Endocrinology Flashcards
When should you screen for T2DM?
Age 45, screen ever 3 yrs or earlier in high risk groups
What is a sensitive indicator of thyroid function, it is generally recommended as a first-line test for thyroid disorders.
TSH
weight of pituitary gland
~600g
Blood supply of the posterior pituitary
The posterior pituitary is supplied by the inferior hypophyseal arteries
In contrast to the anterior pituitary, the posterior lobe is directly innervated by hypothalamic neurons (supraopticohypophyseal and tuberohypophyseal nerve tracts) via the pituitary stalk
Lactotropes constitute __% of anterior pituitary cells
20
Peak serum PRL levels (up to 30 μg/L) occur between ____ a.m.
4:00 and 6:00
What makes prolactin unique among the pituitary hormones?
PRL is unique among the pituitary hormones in that the predominant hypothalamic control mechanism is inhibitory, reflecting tonic dopamine-mediated suppression of PRL release.
In what instances does serum prolactin rise?
after exercise, meals, sexual intercourse, minor surgical procedures, general anesthesia, chest wall injury, acute myocardial infarction, and other forms of acute stress
Also increases (10 fold) during pregnancy then declines rapidly within 2 weeks of parturition
What is the function of prolactin?
PRL acts to induce and maintain lactation and to suppress both reproductive function and sexual drive.
PRL inhibits reproductive function by suppressing hypothalamic (GnRH) and pituitary gonadotropin secretion and by impairing gonadal steroidogenesis in both women and men.
In the ovary, PRL blocks folliculogenesis and inhibits granulosa cell aromatase activity, leading to hypoestrogenism and anovulation.
PRL also has a luteolytic effect, generating a
shortened, or inadequate, luteal phase of the menstrual cycle. In men, attenuated LH secretion leads to low testosterone levels and decreased spermatogenesis.
These hormonal changes decrease libido and reduce fertility in patients with hyperprolactinemia.
Most abundant anterior pituitary hormone
Growth hormone
Somatotrope -50%
How does ghrelin affect GH?
Induces GHRH and GH release
Peripheral target for GH
IGF-1
Peak levels of GH secretion occurs when?
GH secretion is pulsatile, with highest peak levels occurring at night, generally correlating with sleep onset.
In what instances does GH secretion increase?
Elevated GH levels occur within an hour of deep sleep onset as well as after exercise, physical stress, and trauma and during sepsis.
What stimulates GH release?
GH is stimulated by oral ghrelin receptor agonists, intravenous l-arginine, dopamine, and apomorphine (a dopamine receptor agonist), as well as by α-adrenergic pathways.
β-Adrenergic blockade induces basal GH and enhances GHRH- and insulin-evoked GH release.
On the other hand, glucose decreases GH secretion
Which organs express the highest amount of GH receptors?
The liver and cartilage express the greatest
number of GH receptors.
Organ that is the major source of IGF-1
Liver
What is the effect of IGF-1 on glucose levels
induces hypoglycemia and improves insulin sensitivity
Peak time of ACTH secretion
ACTH secretion is pulsatile and exhibits a
characteristic circadian rhythm, peaking at about 6:00 a.m. and reaching a nadir about midnight
What peptide regulates GnRH release?
Brain kisspeptin, a product of the KISS1 gene, regulates hypothalamic GnRH release
syndrome that results from defective hypothalamic (GnRH) synthesis and is associated with anosmia or hyposmia due to olfactory bulb agenesis or hypoplasia
Kallman syndrome
Classically, the syndrome may also be associated with color blindness, optic atrophy, nerve deafness, cleft palate, renal abnormalities, cryptorchidism, and neurologic abnormalities such as mirror movements
Syndrome characterized by intellectual disability, renal abnormalities, obesity, and hexadactyly, brachydactyly, or syndactyly
Bardet-Biedl Syndrome
Retinal degeneration begins in early childhood, and most patients are blind by age 30.
Syndrome associated with hypogonadotropic hypogonadism, hyperphagia-obesity, chronic muscle hypotonia, mental retardation, and adult-onset diabetes mellitus
Prader Willi
Hormone that is more likely to be affected by cranial irradiation
GH
GH deficiency is most common, followed by gonadotropin, thyroid, and ACTH deficiency
The development of hypopituitarism occurs over 5–15 years and usually reflects hypothalamic damage rather than primary destruction of pituitary cells.
Lymphocytic hypophysitis occur most commonly in which subset of the population
post partum women
Most patients manifest symptoms of progressive mass effects with headache and visual disturbance.
The ESR often is elevated. Because it may be indistinguishable from a pituitary adenoma on MRI, hypophysitis should be considered in a postpartum woman with a newly diagnosed pituitary mass before an unnecessary surgical intervention is undertaken.
Syndrome that occurs during post partum and presents with acute intrapituitary hemorrhagic vascular events can cause substantial damage to the pituitary and surrounding sellar structures.
Sheehan’s syndrome
ACTH reserve is most reliably assessed by measuring
ACTH and cortisol levels during insulin-induced hypoglycemia
Administering insulin to induce hypoglycemia is contraindicated in patients with active coronary artery disease or known seizure disorders
Syndrome with Homozygous or heterozygous mutations of the GH receptor are associated with partial or complete GH insensitivity and growth failure
(Laron syndrome)
Short stature should be evaluated comprehensively if a patient’s height is > __ standard deviations below the mean for age or if the growth rate has decelerated
3
Sequence of hormone loss in pituitary deficiency
The sequential order of hormone loss is usually GH → FSH/LH → TSH → ACTH.
The most validated test to distinguish pituitary-sufficient patients from those with AGHD is
insulin-induced (0.05–0.1 U/kg) hypoglycemia
Expected response of AGHD after insulin induced hypoglycemia
About 90% of healthy adults exhibit GH responses >5 μg/L; AGHD is defined by a peak GH response to hypoglycemia of <3 μg/L.
Contraindicated in patients with diabetes, ischemic heart disease, cerebrovascular disease, or epilepsy and in elderly patients.
Alternative stimulatory tests include intravenous arginine (30 g), GHRH (1 μg/kg), oral ghrelin receptor agonist (0.5 mg/kg), and glucagon (1 mg).
Contraindications to GH therapy
Contraindications to therapy include the presence of an active neoplasm, intracranial hypertension, and uncontrolled diabetes and retinopathy
Women require higher doses than men, and elderly patients require less GH.
Type of cholesterol increased by GH administration
HDL
In ACTH deficiency, The total daily dose of hydrocortisone replacement preferably should generally not exceed ___ mg daily, divided
into two or three doses.
20
most common presenting feature of adult hypopituitarism even when other pituitary hormones are also deficient.
Hypogonadism
Screening test for
Acromegaly?
Prolactinoma?
See table
Screening test for Cushing’s dse
See table
Screening test for Gonadotropinoma
See table
Screening test for TSH-producing adenoma
See table
Transsphenoidal resection is the desired surgical approach for pituitary tumors, except for
rare invasive suprasellar mass surrounding the frontal or middle fossa or the optic nerves or invading posteriorly behind the clivus, which may require transcranial approaches.
Treatment of choice for prolactinoma
Dopamine agonists
Treatment for acromegaly
For acromegaly, somatostatin receptor ligands
(SRLs) and a GH receptor antagonist are indicated.
______ are benign, suprasellar cystic masses that present with headaches, visual field deficits, and variable degrees of hypopituitarism. They are derived from Rathke’s pouch and arise near the pituitary stalk, commonly extending into the suprasellar cistern.
Craniopharyngiomas
Hypopituitarism is documented in ~90%, and diabetes insipidus occurs in ~10% of patients.
Treatment for craniopharyngioma
Treatment usually involves transcranial or transsphenoidal surgical resection followed by postoperative radiation of residual tumor.
the most common cause of pituitary hormone hypersecretion and hyposecretion syndromes in adults.
