Endocrinology Flashcards
Chronic alcoholic patient with HTN and obesity presents with: Concentration of fat in the truncal region Development of small cervicodorsal fat pad Slightly ↑ urine free cortisol level 1 mg overnight dexamethasone suppression test: suppression of a.m. cortisol production What is the diagnosis?
Pseudo-Cushing
Young marathon runner with BMI < 18 develops: Amenorrhea Urine pregnancy test: Negative Mild ↓ FSH and LH Normal TSH Normal prolactin What is the diagnosis?
Functional hypothalamic amenorrhea - context of a patient who exercises excessively - Other causes include eating disorders, stress and illness, nutritional disease (e.g., celiac disease), and > 10% loss of body weight. Dx: Clinical + low FSH and LH. May need MRI. Tx: Supportive. Less exercise, more calories, and possibly OCPs
Functional hypothalamic amenorrhea. Diagnosis depends on?
Dx: Clinical + low FSH and LH. May need MRI.
Type 1 diabetic develops gradual onset: Fever, weakness, nausea, vomiting, sporadic abdominal pain, and tanned skin Alopecia Episodes of hypoglycemia on a previously stable insulin regimen ↓ BP Delayed reflexes ↓ Serum Na, ↑ K, and ↑ TSH Diagnosis?
Polyglandular autoimmune syndrome 2, also called Schmidt syndrome Diagnoses are hypothyroidism and adrenal insufficiency. Explanation These diagnoses can occur together as part of the polyglandular autoimmune syndrome 2, also called Schmidt syndrome. Know that you must replace the cortisol before you replace the thyroid hormone. Hopefully, you recognize the collection of classic signs and symptoms for both adrenal insufficiency and hypothyroidism. Then think about the relationships that you know exist between the 2. Recognize that this patient is not presenting with pituitary disease because the TSH is high, not low, and that the patient is tanned, so the ACTH is high, not low. Therefore, both the thyroid and adrenal diseases are primary. Three failing glands (pancreas, thyroid, and adrenal) suggest a polyglandular syndrome. Dx: Clinical + TSH + electrolytes + cosyntropin test (cortisol does not increase after ACTH). Tx: Replacement of levothyroxine, glucocorticoids, and mineralocorticoids.
Schmidt syndrome. Diagnosis depends on?
Dx: Clinical + TSH + electrolytes + cosyntropin test (cortisol does not increase after ACTH).
What is the reason for the tanned appearance in Schmidt syndrome?
ACTH is high
Three failing glands (pancreas, thyroid, and adrenal) suggest a ________ syndrome.
Three failing glands (pancreas, thyroid, and adrenal) suggest a polyglandular syndrome.
Positive cosyntropin test
Cortisol does not increase after ACTH.
In Schmidt syndrome, what is the pre-treatment trigger?
Replace the cortisol before you replace the thyroid hormone.
Postmenopausal female on no meds presents with: Headaches and loss of peripheral vision Weight gain, constipation, alopecia Delayed reflexes ↓ Serum Na+ ↓ FSH and LH What is the diagnosis?
pituitary tumor causing mass effect, hypogonadism, and secondary hypothyroidism. Clues to a diagnosis of thyroid disease: weight gain, constipation, alopecia, delayed reflexes, hyponatremia, and the decreased gonadotropins. FSH and LH in a postmenopausal female are increased, not decreased. The presence of multiple endocrine derangements (thyroid disease + low gonadotropins) and headaches with vision loss suggest that the diagnosis is in the pituitary. Dx: Brain MRI + serum levels of pituitary hormones to screen for excess or deficiency is done for all tumors > 1 cm. Tx: Nonfunctional tumors that do not produce hormones but cause neurologic impairments are referred for transsphenoidal resection + replacement of deficiencies.
FSH and LH in a postmenopausal female are __creased, not __creased.
FSH and LH in a postmenopausal female are increased, not decreased.
Rx: nonfunctional pitituary tumor
Transphenoidal resection + hormone replacement
Highest LR+ for signs of hypothyroidism
- coarse skin - bradycardia - delayed ankle reflex C: The combination of signs that had the highest likelihood ratios (c) was associated with modest accuracy (LR+ 3.75; LR- 0.48).
Patient with diabetes ± warfarin use develops: Acute onset of headache Bitemporal hemianopsia ± Neck stiffness ± Confusion or loss of consciousness MRI: High density mass in the sella What is the diagnosis?
Pituitary apoplexy. Explanation The clue that the problem is in the pituitary is the presence of the bitemporal hemianopsia, which suggests a problem around the area of the optic chiasm. Compromise of vascular supply due to growth of adenoma usually is associated with antecedent adenoma symptoms, but hemorrhage into the gland usually is not. Dx: Brain MRI. Tx: Emergent glucocorticoids + neurosurgery consult.
Bitemporal hemianopsia suggests a problem near the ___ ___.
Bitemporal hemianopsia suggests a problem near the optic chiasm.
Compromise of vascular supply due to growth of adenoma usually is associated with antecedent adenoma symptoms, but _____ into the gland usually is not.
Compromise of vascular supply due to growth of adenoma usually is associated with antecedent adenoma symptoms, but hemorrhage into the gland usually is not.
Rx: pitituary apoplexy
Glucocorticoids+ emergency Surgery
The management of pituitary apoplexy includes emergency neurosurgical consult and ____
Glucocorticoids
Patient with +FH of MEN1 develops: Diabetes Weight loss Chronic diarrhea A beefy red tongue and cheilitis A painful, pruritic blistering rash What is the diagnosis?
Glucagonoma Explanation Dx: Clinical + serum glucagon concentration (> 500 pg/mL) + measurement of multiple molecular weight forms of glucagon + imaging to localize tumor (helical CT or MRI of abdomen) with biopsy. Tx: Surgical resection, if localized. Difficult and specialized treatment if metastases are present at diagnosis. All patients need good nutritional support.
Glucagonoma: Dx features
Clinical + serum glucagon concentration (> 500 pg/mL) + measurement of multiple molecular weight forms of glucagon + imaging to localize tumor (helical CT or MRI of abdomen) with biopsy.
Tx: Glucagonoma
Surgery C: Surgical resection, if localized. Difficult and specialized treatment if metastases are present at diagnosis. All patients need good nutritional support.
Patient presents with gradual onset: Weight gain Cold intolerance Constipation Alopecia Galactorrhea Amenorrhea Coarse hair Periorbital edema Nonpitting ankle edema ↓ HR and delayed reflexes ↓ Hgb and Hct with normal MCV and MCHC ↓ Serum Na ↑ Total cholesterol and serum prolactin ↑ TSH and ↓ FT4 What is the diagnosis?
primary hypothyroidism. Explanation Recognize that this script includes some manifestations of hypothyroidism, and then note that symptoms of other potential endocrine abnormalities also are present (galactorrhea and amenorrhea—which suggest hyperprolactinemia). Then, consider the relationship between thyroid disease and the prolactin levels. Remember that hypothyroidism causes hyperprolactinemia. Do not diagnose a prolactinoma until you have looked at the thyroid 1st. The labs tell you that the thyroid problem is not originating in the pituitary because the TSH is high, not low. Dx: Clinical + TSH + FT4. Tx: Replacement of levothyroxine.
