Endocrine Flashcards
(90 cards)
1
Q
subclinical hypothyroidism
A
clinical
- elevated TSH (verified on repeat measurements)
- normal free T4
- mild symptoms may or may no be present
indications for treatment
- TSH at least 10
- TSH 7-9.9
- age less than 70 - treat
- age 70 and up - treat if convincing hypothyroid symptoms
- TSH upper limit of normal - 6.9
- age less than 70 - treat if convincing hypothyroid symptoms, enlarging goiter, or elevated TPO anti-TPO titer
- 70 and up - do not treat (possible harm)
subclinical hypothyroid is defined as elevated TSH with normal free thyroxine. Most common cause is hashimoto (chronic lymphocytic) thyroiditis.
It’s associated with increased risk of pregnancy complications including recurrent miscarriage, severe preeclampsia, preterm birth, low birth weight, and placental abruption.
Anti-thyroid peroxidase antibodies (anti TPO) are associated with increased risk of pregnancy loss even in women who are euthyroid.
2
Q
Glucagonoma
A
Rash - necrolytic migratory erythema. “rash started 3 weeks ago on forearm as a small elevated red area. gradually involved surrounding skin and became an erythematous itchy painful rash that did not respond to 1% hydrocortisone. 1 week ago the rash started clearing up from the center”
Rare pancreatic tumor associated with mild diabetes and a classic skin rash. Most are malignant and have mets, mainly in liver at the time of diagnosis. Some clinical manifestations are due to secretion of other peptides like VIP, calcitonin, and GLP1.
Diagnosis is suspected clinically and confirmed by measuring glucagon levels which are usually very high. Primary treatment is surgical
3
Q
Postpartum thyroiditis
A
Primary hyperthyrodiism (elevated T4, suppressed TSH)
nontender goiter and recent pregnancy
Occurs less than a year following pregnancy
similar to silent thyroidism with thyroid peroxidase antibody. Transient hypothyroid phase before returning to a normal euthroyid state whereas patients with classic hashimoto have residual hypothyroidism
Radioactive iodine uptake scan can distinguish graves which causes increased thyroid hormone synthesis from postpartum thyroidism which are characterized by thryoid inflammation and release of preformed hormone. Graves has high RAIU.
4
Q
postpartum pituitary necrosis
A
Sheehan syndrome. seen following severe OB hemorrhage and hypotension. Failure of lactation is a common presenting symptom but patients have central hypothyroidism rather than primary hyperthyroidism
5
Q
type 1 vs 2 DM
A
Type 1
- insulin deficiency
- childhood or early adulthood, more common in whites
- usually rapid onset of clinical symptoms with osmotic symptoms
- DKA more common
- low C peptide levels
- pancreatic antibodies are usually present (glutamic acid decarboyxlase antibody)
Type 2
- insulin resistance with relative insulin deficiency
- adulthood, more common in nonwhites, more common in obese, positive family history
- asymptomatic at onset
- DKA less common
- C peptide usually elevated
- pancreatic antibodies usually absent
6
Q
Diagnosis of hyperCa
A
1) Confirm hyperCa
- repeat testing
- correct for albumin or measure ionized calcium
2) next step is measur PTH
- high normal or high (PTH dependent)
- primary or tertiary hyperparathyroidism
- familial hypocalciuric hypercalcemia
- lithium
- suppressed PTH (PTH independent)
- measure PTHrP, 25-hydroxyD, 1,25-dihydroxyD
- malignancy’vit d def
- granulomatous dz
- drugs (thiazides)
- milk-alkali
- vit A roxicity
- thyrotoxicity
- immobilization
- measure PTHrP, 25-hydroxyD, 1,25-dihydroxyD
urinary calcium should be measured in patients iwht pTH dependent hyperCa to differentiate familial (rare dz due to mutations in calcium sensing receptor and leading ot low urinary ca excretion) from primary hyperpara (urinary ca is normal or high) but only after PTH-dependent hyperCa is confirmed
7
Q
hyperCa of malignancy
A
Cause (3 causes)
1) PTHrP
- tumor type
- SCC
- renal and bladder
- breast and ovarian
- mechanism
- PTH mimic
- diagnosis
- low PTH
- high PTHrP
2) bone mets
- tumor type
- breast
- MM
- mechanism
- increased osteolysis
- diagnosis
- low PTH and PTHrP
- low Vitamin D
3) 1-25 dihydroxyD
- tumor type
- lymphoma
- mechanism
- increased calcium absorption
- diagnosis
- low PTH
- increased vitamin D
hyperCa of malignancy is associated with rapid onset of increased calcium levels.
8
Q
Cushing’s Syndrome
A
HTN, hyperglycemia, osteoporosis, mood swings, hypoK, and metabolic alkalosis.
Screening for cushing’s can be done by overnight dexamethasone suppression test or 24h urinary free cortisol. In normal people, serum cortisol is typically suppressed below 3 mcg after giving 1 mg of dexamethasone. False positive results can be seen in alcoholism and malabsorption of dexamethasone
Screen young patients with diabetes, osteoporosis, HTN, and hypoK for cushings syndrome
9
Q
Pioglitazone
A
Member of the thiazolidinedione class. It’s a PPAR-y agonist. PPAR-y receptors are in the collecting tubule of the nephron and stimulation by the drug leads to increased sodium reabsorption. This is the same channel via which aldosterone mediates effects on sodium retention
Fluid retention can occur in 4-6% of patients on thiazolidinediones, but most of these patients likely have underlying CHF
If these drugs cause fluid retention, treatment can be an aldosterone antagonist like spironolactone
10
Q
Hyperthyroidism
A
Clinical features
- behavior disturbances (inattention, moodiness, poor school performance)
- weight loss
- goiter
- proptosis
- tachycardia, wide pulse pressure
- tremor, hyperreflexia
- warm, sweaty skin
diagnosis
- increased T3/T4, low TSH
- Thyroid stimulating immunoglobulin (Graves)
Tx
- methimazole
- plus/minus radioactive iodine
Complications
- arrhythmia, cardiomyopathy
- osteoporosis (elevated TH stimulates calcium and phosphate release from bone)
11
Q
insulin dose and exercise
A
Physical activity promotes noninsulin-mediated uptake of glucose into skeletal muscles and increases risk of hypoglycemia in patients with diabetes. Risk is highest in type 1DM and type 2DM treated with insulin or insulin secretagogues (sulfonylureas)
Should decrease dose of short-acting insulin (lispro) within 1-3 hours prior to exercise, with reduction proportionate to exercise intensity. If prolonged (more than 60mins) or will occur in AM before breakfast, dosal of basal insulin (glargine) should also be reduced.
if glucose is less than 100 before, during or after exercise, additional carbs should be consumed.
