Endo Review by Garry

Endocrinology Review

Review Outline

• Adrenal

• Pituitary

• Thyroid

• Calcium

• Diabetes

Adrenal

Disorders

Adrenal Insufficiency

Primary

• autoimmune

• hemorrhage

• tuberculosis (TB)

Secondary

• steroid treatment*

• pituitary disease

CRH

Cortisol ACTH

Primary Low High

Secondary Low Low or

(central) normal

Primary AI Secondary AI

ACTH high low or normal

Hyperpigmentation yes no

Aldosterone low normal

Symptoms +++ +

Na low low or normal

K high normal

Adrenal Insufficiency

Suspected

ACTH Stimulation Test:

Cortisol >20 ug/dl

Normal HPA axis

Cortisol < 20 ug/dl

Adrenal Insufficiency

Plasma ACTH

Elevated Normal or Low

Primary Adrenal

Insufficiency

Secondary Adrenal

Insufficiency

Adrenal Insufficiency Imaging

• Primary: get adrenal CT of abdomen

• Secondary: pitutiary MRI (if not on steroids)

1o AI 2o AI Stress HC 100 q 8 HC 100 q 8

Maint. HC 20/10 HC 20/10

fludrocortisone

Treatment with hydrocortisone (HC):

Cushing’s Syndrome: Etiology

• Pituitary tumor 70%

• Adrenal tumor 15%

• Ectopic tumor 15%

Cushing’s Syndrome

• Do one of the three. If positive then do a second one.

• Establish hypercortisolism: 24 hr. Urine Free Cortisol

1 mg ODST

• Biochemical localization: ACTH, 8 mg ODST

– Remember, ectopic will not supress with dex.

• Radiographic localization: MRI, CT, octreotide

+/- petrosal sinus sampling

• Treatment: surgically resect tumor

Cushing’s Syndrome Suspected

24 hour urine-free cortisol

Overnight dexamethasone (1 mg) suppression test

Abnormal

ODST: serum cortisol > 2 ug/dl

urine free cortisol > 100 mcg/24

Plasma ACTH

Normal

ODST: serum cortisol < 2 ug/dl

urine free cortisol < 100 mcg/24

ACTH < 10

Adrenal

(Adrenal CT scan)

ACTH normal or high

8 mg ODST

Suppression

Pituitary

(Sella MRI)

Non-suppression

Ectopic ACTH

(CXR, CT chest, ? octreoscan)

Cushing’s syndrome

• pituitary MRI

• inferior petrosal venous sampling

Primary Aldosteronism

• clinical: hypertension, low K, metabolic alkalosis

• screening: aldosterone/renin ratio > 20 and

absolute aldosterone >15

• confirmation: saline suppression test

• localization: CT scan, +/- adrenal vein sampling

• treatment: adenoma-surgery

hyperplasia-spironolactone

eplerenone

Multiple Endocrine Neoplasia Syndromes

MEN 1 MEN 2a MEN 2b

Pancreas MTC MTC

Pituitary Pheo Pheo

1o HPT 1o HPT mucosal neuromas,

marfanoid habitus

MEN Syndromes

• MEN1 looks like a kite, pituitary,

parathyroid and pancreas.

• MEN 2 A looks like a square. Pheo and

parathyroid.

• MEN 2 B looks like a triangle.

Oral/intestinal ganglioneuromatosis (think

of the top of the triangle as the mouth/GI

tract) and also pheo.

• Both MEN 2 are ret mutation and

medullary thyroid

Pituitary

Disorders

Pituitary Gland Hormones

• FSH

• LH

• TSH

• ACTH

• Prolactin

• Growth Hormone

Pituitary Gland Tumors

• Prolactinoma 50%

• Non-secreting 30%

• GH-secreting 10%

• ACTH-secreting 10%

Provided by: Eric Tay, MD

Microadenoma vs. Macroadenoma: 1.0 cm

Hyperprolactinemia: the “4 P’s”

• Pregnancy

• Primary Hypothyroidism

– TRH is a prolactin release hormone!

