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Questions and Answers
In patients with CKD, GH levels are typically decreased after a glucose challenge.
In patients with CKD, GH levels are typically decreased after a glucose challenge.
False (B)
Cabergoline is a somatostatin analogue used to treat acromegaly.
Cabergoline is a somatostatin analogue used to treat acromegaly.
False (B)
Pegvisomant is a GH-receptor agonist used to treat acromegaly.
Pegvisomant is a GH-receptor agonist used to treat acromegaly.
False (B)
Surgery is usually the second-line treatment for acromegaly in CKD.
Surgery is usually the second-line treatment for acromegaly in CKD.
IGF-1 levels are typically increased in patients with CKD and acromegaly.
IGF-1 levels are typically increased in patients with CKD and acromegaly.
Pasireotide is a dopamine agonist used to treat acromegaly in CKD.
Pasireotide is a dopamine agonist used to treat acromegaly in CKD.
Somatostatin analogues target GH receptors in pituitary tumors.
Somatostatin analogues target GH receptors in pituitary tumors.
There is a wealth of literature on the medical treatment of acromegaly in patients with CKD.
There is a wealth of literature on the medical treatment of acromegaly in patients with CKD.
Cabergoline is effective in controlling acromegaly in approximately two-thirds of patients.
Cabergoline is effective in controlling acromegaly in approximately two-thirds of patients.
IGF-1 level is not a reliable diagnostic criterion for acromegaly in patients with CKD.
IGF-1 level is not a reliable diagnostic criterion for acromegaly in patients with CKD.
Pasireotide LAR is a short-acting somatostatin analogue.
Pasireotide LAR is a short-acting somatostatin analogue.
Dose adjustment of cabergoline is necessary in patients with CKD.
Dose adjustment of cabergoline is necessary in patients with CKD.
Octreotide LAR is a long-acting somatostatin analogue used to control acromegaly.
Octreotide LAR is a long-acting somatostatin analogue used to control acromegaly.
Lanreotide depot is a somatostatin analogue used to treat prolactin disorders.
Lanreotide depot is a somatostatin analogue used to treat prolactin disorders.
AVP and copeptin are secreted in a 2:1 ratio upon stimulation by an increase in serum osmolarity.
AVP and copeptin are secreted in a 2:1 ratio upon stimulation by an increase in serum osmolarity.
Intramuscular injection of octreotide LAR depot has no effect on GH and IGF-1 levels in patients with acromegaly and CKD.
Intramuscular injection of octreotide LAR depot has no effect on GH and IGF-1 levels in patients with acromegaly and CKD.
Cabergoline is FDA approved for the treatment of Cushing's disease in the United States.
Cabergoline is FDA approved for the treatment of Cushing's disease in the United States.
Mifepristone is primarily used to target the adrenal gland in the treatment of Cushing's disease.
Mifepristone is primarily used to target the adrenal gland in the treatment of Cushing's disease.
Etomidate requires a higher dose in patients with renal insufficiency.
Etomidate requires a higher dose in patients with renal insufficiency.
Pasireotide targets the adrenal gland in the treatment of Cushing's disease.
Pasireotide targets the adrenal gland in the treatment of Cushing's disease.
Mitotane is FDA approved for the treatment of Cushing's disease in the United States.
Mitotane is FDA approved for the treatment of Cushing's disease in the United States.
Somatostatin receptor agonists, such as pasireotide, are used to treat acromegaly.
Somatostatin receptor agonists, such as pasireotide, are used to treat acromegaly.
An MRI with intravenous contrast is usually required to confirm the presence of a pituitary lesion in patients with acromegaly.
An MRI with intravenous contrast is usually required to confirm the presence of a pituitary lesion in patients with acromegaly.
Ketoconazole requires a dose adjustment in patients with renal impairment.
Ketoconazole requires a dose adjustment in patients with renal impairment.
Copeptin levels are decreased in patients with CKD.
Copeptin levels are decreased in patients with CKD.
Measurement of AVP is less exacting than measurement of copeptin.
Measurement of AVP is less exacting than measurement of copeptin.
Lanreotide depot requires dose adjustment in patients with normal renal function.
Lanreotide depot requires dose adjustment in patients with normal renal function.
Pasireotide is a somatostatin analogue used to treat acromegaly in CKD.
Pasireotide is a somatostatin analogue used to treat acromegaly in CKD.
