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381 Cards in this Set

  • Front
  • Back
The posterior pituitary stores which hormones? What actually produces them?
Vasopressin and oxytocin secreted by neurons with bodies the supraoptic and paraventricular nuclei (and neurohypophyses in the hypothalamus).
Anatomically the hypothalamus forms the floor of the ___.
Third ventricle.
What bone does the hypothalamus sit in?
The sphenoid bone, within the sella turcica.
Rathke's pouch?
Evagination of ectoderm that ends up forming the anterior pituitary.
Superior middle and inferior hypophyseal arteries are branches of what, and what do they supply?
All off the internal carotid. Superior supplies the hypothalamus and portal vessels drain to the ant. pituitary. Middle supplies the stalk/infundibulum and inferior the posterior pituitary.
Which hypothalamic location is activated during hunger and what hormone activates the nucleus? What about satiety? Where does the final common pathway to regulate appetite begin at?
Hunger - ghrelin, lateral hypothalamus.
Satiety - leptin, ventromedial and dorsal hypothalamus.
Arcuate nucleus.
Craniopharyngiomas are tumors derived from what tissue?
Rathke's pouch (ectodermal tissue comprising the ant pituitary).
Lesions of the ventral medial nucleus of the hypothalamus result in what symptoms?
Obesity, excitability. Remember medial hypothalamus controls satiety so when it's defective...
Lesions of the preoptic area of the hypothalamus lead to what symptoms?
Adipsia (lack of thirst).
Lesions of what hypothalamic nuclei lead to diabetes insipidus?
Paraventricular nucleus, supraoptic nucleus, or the pituitary infundibulum (anything to disturb the pathway of neurons secreting AVP to the PP).
Secondary hypothalamic insufficiencies result in what characteristic hormonal increase?
Hyperprolactinemia usually due to a disruption in signaling from the hypothalamus to the pituitary (all other hormones are stimulated but prolactin secretion is inhibited by dopaminergic innervation). "Stalk effect".
Hypopituitism with hyperprolactinemia and diabetes insipidus is a hallmark sign of what?
A hypothalamic lesion.
Kallmann's syndrome patients present with which two main symptoms? Cause?
Hypogonadotropic hypogonadism and poor smell due to hypoplasia of olfactory lobes. X-linked KAL gene mutation causing abnormal migration of neurons.
What happens to growth hormone in the setting of anorexia nervosa? ADH?
GH is nl to high but IGF-1 is low. ADH is high.
Fergusson reflex?
Oxytocin-induced cervical dilation.
Oxytocin's physiologic functions?
Parturation (initiation and completion of labor with uterine contractions and vasoconstriction) and lactation (inducing milk secretion, not production as prolactin does).
What physiological effect does AVP have based on its action wrt V1 V2 and V3 receptors?
V1 - vasoconstriction.
V2 - inc production and exocytosis of aquaporin-2 channels to the luminal side of the collecting ducts.
V3 - enhanced ACTH release.
What are some common causes of nephrogenic diabetes insipidus?
Hypokalemia, hypercalcemia, patients on lithium or amphotericin B, and multiple myeloma pts (via hypercalcemia).
What is the classic method to diagnose the presence diabetes insipidus and its type?
Water deprivation test - deprive water then administer DDAVP to see if urine osm responds.
T/F: DDAVP response is 10-50% in patients with primary polydipsia.
False, it should be ~0 because AVP is already maximally active. Primary = not drinking water!
Pituitary tumors that overproduce growth hormone tend to also overproduce what hormone and why?
Prolactin bc somatotropes and lactotropes are descended from similar cell lines expressing Prop-1 and Pit-1.
What hormones share the same alpha subunits?
FSH, LH, and TSH. beta-HCG too.
What are three non-hormonal symptoms or a pituitary mass?
Visual field defects (superior temporal quadrantanopsia/ hemianopsia), disconjugate gaze, CSF rhinorrhea.
What genetic defect causes MEN-1, and what are the main tissues of origin?
Mutation in A(d) menin, 3 P's - pituitary adenomas, parathyroid hyperplasias, pancreatic neuroendocrine tumors (carcinoids).
What are the most common genetic defects to lead to pituitary adenomas?
Menin (MEN-1 syndrome - usu prolactinoma), Gs-alpha1 (McCune Albright syndrome - GH), and PKA type 1 reg subunit (Carney Complex - GH).
T/F: Men with hyperprolactinemia present with galactorrhea.
False, very rare for men, instead have dec libidio and impotence.
24-yr old female presents with hyperprolactinemia. Tests to form a DDx?
1. Pregnancy test! 2. Thyroid function tests. 3. Other hormones (IGF-1, LH, FSH, AM cortisol). 4. MRI w Gad enhancement.
What thyroid disfunction is associated with hyperprolactinemia?
Primary hypothyroidism (thyroid ain't producin' shit) bc feedback inc in TRH induces prolactin release instead.
"Hook effect"?
Prolactinoma presenting with abnormally low levels due to the assay being overwhelmed with too much prolactin.
What common condition contraindicates the use of Cabergoline or Pergolide to treat pituitary adenomas?
Pregnancy. Use bromocriptine instead.
Which visceral organs enlarge with GH excess?
Heart (LVH and valvular dz), thyroid, liver, kidneys, prostate.
What is the most popular measurement to confirm a diagnosis of acromegaly? What other serum measurement is better than serum GH?
Glucose tolerance test since most pts are insulin resistant and will not lower GH in response to a challenge. Elevated IGF-1 since it has a longer half-life than GH.
The glucose tolerance test predicts a GH response of what sort for normal patients?
Administering glucose should lower GH in most patients.
What is the only pituitary adenoma where surgery is not considered first-line? Treatment? Side effects?
Prolactinomas. First with dopamine agonists. Disinhibition just like in Parkinson's tx.
When in the day is cortisol secretion in the body lowest?
At night.
What's the plasma half-life of ACTH?
Less than 20 minutes.
Which corticosteroid is not detectable on a cortisol assay and what is the functionality of this?
Dexamethasone, a candidate for use in pts with adrenal insufficiency for whom you still want to monitor their endogenous production of cortisol.
Where does acanthosis commonly appear on the body and what is the most common cause?
Neck and axilla darkening, insulin resistance such as obesity, DM type 2, and polycystic ovary syndrome.
What is the primary culprit behind Cushing's associated hirsutism?
Accumulation of steroid biosynthesis mid-products (primarily DHEA) due to excess ACTH stimulation of steroid production.
Why does cortisol not normally affect the mineralocorticoid receptors of the kidney? How is this relevant to Cushing's disease? Manifestations?
The kidney has the 11B-hydroxy dehydrogenase type 2 enzyme to break down cortisol. This becomes overwhelmed in Cushing's leading to hypertension, hypokalemia, hypernatremia, metabolic alkalosis.
Cushing's syndrome and nephrolithiasis why???
Excess glucocorticoids increase calcium excretion in the kidneys.
What is Megace and what is it prescribed for? Adverse effect?
A progesterone receptor agonist to increase appetite in pts with cachexia. Cushing's syndrome since it also affects glucocorticoid receptors.
What are the two leading causes of ectopic ACTH production leading to Cushing's syndrome?
Small cell lung cancer and carcinoid syndrome
What is the first most important test to diagnose Cushing's syndrome? Confirm with what test?
A 24h urine free cortisol test. Dexamethasone suppression test.
Patients with Cushing's syndrome administered dexamethasone at night will have:
A higher than normal cortisol measurement in the morning due to lack of normal feedback inhibition.
What causes pseudo-Cushing's syndrome?
Obesity (positive DST although their 24hr cortisol is normal) and alcoholism (11BHSD enzyme is depressed so they don't metabolize cortisol properly).
