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ENDOCRINOLOGY TiKi TaKa

_________________________
. THYROID DISEASES:
___________________
___________________
. P.O.C.
idism

___________________ HYPOthyroidism ______________ HYPERthyro


----------------

-----* Labs
TSH
* Weight
* Intolerance
* Hair
* Skin
* Mental
* Heart
a & Af
* Muscles
* Reflexes
e
* Fatigue
* Menstrual changes

-----------

___________________ -- T4 & ++ TSH ______________ ++ T4 & -___________________


___________________
___________________
___________________
___________________
___________________

Gain
Cold
Coarse
Dry
Depressed
Bradycardia

______________
______________
______________
______________
______________
______________

Loss
Heat
Fine
Moist
Anxious
Tachycardi

___________________ Week
___________________ Diminished

______________ Week
______________ Hyperactiv

___________________ Yes
___________________ Yes

______________ Yes
______________ Yes

. HYPOTHYROIDISM:
_________________
* PRIMARY Hypothyroidism * * Secondary Hypothyroidism *
idism *
________________________
_________________________
______
. -- T3 & T4.
. -- T3 & T4.
. ++ TSH.
. -- or normal TSH.
. Ex: Auto-immune Hashimoto's.

* TERTIARY Hypothyro
___________________
. -- T3 & T4.
. -- or normal TSH.

. HASHIMOTO's THYROIDITIS:
__________________________
. Hypothyroidism symptoms: Slow, tired, fatigued pt with weight gain.
. Anti-TPO Abs (Anti-thyroid peroxidase antibodies).
. -- T4 & ++ TSH.
. Tx -> T4 or thyroxine replacement.
. High risk of developing THYROID LYMPHOMA.
. GENERALIZED RESISTANCE to thyroid hormones:
_____________________________________________
. ++ T3 & T4 levels.
. ++ or Normal TSH level.
. features of HYPO-thyroidism despite having ++ free T3 & T4.
. N.B. HYPOTHYROIDISM & MYOPATHY:
_________________________________
. Un-explained ++ ofe serum CPK creatinine kinase.
. ANA Anti-nuclear antibodies may be +ve in HASHIMOTO's thyroiditis.
. Serum TSH level is the most sensitive test to diagnose hypothyroidism.
. HYPERTHYROIDISM -> "Grave's disease" - "Silent"
adenoma":

- "Subacute" - "Pituitary

________________________________________________________________________________
__________
. Physical findings: . Eye,skin,nails - Not tender - Tender gland - None.
. RAIU scan:
.
(++)
- (--)
(--)
- (++).
. TTT:
. Iodine ablation - None
Aspirin - Surgical r
emoval.
.1. GRAVE's DISEASE:
____________________
. Symptoms of thyrotoxicosis (weight loss - insomnia - hperactivity - tachycard
ia).
. Ophthalmopathy (Exophthalmos & proptosis - Abs against the extra-ocular muscl
es).
. Dermopathy (Thickening & redness of the skin just below the knee).
. Onycolysis (Separation of the nail from the nailbed).
. Peri-orbital lymphocytic infiltration -> Gritty sandy sensation.
. Fibroblast proliferation, hyaluronic acid deposition, edema & fibrosis.
. Throid stimulating immunoglobulins.
. RAIU -> HIGH.
. Tx -> Propylthiouracil (PTU) or methimazole.
. Use radioactive iodine to ablate the gland (May cause permanent HYPO-thyroidi
sm).
. BB (propranolo) to treat sympathetic symptoms, such as tremos & palpitations.
.2. SILENT Thyroiditis:
_______________________
. Auto-immune process.
. Symptoms of thyrotoxicosis (weight loss - insomnia - hperactivity - tachycard
ia).
. NON-tender gland.
. No skin, eye or nail diseases.
. RAIU -> NORMAL.
. Tx -> NONE !
.3. SUB-ACUTE Thyroiditis = De QUERVAIN's THYROIDITIS:
______________________________________________________
. Viral etiology.
. ++ ESR > 50 mm/hr.
. Thyroid TENDRNESS.
. Syms last for < 8 wks due to thyroid depletion.
. RAIU -> LOW.
. Tx -> ASPIRIN to relieve pain.
.4. PITUITARY ADENOMA:
______________________
. THE ONLY CAUSE OF HYPERTHYROIDISM WITH ++ T4 & ++ TSH !
. Dx -> Brain MRI.
. Tx -> Surgical removal.
.N.B. EXOGENOUS THYROID HORMONE ABUSE:
______________________________________
. ++ T4 & -- TSH.
. The galnd will atrophy to the degree of non-palpability on exam.
. N.B. THYROID STORM:
_____________________
. Acute, severe life threatening hyperthyroidism.
. Tx -> IODINE -> Blocks uptake of iodine into the gland.
. Tx -> Propylthiouracil or methimazole -> Blocks the production of thyroxine.
. Tx -> Dexamethazone -> Blocks peripheral conversion of T4 to T3.

. Tx -> Propranolol -> Blocks target organ effect.