Cabergoline is used to target GH receptors in pituitary tumors.
Cabergoline is used to target GH receptors in pituitary tumors.
The increase in copeptin in CKD is similar to that of AVP.
The increase in copeptin in CKD is similar to that of AVP.
Neurophysin II is a product of proteolytic cleavage of AVP.
Neurophysin II is a product of proteolytic cleavage of AVP.
The peptide content in secretory vesicles accounts for the faint signal observed on the T1-weighted MRI of the neurohypophysis.
The peptide content in secretory vesicles accounts for the faint signal observed on the T1-weighted MRI of the neurohypophysis.
In patients with CKD, the diagnosis of acromegaly is facilitated by the typical decrease in growth hormone after an oral glucose load.
In patients with CKD, the diagnosis of acromegaly is facilitated by the typical decrease in growth hormone after an oral glucose load.
Arginine vasopressin levels are decreased in patients with renal impairment due to increased clearance.
Arginine vasopressin levels are decreased in patients with renal impairment due to increased clearance.
Diabetes insipidus can be diagnosed early in patients with advanced kidney disease.
Diabetes insipidus can be diagnosed early in patients with advanced kidney disease.
Hypothalamic dopamine stimulates the secretion of prolactin.
Hypothalamic dopamine stimulates the secretion of prolactin.
Prolactin levels are typically decreased in patients with chronic kidney disease (CKD).
Prolactin levels are typically decreased in patients with chronic kidney disease (CKD).
Surgery is the first-line treatment for acromegaly in patients with CKD.
Surgery is the first-line treatment for acromegaly in patients with CKD.
PRL levels follow a circadian rhythm with higher levels during the daytime and lower levels during sleep.
PRL levels follow a circadian rhythm with higher levels during the daytime and lower levels during sleep.
The diagnosis of the syndrome of inappropriate antidiuretic hormone is similar in patients with advanced kidney disease as in normal subjects.
The diagnosis of the syndrome of inappropriate antidiuretic hormone is similar in patients with advanced kidney disease as in normal subjects.
What is the effect of V2R activation in vascular endothelial cells?
What is the effect of V2R activation in vascular endothelial cells?
What is the primary site of action for V1a receptors?
What is the primary site of action for V1a receptors?
What is the reason for increased AVP levels in patients on HD?
What is the reason for increased AVP levels in patients on HD?
Which receptor is responsible for the stimulatory effect of AVP on ACTH secretion?
Which receptor is responsible for the stimulatory effect of AVP on ACTH secretion?
What is the site of arginine vasopressin synthesis?
What is the site of arginine vasopressin synthesis?
What is the primary metabolic pathway for pasireotide LAR?
What is the primary metabolic pathway for pasireotide LAR?
What is the recommended dosage adjustment for octreotide in acromegalic patients with CKD?
What is the recommended dosage adjustment for octreotide in acromegalic patients with CKD?
What is the function of V2Rs in the kidney?
What is the function of V2Rs in the kidney?
What is the primary mechanism of V2R activation by AVP?
What is the primary mechanism of V2R activation by AVP?
What is co-secreted with AVP in equimolar amounts?
What is co-secreted with AVP in equimolar amounts?
Which somatostatin analogue does not require dose adjustment in patients with CKD?
Which somatostatin analogue does not require dose adjustment in patients with CKD?
What is the effect of AVP on the kidney in patients with CKD?
What is the effect of AVP on the kidney in patients with CKD?
What is the primary site of action for V2 receptors?
What is the primary site of action for V2 receptors?
What is the recommended dosage adjustment for oral octreotide in acromegalic patients with CKD?
What is the recommended dosage adjustment for oral octreotide in acromegalic patients with CKD?
What is a possible effect of ineffective deactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase 2 in patients with CKD?
What is a possible effect of ineffective deactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase 2 in patients with CKD?
Which of the following medications has a shortened half-life in patients with CKD?
Which of the following medications has a shortened half-life in patients with CKD?
What is a potential consequence of CKD on the metabolism of exogenous glucocorticoids?
What is a potential consequence of CKD on the metabolism of exogenous glucocorticoids?
Which of the following medications is used to treat nausea in patients with CKD?
Which of the following medications is used to treat nausea in patients with CKD?
Why may hyperkalemia occur in patients with advanced CKD?
Why may hyperkalemia occur in patients with advanced CKD?
What is a potential side effect of glucocorticoid therapy in patients with CKD?