What is a test to differentiate between pseudo-Cushing's and Cushing's syndromes?
The dexamethasone-suppressed CRH stimulation test.
What are two ways to delineate a pituitary source of Cushing's disease versus ectopic?
CRH stimulation test (pituitary tumors respond, ectopic ones do not) and high dose dexamethasone test (pituitary tumors are suppressed where ectopic tumors aren't).
What drugs can be used to medically treat Cushing's by lowering cortisol levels?
Ketoconazole, metyrapone, aminoglutethamide, and mitotane (which causes full adrenalectomy and atrophy).
Nelson's disease?
Removal of adrenal tumors with a bit of tumor remaining which then hyperplases due to lack of feedback inhibition and becomes very difficult to treat, inducing Cushing's and hyperpigmentation.
Patients with acute severe pituitary apoplexy will have what associated symptoms?
Severe headache and visual disturbances (dysconjugate gaze due to effects on CN3, 4, or 6), N/V, blood in CSF.
What are the first hormones to be lost in hypopituitarism due to apoplexy?
1. GH (somatotropes), 2. ACTH (corticotropes), 3 FSH/LH (gonadotropes), 4. TSH (thyrotropes).
The gold standard for examining pituitary hormone secretion is the:
Insulin tolerance test.
What are the contraindications to performing an insulin tolerance test to check pituitary function?
Any patient with a history of seizures or cardiovascular disease.
Patients with hypopituitarism will not be able to raise what hormones in response to insulin tolerance?
Growth hormone and cortisol/ACTH (glucagon is not produced by the pituitary).
What sized pituitary lesions are more likely to lead to endocrinopathy symptoms?
Microadenomas (<10mm) primarily, but also macroadenomas inducing hyperprolactinemia via the stalk effect.
What visual defect is produced by a pituitary adenoma impinging upon the optic chiasm from below?
Initially a bitemporal (superior) quadrantanopsia but eventually a bitemporal hemianopsia (lateral fields gone).
What is the most common endocrinopathy resulting from a pituitary adenoma?
Hyperprolactinemia.
T/F: Acromegaly due to GH tumors are benign.
False. Pts can die of diabetes or heart failure.
What is the second most common tumor in the pituitary stalk region behind the pituitary adenoma? Symptomatology?
Sellar region meningioma, with neurologic defects (bitemporal hemianopsia with some CN findings) and potential stalk effects. NO endocrinopathy.
Over half the tumors that occur in the pineal gland are what? What is the most common type of this tumor in the pineal gland? Cellular composition?
Germ cell tumors. Germinoma with biphasic distribution of large cells w prominent nucleoli and then lymphocytes.
What are the constellation of neurologic findings for a pineal gland tumor (pinealoma)?
Vertical gaze defects, pupillary control (accomodation), convergence (CN3/4) (internuclear ophthalmoplegia), and hydrocephalus.
What is the most common cause of hypothyroidism?
Hashimoto's thyroiditis.
Thinning lateral third of eyebrows?
Hypothyroidism.
Slow relaxation of deep tendon reflexes?
Hypothyroidism.
What is the most common cause of TSH suppression?
Iatrogenic administration of excess thyroxine.
What is the risk for sudden increases in administration of thyroid hormone for elderly and cardiac risk pts?
Sudden exacerbation of angina most commonly. Start low and go slow!
What are two conditions mandating higher than expected thyroid hormone administration?
Pregnant women and patients with malabsorption due to celiac sprue or other causes (drug use).
In mild thyroid failure what are the measurements for T3, T4, and TSH?
T3 and T4 are normal but TSH is high bc it is more sensitive to fluctuations than T3 and T4.
What are the risks associated with suppressed TSH due to excess T4 administration esp in the elderly?
Dec bone density and inc risk heart dz like A-fib from tachycardia.
What pharmacotherapies for hyperthyroidism are available, which one is associated with agranulocytosis, cholestasis, and hepatitis, and which one is indicated in pregnant patients?
Thionamides: Methimazole - cholestasis; propylthiouracil - agranulocytosis and hepatitis, pregnancy (crosses the placenta less). Also lithium.
What step in thyroid hormone synthesis do thionamides block?
Iodination, organification and coupling. PTU can also block conversion of T4 to T3.
What step in thyroid hormone synthesis do iodide and lithium block?
Endocytosis of colloid vesicles.
Butterfly scan on RAIU?
Graves' disease (uniform hyperthyroidism).
Hot nodule on RAIU?
Toxic nodular goiter with suppression of the rest of the thyroid gland.
Classic presentation: 36yo female 6wks after pregnancy presents with fatigue. She has a positive hx for type 1 diabetes.
Do a workup for postpartum thyroiditis, check T4 and TSH levels.
What are the most common causes of de Quervain's thyroiditis? Treatment?
Postviral URI: Coxsackie, adenovirus, measles, mumps. Self-limited dz, treat symptoms (high dose NSAID, if hyperthyroid then B-blockers).
Patients taking what common heart disease drug are at risk for developing hypothyroidism?
Amiodarone bc it contains iodine.
What is the most common form of thyroid cancer?
Papillary carcinoma.
What cause of congenital bilateral adrenal hyperplasia presents with hypertension, hypokalemia, and males that are phenotypically female w/o maturation and cannot respond to stress?
17alpha-hydroxylase deficiency.
What cause of congenital bilateral adrenal hyperplasia causes masculinization, hypotension, hyperkalemia, inc plasma renin, volume depletion, salt wasting, and hypovolemic shock in the newborn?
21alpha-hydroxylase deficiency.
What cause of congenital bilateral adrenal hyperplasia causes masculinization, hypertension, and hypokalemia?
11B-hydroxylase deficiency.
Acromegaly has what associated effects from tumor compression of the hypothalamus (excluding effects on the pituitary gland due to loss of hypothalamic stimulation)?
Headache, appetite-related compulsions.
First line treatment for acromegaly?
Transsphenoidal resection of pituitary tumor.
Pharmacologic therapies for acromegaly?
Short and long acting somatostatin analogs: octreotide TID, sandostatin LAR, lanreatide. GH receptor blockers: pegvisomant. Ergot derivatives/dopamine agonists: bromocriptine, cabergoline.
Pegvisomant?
GH receptor antagonist used in treatment of acromegaly.
Octreotide (Sandostatin) and lanreotide (Somatuline)?
Short and long acting somatostatin analogs to treat acromegaly.
What are all the diseases that present with hyperprolactinemia?
1. Pregnancy. 2. Primary pituitary adenoma (prolactinoma most common). 3. Acromegaly (GH tumors co-produce prolactin due to similar cell lineage). 4. Primary hypothyroidism (pituitary pumps out extra TRH stimulating prolactin synthesis). 5. Any stalk effect tumor. 6. Dopamine antagonizing drug use (antipsychotics, metaclopramide). 7. Excess chest wall stimulation particularly postpartum.
Crow's feet around eyes?
Growth hormone deficiency.
In what clinical setting would T3 levels be useful in?
Some hyperthyroidisms where T4 is normal/borderline but T3 is high. Useless in hypothyroidism.
Where does thyroid tissue originate from embryologically?
Endodermal tissue of the second branchial arch from the foramen cecum at the base of the tongue, traveling caudally through the thyroglossal duct to reach its anatomic location. Ultimobranchial body of the 4th arch gives rise to parafollicular/C-cells in the thyroid.
Recurrent acute thyroiditis?
Thyroglossal duct cysts or pyriform sinus fistulae.
Thyroid surgeries run the risk of injuring what structure which runs posterior to the thyroid?
Recurrent laryngeal nerves.
Thyroid hormones are built off a backbone of what amino acid?
Tyrosine (recall: MIT = monoiodotyrosine, DIT = diiodotyrosine).
