- Zona glomerulosa: outer, mineralcorticoids (aldosterone)

-Zona fasciculata: middle, glucocorticoids (cortisol)

-Zona reticularis: inner, gonadocorticoids (estrogens/androgens)

Na⁺ resorption & K⁺ secretion

Controlled by the Renin-Angiotensin system

Metabolism regulation and stress resistance

Cortisol

1. Normal metabolism

2. Stress resistance

3. Anti-inflammatory

Genetic disorder characterized by enlarged adrenal glands.

Cause?

Result?

Congenital adrenal hyperplasia

Cause: deficiency in enzyme needed for cortisol synthesis

Results: Virulism & masculinization

Pheochromocytoma

hypersecretion of epi/norepi causes vasoconstriction = HTN

10% are:

bilateral

not in the adrenals

malignant

not assoc w/ HTN

in children

5% of pheochromocytomas are assoc w/ ___ ________.

Triad?

MEN syndrome

(type II multiple endocrine neoplasia)

Triad of hyperparathyroidism, pheochromocytoma and medullary thyroid cancer

-Recklinghausen's disease (neurofibromatosis)

-Sturge-Weber (cerebellar ataxia)

- Von Hippel-Lindau syndrome

Pheochromocytoma

(may also have sweating, angina, tachycardia, face flushing, hyperglycemia or tremor)

MUST DDX FROM ANXIETY ATTACK

- 24hr urine for catecholamines

-Serum chromogranin A

-CT or MRI scan for tumor

-Plasma fractionation for metanephrines- most sensitive

-Iatrogenic: steroids

-Adrenal adenoma or carcinoma

-Pituitary tumor (Cushing's disease): usually anterior, ACTH hypersecretion (*women)

-Ectopic: non-pituitary tumors (*SCLC, men)

Dexamethasone suppression test (easiest, < 5 = exclusion)

24hr urine for free cortisol (confirmed if  >125ug/dl)

-Tumor: surgical removal tx of choice

-Metyrapone

-Glucocorticoid taper

Pathology of adrenal glands, ie. Addison's disease

(= little/no cortisol secretion)

Lack of ACTH secretion from the pituitary

(= low cortisol)

Lack of CRH secretion from the hypothalamus

(= low ACTH = low cortisol)

Cortisol AND Aldosterone

(Aldosterone normal in secondary & tertiary)

Autoimmune: Addison's disease

May occur with polyglandular autoimmune syndrome type 1

Addison's disease

(hyperkalemia in primary only)

- Plasma cortisol @ 8am

-ACTH elevation (primary)

-Cosyntropin stimulation test (synthetic ACTH to stimulate cortisol;

+ if cortisol fails to rise)

-Abdominal CT for tumors or calcified lesions

Cortisol: hydrocortisone

Aldosterone: Fludrocortisone

Dx: Acute Addisonian/adrenal crisis

Tx: Hydrocortisone immediately

- Solitary (unilateral) aldosterone-producing adenoma (aka. Conn's syndrome, 70%) 

- Bilateral adrenal hyperplasia

Primary hyperaldosteronism

(Conn's should always be considered in a pt w/ HTN + Hypokalemia)

Conn's: adrenalectomy

Hyperplasia: medically, spironolactone for HTN & K⁺

Oxytocin, ADH/AVP (Arginine, vasopressin)

(These hormones are produced by the hypothalamus but stored and secreted by the posterior pituitary)

What TSH and T3/4 lab results would you expect in a pt with primary hypothyroidism? Secondary/Tertiary?

For each of these, where is the dysfunction located?

Primary (thyroid dysfxn): Inc TSH, Low or N T3/4

Secondary(pituitary)/tertiary (hypothalamus): Low to N TSH, low T3/4

Child: growth retardation/short stature, late puberty, fasting hypoglycemia

Adult: Inc BP and LDL, central obesity, mm weakness, small heart

Insulin hypoglycemia test

Contraindicated in the elderly & CV disease pts

-Stimulation of cortisol synthesis at adrenals

-Maintain adernal size (so dec ACTH = atrophy w/in 2 wks)

-ACTH serum levels (morning)

-1-hour cortisol stimulation test (confirmatory)

Primary: adrenal defect, ACTH normal or elevated

Secondary: Decreased pituitary ACTH secretion

Kallman's

S/Sx: delayed puberty, micropenia, cryptordhidism, dec smell, ASD

Flattening (primary) or shrinking (secondary) of the pituitary gland

Primary: fluid compression from hole in pituitary membrane

Secondary: Trauma, tumor, surgery

Transphenoidal lesion removal

SE: Post-operative hyponatremia

Mainstay of tx for anterior hypopituitarism?

