10/14- Disorders of Adrenal Glands Flashcards
1
Q
What are diseases of adrenal gland (list)?
A
- Adrenal Insufficiency*
- Selective Hypoaldosteronism
- Cushing’s syndrome
- Hyperaldosteronism*
- Pheochromocytoma
- Adrenogenital syndromes
- Adrenocortical carcinoma
2
Q
Describe anatomy of adrenal glands
A
- 4g
- 2 cm x 5 cm x 1 cm
- Yellow due to cholesterol content
3
Q
What are the different layers of the adrenal gland?
Hormones produced there?
A
(Inner -> outer)
- Zona reticularis: DHEA, androstenedione, cotisol (loss)
- Zona fasciculata: cortisol
- Zona glomerulosa: aldosterone
4
Q
What controls cortisol secretion/contributing factors?
A
CRH produced by hypothalamus
- Stressors (IL-1, 6, TNF-a, fever, surgery, burns, exercise)
- Hypoglycemia
- Hypotension
- Circadian regulation
- Negative feedback by cortisol itself
POMC/ACTH by anterior pituitary
- Triggered by CRH
Cortisol by adrenal
- Triggered by ACTH
5
Q
Describe steroidogenesis
A
GLOMERULOSA
- Pregnenolone —(3-BHSD)–> Progesterone —(CYP21A2) –> Deoxy-corticosterone —(CYP11B1)–> Corticosterone - In the glomerulus, corticosterone is converted into aldeosterone
FASCICULATA
- Pregnenolone can also be converted into 17-OH pregnenolone
- Progesterone can be converted into 17-OH progesterone
- Then converted into deoxycortisol and eventually cortisol
RETICULARIS
- 17OH pregnenolone can be converted into DHEA
- 17OH progesterone can be converted into androstenedione
6
Q
Recap: production of cortisol
A
7
Q
What are the key hormone influences (which hormones and are levels high/low) for:
- Primary adrenal insufficiency
- Secondary adrenal insufficiency
- Tertiary adrenal insufficiancy
A
- Primary adrenal insufficiency: elevated ACTH
- Secondary adrenal insufficiency: ACTH deficiency
- Tertiary adrenal insufficiancy: CRH deficiency
8
Q
Describe the characteristics of primary adrenal insufficiency
- Severity
- Hormone levels
A
- Elevated ACTH levels
- Symptoms and signs usually are more severe as patients with primary adrenal disease have a deficiency of glucocorticoids and mineralocorticoids as well as androgens
- Suddenness of onset affects severity of symptoms and signs
9
Q
Describe the characteristics of secondary adrenal insufficiency
- Hormone levels
A
- ACTH deficiency
- Most cases of secondary and tertiary deficiency are associated with adequate secretion of aldosterone and deficient secretion of cortisol and adrenal androgens
10
Q
Describe the characteristics of tertiary adrenal insufficiency
- Hormone levels
A
- CRH deficiency
- We do not differentiate between secondary and tertiary AI in clinical practice
11
Q
What are the main/broad things causing primary adrenal insufficiency?
A
- Adrenal dysgenesis/hypoplasia
- Adrenal destruction
- Impaired steroidogenesis
12
Q
What may cause adrenal destruction?
A
Autoimmune
- Sporadic PGA I and II
ALD
Infectious
- Sporadic
- Tuberculosis
- Histo, Blasto, Coccidio, Crypto
- Toxo
- Septicemia
- HIV-associated
- CMV
- MAI
- Kaposi’s
Hemorrhagic
- Anticoagulation
- Antiphospholipid syndrome
- Waterhouse-Friedrichsen/sepsis
- Heparin-induced thrombocytopenia
Metastatic
- Lung, breast, gastric, melanoma, lymphoma
Amyloidosis
13
Q
What may cause adrenal dysgenesis/hypoplasia?
A
- SF1
- DAX1
- ACTHR
14
Q
What may cause adrenal impaired sterogenesis?
A
Cholesterol biosynthesis:
- Smith Lemli Opitz syndrome
- Abetalipoproteinemia
Steroid biosynthesis:
- StAR protein
- Mitochondrial DNA deletion
- CAH
15
Q
What are etiologies of 2’ adrenal insufficency?