# THYROID NODULE APPROACH:
__________________________
A . 1st step -> Cilinical evaluation - TSH level & thyroid ULTRA$OUND.
______________________________________________________________________
B . CANCER risk factors or suspicious U$ findings ??
____________________________________________________
. YES -> FNAB (Fine Needle Aspiration Biopsy).
. NO -> C. (TSH level).
C . TSH LEVEL ??
________________
. Normal or ++ -> FNAB.
. -- Low -------> D. (I 123 scintigraphy).
D . I - 123 scintigraphy:
_________________________
. HYPER-functional (HOT) nodule -> Treat hyperthyroidism.
. HYPO-functional (COLD) nodule -> FNAB.
. MOST thyroid nodules are BENIGN COLLOID nodules.
__________________________________________________
. SICK EUTHYROID $YNDROME = LOW T3 $YNDROME:
____________________________________________
. Abnormal thyroid function tests with an acute severe illness.
. May be due to caloric deprivation.
. Fall in total & free T3 levels with NORMAL T4 & TSH.
. FACTITIOUS THYROTOXICOSIS:
____________________________
. Due to exogenous thyroid hormone.
. H/O of psychiatric illness or attempted weight loss (Herbal remedy!).
. Thyrotoxicosis syms (Palpitations - sweating - weight loss - hyperactivity &
diarrhea).
. Lid lag may be present but NO exophthalmos (Excluding Grave's dis.).
. The ingested thyroid hormone disturbs the native thyroid axis !
. RAIU is decreased (-- Radio Active Iodine Uptake).
. Dx -> "LOW SERUM THYROGLOBULIN" is the main stay of diagnosis.
. Dx -> -- TSH & ++ T3 &/or T4.
. TOXIC ADENOMA:
________________
. ++ T4 & -- TSH levels.
. Symptoms suggestive of thyrotoxicosis.
. Radioactive uptake in the nodule & suppression of uptake ith rest of the thyr
oid gland.
. No infiltrative ophthalmopathy.
. THYROID RADIOACTIVE IODINE SCAN:
__________________________________
. HASHIMOTO's THYROIDITIS -> Heterogenous pattern.
. GRAVE's DISEASE ---------> Diffusely ++ uptake.
. MULTINODULAR GOITER -----> PATCHY.
. PAINLESS THYROIDITIS ----> -- markedly reduced uptake.
. SIDE EFFECTS OF RADIO-IODINE THERAPY -> HYPO or HYPER thyroidism !!

_____________________________________________________________________
. HYPOTHYROIDISM:
_________________
. Destruction of thyroid flollicles by radioactive iodine.
. Tx of hypothyroidism is Levo-thyroxine.
. Ophthalmopathy may worsen in 10 % of cases.
. THYROTOXICOSIS:
_________________
. may be a side effect of RADIO-IODINE theray !!
. I - 131 is taken up by thyroid follicles & then destroys them by emitting B-r
ays.
. Dying thyroid cells may release excess thyroid hormone into the circulation.
. Aggravating the hyperthyroid state.
. CONTRA-INDICATIONS to RADIO-ACTIVE IODINE THERAPY:
____________________________________________________
. PREGNANCY.
. VERY SEVERE OPHTHALMOPATHY.
. SIDE EFFECTS of ANTI-THYROID DRUGS (PROPYLTHIOURACIL):
________________________________________________________
. AGRANULOCYTOSIS (fever & sore throat) -> Stop the drug !
. SURGERY SIDE EFFECTS:
_______________________
. Permanent hypothyroidism.
. Risk of recurrent laryngeal nerve damage.
. COMPLICATIONS of UN-TREATED HYPER-THYROID PATIENTS:
_____________________________________________________
-> RAPID BONE LOSS -> due to ++ osteoclastic activity .
-> CARDIAC TACHYARRHYTMIA (Af).
. N.B. HYPERTENSION in pts with THYROTOXICOSIS:
_______________________________________________
. is predominantly SYSTOLIC.
. caused by HYPERDYNAMIC CIRCULATION.
. N.B. INDICATIONS OF THYROID FUNCTION TESTS:
_____________________________________________
-> HYPERLIPIDEMIA.
-> Un-explained hyponatremia.
-> Un-exlained ++ CPK.
# THYROID MALIGNANCIES:
_______________________
1 * PAPILLARY CARCINOMA:
________________________
-> MOST COMMON TYPE & BEST PROGNOSIS.
-> Slow infiltrative local spread.
-> Presence of PSAMMOMA bodies.
2 * MEDULLARY CARCINOMA:
________________________
-> CALCITONIN secretion.
3 * FOLLICULAR CARCINOMA:
_________________________
-> Invasion of the tumor capsule & blood vessels.
-> Early metastasis to distant organs.