Why can a patient with primary hypothyroidism have galactorrhea and amenorrhea?
Hypothyroidism causes hyperprolactinemia. Explanation: Hypothyroidism predisposes to hyperprolactinemia. However, basal serum prolactin concentrations are normal in most hypothyroid patients [38], and only the serum prolactin response to stimuli, such as thyrotropin-releasing hormone (TRH), is increased [39]. In the few hypothyroid patients who have elevated basal serum prolactin concentrations, the values return to normal when the hypothyroidism is corrected [40,41]. It is important to recognize hypothyroidism as a potential cause of an enlarged pituitary gland (due to thyrotroph hyperplasia, lactotroph hyperplasia, or both) and hyperprolactinemia, and not to confuse this entity with a lactotroph adenoma. (See “Causes, presentation, and evaluation of sellar masses”.) The mechanism of hyperprolactinemia in hypothyroidism is not known
How does hypothyroidism cause enlargement of the pituitary gland?
- thyrotroph hyperplasia - lactotroph hyperplasia It is important to recognize hypothyroidism as a potential cause of an enlarged pituitary gland (due to thyrotroph hyperplasia, lactotroph hyperplasia, or both) and hyperprolactinemia, and not to confuse this entity with a lactotroph adenoma.
Middle-aged patient with h/o alopecia and fatigue develops: Confusion Hypothermia, ↓ BP, ↓ HR Delayed reflexes Nonpitting ankle edema ↓ Hgb and Hct with normal MCV and MCHC What is the diagnosis?
Myxedema coma
Features of myxedema coma + hypoglycemia suggests _ _ in addition to hypothyroidism.
Adrenal insufficiency
Mx: myxedema coma. Trigger
Hydrocortisone T3+T4 Parenteral T3 and T4 replacement + careful administration of IVF and replacement of electrolytes + passive warming + broad-spectrum empiric antibiotics ± parenteral glucocorticoids
Why should we think about stress dose steroids in myxedema coma before T4/T3 replacement?
Adrenal insufficiency Explanation: Adrenal insufficiency may be present. Thyroid hormone replacement prior to steroid replacement will cause “decompensation” because of increased metabolism without adequate steroid support.
35-year-old female with no PMH, on no medications, develops: ↑ BP ↓ Serum K ↓ Plasma renin activity ↑ Plasma aldosterone concentration What is the diagnosis? What are other names for this condition?
Conn syndrome or bilateral adrenal hyperplasia - alias primary hyperaldosteronism Explanation: Since the patient is hypokalemic, consider causes of secondary HTN regardless of age. Next, interpret the renin and aldo results. Renin is low in states where aldo is in excess as the primary abnormality, such as with an adrenal tumor or hyperplasia. Dx: Clinical + PAC:PRA (ratio of plasma aldosterone concentration to plasma renin activity; > 20 in an adrenal tumor) + measure aldosterone after oral or parenteral sodium load (when adrenal hyperplasia or tumor present, aldo does not suppress after sodium) + CT of the adrenals to assess for bilateral adrenal hyperplasia or an adrenal tumor. Tx: Depends on cause: Treat hyperplasia with aldosterone receptor blocker (aldactone) and send tumors for surgical resection.
In states where aldosterone is in excess as the primary abnormality (tumor or hyperplasia), renin concentrations will be __.
In states where aldosterone is in excess as the primary abnormality (tumor or hyperplasia), renin concentrations will be low.
What does renin do?
AGT -> AG I Renin cleaving its substrate, angiotensinogen (AGT), to produce the inactive peptide, angiotensin I, which is then converted to angiotensin II by endothelial angiotensin-converting enzyme (ACE).
Angiotensin II mediates _______ as well as ___ release from the adrenal gland, resulting in sodium retention and increased blood pressure.
Angiotensin II mediates vasoconstriction as well as aldosterone release from the adrenal gland, resulting in sodium retention and increased blood pressure.
What is the difference between the classical view of the RAS and current views?
Several RAS systems Instead of one simple circulating RAS, it is recognized that there are also several tissue (local) renin-angiotensin systems that function independently of each other and of the circulating RAS. In particular, angiotensin II generation at the tissue level by these local systems appears to have physiologic effects that are as important as circulating angiotensin II and, under some circumstances, more important than circulating angiotensin II.
Where is renin secreted?
JGA
Why does anti-aldosterone therapy work in heart failure?
Existence of local RAS systems in the heart Explanation: local systems, activation of angiotensin II results in harmful effects and target-organ damage that extend beyond vascular and renal hemodynamics to direct tissue actions, including tissue remodeling, endothelial dysfunction, and fibrosis. A more detailed review appears below. (See ‘Tissue renin-angiotensin systems’ below.)
PAC/PRA ratio is used to diagnose
primary hyperaldosteronism Explanation: The first test used in patients suspected to have primary hyperaldosteronism measures the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio
The mean value for the PAC/PRA ratio in normal subjects and patients with primary hypertension is _ to _, compared with more than _ to _ in most patients with primary aldosteronism
4 10 30 50 Explanation: The mean value for the PAC/PRA ratio in normal subjects and patients with primary hypertension (formerly called “essential” hypertension) is 4 to 10, compared with more than 30 to 50 in most patients with primary aldosteronism
Aldosterone is a steroid hormone, “the main mineralocorticoid hormone”, produced by the _ _ of the adrenal cortex in the adrenal gland.
zona glomerulosa Aldosterone is a steroid hormone, “the main mineralocorticoid hormone”, produced by the outer section (zona glomerulosa) of the adrenal cortex in the adrenal gland.
Aldosterone causes the conservation of _, secretion of _.
sodium potassium Aldosterone causes the conservation of sodium, secretion of potassium
Young female with a history of other autoimmune diseases (e.g., chronic autoimmune hypothyroidism) develops: Amenorrhea Episodes of diaphoresis and heat intolerance Negative pregnancy test ↑ FSH and LH Normal TSH Normal prolactin What is the diagnosis?
(primary ovarian insufficiency )|(premature ovarian failure)
Healthy patient presents with: Fatigue Painful swallowing Neck pain Very tender goiter ↓ RAIU What is the diagnosis? And what is the usual cause?
Subacute thyroiditis Viral
RAIU is __ in all forms of thyroiditis Increased/Decreased
RAIU is decreased in all forms of thyroiditis
What historical feature distinguishes psychogenic polydipsia from nephrogenic polydipsia?ea
Nocturia Explanation: Patients with psychogenic polydipsia do not continue to drink while asleep, so they do not have nocturia; but nocturia is an early symptom of DI.