12
Q
Clinical features of thyrotoxicosis in older patients
A
CV
- AFib
- tachycardia (can be absent due to BBs or conduction defects)
- heart failure
Neuro
- apathy, confusion, depression
- tremor (often absent)
- proximal muscle weakness/wasting
endo
- proptosis, lid leg, thyromegaly
GI
- decreased appetite
- constipation
most common causes of AMS in elderly are meds, infections, and metabolic. dont forget thyroid. Thyroid stuff often presents atypically in an old person
13
Q
Managing hyperglycemia in the hospital
A
1) Classify diabetes
- type 1 (do not stop basal insulin)
- type 2
- stress induced hyperglycemia
2) determine dietary status (eating normally, etc)
3) determine preadmission glycemic control and regimen
4) d/c oral drugs
5) determine insulin regimen
- basal-bolus
- patients with type 1
- patients with type 2 treated before admission with basal bolus regimen
- patients with type 2 not well controlled by ISS alone
- patients with newly diagnosed diabetes and high glucose levels
- ISS alone
- appropriate initially in pts whose type 2 is well controlled with diet and/or oral meds before admission. Adding basal insulin if glucose is suboptimally controlled on ISS alone
- insulin infusion (ICU)
- type 1 patients who are not eating and with glucose levels suboptimally controlled with subq insulin
- type 1 patients perioperatively or during labor
- hyperglycemic emergencies
in the hospital, goal is gluc in 140-180 range. Use 3 components
1) basal (intermediate or long acting) for controlling glucose levels btw meals. Needed for all type 1 patients and most type 2.
2) nutritional boluses (short acting) for controlling postprandial glucose excursions (not needed if pt not eating)
3) correctional boluses (short acting) for correcting high glucose levels (sliding scale)
basal (glargine, detemir, NPH)
short acting (aspart, lispro, glulisine)
generally, dose of prehosptal basal insulin should be lowered for admission bc they usually eat less in the hospital (25-50%)
14
Q
Prolactinoma
A
clinical
- premenopausal women - oligo/amenorrhea, infertility, galactorrhea, hotflashes, decreased bone density
- post women - mass effect symptoms (HA, visual field defects)
- men - infertility, decreased libido, impotence, gynecomastia
labs/imaging
- serum prolactin often above 200
- rule out renal insufficiency (Cr) and hypothyroidism (TSH, thyroxine)
- MRI brain/pituitary
tx
- dopamine agonist (cabergoline, bromocriptine)
- trans-spneoidal surgery
High prolactin suppresses gonadotropin releasing hormone, LH, and estradiol leading to symptoms of hypogonadism like hot flashes, vaginal dryness, and osteoporosis***
15
Q
Indications for diagnostic testing for pheo
A
Signs/symptoms
- episodic HAs, diaphoresis, tachycardia
- hyperadrenergic spells (nonexertional palpitations, pallor)
- resistant HTN or onset of HTN at young age
FHx
- pheo
- predisposing syndromes (MEN2, NF1, VHL)
Other
- adrenal incidentaloma on imaging
- pressor response during surgery/anesthesia
- idiopathic dilated cardiomyopathy
Measurement of 24h fractionated urinary metenephrines and catecholamine levels is one of the preferred screening tests. Also plasma free metanephrines. Prior to testing, stop TCAs, OTC decongestants) for 2 weeks.
24h urinary vanillylmandelic acid is much less sensitive
Beta block before alpha block may worsen HTN in pheo as unopposed alpha adrenergic activity may cause casoconstriction
Don’t start alpha blockers until after confirming diagnosis bc they can lead to a false positive (falsesly elevate catecholamines and metanephrines)
16
Q
Steps for diagnosing a Pheo
A
High level of suspicion leads to 24h urine fractionated metanephrines/catecholamines or plasma fractionated metanephrines. If normal, recheck during a spell. If elevated (double/triple normal), next step is imaging (CT or MR abdomen)
If negative, consider further imaging
- MIBG scan
- octreotide scan
- whole body MR
- PET
If positive
- surgical eval
- genetic testing
- alpha and beta block prior to surgery
- MIBG scan if tumor more than 5cm and suspicion for extra-adrenal disease (younger patients and those with familial disorder)
removal is only performed after localization, adequate preop BP control for 10-14 days with an alpha blocker and intravascular fluid volume repletion with liberal fluid and salt.
intraop complications are much higher with inadequate preop alpha blockade and fluid deficiency. BBs are only given to patients with adequate and complete alpha blockade. Starting BB prior to AB leads to paradoxical increase in BP due to unopposed alpha adrenergic activity
17
Q
surgical complications of adrenalectomy for pheo
A
Hypertensive crisis
- increased catecholamine release due to endotracheal intubation and adrenal gland manipulation
- increased serum norepinephrine with larger tumors (over 4cm)
- treat with iv nitroprusside, phentolamine or nicardipine
Hypotension
- reduced catecholamines after tumor removal
- persistent alpha blockade from preop long acting alpha blocker (phenoxybenzamine)
- treat with NS bolus, pressors if unresponsive
Hypoglycemia
- increased insulin secretion following tumor removal (catecholamines supress insulin secretion)
- treat with iv dextrose infusion
cardiac tachyarrhythmias
- increased catecholamine release from adrenal gland handling
- treat with iv lidocaine or esmolol
18
Q
Treating Graves
A
Patients with symptomatic hyperthyroidism should be started on a beta blocker (propranolol) FIRST to reduce symptoms with additional measures to decrease thyroid hormone production and achieve euthyroid state. Options include antithyroid drugs, radioactive iodine, and thyroidectomy.
drugs inbibit synthesis of thyroid hormone. they can be used in short courses to achieve remission in mild cases and for chronic management in poor operative candidates or those who wish to avoid surgery/RAI. In patients with more severe symptoms, drugs can induce euthyroid state in preparation for surgery/RAI.
- methimazole is usually preferred due to risk of hepatotoxicity with propylthiouracil.