. BIOCHEMISTERY IMPORTANT INFO:


_______________________________
. GLUCONEOGENESIS main substrates:
__________________________________
. Alanine - Lactate - Glycerol 3 phosphate.
. PYRUVATE is an INTERMEDIATE of Alaninie.
. MULTIPLE ENDOCRINE NEOPLASIA (MEN):
_____________________________________
* MEN TYPE 1:
______________
. Parathyroid adenoma.
. Pituitary tumor.
. Pancreatic tumor.
. {Mutation in the MEN 1 tumor suppressor gene}.
* MEN TYPE 2A:
______________
. Medullary thyroid cancer (HARD NODULE - ++ Calcitonin - Malignant cells on FN
AB).
. Pheochromocytoma.
. Parathyroid hyperplasia.
. Less aggressive (No associated cancers).
* MEN TYPE 2B:
______________
. Medullary thyroid cancer (HARD NODULE - ++ Calcitonin - Malignant cells on FN
AB).
. Pheochromocytoma (++ urinary metanephrines & nor-epinephrines levels).
. Neuromas (mucosal & intestinal).
. Marfanoid habitus (-- upper to lower body ratio - hypermobile joints - scolio
sis).
. {Mutation in the RET proto-oncogene located on chromosome 10}.
. DNA testing is used for screening.
. More aggressive (Associated cancers).
. DM SCREENING TESTS:
_____________________
.1. GLYCOSYLATED HEMOGLOBIN Hb A 1C:
_____________________________________
. It is used to monitor chronic glycemic control.
. It is reflective of the pt's average glucose levels over the past 100-120 day
s.
. Preferred test in non fasting state.
. > 6.5 -> DM.
. < 5.7 -> Normal.
.2. FASTING BLOOD GLUCOSE:
___________________________
. No caloric intake for 8 hours.
. > 126 mg/dl -----> DM.
. 100 - 125 mg/dl -> Impaired fasting glucose.
. 70 - 99 mg/dl ---> NORMAL.
.3. RANDOM GLUCOSE LEVEL:
__________________________
. > 200 mg/dl with symptoms of hyperglycemia.

.4. ORAL GLUCOSE TOLERANCE TEST:


_________________________________
. MOST SENSITIVE TEST.
. 75 g glucose load with glucose testing for 2 hours.
. > 200 mg/dl -----> DM.
. 140 - 199 mg/dl -> Impaired glucose tolerance.
. DKA DIABETIC KETOACIDOSIS:
____________________________
. Blood glucose level > 250.
. pH < 7.3
. Low serum HCO3 < 15-20
. Detection of plasma ketones.
. ++ ANION GAP {(Na) - (Cl+HCO3)} ----> AG > 8-12.
. H/O of previous stressor e.g. recent GIT infection.
. H/O of weight loss, ployurea & polydipsia.
. Deep rapid breathing (Kussmaul's respiration).
. Osmotic diuresis -- total body K (But : Serum K may be elevated!).
. ++ in K level due to EXTRA-CELLULAR SHIFT.
. PARADOXICAL HYPERKALEMIA (The body potassium reserves are actually depleted!)
. 1st initial simple step to detect DKA --> FINGER-STICK GLUCOSE !
. DKA MANAGEMENT:
_________________
.1. RAPID INTRAVENOUS NORMAL SALINE (0.9% SALINE).
.2. RAPID INTRAVENOUS REGULAR INSULIN.
.3. K correction.
.4. TTT of infections e.g. Abs.
. ARTERIAL pH or ANION GAP is the most reliable indicator of metabolic recovery
in DKA.
________________________________________________________________________________
_______
. HYPER-GLYCEMIC HYPER-OSMOLAR NON-KETOTIC COMA:
________________________________________________
-> Very high glucose levels.
-> Very high plasma osmolality.
-> NORMAL ANION GAP.
-> NEGATIVE SERUM KETONES.
. Non ketotic - Hyperglycemic coma management:
______________________________________________
. Fluid replacement with NORMAL SALINE.
_______________________________ .................... __________________________
______
. DIABETIC KETOACIDOSIS (DKA) .................... HYPEROSMOLAR HYPERGLYCEMIC
STATE
________________________________ .................... __________________________
______
. Type (1) DM usually.
____________________ . Type (2) DM.
. YOUNGER age.
____________________ . Older.
. LESS confusion.
____________________ . MORE confusion.
. Hyperventillation MORE common ____________________ . Less common.
. Abdominal pain MORE common. ____________________ . LESS common.
_______________________________________________________________________________
_______

.
.
.
.
.

Glucose 250 - 500 mg/dl.


HCO3 < 18 meq/L.
+++++ ANION GAP.
POSITIVE serum ketones.
Serum osmolality < 320

____________________
____________________
____________________
____________________
____________________

.
.
.
.
.

> 600
> 18
NORMAL.
NEGATIVE.
> 320.

