Term
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Definition
| So as you're aware, we have two adrenal glands, the right and the left, and they sit right above the kidney on both sides. They're tiny glands, but they're very vascular, and they do a lot of work for the body. The adrenal gland can be divided into two parts. |
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Definition
| The outer part is the adrenal cortex, and then you have, in the middle, the adrenal medulla. And it's surrounded by a capsule, but the two parts which are hormonally active are the adrenal cortex and the adrenal medulla. The cortex is again divided into three distinctive parts-- the outside |
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Definition
The first one is glomerulosa, which secretes aldosterone.
Then we have the fasciculata that is responsible for secreting cortisol, and the reticularis that secretes the androgens. Now, in women, most of the androgens come from the adrenal gland. However, in males, as you know, the dominant androgen is testosterone that comes from the testes, but in females, DHEA is what comes from the adrenal glands, and it's the majority of the androgens.
The next-- the innermost part, which is about 20% of the adrenal gland, is the medulla, which secretes epinephrine and norepinephrines, which are called the catecholamines. So just so that we can remember the different parts, we just remember it as GFR-- Granulosa for mineralocorticoids. The main mineralocorticoid is aldosterone, and we will talk more about it. Then we come fasciculata-- the glucocorticoids-- reticularis-- the sex steroids-- and medulla, which is the catecholamines. |
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Term
| 4 layers of adrenal gland and components |
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Definition
• Granulosa – mineralocorticoids
• Fasciculata – glucocorticoids
• Reticularis – sex steroids
• Medulla - catecholamines |
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Definition
So when we talk about the endocrine system, it's like an orchestra where there are different organs that have to communicate and talk to each other so that the system functions well. So the highest command center would be the hypothalamus. That secretes hormones and stimulates the pituitary gland.
The pituitary gland then sends out signals to different organs to either secrete hormones, or if there's too much of the hormone, to shut that off. So we have TSH from the pituitary controlling the thyroid. Similarly, we have ACTH, which then goes and stimulates the adrenal gland.
So the pituitary gland secretes five hormones that basically control different organs-- the thyroid, the breast tissue, the adrenal glands, growth hormone, and the otropins-- the FSH, LH-- that controls either the ovaries or the testes. |
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Definition
Controlled by HPA axis Hypothalamus
CRH
Anterior Pituitary ACTH
Adrenal cortex Cortisol |
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Definition
Now, just like we have releasing hormones and stimulating hormones that stimulate the adrenal glands to secrete cortisol, the higher centers also need a signal to shut off, otherwise we would have uncontrolled hormonal secretion.
So once we have enough cortisol in the system, that will go back by negative feedback inhibition, turn off the ACTH secretion in the pituitary gland and the CRH secretion in the hypothalamus so that we have a balance between secretion and when the secretion needs to be turned off. |
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Term
| Glucocorticoid Effects via Intracellular Receptor |
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Definition
• Decrease in immune response
• Activationofglycogensynthase
• Increase in hepatic glucose production
• Inhibit glucose uptake and utilization by peripheral tissues
• Activatelipolysisinadiposetissue
• Decrease osteoblast function
• Cataboliceffectonmuscles
• Weak mineralocorticoid – increase BP
• Mood, CNS |
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Term
| Mineralocorticoid Effects: |
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Definition
• Increase in renal distal tubular Na reabsorption
• H2O retention
• K loss through distal renal tubule |
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Term
| Different types of adrenal gland pathologies |
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Definition
• GC lack - Adrenal insufficiency
• GC excess - Cushing’s syndrome and disease
• Aldosterone excess - Primary HyperAldo = Conns’ syndrome
• Catecholamine excess – Pheochromocytoma
• Adrenal Incidentaloma |
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Term
• 40 year old man with history of HIV presented to ER with productive cough and fever. BP was 60/40. After 3 l on NS BP is 70/40. Transferred to ICU on pressors.
CXR – acute pneumonia.
