastatic carcinoma.
Granulomata:
Sarcoidosis, histiocytosis X.
Infection:
Pyogenic/tuberculous basal meningitis.
Encephalitis.
Vascular:
Aneurysm.
External irradiation.
Features:
Dehydration, polyuria, polydipsia, high blood osmolarity.
Diagnosis:
Paired measurements of plasma and urine osmolarity:
Used if hypernatremia.
Diagnostic if plasma osmolarity is high while urine’s is low.
Water deprivation test:
Careful monitoring to prevent serious dehydration.
Followed by DDAVP if DI is confirmed but cause is uncertain.
Treatments:
Synthetic analog desmopressin/DDAVP (oral, nasal and injection).
Nephrogenic:
Normal production but kidney fails to respond.
Not responding to DDAVP.
Causes:
Lithium and tetracycline antibiotics.
Hypercalcemia:
Induce autophagic degradation of aquaporin 2 channels.
Features:
Dehydration, polyuria, polydipsia, high blood osmolarity.
Treatment:
Drink lots of water.
Treat the cause.
Use diuretics (thiazide diuretics) that cause sodium excretion (decrease blood osmolarity).
Reduce sodium intake.
Syndrome of inappropriate ADH secretion (SIADH):
 Increased secretion of ADH.
Causes:
Small cell lung carcinoma.
Features:
Hyponatremia.
Water retention.
Swelling of neurons (disorientation, headache, nausea, lethargy).
Seizures, coma, permanent brain damage, death.
Swelling of brain (causing brain herniation).
Treatment:
Hypertonic saline (treat hyponatremia, given slowly to prevent demyelination).
Hyperthyroidism/thyrotoxicosis:
Hypersecretion of thyroid hormone.
Causes:
Primary:
Graves’ disease/diffuse toxic goitre:
Causes:
Autoimmune, more in women, where antibody (TSAb) binds to TSH receptor and
stimulates thyroid hormone production.
TGI can also bind to TSHR but cannot stimulate thyroid hormone production.
Presentations:
Pretibial myxedema:
Skin thickening over lower legs.
Highly related with ophthalmopathy (bulging reddened eyes).
Occur when TSH receptor in tissues acts as antigen for TSH antibodies,
causing stimulation of fibroblasts and production of glycosaminoglycans.
Exophthalmos:
Due to infiltrative ophthalmopathy, where retro-orbital fibroblasts and T cells
accumulate in eye tissue.
Orbital fibroblasts:
Proliferation, adipogenesis, overproduction of extracellular matrix
GAGs/glycosaminoglycans, including hyaluronan (HA).
T cells:
Produce inflammatory cytokines, increasing glycosaminoglycans and
anti-orbital muscle antibodies.
Single-nodule goitre.
Acropachy/clubbing:
Swollen fingertips.
Features:
High TH, low TSH.
Antibody presentation.
Adenoma:
 Features:
Absence of antibodies.
Radioactive iodine uptake (I123) in hot nodule.
Toxic multinodular goitre:
Causes:
Iodine deficiency so less T4 production, causing hyperplasia since thyroid gland
wants to produce more TH.
More replications induce higher risk of mutation in TSHR. TSHR may be mutated in
a way that it is always active, causing excess T3/T4 production.
Iodine-induced, trophoblastic tumor.
Secondary:
High TSH: multifocal thyrotroph hyperplasia
High TRH: tumors, granulomatous diseases.
Causes divided by radioactive iodine uptake (RAIU):
Normal/high RAIU:
Graves’ disease.
Toxic multinodular goitre.
Solitary toxic nodule.
Choriocarcinoma/hydatiform mole.
Hyperemesis gravidarum (gestational hyperthyroidism).
TSH-secreting pituitary adenoma.
Pituitary selective thyroid hormone resistance syndrome.
Low RAIU:
Subacute thyroiditis.
Painless (silent) thyroiditis.
Postpartum thyroiditis.
Factitious hyperthyroidism.
Iodine-induced hyperthyroidism.
Struma ovarii.
Metastatic functioning thyroid carcinoma.
Features:
Increased basal metabolic rate, heat intolerance, excessive sweating, weight loss, increased
appetite, diarrhea, nervousness, anxiety, insomnia, tremor, infertility, menstrual abnormalities
(oligomenorrhea, menorrhagia). Palpitation.
