Endocrinology Flashcards
1
Q
What is SIADH and what are the causes?
A
Excess release of ADH from the neurohypophysis Caused by: 1. Malignancies - Small cell carcinomas - Carcinoma of the pancreas - Ectopic ADH secretion 2. Non-malignant pulmonary disease - TB - Pneumonia - Lung access 3. CNS disorders - Head injury - Cerebral vascular accident - Encephalitis 4. Drugs - Chlorpropramide - Clofibrate - Vincristine - Vinblastine - Cyclophosphamide - Carbamazepine
2
Q
What are the clinical findings in SIADH?
A
- Water retention and extracellular fluid volume expansion without edema or hypertension, owning to natriuresis
- Hyponatremia results from water retention and sodium loss
- Concentrated urine with Uosm > 300 most
- Irritability, confusion, seizures and comma may result in severe hyponatremia ( < 120 mOsm)
3
Q
How is SIADH diagnosed?
A
- Hyponatremia <130 mEq/L and Posm <270 mOsm/kg
- Urine sodium concentration >20 mEq/L (inappropriate natriuresis), maintained hypervolemia, suppression of renin-angiotensin system and no equal conc. of ANP
- Low BUN, low creatinine, low serum uric acid and low albumin
4
Q
How is SIADH treated?
A
Fluid restriction to inder 1 L/d
Demeclocycline can be used
5
Q
Type I Diabetes increases the risk of developing what other diseases?
A
Other autoimmune disorders such as Hashimoto thyroiditis and autoimmune adrenalitis (most common cause of primary adrenal insufficiency “addisons”)
6
Q
Primary Adrenal Insufficiency
“ Addisons Disease”
A
- Results from autoantibody against all 3 zones of the adrenal cortex
- Exogenous ACTH does not increase serum cortisol
- Increased ACTH due to loss of negative feedback from cortisol
- MSH (melanocyte stimulating hormone) is a byproduct of ACTH production and is increased.
- Deficiency of aldosterone and cortisol production
- Lack of aldosterone decreases Na+ reabsorption and K+ and H+ excretion
- Decrease in H+ excretion cause non-anion gap metabolic acidosis with low serum HCO3
- Leads to compensatory Cl- retention to maintain electrical neutrality
- Hypotension, (hyponatremic volume contraction), hyperkalemia, hyperchloremia, metabolic acidosis, skin and mucosal hyperpigmentation (due to increased MSH).
7
Q
Acute Primary Adrenal Insufficiency
A
- Sudden onset ( may be due to massive hemorrhage)
- May present with shock in acute adrenal crisis
- Waterhouse-Friderichsen Syndrome is usually due to an adrenal hemorrhage associated with septicemia from N. meningitidis, DIC or endotoxic shock.
8
Q
Chronic Primary Adrenal Insufficiency
A
- Usually due to adrenal atrophy or destruction by disease
- Western world: autoimmune destruction
- Developing world: Tuberculosis:
9
Q
Secondary Adrenal Insufficiency
A
- Seen with decreased pituitary ACTH production
- No skin/mucosal hyperpigmentation
- No hyperkalemia (aldosterone synthesis is preserved from RAAs)
- Labs show low cortisol and low ACTH
10
Q
Tertiary Adrenal Insufficiency
A
- Seen in patients with chronic exogenous steroid use
- Precipitated by abrupt withdrawal
- Aldosterone synthesis is unaffected
- Labs show low cortisol and low ACTH
11
Q
What are the typical symptoms seen in adrenal insufficiency?
A
- Weakness
- Fatigue
- Orthostatic hypotension
- Muscle aches
- Weight loss
- GI disturbances
- Sugar/salt cravings
12
Q
How is adrenal insufficiency treated?
A
- Glucocorticoid/mineral corticoid replacement
13
Q
What is the metyrapone stimulation test?
A
- Tests for adrenal insufficiency
- Blocks the last step in cortisol synthesis
- Blocks 11-deoxycortisol => cortisol
- Normal response: shows decreased cortisol and increased ACTH and 11-deoxycortisol
- Primary adrenal insufficiency: shows increased ACTH and decreased 11-deoxycortisol
- Secondary adrenal insufficiency: shows decreased ACTH and 11-deoxycortisol
14
Q
MEN type 1
A
- Parathyroid Adenoma (Primary Hyperparathyroidism)
- Hypercalcemia - Pituitary Endocrine Tumors
- Prolactin, visual defects or GH - Pancreatic Tumors
- Gastrinoma (most common)
- Zollinger Ellison syndrome
- Insulinoma
- VIPomas
- Glucagonoma (rare)
15
Q
MEN Type 2A
A
- Medullary Thyroid Cancer
- Neoplasm of parafolicular C Cells
- Secretes calcitonin
- Prophylactic Thyroidectomy Required - Pheochromocytoma
- Metanephrines
- Headaches
- Mutation in RET in cells of neural crest origin - Parathyroid Hyperplasia
16
Q
MEN Type 2B
A
- Medullary Thyroid Cancer (Calcitonin)
- Pheochromocytoma
- Mucosal Neuromas / Marfinoid Habitus
- Mutation in RET gene
17
Q
What is Marfinoid Habitus?