Pituitary adenomas
Syndrome associated with Pituitary hyperplasia and adenomas (10%), Atrial myxomas, Schwannomas, Adrenal hyperplasia, Lentigines
Carney Complex
autosomal dominant syndrome characterized primarily by a genetic predisposition to parathyroid, pancreatic islet, and pituitary adenomas
MEN 1
syndrome that consists of polyostotic fibrous dysplasia, pigmented skin patches, and a variety of endocrine disorders, including acromegaly, adrenal adenomas, and autonomous ovarian function
McCune Albright
most common pituitary hormone hypersecretion syndrome in both men and women
Hyperprolactinemia
Effect of chronic renal failure on prolactin levels
Elevates by decreasing clearance
the hallmarks of hyperprolactinemia in women.
Amenorrhea, galactorrhea, and infertility
When is galactorrhea suspected in patients who just gave birth?
the inappropriate discharge of milk-containing fluid from the breast, is considered abnormal if it persists longer than6 months after childbirth or discontinuation of breast-feeding.
In patients with markedly elevated PRL levels (____ μg/L), reported results may be falsely lowered because of assay artifacts;
> 1000
Macroadenomas are >___ in diameter and may be locally invasive and impinge on adjacent structures.
1 cm
Tumor size generally correlates directly with PRL concentrations; values >250 μg/L usually are associated with macroadenomas.
The drug Cabergoline effectively suppresses PRL for >___days after a single oral dose and induces prolactinoma shrinkage in most patients.
14
Preferred dopamine agonists in pregnant patients
Bromocriptine
B for buntis
What level of prolactin should you consider surgery in microadenoma
> 50 ug/L
When should you repeat MRI after starting patient with macroadenoma on dopamine agonist?
4 months
The most significant clinical impact of GH excess occurs with respect to the ____ system
cardiovascular
Confirmatory test for acromegaly
The diagnosis of acromegaly is confirmed by demonstrating the failure of GH suppression to <0.4 μg/L within 1–2 h of an oral glucose load (75 g)
Initial tx for acromegaly
Surgical resection of GH-secreting adenomas is the initial treatment for most patients
Transsphenoidal surgical resection by an experienced surgeon is the preferred primary treatment for both microadenomas (remission
rate ~70%) and macroadenomas (<50% in remission).
Drug that antagonizes endogenous GH action by blocking peripheral GH binding to its receptor. Consequently, serum IGF-1 levels are suppressed, reducing the deleterious effects of
excess endogenous GH.
Pegvisomant
Next step after surgery of acromegaly
Serotonin receptor ligands eg. octreotide, lanreotide, pasireotide
Account for 70% of patients with endogenous causes of Cushing’s syndrome.
Pituitary corticotrope adenomas (Cushing’s
disease)
most common cause of cushingoid features
iatrogenic hypercortisolism
Primary cause of death in Cushing’s syndrome
Cardiovascular
Most common clinical feature of Cushing syndrome
Obesity and Thick skin
Screening test for Cushing syndrome
24hr urinary free cortisol
Alternatively, overnight 1mg dexa test
how do you differentiate ACTH secreting tumor vs ectopic ACTH secretion
see table
Treatment of choice for cushing disease
Selective transphenoidal resection
The remission rate for this procedure
is ~80% for microadenomas but <50% for macroadenomas
What is the effect of pasireotide on sugar levels
Notably, hyperglycemia and new-onset diabetes develop in up to 70% of patients, likely due to suppressed pancreatic secretion of insulin and incretins.
What is an oral 11β-hydroxylase inhibitor used for Cushing dse that blocks adrenal gland cortisol biosynthesis, normalizes 24-h UFC in 86% of patients.
Osilodrostat (2 mg twice daily titrated up to 30 mg twice daily)
Elevated adrenal hormone precursors may lead
to hypokalemia and hypertension.
QTc prolongation and possibly
increased tumor volume are also reported.
What is a drug used in Cushing syndrome that is a glucocorticoid receptor antagonist, blocks peripheral cortisol action and is approved to treat hyperglycemia in Cushing’s disease?
Mifepristone (300–1200 mg/d)
Because the drug does not target the pituitary tumor, both ACTH and cortisol levels remain elevated, thus obviating a reliable circulating biomarker.
Side effects are largely due to general antagonism of other steroid hormones and include hypokalemia, endometrial hyperplasia, hypoadrenalism, and hypertension.
Drug that inhibits 11β-hydroxylase activity and normalizes plasma cortisol in up to 75% of patients with Cushing syndrome
Metyrapone (2–4 g/d)
Adrenalectomy in the setting of residual corticotrope adenoma tissue predisposes to the development of _____ syndrome, a disorder characterized by rapid pituitary tumor enlargement and increased pigmentation secondary to high ACTH levels.
Nelson’s
most common type of pituitary adenoma and are usually macroadenomas at the time of diagnosis
non functioning pituitary adenoma
If PRL levels are <100 μg/L in a patient harboring a pituitary mass, what should be considered?
a nonfunctioning adenoma causing pituitary stalk compression should be considered
Sources of ectopic ACTH secretion
Bronchial, abdominal carcinoid
Small-cell lung cancer
Thymoma
critical first step in thyroid hormone synthesis.
Iodide uptake
Mutation of the _____ gene causes Pendred syndrome, a disorder characterized by defective organification of iodine, goiter, and sensorineural deafness.
pendrin gene
The Recommended Dietary Allowance (RDA) is
___ μg iodine per day for pregnant women and ____ μg iodine per dayfor breastfeeding women
220, 290
Urinary iodine is > ___ in iodine-sufficient populations.
100 μg/L
Excess iodide transiently inhibits thyroid iodide organification, a phenomenon known as the ____
Wolff-Chaikoff effect
Five factors alter thyroid function in pregnancy
(1) the transient increase in hCG during the first trimester, which weakly stimulates the TSH-R
(2) the estrogen-induced rise in TBG during the first trimester, which is sustained during pregnancy
(3) alterations in the immune system, leading to the onset, exacerbation, or amelioration of an underlying autoimmune thyroid disease
(4) increased thyroid hormone metabolism by the placental type III deiodinase; and
(5) increased urinary iodide excretion, which can cause impaired thyroid hormone production in areas of marginal iodine sufficiency.
Women with a precarious iodine intake (<___) are most at risk of developing a goiter during pregnancy or giving birth to an infant with a goiter and hypothyroidism.
50 μg/d
Thyroid hormone requirements are increased by up to __% during pregnancy in levothyroxine-treated hypothyroid women.
45
What are the differentiating factors of t3 vs t4
see table
Medications that decrease conversion of T4 to T3
propranolol, ipodate, iopanoic acid,
amiodarone
Expected TFT in thyroid hormone resistance
Increased unbound T4, T3
Normal or increased TSH
Individuals with RTH do not, in general, exhibit signs and symptoms that are typical of hypothyroidism because hormone resistance is partial and is compensated by increased levels of thyroid hormone.
Large retrosternal goiters can cause venous distention over the neck and difficulty breathing,
especially when the arms are raised _____
(Pemberton’s sign)
What is the effect of biotin supplement on TSH levels
falsely low
What is the effect of androgens and nephrotic syndrome on TBG
dec
Serum Tg levels are increased in all types of thyrotoxicosis except
thyrotoxicosis factitia
Sonographic findings that are highly suggestive of thyroid malignancy
Sonographic patterns that combine suspicious sonographic features are highly suggestive of malignancy (e.g., hypoechoic solid nodules with infiltrative borders and microcalcifications, >90% cancer risk)
Sonographic findings that are highly suggestive of benign pattern of thyroid mass
(isoechoic solid nodules, 5–10% cancer risk).
Some patterns suggest benignity (e.g., spongiform nodules, defined as those with multiple small internal cystic areas, or simple cysts, <3% cancer risk)
Starting dose for LT4 for congenital hypothyroidism
When the diagnosis is confirmed, T4
is instituted at a dose of 10–15 μg/kg per d,
Most common symptom and sign of hypothyroidism
symptom: tiredness, weakness
sign: dry coarse skin, weak peripheral pulses
Next step when TSH is high but FT4 is normal
Request for TPO antibodies
if symptomatic, consider LT4 tx
if symptomatic, annual ff up
Dose of LT4 for clinical hypothyroidism
If there is no residual thyroid function, the daily replacement dose of LT4 is usually 1.6 μg/kg body weight (typically 100–150 μg), ideally taken at least 30 min before breakfast.
when does symptoms of hypothyroidism resolve after treatment with LT4
Patients may not experience full relief from symptoms until 3–6 months after normal TSH levels are restored
In patients of normal body weight who are taking ≥ ____ of LT4 per d, an elevated TSH level is often a sign of poor adherence to treatment.