Exophthalmos (protrusion of eyeball).
Lid lag (lid retraction, upper eyelid is higher than normal during downgaze), goitre, hyper-reflexia,
pre-tibial myxedema.
Thyroid eye signs:
Lid retraction, lid lag (sympathetic overtone).
Periorbital puffiness.
Chemosis:
Swelling of conjunctiva.
Proptosis, corneal ulceration.
Ophthalmoplegia:
Paralysis/weakness of eye muscles.
Optic nerve compression.
Complications:
Diabetes mellitus, systolic hypertension, atrial fibrillation.
Liver derangement:
Related directly to state of thyrotoxicosis.
Maybe due to:
Thyrotoxic heart disease -> congested liver.
Reactions to thionamides ATDs.
Related to Grave’s disease: autoimmune hepatitis, primary biliary cirrhosis.
Treatments:
Antithyroid drugs (thionamides/ATD):
Examples:
Propylthiouracil, methimazole, carbimazole.
1 course: 9months – 2years.
Indications:
Strongly suggested:
Thyrotoxic crisis/severe case.
 Preparation for RAI/SX.
Pregnancy.
Young Graves’ disease.
Not recommended:
Long-term treatment in toxic nodules or toxic multinodular goitre.
Release of Graves’ disease after first course of ATD/SX.
Large vascular or nodular goitre.
Poor drug compliance.
Contraindicated:
Fatal allergy to thionamides:
E.g. blood dyscrasia, hepatotoxicity.
Side effects:
Skin rash, pruritus.
Try another ATD.
Agranulocytosis:
Stop and never take ATD again or need admission to take.
Recovery in 1 week, may be shortened with G-CSF.
Cholestatic hepatitis:
Stop and evaluate, may try other ATD.
Radioactive iodine (RAI):
MOA:
Can destroy secretory cells.
Indications:
First-line treatment of:
Toxic nodular goitre.
Age >50years.
Post-thyroidectomy.
Strongly indicated:
Relapse after SX.
Intolerance of ATD.
Thyrotoxic heart disease after stabilization.
Complications from thyrotoxicosis:
TTP (thrombotic thrombocytopenia purpura), CHF, fast AF, cardiac problems,
psychosis.
Not recommended:
Young, <20years.
Large compressing/retrosternal goitre.
Unstable significant Graves’ ophthalmopathy.
Contraindicated:
Pregnancy & breast feeding.
Known allergy to iodine.
Severe Graves’ ophthalmopathy.
 Retrosternal goitre.
Thyrotoxic crisis.
Side effects:
Radiation gastritis, radiation thyroiditis, development/worsening of infiltrative
ophthalmopathy.
Subtotal thyroidectomy (SX):
Indications:
Strongly indicated:
Large/nodular goitre with pressure symptoms.
Rapidly growing goitre with suspicion of cancer.
When ATD fails.
Not recommended:
Relapse after first operation.
Patients rely on their voice for job.
Contraindicated:
Thyrotoxicosis that is not controlled by drugs.
Beta blockers:
Propranolol.
Special clinical issues:
Thyrotoxic periodic paralysis:
Southern Chinese/Asian male thyrotoxicosis.
Common for: nasal pharyngeal cancer, treated with radiotherapy so cause hypopituitarism.
Thyrotoxic heart disease:
Use beta-blocker.
Hypothyroidism:
Primary causes:
Autoimmune:
Hashimoto’s disease:
About:
Autoimmune thyroiditis.
More common in women.
Features:
Anti-thyroid peroxidase/antithyroglobulin antibodies.
TPO: Thyroid peroxidase antibody assay.
Tg: may also present in healthy ones, not used.
Myxedema 黏液水腫 (swelling and thickening of skin).
Thyroid enlargement (hyperplasia and hypertrophy).
Lymphocytic infiltration.
All these lead to graduate thyroid destruction by fibrosis.
Iatrogenic:
Drugs-induced:
Carbimazole:
 Amiodarone:
Contain large amount of iodine that induces anti-thyroid action via Wolff-Chaikoff
effect (many iodine in environment can inhibit production of thyroid hormones).
Lithium:
A drug to treat mood disorders (e.g. bipolar disorder).
Can be concentrated inside thyroid, inhibiting thyroidal iodine uptake,
iodotyrosine coupling, thyroid hormone secretion.