Hormone characteristics?
A
Low ACTH and cortisol
Etiology:
- Pituitary tumor, craniopharyngioma, metastatic tumor
- Hypophysectomy
- Surgery/radiations in the pituitary hypothalamus area
- Sheehan’s syndrome (pituitary infarction)
- Infection (tuberculosis, syphilis)
16
Q
What are etiologies of 3’ adrenal insufficency?
A
- Cessation of treatment with glucocorticoids
- Head trauma
- Sarcoidosis
- Langerhans cell histiocytosis
- Drugs that inhibit CRH secretion (morphine, fentanyl, barbiturates)
- Traumatic Brain injury (up to 30% develop AI)
17
Q
Describe acute adrenal insufficiency or adrenal crisis.
What causes it?
A
An adrenal crisis can occur when there is a sudden change in the concentration of cortisol
Examples:
- Patient who had bilateral adrenal infarction or adrenal hemorrhage
- Patient with chronic adrenal insufficiency using hormonal replacement who has an acute infection or another acute stress, requiring higher doses of cortisol
Symptoms and signs:
- Dramatic presentation
- Fever, N/V
- Postural hypotension, shock, fatigue
- Abdominal pain
- Altered mental state
18
Q
What are signs/symptoms of chronic adrenal insufficiency?
A
Symptoms:
- Weakness and fatigue (100%)
- N/V (80%)
- Anorexia (50%)
- Depression (20-40%)
- Psychoses (20-40%)
- Diarrhea (15%)
- Muscle, joint, abdominal pain (10%)
Signs:
- Weight loss (100%)
- Hyperpigmentation (9)%)
- Orthostatic hypoTN (90%)
- Adrenal calcification (10%)
- Vitiligo (5%)
19
Q
What is seen here?
A
- Hyperpigmentation
- Vitiligo (primary adrenal insufficiency)
20
Q
What is seen here?
A
Hyperpigmentation
- Seen here on aereolas
- Can also be seen on inside of lip or gums around teeth
21
Q
What is seen here indicative of primary adrenal insufficiency?
A
Palmar crease hyperpigmentation
22
Q
What is included in lab diagnosis of adrenal insufficiency for:
- Cortisol
A
- 8 am plasma cortisol level
- < 3 µg/dL strongly suggests AI
- However measurement of cortisol alone not reliable, ACTH stim test should be done
- Plasma cortisol level < 18-20 µg/dL in the setting of shock is suggestive of AI (the patient is stressed, cortisol should be much higher)
23
Q
What is included in lab diagnosis of adrenal insufficiency for:
- Plasma ACTH
A
Plasma ACTH level is high in the presence of low plasma cortisol in primary AI
- Nl value at 8am 5-20 pg/mL, will be low/normal in secondary AI
24
Q
What is included in lab diagnosis of adrenal insufficiency for:
- P450c21 Abs
A
P450c21 antibodies (for autoimmune adrenal insufficiency)
25
What is included in lab diagnosis of adrenal insufficiency for:
- Aldosterone
Aldosterone will be low with high renin in primary adrenal insufficiency
26
What is included in lab diagnosis of adrenal insufficiency for:
- ACTH stimulation tesets
God standard for diagnosing adrenal insufficiency!
**Short synthetic ACTH (cosyntropin) stimulation test:**
- Give 1 µg or 250 mg bolus of synthetic ACTH and measure plasma cortisol levels at -15, 0, 30 and 60 minutes
- Normal individuals will have baseline and/or stimulated values of \>18/20 µg/dl
27
What is included in lab diagnosis of adrenal insufficiency for:
- CRH stimulation tests (what will be seen in the different types of adrenal insufficiency)
(Not done in routine clinical practice)
- Primary deficiency: **exaggerated rise in ACTH**
- Secondary deficiency: **inadequate rise in ACTH**
- Tertiary deficiency: **a delayed and prolonged rise in ACTH**
28
What is included in lab diagnosis of adrenal insufficiency for:
- Insulin Tolerance Test
Gold standard
- Use stress of hypoglycemia to increase ACTH and cortisol secretion
- Do not use this test in patients with angina or seizures
- Must observe signs of hypoglycemia or a nadir glucose value of under 45 mg/dL 0.1 U / Kg
- A physician must be in attendance
- Give D50W IV if symptoms and signs of hypoglycemia become too severe
- Normal response: Cortisol \> 18 ug/dl
29
What is included in lab diagnosis of adrenal insufficiency for:
- Aldosterone and renin
- Primary adrenal insufficiency causes loss of aldosterone secretion and a secondary increase in renin secretion
- Reduced aldosterone secretion contributes to volume contraction, hypotension and hyperkalemia
30
What imaging modality used for diagnosis of adrenal insufficiency?
