Adrenal

Question 1

Describe the difference between the short-term and long-term stress response in terms of the HPA axis and the adrenal cortex.

Answer 1

• Short-term causes stimulation of the adrenal medulla to ↑ release of catecholamine (NE and epinephrine)
• Long-term causes stimulation of the adrenal cortex and ↑ release of mineralocorticoids and glucocorticoids

Question 2

What are the effects of angiotensin II on the adrenal cortex and pituitary gland?

Answer 2

• Adrenal cortex: stimulates secretion of aldosterone
• Posterior pituitary: stimulates the secretion of ADH

Question 3

What are the 3 mainstays of treatment in an infant in crisis due to congenital adrenal hyperplasia (21-hydroxylase deficiency)?

Answer 3

• Hydrocortisone (IV or IM)
• Fluids/glucose (IV)
• Management of hyperkalemia: get K⁺ levels ↓

Question 4

Summarize the purpose of mandatory newborn screening, which 7 major classes of disorders are screened for?

Answer 4

• Amino acid disorders
• Endocrine disorders
• Fatty acid oxidation disorders
• Hemoglobin disorders
• Lysosomal storage disorders
• Organic acid conditions
• Others: CF, hearling loss, classic galoctosemia, congenital HD, SCID

Question 5

What is the most common cause of adrenal destruction responsible for primary adrenal insufficiency (Addison disease) in the US?

Answer 5

Autoimmune

Question 6

Which autoimmune causes of adrenal destruction are associated with neurological deterioration which may mimic multiple sclerosis?

Answer 6

Adrenoleukodystrophy and adrenomyeloneuropathy

Question 7

What is the inheritance pattern and what is seen with familial glucocorticoid deficiency (ACTH, cortisol, and mineralocorticoid levels)?

Answer 7

• Autosomal recessive
• ACTH resistance due to mutations in the adrenal ACTH receptors –> isolated cortisol deficiency
• ↑ ACTH causes skin pigmentation
• Mineralocorticoid production is always normal

Question 8

Which disease of adrenal dysgenesis is associated with hypogonadotropic hypogonadism, myopathy, and high-frequency hearing loss?

Answer 8

Congenital adrenal HYPOplasia (x-linked) = absence of adrenal cortex

Question 9

What is the most common cause of impaired steroidognesis leading to primary adrenal insufficiency; what are the levels of adrenal hormones like?

Answer 9

• 21-hydroxylase deficiency
• Deficiency of aldosterone = salt-wasting
• Deficiency of cortisol
• Excessive androgens (virilization of females)

Question 10

Nearly all patients with primary adrenal insufficiency complain of what signs/sx’s?

Answer 10

• Fatigue + reduced stamina + weakness + anorexia + weight loss
• Skin hyperpigmentation

Question 11

What is the serum Na⁺, K⁺, glucose, and calcium like in primary adrenal insufficiency?

Answer 11

• Low serum Na⁺
• High serum K⁺
• Fasting HYPOglycemia
• HYPERcalcemia may be present (↓ renal filtration)

Question 12

What is the confirmatory test for primary adrenal insufficiency?

Answer 12

- Cosyntropin (synthetic ACTH) stimulation test

- If cortisol levels do no respond after 45 mins., confirms

Question 13

Which serum markers can be used to confirm autoimmun Addison disase and which is required for diagnosis of 21-hydroxylase deficiency?

Answer 13

• Serum antibodies to 21-hydroxylase confirm dx of autoimmune Addison disease
• ↑ serum levels of 17-OH progresterone are required for diagnosis

Question 14

What is the treatment for primary adrenal insufficiency (Addison disease)?

Answer 14

• Glucocorticoid replacement therapy: hydrocortisone, predisone, prednisolone
• Mineralocorticoid replacement therapy: fludrocortison acetate (Na⁺ sparing)
• DHEA: given to some post-menopausal women (libido, done density, hormonal balance)

Question 15

List 5 labs which can be ordered to help diagnose acute adrenal crisis?

Answer 15

• ACTH (cosyntropin) stimulation test
• Cortisol level
• Blood sugar
• Serum K⁺
• Serum Na⁺

Question 16

If you are dealing with an infant in the first several weeks of life with suspected acute adrenal crisis, what lab needs to be drawn?