Rx: nephrogenic DI
(Thiazide diuretic) | (Thiazide)
What is the response to water restriction in patients with nephrogenic DI?
- Hypernatremia - Persistent low specific gravity urine
Patient presents with episodes of: Anxiety Diaphoresis Fogginess that occurs during fasting and resolves with eating Plasma glucose < 55 mg/dL during an episode During hypoglycemia: Normal insulin level Proinsulin > 20% Normal C-peptide
Insulinoma
Insulinoma. Rx?
Resection
Normal proinsulin, normal insulin, normal C-peptide during hypoglycemia. Causes?
- Sulfonylurea ingestion - Insulinoma
_ _ intake is associated with increased insulin and low C-peptide levels.
Exogenous insulin intake is associated with increased insulin and low C-peptide levels.
Hypoglycemia workup
- plasma glucose (low) - insulin (normal or high) - proinsulin (normal or high) - C-peptide (normal or increased) - Sulfonylurea screen Explanation: Check during hypoglycemic episode
Dx: Anxiety and tremor Gradual onset of anxiety and tremulousness Palpable thyroid nodule Undetectable TSH Thyroid scan = single hot nodule
Toxic adenoma Explanation: hot nodules are rarely associated with malignancy and do not require biopsy. Dx: Clinical exam + TSH + ultrasound + uptake scan. Tx: Radioiodine ablation.
Rx: toxic adenoma
- Surgery - Radioiodine therapy Explanation: For patients with toxic adenoma or MNG, surgery or radioiodine rather than prolonged thionamide therapy. Choice depends upon individual patient factors and availability of thyroid surgeons.
Dx-process: toxic adenoma
Clinical exam + TSH + ultrasound + uptake scan
Fevers and weakness Nausea and vomiting Sporadic abdominal pain Tanned skin ↓ BP ↓ Serum Na, ↑ K, and ↓ glucose ± eosinophilia 60 minutes after cosyntropin, serum cortisol: 7 μg/dL Dx?
primary adrenal insufficiency. Explanation: This patient is tanned because ACTH is increased. If the AI is primary, it is associated with hyperkalemia and tanned skin because all layers of the adrenal cortex are diseased, resulting in mineralocorticoid and glucocorticoid deficiencies. But secondary AI is not associated with hyperpigmentation (because ACTH is low) or hyperkalemia (because the glomerulosa layer of the adrenal cortex is not diseased and continues to be stimulated by the renin-angiotensin system). Keep straight the electrolyte differences in primary AI (hyperkalemia and metabolic acidosis because of deficiencies of both cortisol and aldosterone) and Cushing syndrome (hypokalemic metabolic alkalosis because of excess aldosterone effect). Dx: Clinical + cosyntropin test. Tx: Glucocorticoid and mineralocorticoid replacement.
Why are patients with primary adrenal insufficiency tanned?
ACTH increased Explanation: ACTH is a cleavage product of the pro-hormone, proopiomelanocortin (POMC), which also produces other hormones including α-MSH that stimulates the production of melanin.
Adrenocorticotropic hormone (ACTH), is a polypeptide tropic hormone secreted by the __ __ gland.
Adrenocorticotropic hormone (ACTH), is a polypeptide tropic hormone secreted by the anterior pituitary gland.
Dx-process: primary adrenal insufficiency
Clinical + cosyntropin test
Secondary adrenal insufficiency is not associated with hyperkalemia because the _ _ is not diseased and continues to be stimulated by the _-_ system.
Secondary adrenal insufficiency is not associated with hyperkalemia because the zona glomerulosa is not diseased and continues to be stimulated by the renin-angiotensin system.
The electrolyte disturbances in primary adrenal insufficiency are due to diminished secretion of c_ and a_.
The electrolyte disturbances in primary adrenal insufficiency are due to diminished secretion of cortisol and aldosterone.
A major function of aldosterone is to increase urinary _ secretion. As a result, hypoaldosteronism can be associated with _ and mild metabolic acidosis.
- potassium - hyperkalemia A major function of aldosterone is to increase urinary potassium secretion. As a result, hypoaldosteronism can be associated with hyperkalemia and mild metabolic acidosis.
Hypo_ and Hyper_ are the two major electrolyte abnormalities of primary adrenal insufficiency.
- natremia - kalemia Explanation: Hyponatremia and hyperkalemia are the two major electrolyte abnormalities of primary adrenal insufficiency.
Aldosterone increases/decreases sodium reabsorption
Aldosterone normally increases sodium reabsorption.
In adrenal insufficiency: hyponatremia is mediated by increased release of _ which results in water retention and a reduction in the plasma sodium concentration]. Both cortisol and aldosterone deficiency contribute to this problem.
ADH In adrenal insufficiency: hyponatremia is mediated by increased release of ADH which results in water retention. Both cortisol and aldosterone deficiency contribute to this problem.
only _ to _ percent of patients with primary adrenal insufficiency develop hyperkalemia [17-19]. The normokalemia found in many hypoadrenal patients is attributable to aldosterone-independent regulation of potassium secretion by the distal nephron
only 50 to 60 percent of patients with primary adrenal insufficiency develop hyperkalemia [17-19]. The normokalemia found in many hypoadrenal patients is attributable to aldosterone-independent regulation of potassium secretion by the distal nephron
Hyponatremia in adrenal insufficiency is rapidly corrected by _ and _ repletion, which shuts off ADH release and allows excess water to be excreted.
Hyponatremia in adrenal insufficiency is rapidly corrected by cortisol and volume repletion, which shuts off ADH release and allows excess water to be excreted.
Hospitalized in the ICU: ↓ TSH, ↓ FT4, ↓ FT3
Euthyroid sick syndrome.
Secure-dx: Euthyroid sick syndrome
rT3 Explanation: The levels of rT3 increase because its clearance decreases while its production stays the same. The decreased clearance is possibly from lower 5’-deiodinase activity in the peripheral tissue or decreased liver uptake of rT3. Rarely done
Postpartum patient develops: Anxiety and tremulousness Nontender goiter +Anti-TPO antibodies What is the diagnosis?
Postpartum thyroiditis.
long-term complication includes chronic _, especially in patients with anti-TPO antibodies.
long-term complication includes chronic hypothyroidism, especially in patients with anti-TPO antibodies.
Patient presents with gradual onset: Tremulousness Anxiety Weight loss Diffuse muscle weakness Diarrhea Amenorrhea or erectile dysfunction ↑ BP and HR ± atrial fibrillation and exophthalmos ↓ Hgb and Hct with normal MCV and MCHC ↑ Serum Ca and alkaline phosphatase Uptake and scan: Diffusely increased What is the diagnosis?
Graves disease
Which antibodies are positive in Grave’s disease?