Does T3 or T4 serve as the primary feedback molecule to the pituitary and hypothalamus?
T3, just like any other site in the body, is the hormone with regulatory activity.
Procedure of choice for imaging the thyroid gland?
Ultrasonography.
What does T4 bind to in serum?
70% thyroid-binding globulin (TBG), 15% albumin, 10% transthyretin.
Albumin and TBP levels in the context of pregnancy?
Increase since pregnancy is like a hypercoagulable state inducing umbrella-effect inc in liver synthesis. Inc TBP = inc total circulating T4 reserves = slightly hyperthyroid.
In the T3 resin test, high resin uptake indicates what?
Low TBP in serum and effective hypothyroid.
Which antibodies to the thyrotropin receptor are activating and inhibiting?
TSI - activating (Graves' disease).
TBII - inhibiting,
What is a disease in which serum thyroglobulin (Tg) is decreased?
None, unless the thyroid has been resected at which point you want it to be zero (presence indicates remaining thyroid tissue).
What two hyperthyroid causes present with a low RAIU image?
Hashimoto's subacute thyroiditis and hormone ingestion.
Hurthle cell adenoma?
Benign thyroid nodule assoc with Hashimoto's thyroiditis or follicular thyroid cancer.
Between cystic and solid nodules which have higher malignancy potential?
Solid nodules although cystic ones >4cm also have high risk.
Microcalcifications in the thyroid gland are indications for what?
Tissue ischemia/necrosis indicative of high risk of malignancy.
Hair loss, fatigue, depression?
Hypothyroidism.
Hashimoto's thyroiditis is caused by what biochemical mechanism?
Antibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg) and sometimes TSH receptors, inducing thyroid inflammation and destruction.
Cardiac complications from Hashimoto's thyroiditis and why?
Pericardial effusions due to accumulation of thyroglobulins.
Classic presentation: 22yo female presents with fatigue, severe neck pain and tenderness radiating to the jaw and ear, and visible inflammation of the neck (but not erythema). Positive history for URI 1wk prior.
DeQuervain's (subacute) thyroiditis.
What are the most common causes of acute thyroiditis?
Staph aureus, strep pyogenes.
Beef jerky under silk scarf?
Reidel's thyroiditis incl sheety (wok) fibrosis of the thyroid. Painless, woody.
The interaction of ACTH with its receptor drives this first step of steroidogenesis, mediated by this enzyme.
Transport of cholesterol into the mitochondrial matrix. Steroidogenesis acute regulatory protein.
What enzyme is exclusive to the zona glomerulosa of the adrenal cortex?
Aldosterone synthase.
What enzyme is exclusive to the zona fasciculata and reticularis of the adrenal cortex?
17alpha-hydroxylase.
What enzyme is exclusive to the zona reticularis of the adrenal cortex?
17,20 lyase.
Cholesterol is first converted to what in the biochemical process of steroidogenesis?
Pregnenolone.
What main signals activate aldosterone synthesis? Inhibit it?
ACTH, high K, and Angiotensin II+III. ANP, heparin, dopamine inhibit.
What is the most important regulator in adrenal androgen synthesis?
ACTH.
What lab values delineate primary from secondary and tertiary hypoaldosteronism?
Primary has elevated ACTH where secondary has decreased ACTH. Tertiary has decreased CRH. Primary has hypoaldosteronism where the others do not.
What is the triad for autoimmune polyendocrine syndrome type I (APS I)?
Addison's dz, primary hypoparathyroidism, mucocutaneous candidiasis.
What causes autoimmune polyendocrine syndrome type I (APS I)?
Genetic mutation on the AIRE (autoimmune regulator) gene on Chr. 21.
What is the triad for autoimmune polyendocrine syndrome type II (APS II)? Associated with what HLA type?
Addison's dz, type I diabetes mellitus, autoimmune hypothyroidism. DR3, DR4.
What is the most common reason for primary adrenal insufficiency in the US? Internationally?
Autoimmune etiologies (APS/PGA types 1/2). Tuberculosis.
How do AIDS patients present with Addison's disease?
Myriad possibilities, from TB to MAC to CMV adrenalitis, even KS metastasis to the glands, not seen often post-HAART.
What cancers more often metastasize to the adrenal glands than others?
Lung and breast cancer mainly. Also gastric, melanoma, and lymphoma.
Classic presentation: pregnant woman with difficult delivery (significant blood loss) presents 6wks post-partum with a hypotensive crisis.
Sheehan's syndrome (pituitary infarction-induced secondary adrenal insufficiency).
What is the most common Ab produced in autoimmune causes of primary adrenal insufficiency?
Anti-21-hydroxylase Ab's in >60%.
If thyroid is tender to the touch or painful, what etiology is most likely?
Acute (bacterial, fungal infxn) or subacute (post-viral URI) thyroiditis.
What is the triad of Hand-Schuller-Christian's disease? Associated with what cause? What effect on the adrenal glands?
Exophthalmos, lytic bone lesions, diabetes insipidus. Langerhans cell histiocytosis. Tertiary adrenal insufficiency.
Classic presentation: 45-yr old male presents with fever, postural hypotension, shock, weakness, muscle/joint/abd pain which started 1d ago. Diagnosis? Most common causes?
Acute adrenal insufficiency. If pt had chronic primary adrenal insufficiency, causes could be acute infection or stress. If not, then anticoagulant therapy or acute meningococcus or Pseudomonas infxn with bilateral adrenal infarction/hemorrhage.
Which symptoms of chronic (primary) adrenal insufficiency are more specific for the disease and lead you to place it on your differential? Lab tests?
N/V assoc with orthostatic hypotension, and hyperpigmentation (vitiligo in 5%). Absolute eosinophilia.
What symptoms are more and less common in patients with tertiary or secondary adrenal insufficiency versus primary?
Primary - hyperpigmentation, hyperkalemia, hyponatremia, volume contraction.
Secondary/tertiary - hypoglycemia.
The Long ACTH test would yield a definitive diagnosis of what disease if what finding presents?
Addison's disease if no increase in serum cortisol or urine 17 OHCS after 48hr of ACTH therapy (250ug/d).
A CRH stimulation test would demonstrate excess elevation in ACTH for what types of adrenal insufficiency?
Primary and tertiary, but not secondary.
How might type 2 diabetes cause secondary selective hypoaldosteronism?
Interstitial nephropathy - injury to macula densa and JG cells preventing proper renin secretion.
Neuropathy - autonomic degeneration leading to inability to induce renin secretion by B1 stimulation.
What drugs can cause secondary selective hypoaldosteronism?
NSAIDs, Beta blockers, ACE-I's, ARB's, potassium sparing diuretics, cyclosporin.
Unexplained hyperkalemia in a patient over 60yo? Main suspicion? Less likely cause?
Suspect selective secondary hypoaldosteronism. Acquired primary is possible if pt was on heparin.
Plummer syndrome?
Toxic nodule in multinodular goiter inducing hyperthyroidism.
What HLA types are associated with Hashimoto's thyroiditis? Graves' disease?
HLA-DR5. HLA-88 and HLA-DR3.
Granulomatous inflammation of the thyroid gland?
Subacute/de Quervain's thyroiditis.
What differentiates the fibrosis of Hashimoto's and Reidel's thyroiditis?
Hashimoto's fibrosis remains within the capsule where Reidel's is invasive to adjacent tissue.
What differentiates Graves' disease and papillary carcinoma histologically?
Both involve hypertrophy and hyperplasia of follicular epithelial cells with papillary budding into the colloid, but Graves does not include vascular cores within the buds.
Histologic features of this disease include colloid lakes, alternating with hyperplastic follicles, hemorrhage, and hemosiderin deposition, fibrosis, cysts, and calcification.