200 μg
What should be done if you missed 1 dose of LT4?
Because T4 has a long half-life (7 days), patients who miss a dose can be advised to take two doses of the skipped tablets at once
When should subclinical hypothyroidism be treated
There are no universally accepted recommendations for the management of subclinical hypothyroidism, but LT4 is recommended if the patient is a woman who wishes to conceive or is pregnant or when TSH levels are >10 mIU/L.
Target TSH in pregnant women
Because of the known increase in thyroid hormone requirements during pregnancy in hypothyroid women, LT4 therapy should be targeted to maintain a serum TSH in the normal range but <2.5 mIU/L prior to conception
When should be TSH be checked during pregnancy?
thyroid function should be evaluated immediately after pregnancy is confirmed and every 4 weeks during the first half of the pregnancy, with less frequent testing after 20 weeks’ gestation (every 6–8 weeks depending on whether LT4 dose adjustment is ongoing).
Elderly patients may require ___% LESS thyroxine than younger patients
20
In the elderly, especially patients with known coronary artery disease, the starting dose of LT4 is 12.5–25 μg/d with similar increments every 2–3 months until TSH is normalized
How do you treat myxedema coma?
LT4 can initially be administered as a single IV bolus of 200–400 μg, which serves as a loading dose, followed by a daily oral dose of 1.6 μg/kg per d, reduced by 25% if administered IV
Because T4 → T3 conversion is impaired in myxedema coma, there is a rationale for adding liothyronine (T3 ) intravenously or via nasogastric tube to LT4 treatment, although excess liothyronine has the potential to provoke arrhythmias. An initial loading dose of 5–20 μg liothyronine should be followed by 2.5–10 μg every 8 h, with lower doses chosen for smaller or older patients and those at cardiovascular risk
Parenteral hydrocortisone (50 mg every 6 h) should be administered because there is impaired adrenal reserve in profound hypothyroidism
Most common cause of thyrotoxicosis
Graves’ disease accounts for 60–80% of thyrotoxicosis
_____ is a minor risk factor for Graves’ disease and a major risk factor for the development of ophthalmopathy
Smoking
Most common symptom and sign of hyperthyroidism
symptom: hyperactivity, irritability, dysphoria
sign: tachycardia, AF in elderly
Most common cardiovascular manifestation of Graves
The most common cardiovascular manifestation is sinus tachycardia, often associated with palpitations, occasionally caused by supraventricular tachycardia
Where should you auscultate for thrill/bruit of thyroid in Grave’s dse
There may be a thrill or bruit, best detected at the inferolateral margins of the thyroid lobes, due to the increased vascularity of the gland and the hyperdynamic circulation
Earliest manifestation of Grave’s ophthalmopathy
The earliest manifestations of ophthalmopathy are usually a sensation of grittiness, eye discomfort, and excess tearing
_____ refers to a form of clubbing found in <1% of patients with Graves’ disease
Thyroid acropachy
What is the site involved in thyroid dermopathy?
Thyroid dermopathy occurs in <5% of patients with Graves’ disease , almost always in the presence of moderate or severe ophthalmopathy. Although most frequent over the anterior and lateral aspects of the lower leg (hence the term pretibial myxedema), skin changes can occur at other sites, particularly after trauma.
The typical lesion is a noninflamed, indurated plaque with a deep pink or purple color and an “orange skin” appearance
What should you suspect if TFTs revealed TSH normal or increased, high unbound T4
TSH-secreting pituitary adenoma or thyroid hormone resistance syndrome
Next step when TSH is low but FT4 is normal
measure unbound t3
When should you schedule ff up for subclinical hyperthyroidism
6-12 weeks
Clinical course of Grave’s ophthalmopathy
The clinical course of ophthalmopathy does not follow that of the thyroid disease, although thyroid dysfunction can worsen eye signs. Ophthalmopathy typically worsens over the initial 3–6 months, followed by a plateau phase over the next 12–18 months, and then some spontaneous improvement, particularly in the soft tissue changes
When should you follow up patients with hyperthyroidism after starting treatment
Thyroid function tests and clinical manifestations are reviewed 4–6 weeks after starting treatment, and the dose is titrated based on unbound T4 levels.
Most patients do not achieve euthyroidism until 6–8 weeks after treatment is initiated
When should methimazole be stopped prior to RAI and when can it be restarted?
Carbimazole or methimazole must be stopped 2–3 days before radioiodine administration to achieve optimum iodine uptake and can be restarted 3–7 days after radioiodine in those at risk of complications from worsening thyrotoxicosis
% risk of hypothyroidism after RAI
The risk of hypothyroidism after radioiodine depends on the dosage but is at 10–20% in the first year and 5% per year thereafter.
How long shoud you avoid close prolonged contact with children and women after RAI
In general, patients need to avoid close, prolonged contact with children and pregnant women for 5–7 days because of possible transmission of residual isotope and exposure to radiation emanating from the gland
What precautions should be done to avoid thyrotoxic crisis prior to thyroidectomy
Careful control of thyrotoxicosis with antithyroid drugs, followed by potassium iodide (SSKI; 1–2 drops orally tid for 10 days), is needed prior to surgery to avoid thyrotoxic crisis and to reduce the vascularity of the gland
Birth defect associated with methimazole
Aplasia cutis
PTU should be used until 14-16 weeks
However, because of its rare association with hepatotoxicity, propylthiouracil should be limited to the first trimester and then maternal therapy should be converted to methimazole (or carbimazole) at a ratio of 15–20 mg of propylthiouracil to 1 mg of methimazole
How do you manage thyroid storm
Large doses of propylthiouracil (500–1000 mg loading dose and 250 mg every 4 h) should be given orally or by nasogastric tube or per rectum; the drug’s inhibitory action on T4 → T3 conversion makes it the antithyroid drug of choice.
If not available, methimazole can be used in doses of 20 mg every 6 h.
One hour after the first dose of propylthiouracil, stable iodide (5 drops SSKI every 6 h) is given to block thyroid hormone synthesis via the Wolff-Chaikoff effect (the delay allows the antithyroid drug to prevent the excess iodine from being incorporated into new hormone).
Propranolol should also be given to reduce tachycardia and other adrenergic manifestations (60–80 mg PO every 4 h, or 2 mg IV every 4 h).
Treatment for severe Grave’s ophthalmopathy
Pulse therapy with IV methylprednisolone (e.g., 500 mg of methylprednisolone once weekly for 6 weeks, then 250 mg once weekly for 6 weeks) is preferable to oral glucocorticoids, which are used for moderately active disease
In children and young adults, the most common cause of acute thyroiditis
presence of a piriform sinus
usually due to a bacterial infection
Other name for subacute thyroiditis
de Quervain’s thyroiditis, granulomatous thyroiditis, or viral thyroiditis
The patient usually presents with a painful and enlarged thyroid, sometimes accompanied by fever
treatment for subacute thyroiditis
Relatively large doses of aspirin (e.g., 600 mg every 4–6 h) or nonsteroidal anti-inflammatory drugs (NSAIDs) are sufficient to control symptoms in many cases.
If this treatment is inadequate, or if the patient has marked local or systemic symptoms, glucocorticoids should be given. The usual starting dose is 15–40 mg of prednisone, depending on severity. The dose is gradually tapered over 6–8 weeks, in response to improvement in symptoms and the ESR
What subset of population is silent thyroiditis associated?