TRAb Ex: thyrotropin receptor antibodies (TRAb, also called TSI, TBII, or TBI), determination of the radioactive iodine uptake, or measurement of thyroidal blood flow on ultrasonography (table 1).
Impaired glucose tolerance
Two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol/l) on the 75-g oral glucose tolerance test. Exp: A patient is said to be under the condition of IGT when he/she has an intermediately raised glucose level after 2 hours, but less than the level that would qualify for type 2 diabetes mellitus. The fasting glucose may be either normal or mildly elevated.
Diagnostic criteria DM
One of: 1. 8 hour fasting glucose > 126 2. 2 hour glucose > 200 with 75 g GTT 3. A1C > 6.5 4. Random glucose > 200 + classic symptoms + Re-confirmation (ADA criteria)
Necrolytic migratory erythema (NME)
Necrolytic migratory erythema (NME) is a red, blistering rash that spreads across the skin. It particularly affects the skin around the mouth and distal extremities; but may also be found on the lower abdomen, buttocks, perineum, and groin. It is strongly associated with glucagonoma, a glucagon-producing tumor of the pancreas, but is also seen in a number of other conditions including liver disease and intestinal malabsorption
Glucagonoma: SymptomsSigns
Diarrhea, neuropsychiatric symptoms and weight loss of 5–15 kg, Necrolytic migratory erythema
Glucagonoma:DiagnosticCriteria
Glucagon > 1000 pg/mL Normal: 50–200 pg/mL.
MODY
- Age: [10 .. 45] - Lean body - FHx young onset DM - Autosomal dominant - Insulin independent - Absence of antibodies
Normal C-peptide level implies insulin independence. Why?
Adequate insulin production
Half-life of insulin
3-5 minute
Half-life of C-peptide
20-30 minutes
Diabetes meds in pregnancy
- Insulin - Metformin - Glyburide Comment: Metformin and glyburide both have evidence
Cause of hypogonadism in hemochromatosis
Iron deposition in the pituitary
Early SymtpomsSigns of hemochromatosis
- Fatigue - Sexual dysfunction - Arthralgias
IGF
— Insulin-like growth factor 1 (IGF-1) — major mediator of growth hormone (GH)-stimulated — somatic growth mediator of GH-independent anabolic processes — small peptide
How do glucocorticoids cause hyperglycemia?
- Impairment of glucose transport into cells - Direct impairment of B-cell function
Urine N-telopeptide
— assay for bone turnover markers (BTMs). Explanation: assays include bone-specific alkaline phosphatase (BALP), osteocalcin, and N-terminal propeptide of type 1 procollagen (P1NP); markers specific to bone resorption include N-telopeptide of type 1 collagen (NTX), C-terminal telopeptide of type 1 collagen (CTX), and pyridinoline cross-links (table 1). — role in the care of individual patients is not well established
Fecal calprotectin
— increased in intestinal inflammation — may be useful for distinguishing inflammatory from noninflammatory causes of chronic diarrhea
Glucocorticoid remediable aldosteronism
- aldosterone synthase hyperactivity, is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.
Fatigue Headache High blood pressure Hypokalemia Intermittent or temporary paralysis Muscle spasms Muscle weakness Numbness Polyuria Polydipsia Tingling Hypernatraemia Metabolic alkalosis
Features of Glucocorticoid remediable aldosteronism
Diagnosis diabetes is a fasting plasma glucose level of _ mg per deciliter (_ mmol per liter) or more or a glycated hemoglobin level of _% or more; the diagnosis requires confirmation by the same or the other test.
126, 7, 6.5 The diagnostic cutoff point for diabetes is a fasting plasma glucose level of 126 mg per deciliter (7.0 mmol per liter) or more or a glycated hemoglobin level of 6.5% or more; the diagnosis requires confirmation by the same or the other test.
A fasting glucose level of _ to _ mg per deciliter (5.6 to 6.9 mmol per liter) is consistent with prediabetes
100, 125 mg per deciliter (5.6 to 6.9 mmol per liter) is consistent with prediabetes
Causes of spurious results for glycated hemoglobin;
- Hemoglobinopathies - altered red-cell turnover - racial and ethnic differences
What is the point of testing both fasting glucose AND A1C?
- appears to identify different groups of patients with diabetes and prediabetes - yet both tests identify patients at similar risk for complications
Most appropriate test for ovarian reserve
Day 3 FSH or antimullerian hormone at any stage of the cycle
Anti-mullerian hormone
- Expressed by the preantral and early antral follicles.
- AMH level reflect size of the primordial follicle pool
- Best marker of ovarian function
- Undetectable at menopause
- Can be measured at any time of the menstrual cycle.
Pituitiary.empty-sella
ESS: pituitary gland shrinks or isflattened; the sella turcica fills with CSF
ESS can be found in the workup of pituitary disorders, or as an incidental finding when imaging the brain.
Primary ESS: small anatomical defect above transmits pressure and causes the gland to flatten out on the walls of the sella turcica. Associated with obesity and increase in intracranial pressure in women.
Secondary ESS : injury, surgery, or XRT. Individuals with secondary ESS can develop loss of function.
Mx: depends on what else is seen in the sella and the clinical situation. The presence of a sellar mass, requires evaluation for hormonal hypersecretion and hyposecretion.
In the absence of a sellar mass and clinical evidence of hormonal excess or deficiency, measurement of thyroxine (T4) and early morning cortisol could be performed, but the likelihood is that they will be normal.
Why are plain films sufficient for the dx of osteoporosis in patient with kyphosis and loss of height?
Plain films are sufficient to diagnose vertebral fractures.
vertebral fractures ==> osteoporosis
vertebral fractures ==> predicts future fractures
No need for DEXA
Thyrotoxicosis.BestTest
Radionuclide scan
Thyrotoxicosis vs hyperthyroidism
Thyrotoxicosis is the term used to refer to all conditions associated with increased serum levels of thyroid hormone
Hyperthyroidism usually refers to those diseases in which the thyroid gland is actually synthesizing and secreting excessive thyroid hormones
_ disease and _ _ goiter probably account for more than 90% of all hyperthyroidism cases
Graves disease and toxic multinodular goiter probably account for more than 90% of all hyperthyroidism cases
Thyroid: Graves: treatment
No ideal treatment for Graves disease: Antithyroid drugs, radioiodine, and surgery are all effective and have specific advantages and disadvantages (Table 38-4)
Thyroid: Graves: Drug of choice
Meta: Drug of choice
Methimazole (Tapazole) is the drug of choice
Propylthiouracil (PTU), can cause fulminant hepatic failure; its use should be limited to
- allergic reaction with methimazole, and in whom surgery or radioactive iodine is not an option
- Pregnant patients during the first trimester (methimazole is not recommended in the first trimester because of potential to cause rare congenital defects)
▪
Patients with life-threatening thyrotoxicosis or thyroid storm, because of PTU’s ability to inhibit peripheral conversion of T4 to T3
Thyrotoxicosis: how does a radionuclide scan help with ddx?
