Endocrine 2 Flashcards
What is the most common steroidogenic enzyme deficiency?
21-hydroxylase deficiency
What is the effect of 21-hydroxylase deficiency on mineralocorticoids?
Decreased
What is the effect of 21-hydroxylase deficiency on cortisol?
Decreased
What is the effect of 21-hydroxylase deficiency on sex hormones?
Increased
What is the effect of 21-hydroxylase deficiency on blood pressure (BP)?
Low
What is the effect of 21-hydroxylase deficiency on potassium levels ([K+])?
High
What are the lab findings in 21-hydroxylase deficiency?
Increased renin activity & 17-hydroxyprogesterone
What is the presentation of 21-hydroxylase deficiency?
Presents in infancy (salt wasting) or childhood (precocious puberty); XX: virilization
What is the effect of 11-hydroxylase deficiency on mineralocorticoids?
Decreased aldosterone, increased 11-deoxycorticosterone
What is the effect of 11-hydroxylase deficiency on cortisol?
Decreased
What is the effect of 11-hydroxylase deficiency on sex hormones?
Increased
What is the effect of 11-hydroxylase deficiency on blood pressure (BP)?
Increased (due to increased 11-deoxycorticosterone)
What is the effect of 11-hydroxylase deficiency on potassium levels ([K+])?
High
What are the lab findings in 11-hydroxylase deficiency?
Increased renin activity
What is the presentation of 11-hydroxylase deficiency?
XX: virilization
What is the source of cortisol?
Adrenal zona fasciculata
What is cortisol bound to?
Corticosteroid-binding globulin
What are the functions of cortisol?
A BIG FIB: Appetite, BP, Insulin resistance, Gluconeogenesis, lipolysis & proteolysis, Fibroblast activity, Inflammatory & Immune response, Bone formation
How does cortisol increase blood pressure?
Upregulates alpha-1 receptors on arterioles, increasing sensitivity to NE & Epi
At high concentrations, which receptors can cortisol bind?
Mineralocorticoid (aldosterone) receptors
How does cortisol decrease inflammatory/immune responses?
Inhibits production of leukotrienes & prostaglandins, WBC adhesion, blocks histamine release, causes eosinopenia, lymphopenia, and blocks IL-2 production
What can exogenous corticosteroids cause reactivation of?
TB & candidiasis
What regulates cortisol secretion?
CRH stimulates ACTH release, leading to cortisol production in adrenal zona fasciculata
In what forms does Ca2+ exist?
Ionized/free (~45%), Bound to albumin (~40%), Bound to anions (~15%)
What is the effect of pH on Ca2+ levels?
Decreased pH decreases affinity of albumin to bind Ca2+, leading to hypocalcemia
What is the primary regulator of PTH?
Ionized/free Ca2+
What is the source of parathyroid hormone (PTH)?
Chief cells of parathyroid
What are the functions of PTH?
Bone resorption of Ca2+, kidney reabsorption of Ca2+ in DCT, reabsorption of PO43- in PCT, 1,25-(OH)2 D3 production in PCT
How does PTH affect 1,25-(OH)2 D3 production?
By stimulating kidney 1-alpha-hydroxylase in PCT
How does PTH affect serum Ca2+, serum PO43-, urine PO43- & urine cAMP?
Serum Ca2+: increased, serum PO43-: decreased, urine PO43-: increased, urine cAMP: increased
What is PTH known as?
Phosphate-Trashing Hormone
How does PTH trigger bone resorption?
By secreting RANK-L which stimulates osteoclasts
What is PTH-related peptide (PTHrP)?
Functions like PTH, commonly found in malignancies
How does Ca2+ regulate PTH?
Increased serum Ca2+ decreases PTH secretion
How does PO43- regulate PTH?
Increased serum PO43- increases PTH secretion
How does Mg2+ regulate PTH?
Increased serum Mg2+ decreases PTH secretion
What are common causes of decreased Mg2+?
Diarrhea, aminoglycosides, diuretics, alcohol abuse
What is the source of calcitonin?
Parafollicular cells (C cells) of thyroid
What is the function of calcitonin?
Decreases bone resorption of Ca2+
What regulates calcitonin secretion?
Increased serum Ca2+ increases calcitonin secretion
What are thyroid hormones?
Iodine-containing hormones that control body’s metabolic rate
What is the source of thyroid hormones?
Follicles of thyroid
What converts T4 to T3 in peripheral tissue?
5’-deiodinase
What inhibits the conversion of T4 to T3?
Glucocorticoids, beta-blockers, propylthiouracil (PTU)
What are the functions of thyroid peroxidase?
Oxidation, organification of iodide, coupling of MIT & DIT
What are inhibitors of thyroid peroxidase?
PTU and methimazole
What is the Wolff-Chaikoff effect?
Excess iodine temporarily decreases thyroid peroxidase activity and T3/T4 production
What are the functions of T3?
Brain maturation, Bone growth, Beta-adrenergic effects, Basal metabolic rate, Blood sugar, Breakdown of lipids
How does T3 increase basal metabolic rate?