- PTU is recommended in 1st trimester of pregnancy tho bc methimazole is a teratogen
RAI is appropriate for patients who can’t tolerate drugs, those who wish to avoid surgery or peeps who will likely need more than drugs. Most patients treated with RAI for graves develop residual hypothyroidism and require long term thyroid replacement therapy.
- contraindicated in pregnancy and lactation
Surgery is preferred for those with large goiters, obstructive symptoms, or suspected thyroid cancer. Also recommended for significant ophthalmopathy as RAI may cause an exacerbation of symptoms in these patients.
Summary. BB to reduce symptoms (if symptomatic) followed by definitive treatment.
19
Q
how do you monitor thyroid function during use of antithyroid drugs?
A
Use serum total T3/T4 as TSH may remain suppressed for several months following initiation of therapy and doesn’t reflect thyroid function status.
Get these labs 4-6 weeks after starting treatment. If normalized, can proceed to definitive therapy.
20
Q
sulfonylurea overdose
A
Example is Glyburide. These drugs increase insulin secretion and can cause hypoglycemia.
First line treatment is dextrose. Look out for rebound hypoglycemia though.
Give octreotide which is a somatostatin analogue that lowers insulin secretion. Give when suspect large overdose or when patient doesnt know how much they took.
21
Q
MEN1
A
Pituitary adenoma (10-20%)
- secretion of prolactin, growth hormone, ACTH
- mass effects (HA, visual fields)
Primary hyperparathyroidism (over 90%)
- multiple parathyroid adenomas or parathyroid hyperplasia
- hyperCa (polyuria, kidney stones, decreased bone density)
Pancreatic/GI neuroendocrine tumors (60-70%)
- GI - recurrent peptic ulcers
- gastrinoma/zollinger ellison
- insulinoma - hypoglycemia
- VIPoma - secretory diarrhea, hypoK, hypoCl
- glucagonoma - weight loss, necrolytic erythema, hyperglycemia
22
Q
MEN2
A
2A
- medullary thyroid cancer (calcitonin)
- Pheo
- Primary hyperparathyroidism (parathyroid hyperplasia)
2B
- medullary thyroid cancer (calcitonin)
- Pheo
- mucosal neuromas/marfanoid habitus
23
Q
Zollinger-Ellison
A
elevated serum gastrin
Gastrin can be high due to hyperCa or PPIs though. Don’t measure gastrin levels until patient has normal Ca level and has stopped PPI for 2 weeks
24
Q
Congenital adrenal hyperplasia :(
A
CAH is a group of disorders characterized by deficiency in an enzyme involved in making steroids. Most cases are from auto recessive 21-hydroxylase deficiency. This causes low production of mineralocorticoids and glucocorticoids in addition to extra of its substrates. These extra substrates are then shunted towards androgen synthesis leading to ambiguous genitalia in girls and precocious puberty in boys. Adrenocorticotropic hormone levels are also high which causes hyperplasia of adrenal glands which leads to even more androgens.
- labs show low Na, high K, low glucose, high 17OH-progesterone
- treat with glucocorticoids and mineralocorticoids. High salt diet. genital reconstruction for girls. psychosocial support.
Salt wasting syndrome occurs in severe 21-hydrox deficiency and presents in first few weeks of life with life threatening emesis, dehydration and shock. Labs show low Na, high K (no aldosterone), high glucose (no cortisol)
1) 21-hydroxylase deficiency
- low mineralo
- low gluco
- high androgens
- salt wasting
- ambiguous genitalia in girls
2) 11B-hydroxylase deficiency
- high mineralo (low aldosterone but excessive weak mineralocoritcoid 11 deoxycorticosterone)
- low gluco
- high androgens
- HTN, lowK
- ambigious genitalia in girls
3) 17a-hydroxylase deficiency
- high mineralo
- high gluco (low cortisol but excessive weak glucocorticoid corticosterone)
- low androgens
- HTN, lowK
- ambigious genitalia in boys
- absent puberty
25
5 alpha reductase
converts testosterone to dihydrotestosterone
Elevated Testosterone to DHT ratio
autosomal recessive defect in XY males. Impaired verilization during embryo leading to abnormal/feminine external genitalia and normal internal genitalia.
Normal testosterone production. Normal estrogen levels. Normal or a little high LH.
Masculination during puberty when testosterone increases.
26
Management of DKA
IV fluids
* rapid infusion of NS
* add dextrose 5% when serum glucose is below 200
insulin
* IV infusion. Hold If K is less than 3.3
* switch to sq insulin (basal bolus) for the following
* able to eat
* glucose below 200
* anion gap below 12
* serum HCO3 at or above 15
* overlap sq and iv insulin by 1-2 hrs
K
* add iv K if serum K is less than 5.3. Hold if K reaches 5.3 or higher
* nearly all patients K is depleted, even with hyperK
HCO3
* consider for patients with pH of 6.9 or less
PO4
* consider if phosphate is less than 1, cardiac dysfunction, or respiratory depression
* monitor serum calcium
27
amiodarone and the thyroid
1) decreased conversion of T4 to T3.
* high t4
* low t3
* normal/high tsh
* no treatment needed
2) inhibition of thyroid hormone synthesis
* high tsh
* low t4
* give synthroid
3) amiodarone induced thyrotoxicosis type 1 (iodine induced increase in thyroid hormone synthesis)
* low tsh
* high t3 and t4
* low RAIU (radioactive iodine uptake)
* increased vascularity on ultrasound
* treat with antithyroid drugs
4) AIT type 2 (destructive)
* low tsh
* high t3 and t4
* undetectable RAIU
* decreased vascularity on US
* treat with steroids
28
menopausal hormone therapy
Most effective treatment for menopausal hot flashes. Improves vaginal atrophy, bone mass/fractures. Helps colon cancer, type 2 DM, and even has lower all cause mortality in patients under 60.
BUT
higher risk of DVT/PE, breast cancer, heart disease (especially in women over 60)
estrogen alone increases endometrial cancer (so combo is preferred)
Increased risk of stroke in all patients (small in younger patients but still increased) regardless of BP control or other risk factor mitigation.