Painless thyroiditis, or “silent” thyroiditis, occurs in patients with underlying autoimmune thyroid disease and has a clinical course similar to that of subacute thyroiditis. The condition occurs in up to 5% of women 3–6 months after pregnancy and is then termed postpartum thyroiditis
Treatment for silent thyroiditis
Glucocorticoid treatment is not indicated for silent thyroiditis. Severe thyrotoxic symptoms can be managed with a brief course of propranolol, 20–40 mg three or four times daily. Thyroxine replacement may be needed for the hypothyroid phase but should be withdrawn after 6–9 months, as recovery is the rule
The most common clinically apparent cause of chronic thyroiditis is ___________ , an autoimmune disorder that often presents as a firm or hard goiter of variable size
Hashimoto’s thyroiditis
The most common hormone pattern in sick euthyroid syndrome (SES), also called nonthyroidal illness (NTI), is
a decrease in total and unbound T3 levels (low T3 syndrome) with normal levels of T4 and TSH.
TFT abnormalities in the ff
Acute liver disease?
Acutely ill psyciatric patients?
HIV infection?
Renal disease?
Acute liver disease is associated with an initial rise in total (but not unbound) T3 and T4 levels due to TBG release
. A transient increase in total and unbound T4 levels, usually with a normal T3 level, is seen in 5–30% of acutely ill psychiatric patients. TSH values may be transiently low, normal, or high in these patients.
In the early stage of HIV infection, T3 and T4 levels rise, even if there is weight loss. T3 levels fall with progression to AIDS, but TSH usually remains normal.
Renal disease is often accompanied by low T3 concentrations, but with normal rather than increased rT3 levels, due to an unknown factor that increases uptake of rT3 into the liver
Moreover, because amiodarone is stored in adipose tissue, high iodine levels persist for >___ months after discontinuation of the drug
6
Most effective long term solution for amiodarone induced thyroiditis
thyroidectomy
T/F
Thyroid function tests should be performed in all patients with goiter
True
to exclude thyrotoxicosis or hypothyroidism
Low urinary iodine levels (____) support a diagnosis of iodine deficiency
<50 μg/L
What are the UTZ findings suggestive of malignant thyroid mass in terms of composition, echogenicity, shape, margin and echogenic foci
In patients with thyroid mass, Tracheal deviation is common, but compression must usually exceed ___ % of the tracheal diameter before there is significant airway compromise
70
In hyperfunctioning solitary nodule, Thyrotoxicosis is usually mild and is generally only detected when a nodule is >____
3 cm
Tx of choice for hyperfunctioning solitary nodule
RAI
the most common malignancy of the endocrine
system
Thyroid carcinoma
Risk Factors for Thyroid Carcinoma in Patients with Thyroid Nodule from History and Physical Examination
Activation of the _____ signaling pathway is seen in up to 70% of PTCs, although the types of mutations are heterogeneous
RET-RAS-BRAF
Most common type of thyroid CA
PTCA
T/F
Micrometastases is associated with poorer prognosis in PTCA
F
Micrometastases, defined as <2 mm of cancer in a lymph node, do not affect prognosis
However, gross metastatic involvement of multiple 2- to 3-cm lymph nodes indicates a 25–30% chance of recurrence and may increase mortality in older patients
Therefore, near-total thyroidectomy is appropriate for tumors >___ or in the presence of metastases or clinical evidence of extrathyroidal invasion.
4 cm
Mainstay of thyroid CA tx
Because most tumors are still TSH-responsive, LT4 suppression of TSH is a mainstay of thyroid cancer treatment
Target TSH for PTCA with the ff risk
Low risk?
Intermediate ?
High?
Known mets?
low risk = 0.5–2.0 mIU/L
Intermediate = 0.1–0.5 mIU/L
high risk of recurrence and known mets <0.1 mIU/L
Ideal TSH level before RAI for well differentiated thyroid CA
> 25 mIU/L
sensitive marker of residual/recurrent thyroid cancer after ablation of the residual postsurgical thyroid tissue
Serum thyroglobulin
Prognosis of anaplastic thyroid CA
The prognosis is poor, and most patients die within 6 months of diagnosis
Most common type of lymphoma of the thyroid
DLBCL
highly sensitive to external radiation
Surgery should be avoided (may spread dse)
which type of MEN has more aggresive form of MTC
MEN2B>2A
Next step if FNAB showed follicular neoplasm
consider molecular testing
25–40% risk of malignancy
Next step if FNAB showed Atypia or follicular lesion of undetermined significance
Repeat or consider molecular testing
~10–30% risk of malignancy
In dibetes insipidus, The 24-h urine volume exceeds __mL/kg body weight, and the 24-h urine osmolarity is < ___ mosm/L
The 24-h urine volume exceeds 40 mL/
kg body weight, and the 24-h urine osmolarity is <280 mosm/L
If symptoms of urinary frequency, enuresis, nocturia, and/or persistent thirst are present in the absence of glucosuria, the possibility of DI should be evaluated by
collecting a 24-h urine on unrestricted fluid intake
If the osmolarity is <280 mosm/L and the volume >50 mL/kg per day, the patient has DI and should be evaluated further to determine the type.
Next step in evaluating for DI after 24 hr urine volume and osmolarity
Get the basal plasma AVP
How do you differentiate primary polydipsia from pituitary DI
Pituitary bright spot is present in primary polydipsia since it reflects AVP stores
When treating DI with desmoperessin, Hyponatremia rarely develops unless urine volume is reduced to < ____ per day or fluid intake is excessive due to an associated abnormality in thirst or cognition
10 mL/kg
Treatment for hypodipsic hyponatremia
administering water orally if the patient is alert and cooperative or by infusing hypotonic fluids (0.45% saline or 5% dextrose and water) if the patient is not
Most common form of SIADH
The most common is one in which the AVP secretion responds normally to osmotic stimulation and suppression but the threshold or set point of the system is lower than normal
In SIADH, the excess body water should be eliminated. If the hyponatremia is mild and largely asymptomatic, restricting total water intake to ~_______ less than urine output for several days or until the syndrome remits spontaneously will usually suffice
30 mL/kg per day
Alternative treatment for SIADH if water restriction does not suffice
Infusion of 3% saline at a rate of ~0.05 mL/kg body weight per min raises serum sodium at a rate of ~1–2 meq/L per h, not only by replacing the slight sodium deficit but also by promoting a solute diuresis, which reduces total body water.
Alternatively, a vaptan can be used to reduce body water by increasing urine output.
Glucocorticoid excess is diagnosed by employing
dexamethasone suppression test.
How do you assess glucorticoid deficiency
to assess glucocorticoid deficiency, ACTH stimulation of cortisol production is used
How is ACTH stimulation done?
The standard ACTH stimulation test involves administration of cosyntropin (ACTH 1-24), 0.25 mg IM or IV, and collection of blood samples at 0, 30, and 60 min for cortisol.
A normal response is defined as a cortisol level >15–20 μg/dL (>400–550 nmol/L) 30–60 min after cosyntropin stimulation, with the precise cutoff dependent on the assay used
How is insulin tolerance test done?
The ITT involves administration of regular insulin 0.1 U/kg IV (dose should be lower if hypopituitarism is likely) and collection of blood samples at 0, 30, 60, and 120 min for glucose, cortisol, and growth hormone (GH), if also assessing the GH axis.
Oral or IV glucose is administered after the patient has achieved symptomatic hypoglycemia (usually plasma glucose <40 mg/dL).
A normal response is defined as a cortisol >20 μg/dL and GH >5.1 μg/L, again with assay-specific cutoff variability.
Cortisol is inactivated to cortisone by this microsomal enzyme
11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)
Cortisol and aldosterone bind the mineralocorticoid receptor (MR) with equal affinity; however, cortisol circulates in the bloodstream at about a 1000-fold higher concentration.
Thus, only rapid inactivation of cortisol to cortisone by 11β-HSD2 prevents MR activation by excess cortisol, thereby acting as a tissue-specific modulator of the MR pathway
Ectopic ACTH production is predominantly caused by occult carcinoid tumors, most frequently in the ___
lung, but also in thymus or pancreas.