Answer 16

17-OH-progesterone level; must rule out 21-hydroxyase deficiency

Question 17

What are the 3 components of treatment for acute adrenal crisis?

Answer 17

• Hydrocortisone
• Fluids/glucose
• Treat HYPERkalemia if needed

Question 18

Low serum ACTH in the setting of low serum cortisol is indicative of what type of adrenal abnormality?

Answer 18

Secondary adrenal insufficiency

Question 19

What are 3 possible causes of ACTH-dependent Cushing Syndrome?

Answer 19

• Exogenous ACTH use
• Cushing disease (ACTH-secreting pituitary adenoma)
• Ectopic ACTH syndrome –> small cell carcinoma of lung

Question 20

What are some of the possible causes of ACTH-independent Cushing Syndrome?

Answer 20

• Exogenous corticosteroid use (MOST COMMON)
• Adrenocortical tumor
• Bilateral primary adrenocortical hyperplasia: PPNAD, Carney complex, massive macronodular adrenal hyperplasia, McCune-Albright syndrome

Question 21

What is seen in McCune-Albright Syndrome?

Answer 21

• Polyostotic fibrous dysplasia
• Café-au-lait spots
• Endocrine hyperfunction from mutliple organs —> bilateral primary adrenocortical hyperplasia

Question 22

All (even normotensive) patients with an adrenal incidentaloma require testing for what?

Answer 22

Pheochromocytoma w/ plasma fractionated free metanephrines

Question 23

What is the most common cause of refractory HTN in youths and middle-aged adults?

Answer 23

Primary aldosteronism (hyperaldosteronism)

Question 24

Conn sydrome is primary hyperaldosteronism secondary to what?

Answer 24

Unilateral aldosterone-producing adrenal adenoma

Question 25

40% of pt's w/ primary hyperaldosteronism (Conn Syndrome) have a mutation in a gene encoding what?

Answer 25

**K⁺ channel**

Question 26

What are the signs and sx's of primary hyperaldosteronism?

Answer 26

- **HTN** = moderate to severe; some only diastolic HTN - **HYPOkalemia** --\> muscle weakness, parasthesias w/ tetany, HA, polyuria and polydipsia

Question 27

Which acid-base disorder is commonly seen with primary hyperaldosteronism?

Answer 27

**Metabolic alkalosis** (proton loss, **H⁺** w/ **K⁺**)

Question 28

All patients with biochemically confirmed primary aldosteronism require what type of imaging?

Answer 28

**T****hin-section CT scan**of adrenal to screen for**adrenal carcinoma**(although**rare**)

Question 29

How does the secretory products differ between pheochromocytomas and paragangliomas?

Answer 29

- **Pheochromocytomas** secrete **BOTH** epi and NE - **Paragangliomas** secrete NE or are non-secretory

Question 30

What is the inheritance pattern of Von Hippel-Lindau disease type 2?

Answer 30

Autosomal Dominant

Question 31

What are some of the underlying abnormalities associated with Von Hippel-Lindau disease type 2?

Answer 31

- 20% develop **pheochromocytomas** (which secrete **_only_** NE) - **Hemangiomas** of **retina, cerebellum, brainstem,** and **SC** - **Hyperthyroidism** - **Pancreatic cysts + Renal cyts** - **Endolymphatic sac tumors** - **Cystadenomas** of the **adnexa** or **epididymis** - **Pancreatic neuroendocrine tumors** - **Adenomas** + **Carcinomas**

Question 32

What is the single most sensitive test for secretory pheochromocytomas and paragangliomas?

Answer 32

Plasma fractionated **free metanephrines**

Question 33

If the abdomen becomes "seeded" during surgery for a pheochromocytomas this can result in multifocal intra-abdominal tumors known as what?

Answer 33

Pheochromocytomatosis

Question 34

Will surgical histopathology for pheochromocytoma and paragangliomas determine if a tumor is malignant?

Answer 34

- **NO** - All pheo's and paragangliomas must be approached as possibly malignant - **Follow-up** has to be **lifelong**