Radiotherapy/radioactive iodine.
Thyroid surgery.
Other:
Iodine deficiency:
Likely in:
Hilly areas.
Treatment:
Iodized salt.
Postpartum thyroiditis:
Causes:
Immunologic suppression during pregnancy to prevent fetus rejection (allograft)
rebounds after delivery. This raises autoimmune thyroid antibodies.
Timeline:
Firstly mild hyperthyroidism, then mild hypothyroidism, finally normalization.
Symptoms:
Reduced milk production, painless goiter, hair loss, fatigue, depression, anxiety,
moodness.
Congenital hypothyroidism.
Thyroid agenesis/dysgenesis.
Clinical features:
High TSH.
Stimulate secretion of colloid containing thyroglobulin.
Thyroid gland enlarges (goitre/hypertrophy).
With low T4.
With normal T4 (subclinical).
Secondary & tertiary causes:
Pituitary or hypothalamus problem (central hypothyroidism).
Low T4 and normal/low TSH.
Generalized/peripheral thyroid hormone resistance.
Features:
Increase sleep, fatigue, infertility, menstrual abnormalities, sluggish muscles (slow muscle
relaxation during ankle jerk), weight gain, loss of appetite, constipation, mental sluggishness,
memory loss, depression.
Loss of hair, scaly dry skin, husky voice, eye bagginess, face swelling/puffiness. Bradycardia.
Myxedema:
 Severe hypothyroidism characterized by firm inelastic edema, dry skin & hair, loss of mental
& physical vigor.
Non pitting type of edema. Change in synthesis & degradation of glycosaminoglycans as in
lack of thyroid hormones. Glycosaminoglycan accumulation forms complex protein that
binds water, causing non-pitting edema.
Complications:
Atherosclerosis.
Treatments:
Levothyroxine:
Titrate according to TSH for primary hypothyroidism.
Monitor FT4 for central hypothyroidism.
Careful in ischemic heart disease (IHD) or elderly.
Replace steroids before thyroxine if suspect adrenal insufficiency or hypopituitarism.
Euthyroid sick syndrome:
Causes:
Critical illness (sepsis, burn, trauma, surgery) causes cytokine production.
Thyroid gland is functioning well.

D1 and D2 removes iodine from T4 to form T3.

Low hormone maybe a protective mechanism.
Stages:
Normal/elevated TSH, high T4, reduced T3.
Normal/elevated TSH, normal T4, reduced T3.
Reduced TSH, T4, T3.
High TSH, normal T4, reduced T3.
 Features:
High rT3. Different from hypothyroidism that has low rT3.
Hypoparathyroidism:
Causes:
Thyroidectomy.
Features:
Low PTH, low vitamin D, low blood calcium.
Signs:
Chvostek sign:
Tap facial nerve in front of ear tragus, causing contraction of facial muscles.
Trousseau sign:
Inflating BP cuff, causing spasm of hand muscle.
Symptoms:
Tetany.
Treatments:
Calcium gluconate injection, PTH, vitamin D.
Pseudohypoparathyroidism:
Causes:
Resistance to parathyroid hormone.
X-linked dominant or autosomal dominant.
Features:
Low blood calcium, high PTH, less bone mineralization, short bones (impaired growth).
Symptoms:
Paresthesia 感覺異常, numbness, seizures, tetany 抽搐 (muscle twitches, hand and foot
spasms)
Treatments:
Calcium, vitamin D.
Hyperparathyroidism:
About:
Hypercalcemia, deposit of excess calcium in kidneys and arteries.
Causes:
Primary:
Parathyroid adenoma (mostly), parathyroid carcinoma, hyperplasia.
About:
More osteoclastic activity, causing more cystic areas lined with osteoclasts.
Osteitis fibrosa cystica (bone pain, subperiosteal bone resorption in middle
phalanges and distal radius, thinning of distal clavicle, bone cyst formation) =
brown tumor (demineralization of bone, color due to hemosiderin deposition).
Features:
High blood calcium, low phosphate level, high chloride (metabolic acidosis).
Increased alkaline phosphatase (liver damage/bone disorder), bone fractures.
High PTH.