. DIABETIC NEPHROPATHY:
_______________________
. Begins with HYPERFILTRATION (++GFR) & MICROALBUMINURIA.
. If not ttt well .. Micro becomes Macroalbumiuria > 300 mg/dl.
. INTENSIVE BLOOD PRESSURE CONTROL to prevent worsenening of the condition.
. Use ACE Is with blood pressure goal 130/80 mmHg.
. Most sensitive screening test is -> RANDOM URINE MICRO-ALBUMIN/CREATININE RAT
IO.
. DIABETIC NEUROPATHY:
______________________
. DISTAL SYMMETRIC SENSORIMOTOR PLOYNEUROPATHY.
. STOCKING GLOVE pattern.
. It is the most common risk factor of foot ulcerations in diabetics.
. Tx -> TCAs (Amitriptyline - Gabapentin).
. DIABETIC GASTROPATHY:
_______________________
. Autonomic neuropathy of the GIT.
. Symptoms of delayed gastric emptying & gastroparesis.
. -- Esophageal dysmotility -> Dysphagia.
. -- Gastric emptying -------> Gastroparesis.
. Gastroparesis (Nausea - vomiting - early satiety - postprandial fullness).
. -- intestinal function ----> diarrhea - constipation - incontinence.
. Tx -> DN control - SMALL FREQUENT MEALS - METOCLOPROMIDE (prokinetic & Antiem
itic).
. SEs of Metoclopromide -> Extrapyramidal syms -> Tardive dyskinesia (Give Eryt
hromycin).
. ERECTILE DYSFUNCTION in D.M.:
_______________________________
. Due to vascular complications & neuropathy.
. 1st line of ttt is phosphodiesterase inhibitor (Sildenafil).
. Contr'd in pts being ttt with NITRATES.
. Sildenafil may predispose to PRIAPISM.
. When combined with an Alpha blocker (Prazosin), it is imp. to give them 4 hrs
apart,,
. to avoid SEVERE HYPOTENSION.
. DIABETIC FOOT management -> DEBRIDEMENT & proper wound care.
______________________________________________________________
. CAUSES OF HYPOGLYCEMIA in NON-DIABETIC pts:
_____________________________________________
1 - INSULINOMA (BETA cell tumor).
2 - SURREPTITIOUS use of insulin or sulfonylurea.
. INSULINOMA:
_____________
. BETA CELL TUMOR.
. Normally, blood glucose < 60 mg/dl result in complete suppression of insulin
secretion.
. Hypoglycemia in the presence of inappropriately ++ serum insulin levels = ins
ulinoma.

. ++ C-peptide level.
. ++ Pro-insulin.
. DIABETES INSIPIDUS:
_____________________
. Due to ADH defeciency or resistance.
. Urine osmolality is < serum osmolality.
. Polyurea & polydipsia.
. H/O of tendency to COLD BEVERAGES to QUENCH THIRST.
. Exclude psychogenic polydipsia using water deprivation test.
. Differentiate bet. central & nephrogenic DI using ARGININE VASOPRESSIN.
. Tx -> NORMAL SALINE.
. Tx -> CENTRAL -> INTRANASAL SPRAY DDAVP.
. Tx -> NEPHROGENIC -> NSAIDs & HCZ.
. HOW CAN U DIFFERENTIATE BET. DI & PSYCHOGENIC POLYDIPSIA:
___________________________________________________________
. WATER DEPRIVATION TEST:
__________________________
. Failure to concentrate urine after deprivation -> DI.
. Production of concentrated urine ---------------> Psychogenic polydipsia.
. HOW CAN U DIFFERENTIATE BET. CENTRAL & NEPHROGENIC DI:
________________________________________________________
. ARGININE VASOPRESSIN (AVP) or DESMOPRESSIN adminstration:
____________________________________________________________
. CENTRAL DI -----> ++ in urine osmolality.
. NEPHROGENIC DI -> No significant ++ !
. SYNDROME OF INAPPROPRIATE ADH SECRETION (SIADH):
__________________________________________________
. ++ ADH levels without stimuli of its release.
. NORMAL SERUM osmolality -> 275 - 295 mOsm.
. NORMAL URINE osmolality -> 50 - 1400 mOsm.
. Dx -> Simultaneous measurment of urine & plasma osmolality.
. The normal response to hypotonicity (low plasma osmolality) is ,
. the production of maximally diluted urine (low urine osmolality -> < 100 mOsm
.)
. LOW plasma osmolal. (<280 mOsm.) & HIGH urine osmolality (>100-150mOsm) is di
agnostic.
. Tx of SIADH:
-> Mild symptoms (forgetfulness & unstable gait) -> Fluid restriction.
-> Moderate symptoms (Confusion & lethargy) -> HYPERTONIC SALINE (3%).
-> Severe symptoms (seizures & coma) -> Hypertonic saline + Conivaptan.
. BOTTOM LINE:
______________
* Diabetes insipidus:
______________________
. Polyurea - polydipsia - excretion of diluted urine with ++ serum osmolality.
* 1ry (Psychogenic) polydipsia:
________________________________
. Excessive water drinking -> BOTH plasma & urine are diluted.
* SIADH:
_________
. Hyponatremia - LOW serum osmolality & inappropriately high urine osmolality.
. P.O.C.------- # DIABETES INSIPIDUS -------- # PSYCHOGENIC POLYDIPSIA ---------

# SIADH
_____
__________________
_____
-> SERUM osm. --->
(+)
(-)
-> URINE osm. --->
(-)
(+)

______________________
(-)
(-)

. HYPER-VITAMINOSIS "D":
________________________
. H/O of trials of weight loss with vitamin supplementations.
. Vit. D ++ Ca absorption -> Hypercalcemia.
. Constipation - Abd. pain - Polyurea - Polydipsia.
. METABOLIC $YNDROME:
_____________________
1- ABDOMINAL OBESITY ->
2- DIABETIS MELLITIS ->
3- HYPERTENSION ------>
4- HYPERLIPIDEMIA ---->
mg/dl).