Abdominal CT scan:
31
What could cause small adrenals on abdominal CT in person with adrenal insufficiency?
- Idiopathic or autoimmune disease
- Adrenal calcification in patients with tuberculous Addison's disease of \>2 years duration
32
What could cause large adrenals on abdominal CT in person with adrenal insufficiency?
- Tuberculosis for \< 2 years duration
- Carcinomatous replacement of the adrenals
- Systemic fungal diseases
- Cytomegalovirus
- Amyloidosis
- Sarcoidosis
- Hodgkin's disease
33
What is seen in these images?
- Top left: **Histoplasmosis**
- Top right: **Metastatic melanoma**
- Bottom left: **Bilateral adrenal hemorrhage**
- Bottom right: **Tuberculomas**
34
What therapy can be given to AI pts?
**Primary AI:**
- Replacement with a Mineralocorticoid and Hydrocortisone
**Secondary and tertiary AI:**
- Replacement with Hydrocortisone
35
A 60 y/o male who is admitted with suspected pulmonary embolism and is treated with heparin, suddenly develops hypotension that does not respond to volume and vasopressors, but it responds immediately to IV glucocorticoids.
Which of the following etiologies would you consider the most likely cause?
A. Tuberculosis
B. Autoimmune adrenal insufficiency
C. Adrenal hemorrhage
D. Previous prednisone (glucocorticoid) use
E. Sepsis
A. Tuberculosis
B. Autoimmune adrenal insufficiency
**C. Adrenal hemorrhage**
D. Previous prednisone (glucocorticoid) use
E. Sepsis
- No evidence for TB, autoimmune cause, glucocorticoid use or sepsis
- Renal hemorrhage most likely b/c of history of heparin
36
What factors contribute to the control of aldosterone secretion?
**JG cells produce renin in response to:**
- Decreased arterial pressure (e.g. hypotension)
- Increased B-adrenergic action
- Increased prostaglandins
**Renin converts angiotensinogen (from liver) into angiotensin I**
- Ang I converted to Ang II by ACE in the lungs
- Ang II acts on adrenals to secrete aldosterone
37
Describe the function of the mineralocorticoid receptor
- Aldosterone acts by binding to the cytosolic mineralocorticoid receptor
- Highest levels of expression in the distal nephron, distal colon, hippocampus
- Classic action of aldosterone involves epithelial cells in distal nephron and colon, mediates Na flux
38
**T/F:** The MR binds aldosterone and cortisol equally
True
39
Describe the function/activity of aldosterone in the principal cells of the kidney (CD)
- Aldosterone increases the abundance of the alpha subunit of the Na channel (more Na uptake into cell from tubular lumen)
- Aldosterone increases the activity of the Na-K-ATPase pump (sending Na into peritubular caps)
40
What are the 2 types of hyperaldosteronism?
- Hormone levels
- Clinical presentation
**Primary Hyperaldosteronism:**
- High aldosterone with low renin
- Hypertension, hypokalemia (not always), metabolic alkalosis
**Secondary Hyperaldosteronism:**
- High aldosterone with unsuppressed or high renin
- Hypertension (not always), hypokalemia (not always), metabolic alkalosis
41
What may cause primary hyperaldosteronism?
- Genetics involved?