• Prescription Drugs

• Prolactinoma*

7’ 2”

Prolactinomas

Women

• microadenomas

• amenorrhea

• galactorrhea

Men

• macroadenomas

• headache

• visual complaints

• hypogonadal

after one year of

bromocriptine therapy before treatment

Macroprolactinoma

Hyperprolactinemia

• diagnosis: 4 P’s

• macroprolactinoma if PRL > 200

• MRI to confirm

• treatment: MEDICAL!

bromocriptine or cabergoline

Acromegaly

• diagnosis: GH, IGF-1, + Oral Glucose

Tolerance test

– Ideally GH should suppress with ORGTT

(but if it doesn’t)

• localization: MRI

Radiation

Surgery Somatostatin

receptor ligands:

octreotide,

lantreotide

GH receptor

antagonists:

pegvisomant

Diabetes Insipidus

• polyuria, polydipsia

• high serum Na

• high serum osmolality

• low urine osmolality < 200

• therapy: DDAVP

– The urine should concentrate with DDAVP which is a

ADH analog

DI

• Two types

• Central DI

– There is a central deficit in the production of

ADH. The way to treat this is to give them

DDAVP.

• Nephrogenic DI

– The kidneys do not respond to ADH

– The kidney does not respond to the

desmopresin test

Thyroid

Disorders

Hypothyroidism: Symptoms

Fatigue

Weight gain

Depression

Constipation

Menstrual irreg.

Cold intolerance

Dry skin

Hair loss

Free T4 TSH

*Primary Low High

Secondary Low Low/normal

Hypothyroidism

• Hashimoto’s is most common cause

– antiTPO

• Dx.: TSH and FT4 and exam (no nodules)

• Imaging rarely needed

• Treatment: levothyroxine

– Follow the TSH. If they still have symptoms with nl

TSH then refer them out and give them to social work

(cause were super awesome surgeons)

Hyperthyroidism: Causes

Common:

a. Graves’ disease

Anti-TSH Ab

b. Toxic MNG

c. Solitary toxic nodule

d. Subacute thyroiditis

e. Iodine-induced

f. Iatrogenic

Hyperthyroidism: Symptoms & Signs

• Nervousness/Anxiety

• Palpitations

• Weight loss

• Increase appetite

• Diaphoresis

• Muscle Weakness

• Dry bulging eyes

• Diarrhea

• Heat intolerance

• Menstrual irregularity

• Tremor

• Tachycardia (60%)

• Warm, moist skin

• Heart failure (HO)

• Proximal myopathy

• Lid retraction/lag (Graves)

• Proptosis* (Graves)

• Thyroid bruit*

• Goiter

Differential Dx: 24 hour RAIU

High RAIU (>30%)*

• Graves’ disease

• toxic MNG

• solitary toxic nodule

Low RAIU (<5%)**

• subacute thyroiditis

– hyper->hypo->eu

– Generally viral etiology

• iodine-induced

• factitious/iatrogenic

**self-limited conditions

*require “definitive therapy”

Definitive Treatments:

Hyperthyroidism

Hyperthyroidism: Treatment

High uptake hyperthyroid

• I-131

• anti-thyroid drugs

– Agranulocytosis

– Hepatic Damage c PTU

• Black box warning!!!!!!!

• thyroidectomy

Low uptake hyperthyroid

• treat symptoms

-B blockers

(also blocks some

peripheral conversion

like PTU)

-NSAID’s for SAT

TSH & FT4

Normal Hyperthyroid Hypothyroid

“Idiopathic”

radioactive

iodine

replace LT4

and follow

Goiter

1. follow

2. suppress

3. surgery

Graves’ or toxic MNG Hashimotos’s thyroiditis

Thyroid Nodules

• 5% of adult population has palpable nodule

• < 10% of palpable nodules are malignant

• > 95% are euthyroid

• After obtaining serum TSH, the best initial test:

FNA thyroid biopsy

• Incidentalomas: U/S guided bx. if > 10 mm

TSH

Normal

Low High FNA

biopsy

24 hr. RAIU Replace LT4

and follow

Thyroid Nodule

Benign Malignant

Surgery Follow

Thyroid Cancers:

