ENDOCRINOLOGY TiKi TaKa

. THYROID DISEASES:
. P.O.C.

HYPO-thyroidism

* Labs

-- T4 & ++ TSH

HYPER-thyroidism
++ T4 & -- TSH

* Weight

Gain

Loss

* Intolerance

Cold

Heat

* Hair

Coarse

Fine

* Skin

Dry

Moist

* Mental

Depressed

Anxious

* Heart

Bradycardia

Tachycardia & Af

Week

Week

* Muscles
* Reflexes

Diminished

Hyperactive

* Fatigue

Yes

Yes

* Menstrual changes

Yes

Yes

. HYPOTHYROIDISM:
* PRIMARY Hypothyroidism *

* Secondary Hypothyroidism *

* TERTIARY Hypothyroidism *

. -- T3 & T4.

. -- T3 & T4.

. -- T3 & T4.

. ++ TSH.

. -- Or normal TSH.

. -- Or normal TSH.

. Ex: Auto-immune Hashimoto's.

. 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 ++ of 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"

- "Subacute"

- "Pituitary adenoma"

. Physical findings:

. Eye, skin, nails

- Not tender - Tender gland

- None.

. RAIU scan:

- (--)

- (++).

. TTT:

. Iodine ablation

- None

- Aspirin

(++)

(--)

- Surgical removal.

.1. GRAVE's DISEASE:

. Symptoms of thyrotoxicosis (weight loss - insomnia - hyperactivity - tachycardia).
. Ophthalmopathy (Exophthalmos & proptosis - Abs against the extra-ocular muscles).
. 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.
. Thyroid stimulating immunoglobulins.
. RAIU -> HIGH.
. Tx -> Propylthiouracil (PTU) or methimazole.
. Use radioactive iodine to ablate the gland (May cause permanent HYPO-thyroidism).
. BB (propranolol) to treat sympathetic symptoms, such as tremors & palpitations.

.2. SILENT Thyroiditis:

. Auto-immune process.
. Symptoms of thyrotoxicosis (weight loss - insomnia - hperactivity - tachycardia).
. 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 gland 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 -> Dexamethasone -> Blocks peripheral conversion of T4 to T3.
. Tx -> Propranolol -> Blocks target organ effect.

# THYROID NODULE APPROACH:

A . 1st step -> Clinical 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 of the rest of the thyroid gland.
. No infiltrative ophthalmopathy.

. THYROID RADIOACTIVE IODINE SCAN:

. HASHIMOTO's THYROIDITIS -> Heterogeneous 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 follicles 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 therapy!!
. I - 131 is taken up by thyroid follicles & then destroys them by emitting B-rays.
. 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-explained ++ 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 Alanine.

. 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 FNAB).
. Pheochromocytoma.
. Parathyroid hyperplasia.
. Less aggressive (No associated cancers).
* MEN TYPE 2B:
. Medullary thyroid cancer (HARD NODULE - ++ Calcitonin - Malignant cells on FNAB).
. Pheochromocytoma (++ urinary metanephrines & nor-epinephrines levels).
. Neuromas (mucosal & intestinal).
. Marfanoid habitus (-- upper to lower body ratio - hypermobile joints - scoliosis).
. {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 days.
. 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!)

. DKA MANAGEMENT:
. 1st initial simple step to detect DKA --> FINGER-STICK GLUCOSE!
.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.

. Hyperventilation MORE common

Less common.

. Abdominal pain MORE common

LESS common.

. Glucose 250 - 500 mg/dl

> 600

. HCO3 < 18 meq/L

> 18

. +++++ ANION GAP

NORMAL.

. POSITIVE serum ketones

NEGATIVE.

. Serum osmolality < 320

> 320.

. DIABETIC NEPHROPATHY:
. Begins with HYPERFILTRATION (++GFR) & MICROALBUMINURIA.
. If not ttt well .. Micro becomes Macroalbumiuria > 300 mg/dl.
. INTENSIVE BLOOD PRESSURE CONTROL to prevent worsening of the condition.
. Use ACE Is with blood pressure goal 130/80 mmHg.
. Most sensitive screening test is -> RANDOM URINE MICRO-ALBUMIN/CREATININE RATIO.

. 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 -> DM control - SMALL FREQUENT MEALS - METOCLOPROMIDE (prokinetic & Antiemetic).
. SEs of Metoclopramide -> Extrapyramidal syms -> Tardive dyskinesia (Give Erythromycin).

. 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 = insulinoma.
. ++ C-peptide level.
. ++ Pro-insulin.

. DIABETES INSIPIDUS:
. Due to ADH deficiency or resistance.
. Urine osmolality is < serum osmolality.
. Polyuria & 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 administration:
. 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 measurement 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 diagnostic.
. 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:
. Polyuria - 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 - Polyuria - Polydipsia.

. METABOLIC $YNDROME:
1- ABDOMINAL OBESITY -> Waist circumference (Men > 40 & Women > 35 inches).
2- DIABETIS MELLITIS -> Fasting glucose > 100 - 110 mg/dl.
3- HYPERTENSION ------> Blood pressure > 130/80 mmHg.
4- HYPERLIPIDEMIA ----> Triglycerides > 150 mg/dl & HDL (Men < 40 & Women < 50 mg/dl).
. 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 deceiving).
. 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 BROMOCRIPTINE).
. 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!
. Pts with hypo-albuminuria can have a low level of total plasma ca,
. However, they may NOT present with clinical hypocalcemia,
. Because their level of ionized calcium (physiologically active form) remained 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 (Hypercalcemia) 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 parathyroids.
. -- Ca -> perioral tingling - numbness - ms cramps - carpopedal spasms - seizures.
. EKG -> prolongation of the QT interval.