Increases Na+/K+-ATPase activity, increasing O2 consumption, respiratory rate, body temperature
How are thyroid hormones regulated?
TRH stimulates TSH release, primarily regulated by free T3/T4
What increases thyroid-binding globulin (TBG) levels?
Pregnancy, OCP use
What decreases TBG levels?
Hepatic failure, steroids, nephrotic syndrome
What hormones use cAMP as a second messenger?
FLAT ChAMP: FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2-receptor), MSH, PTH
What hormones use cGMP as a second messenger?
BAD GraMPa: BNP, ANP, EDRF (NO)
What hormones use IP3 as a second messenger?
GOAT HAG: GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin
What hormones have intracellular receptors?
PET CAT on TV: Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4, Vitamin D
What hormones have a receptor tyrosine kinase?
Insulin, IGF-1, FGF, PDGF, EGF
What hormones utilize a nonreceptor tyrosine kinase?
PIGGLET: Prolactin, Immunomodulators, GH, G-CSF, Erythropoietin, Thrombopoietin
What increases the solubility of steroid hormones?
Steroid hormones are lipophilic and must circulate bound to specific binding globulins
What is the impact of increased SHBG in men?
Increased SHBG decreases free testosterone, leading to gynecomastia
What is the impact of decreased SHBG in women?
Decreased SHBG raises free testosterone, leading to hirsutism
What is the impact of OCPs/pregnancy on SHBG levels?
OCPs and pregnancy increase SHBG
What is the most common cause of Cushing syndrome?
Exogenous corticosteroids
What is responsible for the majority of endogenous cases of Cushing syndrome?
Cushing disease (ACTH-secreting pituitary adenoma)
What are the etiologies of Cushing syndrome?
Exogenous corticosteroids, adrenal adenoma, hyperplasia, or carcinoma, ACTH-secreting pituitary adenoma, paraneoplastic ACTH secretion
What are the clinical findings in Cushing syndrome?
HTN, weight gain, moon facies, abdominal striae, truncal obesity, buffalo hump, skin changes, hirsutism, osteoporosis, hyperglycemia, amenorrhea, immunosuppression
What are the screening tests for Cushing syndrome?
Free cortisol on 24-hr urinalysis, midnight salivary cortisol, no suppression with overnight low-dose dexamethasone test
What should be the next step if a patient presents with increased free cortisol on 24hr urinalysis, increased midnight salivary cortisol, no suppression with overnight low-dose dexamethasone & increased serum ACTH?
Measure serum ACTH
What is the next step if a patient presents with increased free cortisol on 24hr urinalysis, increased midnight salivary cortisol, no suppression with overnight low-dose dexamethasone & increased serum ACTH?
Distinguish between Cushing disease & ectopic ACTH secretion
How to interpret results of high-dose dexamethasone suppression test?
Determines etiology of ACTH-dependent Cushing syndrome: No suppression indicates ectopic ACTH secretion; Adequate suppression indicates Cushing disease
How to interpret results of CRH stimulation test?
Determines etiology of ACTH-dependent Cushing syndrome: Increased ACTH & cortisol indicates Cushing disease; No increase indicates ectopic ACTH secretion
What is adrenal insufficiency?
Inability of adrenal glands to generate enough glucocorticoids and/or mineralocorticoids for the body’s needs
What are the symptoms & treatment for adrenal insufficiency?
Symptoms: weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI disturbances, sugar &/or salt cravings. Treatment: glucocorticoid/mineralocorticoid replacement
How to diagnose adrenal insufficiency?
Measurement of serum electrolytes & morning/random serum cortisol, ACTH response to ACTH stimulation test, metyrapone stimulation test
What are cortisol & ACTH levels in primary adrenal insufficiency?
Decreased cortisol, increased ACTH
What are cortisol & ACTH levels in secondary/tertiary adrenal insufficiency due to pituitary/hypothalamic disease?
Decreased cortisol, decreased ACTH
What is the metyrapone stimulation test?
Metyrapone blocks last step of cortisol synthesis; normal response is decreased cortisol & compensatory increased ACTH & 11-deoxycortisol
What are the results of metyrapone stimulation test in primary adrenal insufficiency?
ACTH is increased but 11-deoxycortisol remains decreased after test
What are the results of metyrapone stimulation test in secondary/tertiary adrenal insufficiency?
Both ACTH & 11-deoxycortisol remain decreased after test
What is oxycortisol used for?
Used to diagnose adrenal insufficiency.
What are the results of the metyrapone stimulation test in primary adrenal insufficiency?
ACTH is increased, but 11-deoxycortisol remains low after the test.
What are the results of the metyrapone stimulation test in secondary/tertiary adrenal insufficiency?
Both ACTH and 11-deoxycortisol remain low after the test.
What is primary adrenal insufficiency?
Deficiency of aldosterone and cortisol production due to loss of gland function.
What are the symptoms of primary adrenal insufficiency?