Symptoms:
Psychosis (fail to know what is real), peptic ulcer, constipation, abdominal pain,
metastatic calcification in lungs, kidney, blood vessels, renal stones, bones
(painful), groans (GIT involved because of muscle movement, constipation), moans
(mental, e.g. depression, fatigue).
Treatments:
Surgery:
For:
Symptomatic.
Markly increased serum calcium, life-threatening hypercalcemia,
decreased RFT/renal stones, increased urinary calcium, decreased bone
mass, PTH-related symptoms.

Medication:
For:
Asymptomatic mild cases, without renal/skeletal complications.
Management:
Adequate hydration.
Active, ambulatory lifestyle.
Moderate dietary calcium intake.
Estrogen:
For:
Post-menopause.
MOA:
Suppress bone turnover, so less serum calcium and high BMD
(bone mineral density).
Reduce urinary calcium excretion.
Bisphosphonates:
e.g. Alendronate.
Inhibit bone resorption.
Calcimimetic agent (Norcalcin, NPS-568):
Bind to calcium sensing receptor and suppress PTH release.
 Secondary:
Low calcium (due to vitamin D deficiency or renal disease).
e.g. renal osteodystrophy.
Renal osteodystrophy:
About:
Renal failure decreases activation of vitamin D so less absorption of calcium.
Phosphate excretion also decreases due to renal failure.
Phosphate binds with calcium in blood, further depleting free calcium level.
PTH secretion is stimulated, causing bone resorption.
Features:
Painful bones and fractures.
Vitamin D deficiency:
Rickets:
In children, less exposure to sunlight.
Osteomalacia:
Bone softening in adults due to lack of vitamin or mineral.
Causes:
Abnormal vitamin D metabolism:
Deficient intake or absorption:
Inadequate sun exposure.
Diet.
Pancreatic insufficiency.
Partial gastrectomy.
Malabsorption.
Small bowel disease.
Defective 25 hydroxylation:
Biliary, alcoholic cirrhosis.
Anticonvulsants 抗驚厥藥.
Loss of vitamin d binding protein:
Nephrotic syndrome.
Defective 1alpha 25 hydroxylation:
Renal failure.
Hypoparathyroidism.
Vitamin D dependent rickets type 1.
Defective target organ response to calcitriol:
Vitamin D dependent rickets type 2/hereditary vitamin D resistant rickets.
Mineralization defects:
Abnormal matrix:
Osteogenesis imperfecta.
Enzyme deficiencies:
Hypophosphatasia.
Inhibition of mineralization:
 Fluoride, aluminium.
Phosphate deficiency:
Decreased intake.
Impaired renal absorption:
Hereditary hypophosphatemic rickets with hypercalciuria.
X-linked hypophosphatemic rickets (vitamin D resistant).
Fanconi syndrome.
Secondary defects:
Primary & secondary PTH.
Oncogenic osteomalacia.
Clinical features:
Radiological detection osteopenia.
Diffuse bone pain.
Muscle weakness:
Proximal.
Muscle wasting, hypotonia.
Waddling gait.
Features:
Less bone mineralization, leg bowing.
Adequate matrix but poorly mineralized.
Increased osteoblastic activity, so high ALP.
Treatments:
Vitamin D, dietary intake of calcium and phosphate.
Hypercalcemia:
Category:
Total plasma calcium concentration >10.4 mg/dL.
Causes:
Hyperparathyroidism.
Malignancy (PTHrP/PTH-related protein).
Drugs:
Vitamin D, thiazides, lithium, vitamin A, estrogen/antiestrogen.
Familial hypocalciuric hypercalcemia:
Mild hypofunction of CaSR.
Neonatal severe hyperparathyroidism:
Severe hypofunction of CaSR.
Immobilization, hyperthyroidism/thyrotoxicosis, granulomatous diseases (tuberculosis, fungal
diseases, sarcoidosis, histoplasmosis (reduced calcium excretion in urine)), acute/chronic renal
failure.
Multiple endocrine neoplasia syndromes (MEN).
Pheochromocytoma, adrenal insufficiency, milk-alkali syndrome, parenteral hyperalimentation.
Clinical features:
General:
 Weakness, dehydration (lead to more concentrated calcium in blood), lethargy, headache,
somnolence, impaired memory, depression.
Stones, bones, groans, psychic moans.
Cardiovascular:
Shortened QT interval, sensitivity to digitalis, arrhythmias, hypertension.
