ENDOCRINOLOGY TiKi TaKa

. THYROID DISEASES:

. P.O.C. HYPO-thyroidism HYPER-thyroidism

* Labs -- T4 & ++ TSH ++ T4 & -- TSH

* Weight Gain Loss

* Intolerance Cold Heat

* Hair Coarse Fine

* Skin Dry Moist

* Mental Depressed Anxious

* Heart Bradycardia Tachycardia & Af

* Muscles Week Week

* 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 dependent PTH-Independent

Measure urinary Ca

+PTHrP +1,25(OH)

+25(OH)D NORMAL LABS

Familial Hypocalciuria

Hypercalcemia

1ry or 3ry Hyperpara-thyroidism

> 250 < 100

TUMOR Lymphoma-Sarcoid

Vit.D toxicity

. HYPERTHYROIDISM

. MULTIPLE MYELOMA

. Adrenal tumor

. Acromegaly

. Immobilization

. Vit. A toxicity

Measure 24 hours urinary calcium

++ --

. 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

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. 250Mg COSYNOTROPIN stimulation test with CORTISOL & ACTH levels

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. Minimal response i.e. LOW BASAL CORTISOL

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. 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

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2ry HYPERALDOSTERONISM 1ry HYPERALDOSTERONISM Other causes of ++ Aldosterone

* Diuretic use. * Do a CT ADRENAL to *Congenital adrenal hyperplasia

* Liver cirrhosis. detect the etiology! * 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