More specifically, TSH, gonadotropin, GH or ACTH deficiency?

Hormone replacement

TSH: levothyroxine

Gonadotropin: testosterone/estrogen

GH: somatotropin, rhGH

ACTH: prednisone

Women: a/oligo-menorrhea, infertility, galactorrhea

Men: ED, dec libido, gynecomastia

Both: Inc risk of osteoporosis

Tumors may also secrete GH => acromegaly

-Prolactin-secreting tumor

-Excessive exercise

-Pregnancy

-Pueriperium

-Stress/trauma/surgery

-Breast suckling/surgery

-Medications

ADH (vasopressin) and oxytocin

Stimulated by the hypothalamus

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion

S/Sx?  Dx requirements?

-High ADH

S/Sx: hyponatremia, retaining H₂O w/o edema

Dx: absence of hypervolemia, normal renal, thyroid, adrenal fxn

1. Primary central DI: hypothalamic

2. Secondary central DI: trauma to pituitary/hypothalamus stalk

3. Vasopressinase-induced: pregnancy

4. Nephrogenic DI: renal, vasopressin-resistant

1/3 are Primary DI

MRI: no lesions

Causes: autoimmune, stalk thickening, genetic (dominant: presents at 2y, recessive:Wolfram syndrome)

Vasopressinase

Associated w/ oligohydramnios, preeclampsia, hepatic dysfxn

-Defect in renal tubules, preventing water resorption

-Congenital: X-linked

Both are non-responsive to vasopressin

-24hr CrCl

-BMP: Na⁺, glucose, Ca, BUN/Cr, N

-Uric acid

-Vasopressin challenge test

-MRI

Desmopressin acetate

Nephrogenic: HCTZ, indomethacin, desmopressin

-Inc BMR

-Inc catecholamine sensitivity

-Protein synthesis

-Food & vitamin metabolism

Weakness, cold intolerance, weight gain, dry skin, goiter, facial edema

"Things are slowed down"

-Cardiac in pts w/ CAD and CHF

-Miscarriage/developmental problems in newborn

-Organic psychoses

Addison's, alopecia, celiac disease, DM1, myasthenia gravis, hypokalemic paralysis

Pregnancy: spontaneous abortion, low birth weight, preeclampsia

Tapazole

Pregnancy: PTU (Proplythiouracil), dose <200mg/d

-Thioureas

-Ipodate sodium: begun 1hr post-thiourea

-Iodide: begun 1hr post-ipodate

-Propanolol: for cardiac sx

-Hydrocortisone

NO ASPIRIN: raises FT4

Thyroiditis

Acute: May put pressure on the internal structures of the neck

Chronic: Painless enlargement, rubbery firmness

Drug-induced

Hashimoto

Postpartum

Reidel

Subacute (Quervain)

Suppurative

Hashimoto thyrioditis

Tx: levothyroxine

1-6mo post-delivery: hyperthyroidism lasting 1-2mo

4-8mo post-delivery: hypothyroidism, 80% recover

70% recurrence w/ subsequent pregnancies

Subacute/Quervain thyroiditis

Tx: Aspirin, propanolol for sx

Suppurative thyroiditis

(suppurative means "pus/purulent")

Reidel thyroiditis

Tx: Tamoxifen

-Respiratory distress/failure

-Dysphagia

-GI bleeding from esophageal varices

-Nerve palsies (phrenic & recurrent laryngeal)

-Cerebral ischemia/CVA

-Superior vena cava syndrome

Tx: Levothyroxine

Do not give to pts with suppressed TSH levels (indicates elevated T4)

Benign, hot

BUT, need to be followed up for function and malignancy

- Irregular margins/borders

- Hetergenous echogenicity

-Microcalcifications

-Complex cyst

- >1cm diameter

Cold lesion: An area of the thyroid that fails to concentrate the tracer

- Often characteristic of a thyroid cyst or neoplastic growth

-Hot lesion: An area of the thyroid that appears to concentrate the tracer

-Often characteristic of benign adenomatous growths

Levothyroxine (prevents enlargement, but does not shrink)