• ROS – chr. abdominal pain, nausea and dizziness
PE
• Weight loss
• Hypotention
• Hyperpigmentation
• Vitiligo
• Auricular calcification |
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Definition
| adrenal insufficiency case number 1 |
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Term
• Symptoms: • Fatigue
• Anorexia
• N/V/Diarrhea
• Abdominal pain
• Salt craving
• Dizziness
• Muscle and joint pain
• Labs:
• Hyponatremia
• Hyperkalemia
• Anemia
• Hypoglycemia |
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Definition
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Term
| Adrenal Crisis – Acute Presentation |
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Definition
• Triggers: acute, major stress (illness, surgery, infection), stop GCs, bilat adrenal hemorrhage
• Dehydration, hypotension, shock
• N/V/acute abdomen
• Unexplained hypoglycemia
• Unexplained fever |
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Term
| hypothalamus and adrenal insufficiency |
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Definition
So let's focus on the hypothalamus. What are the common conditions where hypothalamus gets involved? Tumors, can be head trauma, could be some infection or radiation-- head and neck radiation-- for some unrelated condition
Abrupt stop of GCs Tx of Cushing’s Destruction by tumor, Infection or RT -> CRH |
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Term
| pituitary and adrenal insufficiency |
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Definition
pituitary glands again. You can have a pituitary tumor-- patient's had radiation to the head region.
The most common cause that we are seeing recently is patients who are on opioids. We know there's an opioid epidemic. Patients who are on long-standing opioids tend to have suppression of their pituitary gland, and as a result, the ACTH secretion is decreased, and so cortisol secretion is decreased.
Panhypopituitarism ACTH deficiency Megace
Opiates -> ACTH |
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Term
| adrenals and adrenal insufficiency |
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Definition
Adrenal glands can be affected independently by an autoimmune process. When there is destruction of the adrenal gland by an autoimmune process, that condition is called Addison's disease. They can be infected by fungal infections, fairly common in patients who have HIV or TB, and then we can have metastatic disease to the adrenal gland.
Autoimmune adrenalitis PAS 1 and 2
TB, HIV, fungal infection Metastatic CA |
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Term
| diagnosing adrenal insufficiency |
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Definition
• To show low cortisol secretion
• Is it ACTH dependent or not?
• Seek a treatable cause of primary disorder |
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Term
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Definition
So if the defect or the destruction is at the level of the adrenal gland, that is called primary adrenal insufficiency. So you can imagine, if the adrenal gland is destroyed, there's no cortisol secretion. However, the pituitary gland and the hypothalamus are normal, so they will continue to secrete ACTH because the body recognizes there's low cortisol, and so the normal response from the pituitary would be to increase the ACTH level, correct?
So in patients with primary adrenal insufficiency, they have low cortisol but high ACTH levels. So we say that it's an ACTH-dependent adrenal insufficiency. However, if there is a problem at the pituitary level, that is called secondary adrenal insufficiency. That means the adrenal gland is functioning OK, however, there is adrenal insufficiency because there is no signal coming from the pituitary gland, so that's called secondary adrenal insufficiency.
If the problem is at the hypothalamus level, it's called tertiary adrenal insufficiency. The pituitary gland is functioning fine, and the adrenal gland is functioning fine, but the higher signal from the hypothalamus is missing |
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Term
| determining level of defect w adrenals |
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Definition
Low cortisol, Low ACTH -> Secondary or tertiary Adrenal insufficiency
Low cortisol, High ACTH -> Primary adrenal insufficiency |
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Term
| Subnormal Cortisol Secretion |
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Definition
So how do you diagnose cortisol hyposecretion? So the easiest way to do it is to check a morning cortisol. The cortisol half-life is short, and the normal circadian rhythm is that if the morning cortisol levels go high, then as the day progresses, the cortisol levels normally decrease. So if you take a morning cortisol level and the cortisol secretion is less than 3, then we know that the patient is adrenal insufficient.
• AM cortisol <3 mcg/dL (10 – 20)
• High dose (250 mcg) ACTH stim test - <20 mcg/dL
• Low dose (1 mcg) ACTH stim test - <17-22 mcg/dL – r/o secondary
• Insulin induced hypoglycemia test (ITT) |
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Term
| Adrenal insufficiency treatment |
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Definition
- Adrenal crisis:
• IV fluids and GC (dexamethasone or
hydrocortisone)
- Longterm management:
• lowest dose
• mimic normal physiology
• add MC if primary
- Patient education |
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Term
• A 39 y/o female is easily fatigued, has dyspnea on exertion, is depressed and has noted 75 lbs weight gain over the past year.
• On ROS, she has polyuria and polydipsia and does not sleep well.
PE
BP – 150/95, pulse – 80, Wt – 220 lbs
• Central obesity
• Moon face
• Plethora
• Supraclavicular fat pads
• Hirsutism
• Purple striae
• Ecchymoses
• Also:
• Bone loss
• Proximal muscle weakness
• Thromboembolic events
• Menstrual irregularities
• Glucose intolerance or DM2
• Infections (esp. fungal)
• Glaucoma |
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Definition
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Term
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Definition
• Latrogenic–mostcommon • ACTHdependent-80%
- Pituitary ACTH dependent (Cushing’s disease)
- Ectopic ACTH/CRH – CA: lung, brochus, thymus, pancreas, carcinoid, pheo
• ACTHindependent-Cushing’sSyndrome(CS)– 20%
Adenoma, CA, hereditary syndromes |
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Term
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Definition
• Exclude exogenous GC !!!
