Lecture 2: Adrenal Flashcards
Describe the difference between the short-term and long-term stress response in terms of the HPA axis and the adrenal cortex.
- 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
What are the effects of angiotensin II on the adrenal cortex and pituitary gland?
- Adrenal cortex: stimulates secretion of aldosterone
- Posterior pituitary: stimulates the secretion of ADH
What are the 3 mainstays of treatment in an infant in crisis due to congenital adrenal hyperplasia (21-hydroxylase deficiency)?
- Hydrocortisone (IV or IM)
- Fluids/glucose (IV)
- Management of hyperkalemia: get K+ levels ↓
Summarize the purpose of mandatory newborn screening, which 7 major classes of disorders are screened for?
- 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
What is the most common cause of adrenal destruction responsible for primary adrenal insufficiency (Addison disease) in the US?
Autoimmune
Which autoimmune causes of adrenal destruction are associated with neurological deterioration which may mimic multiple sclerosis?
Adrenoleukodystrophy and adrenomyeloneuropathy
What is the inheritance pattern and what is seen with familial glucocorticoid deficiency (ACTH, cortisol, and mineralocorticoid levels)?
- Autosomal recessive
- ACTH resistance due to mutations in the adrenal ACTH receptors –> isolated cortisol deficiency
- ↑ ACTH causes skin pigmentation
- Mineralocorticoid production is always normal
Which disease of adrenal dysgenesis is associated with hypogonadotropic hypogonadism, myopathy, and high-frequency hearing loss?
Congenital adrenal HYPOplasia (x-linked) = absence of adrenal cortex
What is the most common cause of impaired steroidognesis leading to primary adrenal insufficiency; what are the levels of adrenal hormones like?
- 21-hydroxylase deficiency
- Deficiency of aldosterone = salt-wasting
- Deficiency of cortisol
- Excessive androgens (virilization of females)
Nearly all patients with primary adrenal insufficiency complain of what signs/sx’s?
- Fatigue + reduced stamina + weakness + anorexia + weight loss
- Skin hyperpigmentation
What is the serum Na+, K+, glucose, and calcium like in primary adrenal insufficiency?
- Low serum Na+
- High serum K+
- Fasting HYPOglycemia
- HYPERcalcemia may be present (↓ renal filtration)
What is the confirmatory test for primary adrenal insufficiency?
- Cosyntropin (synthetic ACTH) stimulation test
- If cortisol levels do no respond after 45 mins., confirms
Which serum markers can be used to confirm autoimmun Addison disase and which is required for diagnosis of 21-hydroxylase deficiency?
- Serum antibodies to 21-hydroxylase confirm dx of autoimmune Addison disease
- ↑ serum levels of 17-OH progresterone are required for diagnosis
What is the treatment for primary adrenal insufficiency (Addison disease)?
- 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)
List 5 labs which can be ordered to help diagnose acute adrenal crisis?
- ACTH (cosyntropin) stimulation test
- Cortisol level
- Blood sugar
- Serum K+
- Serum Na+
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?
17-OH-progesterone level; must rule out 21-hydroxyase deficiency
What are the 3 components of treatment for acute adrenal crisis?
- Hydrocortisone
- Fluids/glucose
- Treat HYPERkalemia if needed
Low serum ACTH in the setting of low serum cortisol is indicative of what type of adrenal abnormality?
Secondary adrenal insufficiency
What are 3 possible causes of ACTH-dependent Cushing Syndrome?
- Exogenous ACTH use
- Cushing disease (ACTH-secreting pituitary adenoma)
- Ectopic ACTH syndrome –> small cell carcinoma of lung
What are some of the possible causes of ACTH-independent Cushing Syndrome?
- Exogenous corticosteroid use (MOST COMMON)
- Adrenocortical tumor
- Bilateral primary adrenocortical hyperplasia: PPNAD, Carney complex, massive macronodular adrenal hyperplasia, McCune-Albright syndrome
What is seen in McCune-Albright Syndrome?
- Polyostotic fibrous dysplasia
- Café-au-lait spots
- Endocrine hyperfunction from mutliple organs —> bilateral primary adrenocortical hyperplasia
All (even normotensive) patients with an adrenal incidentaloma require testing for what?
Pheochromocytoma w/ plasma fractionated free metanephrines
What is the most common cause of refractory HTN in youths and middle-aged adults?
Primary aldosteronism (hyperaldosteronism)
Conn sydrome is primary hyperaldosteronism secondary to what?
Unilateral aldosterone-producing adrenal adenoma
40% of pt’s w/ primary hyperaldosteronism (Conn Syndrome) have a mutation in a gene encoding what?
K+ channel
What are the signs and sx’s of primary hyperaldosteronism?
- HTN = moderate to severe; some only diastolic HTN
- HYPOkalemia –> muscle weakness, parasthesias w/ tetany, HA, polyuria and polydipsia
Which acid-base disorder is commonly seen with primary hyperaldosteronism?
Metabolic alkalosis (proton loss, H+ w/ K+)
All patients with biochemically confirmed primary aldosteronism require what type of imaging?
Thin-section CT scanof adrenal to screen foradrenal carcinoma(althoughrare)
How does the secretory products differ between pheochromocytomas and paragangliomas?
- Pheochromocytomas secrete BOTH epi and NE
- Paragangliomas secrete NE or are non-secretory
What is the inheritance pattern of Von Hippel-Lindau disease type 2?
Autosomal Dominant
What are some of the underlying abnormalities associated with Von Hippel-Lindau disease type 2?
- 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
What is the single most sensitive test for secretory pheochromocytomas and paragangliomas?
Plasma fractionated free metanephrines
If the abdomen becomes “seeded” during surgery for a pheochromocytomas this can result in multifocal intra-abdominal tumors known as what?
Pheochromocytomatosis
Will surgical histopathology for pheochromocytoma and paragangliomas determine if a tumor is malignant?
- NO
- All pheo’s and paragangliomas must be approached as possibly malignant
- Follow-up has to be lifelong