***Aldosterone producing adenomas (35%)***
- Mutations of KCNJ5 (47%), ATP1A1 (5.2%), ATPB3 (1.6), CACNA1D (10%) CTNNB1 (3 cases reported)
***Bilateral idiopathic hyperaldosteronism (bilateral adrenal hyperplasia) (60%)***
- No mutations detected
**Familial hyperaldosteronism**
- **Type I** (glucocorticoid remediable aldosteronism) (0.66%)
* AD
* Associated with normokalemia
- **Type II** (Familial occurrence of aldosterone producing adenoma or bilateral idiopathic hyperplasia) (2%)
- **Type III** (mutations of the KCNJ5 gene)
* AD
**Pure aldosterone producing adrenocortical carcinomas**
**Ectopic aldosterone producing tumores**
42
What may cause secondary hyperaldosteronism?
Activation of the renin angiotensin-aldosterone (R-A-A) axis as a homeostatic mechanism designed to maintain serum electrolyte concentrations or fluid volume
**- *Renovascular hypertension***
- **Renin-producing tumors**
- **Pregnancy**
- **Diuretic therapy (no HTN)**
- **Edema disorders** (eg, cardiac failure and nephrotic syndrome)
- **Bartter syndrome** (reduced activity of one of several electrolyte transporters in the thick ascending limb) (no HTN, low K, met alk)
- **Gitelman syndrome** (inactivating mutations in the gene coding for the thiazide-sensitive Na-Cl cotransporter in the distal tubule) (no HTN)
43
What is the usual presentation of primary hperaldosteronism? Symptoms?
- High aldosterone
- Suppressed renin (Aldosterone Renin ratio \> 20)
- Hypertension requiring treatment with 3 or more medications
- Hypokalemia (not always)
- Metabolic alkalosis
- Low ionized calcium from hypokalemic metabolic alkalosis causes tetany, as in Conn’s index patient
- Can be associated with secondary hyperparathyroidism
_Symptoms:_
- Weakness
- Myalgias
- Muscle spasms
- Headaches
- Palpitations
44
What is the algorithm for the detection, confirmation, subtype testing, and treatment of PA?
45
The Endocrine Society recommends use of what to detect cases of PA?
**Plasma ARR**
- The ARR is currently the most reliable available means of screening for PA.
- An ARR cutoff of 23.6 ng/dL per ng/mL/hour had a sensitivity of 97% and specificity of 94%
46
What is the prevalence of primary hyperaldosteronism in pts with resistant HTN?
- About 21% of resistant HTN pts had ARR \> 20
- About 11% were later confirmed with suppression test
47
What are the classes of HTN medications and the effects on ARR?
**No effect on ARR**:
- Verapamil
- Hydralazine (vasodilator)
- Alpha blockers (--azosin)
**Increase ARR** (decrease aldo, more greatly decrease renin)
- Beta blockers
- NSAIDs
- Clonidine
**Decrease ARR** (increase aldo, more greatly increase renin)
- K wasting
- K sparing
- ACEI
- ARBs
- CCBs
48
Describe the salt loading dynamic test for primary hyperaldosteronism?
In normal subjects, volume expansion with saline -\> suppression of PRA and PAC
**1. Dietary Na intake**:
\>200mEq/d x 3 days -\> urinary aldosterone \< 12 mcg/24h with 24 urinary NA \> 200 MEq/L
**2. Saline infusion:**
2 L NS over 2-4h -\> PAC under 5 ng/dl
**3. Fludrocortisone:**
high Na diet plus Fludrocortisone 0.1 mg qid x 4 days, PAC value \> 6ng/dl and PRA under 1 in patients with primary hyperaldosteronism
**4. Captopril test:**
25 mg PO, 2h PAC under 15 ng/dl
For reliability of tests, normal K levels, and suppression of PRA to under 1 ng/ml/hr
49
Spironolactone can be used to medically treat hyperaldosteronism.
Side effects?
Anti-androgen
- Can cause gynecomastia in men
- Still better than the alternative med
50
What conditions may cause: HTN, metabolic alkalosis, and hypokalemia?
Also low renin and low aldosterone:
- Syndrome of apparent mineralocorticoid excess
- Licorice ingestion
- Ectopic ACTH
- Liddle's syndrome (pseudohyperaldosteronism)
- CAH (11b and 17a Hydroxylase deficiency)