A
- Tall and slender build with disproportionately long arms, legs and fingers
- Found in MEN type 2B
- Mutation in RET proto-oncogene
18
Q
Medullary Thyroid Carcinoma
A
- Neoplasm that originates from parafollicular “C Cells”
- Produces Calcitonin
- Sheets of cells in an amyloid stroma (stains with congo red)
- Associated with MEN 2A and 2B
- RET mutations
- Physical exam may show unilateral or bilateral thyroid mass
- Diagnosed with fine needle aspiration
- Treated with thyroidectomy
19
Q
What is an important predictor of insulin resistance?
A
- Visceral obesity as measured by waist circumference or wist-to-hip ratio
- ## Because excess visceral fat (surrounding internal organs) correlates more with insulin resistance than subcutaneous fat
20
Q
When do you start a patient with PCOS on metformin?
A
When their insulin levels are elevated
21
Q
17-Hydroxylase Deficiency
A
- Impaired sex steroid and cortisol synthesis
- Increased production of mineralcorticoids (aldosterone)
- Females are born with normal genitalia
- Males are born with ambiguous genitalia (undervirilized)
- Affected individuals develop hypokalemia due to aldosterone excess
- Do not undergo puberty (no sex steroids)
22
Q
21-Hydroxylase Deficiency
A
- Decreased mineralocorticoid (aldosterone) and glucocorticoid (cortisol) synthesis
- Increased adrenal androgen production
- Females are born with ambiguous genitalia due to androgen excess
- They frequently develop hypotension and hyperkalemia due to aldosterone deficiency.
23
Q
11-Hydroxylase Deficiency
A
- Results in excessive androgen production
- Result sin excess weak mineralocorticoid production (11-deoxycorticosterone
- Leads to hypertension and hyperkalemia due to 11- deoxycorticosterone acting as aldosterone
- Females are born with ambiguous genitalia (virilization)
24
Q
5Alpha-Reductase Deficiency
A
- Results in ambiguous genitalia in males
- Defective conversion of testosterone to dihydrotestosterone
- Females have normal genitalia
- Blood pressure and electrolytes are unaffected
25
What is side-chain cleavage enzyme?
| What does its deficiency lead to?
- It is the first enzyme in the steroidogenic pathway
- It converts cholesterol to pregnenolone
- Deficiency leads to impaired synthesis of all steroid hormones
- Complete deficiency is lethal due to absent placental progesterone synthesis
26
Pheochromocytoma
| pathogenesis?
- Arises from neuroendocrine cells in adrenal medula
- 25% are inherited
1. VHL (von Hippel-Lindau)
2. RET gene (multiple endocrine neoplasia type 2)
3. NF1 gene (neurofibromatosis)
- Symptoms result from increased catecholamine secretion
27
What are the symptoms from a pheochromocytoma?
- Headaches
- Tachycardia/palpitations
- Sweating
- Hypertension (may be paroxysmal or persistent)
- DIaphoresis
28
What are the rule of 10s?
Pheochromocytoma
- 10 % are bilateral
- 10% are extra adrenal (paragangliomas)
- 10% are malignant
29
How to do you diagnose pheochromocytoma?
- Elevated urinary and plasma catecholamines and metanephrines
- CT scan
30
What are the counterregulatory hormones that play a role in maintaining blood glucose levels?
- Insulin secretion decreases leading to decreased peripheral glucose utilization and increase hepatic gluconeogenesis and glycogenolysis
- Glucagon secretion increases leading to increased hepatic gluconeogenesis and glycogenolysis
- Epinephrine secretion increases leading to increased hepatic gluconeogenesis and glycogenolysis
and increased mobilization of gluconeogenic substrates
- Increased cortisol and growth hormone leads to alteration of many genes to conserve glucose
31
Out of all the counterregulatory hormones that maintain blood glucose levels, which has receptors located within the cytoplasm and translocate to the nucleus?
Cortisol