Contraindications: cardiac disease (angina/A-fib), osteoporotic pts

Papillary

Follicular

Medullary

Anaplastic

US: intial Dx and followup

CT & PET: to identify metastases

Papillary thyroid carcinoma

However, slow-growing and not very aggressive

Medullary thyroid carcinoma

Calcitonin is usually elevated

Surgery

Total thyroidectomy: differentiated

Subtotal: <45yo w/ tumor <1cm

1. Stimulates osteoclasts to mobilize calcium

2. Stimulates kidneys to resorb calcium

3. Stimulates kidneys to activate D3, resulting in increased absorption of Ca from the small intestine

4. Inhibits resorption of phosphate and bicarb by renal tubules

Autosomal dominant hypocalcemia w/ hypercalciuria (ADHH)

Hypocalcemia without elevations in serum PTH b/c of deficient secretion of PTH

HDR/Barakat syndrome

(Hyperparathyroidism Deafness Renal dysplasia)

- Heavy metals: magnesium deficiency, copper or iron poisioning

-Tumors, granulomas or Reidel's thyroiditis

-Infection

-Radiation

-Autoimmune: PGA-1, APECED

-Fat malabsorption (VitD is fat soluble)

Low serum Ca^2+, urinary Ca²⁺, and PTH

High serum phosphate

-Autoimmuity: sprue syndrome, pernicious anemia, Addison's

-Cataract formation

-Parkinsonian sx

-Paravertebral ligament ossification & nerve root compression

-Seizures

-Heart failure

Immediate Tx!

-Ensure adequate airway

-IV calcium gluconate given slowly

-Oral calcium/calcium salts

-Administer VitD or calcitriol

-Mg²⁺ replacement (sulfate for acute, oxide for chronic)

-Calcitriol

-Ergocalciferol ergosterol (VitD2, calciferol)

-Cholecalciferol (VitD3)

Most common cause of hyperparathyroidism

3 other possible etiologies?

Hypersecretion of PTH by a single parathyroid adenoma

-Hyperplasia of 2+ parathyroid glands

-Carcinoma

- < 30yo: multiglandular disease

-Increased excretion phosphate by the kidneys

-Increased osteoclast activity (cystic bone lesions)

- Increased excretion of calcium due to overwhelmed tubular resorption capacity

T or F

The serum PTH level often correlates with the size of the parathyroid adenoma

1. Parathyroid-related*

2. Malignancy-related*

3. Vitamin D-related

4. High bone turnover

5. Renal failure

*Account for 90% of hypercalcemia

1. MEN syndrome (esp MEN-1), 90%

2. Familial hypercalciuric hypercalcemia

3. Jaw tumor syndrome

-Hyperparathyroidism, 90% (early onset, multiple glands)

-Gastrinoma, 45%

-Pituitary tumor, 25%

-Facial angiofibroma, 85%

-Collangenoma, 70%

-Loss of cortical bone, gain of trabecular bone

-Osteitis fibrosa cystica: "brown tumors"

-Diminished DTRs

-Kidney stones/nephrocalcinosis

-Calcium precipitation in the corneas of soft tissue

-CV effects: HTN, EKG effects, heart block, asystole

Complications of hyperparathyroidism during pregnancy.

Fetal effects?

Nephrolithiasis, hyperemisis, pancreatitis, muscle weakness, hypercalcemic crisis

Fetus: fetal demise, prematurity, low birth weight, neonatal tetany, permanent hypoparathyroidism

-Elevated PTH, serum calcium and/or ionized calcium

-Low-normal serum phosphate

-24h urine: r/o familial hypocalciuric hypercalcemia

-DEXA: wrist, hip, spine

-KUB, IVP or CT for kidney stones

Primary: High calcium, low-normal phorphorus

Secondary: Low-normal calcium, high phosphorus

Tertiary: High calcium and phosphorus

-Sestamibi scanning & neck ultrasonography to localize adenomas

-MRI for ectopic parathyroids

-Symptomatic pt, kidney stones, or bone disease

-Asymptomatic:

-Serum Ca >1mg/dL above upper limit of normal w/ calciuria >50mg/24h

-cortical bone density 2 SD below normal

-Age < 50yo

-Pregnancy

-Calcimemetics (cinacalcet hydrochloride)- increase sensitivity of the PT to calcium