- Graves: diffuse uptake
- Toxic nodular: focal uptake
Thyroid: Graves
Antibodies specific to Graves
TrAb
Thyrotropin Receptor Antibodies: highly specific, highly sensitive
anti-TPO can be up in other causes of thyroiditis such as Hashimoto
Thyroid: Graves: Methimazole
Adverse reaction
reversible agranulocytosis
Hyperlipidemia
How frequently should lipid levels be measured in a 40s aged patient with borderline lipids?
4-6 years
Reproductive-Endocrinology: Differential diagnosis of pathologic secondary amenorrhea consists of four main types
- Hyperprolactinemia (e.g., prolactinoma, drugs)
- Anovulatory (PCOS)
- Androgen excess (e.g., androgen-secreting tumors)
- Hypothalamic amenorrhea (e.g., stress, anorexia, excessive exercise
Reproductive-Endocrinology: Primary amenorrhea: Causes
testicular feminization and müllerian defects
Reproductive-Endocrinology: Testicular-feminization: Karyotype
XY
Caused by androgen insensitivity
XY karyotype
Normal male testosterone levels
Physical features: Breasts and feminine appearance, absence of axillary or pubic hair, and blind-ending vagina
Reproductive: Mullerian defects: Xfx
Meta: XFx PhysicalFindings
Imperforate hymen, abnormal cervix, absence of vagina
Reproductive-Endocrinology: Causes of primary amenorrhea
- Chromosomal abnormalities causing gonadal dysgenesis – 50 percent
- Hypogonadotropic hypogonadism, including functional hypothalamic amenorrhea – 20 percent
- Absence of parts, müllerian agenesis – 15 percent
- Transverse vaginal septum or imperforate hymen – 5 percent
- Pituitary disease – 5 percent
- Androgen insensitivity due to mutations in the androgen receptor, CAH, and (PCOS)
Chromosomal abnormalities causing gonadal dysgenesis (ovarian insufficiency due to the premature depletion of all oocytes and follicles) – 50 percent
- Hypogonadotropic hypogonadism, including functional hypothalamic amenorrhea – 20 percent
- Absence of the uterus, cervix, and/or vagina, müllerian agenesis – 15 percent
- Transverse vaginal septum or imperforate hymen – 5 percent
- Pituitary disease – 5 percent
- The etiology in the remaining 5 percent of cases includes a combination of disorders, such as androgen insensitivity due to mutations in the androgen receptor, congenital adrenal hyperplasia, and polycystic ovary syndrome (PCOS)
Reproductive-Endocrinology: Adhesions and obliteration of the uterine cavity
Asherman syndrome
Reproductive-Endocrinology: PCOS: cause
Thought to be caused by stimulatory effects of excess insulin on
ovarian androgen production
Reproductive-Endocrinology: PCOS: Rx for hirsuitism
Weight loss and OCP
spironolactone
Our approach to the management of hirsutism is consistent with the 2008 Endocrine Society Clinical Practice Guidelines on Hirsutism, which suggest an estrogen-progestin contraceptive as first-line pharmacologic therapy for most women [8]. In addition, the 2013 Endocrine Society Clinical Practice Guidelines on the Diagnosis and Treatment of Polycystic Ovary Syndrome also suggest OCs as first-line therapy for menstrual irregularities and hirsutism [1]. An antiandrogen is then added after six months if the cosmetic response is suboptimal (see “Treatment of hirsutism”). OCs and an antiandrogen may sometimes be started simultaneously at the outset, particularly when the cutaneous manifestations are particularly bothersome to the patient.
For women with hirsutism and contraindications to OCs, we sometimes use spironolactone alone, but an alternative form of contraception is essential because, if pregnancy occurs, an antiandrogen such as spironolactone could prevent development of normal external genitalia in a male fetus. Spironolactone alone does not regularize menstrual cycles, and in fact, is sometimes associated with menstrual irregularities. Therefore, in women using spironolactone as monotherapy for hyperandrogenism, progestin therapy is often needed. (See ‘Endometrial protection’ above and “Treatment of hirsutism”, section on ‘Antiandrogen therapy’.)
Reproductive-Endocrinology: Breast tenderness, galactorrhea: Implies
Prolactin excess: Breast tenderness, galactorrhea
Reproductive-endocrinology: Hirsutism, acne, increased muscle mass, clitoromegaly: Implies
Meta: implies, signifies
Androgen excess
Reproductive-endocrinology: Hirsuitism: EtiologicTypes
- Ovarian
- Adrenal
- High prolactin
- Drugs
- Physiologic
Reproductive-Endocrinology: Hirsuitism: Drug-causes
androgens, phenytoin, cyclosporine
Reproductive-Endocrinology:
Inherited defects in adrenal cortisol synthesis result in overproduction of other adrenal hormones, including androgens
CAH
Late-onset or nonclassic 21-hydroxylase deficiency is the most common form, occurring in 0.1–1% of women
Reproductive-Endocrinology:
Hirsutism begins at menarche
Menstrual irregularities begin in adulthood
CAH
Diagnosis
17-Hydroxyprogesterone will be elevated (stimulation with synthetic ACTH may be necessary to elicit the abnormality)
Treatment
Hydrocorticosone will decrease the excess androgen production
Reproductive-Endocrinology:
Sudden onset, rapid course, and/or presence of virilization suggestive of
Meta: should be a Dx question
Malignancy
Most common cause of primary hypogonadism in men is
Klinefelter syndrome
Male hypogonadism: Causes
Hypergonadotropic and Hypogonadrotropic hypogonadism
Primary Hypogonadism (Hypergonadotropic Hypogonadism)
Trauma to genital organs
Autoimmune destruction
Mumps orchitis
Medications
Cyclosporine
Chemotherapeutic agents
Congenital disorders
Klinefelter syndrome
Bilateral anorchia
Secondary Hypogonadism (Hypogonadotropic Hypogonadism)
- Chronic illness
- Medications
- Opiates
- Glucocorticoids
- Leuprolide
- Prolactinoma
- Damage to hypothalamus or pituitary
- Radiation
- Tumor
- Trauma
- Hereditary
- Hemochromatosis (pituitary iron deposition)
- Congenital disorders
- Kallman syndrome
Reproductive-Endocrinology: Klinefelter: Karyotype
XXY
Klinefelter syndrome is the most common congenital abnormality causing primary hypogonadism, occurring in approximately 1 in 1000 live male births [1,2]. This syndrome is the clinical manifestation of a male who has an extra X chromosome. The most common genotype is 47,XXY (figure 1), but greater and lesser numbers of X chromosomes have also been reported, resulting in karyotypes such as 48,XXXY and 46,XY/47,XXY mosaicism [3]. 46,XX males also have Klinefelter syndrome; the development of testes in this setting is presumably due to translocation of a small portion of chromosomal material containing the testis-determining factor to an X chromosome.