Multinodular goiter.
Thyroid follicular carcinomas are separated from adenomas by what?
Invasion into adjacent tissue.
What are popular sites of metastasis for follicular and papillary carcinomas of the thyroid?
Papillary - lymphatic spread, also to the lungs.
Follicular - bone mets.
Which thyroid cancer characteristically shows clear nuclei with much of chromatin marginated to edge of nuclear envelope?
Papillary carcinoma.
Anaplastic carcinomas arise from what other thyroid disease?
Goiters oftentimes due to previously indolent papillary carcinoma which then de-differentiates to anaplastic.
What embryologic tissue do the parathyroid glands arise from?
3rd and 4th pharyngeal pouches.
What are the most common causes of hypercalcemia?
Primary hyperparathyroidism and malignancy about equally.
What are the causes of primary hyperparathyroidism?
Parathyroid adenoma (75%), parathyroid hyperplasia (15%), parathyroid carcinoma (<5%).
Secondary hyperparathyroidism almost always occurs in pts under the context of what superceding diseases? Phosphate and calcium levels in these pts? Why?
1. Chronic renal failure. Low calcium bc of insufficient vit D production, high phosphate bc kidney cannot excrete phosphorus. 2. Intestinal malabsorption->vit D deficiency, low Ca AND low PO4 due to malabsorption of everything.
Congenital absence of parathyroid glands?
DiGeorge syndrome.
What happens physiologically to serum calcium in states of metabolic acidosis?
Calcium is displaced from albumin leading to higher readings of ionized free calcium (hypercalcemia).
Where is the CaSR expressed in the body?
Parathyroid glands, kidney, bone marrow, osteoclasts, breast, C-cells of thyroid, G-cells of the stomach.
Acute hypomagnesemia can have what effects upon the parathyroid glands?
Impair secretion of PTH.
Calcitriol has what effect upon the intestines, bone, and kidney?
Intestines- inc absorption of Ca and PO4.
Bone- potentiates the PTH-induced resorption of bone leading to inc serum Ca and PO4.
Kidney- inc reabsorption of both Ca and PO4.
Vitamin D 25-hydroxylation occurs where in the body?
Liver. Kidney handles the activating step via 1-alpha hydroxylase.
Rickets disease?
Dietary lack of vitamin D or calcium in children. The adult form is osteomalacia.
What stimuli induce calcitonin secretion?
High serum calcium or gastrin (protecting against calcium overload after a meal).
T/F: Medullary thyroid cancer patients present initially with hypocalcemia.
False, hypocalcemia does not occur with these tumors (excess calcitonin).
What drugs risk causing hypercalcemia?
Thiazide diuretics, theophylline, and lithium (which can even induce parathyroid hyperplasia leading to hypercalcemia).
What infections can cause hypercalcemia and how?
TB, Leptospirosis, Coccidiodes, Histoplasmosis, by endogenously producing activated vit D (calcitriol).
Which MEN syndromes are associated with primary hyperparathyroidism?
MEN-I and IIa.
Which MEN syndromes are associated with pheochromocytoma?
MEN IIa and IIb (III). Also neurofibromatosis.
Which MEN syndromes are associated with medullary thyroid carcinoma?
MEN-IIa and IIb (III).
Hemosiderin deposition in nodules of bones? Cause?
"Brown tumors" of osteitis fibrosa cystica due to primary or secondary hyperparathyroidism.
How do primary and tertiary hyperparathyroidism present similarly? Differently?
They both induce high serum Ca from high PTH, but tertiary is preceded by a secondary cause of chronic renal failure.
What tumors are commonly associated with the paraneoplastic syndrome humoral hypercalcemia of malignancy? Electrolyte findings?
Squamous cell carcinomas (lung, esophagus, H/N, skin, cervix), renal, bladder, breast, ovarian CA, lymphoma. (PTHrP - high Ca low PO4 low PTH)
What lab value differentiates PTHrP-derived neoplastic syndromes from lytic metastases to bone?
Both have inc serum Ca, dec PTH, but PTHrP mimics hyperPTH with low PO4 where lytic mets have normal levels. Get a PTHrP reading!
What might cause endogenous activated calcitriol production and what would the lab values look like?
Lymphomas. High Ca, high PO4, low PTH, nl 25-vit D, high 1,25-vit D.
What disease is associated with a heterozygous mutation of CaSR? Homozygous?
Familial hypocalciuric hypercalcemia. Severe Neonatal Hyperparathyroidism.
What is the effect of bisphosphonates? Clinical use? What other drug can have a similar effect and why are bisphosphonates preferred?
Decrease bone resorption in patients with hyperparathyroidism or hypercalcemia. Calcitonin, bad SE like anaphylaxis and shorter duration of effect.
What is the most common cause of hypocalcemia?
Vitamin D deficiency.
Cupping and fraying of distal radius?
Rickets disease in children with vit D deficiency. Also look for genu varum (bow-leggedness).
Rachitic rosary pattern?
Rickets disease in children with vit D deficiency. Demineralized osteiod in the chest wall.
Osteomalacia will present with what lab values?
Low serum Ca*PO4 product. High alkaline phosphatase.
Looser's zones?
Demineralized osteoid in osteomalacia, "pseudofractures", aka Milkman's fractures.
What are the clinical features of hypocalcemia?
Perioral, tongue, extremity paresthesias, facial spasms, myalgias, cramps, tetany, carpopedal spasm, Chvostek's, Trousseau's signs, arrhythmias (prolonged QT).
Chvostek's sign?
Contraction of facial muscles when tapping just below the zygomatic arch at the facial nerve area, positive in hypocalcemia.
Trousseau's sign?
Flexion of thumb and hyperextension of other fingers when taking someone's BP (10mmHg over systolic) positive for hypocalcemia.
What are the most common causes of goiter?
Chronic iodine deficiency in endemic countries, Hashimoto's thyroiditis and Graves' disease in sporadic countries.
Chronic lithium use risks what endocrine diseases?
Nephrogenic DI. Hypothyroidism with goiter due to prevention of hormone release from the thyroid. Parathyroid hyperplasia leading to hyperparathyroidism and hypercalcemia.
What differentiates overt from subclinical hyperthyroidism?
In subclinical T3/T4 levels normal but TSH low (TSH is a much more sensitive marker) whereas overt involves inc T3/T4.
What are the treatment options for patients with a non-toxic goiter presenting with compressive symptoms?
RAI ablation and surgery.
What is the extreme form of acute onset hyperthyroidism with a 20% mortality, and how does it usu kill?
Thyroid storm, cardiac arrhythmias like A-fib, V-tach, sinus tach.
An elderly patient with no symptoms besides a sinus tachycardia or atrial fibrillation +/- some weight loss would lead you to suspect what endocrine disease on your differential?
Apathetic hyperthyroidism (no tremor, diaphoresis, heat-intolerance, or other classic hyperthyroid sx).
Treatment of hypothyroidism with Levothyroxine prevents what complications of hypothyroidism?
All of them, but the most severe are bone loss, cardiomyopathy, myxedema.
What is the extreme form of hypothyroidism with a high mortality rate and how does it kill?
Myxedema coma, kills by hypothermia, hypoglycemia, hypotension, hyponatremia, bradycardia, and hypoventilation. Usu precipitated by infection, stress, MI, CVA, drugs, etc.
Which thyroid cancer is associated with activation of receptor tyrosine kinases (RET/PTC, TRK, MET)?
Papillary thyroid cancer. Perhaps medullary thyroid cancer also.
How do high TSH levels induce irregular menstrual cycles?
They dysregulate the GnRH/LH FSH/androgen axis and also induce excess prolactin secretion (galactorrhea).