-VitD

-High-dose estrogen

-SERMS: raloxifine

-Bisphosphonates

-Propanolol for cardiac effects

-Phosphate binders for secondary HPT

NO DIGOXIN

-Lowers blood glucose

-Glycogen synthesis

-Glycolysis

-Fatty acid synthesis

1. Insulin resistance (peripheral)

2. Relative insulin deficiency resulting from insulin resistance (pancreatic failure)

-Placenta produces anti-insulin hormones which cause insulin resistance in the mother

-Pancreas compensates by producing more insulin, but it cannot overcome the resistance, leading to GD

Dysmetabolic syndrome

Atherosclerotic disease

-> 45yo: every 3 years (earlier if + risk factors)

-Children/adolescents: BMI in 85th percentile and 2+ risk factors, every 2 years

-If pt has s/sx: do a diagnostic test, not screening

Normal FPG <100 mg/dL

Normal RPG <125 mg/dL

FPG >126 mg/dL

RPG: >200 mg/dL and symptomatic

OGTT >200

All must be confirmed on different day

Diabetes: > 6.5%

High risk: 6.0-6.5%

3 major microvascular complications of diabetes mellitus.

What effect does tight glycemic control have on these complications?

Retinopathy

Nephropathy

Neuropathy [autonomic and peripheral (bilateral peripheral polyneuropathy)]

-Tight glycemic control may reverse these complications in their early stages

Microalbuminuria

ACEi & ARBs

Macrovascular complications of diabetes mellitus.  

What effect does tight glycemic control have on these complications?

Coronary artery disease

Peripheral artery disease

Cerebral vascular disease

Improving glycemic control does not reduce the risk of macrovascular seqelae.

BP & foot check- every visit

HbA1C- every 3mo

fasting lipid profile, microalbumin:Cr, and eye exam: yearly

HbA1C: < 7

FLP < 100 (LDL)

BP <130/80

Glycosylated hemoglobin (HbA1C)

Goal: < 7%

Fructosamine test

Goal: 2

False low: low albumin (b/c fructosamine is produced by the glycosylation of albumin)

Metformin: initial drug treatment of choice

Secretagogues

Thiazolidinediones (TZDs)

DPP-IV inhibitors

Metformin (Glucophage)

Decreases hepatic glucose production and increases insulin sensitivity in the muscles and liver.

metformin

BG 140-200:  0.4 u/kg x 50% 

BG 201-400: 0.5 u/kg x 50%

Post-prandial: then divide each by 3

0.3 u/kg: elderly, CKD, hypoglycemia

0.5 u/kg: Normal

0.7 u/kg: Obese

Hydration

IV insulin until anion gap is corrected

IV dextrose to maintain blood sugar

Replace potassium and phosphate

Hyperglycemic hyperosmolar nonketotic syndrome (HHNKS)

Serum glucose >600, osmolality >310

 TC = LDL + HDL + VLDL

Normal: < 200 mg/dL

High: > 240mg/dL

Goal: > 60 mg/dL

Risk: M < 45; W < 35

Optimal <100

High: 160-189

N= <150

High: 200-499

Prior MI, ischemia, hx of angina, prior CABG or angioplasty/stent placement

Goal LDL: < 100 mg/dL

PAD, carotid AD, atherosclerotic disease, diabetes, >2 major risk factors

Goal: < 100 mg/dL

Smoking, HTN, low HDL (<40), FHx of CHD, age (M >45, W >55)

Goal: <130 mg/dL

-Therapeutic lifestyle changes (diet, exercise)

-Return visit in 6 wks

-Evaluate LDL response

-Intensify LDL-lowering therapy if needed (reinforcement, stricter diet)

-Return in 6 weeks

-Evaluate LDL response

-Continue lifestyle if goal achieved

-Consider LDL-lowering drug

-Dietitian referral

-Reduce the liklihood of major coronary events

- Reduce CHD mortality

Lowers LDL 15-20%

Can be combined w/ a statin

A pt presenting with 3+ of the following factors:

-Central obesity: waist M >40", W >35"

-High BP

-High triglycerides >150

-Low HDL: M <40, W <50

-Insulin resistance: FBG >110

A genetic disorder such as:

-Monogenic familial hypercholesterolemia

-Familial defective apolipoprotein B-100

-Polygenic hypercholesterolemia