• Papillary thyroglobulin

– Major complication of neck radiation

• Follicular thyroglobulin

• Anaplastic no marker

– Comes on in old people the most. Refractory to Tx

• Medullary calcitonin

– C cell derived. ALWAYS THINK MEN2!!! Concurrent PHEO

Thyroid Cancers: Treatment

• Papillary - surgery, I-131, LT4

• Follicular - same as PTC

• Anaplastic - palliative

• Medullary – surgery

Thyroid Cancer Treatment

Surgery I-131 LT4

suppression

Papillary + + +

Follicular + + +

Medullary + -- --

Anaplastic -- -- --

Calcium

Disorders

Pathophisiology of

Hypercalcemia:

• 1. Increased bone resorption

• 2. Increased renal resorption of calcium

• 3. Increased gut absorption of calcium

Causes of Hypercalcemia

Common

1. Primary HPT

2. Malignancy

Uncommon

1. Lithium, HCTZ

2. Vitamin D or A toxicity

toxicity

3. Hyperthyroidism

4. Granulomatous disease

5. Immobilization

6. FHH

7. Milk-alkali

Diagnosis: PTH Level

High PTH

• Primary HPT

• FHH*

* Check 24 hr. urine calcium

Low PTH

• Malignancy

– He says this is “low

yield” but this also

comes from the guy who

said peritibial myxedema

is low yield

• Everything else

Primary HPT Malignancy

Serum calcium < 12 > 12

Symptoms +/- +++

Duration > 6 mos. < 6 mos.

PTH high low

PTHrP low high

Hypocalcemia: Causes

• Vitamin D deficiency

– Low calcium and phos

• Hypoparathyroidism

-post-surgical (most common)

-autoimmune (very rare)

• Low magnesium (primes the Ca sensitive sensor to

sense Ca)

• Pseudohypoparathyroidism

– PTH levels are actually elevated but dysfunctional G proteins

make it so PTH can’t work on the receptor. The pt has other

problems besides just hypocalcemia

Vitamin D deficiency: Common

• low serum calcium

• low serum phosphate

• high PTH – secondary hyperparathyroidism

– The body tries to restore Vit D balance. Recall that PTH

increases 1ahydrolyase activity in the kidney. 1,25OH is the

main active form.

– Low Ca with Low PTH is Primary hyperpara

• low 25-OH vitamin D

• low 24 hour urine calcium

Osteoporosis

Primary Osteoporosis

Women

• postmenopausal

• senile

Men

• senile

Secondary Osteoporosis

• vitamin D deficiency

• primary HPT

• hypercalciuria

• glucocorticoid excess

• hyperthyroidism

• multiple myeloma

• hypogonadism in both women and men

Secondary Osteoporosis

• Women: up to 40% have 2o cause

• Men: 60% have 2o

cause

1. testicular failure

2. glucocorticoid excess

3. ETOH

Osteoporosis Treatment: Non-pharmacologic

• calcium and vitamin D supplements

• exercise

• fall precautions

Osteoporosis Treatment: Pharmacologic

Antiresorptive

decrease formation and resorption

• Bisphosphonates

• SERMS: raloxifene

• Calcitonin

• Estrogen therapy

Bone Formation Stim

increase formation and resorption

• Teriparatide (PTH)

– Intermittent exposure

to PTH will activate

blasts more than

clasts.

Osteoporosis

• Diagnosis: T-score < -2.5 or fragility fracture

• R/O secondary causes

• Treatment (if no secondary cause)

-calcium and vit D, exercise, fall precautions

-bisphosphonates, raloxifene or PTH

Diabetes

Diabetes: Pathogenesis

Type 1

• absolute insulin

deficiency

Type 2

• partial insulin deficiency

• defect in insulin secretion

• insulin resistance

• increase hepatic glucose

production

Fuel Metabolism: Normal “Balance”

Anabolic

• Insulin

Catabolic (“counteregulatory”)

• catecholamines

• glucagon

• cortisol

• growth hormone

DKA:

• Insulin

• (no insulin is around so

ketones can be made…)