MHT is safe for short period (3-5 years) in younger, low risk women (nonsmokers, no hx of breast cancer, clots, or CHD)
29
Maternal hypothyroidism in pregnancy
TSH
* low/suppressed in first trimester due to thyroid-stimulating actions of bhcg. Basically thyroid hormone increases during pregnancy and may cause a picture resembling subclinical hyperthyroidism
* pregnancy reference range for TSH
* first trimester: 0.1 - 2.5
* second 0.2 - 3
* third 0.3 - 3
Management
* increase levothyroxine dose by 30%
* monitor TSH levels every 4 weeks
* adjust dosage to maintain TSH within pregnancy reference ranges by trimester
30
Pernicious anemia
Look out! patients with autoimmune diseases (primary hypothyroidism) can get other ones!
Loss of intrinsic factor from parietal cells in stomach. Autoimmune destruction of parietal cells. Leads to b12 deficiency.
Neuro involvement of b12 deficiency leads to ataxia, loss of proprioceptive and vibratory sensations. Severe spasticity, weakness and peripheral nerve involvement too. Symptoms are usually worse in lower extremities.
when treating with b12 watch out for severe hypokalemia in first 48h. Closely monitor and supplement
31
SGLT2 inhibitors
Sodium-glucose cotransporter 2. Example is canaglifozin or dapaglifozin.
They lower blood glucose by reducing reabsorption of glucose in the kidney which leads to low insulin to glucagon ratio bc high blood glucose levels are the primary driver of insulin release.
Side effects
1) GU infections
* vulvovaginal candidiasis
* UTI
2) Fluid loss
* symptomatic hypotension
* AKI
3) Metabolic
* hyperK
* hyperlipidemia
* euglycemic DKA (gluc less than 250. manage with fluids, stopping drug, and control of glucose with insulin) - abdominal pain, metabolic acidosis, n/v, tachypnea
4) miscellaneous
* low trauma fractures
* amputation
32
hypoglycemia
blood glucose less than 60
whipple's triad is strongly suggestive of true hypoglycemia. low glucose, symptoms of hypoglycemia, and improvement when given glucose.
33
familial hypocalciuric hypercalcemia vs primary hyperparathyroidism
FHH
* normal or mildly high serum Ca
* normal or high PTH
* no hypercalcemic symptoms
* normal bone density
* low urinary calcium excretion (Calcium to creatinine clearance ratio less tha 0.01 or 24h calcium less than 100mg)
* treatment is reassurance
PHPT
* high serum Ca
* normal or high PTH
* may have hyperCa symptoms
* often low bone density
* high CCCR (above 0.02) or 24h urinary calcium above 300 mg
* treat with parathyroidectomy or serial monitoring
Although PHPT causes increased reabsorption of calcium, net excretion is increased due to accelerated bone turnover. untreated PHPT can lead to CKD, renal stones and osteoporosis
34
short vs long insulin
short insulin has higher risk of hypoglcyemia than long acting.
35
Addison's Disease
Chronic adrenal insufficiency
Weight loss, abdominal pain, fatigue, amenorrhea, asthenia, weakness, poor appetitie.
Muscle tenderness on exam, decreased axillary and pubic hair (low adrenal androgen production), increased pigmentation (co-secretion of ACTH and melanocyte stimulating hormone)
HypoNa, hyperK and mild hyperchloremic metabolic acidosis.
In evaluating the patient, measure morning plasma cortisol with concurrent ACTH. Low cortisol with high ACTH is diagnostic for primary adrenal insufficiency. If results are equivocal, they can be followed by ACTH stimulation test.
signs/symptoms of adrenal insufficiency
* get 250ug cosyntropin stimulation and ACTH/Cortisol levels
* indetermine
* further testing to assess pituitary function
* basal cortisol low, ACTH high, minimal cortisol response to cosyntropin
* primary adrenal insufficiency
* basal cortisol low, ACTH low, minimal or suboptimal cortisol response to cosyntropin
* secondary or tertiary adrenal insufficiency
* normal response (cortisol level above 20 30-60 mins after cosyntropin)
* unlikely to be adrenal insufficiency. Investigate other causes
36
delayed puberty in boys
Defined as lack of testicular enlargement by age 14
causes
* primary hypogonadism (elevated FSH and LH)
* klinefelter (47 xxy)
* secondary hypogonadism (due to impaired GnRH, low to normal FSH and LH)
* constitutional delay, chronic illness, malnutrition
* hypothyroidism, hyperprolactinemia
* kallmann syndrome
* craniopharyngioma
clinical
* absent testicular enlargement by age 14
* delayed growth spurt
initial workup
* FSH, LH, testosterone, TSH, prolactin
* bone age radiograph
37
Conditions that alter TBG concentration
Increased thyroxine binding globulin
* estrogens
* pregnancy, OCPs, HRT, tamoxifen
* acute hepatitis
Decreased TBG
* androgenic hormones
* high dose steroids/hypercortisolism
* hypoproteinemia (nephrotic syndrome, starvation)
* chronic liver disease
Other
* salicylates displace thyroid hormone from protein binding sites
More than 99% of circulating thyroid hormone (T3, T4) is bound to plasma proteins. Most use thyroxine binding globulin. Free thyroid hormone is cleared by teh kidneys so you need the proteins to deliver adequate hormone to the tissues.
elevated estrogen levels (pregnancy, OCPs) stimulate hepatic synthesis of TBG. This leads to less thyroid hormone in the blood, stimulating TSH to produce more thyroid hormone. Patients with normal thyroid function can increase thyroid hormone production to saturate the additional protein binding sites, but those with hypothyroidism are unable to increase thyroid hormone synthesis. OCPs in these patients can induce a relative hypothyroid state. Most will need increased dose of synthroid prior to starting OCPs.
38
Stress hyperglycemia
Pathogenesis
* increased cortisol/catecholamines and pro-inflammatory cytokines resulting in trasniently elevated blood glucose in patients without known diabetes
risks
* ICU admission
* temp above 39C
* severe illness
* sepsis
* CNS infection
Treatment
* adults - minimize glucose-containing IV fluids, consider insulin to achieve a blood glucose target of 140-180
* children - inconclusive evidence for insulin
39
diagnostic criteria for diabetes
Random plasma glucose of at least 200 in patients with classic symptoms of hyperglycemia (polyuria, polydipsia, polyphagia) OR
A1c at least 6.5 OR
Fasting plasma glucose of at least 126 OR
2hr plasma glucose of at least 200 during oral glucose tolerance test
40
congenital hypothyroidism
It's a common and preventable cause of intellectual disability. Most cases due to thyroid dysgenesis (agenesis, hypoplasia, ectopy). T4 is critically important for normal brain development and myelination. Congenital hypothyroidism can lead to permanent intellectual disability if hormone replacement isnt started by age 2 weeks.