> Hypotension (hyponatremic volume contraction)
Hyperkalemia
Metabolic acidosis
Skin/mucosal hyperpigmentation (due to MSH, a byproduct of ACTH production from POMC)
Associated with autoimmune polyglandular syndromes.
What is acute primary adrenal insufficiency?
> Sudden onset (e.g., due to massive hemorrhage)
May present with shock in acute adrenal crisis.
What is chronic primary adrenal insufficiency?
Addison disease due to adrenal atrophy or destruction by disease.
What is the most common cause of Addison disease in the Western world?
Autoimmune destruction.
What is the most common cause of Addison disease in the developing world?
Tuberculosis (TB).
What is Waterhouse-Friderichsen syndrome?
Acute primary adrenal insufficiency due to adrenal hemorrhage associated with septicemia (usually Neisseria meningitidis), DIC, and endotoxic shock.
What characterizes secondary adrenal insufficiency?
> Seen with decreased pituitary ACTH production.
No skin/mucosal hyperpigmentation.
No hyperkalemia (aldosterone synthesis preserved due to intact RAAS).
What characterizes tertiary adrenal insufficiency?
> Seen in patients with chronic exogenous steroid use, precipitated by abrupt withdrawal.
Aldosterone synthesis unaffected.
What are the clinical features of hyperaldosteronism?
> Increased secretion of aldosterone from the adrenal gland.
Clinical features include hypertension, hypokalemia or normal potassium levels, and metabolic alkalosis.
How does primary vs secondary hyperaldosteronism affect edema?
> Primary hyperaldosteronism does not directly cause edema due to aldosterone escape mechanism.
Certain secondary causes of hyperaldosteronism (e.g., heart failure) may impair aldosterone escape mechanism, worsening edema.
What is primary hyperaldosteronism associated with?
> Seen with adrenal adenoma (Conn’s syndrome) or bilateral adrenal hyperplasia.
Increased aldosterone, decreased renin.
Causes resistant hypertension.
What is secondary hyperaldosteronism associated with?
> Seen in patients with renovascular hypertension, juxtaglomerular cell tumors (renin-producing), and edema (e.g., cirrhosis, heart failure, nephrotic syndrome).
What are neuroendocrine tumors?
A heterogeneous group of neoplasms that begin in neuroendocrine cells, which have traits similar to nerve cells and hormone-producing cells.
What do neuroendocrine tumor cells contain and secrete?
> Contain amine precursor uptake decarboxylase (APUD).
Secrete different hormones (e.g., serotonin, histamine, calcitonin, neuron-specific enolase [NSE], chromogranin A).
Where do most neuroendocrine tumors arise?
Most tumors arise in the GI system, pancreas, and lungs.
What neuroendocrine tumors arise from the GI system?
> Carcinoid
Gastrinoma.
What neuroendocrine tumors arise from the pancreas?
> Insulinoma
Glucagonoma.
What neuroendocrine tumor arises from the lungs?
Small cell carcinoma.
What is the most common tumor of the adrenal medulla in children?
Neuroblastoma, usually occurring in kids under 4 years old.
Where does neuroblastoma originate and occur?
> Originates from neural crest cells.
Occurs anywhere along the sympathetic chain.
What is the presentation of neuroblastoma?
> Abdominal distension.
Firm, irregular mass that can cross midline (vs Wilms tumor: smooth/unilateral).
Less likely to develop hypertension than with pheochromocytoma (neuroblastoma is normotensive).
Can also present with opsoclonus-myoclonus syndrome (‘dancing eyes-dancing feet’).
What will you see in the urine of a neuroblastoma patient?
Increased HVA and VMA (homovanillic acid and vanillylmandelic acid, catecholamine metabolites).
What are the histological characteristics of neuroblastoma?
> Homer-Wright rosettes (characteristic of neuroblastoma and medulloblastoma).
Bombesin and NSE (neuron-specific enolase).
How is neuroblastoma classified and what oncogene is it associated with?
> Classified as an APUD tumor (amine precursor uptake decarboxylase, common to neuroendocrine cells).
Associated with overexpression of N-myc oncogene.
What is the most common tumor of the adrenal medulla in adults?
Pheochromocytoma.
What is pheochromocytoma derived from and associated with?
> Derived from chromaffin cells (arise from neural crest).
Associated with germline mutations (e.g., NF-1, VHL, RET [MEN 2A, 2B]).
What is the ‘rule of 10s’ for pheochromocytoma?
> 10% malignant.
10% bilateral.
10% extra-adrenal (e.g., bladder wall, organ of Zuckerkandl).
10% calcify.
10% in kids.
What is the organ of Zuckerkandl?
> Chromaffin body derived from neural crest.
Located at the bifurcation of the aorta or at the origin of the inferior mesenteric artery.
Can be a source of a paraganglioma (extra-adrenal pheochromocytoma).
What are the symptoms of pheochromocytoma?
> Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension.
May also secrete EPO, leading to polycythemia.
Symptoms occur in ‘spells’ (relapse and remit).