Screening tests for Cushings syndrome
Next step after having positive screening test for Cushing syndrome
Get ACTH level
Cutoff ACTH value for distinguishing ACTH dependent from independent Cushing
Next step after confirming ACTH INdependent Cushings
CT of the adrenals
Next step after confirming ACTH dependent Cushings
For ACTH-dependent cortisol excess, ______ is the investigation of choice
magnetic resonance image (MRI) of the pituitary
but it may not show an abnormality in up to 40% of cases because of small tumors below the sensitivity of detection
Oral agents with established efficacy in Cushing’s syndrome are
metyrapone and ketoconazole
Metyrapone inhibits cortisol synthesis at the level of 11β-hydroxylase , whereas the antimycotic drug ketoconazole inhibits the early steps of steroidogenesis
most common cause of mineralocorticoid excess is
primary aldosteronism
The clinical hallmark of mineralocorticoid excess is
hypokalemic hypertension
Diagnostic screening for mineralocorticoid excess is not currently recommended for all patients with hypertension but should be restricted to those who
exhibit hypertension associated with drug resistance
hypokalemia
an adrenal mass
or onset of disease before the age of 40 years
How long should you hold MR antagonists before doing ARR?
4 weeks
What is a positive ARR
ARR screening is positive if the ratio is >750 pmol/L per ng/mL per hour, with a concurrently high normal or increased aldosterone
What are the confirmatory tests for mineralocorticoid excess
The most straightforward is the saline infusion test, which involves the IV administration of 2 L of physiologic saline over a 4-h period.
Failure of aldosterone to suppress <140 pmol/L (5 ng/dL) is indicative of autonomous mineralocorticoid excess.
Alternative tests are the oral sodium loading test (300 mmol NaCl/d for 3 days) or the fludrocortisone suppression test (0.1 mg q6h with 30 mmol NaCl q8h for 4 days);
Next step when Primary aldosteronism is confirmed but CT of adrenals is normal and with family of early onset hypertension
Dexa 0.125-0.5 mg/day
What age should adrenal vein sampling be done in px with primary aldosteronism and unilateral adrenal mass?
> 40
Screening test for incidentaloma
CT scan features of an incidentaloma that makes it likely malignany
Tumor >= 4cm and >=20 HU
Patients with confirmed ACC and successful removal of the primary tumor should receive adjuvant treatment with ______, particularly in patients with a high risk of recurrence as determined by tumor size >8 cm, histopathologic signs of vascular invasion, capsule invasion or violation, and a Ki67 proliferation index ≥10%
mitotane (o,p’DDD)
Adjuvant mitotane should be continued for at least 2 years, if side effects are tolerated. Regular monitoring of plasma mitotane levels is mandatory (therapeutic range 14–20 mg/L; neurotoxic complications more frequent at >20 mg/L).
Mitotane is usually started at 500 mg tid, with stepwise increases to a maximum dose of 2000 mg tid in days (high-dose saturation) or weeks (low-dose saturation) as tolerated.
Most common cause of adrenal insufficiency
Hypothalamic-pituitary origin of disease
Most common cause of primary adrenal insufficiency
autoimmune adrenalitis
Electrolyte abnormalities present in primary adrenal insufficiency
adrenal insufficiency and is found in 80% of patients at presentation. Hyperkalemia is present in 40% of patients at initial diagnosis.
Confirmatory test for adrenal insufficiency
The diagnosis of adrenal insufficiency is established by the short cosyntropin test
The cutoff for failure is usually defined at cortisol levels of <450–500 nmol/L (16–18 μg/dL) sampled 30–60 min after ACTH stimulation;
Next step when adrenal insufficiency is confirmed
Once adrenal insufficiency is confirmed, measurement of plasma ACTH is the next step
Treatment for acute adrenal insufficiency
Acute adrenal insufficiency requires immediate initiation of rehydration, usually carried out by saline infusion at initial rates of 1 L/h with continuous cardiac monitoring.
Glucocorticoid replacement should be initiated by bolus injection of 100 mg hydrocortisone, followed by the administration of 200 mg hydrocortisone over 24 h, preferably by continuous infusion or alternatively by bolus IV or IM injections.
Mineralocorticoid replacement can be initiated once the daily hydrocortisone dose has been reduced to <50 mg because at higher doses hydrocortisone provides sufficient stimulation of MRs.
At what level of hydrocortisone requirement can you start the patient with acute adrenal insufficiency with mineralocorticoid replacement?
Mineralocorticoid replacement can be initiated once the daily hydrocortisone dose has been reduced to <50 mg because at higher doses hydrocortisone provides sufficient stimulation of MRs.
Mineralocorticoid replacement in primary adrenal insufficiency should be initiated at a dose of 100–150 μg fludrocortisone.
Supraphysiologic glucocorticoid treatment with doses equivalent to _____ hydrocortisone or more will affect bone metabolism, and these patients should undergo regular bone mineral density evaluation
30 mg
How is adequacy of treatment with mineralocorticoid replacement in px with acute adrenal insufficiency be measured
The adequacy of treatment can be evaluated by measuring blood pressure, sitting and standing, to detect a postural drop indicative of hypovolemia. In addition, serum sodium, potassium, and plasma renin should be measured regularly. Renin levels should be kept in the upper normal reference range
Next diagnostic step when primary adrenal insufficiency is confirmed
Adrenal autoantibodies
Next diagnostic step when secondary adrenal insufficiency is confirmed
MRI of the pituitary
the most common syndromic cause of obesity
Prader-Willi syndrome (PWS)
Cancers associated with obesity
The largest effects are on colorectal, kidney, and pancreatic cancer, adenocarcinoma of the esophagus, and, in women, endometrial carcinoma
For obese patietns it is recommended to initiate treatment with a calorie deficit of _____ compared with the patient’s habitual diet
500–750 kcal/d
Alternatively, a diet of 1200–1500 kcal/d for women and 1500–1800 kcal/d for men (adjusted for the individual’s body weight) can be prescribed
How is very low calorie diet defined?
The primary purpose of a VLCD is to promote a rapid and significant (13- to 23-kg) short-term weight loss over a 3- to 6-month period. The proprietary formulas designed for this purpose typically supply ≤800 kcal, 50–80 g of protein, and 100% of the recommended daily intake for vitamins and minerals
When is surgery indicated in obese patients?
MOA of Lorcaserin for weight loss
5-HT2C receptor agonist
Orlistat is a synthetic hydrogenated derivative of a naturally occurring lipase inhibitor, lipostatin,
that is produced by the mold
Streptomyces toxytricini.
Definition of moderate and severe obesity
severe obesity (BMI ≥40 kg/m2 ) or for those with moderate obesity (BMI ≥35 kg/m2 )
the most commonly undertaken and most accepted bypass procedure for obesity
Roux-en-Y
Criteria for diagnosing DM
How frequent should a person diagnsed with GDM be worked up for DM
ADA recommends that women with a history of GDM undergo lifelong screening for the development of diabetes or prediabetes at least every 3 years
Criteria for screening for T2DM
useful marker of insulin secretion and allows discrimination of endogenous and exogenous sources of insulin in the evaluation of hypoglycemia
C peptide
Glucose levels > ____ mmol/L or ____ mg/dK stimulate insulin synthesis
3.9 mmol/L (70 mg/dL)
The major susceptibility gene for type 1 DM is located in the HLA region on chromosome ___ .
6
Most prominent gene that is a variant of the _____that has been associated with both type 2 DM and IGT in several populations
transcription factor 7-like 2 gene
The ADA suggests that metformin be considered in individuals with both IFG and IGT who are at very high risk for progression to diabetes (age <__ years, BMI ≥__ kg/m2, and women with a history of GDM)
60 yrs
BMI >=35
When should you screen for distal symmetric polyneuropathy in patients with DM?