• Exclude pseudo-Cushing’s:
depression, ETOH, stress
• Confirm increased cortisol secretion
• Determine the etiology
• Need 2 abnormal tests:
- 24 h urinary free cortisol – 3 x norm
- Elevated MN salivary cortisol x 2
- Low dose (1 mg) dexa suppression test – am cortisol >1.8 mcg/d |
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Term
| Therapeutic Targets in Cushing’s Disease |
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Definition
-surgery (transphenoidal), radiotherapy (fractionated, stereotaxic radio surgery), medications (cabergoline, Pasireotide)
-inhibitors of steroidogenesis (Metyrapone/Ketaconazole), Adrenolytic (Lysodren), Bilateral Adrenalectomy
-Anti-glucocorticoid (Mifepristone) |
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Term
• 45 y/o female with
• hx of uncontrolled HTN c/o episodic headaches, palpitations and sweating.
• 4 weeks ago she underwent surgery for appendicitis. Surgery was complicated by hypertensive crisis. |
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Definition
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Term
| Pheochromocytoma and Paraganglioma |
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Definition
- Derived from Chromaffin cells of the Embroynic neural crest origin
- Tumors cause problems
• Mass effect
• Over secretion of Catecholamines / metanephrines • Leads to HTN, Heart Disease , Stroke and Death
• Malignancy/Recurrence
-Just so that there is no confusion in the terminology, if there is a chromaffin-secreting tumor in the adrenal gland, that is is called pheochromocytoma. If the tumor is along the parasympathetic chain, those tumors are called paragangliomas. But I will not be talking about the paragangliomas today. We will just be concentrating on the pheochromocytomas. |
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Term
| Anatomical Distribution of Chromaffin Tissue |
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Definition
Tumors of the Adrenal Gland and Extra Adrenal Paraganglia
Adrenal Medulla Tumors = Pheochromocytoma ( PCC )
Tumors of other sites Paragangliomas ( PGL) |
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Term
| clinical presentation of pheochromocytoma/paragangliomas |
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Definition
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Term
| Old Dogma Tumor of 10 VS Current Knowledge |
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Definition
• 10% Extra Adrenal ~ 20%
• 10% Bilateral- 10%
• 10% malignant ~20%
• 10%Asymptomatic - 13-55%
• 10% Hereditary - 30-40% |
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Term
| So what do these pheochromocytomas do? |
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Definition
| We know that these are the tumors that arise from the medulla-- the innermost part of the adrenal gland. They secrete hormones, catecholamines-- excessive, that is norepinephrine-- epinephrine, and dopamine. |
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Term
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Definition
Now, epinephrine, norepinephrine have a very short half-life so if you start measuring-- tried to measure that, we may not be able to catch them at the time where there is increased secretion.
So we actually measure the metabolite of epinephrine that is the metanephrine, and normetanephrine for norepinephrine, which have a longer half-life and easier to measure. We used to measure VMA in the past. That test is almost obsolete now. We generally just do normetanephrines, metanephrines, and then methoxytyramine if we suspect a dopamine-secreting tumor.
There's always a debate whether we should be doing plasma metanephrines as our screening tests, or should we be doing a 24-hour urine? I would say that both these tests are fairly good, whichever is easier for you to use that as your screening test. And they have a pretty high sensitivity, so if your clinical suspicion is there, then you can order either of these tests to confirm your diagnosis.