What is the best way to rule out a thyroglossal duct cyst if a patient presents with a mass in the throat?
Ask the patient to stick their tongue out. A thyroglossal duct cyst would move substantially.
What is the differential for masses in the neck that would move with deglutition (swallowing)? Which is the most common?
Thyroid and parathyroid nodules, with thyroid being far more common. Lymphadenopathy, developmental cysts, and aneurysms can be ruled out in this manner.
What does taking an oral contraceptive pill do to thyroid hormone levels?
It induces an inc synthesis of products of the liver including TBG. fT4 dec transiently but then returns to normal with feedback inc TSH secretion, which returns to nl but eventually induces a steady-state inc bound T4 conc with nl fT4 conc. Pt is "euthyroid" with inc total T4 levels accounted for by in TBG concs.
Serum marker denoted increased bone formation?
Alkaline phosphatase (bone specific).
Markers of increased bone resorption found in the urine?
UNTx (Urine N-telopeptide) and CTx (C-telopeptide).
What signals influence osteoblasts to express RANKL to activate osteoclasts? What blocks this RANKL binding?
PTH, PTHrP, or calcitriol. OPG (osteoprotegerin) and Denosumab, the synthetic mAb analog to OPG.
What signals do the old bone matrix and osteoclast send to activate osteoblasts following bone resorption?
Matrix - TGF-beta.
Osteoclasts - IGF-1 and FGF-2.
In estrogen deficiency what biochemical signals are responsible for the subsequent loss of bone density and how do they work?
OPG decrease releasing osteoclast RANK inhibition. Also IL-1, IL-6, TNF-alpha go up activating osteoblast RANKL signaling, and TGF-beta goes down releasing osteoclast suppression/failing to activate osteoblasts. RunX2, another osteoblast activator, also goes down.
What are the most common sites of fracture related to osteoporosis?
Spine, distal radius, proximal femur (hip).
RunX2?
An osteoblast maturation factor that decreases in conditions of androgen insufficiency.
FRAX algorithm?
Fracture risk algorithm used to determine whether or not to treat osteopenic/porotic patients. Treat if 10-yr risk of hip fracture or any fracture are higher than 3% or 20% respectively.
What is the key diagnostic test for osteoporosis if no fracture has occurred yet? Other values?
Bone mineral density test. Serum Ca, P, alk phos, LFT, Cr, CBC, serum PTH, 25,OH vit-D. UNTx and Cx not useful in diagnosis but may clue into pathogenesis origins and monitoring progression.
What is the difference between the T score and Z score in the bone mineral density test?
T scores compare the pt's BMD to that of the peak BMD of a young adult of the same race and gender. Z scores compare the pt's BMD to the average BMD of that pt's age, race, and gender.
T/F: Smoking and alcohol use can promote bone density loss.
True.
Calcium ingestion in the treatment of osteopenia/osteoporosis should be administered with what else?
Vitamin D.
What are the pharmacologic options for treatment of osteoporosis?
Anti-resorptives (bisphosphonates (____dronate) 1st line, SERMs (Raloxifene), HRT). Anabolic agent (Teriparatide, a PTH analog), calcitonin, Denosumab (mAB to RANKL mimicking OPG).
How do bisphosphonates act to stop bone resorption?
They block GTPase binding and thus flatten out the ruffled border within Howship's lacunae.
How is Paget's disease diagnosed radiographically?
Radiographic findings of long bone expansion/enlargement, cortical thickening, coarsening of trabecular markings, "cotton wool" skull. Inc uptake of 99Tc in a bone scan in pagetic bones. Femur has bowing deformity.
How is Paget's disease diagnosed by lab values?
Alk phos inc, UNTx and SNTx inc, CTx inc.
What is the treatment for Paget's?
Bisphosphonates.
"Cotton wool" skull radiograph?
Osteoporosis circumscripta of Paget's disease.
Albers-Schonberg disease?
Osteopetrosis (marble bone dz).
What lab value is increased in osteopetrosis?
TRAP (osteoclast-derived tartrate-resistant acid phosphatase).
How do peptic ulcers come about under the setting of hypercalcemia?
Hypercalcemia stimulates gastrin secretion, and excess gastrin induces excess HCl in the stomach leaking to the duodenum->peptic ulcers.
Band keratopathy occurs under what setting?
Hypercalcemia, horizontal midline deposits to either side of the iris bc that is the least well oxygenated area.
What infectious etiologies induce hypercalcemia?
TB/granulomatous infections, sarcoidosis, lymphoma. Macrophages in these dz'es produce 1,25-hydroxylase.
What are the three main ways neoplasms lead to hypercalcemia?
1. Produce PTHrP, produced by squamous cell carcinoma of lung and solid tumors like breast cancer.
2. Bone metastasis - lytic lesions with Ca release.
3. Osteoclast-activating factors- tumors produce cytokines like IL-1, TNF-alpha; multiple myeloma commonly does this.
"Milk alkali syndrome"/Burnett's syndrome?
Hypercalcemia with metabolic alkalosis and volume contraction usu due to excess calcium supplementation w vit D or excess calcium carbonate antacid ingestion, also seen with excess thiazide use.
How are patients with Familial Hypercalcemic Hypocalciuria diagnosed?
Pts usu asx, PTH mild inc, but the giveaway is urine Ca, FECa <1%.
What diseases present with elevated PTH and elevated serum Ca?
Parathyroid hyperplasia, parathyroid adenomas and carcinomas, and FHH (milder course).
How are parathyroid hyperplasias and adenomas differentiated?
FNA histology or a Sestamibi scan. All four light up if hyperplasia, only one lights up if adenoma.
What endocrine syndromes can present with hypercalcemia?
Hyperparathyroidism of any cause (hyperplasia, adenoma, FHH), Addison's disease, hyperthyroidism inducing bone resorption, MEN I and MEN IIa.
T/F: Hyperthyroidism causes more lower extremity muscle weakness than upper.
False. Upper more.
How can a partial gastrectomy in an older woman precipitate osteoporosis and anemia?
Malabsorption of calcium and iron.
What are the cutoffs for diagnosis of diabetes mellitus in the Fasting Plasma Glucose and Oral Glucose Tolerance Tests? Why are these values used?
FPG - >126mg/dL
OGTT - >200mg/dL
Beyond these values the risk of microvascular complication jumps.
What does a patient with a FPG of 100-126 mg/dL or a OGTT of 140-200 mg/dL have?
FPG - Impaired fasting glucose.
OGTT - Impaired glucose tolerance.
Diabetic ketoacidosis is more classically associated with which DM type?
DM type 1.
Patients with which type of diabetes are sensitive to insulin?
Type 1 DM.
Patients with which type of diabetes will respond to oral hypoglycemic agents?
Type 2 DM.
Type 1 diabetes involves destruction of B cells associated with a dense infiltration of the islets by?
Lymphocytes (T cells do the attacking).
Type 1 diabetes is assoc with genetic factors on which HLA loci on which chromosome?
Chr. 6, HLA-DQA, HLA-DQB, HLA-DRB.
Type 1 diabetes is associated with islet cell autoantibodies against what?
Tyrosine phosphatase (IA-2), glutamic acid decarboxylase (GAD-65, 67), ZnT8, and insulin itself.
"Honeymoon period"?
The period in pts with juvenile type 1 DM when after the initial presentation the need for insulin declines or disappears. Ends within 5-10yrs.
T/F: MODY (maturity onset diabetes of youth) genes are autosomal recessive.
False, auto dom.
A contribution to insulin resistance may be made by adipocytes secreting what?
TNF-alpha leading insulin resistance in muscle and liver. "Resistin", a hormone secreted into circulation reducing insulin action. Even FFA mediate some resistance.