# Causes of ++ Ca & + PTH: 1ry Hyperparathyroidism & familial hypocalciuric hypercalcemia:

. 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 hyper-calcemia).
. Dx -> 3Ds SESTAMIBI scan + U/$ to locate the hyperactive parathyroid tissue presurgery.
. 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)

Measure PTH level

++

--

PTH-Independent

PTH dependent

Measure urinary Ca

Measure 24 hours urinary calcium

> 250

1ry or 3ry
Hyperparathyroidism

< 100

Familial
Hypocalciuria
Hypercalcemia

+PTHrP

+1,25(OH)

+25(OH)D

TUMOR

Lymphoma
-Sarcoid

Vit.D
toxicity

NORMAL LABS
. HYPERTHYROIDISM
. MULTIPLE MYELOMA
. Adrenal tumor
. Acromegaly
. Immobilization
. Vit. A toxicity

. 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 calcium.
. ++ 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 deficiency (2ry adrenal insufficiency): "-- 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 deficiency in ADULTS.
. Bony pain & tenderness.
. -- 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 activity.

. CAUSES of HYPOKALEMIA & --BICARBONATE HCO3 {Metabolic Alkalosis} -> (Check RENIN):
.. CAUSES of HYPOKALEMIA & ++ ALDOSTERONE & -- RENIN -> PRIMARY HYPER-ALDOSTERONISM.
.. CAUSES of HYPOKALEMIA & ++ BOTH ALDOSTERONE & RENIN -> (Check Cl):

(A) WITH ++ CHLORIDE (Check Na):

(B) WITH -- CHLORIDE:

1- -- Na -----> (Diuretic use).

1- Surreptitious vomiting.

2- Normal Na -> (Bartter's $).

2- Factitious diarrhea.

3- ++ Na -----> (Renin secreting tumor).

. SURREPTITIOUS VOMITING:
. Scars & calluses on the dorsum of the hands & dental erosions.
. Result from chemical & mechanical injury as the pt uses his hands to induce vomiting.
. 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 suppress the 8 a.m. level.
. A NORMAL 1 mg overnight dexamethasone suppression test EXCLUDE
hypercorticolism.
. 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
falsely ++.
. Sources of Cushing $:
Pituitary tumor

Ectopic

ACTH Adrenal
adenoma

ACTH

HIGH

HIGH

LOW

High dose dexamethasone

Suppression

No

No

Specific tests

MRI

CT

CT adrenals

Tx

Removal

Removal

Removal

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

1- 24 hour urine cortisol.
2- 1 mg overnight 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 administration.
. NO RISE IN CORTISOL -> Adrenal insufficiency.
. Dx -> CT adrenals.
. Tx -> FLUIDS + Steroid replacement (IV HYDROCORTISONE).
. CAUSES:
.1- Auto-immune adrenalitis -> Responsible of 80% of cases in developed countries.
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 Corticotrophin Releasing Hormone secretion from hypothalamus,
. Also .. Block the action 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 deficiency in central adrenal 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 insufficiency
|
. 250Mg COSYNOTROPIN stimulation test with CORTISOL & ACTH levels
|
. Minimal response i.e. LOW BASAL CORTISOL
|
. ACTH HIGH = PRIMARY AI

|
. ACTH LOW = SECONDARY or TERTIARY AI

.3. PRIMARY HYPER-ALDOSTERONISM:

. Hypokalemia + Hypertension + Proximal muscle weakness & numbness.
. Hypernatremia + metabolic 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

2ry HYPERALDOSTERONISM

1ry HYPERALDOSTERONISM

* Diuretic use.

* Do a CT ADRENAL to

* Liver cirrhosis.

detect the etiology!

|
Other causes of ++ Aldosterone
*Congenital adrenal hyperplasia
* Glucocorticoid resistance.

* Congestive heart failure.

* Exogenous mineralocorticoid.

* 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 Alpha 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 deficiency

11 hydroxylase deficiency

17 hydroxylase deficiency

++ Adrenal androgens

++ Adrenal androgens

-- Adrenal androgens

Hirsutism

Hirsutism

NO hirsutism

++ 17 hydroxy-progesterone

NO

NO

NO hypertension

HYPERTENSION

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 urethral tear).
. * VENOGENIC -> Disruption of tunica albuginea (# penis).
. * ENDOCRINOLOGIC -> ++ prolactin & -- Testosterone.
. * SITUATIONAL -> Anxiety (Nighttime & morning erections are preserved).

. N.B. NOCTURNAL PENILE TUMESCENCE:

. Helps to differentiate psychogenic from organic causes of male erectile dysfunction.
. +ve in psychogenic causes.
. -ve in organic causes.

. PROLACTINOMA = LACTO-TROPH ADENOMA:

. The MOST COMMON pituitary tumor.
. ++ PRL.
. Hypogonadism & galactorrhea.

Dr. Wael Tawfic Mohamed