The true positive values-- so you can have mild metanephrine elevation depending on some of the drug interactions the patient is having, or the metanephrines were drawn when the patient is rushed into the lab. But if they are three to four times elevated, then your diagnosis is pretty confirmed. |
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Term
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Definition
• True positive values are 3-4 times greater than normal
• If borderline value can repeat in supine after rest and or order 24 hour urine metanephrines and catecholamine |
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Term
| Tumor Localization testing |
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Definition
High sensitivity tests:
• CTorMRIofabdomenandpelvis • CTorMRIofneckandchest
High specificity tests:
• 123I-labeledmeta-iodobenzylguanide(MIBG) scintigraphy
• Octreotidescan,Fluorodopamine-PETscan |
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Term
| Pre-Operative adrenal tumor Blockade Regimen |
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Definition
• Endo Society Guidelines
• Alpha blockers as 1st line
• Calcium Channel Blocker as 2nd line
• Add beta Blocker to control expected reflex tachycardia
• Increase salt and fluid intake |
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Term
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Definition
• Laparoscopic surgery
• Pre-op preparation:
α-blockade with phenoxybenzamine, terazosin or doxazosin for 2 weeks
• β-blockade – after α-blocked
• Follow up for remaining disease, reccurence and mets
• RT, chemo, 123I-MIBG
Surgical Options
- Laproscopic adrenalectomy
- Adrenocoiticoid sparing surgery
• For bilateral tumors
• For patients with tumors with genetic syndromes at risk for future contralateral tumors
• Risk of recurrence |
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Term
• 42 y/o female with hx of uncontrolled HTN x 5 years c/o episodic headaches
• BP 155/95 on 3 BP meds and kCl
• Labs:K3.7,Renin1andAldo47 |
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Definition
| increased aldosterone secretion. Primary hyperaldosterone secreting tumor is also called Conn's syndrome. This has to be differentiated from renal artery stenosis, which presents with higher renin and normal or high aldosterone levels |
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Term
| Pathophysiology of Primary Hyperaldosteronism |
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Definition
| Aldosterone-producing tumour -> Aldosterone -> ↑ blood volume ↑ blood pressure ↑ urine K+ -> Renin -> angiotensin -> angiotensin I (ACE)-> Angiotensin II -> Thus Aldo ↑, Renin ↓ A/R ratio ↑ ↑ |
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Term
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Definition
Primary Hyperaldosteronism
• Low Renin • HighAldo |
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Term
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Definition
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Term
Primary Hyperaldosteronism
Who to screen ? |
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Definition
• HTN + Spontaneous Hypokalemia
• Patients with resistant HTN
• Patients with HTN at age <40
• HTN + known adrenal mass |
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Term
Primary Hyperaldosteronism
Treatment : |
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Definition
• Surgery:RxofchoiceforAdenoma
• Medications:(AldosteroneAntagonist–Ksparing)
- Spironolactone 100-200 mg /day
- Eplerenone 50 mg daily or BID |
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Term
| • 65 y/o female with hx of HTN (well controlled on HCTZ 25 mg daily) presented to ER 2 weeks ago with acute onset of diffuse abdominal pain. CT of the abdomen was done and showed no acute pathology, but revealed a 3 cm right adrenal mass. Pain resolved after a BM in ER. She is referred to you for the evaluation. |
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Definition
| We are doing so many CTs and MRIs these days, and we find adrenal masses-- what we call incidentally. So adrenal incidentaloma is usually a 1 centimeter or larger adrenal lesion, which is picked up when adrenal imaging was done for some other reason. |
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Term
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Definition
• Adrenal “incidentaloma” is an adrenal mass (generally 1 cm or more) discovered during the radiological examination performed for indications other then an evaluation for adrenal disease.
• Increase use in radiological imaging procedures resulted in this clinical dilemma.
• 4.7% - adrenocortical carcinoma*
• 2.5% - metastatic cancer*
• 15% - 20% hormonally active**:
- 9% subclinical Cushing’s
- 4% pheo
- 2% aldosteroma |
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Term
| Evaluation for malignancy |
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Definition
1. Size is predictive of malignancy
>4 cm is size has 90% sensitivity, but only 24%
specificity*
2. CT or MRI
Hounsfield units <10 – density of the fat
Borders /Texture/
Contrast medium washout >50% in 10 min has a 100% sens and spec for adenoma** |
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Term
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Definition
Round, homogeneous Smooth contour
<4cm
<10 HU
Isointensity with liver Rapid contrast washout
[image] |
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Term
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Definition
>20 HU
Increased vascularity Delayed contrast washout Heterogeneous
High signal intensity on T-2 Weighted MRI
[image] |
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Term
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Definition
Irregular Heterogeneous Calcifications >4cm
>20 HU
Delayed contrast washout Hypodense to liver
[image] |
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Term
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Definition
• Can not distinguish a benign adenoma from adrenal CA
• Can distinguish adrenal tumor from metastatic tumor
• Safe if pheo is excluded |
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Term
Hormonal Evaluation
• From least likely: |
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Definition
• Androgen producing tumors
• Aldosteroma
• Pheochromocytoma
• Subclinical Cushings syndrome |
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Term
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Definition
• You should have a high degree of suspicion
• Establish biochemical dx first, then proceed with imaging
• Refer to endo:
- positive screening tests
- incidentally found adrenal mass |
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