Waist circumference (Men > 40 & Women > 35 inches).


Fasting glucose > 100 - 110 mg/dl.
Blood pressure > 130/80 mmHg.
Triglycerides > 150 mg/dl & HDL (Men < 40 & Women < 50

. The main mechanism of DM development in metabolic $ is INSULIN RESISTANCE.


. ACROMEGALY:
_____________
. ++ GROWTH hormone by SOMATOtroph PITUITARY ADENOMA.
. GH -> ++ IGF-1.
. IGF-1 ++ growth of bones & soft tissues.
. Coarse facial features - arthralgia - uncontrolled HTN - skin tags.
. Carpal tunnel $.
. Dx -> The MOST SENSITIVE TEST is -> IGF-1 level (GH level fluctuations is dec
eiving).
. Suppression of GH by giving glucose excludes acromegaly.
. MRI -> Pituitary lesion.
. Tx -> Surgical resection with trans-sphenoidal removal.
. Tx -> Somatostatin - Cabergoline or bromocriptine.
. MOST COMMON CAUSE OF DEATH is CONGESTVE HEART FAILURE.
. Non cardiac causes of death: stroke - cancer colon - renal failure.
. ANDROGEN PRODUCING ADRENAL TUMOR in FEMALES:
______________________________________________
. Best indicator is DHEA-S = De-Hydro Epi-Androsterone Sulfate.
. PROLACTINOMA:
_______________
. Prolactin secreting micro-adenoma.
. Pituitary tumor < 10 mm in diameter is called micro-adenoma.
. Amenorrhea & galactorrhea in females.
. Hypogonadism in males.
. Its small size can't lead to mass effects of ++ ICT.
. Tx -> 1st line is medical ttt with Dopamine agonists (CABERGOLINE or BROMOCRI
PTINE).
. Cabergoline normalizes the prolactin level & shrinks the tumor's size.
# CALCIUM HOMEOSTASIS:
______________________
. 3 forms of calcium (ionized Ca 45% - Albumin bound Ca 40% - Inorganic anions
bound Ca).
. Albumin plays an imp. role !

.
.
.
ed
.
.
.
.
.

Pts with hypo-albuminemia can have a low level of total plasma ca,
However ,, They may NOT present with clinical hypocalcemia,
Because their level of ionized calcium (physilologically active form) remain
normal.
So .. it is imp. to calculate the CORRECTED SERUM CALCIUM LEVEL.
CORRECTED SERUM CALCIUM LEVEL = TOTAL Ca + 0.8 (4 - Serum Albumin).
Another rough method,
With every 1 g/dl change in serum albumin level from 4 g/dl,
there is a change in total plasma Ca level by 0.8 mg/dl.

# ++ Ca (Hyperclacemia) Approach -> Measure Parathormone (PTH):


_______________________________________________________________
* ++ Ca & ++ PTH -> 1ry hyperparathyroidism (abd. groans - renal stones - bones
- moans).
________________
* ++ Ca & -- PTH -> Malignancy - vit. D toxicity - Sarcoidosis.
________________
# -- Ca & ++ PO4 causes -> CRF & Primary hypothyroidism.
________________________________________________________
. CHRONIC RENAL FAILURE:
________________________
. -- Ca & ++ PO4 & ++ PTH.
. Exclude CRF by NORMAL renal function tests (urea & creatinine).
. PRIMARY HYPO-THYROIDISM:
__________________________
. Causes -> post-surgical- congenital absence - autoimmune.
. Post surgical may occur after thyroidectomy & removal of 3.5 out of 4 parathy
roids.
. -- Ca -> perioral tingling - numbness - ms cramps - carpopedal spasms - seizu
res.
. EKG -> prolongation of the QT interval.
# Causes of ++ Ca & + PTH: 1ry Hyperparathyroidism & familial hypocalciuric hype
rcalcemia:
________________________________________________________________________________
__________
. Differentiated by 24 hour urinary calcium:
____________________________________________
. Primary Hyper-parathyroidism ---------> > 250 mg.
. Familial hypocalciuric hypercalcemia -> < 100 mg.
. PRIMARY HYPER-PARA-THYROIDISM:
________________________________
. Causes -> Parathyroid adenoma (90%) - hyperplasia (6%) & carcinoma (2%).
. Associated with MEN 1 & 2A.
. 80 % of pts are asymptomatic.
. Abdominal groans, renal stones, bones #s & psychic moans.
. ++ Ca & -- PO4 & ++ or normal PTH.
. 24 hours urinary calcium > 250 mg.
. Urinary calcium/creatinine > 0.02 (To rule out familial hypo-calciuric hypercalcemia).
. Dx -> 3Ds SESTAMIBI scan + U/$ to locate the hyperactive parathyroid tissue p
resurgery.
. Tx -> Parathyroidectomy for symptomatic pts.
. Surgery indications:
_____________________
-> Serum Ca level > 1 mg/dl above the upper limit of normal (11mg/dl).
-> Young age < 50 ys.