Neuromuscular:
Hyporeflexia, myopathy, paralysis, confusion, psychosis, stupor, coma.
Renal:
Polydipsia, polyuria nephrolithiasis, nephrocalcinosis, renal failure, kidney stone,
hyposthenuria (abnormally low urinary specific gravity/low osmolarity).
GI:
Anorexia, nausea, vomiting, constipation, ileus.
Skeletal:
Pain, fracture, loss of height.
Miscellaneous:
Anemia, fever, metastatic calcification.
Associated syndromes:
Multiple endocrine neoplasia, pancreatitis (calcium affects cellular signaling pathway,
overproduction of digestive enzymes lead to autodigestion), peptic ulcer.
Management:
Correct dehydration:
Saline infusion.
Increase Ca excretion:
Loop diuretics.
Dialysis:
With low calcium dialysate and PD.
Useful for renal failure/CHF where safe saline load cannot be given.
Inhibit bone resorption:
Bisphosphonates:
Drugs:
Pamidronate (IV 30-90mg over 4-6hrs).
Zoledronic acid (IV 4mg over 15mins).
MOA:
Potent osteoclast inhibitors.
May help in multiple myeloma and CA breast.
Highly effective and well tolerated (short/long term).
Phosphate:
About:
Oral, 3mg/day for mild hypercalcemia with normal/low serum phosphate.
MOA:
Chelation of ionized calcium, inhibition of osteoclasts.
SE:
 Ectopic deposition of calcium phosphate complexes.
Calcitonin:
Salmon calcitonin (more potent).
Low toxicity, used in initial management (specifically high bone tumor, e.g.
immobilization, thyrotoxicosis).
IV/IM, Q6-12H 3-10 IU/Kg/day
Reduce calcium uptake:
Glucocorticoids:
Prednisone 30-60mg/day.
For disorders of excess vitamin D metabolites.
Inhibit intestinal calcium transport.
If ineffective/not tolerated, try chloroquine, hydroxychloroquine, ketoconazole.
Mobilization.
Drugs:
Mithramycin.
Corticosteroids.
Phosphate.
Gallium nitrate.
Therapy of underlying aetiology
Ectopic vitamin D production:
Chronic granulomatous diseases:
Sarcoidosis.
Tuberculosis.
Coccidioidomyocisis.
Histoplasmosis.
Candidiasis.
Leprosy.
Foreign body granuloma (silicone implantation, lipoid pneumonia).
Berylliosis.
Malignancy:
Lymphomas.
Hodgkin disease.
Seminoma.
Renal cell carcinoma.
Hypercalcemia of malignancy:
PTHrp-related:
About:
Tumors like breast cancer and squamous cell carcinoma of lung produce parathyroid
hormone related protein (PTHrp) that acts like PTH.
Roles of PTHrP:
May help in fetal calcium metabolism, it presents in fetal parathyroid and placenta,
secreted by lactating breast, causing hypercalcemia of infancy.
 Concentrated in various smooth muscle and take part in muscle contraction regulation.

Features:
Low PTH.
Treatments:
Treat the cause.
Bisphosphonates (decrease osteoclastic activity).
Others:
About:
Multiple myeloma, plasma cell malignancy can produce immunoglobulins that cause
osteolytic lesions in bone.
Features:
Hypercalcemia.
Hypocalcemia:
Category:
Total plasma calcium concentration <8.0 mg/dL.
Causes:
Hypoalbuminemia.
Hypoparathyroidism.
Poor intake/impaired absorption of calcium.
Vitamin D deficiency.
PTH & vitamin d resistance.
Pseudopseudohypoparathyroidism (PPHP) (short stature, round face, short hand bones, with
parathyroid hormone resistance).
Liver and renal diseases.
Osteoblastic metastases.
Signs:
 Chvostek’s sign.
Trousseau’s sign.
Complications:
Depressions, anxiety, hair loss, brittle nails, perioral tingling, cataract, low BPM (prolonged Q-T
interval), stomach pain, diarrhea, increased urination, dry skin, muscle weakness/tetany/cramps,
increased reflexes (hyperreflexia), hypocalcemic tetany (threshold for neuron activation is lower,
so higher neuromuscular excitability), paresthesia (tingling and cramping of hands and feet).
Treatments:
Acute case:
10-20ml 10% calcium gluconate (IV) over 10mins.