Signs
* normal at birth
* age less than one month
* jaundice
* poor feeding
* hypothermia
* age 1-4 months
* FTT
* constipation
Diagnosis
* newborn screening
* increased TSH, low T4
Management
* confirm TSH, T4
* start synthroid immediately
* order US of thyroid
* refer to endocrine
Prognosis
* excellent with tx
* at risk for permanent neuro defects without treatment
41
gestational diabetes
During second and third trimesters, the placenta secretes increasing amounts of hormones (human placental lactogen) that induce maternal insulin resistance. This maternal insulin resistance insures that there is enough glucose for fetal development. GDM though is associated with preeclampsia, neonatal hypoglycemia, neonatal polycythemia.
patients who are at risk of undiagnosed pregestational diabetes (obese, prior macrosomic infant) are screened as early as initial prenatal visit. Patients without risk factors are screened at 24-28 weeks.
Screening involves a 2 step approach
Step 1
* give 50g oral glucose load
* check glucose 1 hr later
* if less than 140, no further testing as GDM unlikely
* if 140 or up, go to step 2
step 2
* 100g oral glucose load
* check fasting glucose every hr for 3 hrs. it's gdm if
* more than 95-105 fasting
* more than 180-190 at 1h
* more than 155-165 at 2h
* more than 140-145 at 3h
Patients with GDM diagnosed monitor fasting and either 1 or 2h postprandial glucose levels with goals of 95 for fasting and 140 for 1h, 120 for 2h. Glycemic control is important to minimize risk of uteroplacental insufficiency (growth restriction), shoulder dystocia, macrosomia, fetal hyper/hypoglycemia, fetal hyperinsulinemia, preeclampsia
If control can't be obtained with diet/exercise, then insulin, metformin and glyburide are ok in pregnancy.
Glipizide has higher risk of neonatal hypoglycemia
42
Precocious puberty
Early development of secondary sexual characteristics (girls before age 8, boys before 9)
Is bone age advanced (like real tall?)
* yes
* high basal LH
* central precocious puberty
* low basal LH - do GnRH stimulation test next
* low LH
* peripheral precocious puberty
* high LH
* central
* no
* isolated pubic hair development
* premature adrenarche
* isolated breast development
* premature thelarche
central is from early actiation of hypothalamic-pituitary-gonadal axis, resulting in increased LH and FSH. Most cases are idiopathic but pathologic causes include CNS tumors. Treatment is with a gonadotropin-releasing hormone agonist that downregulates FSH and LH
peripheral is caused by abnormal secretion of sex hormones from other organs (adrenals, ovaries, testes) and results in suppresion of HPG axis and decreased LH and FSH
43
McCune Albright
irregular cafe-au-lait spots, fibrous dysplasia and peripheral precocious puberty from elevated estrogens from ovarian cysts
44
thyroiditis
1) Chronic autoimmune thyroiditis (Hashimoto)
* predominant hypothyroid features
* diffuse goiter
* positive TPOantibody
* variable radioiodine uptake
2) painless thyroiditis
* variant of chronic autoimmune thyroiditis
* mild, brief hyperthyroid phase
* small nontender goiter
* spontaneous recovery
* positive TPO antibody
* low radioiodine uptake
3) subacute thyroiditis (De Quervain) - likely from release of stored thyroid hormone after follicular injury
* likely postviral inflammatory process
* prominent fever and hyperthyroid symptoms
* can see leukocytosis and mild anemia
* painful/tender goiter
* elevated ESR and CRP
* low radioiodine uptake
* hyperthyroid phase lasts a few weeks followed by a transient hypothyroid phase and return to euthyroid.
* tx is supportive with NSAIDs with steroids sometimes for severe/refractory cases. BB's can be given to minimize hyperadrenergic symptoms (sweating, palpitations)
45
Primary hyperaldosteronism
Conn's syndrome
HTN and low K. Hypokalemia causes polyuria.
Screening test is plasma aldosterone to renin activity ratio. Ratio above 30 suggests too much aldosterone secretion from adrenals have suppressed renin activity. Since many people with HTN have low renin activity anyway, you need an aldosterone level of at least 15 to even interpret the test.
Secondary hyperaldosteronism is seen in patients with renal artery stenosis. A common cause is fibromuscular dysplasia.
46
euthyroid sick syndrome
Encompasses a variety of alterations in thyroid physiology, the most common of which is "low T3 syndrome" and is thought to be the result of decreased conversion of T4 to T3. Factors in acute illness can inhibit peripheral deiodination to T3. These include
* high cortisol
* inflammatory cytokines (TNF)
* starvation
* meds (steroids, amiodarone)
TSH and T4 levels are often normal in ESS, although they also may fall in severe or prolonged cases and ESS may represent a transient central hypothyroidism rather than a true euthyroid state.
Treatment is deferred unless abnormal thyroid function persists after the patient has returned to baseline heatlh .
47
diabetic neuropathy
suspect in patients with diabetes who have symmetric sensory changes in the feet that consist of injury to nerve fibers controlling pain, temp, vibration, and proprioception. Tuning fork test is easy and cheap way to assess for loss of vibratory sense in patients with diabetic neuropathy
Aggressive glycemic control is most important management. For patients with severe associated pain, treatment with TCAs (amitriptyline), duloxetine or certein anticonvulsant meds (gabapentin, pregabalin) can help. SSRIs do nothing.
48
Evaluation of hyperthyroidism
Measure TSH, free T3, and free T4
Secondary hyperthyroidism - TSH high, Free T3/T4 high.
* get MRI pituitary
Primary hyperthyroidism - TSH low, Free T3/T4 high
* Signs of Graves Disease (goiter and ophthalmopathy)
* Yes - Graves
* No - look at RAIU
* High
* Diffuse pattern - graves
* nodular pattern - toxic adenoma or multinodular goiter
* low - measure thyroglobulin
* high - thyroiditis, iodine exposure
* low - exogenous hormone
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synthroid treatment for differentiated epithelial (papillary and follicular) thyroid cancer
After treating thyroid cancer with surgery and ablative radioiodine therapy, patients often require thyroid hormone replacement therapy. In addition, high TSH levels stimulate the growth of residual thyroid cancer cells and suppressing TSH with synthroid has been shown to decrease recurrent disease. BUT, suppressive doses of synthroid are linked to increased risk of bone loss and AFib. So degree of suppression will depend on initial tumor stage and risk of recurrence
Small, low risk tumors - target TSH is 0.1-0.5 for 6-12 months then low normal range
Intermediate risk tumors - target 0.1 - 0.5
Large, aggressive tumors - raget less than 0.1. Continue for several years.