-> Bone mineral density < T-2.5 at any stage.


-> -- Renal function (GFR < 60ml/min.).
. HYPERCALCEMIA of MALIGNANCY:
______________________________
. ++ Ca -> confusion - lethargy - fatigue - anorexia - polyuria & constipation.
. Associated with SQUAMOUS cell lung cancer.
. CXR finding of lung cancer (lobar mass & perihilar lymphadenopathy).
. Malignancy produces PTH related peptide PTHrP -> ++ Ca & -- PO4.
. HYPERCALCEMIA (++Ca) ALGORITHM:
_________________________________
.(++Ca)
.|
.Measure PTH level
__________________
.|
.____________________________________________________
.|
.|
.(+++)
.(---)
.(PTH dependent)
. (PTH-INdependent)
________________
___________________
.|
.|
.Measure urinary Ca
._____________________________________________
__
.|

.|

.|

.|

.+1,25(OH)D

.+25(OH)D

.|

.|

.|
.________________
.+PTHrP
AL LABs
.|
.|
.|
.|
.> 250
.< 100
.TUMOR
THYROIDISM
.|
.|
P. MYELOMA
1ry or 3ry
.Familial
al tumor
Hyperpara.Hypercalcemic
egaly
thyroidism
.Hypocalciuria
toxicity

.NORM

.Lymphoma-Sarcoid .Vit.D toxicity.HYPER


.MULTI
.Adren
.Acrom
.Vit.A
.Immob

ilization
. IMPORTANT CASE SCENARIO:
__________________________
. Rapid ascent to a height of 10000 feet -> HYPO-calcemia ! HOW ?? (++ Albumin
bound Ca).
________________________________________________________________________________
__________
. Respiratory alkalosis = ++ pH level -> ++ the affinity of serum albumin to ca
lcium.
. ++ the levels of ALBUMIN-bound Ca -> -- the level of IONIZED Ca (Active form)
.
. -- Ionized Ca (Active form) -> Hypocalcemia manifestations.
. PAN-HYPO-PITUITARISM:
_______________________
* Pituitary tumors are the most common cause by exerting pressure on pituitary

cells.
* ACTH defeciency (2ry adrenal insuffeciency): "-- Glucocorticoids":
____________________________________________________________________
-> Postural hypotension & tachycardia.
-> Fatigue & weight loss.
-> -- libido, hypoglycemia & eosinophilia.
* HYPOTHYROIDISM (Central):
___________________________
-> Fatigue, cold intolerance, -- appetite, constipation & dry skin.
-> Bradycardia, delayed relaxation phase of DTRs & anemia.
* -- GONADOTROPINS:
___________________
-> Women -> Amenorrhea, infertility & hot flashes.
-> Men -> -- energy & libido.
. OSTEOPOROSIS:
_______________
. Postmenopausal woman.
. presenting with multiple bony #s.
. NORMAL serum Ca - PO4 & PTH.
. OSTEOMALACIA:
_______________
. Vit. D defeciency in ADULTS.
. Bony pain & tendrness.
. -- serum Ca & PO4.
. -- urinary Ca.
. ++ ALP & ++ PTH.
. -- 25 OH-D.
. X-ray -> BILATERAL SYMMETRIC PSEUDO-FRACTURES (LOOSER ZONES).
. PAGET's DISEASE:
__________________
. NORMAL serum Ca - PO4 & PTH.
. INCREASED ++ ALKALINE PHOSPHATASE.
. Tx -> BIPHOSPHONATES -> inhibit OsteoCLASTs asctivity.
. CAUSES of HYPOKALEMIA & --BICARBONATE HCO3 {Metabolic Alkalosis} -> (Check REN
IN):
________________________________________________________________________________
____
.. CAUSES of HYPOKALEMIA & ++ ALDOSTERONE & -- RENIN -> PRIMARY HYPER-ALDOSTERON
ISM.
_____________________________________________________
.. CAUSES of HYPOKALEMIA & ++ BOTH ALDOSTERONE & RENIN -> (Check Cl):
_____________________________________________________________________
(A) WITH ++ CHLORIDE (Check Na):
_________________________________
1- -- Na -----> (Diuretic use).
2- Normal Na -> (Bartter's $).
3- ++ Na -----> (Renin secreting tumor).
. SURREPTITIOUS VOMITING:
_________________________

(B) WITH -- CHLORIDE:


_____________________
1- Surreptitious vomiting.
2- Factitious diarrhea.

. Scars & calluses on the dorsum of the hands & dental erosions.
. Result from chemical & mechanical injury as the pt uses his hands to induce v
omiting.
. Dental erosions result due to ++ exposure to gastric acid..
. May lead to hypovolemia & hypochloremia -> Low urine Cl level.
. CAUSES OF HYPERTENSION & HYPOKALEMIA:
_______________________________________
. Primary hyperaldosteronism & Reno-vascular hypertension.
. Check the PLASMA RENIN ACTIVITY (PRA).
. Primary hyperaldosteronism -> LOW PRA.
. Reno-vascular hypertension -> HIGH PRA.
# ADRENAL DISORDERS:
____________________
____________________
.1. CUSHING $YNDROME = HYPER-Corticolism:
_________________________________________
. ++ Cortisol.
. Fat redistribution -> Truncal obesity - moon face - buffalo hump - thin arms
& legs.
. Easy bruising & striae -> Cortisol leads to loss of collagen.
. Hypertension -> From salt & water retention.
. Ms wasting.
. Hirsutism -> due to ++ adrenal androgen levels.
. Hyperglycemia - Hyperlipidemia - Leukocytosis - Metabolic alkalosis.
. Dx -> 1 mg over-night dexamethasone suppression test:
_______________________________________________________
. Give dexamethasone at 11 a.m. the night before.
. A normal person will will suppress the 8 a.m. level.
. A NORMAL 1 mg overnight dexamethasone suppression test EXCLUDES hypercorticol
ism.
. Abnormal test may be false elevated due to stress or alcoholism.
. Dx -> 24 hour urine cortisol:
_______________________________
. Done to confirm that an overnight dexamethasone suppression test is not false
ly ++.
_______________________________________________________________________________
_
. Sources of Cushing $ ------> Pituitary tumor - Ectopic - ACTH Adrenal adenoma
:
_______________________________________________________________________________
_
.
.
.
.

ACTH ---------------------->
High dose dexamethazone --->
Specific tests ------------>
Tx ------------------------>

HIGH
Suppression
MRI
Removal

- HIGH
No
CT
- Removal

LOW.
No.
CT adrenals.
Removal.

. TO DIAGNOSE THE PRESENCE OF CUSHINNG $, Do the following tests:


__________________________________________________________________
1- 24 hour urine cortisol.
2- 1 mg over night dexamethasone test.
. To diagnose the origin of CUSHING $, Check the ACTH level:
_____________________________________________________________
* ACTH -> HIGH -> PITUITARY or ECTOPIC source.
* ACTH -> LOW -> ADRENAL source.

.2. ADRENAL INSUFFECIENCY = ADDISON DISEASE:


____________________________________________
. Fatigue, anorexia, weight loss, weakness & hypotension.
. Thin pt with hyperpigmented skin.
. Labs -> ++ K, -- Na, -- BP & EOSINOPHILIA.
. Dx -> COSYNOTROPIN (Synthetic ACTH) stimulation test:
_______________________________________________________
. Measure the level of cortisol bef. & aft. cosynotropin adminstration.
. NO RISE IN CORTISOL -> Adrenal insuffeciency.
. Dx -> CT adrenals.
. Tx -> FLUIDS + Steroid replacement (IV HYDROCORTISONE).
. CAUSES:
__________
. 1- Auto-immune adrenalitis -> Responsible of 80% of cases in developed countr
ies.
. 2- Adrenal Tuberculosis -> CT: CALCIFICATION of both glands.
. CENTRAL (TERTIARY) ADRENAL INSUFFECIENCY:
___________________________________________
. Due to long term supra-physiologic doses of prednisone.
. Suppressing the hypothalamic pituitary adrenal (HPA) axis.
. Glucocorticoids suppress Corticotropin Releasing Hormone secretion from hypot
halamus,
. Also .. Block the action of of CRH on the anterior pituitary to release ACTH.
. ACTH acts on adrenal cortex & is responsible for the secretion of cortisol &
androgen.
. ACTH has mild stimulatory effect on Aldosterone secretion,
. so .. Aldosterone level is relatively normal in ACTH defeciency in central ad
renal def.
. NORMALLY, Cortisol suppresses ADH production by the posterior pituitary.
. In case of central adrenal def. -> -- cortisol -> ++ ADH secretion.
. ++ ADH -> Water retention -> Hyponatremia.
. TYPES OF ADRENAL INSUFFECIENCY ALGORITHM:
___________________________________________
.Symptoms & signs of adrenal insuffeciency
__________________________________________
.|
. 250Mg COSYNOTROPIN stimulation test with CORTISOL & ACTH levels
.________________________________________________________________
.|
. Minimal response
._________________
|
._________________________________________________
.|
|
. Basal cortisol LOW
. Basal cortisol
LOW
. ACTH HIGH
.____________________