The ADA recommends annual screening for distal symmetric polyneuropathy beginning with the initial diagnosis of diabetes and annual screening for autonomic neuropathy 5 years after diagnosis of type 1 DM and at the time of diagnosis of type 2 DM. This testing is aimed at detecting loss of protective sensation (LOPS) caused by diabetic neuropathy
mnemonic: T2DM–> 2day mo na itest
Is nephropathy considered micro or macrovascular complication of DM?
microvascular
Recommended BP for px with T2DM
The American Diabetes Association (ADA) recommends blood pressure control <130/80 mmHg for individuals with high cardiovascular risk and <140/90 mmHg for individuals with lower cardiovascular risk.
hallmark of proliferative diabetic retinopathy
The appearance of neovascularization in response to retinal hypoxemia is the hallmark of proliferative diabetic retinopathy
When should you screen for albuminuria for px with T2DM
commence 5 years after the onset of type 1 DM and at the time of diagnosis of type 2 DM
basically same timeline with dx dystal symmetric neuropathy
The ADA suggests a protein intake of _____ in individuals with diabetic kidney disease.
0.8 mg/kg of body weight/day
In px with DM, Nephrology consultation should be considered when the estimated GFR is <____ or with atypical features such as hematuria, rapidly declining renal function, or proteinuria > 3 g/day.
Referral for transplant evaluation should be made when the GFR approaches _____
30 mL/min per 1.743 m2
20 mL/min per 1.73 m2
Most commonly involved CN in DM neuropathy
CN III
The most prominent GI symptoms for DM neuropathy are
delayed gastric emptying (gastroparesis) and altered small- and large-bowel motility (constipation or diarrhea).
treatment for DM cystopathy
Diabetic cystopathy should be treated with scheduled voiding or self-catheterization.
Class of DM drugs that cannot be used for CHF
TZD
A possible increased risk of lower limb amputation and Fournier’sgangrene has been reported with what type of OHAS
SGLT-2 inhibitor therapy.
most common pattern of dyslipidemia in DM
The most common pattern of dyslipidemia is hypertriglyceridemia and reduced HDL cholesterol levels.
Statin of choice in px with renal dse
Atorvastatin
Providers should consider screening for asymptomatic PAD in individuals >50 years of age who have diabetes and other risk factors using _____
ankle-brachial index testing
The most common skin manifestations of DM are ____ and ___and are usually relieved by skin moisturizers.
xerosis and pruritus
What constitutes the Whipples triad of hypoglycemia?
Whipple’s triad: (1) symptoms consistent with hypoglycemia, (2) a low plasma glucose concentration measured with a precise method, and (3) relief of symptoms after the plasma glucose level is raised.
When hypoglycemia is prolonged beyond ~___, cortisol and growth hormone also support glucose production and restrict glucose utilization to a limited amount (both mechanisms are reduced by ~80% compared to epinephrine).
~4h
Thus, cortisol and growth hormone play no role in defense against acute hypoglycemia.
What is the primary secondary and third defense against hypoglycemia
Many other drugs have been associated with hypoglycemia. These include commonly used drugs such as ______
angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, β-adrenergic receptor antagonists, quinolone antibiotics, indomethacin, quinine, and sulfonamides.
what is the IGFII to IGF I ratio in non beta cell tumor that cause hypoglycemia
The tumors are usually apparent clinically, plasma ratios of IGF-II to IGF-I are high, and free IGF-II levels (and levels of pro-IGF-II [1–21]) are elevated.
Critical diagnostic findings in insulinoma
Critical diagnostic findings are a plasma insulin concentration ≥3 μU/mL (≥18 pmol/L), a plasma C-peptide concentration ≥0.6 ng/ mL (≥0.2 nmol/L), and a plasma proinsulin concentration ≥5.0 pmol/L when the plasma glucose concentration is <55 mg/dL (<3.0 mmol/L) with symptoms of hypoglycemia.
A low plasma β-hydroxybutyrate concentration (≤2.7 mmol/L) and an increment in plasma glucose level of >25 mg/dL (>1.4 mmol/L) after IV administration of glucagon (1.0 mg) indicate increased insulin (or IGF) actions
Treatment for insulinoma
Surgical resection of a solitary insulinoma is generally curative.
Diazoxide, which inhibits insulin secretion, or octreotide can be used to treat hypoglycemia in patients with unresectable tumors
everolimus, an mTOR inhibitor, has also been successful in combination with the above approaches
Treatment for hypoglycemia
If the patient is able and willing, oral treatment with glucose tablets or glucose-containing fluids, candy, or food is appropriate. A reasonable initial dose is 15–20 g of glucose. If the patient is unable or unwilling (because of neuroglycopenia) to take carbohydrates orally, parenteral therapy is necessary. IV administration of glucose (25 g) should be followed by a glucose infusion guided by serial plasma glucose measurements. If IV therapy is not practical, SC or IM glucagon (1.0 mg in adults) can be used, particularly in patients with T1DM.
oral glucose –> IV glucose –> SC/IM glucagon
Symptoms of diabetes usually resolve when the plasma glucose is < ______, and thus most DM treatment focuses on achieving the second and third goals.
<11.1 mmol/L (200 mg/dL)
What are the treatment goals for DM?
To avoid exercise-related hyper- or hypoglycemia, individuals with type 1 DM should (1) monitor blood glucose before, during, and after exercise
(2) delay exercise if blood glucose is ______ and ketones are present
(3) if the blood glucose is ____ , ingest carbohydrate before exercising
(4) monitor glucose during exercise and ingest carbohydrate as needed to prevent hypoglycemia
(5) decrease insulin doses (based on previous experience) before and after exercise and inject insulin into a nonexercising area
(6) learn individual glucose responses to different types of exercise.
(2) >14 mmol/L (250 mg/ dL)
(3) <5.0 mmol/L (90 mg/dL)
In individuals with type 2 DM, exercise-related hypoglycemia is less common but can occur in individuals taking either insulin or insulin secretagogues.
Frequency of SMBG monitoring in px with T1DM or T2DM
> 3x/day
In patients achieving their glycemic goal, the ADA recommends measurement
of the HbA1c at least _____
twice per year.
Longest acting insulin
Degludec
Short-acting insulin analogues should be injected just before (______) and regular insulin (____) prior to a meal. Sometimes short-acting insulin analogues are injected just after a meal (gastroparesis, unpredictable food intake
<10 min
30–45 min
Highest Hba1c reduction
Biguanides and sulfonylureas
OHAS associated with pancreatitis
GLP 1 agonists
OHAS associated with inc risk of hyperkalemia
SGLT 2 inh
OHAS associated with elevated LFT
a glucosidase inhibitor
OHAS associated with Angioedema/urticarial and immune-mediated dermatologic effects
DPP4 inhibitor
OHAS associated with CHF
Thiozolidinediones
** also contraindicated in hepatic insuffiency
OHAS associated with Vit B12 deficiency
Biguanides
OHAS that can cause weight gain
TZD and Insulin secretagogues
Contraindications to alpha glucosidase inhibitor
These agents should not be used in individuals with inflammatory bowel disease, gastroparesis, or a serum creatinine >177 μmol/L (2 mg/dL)
Effect of TZD on lipid profile
Rosiglitazone raises low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides slightly. (Lipid profile rose sa rosi-glitazone)
Pioglitazone raises HDL to a greater degree and LDL a lesser degree but lowers triglycerides
SGLT 2 inhibitor assoc with inc risk of bladder CA
dapagliflozin
Individuals who require >____ per day of long-acting insulin should be considered for combination therapy with metformin a GLP-1 receptor agonist, or a thiazolidinedione as these can reduce insulin requirements in some individuals with type 2 DM.
1 unit/kg
The ADA clinical guidelines state that metabolic
surgery should be considered in individuals with type 2 DM and a body mass index >___ kg/m2
if hyperglycemia is inadequately controlled
despite optimal medical therapy
30
How do you differentiate DKA vs HHS vs euglycemic DKA
See table
Formula for corrected Na
(1.6-mmol/L [1.6-meq] reduction in serum sodium for each 5.6-mmol/L [100-mg/dL] rise in the serum glucose)
Why do you shift fluid to 0.45 saline in DKA
The change to 0.45% saline or using lactated Ringer’s helps to reduce the trend toward hyperchloremia later in the course of DKA
When should long acting insulin be administered in tx patients with DKA?