What cluster of metabolic abnormalities (aka the "Metabolic Syndrome") is associated impaired glucose tolerance?
Hypertension, hyperglycemia, hypertriglyceridemia, HDL < 50, abdominal obesity (waist circumference).
Conn's syndrome?
Primary hyperaldosteronism (low renin, hypertension, hypokalemia, metabolic alkalosis) due to an adrenal adenoma.
Diabetes is a chronic illness characterized by (definition)?
1. Hyperglycemia
2. Abnormal carbohydrate, lipid, and protein metabolism.
3. Propensity for renal, eye, neurologic complications, and premature occlusive vascular disease.
What are some endocrinopathies associated with diabetes mellitus?
Cushing's syndrome, Addison's dz, acromegaly, PCOS.
Pts with Turner's syndrome (one X only) or Klinefelter's syndrome (extra X chr) are predisposed to getting what endocrine disease?
DM type 2.
Rabson-Mendenhall syndrome?
Extremely rare genetic defect in the insulin receptor leading to severe type 2 DM with insulin levels in the thousands and acanthosis nigricans.
Gestational diabetes usually presents at what gestational period?
2nd or 3rd trimester because that is when the majority of fetal growth is taking place.
What infectious agent is assoc with type 1 diabetes?
Coxsackie B infection.
What is by far the most common cause of hypoglycemia?
Iatrogenic - insulin overdose.
Among the symptoms of hypoglycemia, which class has the lower threshold (presents itself first) and which class may disappear over continual hypoglycemic states?
Neurogenic symptoms for both - occur at blood glucose 60-65 where neuroglycopenic are lower, and may depart due to destruction of autonomic nerves.
Immediate infusion of insulin into a physiologically normal body will induce secretion of counter-regulatory hormones in what order?
W/in mins: Epi (adrenal) and nore (auton nerve endings). Later: glucagon and cortisol (adrenal). Finally: GH (pit).
Diabetic ketoacidosis classically occurs in patients with what balance of hormones?
High Glucagon:Insulin ratio. Also high cortisol, catecholamines, GH.
Insulin deficiency causes what in adipose tissue? Muscle tissue?
Adipose - lipolysis and release of FFA + glycerol.
Muscle - inhibited AA uptake and protein synthesis; promoted proteolysis and lactic acid generation.
What signals tells the liver to oxidize FFA's to ketones rather than reesterification into VLDLs?
Mimics the fasting state - requires high serum FFA, high glucagon, low malonyl-CoA (recall that the carnitine shuttle turns on in this setting, FFA-CoA enters the mito where B-oxidation and ketogenesis occurs).
What two main processes lead to hyperglycemia in the DKA patient?
Increase hepatic gluconeogenesis and decreased peripheral use of glucose.
Above what threshold for serum glucose will the kidneys' capacity for tubular reabsorption be overcome?
180-200mg/dL.
Between Na and K depletion that occur in DKA, which one is more significant and why?
K depletion because on top of hyperosmolar diuresis and isotonic fluid loss induced by hyperglycemia, the metabolic acidosis also forces K out of cells, being displaced by H+ ions. Finally, volume depletion and hypotension activate RAAS which retains Na but further wastes K.
What happens to phosphate balance in the setting of DKA?
PO4 is wasted due to intracellular organic polyphosphate breakdown, ECF shift, inc serum PO4, and electrolyte dysregulation which reduces PO4 tubular reabsorption.
"Fruity breath"?
DKA.
Kussmaul breathing?
DKA. Initially short rapid breaths which become more drawn out (still rapid) and deeper over time.
What are common precipitants of diabetic ketoacidosis?
Alcohol, drugs, infection, MI/stroke, trauma, pregnancy, cessation of insulin.
What kind of Na serum conc do DKA patients usually present with, and how do you correct this to unmask the true etiology (which is)?
Low Na which is misleading due to hyperglycemia which may be masking dehydration (high Na). Use the eqn to guess the expected Na if there were no hyperglycemia: Na + 1.6*(Measured glucose - 100)/100.
What kind of K serum conc do DKA pts usu present with? Why?
Elevated although they are K-depleted, due to shift of K extracellular by displacement from H+ ions and insulinopenia.
What are the two most important things to administer a patient with DKA?
IV saline and insulin drip simultaneously.
For elderly patients with blood sugars 1200-2800mg/dL suspect what?
Hyperosmolar Hyperglycemia Non-ketotic State (or HONK)
How does HHNS differ from DKA in terms of the serum imbalances?
More serum insulin than DKA, thus less lipolysis, less substrate for ketogenesis so no ketosis or metabolic acidosis, more hyperglycemia, more severe dehydration.
What is the cause of primary lactic acidosis?
Pyruvate dehydrogenase deficiency.
What is the primary contraindication for metformin use?
Pts with liver or kidney disease who are at risk for lactic acidosis.
What popular diabetes drug can precipitate lactic acidosis?
Metformin by interfering with hepatic gluconeogenesis.
Dichloroacetate?
A candidate drug for DKA pts, esp children, stimulates PDH to produce more glucose in the liver.
T/F: Bicarbonate therapy is indicated in patients to restore the pH in patients with lactic acidosis.
Usually false, NaHCO3 increases lactate. Carbicarb (a mix of N2CO3 and NaHCO3) is sometimes used but not widely.
What are main examples of macrovascular complications assoc with diabetes?
Cardiovascular disease incl acute MI and CVA (stroke).
What enzyme converts D-glucose to sorbitol? Sorbitol to D-fructose?
Aldose reductase.
Sorbitol dehydrogenase.
What amino acid gets glycosylated on many proteins in the context of hyperglycemia, and what is the new compound a type of?
Lysine, a labile Schiff base or "advanced glycosylation end products" which promote protein-protein cross-linking and cellular dysfunction.
What biochemical pathway is activated in diabetic retinopathy to promote neovascularization and impaired vasodilation?
Neovascular - hypoxia-induced protein kinase C-beta activation, inc VEGF activity.
Impaired vasodilation - dec eNOS on endothelial cells.
Which stage of diabetic retinopathy is characterized by microaneurysms, dot and blot hemorrhages and hard exudates?
Background (non-proliferative) retinopathy (stage 1).
Dot and blot hemorrhages?
Diabetic retinopathy, stage 1 (non-proliferative).
Cotton-wool spots on fundoscopic exam?
Diabetic retinopathy, stage 2 (pre-proliferative).
Which stage of diabetic retinopathy is characterized by neovascularization into the vitreous cavity?
Proliferative (stage 3) retinopathy.
In what stage of diabetic retinopathy does angiogenesis begin?
Stage 3, proliferative retinopathy.
Vitreous fibrosis and retinal detachment?
Stage 3 proliferative diabetic retinopathy.
Macular edema?
Diabetic maculopathy accompanying retinopathy, clinically manifested as loss of visual acuity and central vision. Can occur in background retinopathy.
Rubeosis Iridis?
Diabetic retinopathy, rare form of neovascularization of the iris.
End stage renal disease is a more common cause of morbidity in which type diabetes patients?
Type 1 > type 2.
Early in the course of diabetic nephropathy the GFR and creatinine do what?
GFR goes up, creatinine goes down as a result of inc GFR.
What is the earliest clinical sign of diabetic nephropathy?
Microalbuminuria (urine albumin over 20 mg/dL).
Kimmelstiel-Wilson lesion?
Nodular type diabetic glomerulosclerosis.
Between glomerular, vascular, and tubulo-interstitial lesions of diabetic nephropathy, which are most common?
Vascular lesions displaying hyalinosis or fibrillosis denoting arteriosclerosis.
Armani-Ebstein lesions?
Rare form of tubulo-interstitial lesion in diabetic nephropathy.