. ACTH LOW
.________________

____
.|
. PRIMARY AI
RY AI
.3. PRIMARY HYPER-ALDOSTERONISM:

.|
. SECONDARY or TERTIA

________________________________
. Hypokalemia + Hypertension + Proximal muscle weakness & numbness.
. Hypernatremia + metbaolic alkalosis.
. Dx -> Measure (PA:PRA) -> Plasma Aldosterone : Plasma Renin Activity ratio.
. Result -> ++ Plasma Aldosterone & -- Plasma Renin Activity i.e. Ratio > 30 !
. (PA:PRA) -> is the most specific test.
. Confirm the diagnosis -> Aldosterone suppression test.
. Give oral or IV NaCl then measure 24 hs urinary or plasma aldosterone level.
. If Aldosterone level > 14 mg/24 hs despite Na loading -> So Dx is confirmed.
. Once u confirm the diagnosis -> Detect the cause,
. CT scan of the adrenals -> Adrenal mass -> Adrenal vein sampling.
. EVALUATION OF SUSPECTED HYPERALDOSTERONISM:
_____________________________________________
. HYPERTENSION & HYPOKALEMIA
_____________________________
|
. Measure PLASMA RENIN ACTIVITY (PRA)
______________________________________
.& PLASMA ALDOSTERONE CONCENTRATION (PAC)
_________________________________________
|
______________________________________________________
|
|
|
. + PRA & + PAC
. - PRA & + PAC
. - PRA & - PAC
________________
________________
________________
|
|
|
SECONDARY HYPERALDOSTERONISM PRIMARY HYPERALDOSTERONISM Other causes of ++ A
ldosterone
____________________________ __________________________ ____________________
__________
* Diuretic use.
* Do a CT ADRENAL to
*Congenital adrenal h
yperplasia
* Liver cirrhosis.
* detect the etiology ! * Glucocorticoid resi
stance.
* Congestive heart failure.
* Exogenous mineraloc
orticoid.
* Reno-vascular hypertension.
* Cushing's $yndrome.
* Renin secreting tumor.
* Malignant hypertension.
* Coarctation of the aorta.
.4. PHEOCHROMOCYTOMA:
_____________________
. Headache, palpitations, tremors, anxiety & flushing.
. Episodic elevations of blood pressue.
. Dx -> BEST INITIAL -> ++ catecholamines level in plasma & urine.
. Dx -> BEST INITIAL -> ++ metanephrines & VMA levels.
. Dx -> MOST ACCURATE -> CT or MRI or MIBG of the adrenal glands.
. Tx -> PHENOXYBENZAMINE (Alpha blocker) "FIRST" to control blood pressure.
. e'out Alpha blockage, BB may lead to CATASTROPHIC ++ in BP due to unopposed A
lpha stim.
. Tx -> Propranolol is used "AFTER" an alpha blocker .
. Tx -> Surgical resection.
. N.B. It is a part of MEN type 2 A & B (DNA testing is imp. RET PROTO-ONCOGENE
).

.5. CONGENITAL ADRENAL HYPERPLASIA (CAH):


_________________________________________
. ++ ACTH.
. -- Aldosterone & cortisol.
. Tx -> Prednisone.
. Types of CAH:
_______________
____________________________ ___________________________
_________
* 21 hydroxylase defeciency - * 11 hydroxylase defeciency
feciency
____________________________ ___________________________
_________
* ++ Adrenal androgens
- * ++ Adrenal androgens
ens
* Hirsutism
- * Hirsutism
* ++ 17 hydroxy-progesterone- * NO
* NO hypertension
- * HYPERTENSION

____________________
- * 17 hydroxylase de
____________________
- * -- Adrenal androg
- * NO hirsutism
- * NO
- * HYPERTENSION

. LEYDIG CELL TUMORS:


_____________________
. Most common type of testicular sex cord tumors.
. ++ ESTROGEN & -- FSH & LH.
. ANDROGEN SECRETING NEOPLASM of the OVARY or ADRENAL:
______________________________________________________
. Rapidly developing hyper-androgenism with verilization.
. Serum TESTOSTERONE & DHEAS levels are diagnostic.
. ++ TESTOSTERONE & NORMAL DHEAS -> OVARIAN source.
. NORMAL TESTOSTERONE & ++ DHEAS -> ADRENAL source.
. PATHOLOGY of bone diseases:
_____________________________
. OSTEOMALACIA -> -- Mineralization of the bone.
. RICKETS ------> -- Mineralization of the bone & CARTILAGE.
. PAGET's ------> Disordered remodeling.
. OSTEOPOROSIS -> NORMAL mineralization but low bone mass.
. ERECTILE DYSFUNCTION:
_______________________
. Failure to achieve a spontaneous erection.
. Causes:
. * NEUROGENIC -> injury of the parasympathetic nerve fibers (# pelvis or ureth
ral tear).
. * VENOGENIC -> Disruption of tunica albuginea (# penis).
. * ENDOCRINOLOGIC -> ++ prolactin & -- Testosterone.
. * SITUATIONAL -> Anxiety (Nighttime & morning erctions are preserved).
. N.B. NOCTURNAL PENILE TUMESCENCE:
___________________________________
. helps to differentiate psychogenic from organic causes of male erectile dysf
unction.
. +ve in psychogenic causes.
. -ve in organic causes.
. PROLACTINOMA = LACTO-TROPH ADENOMA:
_____________________________________
. The MOST COMMON pituitary tumor.

. ++ PRL.
. Hypogoandism & galactorrhea.

Dr. Wael Tawfic Mohamed


_________________________