Long-acting insulin, in combination with SC short-acting insulin, should be administered as soon as the patient resumes eating, because this facilitates transition to an outpatient insulin regimen and reduces length of hospital stay.
It is crucial to continue the insulin infusion or insulin SC until adequate insulin levels are achieved by administering long-acting insulin by the SC route. Even relatively brief periods of inadequate insulin administration in this transition phase may result in DKA relapse
In euglycemic DKA associated with SGLT2 inhibitors, the pharmacologic effect may persist for____ days following discontinuation of SGLT2 inhibitor therapy as evidenced by ongoing glucosuria despite normoglycemia (glucose <180 mg/dL), during which time relapse of ketoacidosis is common if nutritional intake has not advanced (e.g., in the postoperative setting).
10–14
Hyperglycemia usually improves at a rate of ______ per h as a result of insulin-mediated glucose disposal, reduced hepatic glucose release, and rehydration.
4.2–5.6 mmol/L (50–100 mg/dL)
When the plasma glucose reaches ______ , glucose should be added to the 0.45% saline infusion to maintain the plasma glucose in the 8.3–11.1 mmol/L (150–200 mg/dL) range, and the insulin infusion should be continued at a lower rate to inhibit ketogenesis
11.1– 13.9 mmol/L (200–250 mg/dL)
More rapid correction of the serum glucose can precipitate the development of cerebral edema
When may bicarbonate be given in DKA?
in the presence of severe acidosis (arterial pH <7.0), sodium bicarbonate (50 mmol [meq/L] in 200 mL of sterile water with 10 meq/L KCl per h) may be administered for the first 2 h until the pH is >7.0
In DKA, If the serum phosphate is <_____, then phosphate supplement should be considered and the serum calcium monitored
0.32 mmol/L (1 mg/dL)
Glycemic goals in inpx according to ADA
.The ADA suggests the following glycemic goals for hospitalized patients: (1) in critically or non–critically ill patients: glucose of 7.8–10.0 mmol/L or 140–180 mg/dL; (2) in selected patients: glucose of 6.1–7.8 mmol/L or 110–140 mg/dL with avoidance of hypoglycemia; (3) the target range in the perioperative period should be 80–180 mg/dL (4.4–10.0 mmol/L)
Insulin infusion is the preferred method for managing patients with type 1 DM over a prolonged (several hours) perioperative period or when serious concurrent illness is present (______u/h of regular insulin)
0.5–1.0 units
If new-onset hyperglycemia remains during chronic treatment with supraphysiologic doses of glucocorticoid (>___ mg of prednisone or equivalent), the DM may be called “steroid-induced diabetes.”
5
Current recommendations advise screening for glucose intolerance between weeks ____ of pregnancy in women not known
to have diabetes
24 and 28
What constitutes the harmonizing definition of metabolic syndrome?
The most accepted and unifying hypothesis
to describe the pathophysiology of the metabolic syndrome
insulin resistance
what in the lipid profile is an excellent marker of insulin resistance
hyperTAG
The other major lipoprotein disturbance in the metabolic syndrome is a reduction in HDL cholesterol.
How much in % does fibrate decrease TAG
30-45%
How much in % does nicotinic acid decrease TAG
20-35%
only currently available drug with predictable
HDL cholesterol–raising properties
Nicotinic acid
nicotinic acid can increase HDL cholesterol by up to 30% above baseline
Formula for corrected Calcium
An algorithm to correct for protein changes adjusts the total serum calcium (in mg/dL) upward by 0.8 times the deficit in serum albumin (g/dL) or by 0.5 times the deficit in serum immunoglobulin (in g/dL).
Effect of aluminum hydroxide on Phosphate absorption
Decreased
Effect of dec ph in calcium absorption
inc
when should be phosphate measured?
basal, fatsing state due to wide variation throughout the day
Dent’s disease is an X-linked recessive disorder caused by inactivating mutations in ____ , a chloride transporter expressed in endosomes of the proximal tubule;
CLCN5
features include hypercalciuria, hypophosphatemia, and recurrent kidney stones
Respiratory failure and cardiac dysfunction, which are reversible with phosphate treatment, may occur at serum phosphate levels of ____
0.5–0.8 mmol/L (1.5–2.5 mg/dL).
What is the rate of phosphate infusion in patients with hypophosphatemia?
See table
Hypocalcemia, if present, should be corrected before administering IV phosphate
Hyperphosphatemia, defined in adults as a fasting serum phosphate concentration >____, usually results from impaired glomerular filtration, hypoparathyroidism, excessive delivery of phosphate into the ECF (from bone, gut, or parenteral phosphate therapy), or a combination of these factors
1.8 mmol/L (5.5 mg/dL)
What is the treatment for hyperphosphatemia?
> Volume expansion may enhance renal phosphate clearance.
Aluminum hydroxide antacids or sevelamer may be helpful in chelating and limiting absorption of offending phosphate salts present in the intestine.
Hemodialysis is the most effective therapeutic strategy and should be considered early in the course of severe hyperphosphatemia, especially in the setting of renal failure and symptomatic hypocalcemia
Hypomagnesemia usually signifies substantial depletion of body magnesium stores (___mmol/kg)
0.5–1
What is the disadvantage of giving IV MgSO4 over MgCl2 in correcting for hypomagnesemia
MgSO4 may be given IV instead of MgCl2 , although the sulfate anions may bind calcium in serum and urine and aggravate hypocalcemia
How is hypomagnesemia treated?
Mild, asymptomatic hypomagnesemia may be treated with oral magnesium salts (MgCl2 , MgO, Mg[OH]2 ) in divided doses totaling 20–30 mmol/d (40–60 meq/d).
More severe hypomagnesemia should be treated parenterally, preferably with IV MgCl2 , which can be administered safely as a continuous infusion of 50 mmol/d (100 meq Mg2+/d) if renal function is normal.
If GFR is reduced, the infusion rate should be lowered by 50–75%.
How frequent should you repeat serum magnesium monitoring while correcting for hypomagnesemia
aSerum magnesium should be monitored at intervals of 12–24 h during therapy, which may continue for several days because of impaired renal conservation of magnesium (only 50–70% of the daily IV magnesium dose is retained) and delayed repletion of intracellular deficits, which may be as high as 1–1.5 mmol/kg (2–3 meq/kg
The most prominent clinical manifestations of hypermagnesemia are vasodilation and neuromuscular blockade, which may appear at serum magnesium concentrations >__ mmol/L (>_ meq/L; > _ mg/dL)
2 mmol/L (>4 meq/L; >4.8 mg/dL)
How is hypermagnesemia treated?
Vigorous IV hydration should be attempted, if appropriate. Hemodialysis is effective and may be required in patients with significant renal insufficiency.
Calcium, administered IV in doses of 100–200 mg over 1–2 h, has been reported to provide temporary improvement in signs and symptoms of hypermagnesemia
The most specific screening test for vitamin D deficiency in otherwise healthy individuals is a ______
serum 25(OH)D level.
The National Academy of Medicine has defined vitamin D sufficiency as a vitamin D level >____, although higher levels may be required to optimize intestinal calcium absorption in the elderly and those with underlying disease states, including obesity
50 nmol/L (>20 ng/mL)
In patients who are vitamin D replete and are taking adequate calcium supplementation, the 24-h urinary calcium excretion should be in the range of ____ mg/24 h
100–250
Levels >250 mg/24 h predispose to nephrolithiasis and should lead to a reduction in vitamin D dosage and/or calciums supplementation
Most common cause of hypercalcemia
hyperparathyroidism
If hypercalcemia has been manifest for >1 year, malignancy can usually be excluded as the caus
Second most common cause of hypercalcemia
malignancy
When the calcium level is >_____ calcification in kidneys, skin, vessels, lungs, heart, and stomach occurs, and renal insufficiency may develop, particularly if blood phosphate levels are normal or elevated due to impaired renal excretion.