What type neurons tend to be the first ones to die in diabetic neuropathy?
C type fibers (pain afferents) due to dec oxygenation, distal extremities first.
T/F: Symmetric diabetic neuropathy is more common than asymmetric.
True.
Why do diabetics with mixed motor sensory distal polyneuropathy have "cocked up" toes?
Because flexor atrophy is greater than extensor atrophy of the foot muscles.
Diabetic mononeuropathy and polyneuropathy differ in pathophysiology how?
Mono- likely vascular or ischemic process responsible.
Poly- involves a metabolic disorder in nerves brought about by hyperglycemia (symmetric).
Charcot foot?
Bone fractures of the foot due to polyneuropathy and wasting of the balancing muscles (eversion inversion in the foot), seen in diabetes (formerly neurosyphilis).
Optic neuritis (pt presents with ptosis and diplopia) without pupillary disturbance?
Diabetic mononeuritis of the oculomotor nerve with preservation of the peripheral parasympathetic nerves sitting on the rim of CN3.
What are some prominent diabetic autonomic neuropathy symptoms?
Heartburn, dysphagia, orthostatic hypotension, bouts of intermittent tachycardia, sudden death, gastroparesis, erectile dysfxn, cystopathy, sudomotor disorders (loss of sweating in lower extremities), lack of awareness of hypoglycemia.
Necrobiosis lipoidica diabeticorum?
"Horrible necrotic yellow skin" of poorly controlled diabetics, infarction of fat under skin.
Diabetic patients should take what broad pharmacologic therapies to reduce their risk of CVD?
Anti-hypertensives (ala ACE-I's, thiazides), lipid lowering drugs, and anti-platelet therapy (warfarin, aspirin).
What are the four key features unique to diabetic dyslipidemia?
Small, dense LDL which is more atherogenic than normal. Dec HDL. Hypertriglyceridemia. Postprandial lipemia.
T/F: Glycemic control can reduce the risk of cardiovascular disease in diabetics.
False. This only holds true for the microvascular complications.
Eruptive xanthomas are microvascular or macrovascular?
Macrovascular lesions representing peripheral obstructed VLDL or chylomicrons in pts with diabetes.
Insulin normally has what effect on hormone sensitive lipase and lipoprotein lipase?
Inhibits HSL and activated LPL to induce fatty acid net transfer from liver to adipose tissue.
Why is LDL at an unexpectedly low concentration in diabetics?
Just like HDL its cholesterol ester content is depleted by excess CETP enzyme exchange TG's for CE's between VLDL and LDL/HDL.
What drugs can be administered to diabetics to treat the hypertriglyceridemia and low HDL?
Niacin (an anti-lipolytic agent) or fibrates (anti-oxidizing agent).
What drugs can be administered to diabetics to treat the high LDL?
Statins.
How can rhabdomyolysis occur in diabetics?
If they take statins with anti-lipolytic agents (niacin or fibrates) there is a risk.
If insulin resistance is the basis behind diabetes the single most effective way to blunt the resistance is:
Exercise.
What is the potential complication of taking sulfonylurea?
Hypoglycemia bc it's long acting. Other SE's: wt gain, SIADH.
Which class of drugs potentiates the beta cell to secrete more insulin?
Secretagogues (sulfonylurea and the glinides).
What does sulfonylurea do to induce insulin secretion by the beta cell?
Inhibits an ATP-sensitive K channel, decreasing efflux and depolarizing the cell, opening voltage-gated Ca channels which then triggers insulin release.
What drug activates AMPK? What are some of the effects of AMPK activation in the body?
Metformin. Decreases hepatic stores of FFA's/VLDL, decreases hepatic glucose production, decreases GI glucose absorption, increases muscle uptake of glucose.
What drugs are disaccharidase inhibitors?
Acarbose and Miglitol (alpha-glucosidase inhibitors).
Which drugs induce PPAR-gamma nuclear receptor activation? What is the net effect and what is the main side effect?
Thiazolidinediones (Pioglitazone and Rosiglitazone), insulin sensitizers in muscle and fat. SE: heart failure.
Of all the drugs to treat diabetes which are indicated for administration postprandially?
The Glinides/short-acting secretagogues, the alpha-glucosidase inhibitors, pramlintide, and GLP-1 agonists. The non-post-prandials: sulfonylureas, metformin, TZD's.
What kinds of diabetic patients would oral hypoglycemic agents be contraindicated in?
Type 1 DM's, pregnant or lactating women, pts with severe acute or chronic illness, pts with drug allergies.
Which recombinant insulin is slowest acting? Fastest?
Slow - Glargine (for DKA risk pts)
Fast - Lyspro (2-3min, good for kids).
Regular insulin enables somewhat delayed action by forming hexamers around what?
Zinc.
What are the action profiles (duration of effect) of these insulins: Lyspro, regular insulin, NPH, Ultralente, and Glargine?
Lyspro - 4-6hr
Regular - 6-8hr
NPH - 12-20hr
Ultralente - 18-24hr
Glargine - 24hr
Amylin analog? Effects?
Pramlintide. When taken with insulin it slows gastric emptying, inhibits glucagon secretion, and lowers postprandial serum glucose.
What major landmark studies took thousands of patients with type 1 diabetes and monitored them over years? Type 2 diabetics?
Type 1 - DCCT/EDIC
Type 2 - UKPDS
Match the side effects/complications below to the classic oral hypoglycemic drugs that cause them:
Heart failure
Hypoglycemia
Lactic acidosis
Liver inflammation
Precipitates IBD and bowel obstruction
Heart failure - TZD's
Hypoglycemia - secretagogues
Lactic acidosis - Metformin
Liver inflammation - TZD's
IBD/bowel obstruction - alpha-glucosidase inhibitors.
What are the average ages of onset of puberty for boys and girls?
Boys - 11-12yr
Girls - 10-11yr
Docca Jones! Docca Jones!
Growth Hormone Deficiency (Shortround aka Gizmo).
Delayed growth is more common in which gender at infancy?
Boys.
Suspect what disease in a newborn that is quiet, feeds poorly, sleeps excessively, and has growth retardation in early infancy?
Congenital hypothyroidism.
A 7yo girl presents with fatigue over the past year, worsening grades, dry skin, constipation, dry brittle hair, and poor growth over the past year. Suspect what?
Acquired hypothyroidism.
What is the usual first sign in childhood hypopituitarism?
Hypoglycemia due to failure of cortisol and GH to respond to stress.
What are the signs of secondary sexual development which if present in a child of 7-8 may provide evidence of precocious puberty?
Males - testicular enlargement.
Females - breast development.
NOT JUST HAIR!
What are the most common genetic defects that present with short stature and growth retardation?
Turner's syndrome in girls (1:1000) and Down's syndrome. CF?
Webbed neck, low set hairline, wide carrying angle, "milk maid's elbow"?
Turner's syndrome.
What is the problem in a child with both IGF-1 and IGFBP-3 low?
GH deficiency leading to short stature and growth retardation.
Exercise, insulin, arginine, L-dopa, glucagon, and clonidine all stimulate secretion of what hormone?
Growth hormone. These can all be given in stimulation tests to check for children with GH deficiency.
Cushing's disease?
Primary pituitary microadenoma leading to Cushing's SYNDROME (hypercortisolemia).
“Round nested” cells in the adrenal glands?
Glomerular region of the cortex.
"Crooke hyaline change"?
Excess cortisol inducing a pituitary corticotroph change--concentric accumulations of intermediate filaments that displace the PAS-positive, ACTH-immunoreactive secretory granules to the juxtanuclear and peripheral cytoplasm.
Waterhouse-Friderichsen syndrome?
Bilateral adrenal hemorrhage due to Meningococcemia (or Pseudomonas, S. pneumo, H. flu, Staph). Cause of acute adrenal insufficiency.