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amenorrhea, hypogonadism with suppressed LH and FSH and increased alpha subunits
Strongly suggests non-functioning pituitary adenoma
Adenomas often arise from the gonadotropin releasing cells in the pituitary gland. Normally, they secrete FSH and LH (these are dimeric hormones which share a common alpha subunit and have different beta subunits). These dysfunctional cells now just secrete the alpha subunit. Not much clinical significance of the alpha subunit which is why it's "non functioning."
Diagnosis is often not apparent until it's large enough to cause HA or vision problems
Note that mild elevations in prolactin (like around 50) are often seen and does not imply prolactinoma (much bigger increase like 200). Compression of the pituitary stalk by a large adenoma may block the normal hypothalamic inhibition of prolactin secretion, leading to mild elevations.
Preferred treatment is trans-sphenoidal surgery
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toxic thyroid nodule
Characterized by increased radioiodine uptake in the nodule and suppressed uptake in the remainder of the gland.
Definitive treatment with surgery or radioactive iodine ablation is recommended for patients with overt hyperthyroidism. Surgery is preferred for those with large goiters, obstructive symptoms, or suspected thyroid cancer. Patients should be treated with antithyroid drugs to achieve euthyroidism prior to surgery. Methimazole is preffered over PTU in most patients.
52
workup of thyroid nodule
Clinical evaluation, TSH, and US
No cancer risk factors or susipicious US findings
* normal or elevated TSH
* FNA
* treatment based on findings
* low TSH - get iodine 123 scintigraphy
* hyperfunctional (hot) nodule
* treat hyperthyroidism
* hypofunctional (cold) or indeterminate nodule
* FNA
Cancer risk factors or suspicious US findings
* FNA
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adrenal incidentaloma
Before deciding to be conservative or how to manage you must evaluate for hormone production. Get serum lytes, dexamethasone suppression test, 24h urine catecholamine, metanephrine, vanillylmandelic acid and 17-ketosteroid measurement
All functioning masses, masses with rads evidence of malignancy, or masses greater than 4cm should be removed
54
pubertal gynecomastia
common physiologic finding in pubertal boys. Present with small, often tender subareolar masses that may grow but typically resolves in a year. No treatment is needed.
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impaired fasting blood glucose
fasting value between 100-126
These patients are at risk for coronary artery disease (even with normal lipids) and progression to overt diabetes
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TSH secreting pituitary adenoma
clinical
* thyrotoxicosis
* diffuse goiter
* possible mass effect
labs
* elevated (or inappropriately normal) TSH
* elevated T3 and T4
* elevated alpha subunit (85% of patients)
* elevation of other pituitary hormones
MRI
* pituitary mass
Additional
* minimal or no suppresion of TSH by exogenous thyroxine
* elevated sex hormone binding globulin
* normal thyroid hormone receptor beta gene
tx
* somatostatin analogs
* transphenoidal surgery
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gonadotropins
FSH and LH. If low suspect a pituitary thing.
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tight glycemic control is to prevent what?
microvascular complications of DM (retinopathy, nephropathy.
slows progression of neuropathy
no proven effect on macrovascular complications (MI, PAD, stroke) so prevention of these should focus on BP control, lipid lowering therapy, low dose aspirin, and smoking cessation
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subclinical hyperthyroidism
clinical
* suppressed tsh
* normal thyroid hormone levels
* hyperthyroid symptoms may or may not be present
causes
* exogenous thyroid hormones
* graves
* nodular thyroid disease
indications for tx
* TSH persistently less than 0.1
* TSH 0.1-0.5 plus additional risk factors
* age 65 and up
* heart disease
* osteoporosis
* nodular thyroid diseases
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lithium induced hypothyroidism
Patient on lithium with new elevated TSH and fatigue.
Lithium interferes with synthesis and release of thyroid hormone causing a range of thyroid issues that usually pop up in first 2 years
Should examine thyroid and get TFTs prior to starting lithium and every 6-12 months
Treat with synthroid. no need to stop lithium.
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Anabolic steroid abuse
MSK - increased muscle mass
Repro
* low testosterone, FSH, LH
* testicular atrophy
* decreased spermatogenesis
* normal libido and erectile function (during use)
* decreased libido and impotence during withdrawal
Endo
* increased LDL, low HDL
heme
* erythrocytosis
psych
* affective symptoms
* aggression
derm/breast
* acne
* gynecomastia
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pituitary incidentaloma
If small and no clinical/lab abnomrality, no compressive features, no hormonal stuff - just monitor with periodic MRI
63
management of chronic pancreatitis
Pain
* alcohol and tobacco abstinence
* frequent small meals
* pancreatic enzyme supplements
* NSAIDs
* opioids
Malabsorption
* low fat diet
* pancreatic enzyme supplements
* fat soluble vitamin supplements
Diabetes
* metformin (mild hyperglycemia) - metformin is contraindicated in patients with GFR less than 30 and should be used with caution in 30-45.
* insulin (symptomatic)
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metformin
Contraindicated for patients with renal insufficiency, hepatic dysfunction, alcohol abuse, sepsis, or CHF (esp with Cr above 1.5). It can increase the risk of lactic acidosis when combined with large dose IV iodine contrast (coronary cath) so it is held on day of contrast and resumed at least 48h later after documenting stable renal function
Adverse effects are lactic acidosis, GI upset, decreased B12 absorption
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Causes of hypocalcemia
1) Vit D deficiency
* low P, high PTH
2) hypoparathyroidism
* high P, low PTH
3) pseudohypoparathyroidism
* high P, high PTH
4) hyperparathyroidism
* high P, high PTH
Patient with bilateral cataracts and basal ganglia calcs is consistent with chronic hypocalcemia.