Severe hypercalcemia, usually defined as ≥ _______can be a medical emergency; coma and cardiac arrest can occur
3.2 mmol/L (12.8 mg/dL)
3.7–4.5 mmol/L (14.8–18.0 mg/dL)
**factor is 4 in converting mmol to mg/dL
The distinctive bone manifestation of hyperparathyroidism is ____
osteitis fibrosa cystica
Indications for surgery in asymptomatic primary hyperparathyroidism
What tests should be requested for monitoring primary hyperparathyroidism
Annually lahat except for skeletal (1-2 yrs)
when does calcium go down after parathyroidectomy?
A decline in serum calcium occurs within 24 h after successful surgery;
usually, blood calcium falls to low-normal values for 3–5 days until the remaining parathyroid tissue resumes full hormone secretion
What level of Calcium do you usually expect Chovstek’s and Trosseaus
Signs of hypocalcemia include symptoms such as muscle twitching, a general sense of anxiety, and positive Chvostek’s and Trousseau’s signs coupled with serum calcium consistently <2 mmol/L (8 mg/dL)
What is the recommended rate of infusion when correcting for hypocalcemia?
An infusion of 0.5–2 mg/kg per hour or 30–100 mL/h of a 1-mg/mL solution usually suffices to relieve symptoms.
Usually, parenteral therapy is required for only a few days. If symptoms worsen or if parenteral calcium is needed for >2–3 days, therapy with a vitamin D analogue and/or oral calcium (2–4 g/d) should be started (see below). It is cost-effective to use calcitriol (doses of 0.5–1 μg/d) because of the rapidity of onset of effect and prompt cessation of action when stopped, in comparison to other forms of vitamin D
What is the effect of magnesium on PTH?
If magnesium deficiency is present, it can complicate the postoperative course since magnesium deficiency impairs the secretion of PTH
responsible humoral agent in most solid tumors that cause hypercalcemia
PTHrP
histolgy of solid tumor associated with hypercalcemia
Squamous cell tumors are most frequently associated with hypercalcemia, particularly tumors of the lung, kidney, head and neck, and urogenital tract.
___- dependent reduction in 1,25(OH)2 D thus seems to be an important stimulus for the development of secondary hyperparathyroidism
FGF23
The bone disease seen in patients with secondary hyperparathyroidism and CKD is termed ____ and affects primarily bone turnover
renal osteodystrophy
How is hypocalcemia due to secondary hyperparathyroidism treated?
> includes reduction of excessive blood phosphate by restriction of dietary phosphate, the use of nonabsorbable phosphate binders, and careful, selective addition of calcitriol (0.25–2 μg/d) or related analogues.
> Calcium carbonate became preferred over aluminumcontaining antacids to prevent aluminum-induced bone disease. However, synthetic gels that also bind phosphate (such as sevelamer) are now widely used, with the advantage of avoiding not only aluminum retention but also excess calcium loading, which may contribute to cardiovascular calcifications.
> Intravenous calcitriol (or related analogues), administered as several pulses each week, helps control secondary hyperparathyroidism.
Most common form of hyperparathyroidism
Asymptomatic
Lab test that may help differentiate hyperpathyroidism with other causes of hypercalcemia
The immunoassay for PTH usually separates hyperparathyroidism from all other causes of hypercalcemia (exceptions are very rare reports of ectopic production of excess PTH by nonparathyroid tumors).
Patients with hyperparathyroidism have elevated PTH levels despite hypercalcemia, whereas patients with malignancy and the other causes of hypercalcemia (except for disorders mediated by PTH such as lithium-induced hypercalcemia) have levels of hormone below normal or undetectable
How can 1,25(OH)2 D levels differetiate primary hyperparathyroidism from other disorders associated with hypercalcemia?
1,25(OH)2 D levels are elevated in many (but not all) patients with primary hyperparathyroidism. In other disorders associated with hypercalcemia, concentrations of 1,25(OH)2 D are low or, at the most, normal
Measurement of 1,25(OH)2 D is critically valuable in establishing the cause of hypercalcemia in sarcoidosis and certain lymphomas.
What tx option for severe hypercalcemia may present with fever?
Pamidronate
What tx option for severe hypercalcemia has the highest antiresorptive properties?
Denosumab
What tx option for severe hypercalcemia is associated with tachyphylaxis?
Calcitonin
a monoclonal antibody that binds to RANK ligand (RANKL) and prevents it from binding to
the receptor RANK on osteoclast precursors and mature osteoclasts.
Denosumab
Duration of effec of calcitonin
Calcitonin, after 24 h of use, is no longer effective in lowering calcium
The malignancies in which hypercalcemia responds to glucocorticoids include
multiple myeloma, leukemia, Hodgkin’s disease, other lymphomas, and carcinoma of the breast, at least early in the course of the diseases
Approach to management of severe hypercalcemia
Severe hypercalcemia (≥3.7 mmol/L [15 mg/dL]) requires rapid correction. IV pamidronate or zoledronate or subcutaneous denosumab should be administered.
In addition, for the first 24–48 h, aggressive sodium-calcium diuresis with IV saline should be given and, following rehydration, large doses of furosemide or ethacrynic acid, but only if appropriate monitoring is available and cardiac and renal function are adequate
Definition of osteoporosis
2.5 standard deviations (SDs) or more below the mean for young healthy adults of the same sex and race—also referred to as a T-score of –2.5.
Patients who present with hip or spine fractures by definition have osteoporosis and will require treatment for both the fractureitself and the underlying skeletal disorder
How does vitamin d insufficiency cause osteoporosis?
Vitamin D insufficiency leads to compensatory secondary hyperparathyroidism and is an important risk factor for osteoporosis and fractures
How does estrogen deficiency cause bone loss?
Estrogen deficiency causes bone loss by two distinct but interrelated mechanisms: (1) activation of new bone remodeling sites and (2) initiation or exaggeration of an imbalance between bone formation and resorption, in favor of the latter
Loss of estrogen increases production of RANKL and reduces production of osteoprotegerin, increasing osteoclast formation and recruitment
What are the drugs associated with osteoporosis?
See table
Glucocorticoids are the most common cause of medication-induced osteoporosis
What are the indications for BMD testing?
Indications for vertebral testing
When osteoporosis is found associated with symptoms of rash, multiple allergies, diarrhea, or flushing, mastocytosis should be considered and excluded by using ______
24-h urine histamine collection or serum tryptase
Biochemical markers of bone metabolism
Adequate calcium intake per age group
SERM that protects the uterus and breast from effects of estrogen and makes the use of progestin unnecessary
Bazedoxifene
Tamoxifen is protective against breast CA but increases the risk for this type of CA
uterine
unlike raloxifene
Contraindication of alendronate
contraindicated in patients who have stricture or inadequate emptying of the esophagus
Adverse events associated with bisphosphonate
All bisphosphonates have been associated with some musculoskeletal and joint pains of unclear etiology, which are occasionally severe. There is potential for renal toxicity, and bisphosphonates are contraindicated in those with an estimated glomerular filtration rate <30–35 mL/min. Hypocalcemia can occur.
Also associated with osteonecrosis of the jaw and atypical femoral fracture
What treatment for osteoporosis when discontinued is associated with rebound increase in bone turnover and bone loss
When denosumab is discontinued, there is a rebound increase in bone turnover and an apparent acceleration of bone loss. This likely reflects the maturation of osteoclast precursors that have accumulated in marrow when the drug was administered and can become mature bone resorbing cells once the drug is withdrawn
a humanized antibody that blocks the osteocyte production of sclerostin, resulting in an increase in bone formation and decline in bone resorption
romosozumab
a cathepsin K inhibitor, inhibits the osteoclast collagenase enzyme, preventing bone resorption but not affecting osteoclast viability
odanacatib
Currently ______ measured on a fasting serum sample in the morning is the preferred marker of bone resorption, and ____ or ____ the is the preferred marker for formation
collagen C-telopeptide
osteocalcin or propeptide of type 1 collagen (P1NP)
All patients on long-term (>___ months) glucocorticoids should have measurement of bone mass at both the spine and the hip using DXA
3
If only one skeletal site can be measured, it is best to assess the spine in individuals <60 years and the hip in those >60 years.