Recurrent persistent case: 100-160ml 10% calcium gluconate (IV) over 8-12hours.
Monitor calcium level every 2-8hours.
Check Mg level for unexplained hypocalcemia/resistant case.
Chronic case:
Calciferol.
Alfacalcidol.
Calcium supplement.
Osteoporosis:
About:
Decrease in bone matrix and minerals, bone formation, bone mass and strength due to increased
bone resorption, incidence of fracture.
Less severe case known as osteopenia.
Causes:
Aging, immobilized, lack of estrogen in postmenopausal women.
Preventions:
Enough calcium and vitamin D in diet, weight bearing exercise.
Treatments:
Estrogen.
SE: higher incidence of breast cancer.
Bisphosphonates.
Selective estrogen receptor modulators (SERM):
Act like estrogen.
Diabetes mellitus:
Insulin deficiency (type 1) or resistance (type 2).
Types:
Type1:
Destruction of beta cells in islets of Langerhans by T-cells & autoantibodies.
Early onset.
High blood glucose, lipid, ketone (beta-hydroxybutyrate, acetoacetate, acetone).
Type2:
Multi-gene. Associated with excess body weight.
Late onset.
 Hyperinsulinemia at first, then decline of beta-cell function.
No significant ketone rise. There is still insulin to inhibit HMG-CoA synthase that produces
ketone, so less ketone production.
Effects:
No glucose uptake from some cells.
More glycogenolysis, gluconeogenesis.
Less glycogen synthesis, glycolysis.
Features:
Intracellular glucose deficiency:
For cells which are insulin dependent.
Starvation in the midst of plenty, increase protein catabolism.
Intracellular hyperglycemia:
Non-enzymatic glycosylation:
Glycated hemoglobin in RBCs (HbA1c).
Amadori products in blood vessels:
Glucose attaches non-enzymatically to protein amino groups to form amadori
products, then advanced glycosylation end products (AGEs).
This causes cross linkage of matrix proteins which may damage blood vessels,
causing cataract. (Glucose accumulates in lens and turned into sorbitol, cannot go
out again and accumulates in lens, causing stress)

Sorbitol production:
High intracellular glucose activates aldose reductase, forming sorbitol. This inhibits
sodium potassium ATPase activity.
Sorbitol in Schwann cells disrupts the cells’ structure and function.
Sorbitol can also be converted into fructose.
High plasma free fatty acid level:
Normally:
Insulin inhibits hormone-sensitive lipase in adipose tissue that releases fats from
adipose tissue and liver.
Insulin stimulates lipoprotein lipase that increases uptake of FFA into adipose tissue.
Insulin also stimulates synthesis of triglycerides in liver and adipose tissue.
 Absence of insulin:
More hormone-sensitive lipase and less lipoprotein lipase, so transferring more fats
into blood and less fat uptake.
FFA is converted to acetyl-CoA, excess acetyl-CoA into ketone bodies (e.g. acetoacetate,
acetone, beta-hydroxybutyrate).
Ketoacids combine with bicarbonate buffer in plasma, increasing anion gap, causing
acidosis (diabetic ketoacidosis). Ketone in urine (ketonuria).
Low pH causes rapid, deep Kussmaul breathing.
Disturbed protein metabolism:
Normal:
Insulin stimulates uptake of free amino acids into cells.
Stimulate protein synthesis.
Absence of insulin:
More protein breaks down to form amino acids, causing muscle wasting.
Less protein synthesis.
Nitrogen loss in urine causes negative nitrogen balance and protein depletion (poor
resistance to infections).
Glucose in urine:
Renal threshold for glucose: 180mg%.
If plasma glucose is > 180mg%, glucose will be present in urine.
Polyuria (osmotic/too much diuresis), polydipsia, acetone (fruity odor).
Overall symptoms & signs:
Hyperglycemia, fatigue, glucosuria, polydipsia (increased thirst), polyuria (frequent urination),
polyphagia (extreme hunger), ketosis, acidosis, coma, blurred vision (cataract).
Complications:
Microvascular:
Retinopathy, nephropathy, neuropathy (wet grangrene).
Macrovascular:
Stroke, peripheral vascular disease, MI (due to atherosclerosis, more LDL).
Test:
Fasting overnight glucose level (FOG):
Normal: 80-100mg/dL.