PTH maintains Ca levels by triggering Ca reabsorption and phosphate excretion in the kidneys. PTH also promotes Ca release from bone and increases active vitamin D to stimulate intestinal absorption of Ca. Rising serum Ca inhibits PTH release.
Pseudohypoparathyroidism is end-organ resistance to PTH which leads to chronic hypocalcemia despite elevated PTH
True hypoparathyroidism is due to impaired production of PTH
Hypocalcemia causes neuromuscular excitability (tetany) which can manifest as seizures, muscle cramps, paresthesias, hyperreflexia, or laryngospasm. Cardiotoxicity (heart failure, long QT) and psychosis (anxiety, depression) can also occur.
Subtype of pseudohypopara is Albright hereditary osteodystrophy has dysmorphic features (short stature, round face, short 4/5 metacarpals)
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incidentally noted hypothyroidism before planned cardiac surgery
If urgent or emergent (CABG), just do the surgery
Do not load with levothyroxine bc that will lead to myocardial ischemia and worsen shit. Always start it slow in patients with heart disease.
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iodine induced hyperthyroidism
Predisposing conditions
* nodular thyroid disease
* chronic iodine deficiency
Clinical conditions
* symptom onset following iodine exposure (radiocontrast agents/angiography/amiodarone/ kelp based dietary supplements/topical antiseptics)
* no extrathyroidal manifestations of Graves
* suppressed TSH, negative thyrotropin receptor antibodies
* US - increased vascularity, possible nodules
Management
* Beta blockers for symptom control
* antithyroid meds for prolonged (1-2 months) hyperthyroidism, severe thyrotoxicosis, or older patients with cardiac disease
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Anion gap metabolic acidosis
Calculation is Na minus (Cl plus bicarb)
Normal is 10-14
MUDPILES
* methanol
* uremia
* DKA
* propylene glycol/paraldehyde
* isoniazid/iron
* lactic acidosis (metformin)
* ethylene glycol
* salicylates (aspirin)
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cardiovascular effects of thyrotoxicosis
Rhythm
* sinus tachy
* PACs and PVCs
* AFib/flutter
Hemodynamics
* systolic HTN and increased pulse pressure
* increased contractility and cardiac output
* reduced systemic vascular resistance
* increased myocardial oxygen demand
HF
* high output failure
* exacerbation of preexisting low output failure
Angina
* coronary vasospasm
* preexisting coronary atherosclerosis
In anyone with hyperthyroidism give BB to block adrenergic activity while patient is considered for next stage of therapy
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Primary ovarian insufficiency
Clinical
* amenorrhea at age less than 40
* hypoestrogenic symptoms (hot flashes, dryness)
* high FSH
* low estrogen
Major causes
* Turner Syndrome (45XO)
* Fragile X (FMR1 premutation)
* Autoimmune oophoritis
* Anticancer drugs
* Pelvic radiation
* Galactosemia
Management
* estrogen therapy (with progestin if intact uterus)
Patients with POI can rapidly lose bone mass leading to increased risk of fractures.
In absence of risk factors (history of breast cancer), most patients should receive oral or dermal estrogen therapy which should be combined with progestin in women with intact uterus to lower risk of endometrial cancer
Continue until average age of normal menopause (50).
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DKA in kids
Features
* polyuria/nocturia
* polydipsia, polyphagia
* vomiting, abdominal pain
* weight loss, fatigue
* Kussmaul respirations (deep, rapid breathing)
* dehydration
Labs
* glucose above 200
* bicarb less than 15
* pH less than 7.3
* anion gap of 14 or higher
* serum/urine ketones
Management
* 10 ml/kg isotonic fluid bolus over 1 hr
* insulin infusion with isotonic fluids with K
Complications
* cerebral edema
Note that severe DKA (pH less than 7.1, bicarb under 5, AMS) should all go to icu
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Thyroid lymphoma
Patient with esophageal symptoms (difficulty swallowing) with thyroid as source. You can tell this with Pemberton's test (patient raises arms above head for 60s - presence of facial plethora or neck vein engorgement is suggestive of enlarged thyroid)
Look for a patient with rapidly enlarging thyroid gland and hashimoto history
Elevated TSH, low T4 confirm hypothyroid. Positive anti-TPO confirms hashimoto.
Primary risk factor is hashimoto. It can cause enlarged gland but rapid enlargement is rare so that's bad. There is chronic lymphocytic infiltration of the thyroid in hashimoto.
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Insulin secretagogues
Sulfonylureas (Glyburide, glipizide, glimepiride) and meglitinides (nateglinide, repaglinide)
Increase insulin secretion by inibiting B-cell potassium ATP channels
Side effects
* hypoglycemia
* weight gain
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Biguanides
Metformin
Stimulate AMPK and inhibit mitochondrial gluconeogenesis, reduce hepatic glucose production and increase peripheral glucose uptake
Side effects
* diarrhea
* lactic acidosis
Metformin is especially useful in obese diabetic patients and helps with NASH. It lowers triglycerides, and raises HDL
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GLP1 agonists
Exenatide and Liraglutide
Increase glucose-dependent insulin secretion, lower glucagon secretion, delayed gastric emptying
Side effects
* pancreatitis
* weight loss
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DPP4 inhibitors
Sitagliptin and Saxagliptin
Increase endogenous GLP1 and GIP levels.
Side effects
* nasopharyngitis
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alpha glucosidase inhibitors
acarbose and migitol
reduce intestinal disaccharide absorption
Side effects
* diarrhea and flatulence
78
thiazolidinediones
Pioglitazone
Activate transcription regulator PPAR-y and lower insulin resistance
Side effects
* fluid retention/heart failure
* weight gain
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initial staging of thyroid cancer
Ultrasound of neck and cervical lymph nodes. Patients with small (less than 1cm) papillary thyroid tumor may be treated with thyroid lobectomy. Total thyroidectomy is for tumors 1cm and greater, tumor extension outside the thyroid, distant mets, and in patients with history of head or neck radiation exposure
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when is treatment of subclinical hypothyroidism warranted?
1. presence of antithyroid antibodies
2. abnormal lipid profile
3. symptoms of hypothyroidism
4. ovulatory and menstrual dysfunction
5. goiter
6. pregnancy
7. tsh above 10
81
postpartum management of GDM
Remember during the actual pregnancy management was diet (first line) followed by insulin, glyburide, metformin
Now we do a fasting glucose at 24-72h postpartum. And a 2h 75g glucose tolerance test at 6-12 week visit.