Beckwith-Wiedemann syndrome
Adrenal gland tumor. Lobulated adrenals with adrenal cytomegaly, congenital malformations in p53.
What physical exam/ROS questions would help diagnose women with androgen insensitivity syndrome?
Lack of pubic and axillary hair, primary amenorrhea (no periods).
What are the most common acute and chronic causes of renal artery stenosis?
Acute - Thrombus formation;
Chronic - Atherosclerosis or fibromuscular dysplasia in women.
Which renal cell carcinoma type is associated with the MET gene on Chr 7? VHL gene on Chr 3?
MET - Papillary RCC;
VHL - Clear cell carcinoma (von Hippel Lindau);
Chromaffin cells occur where? What do they make?
Adrenal medulla. Catecholamines in secretory granules.
Which zone of the adrenal cortex is thickest? Which part of the adrenal gland is most heavily vascularized? Which zone is the most lipid rich?
Zona fasciculata. Medulla most vascularized. Zona fasciculata (making cortisol).
What is the most common cause of Cushing's syndrome?
Iatrogenic (exogeneous corticosteroid ingestion).
What are the two causes of adrenogenital (virilizing) syndromes?
1. Adrenocortical hyperplasia, often carcinomas.
2. Congenital Adrenal Hyperplasia.
What is the most common deficit in Congenital Adrenal Hyperplasia? Gene? What steroids accumulate instead?
21-alpha hydroxylase deficiency. CYP21B. Androstenedione.
Congenital adrenal hyperplasia (due to 21-OHase deficiency) is marked by what virilizing problems in girls and boys? Non-androgen adrenal problems?
Boys - precocious puberty.
Girls - ambiguous genitalia at birth, masculinization.
Salt wasting.
What are the main causes of Addison's disease?
Globally - TB infection of the adrenals. In the US - Autoimmune adrenalitis, AIDS (CMV, MAI, KS), metastatic cancer (lung, breast, GI) APS 1/2.
Antibodies to what form in autoimmune adrenalitis?
21-hydroxylase and 17-alpha hydroxylase,
What gross and microscopic features differentiate adrenocortical adenomas and carcinomas?
Adenomas - yellow, may have pleomorphism + mitotic figures;
Carcinomas - Hemorrhage w central necrosis, much higher N:C ratio. Vascular invasion = metastatic dz.
What tissue does a myelolipoma of the adrenal glands look like?
Bone marrow.
Where does an organ of Zuckerkandl sit in the body and what kind of tumor can it give rise to?
Pheochromocytoma at the bifurcation of the aorta or inferior mesenteric artery branching.
What familial syndromes is pheochromocytoma assoc with?
MEN-IIa/b. NF-1, VHL, Sturge-Weber syndrome.
What tumor turns dark brown in Zenker's fixative/potassium dichromate?
Pheochromocytoma.
Zellballen pattern?
Pheochromocytoma.
What is the most common extracranial solid tumor in childhood?
Neuroblastoma.
Thymic hyperplasia may be associated with what disorders?
Chronic inflammatory autoimmune diseases like MG, SLE, RA, scleroderma, Graves'.
Thymomas present with what autoimmune finding?
Myasthenia gravis.
What hormones do Sertoli cells produce?
Anti-Mullerian Hormone (AMH) in development, inhibin, activin, estradiol (from aromatase conversion of testosterone).
Between testosterone and DHT, which male sex organs undergo differentiation via the signaling of each?
Testosterone - seminal vesicles, vas deferens, epidydimis.
DHT - prostate, external genitalia.
What risk factors lead to inc SBHG production and less bioavailable testosterone?
Obesity and old age in men.
What symptom of testicular deficiency differs if the patient gets it before or after puberty?
The eunuchoid skeleton.
What is Clomiphene, why is it administered, and what is the expected response?
A weak anti-estrogen, used as a dynamic test to evaluate borderline low basal values of testosterone and LH. Expected - GnRH and LH rises with infusion (blocking of E2 feedback on GnRH).
What is the expected T and LH level in patients with Klinefelter's syndrome?
Low testosterone high LH.
What is the expected T and LH level in patients with androgen insensitivity disorder?
High T high LH.
What is the expected T and LH level in patients with feminization due to prolactinomas/craniopharyngiomas inducing a stalk effect?
Low T low LH. High prolactin inhibits LH release.
What is the phenotype of patients with a 5-alpha reductase deficiency?
Female external genitalia until puberty when virilization occurs.
How would patients with androgen insensitivity disorder first present in the clinic to lead you to suspect a dx?
Complete lack of axillary or pubic hair + amenorrhea in females. US would show cryptorchidism and lack of female secondary genitalia.
What drugs can cause gynecomastia?
Some drugs create awesome knockers. Spironolactone, digitalis, cimetidine, alcohol, ketoconazole. Also finasteride, omeprazole, alkylating agents (chemo), marijuana, dopamine antagonists.
What is the difference between gynecomastia and pseudogynecomastia?
G__ is the result of glandular proliferation. Pseudog__ is the result of adipose proliferation.
What happens to the cervical mucus at the time of ovulation?
Just before ovulation, cervical mucus thickens, "raw egg white", slippery, stretches.
What is the expected effect of the progesterone withdrawal test?
Within a week after administration of progestin, bleeding should occur to demonstrate adequate estrogen present and patent outflow tract.
What hormone is responsible for stimulating the secretion of estrogen by granulosa cells?
FSH. (Remember LH is responsible for stimulating the thecal cells to make androstenedione but the granulosa cell must aromatize it).
Primary amenorrhea is defined as lack of menses by what age?
16. Although the evaluation should be begun at 13.
What symptoms result from a defect in leptin production or signaling via a receptor defect?
1. Obesity due to never-occurring satiety.
2. Hypothalamic hypogonadism bc leptin is required for proper pulsatility of GnRH.
Mayer-Rokitansky-Kuster-Hauser syndrome?
Mullerian agenesis. Wnt4 mutation.
Differentiating features of Mullerian agenesis and complete androgen insensitivity?
Mullerian agenesis pts have pubic/axillary hair, AI pts have excess LH and high serum testosterone.
What is the genetic mutation in pts with complete androgen insensitivity?
Androgen receptor (AR) on X Chr.
Swyer syndrome defect?
Defect in testis determining factor (TDF) coded by the SRY gene on Y Chr., leads to gonadal dysgenesis (female phenotype despite XY genotype).
What reproductive genetic disease predisposes to cardiovascular abnormalities like coarctation of te aorta?
Turner's syndrome.
Short 4th toe, metacarpals, webbed neck, rotated and low-set ears?
Turner's syndrome.
Madelung deformity?
Congenital subluxation of the ulna's lower end in Turner's syndrome pts.
Asherman's syndrome? Most common cause?
Intrauterine adhesions causing secondary amenorrhea and infertility, usu induced by a D&C performed on a recently pregnant uterus.
What are the most common causes of female hirsutism?
Polycystic ovarian syndrome, idiopathic. Then Cushing's disease, hyperprolactinemia, congenital adrenal hyperplasia, ovarian tumors (more virilization), severe insulin resistance.
What endocrine diseases can taking chlorpromazine cause?
SIADH (remember it treats DI) and hyperprolactinemia (it's a dopamine antagonist).
What enzymes do the kidneys use to degrade cortisol and prevent it from activating mineralocorticoid receptors? What is a similar enzyme that has the opposite effect?
11-beta HSD type 2. It oxidizes cortisol to cortisone using NAD+. Type 1 is present in the adrenal glands and does the opposite, reduces using NADPH.
Mumps can cause what endocrine problems?
Primary hypothyroidism (subacute) and hypogonadism.