The 47,XXY genotype results from nondisjunction of the sex chromosomes of either parent during meiotic division, while mosaicism probably results from nondisjunction during mitotic division after conception. The greater the number of extra X chromosomes, the greater the phenotypic consequences, both gonadal and extragonadal [3]:
●Damage to the seminiferous tubules and, usually, damage to the Leydig cells as well. The gonadal manifestations include almost invariably small, firm testes, severely subnormal sperm count, infertility, elevated serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations, variably subnormal serum testosterone concentration and decreased virilization [3,4]. The damage may be increased if the patient also has cryptorchidism, the incidence of which is increased in Klinefelter [5].
●A long bone abnormality, resulting in increased length of the legs, independent of the increased length of both the arms and legs caused by testosterone deficiency.
●A psychosocial abnormality, unrelated to the hypogonadism, which causes difficulty in social interactions throughout life [6] and has been characterized by “marked lack of insight, poor judgment, and impaired ability to learn from adverse experience” [7].
●Impairment of higher level linguistic competence but relative sparing of vocabulary and understanding of language [8].
●Deficit in the ability to sustain attention without impulsivity [8].
●Predisposition to develop morbidities later in life that are unrelated to testosterone deficiency [9]. These include pulmonary diseases such as chronic bronchitis, bronchiectasis, and emphysema [10]; cancers, including germ cell tumors (particularly extragonadal tumors involving the mediastinum) [11], breast cancer [12], and possibly non-Hodgkin lymphoma [13]; varicose veins, leading to leg ulcers [14]; systemic lupus erythematosus, probably due to the extra X chromosome [15]; and diabetes mellitus [16]. (See “Extragonadal germ cell tumors involving the mediastinum and retroperitoneum” and “Breast cancer in men”.)
impotence associated with distal aortic atherosclerosis resulting in claudication of the lower back, buttocks, and thighs)
Lehriche syndrome
Calcium: PTH: responds to levels of
Ca++, Phos, Mg++
PTH level is responsive to level of ionized calcium in the blood as well as to the levels of phosphate and magnesium
Calcium: circulating forms
Ionized, protein-bound, anion-bound
- “Ionized” or the free form: Maintained in very narrow limits (45%)
- Bound to protein (albumin and globulin) (40%)
- Bound to anions (bicarbonate, phosphate, citrate) (15%)
PTH: sites-of-action
Bone, Kidney, GI
PTH: effect of raising Ca++
Goes down in minutes
Calcium regulates not only the release of PTH but also its synthesis and degradation. In normal subjects, a decrease in serum ionized calcium of as little as 0.1 mg/dL (0.025 mmol/L) results in a large increase in serum PTH concentration within minutes; conversely, an equally small increase in serum ionized calcium rapidly lowers the serum PTH concentration
PTH: what does it do to Vitamin D?
25-D -> calcitriol in the kidney
Then transported to kidney, where it is 1-hydroxylated (under the control of PTH) to 1,25-dihydroxyvitamin D; 1,25(OH)2D (calcitriol) is the active form
Vitamin D: what does the skin make it from?
7-dehydrocholesterol
Very few foods naturally contain vitamin D; fatty fish and eggs are the exceptions. Dermal synthesis and foods fortified with vitamin D are the major sources of the vitamin. (See ‘Sources’ above.)
Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)
●The Recommended Dietary Allowance (RDA) for vitamin D is 600 international units (units) daily for adults through age 70 years and for children 1 to 18 years of age (table 2). For adults 71 years and older, 800 units (20 micrograms) daily is recommended for the prevention and treatment of osteoporosis. Vitamin D intake and effective sun exposure are often inadequate in older adults. In older adults, particularly those at increased risk of falls and fracture, we suggest supplementation with vitamin D (Grade 2B). We administer 600 to 800 international units daily. (See ‘Requirements’ above and “Calcium and vitamin D supplementation in osteoporosis”.)
●
Vitamin D: terminology
- Cholecalciferol: D3
- 25-OH-D: D3 after hydroxylation in liver.
- 1,25-(OH)2-D: After the next hydroxylation in the kidney.
- Calcitriol: the double hydroxylated form of Vitamin D and the active form.
Only in fatty fish and eggs are the exceptions. Dermal synthesis and foods fortified with vitamin D are the major sources of the vitamin.
●Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)
●
Vitamin D: which vitamin D form to given in renal failure?
Calcitriol
Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)
Vitamin D: which form to give to folks without sun?
D3
Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)
Calcium: when is a normal calcium actually high?
Hypoalbuminemia
Calcium is bound to albumin (40%); a “normal” total calcium may actually be high if the albumin is low.
0.8 mg/dL for each 1 g by which the serum albumin level is above or below 4 g/dL
Calcium: effect of alkalosis
Decreases ionized Ca++
Acid-base status is also important because alkalosis increases calcium binding to albumin, whereas acidosis decreases it
Hypercalcemia: main causes
Hyperparathyroidism and cancer
The two most common causes are hyperparathyroidism and malignancy, which make up more than 90% of cases.
Primary hyperparathyroidism
Malignancy
- Bone metastases
- Humoral hypercalcemia (related to PTH-rp)
- Conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D
Granulomatous disease: Sarcoidosis, Tuberculosis
Familial hypocalciuric hypercalcemia
Drugs
Thiazide diuretics (stimulate renal resorption of calcium)
Lithium (changes “set point” of PTH release)
Vitamin A or D intoxication
Immobilization
Other
Thyrotoxicosis
Pheochromocytoma
Adrenal insufficiency
Parenteral nutrition
Hypercalcemia: drug-causes
Thiazides, Lithium
Thiazide diuretics (stimulate renal resorption of calcium)
Lithium (changes “set point” of PTH release)
Hypercalcemia: genetic cause
FHH
Hypercalcemia: PathoMechanism in granulomatous disease
Unregulated synthesis of 1,25(OH)2 vitamin D by granuloma-associated macrophages
Not sensitive to negative feedback suppression by ↑calcium
Band keratopathy
Band keratopathy is a corneal disease derived from the appearance of calcium on the central cornea. This is an example of metastatic calcification, which by definition, occurs in the presence of hypercalcemia.[1][
Hypercalcemia: how long does it take for ZA to work?
2 days, nadir at 7 days
- Pamidronate or zoledronate are drugs of choice; potent and effective
- Calcium level begins to decline within 2 days and hits nadir at 7 days
Hypercalcemia: when are steroids useful?
In hypercalcemia due to granulomatous disease
Most useful in treating vitamin D–mediated hypercalcemia (i.e., vitamin D intoxication, granulomatous diseases)
Work via inhibition of 1,25(OH)2D production
Hypocalcemia: when fixing also check?
