Endocrine Flashcards
What are the immunohistochemistry findings in a pheochromocytoma?
Positive for synaptophysin, chromogranin, and neuron-specific enolase
What is the abnormal bone pathology seen in CKD? What causes it?
Renal osteodystrophy. Caused by secondary hyperparathyroidism (caused by hyperphosphatemia and hypocalcemia)
What can lead to permanent diabetes insipidus (DI)
Damage to hypothalamic nuclei, because it results in a loss of vasopressinergic neurons
How is prolactin release regulated?
It is under inhibitory control by dopamine secretion from the hypothalamus
phenylethanolamine-N-methyltransferase (PNMT)
Enzyme in the adrenal medulla that rapidly converts norepinephrine to epinephrine
Mechanism of development of Graves opthalmopathy
Stimulation of orbital fibroblasts and adipocytes by thyrotropin receptor antibodies and activated T cells. Fibroblasts secrete excess amounts of glycosaminoglycans, leading to expansion of the ground substance of retro-orbital tissues. This, along with excess adipose deposition, displaces the globe forward.
When does hyperosmotic volume contraction occur?
In patients with diabetes insipidus or as a result of decreased fluid intake/excessive sweating
What causes hyperosmotic volume contraction?
Loss of free water with retention of electrolytes
Glyburide mechanism
Sulfonylurea - binds to their receptor on pancreatic beta cells to inhibit the ATP-dependent potassium channel. Net result is increased insulins secretion by beta cells independent of blood glucose concentrations
What is a major risk of sulfonylureas?
Hypoglycemia. Increased risk with exercise, missed meals, chronic malnourishment, or organ dysfunction
Name the second generation sulfonylureas. Which are long vs. short acting?
Glipizide, Glyburide, Glimepiride.
Glyburide and Glimepiride are long acting, higher incidence of hypoglycemia. Glipizide is short acting, significantly lower incidence of hypoglycemia
Intense mononuclear infiltrate consisting of lymphocytes and plasma cells, often with germinal centers. Follicles surrounded by large oxyphilic cells with granular cytoplasm (Hurthle cells)
Biopsy findings in chronic lymphocytic (Hashimoto) thyroiditis
Pancreatic islet amyloid deposition
Type 2 Diabetes Mellitus
5 alpha-reductase
Converts testosterone to DHT
Phenotypic male born with feminized external genitalia that masculinize at puberty. What enzyme is deficient?
5-alpha-reductase
Myopathy, cardiomyopathy, hypoketotic hypoglycemia in the setting of decreased muscle carnitine content suggests?
Primary carnitine deficiency. Caused by a defect in the protein responsible for carnitine transport across the plasma membrane
Elevated FSH and LH; low testosterone; long lower extremities; small, firm testes; azoospermia
Klinefelter syndrome (47, XXY)
Maldevelopment of the third and fourth pharyngeal pouches results in?
DiGeorge syndrome
Signs of hypocalcemia
Muscle cramps, perioral paresthesias, hypotension, possible laryngospasm, Chvostek sign, Trousseau sign
Male at age 2-4 years who present with early virilization, increased linear growth, and elevated levels of 17-hydroxyprogesterone and androgens
Classic, non-salt-wasting 21-hydroxylase deficiency
Treatment of congenital adrenal hyperplasia
Low doses of exogenous corticosteroids to suppress ACTH secretion
Leuprolide
GnRH analog. Agonist properties when administered in a pulsatile fashion and can cause transient rise in LH and testosterone production on initial administration. Long term leuprolide use suppresses pituitary LH release and subsequently leads to reduced production of testosterone by Leydig cells
What do decreased parathyroid hormone levels cause?
Decreased calcium and phosphate resoprtion from bone and decreased calcium reabsorption by the kidneys
Statins mechanism
Act through competitive inhibition of HMG-CoA reductase, preventing conversion of HMG-CoA to mevalonic acid. Decreased liver cholesterol synthesis leads to increased hepatic clearance of LDL from the circulation by LDL receptors. Increase in LDL receptor recycling.
Most common complication of statins
myopathy
Ezetimibe
Decreases intestinal absorption of cholesterol
Medullary thyroid cancer, pheochromocytoma, marfanoid habitus, and oral and intestinal mucosal neuromas
Multiple endocrine neoplasia type 2B
Sporadic and medullary thyroid cancers are associated with mutations in which gene?
RET proto-oncogene
Treatment for adrenal crisis
Immediate glucocorticoid supplementation and aggressive fluid resuscitation
Severe hypotension, abdominal pain, vomiting, weakness, and fever
Adrenal crisis
Complications of severe diabetic ketoacidosis
Pulmonary edema, respiratory fatigue, decreased mental status, which may lead to hypoventilation and subsequent hypercarbic respiratory failure
Mechanism for treating hirsutism with combination OCPs
Suppress pituitary LH secretion and subsequently decrease ovarian androgen production
MEN 1 Syndrome
Tumors of the pituitary, parathyroid gland, and pancreas
Neurophysins
Carrier proteins for oxytocin and ADH. Produced within the neuronal cell bodies of hypothalamic nuclei.