Prediabetic: 100-125mg/dL.
Diabetic: >126mg/dL.
Oral glucose tolerance test 糖耐量試驗 (OGTT):
Give large amount of glucose and check the blood glucose after some time.
Normal: <140mg/dL.
Prediabetic: 140-200mg/dL.
 Diabetic: >200mg/dL.
Treatments:
Insulin.
Lifestyle changes.
Oral hypoglycemic drugs:
Metformin (decrease liver release of glucose).
Hypoglycemia:
Causes:
Beta cell tumor produces excess insulin (insulinoma).
Drug overdose; missing meals; exercise.
Symptoms:
Adrenergic:
Palpitation, tremor, anxiety.
Neuroglycopenic:
Confusion, fatigue, lethargy, loss of coordination, seizure, coma.
Normal physiological response:
1. Inhibition of insulin secretion.
2. Secretion of glucagon, epinephrine, and growth hormone.
3. Cortisol secretion.

Treatments:
IV dextrose, glucagon injection.
Candy, sugar, juice for alert patients.
Insulinoma:
Causes:
Beta cell tumors.
Symptoms:
Sugar carving, unusual weight gain, frequent hunger, extreme tiredness, lack of focus and low
blood sugar.
Thyroid tumor:
Types:
 Follicular adenoma:
Benign tumor looking as a solitary, encapsulated nodule.
Papillary thyroid carcinoma:
Malignant tumor with no capsule and has large, tightly packed cells with different inclusions
(e.g. pseudoinclusions, irregular membranes, clear nuclei with open chromatin).
Features:
Low TSH.
Treatments:
Total thyroidectomy:
High Tg after surgery indicates left over thyroid tissue or recurrence of tumor.
Levothyroxine:
Replace thyroid hormone.
Hyporeninemic hypoaldosteronism:
Diabetic nephropathy.
Hirsutism:
Causes:
Polycystic ovary syndrome (PCOS).
Idiopathic hirsutism.
Medications:
Danazol.
OCP with androgenic progestins.
Congenital adrenal hyperplasia (CAH).
Ovarian hyperthecosis.
Cushing’s syndrome.
Ovarian/adrenal tumors.
Hypothyroidism:
Thyroid hormone may affect sex hormone-binding hormonal globulin (SHBG).
Hyperthyroidism may increase testosterone and SHBG concentration.
Prolactinoma.
Sources of serum androgens in women:
Testosterone:
25% ovarian.
25% adrenal.
50% from peripheral conversion of androstenedione.
Androstenedione:
50% ovarian.
50% adrenal.
Dehydroepiandrosterone (DHEA):
90% adrenal.
10% ovarian.
Dehydroepiandrosterone sulfate (DHEA-S):
100% adrenal.
Assessments:
History:
Age of onset, progression, extent of growth.
Current measures of hair removal.
Age at menarche, regularity, fertility.
Change in libido, voice.
Family of hirsutism.
Symptoms of Cushing’s, prolactinoma, thyroid disease.
Medications.
Examinations:
Distribution & degree of hirsutism.
Increased muscle mass, temporal balding, clitoromegaly, acne.
Obesity.
Acanthosis nigricans.
Visual field defects.
Moon facies, plethora, features of Cushing’s.
Galactorrhea.
Goitre, loss of lat eyebrows.
Abdominal or pelvic mass.
Ferriman-Gallwey score:

Investigations:
Testosterone.
SHBG/sex hormone binding globulin, free testosterone.
DHEAS/dehydroepiandrosterone.
LH, FSH.
TSH, PRL.
17OH progesterone, progesterone.

Short synacthen test with 17OH progesterone at 60mins.

Adrenal incidentaloma:
Examples:
Adenoma:
Nonfunctioning.
Cortisol-secreting.
Aldosterone-secreting.
Pheochromocytoma.
Adrenocortical carcinoma.
Metastasis.
Myelolipoma.
Cyst.
Ganglioneuroma.
Managements:
Firstly, look for functional state & malignancy:
E.g. DST, metanephrines, serum K & PAC/PRA for HT.
Non-functional, size <4cm, image suggesting benign adenoma:
No need repeat imaging.
Indeterminant mass, not operated:
Repeat imaging 6-12months later, resection if >1cm increase.
Functional or >4cm:
Resection.