Patients do not require postpartum treatment but we need to check for pre-existing actual diabetes. Patients with GDM should be screened every 3 years as they are at increased risk for T2DM
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Major drug interactions of levothyroxine
1) Lower levothyroxine absorption
* bile acid binding agents (cholestyramine)
* iron, calcium, aluminium hydroxide
* PPIs, sucralfate
2) increased thyroxine binding globulin
* estrogen replacement, OCPs
* tamoxifen
3) lower TBG
* androgens, glucocorticoids
* anabolic steroids
4) increased thyroid hormone metabolism
* Rifampin
* Phenytoin
* Carbamazepine
Synthroid has a narrow therapeutic index. To ensure best results, take on empty stomach with water at least 30-60 mins before breakfast. Take any problem meds separately by like 3-4 hrs.
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Nelson's Syndrome
Pituitary enlargement and hyperpigmentation following bilateral adrenalectomy for Cushing's disease
Cause of pituitary enlargement is loss of feedback by the adrenal glucocorticoids following bilateral adrenalectomy,
The tumor in Nelson's is aggressive and is treated by surgery and/or pituitary radiation.
Following bilateral adrenalectomy, prophylactic pituitary radiation sometimes prevents the development of Nelson's. However, this leads to increased risk of hypopituitarism.
Previously, bilateral adrenalectomy was treatment for Cushing's, but now we have better stuff so transsphenoidal/primary pituitary surgery is the preferred treatment for Cushing's disease.
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Androgen insensitivity syndrome
Disorder of sexual development characterized by phenotypical female features with a male (46XY) karyotype. X linked recessive. Caused by mutation of androgen receptor gene which makes peripheral tissues unresponsive to androgens despite normal concentrations produced by intact testes.
Patients often present in adolescence with primary amenorrhea, defined as absence of menarche by age 15 if breast development is present or by 13 if not.
Breast development is typically normal in this disorder bc excess testosterone is aromatized to estrogen. However, no pubic or axillary hair is present. Cryptorchid testes often reside in the inguinal canal or abdomen, as testicular descent is an androgen-dependent process.
Uterus and fallopian tubes are absent. Vagina ends in blind pouch.
Diagnostic workup includes pelvic ultrasound, karyotype, and testosterone level. Serum testosterone level in the normal adult male range is characteristic.
85
Evaluating primary amenorrhea
Pelvic exam or ultrasound
1) uterus present
* serum FSH
* high - karyotyping
* low - cranial MRI
2) Uterus absent
* karyotype and serum testosterone
* 46XX with normal female testosterone levels
* abnormal mullerian development
* 46XY with normal male testosterone levels
* androgen insensitivity syndrome
86
exercise induced amenorrhea
Due to decrease in pulsatile secretion of LH which leads to decline in estrogen production. It can lead to osteopenia, osteoporosis, breast and vaginal atrophy and mild hypercholesterolemia. Also infertility.
Treatment consists of improving caloric intake. If not possible, start on hormonal replacement with oral contraceptives and supplement with calcium and vitamin D
87
workup of hypercalcemia
1) Confirm hypercalcemia
* repeat testing
* correct for albumin (measured Ca + 0.8[4-albumin]) or measure ionized calcium
2) measure PTH
* High normal or elevated (PTH dependent)
* primary (or tertiary) hyperparathyroidism
* familial hypocalciuric hypercalcemia
* lithium
* suppressed (PTH independent)
* measure PTHrP, 25 hydroxyD, 1-25 dihydroxyD
* malignancy
* vit D toxicity
* granulomatous diseases (sarcoid, TB)
* drug induced (thiazides)
* milk alkali syndrome
* thyrotoxicosis
* vit A toxicity
* immobilization (esp in patients with Paget or teens since they already have high bone turnover at baseline)
88
Evaluation of hypoglycemia
1) Exogenous insulin
* normal/increased serum insulin
* low c peptide
* negative hypoglycemic drug assay
2) oral hypoglycemic agents
* normal/increased serum insulin
* normal/elevated c peptide
* positive drug assay
3) insulinoma
* normal/increased serum insulin
* normal/elevated c peptide
* negative drug assay
Whipples triad must be fulfilled prior to workup. Symptomatic hypoglycemia that improves following glucose
Low blood glucose in normal individuals will suppress production of insulin, C peptide and proinsulin. In the presence of significant hypoglycemia, normal levels of these hormones indicate an abnormal response
Fingerstick glucose measurement is unreliable in hypoglycemic ranges. Low blood glucose recorded by a bedside glucometer must be confirmed with a standard lab assay
blood samples for biochemical testing must be taken when the patient is hypoglycemic and before glucose administration.
C peptide is a byproduct of endogenous insulin secretion. Normal or elevated C peptide confirm ongoing insulin production. Surreptitious insulin injection elevates plasma insulin but C peptide remains low.
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screening tests for DM
1) A1c
* preferred test in nonfasting state
* 6.5 and up is DM
* 5.7 - 6.4 is increased risk
* less than 5.7 is normal
2) Fasting blood glucose
* no caloric intake for at least 8hrs
* 126 and up is DM
* 100-125 is increased risk
* less than 100 is normal
3) random glucose levels
* 200 and up with symptoms of hyperglycemia is DM
* 140-199 is increased risk
* less than 140 is normal
4) oral glucose tolerance
* most sensitive test
* 75g glucose load with glucose testing for 2hrs
* over 200 is DM
* 140-199 is increased risk
* less than 140 is normal
If patient is asymptomatic, confirm results with same test on different day
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Primary hyperparathyroidism
Etiology
* Parathyroid adeoma (most common), hyperplasia or carcinoma
* increased risk in MEN1 and MEN2A
Symptoms
* asymptomatic (most common)
* mild, nonspecific symptoms (fatigue, constipation)
* abdominal pain, renal stones, bone pain, neuropsych symptoms
Diagnostic findings
* hypercalcemia
* elevated or inappropriately normal PTH
* elevated 24h urinary calcium excretion
Indications for parathyroidectomy
* Age less than 50
* symptomatic hypercalcemia
* complications
* osteoporosis (T less than -2.5 or easy fracture)
* CKD (GFR less than 60)
* kidney stone
* elevated risk of complications
* calcium more than 1 mg above normal
* urinary calcium excretion over 400