Clinical presentation of impaired beta oxidation of fatty acids
Hypoglycemia after prolonged fasting and inappropriately low levels of ketone bodies
Most commonly deficient enzyme in impaired beta oxidation of fatty acids
Acyl-CoA dehydrogenase
How do chronically elevated free fatty acid levels contribute to insulin resistance
Impairing insulin-dependent glucose uptake and increasing hepatic gluconeogenesis
Erythrocytosis, testicular atrophy, acne, and virilization in women are sign os what?
Androgenic steroid abuse
What drugs decrease peripheral conversion of T4 to T3?
Lipid-soluble beta blockers, glucocorticoids, PTU
Cause of familial hypocalciuric hypercalcemia
Autosomal dominant disorder caused by defective calcium-sensing receptors in the parathyroid gland and kidneys
What is a feared complication of antithyroid drugs (Methimazole, PTU)
Agranulocytosis - manifesting as fever, sore throat oral ulcerations
Low plasma sodium and osmolality, inappropriately concentrated urine, clinically normal volume status (euvolemic hyponatremia)
Features of SIADH
Glucocorticoids effect on the liver
Increase hepatic gluconeogenesis and glycogenesis
What is responsible for the intracellular effects of the G protein-mediated adenylate cyclase second messenger system
Protein kinase A
Pioglitazone
TZD. Exert glucose lowering effects by improving insulin sensitivity. Bind to PPAR-gamma, an intracellular nuclear receptor that acts as a transcription regulator of many genes in glucose and lipid metabolism
Main side effects of TZDs
Fluid retention, with resultant weight gain and edema
What are symptoms of vitamin D intoxication?
Mental status changes, muscle weakness, constipation, polyuria/polydipsia
1-alpha-hydroxylase
The enzyme that converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D
What do activated macrophages in sarcoidosis and other granulomatous diseases express?
1-alpha-hydroxylase
Why is there a delay in action of TZDs?
The medication is dependent on alteration of gene expression and subsequent protein synthesis
Pretibial myxedema and Graves ophthalmopathy
Features of Graves disease
What causes the pretibial myxedema and opthalmopathy in Graves?
An autoimmune response directed against the TSH receptor that results in the accumulation of glycosaminoglycans within the affected tissue
What are the acute effects of corticosteroids on the white blood cell count?
Increased neutrophil count and decreased lymphocyte, monocyte, basophil, and eosinophil counts
17-alpha hydroxylase deficiency
Boys appear phenotypically female at birth, but girls develop normal genitalia. Patients typically present with hypogonadism, hypertension, and hypokalemia
Functional hypothalamic amenorrhea
Loss of pulsatile gonadotropin-releasing hormone release from the hypothalamus. Caused by weight loss, strenuous exercise, systemic illness, or abnormal eating habits
Cushing disease dexamethasone test results
ACTH is high and cortisol production can be suppressed by high-dose, but not low-dose dexamethasone
Ectopic ACTH production dexamethasone test results
Cortisol and ACTH production are not suppressed by low or high dose dexamethasone
What does long term glucocorticoid use do to the adrenal glands
Leads to bilateral adrenocortical atrophy involving the zona fasciculata and reticularis
Hypoglycemia, ketoacidosis, hepatomegaly, muscle weakness, and hypotonia that present in infancy or childhood. There is cytosolic accumulation of limit dextrans
Debranching enzyme deficiency (Cori disease)
Repaglinide mechanism
Act by binding to and closing the ATP-dependent K+ channel in pancreatic beta cell membrane, inducing depolarization and L-type calcium channel opening. Increased Ca2+ influx stimulates beta cell insulin release
What is the predominant initial means of rapidly increasing blood glucose levels during hypoglycemia?
Glucagon-induced glycogenolysis by the liver
What is the most common cause of adrenal insufficiency?
Suppression of the hypothalamus-pituitary-adrenal axis by glucocorticoid therapy
What is the 2nd most common cause of congenital adrenal hyperplasia?
11 beta-hydroxylase deficiency
Girl with ambiguous genitalia, hypertension, and hypokalemia
11 beta-hydroxylase deficiency
Episodic HTN, tachycardia, headaches, diaphoresis, and tremors
Pheochromocytoma
How is the diagnosis of pheochromocytoma confirmed?
Elevated levels of catecholamines and metanephrines in the urine or plasma
Cause of primary hyperalosteronism
Excessive aldosterone secretion, typically as a result of bilateral nodular hyperplasia of the zona glomerulosa or an aldosterone producing adrenal adenoma
What happens to thyroid hormone with increase in estrogen activity
There is an increase in thyroxine-binding globulin. This leads to increase in total thyroid hormone levels, but feedback control maintains normal free thyroid hormone
Primary hyperparathyroidism skeletal manifestation
Osteitis fibrosa cystica - bone pain, subperiosteal erosions affecting the phalanges of the hand, a “salt and pepper” skull, and brown tumor bone cysts
Pathway used by growth hormone
Binds cell surface receptors, leading to intracellular activation of the JAK-STAT pathway