Check Mg
Severe cases (symptomatic patients): IV repletion with calcium gluconate or calcium chloride slowly
Ensure magnesium is also replete
Mild cases: Oral calcium carbonate or calcium citrate; usually vitamin D as well
Hypocalcemia: EGK
QT prolongation
Osteoporosis: risk factors
- Personal history of a fragility fracture
- first-degree relative
- Thin body habitus (<127 pounds)
- Current smoking
- Current use of glucocorticoid therapy for longer than 3 months
Osteoporosis: steroid use, how long
3 months
- Daily 7.5 mg prednisone are required for bone loss to occur
- Occurs within 3 to 6 months of use
Osteoporosis: T-score and Z-score
- T-score: SDs +/- mean BMD of young adults
- Z-score: SDs +/- mean BMD of same age and gender
Osteoporosis: DEXA: where is it measured?
Hip and spine
Calculates BMD on the basis of tissue absorption of photons from a radionuclide source or x-ray tube
Measures BMD both at axial (spine) and at appendicular (hip) sites
Osteoporosis: DEXA: who to screen
- Women > 65
- Women with 1 risk factor
- Men > 70
- Men with 1 risk factor
All women 65 years of age or older
Women under age 65 years with one or more clinical risk factors
All men 70 years of age or older
Men under age 70 years with one or more clinical risk factors
Aid in decision regarding hormone therapy
Radiologic evidence of osteopenia
Prior osteoporotic fracture
Monitoring therapy for osteoporosis
Osteoporosis: which drugs have been proven to reduce hip/non-spine fractures?
alendronate, risedronate, zoledronic acid, teriparatide, denusomab
Osteoporosis: follow up
2 years
Reassessment by DXA at 2 years is usually reasonable
Pathophysiology: Chaotic osteoclast function with increased bone remodeling (both formation and resorption)
Paget’s
Paget’s: why CHF?
Many vascular shunts
High-output congestive heart failure from numerous vascular shunts
Paget’s: Rx
Bisphosphonates for severe disease
Osteoporosis: FRAX Indications for treatment
P(hip-fracture) > 3% or P(major-fracture) > 20%
f the probability of a hip fracture is 3% or greater and/or the probability of any major osteoporotic fracture is 20% or greater, the patient is a candidate for pharmacotherapy. In this case, the patient’s 10-year risk of hip fracture is 4%, and thus she is a candidate.
Hypertriglyceridemia + untreated DM2: why treat DM2 first?
Because it will fix the hypertriglycerides
Hypertriglyceridemia:
For patients with triglyceride levels persistently above 886 mg/dL (10.0 mmol/L) after nonpharmacologic interventions, we suggest starting drug therapy to lower the risk of pancreatitis (Grade 2C).
We start therapy with a fibrate.
Osteoporosis: when to start bisphosphonates after hip fracture?
Within 1 to 2 months
Theoretical risk of impairing healing in the first 2 weeks
Cholesterol: how frequently to screen for borderline hypercholesterolemia in a middle aged person?
4 to 6 years
Diabetes: Close control target in the ICU
140 to 180
IV insulin continous
While the optimal blood glucose target is unclear, we suggest a blood glucose target of 140 to 180 mg/dL (7.7 to 10 mmol/L)
While most clinicians agree that such glycemic control is a desirable intervention, the optimal blood glucose range is controversial. (See ‘Glycemic control’ above.)
- For hyperglycemic critically ill children and adults, we recommend against using a stringent intensive insulin therapy regimen to achieve a target blood glucose range of 80 to 110 mg/dL (4.4 to 6.1 mmol/L) ((Grade 1A) for adults;(Grade 1B) for children). While the optimal blood glucose target is unclear, we suggest a blood glucose target of 140 to 180 mg/dL (7.7 to 10 mmol/L) rather than a more stringent target or a more liberal target (eg, 180 to 200 mg/dL [10 to 11.1 mmol/L]) (Grade 2C). This preference is based upon clinical trials in critically ill children and adults that suggest that IIT is not beneficial and is associated with an increased risk of severe hypoglycemia. (See ‘Glycemic control’ above and ‘General approach’ above.)
- To achieve the target blood glucose in adult patients, we minimize use of intravenous fluids (IVF) that contain glucose and administer insulin only when necessary. A widely accepted insulin regimen has not been established but short-acting insulin is preferred. The same basic principles apply in pediatric patients with the exception that children (particularly young children) generally require dextrose in maintenance IVF to ensure adequate glucose delivery to avoid hypoglycemia and provide nutrition. Other sources of glucose (eg, IV medications) should be limited in critically ill children. (See ‘General approach’ above.)
- Careful monitoring of blood glucose is necessary to achieve glycemic control while avoiding the potential harmful effects of hypoglycemia. (See ‘General approach’ above and ‘Hypoglycemia’ above.)
Hyponatremia: developing 1 week after trans-sphenoidal resection + normal hormones. Dx/Rx
Dx: SIADH
Rx: Fluid restrict
The SIADH is transient, 7 to 10 days after
Adrenal-insufficiency: why is mineralcorticoid replacement not necessary in central adrenal insufficiency?
Aldosterone is regulated by the RAS, primarily.
Hence, levels are adequate
Thyroid: Hyperthyroidism: why is methimazole prefered over PTU?
Dosing less frequent, less toxic
Thyroid: Hyperthyroidism: Fever+sore throat in a patient on methimazole: Trigger
Check for agranulocytosis
Fever+sore throat: CFx agranulocytosis
Agranulocytosis: Rx
Antibiotics
GM-CSF (no evidence)
Thyrotoxicosis: FirstTest
Radionuclide scan with I-123 or Tc
Thyroid: Graves: serology
Trab
TRAb stimulate the thyroid gland and are specific for Graves’ disease, in contrast to thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies. They bind mainly to the leucine-rich repeat region of the thyroid-stimulating hormone (TSH) receptor (TSHR) ectodomain to which the TSH binds (figure 1). (See ‘Autoantibodies to the TSH receptor’ above.)
Post-prandial hypoglycemia after gastric bypass. Rx
Decrease carb content in meals
Late dumping – Less often, patients complain of the same constellation of symptoms hours after eating, so-called late dumping syndrome. This phenomenon is not strictly due to alterations of osmotic gradients across the gastrointestinal (GI) tract, but rather is thought to result from hypoglycemia following a postprandial insulin peak. (See “Postprandial (reactive) hypoglycemia”.)
●Diagnosis – A suggestive pattern of symptoms in a patient who has undergone gastric surgery should raise the possibility of dumping syndrome. The diagnosis of dumping syndrome is made primarily on clinical grounds [11]. A monitored glucose challenge, upper GI series, or gastric emptying studies have been used to support the diagnosis.
●Treatment – Most patients with dumping can be treated conservatively with dietary changes (frequent small meals that are high in fiber and protein and low in carbohydrates, separation of liquid from solid during meals) [9,10]. Symptoms tend to resolve in most patients as they learn to avoid foods that aggravate the problem (eg, simple sugar).