• catecholamines

• glucagon

• cortisol

• growth hormone

DKA Treatment

• I.V. Insulin

• Replace fluids

• Replace K

– The patient might look eukalemic on labs but they are

actually at a deficet. Insulin will drive K+ back into

cells!!! And then the patient will be hypokalemic on

labs

• Treat precipitating cause (infection or MI)

(until anion gap resolves)

Diabetes: Diagnosis

• Fasting glucose > 126 mg/dL X 2 or

• Random glucose > 200 mg/dL with classic

symptoms of hyperglycemia

Diabetes: Complications

Microvascular

Prevented by glucose control

• nephropathy

• retinopathy

• neuropathy

Macrovascular

Not prevented by glucose control

• Myocardial infarction MI)

• Stroke (CVA)

• Peripheral vascular

disease (PVD)

Diabetes: Treatment Type 1

• insulin

• diet

Type 2

• weight loss: diet/exercise

• oral agents

– Metformin

– Thiazolidinediones

– Sulfonylureas

• exenatide

• insulin

DM-2: Oral agents

Type 2

• partial insulin deficiency.…. Sulfonylurea

• insulin resistance….. Thiazolidinediones

• increase hepatic glucose production… metformin

Insulin Therapy:

• DM-1: need 24 hour insulin coverage

NPH X 2 or glargine X 1

• DM-2: 24 hr. coverage not always necessary

add bedtime NPH to oral agent

Lipid Disorders • High cholesterol

– Familial Hypercholesterolemia

• High LDL. Likely a deficiet in LRL-R (to remove LDL from the circulation). Cholesterol may be deposited around

the body (eg eye xanthelasma palpbrarum), iris arcus senilis corneae, tendons around the body such as the

Achilles or hand)

– Familial defective B-100

• High LDL. Presents like LDL-R. apoB-100 binds to LRL-R to get the LDL out of the system

– Polygenic Hypercholesterolemia

• Presence of Xanthomata can confirm the diagnosis of FH. Only moderate LDL increase (140-300) with TG in

normal range.

• High triglycerides and cholesterol

– Familial Combined Hyperlipidemia

– Dysbetalipoproteinemia

• Increase in LDL, cholesterol, and TG levels with decreased HDL levels. Presents with xanthoma triatum

palmara which is orange or yellow discoloration on the hands. Also with eruptive xanthomas on the elbows and

knees. There is a deficit in ApoE which allows for LDL/IDL/VLDL/chylomicros to be absorbedd into the liver.

• High triglycerides

– Familial hypertriglyceridemia

• Pancreatitis, hepatomegaly, spelanomegaly, xanthomas

– LDL deficiency

– Apo-CII deficiency

• ApoC2 is needed for LPL to hydrolyze TGs. Presents with xanthomas, pancreatitis, and hepatoplenomegaly.

Not at risk for atherosnclerosis

– Sporadic Hypertriglyceridemia

Lipid Disorders: Etiology

• genetic

• obesity

• diabetes

• medications: estrogen, thiazides

• smoking

• hypothyroidism

• chronic renal failure; nephrotic syndrome

• obstructive liver disease

Typical Lipid Pattern: DM-2

• High triglycerides

– No insulin to upregulate LPL

• Low HDL

• Normal or high LDL cholesterol

Lipid Disorders: Treatment

High cholesterol

• statins*

• ezetimibe

• bile acid resins

High triglycerides

• gemfibrozil, fenofibrate*

• niacin

*risk of myositis when used in combination

The “Insulin Resistance Syndrome”

aka The “Metabolic Syndrome”

• obesity

• insulin resistance: high insulin levels

• hyperglycemia/diabetes

• hypertension

• lipid abnormalities

• coronary artery disease

Hypoglycemic Disorders

72 hour fast:

• glucose

• insulin

• C-peptide

• sulfonylurea screen

Hypoglycemic Disorders

72 hour fast:

• insulinoma:

– low glucose

– high insulin

– high C-peptide

• sulfonylureas: same except + sulfonylurea screen

• surreptitious insulin injection:

– low Glucose

– high insulin

– low C-peptide