What is a potential side effect of glucocorticoid therapy in patients with CKD?
Which of the following medications is NOT used to treat gastrointestinal motility disorders in patients with CKD?
Which of the following medications is NOT used to treat gastrointestinal motility disorders in patients with CKD?
What is a difference in the metabolism of exogenous steroids in CKD?
What is a difference in the metabolism of exogenous steroids in CKD?
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Study Notes
Acromegaly Diagnosis in CKD
- Acromegaly diagnosis is challenging in patients with CKD due to changes in GH and IGF-1 metabolism.
- Typical facial and acral features are often considered in patients without CKD.
- Biochemical diagnosis of acromegaly is established with an increased IGF-1 level and nonsuppressed GH levels after a glucose challenge.
- In patients with CKD, GH levels increase but IGF-1 levels remain normal.
- Paradoxical increase in GH after a glucose challenge can be seen in patients with CKD, making diagnosis more difficult.
Treatment of Acromegaly in CKD
- Surgery is usually the treatment of choice for acromegaly.
- Medical treatment is recommended if surgery is not curative or the patient is ineligible.
- Medical treatments target pituitary tumors using dopamine agonists like cabergoline and/or somatostatin analogues.
- Cabergoline is a plausible choice in patients with modest increases of postoperative GH and IGF-1 levels, but it is effective in only approximately one-third of patients.
- No dose adjustment of cabergoline is needed in patients with CKD.
- Long-acting somatostatin analogues (octreotide LAR, lanreotide depot, and pasireotide LAR) are the mainstay for controlling acromegaly.
Treatment of Cushing's Disease in CKD
- Medications used to treat Cushing's disease include cabergoline, pasireotide, etomidate, osilodrostat, ketoconazole, metyrapone, and mitotane.
- Some medications require dose adjustments in patients with renal disease.
Arginine Vasopressin (AVP) and Copeptin
- AVP is secreted in response to various stimuli, including increased serum osmolarity, decreased intravascular volume, stress, and nausea.
- Copeptin is secreted in equimolar amounts with AVP and is proposed as a surrogate marker of AVP secretion.
- Measurement of AVP is difficult, while copeptin measurement is less exacting.
- Copeptin levels are increased in patients with CKD or on chronic hemodialysis.
Hyperprolactinemia
- Prolactin is synthesized and secreted from the lactotrophs in the anterior pituitary.
- Hypothalamic dopamine exerts tonic inhibition of prolactin secretion.
- In patients with CKD, there is an increase in prolactin levels.
Renal Hyperfiltration and Medications
- There are no reports of the use of octreotide LAR or lanreotide depot in patients with CKD, and their package inserts do not contain dose adjustments for renal impairment.
- The manufacturer recommends a lower starting dose of oral octreotide in acromegalic patients with CKD.
- Pasireotide LAR is metabolized mainly in the liver, with a small fraction excreted via the kidney, and its package insert does not recommend dose adjustments for CKD.
- There is one case report of pasireotide LAR use in a patient with acromegaly and CKD requiring hemodialysis.
Arginine Vasopressin (AVP) and Kidney Disease
- AVP is secreted by magnocellular neurons in the hypothalamus and exerts its action at multiple tissues through activation of its various receptors (V1a, V1b, and V2R).
- V1a receptors are found in smooth muscles of arterioles, leading to constriction and increased systemic circulatory resistance and blood pressure.
- V1b receptors are located in the anterior pituitary and are responsible for the stimulatory effect of AVP on ACTH secretion.
- V2R activation results in urinary concentration through the insertion of aquaporin 2 molecules into the apical membrane of principal cells in the kidney.
- V2Rs are also found in extrarenal tissues, including vascular endothelial cells, where they cause release of coagulation factor VIII and von Willebrand factor.
AVP and Hemodialysis
- AVP levels are increased in patients on hemodialysis due to decreased metabolic clearance rate and impermeability of AVP molecules by dialysis membranes.
- Copeptin, co-secreted with AVP, is also increased in patients with CKD.
Other Hormonal Changes in CKD
- In CKD, there is ineffective deactivation of cortisol by 11β-hydroxysteroid dehydrogenase 2, leading to exaggerated activation of mineralocorticoid receptors and hypertension.
- Altered metabolism of exogenous glucocorticoids in CKD results in prolonged half-life of hydrocortisone and prednisolone, but shortened half-life of dexamethasone.
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