Sunitinib: endocrine side effect
Hypothryoidism
Gender dysphoria: first-step
Referral to psychiatrist for dx confirmation
Primary adrenal insufficiency is its principal manifestation, but autoimmune thyroid disease and type 1 diabetes mellitus are also common. About half of the cases are familial, with polygenic modes of inheritance. It occurs later than type 1, usually presenting by age 40 years.
+ Pernicious anemia
Polyglandular autoimmune syndrome 2
Thyroid: frankly elevated TSH
> 10
For patients with subclinical hypothyroidism and TSH concentrations ≥10 mU/L, we suggest treatment with thyroid hormone (T4 [levothyroxine]) (Grade 2B) (algorithm 1). (See ‘Candidates for T4 replacement’ above.)
●For patients with TSH of 7.0 to 9.9 mU/L who are <65 to 70 years, we also suggest treatment with thyroid hormone (Grade 2C). However, for patients >65 to 70 years, we suggest treatment only if they have convincing symptoms of hypothyroidism (algorithm 1). (See ‘Candidates for T4 replacement’ above.)
●For patients with TSH above the upper limit of normal to 6.9 mU/L, we suggest treatment in patients <65 to 70 years who have symptoms of hypothyroidism (Grade 2C). Treatment with T4 can also be considered in such patients with TSH above the upper limit of normal to 6.9 mU/L who have high titers of thyroid peroxidase (TPO) antibodies, which predict progression to overt hypothyroidism, or goiter (algorithm 1). (See ‘Candidates for T4 replacement’ above.)
●For older patients (>65 to 70 years) with subclinical hypothyroidism and TSH above the upper limit of normal to 6.9 mU/L, we suggest not treating (Grade 2C), in view of the uncertain benefits and the potential for both cardiovascular and skeletal morbidity associated with inadvertent overtreatment (algorithm 1). (See ‘Candidates for T4 replacement’ above.)
Ectopic ACTH: tumors that make it
Carcinoid, small cell lung cancer
Morbid obesity after craniopharyngioma resection: Cause
Meta: Never seen a case
Hypothalamic injury
Graves disease: how long to treat with methimazole before tapering?
18 months
Gluconeogenesis: sites
Liver and kidney
Hence: nephrectomy can lead to hypoglycemia in a patient on glyburide. This is the reason why glyburide is contra-indicated in reduced GFR.
Cushing: SpecificTest
24-hour urinary cortisol or midnight salivary cortisol
For patients with a low index of suspicion, we suggest initial testing with one of the following first-line tests: late-night salivary cortisol (two measurements), 24-hour urinary free cortisol (UFC) excretion (two measurements), or the overnight 1 mg dexamethasone suppression test (DST). (See ‘Initial testing’ above.)
For patients with a high index of suspicion, we suggest initial testing with two of the first-line tests: late-night salivary cortisol (two measurements), 24-hour UFC excretion (two measurements), or the overnight 1 mg DST. (See ‘Initial testing’ above.)
●If UFC is chosen as the initial screening test, the result should be unequivocally increased (threefold above the upper limit of normal for the assay), or the diagnosis of CS is uncertain and other tests should be performed. (S
facial plethora, proximal myopathy, striae (>1 cm wide and red/purple), and easy bruising
Cushing
Hashimoto: which antibody
Antibodies to Tg and TPO —
Nearly all patients with Hashimoto’s thyroiditis have high serum concentrations of antibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). These antibodies are also found, although usually in lower concentration, in patients with other thyroid diseases including Graves’ disease and in many subjects
Hashimoto’s thyroiditis is characterized clinically by gradual thyroid failure, with or without goiter formation, due primarily to autoimmune-mediated destruction of the thyroid gland involving apoptosis of thyroid epithelial cells. (See ‘Introduction’ above.)
Contrast induced hyperthyroidism: which scenario?
Multinodular goiter
Some nodules may be functioning autonomously
Adrenal incidentaloma: size for excision
> 4 cm consider, > 6 cm definitely excise
Heterogeneous group of patients with variable titers of antibodies, body mass index (BMI), and frequency of progression to insulin dependence [11]. Patients with high compared with low titers of GAD65 antibodies usually have a lower BMI, less endogenous insulin secretion (as measured by stimulated serum C-peptide concentrations), and progress more quickly to insulin dependenc
LADA
Latent autoimmune diabetes in adults (LADA) — Older studies in predominantly Scandinavian populations have suggested that as many as 7.5 to 10 percent of adults in populations with a high prevalence of type 1 diabetes and with apparent type 2 diabetes may have circulating autoantibodies directed against pancreatic beta cell antigens (islet-cell antibodies [ICA] or GAD65) [2-4]. The prevalence of LADA is almost certainly lower in the more diverse United States population. These adults do not require insulin at diagnosis but progress to insulin dependence after several months to years. This entity is sometimes referred to as “latent autoimmune diabetes in adults” (LADA) and may account for a very small fraction of all cases of diabetes [5-7].
) is a rare inherited connective tissue disorder with many phenotypic presentations. Severely affected patients suffer multiple fractures with minimal or no trauma; most commonly caused by autosomal dominant mutations in genes encoding the alpha-1 and alpha-2 chains of type I collagen (COL1A1 and COL1A2).
Osteogenesis imperfecta (OI)
Diabetes: drugs to avoid in diabetic gastroparesis
GLP-1 agonists and amylin analogues
Diabetes: how do GLP-1 agonists work?
Delay gastric emptying
enhancement of glucose-dependent insulin secretion, slowed gastric emptying, regulation of postprandial glucagon, and reduction of food intake (table 1). They do not usually cause hypoglycemia in the absence of therapies that otherwise cause hypoglycemia.
Exact role is unclear
Amylin analogue: mechanism-of-action
Slows gastric emptying
Pramlintide regulates postmeal blood glucose levels by slowing gastric emptying, promoting satiety, and suppressing the abnormal postprandial rise of glucagon in patients with diabetes [11-13]. Thus, endogenous (liver-derived) and exogenous (meal-derived) glucose influx are better regulated, allowing exogenous insulin therapy to more easily match physiologic needs.
X-linked hypophosphatemia: Rx
Phosphate + calcitriol
Elderly man at risk for falls: which supplement?
Vitamin D
Reproductive-endocrinology: hormonal contraceptive in patient with hypertriglyceridemia
Progestin-only contraceptive
Eg: depot medroxyprogesterone
medullary thyroid cancer (MTC), pheochromocytoma, and primary parathyroid hyperplasia.
MEN2a
Approximately 40% have pheo
MEN1 vs MEN2
MEN1: pancreatic neuroendocrine neoplasia, pitutiary tumors
Hypercalcemia, hyperphosphatemia + low calcitriol
Milk-alkali syndrome
