Acromegaly Diagnosis and Treatment in CKD
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Questions and Answers

In patients with CKD, GH levels are typically decreased after a glucose challenge.

False

Cabergoline is a somatostatin analogue used to treat acromegaly.

False

Pegvisomant is a GH-receptor agonist used to treat acromegaly.

False

Surgery is usually the second-line treatment for acromegaly in CKD.

<p>False</p> Signup and view all the answers

IGF-1 levels are typically increased in patients with CKD and acromegaly.

<p>False</p> Signup and view all the answers

Pasireotide is a dopamine agonist used to treat acromegaly in CKD.

<p>False</p> Signup and view all the answers

Somatostatin analogues target GH receptors in pituitary tumors.

<p>False</p> Signup and view all the answers

There is a wealth of literature on the medical treatment of acromegaly in patients with CKD.

<p>False</p> Signup and view all the answers

Cabergoline is effective in controlling acromegaly in approximately two-thirds of patients.

<p>False</p> Signup and view all the answers

IGF-1 level is not a reliable diagnostic criterion for acromegaly in patients with CKD.

<p>False</p> Signup and view all the answers

Pasireotide LAR is a short-acting somatostatin analogue.

<p>False</p> Signup and view all the answers

Dose adjustment of cabergoline is necessary in patients with CKD.

<p>False</p> Signup and view all the answers

Octreotide LAR is a long-acting somatostatin analogue used to control acromegaly.

<p>True</p> Signup and view all the answers

Lanreotide depot is a somatostatin analogue used to treat prolactin disorders.

<p>False</p> Signup and view all the answers

AVP and copeptin are secreted in a 2:1 ratio upon stimulation by an increase in serum osmolarity.

<p>False</p> Signup and view all the answers

Intramuscular injection of octreotide LAR depot has no effect on GH and IGF-1 levels in patients with acromegaly and CKD.

<p>False</p> Signup and view all the answers

Cabergoline is FDA approved for the treatment of Cushing's disease in the United States.

<p>False</p> Signup and view all the answers

Mifepristone is primarily used to target the adrenal gland in the treatment of Cushing's disease.

<p>False</p> Signup and view all the answers

Etomidate requires a higher dose in patients with renal insufficiency.

<p>False</p> Signup and view all the answers

Pasireotide targets the adrenal gland in the treatment of Cushing's disease.

<p>False</p> Signup and view all the answers

Mitotane is FDA approved for the treatment of Cushing's disease in the United States.

<p>False</p> Signup and view all the answers

Somatostatin receptor agonists, such as pasireotide, are used to treat acromegaly.

<p>True</p> Signup and view all the answers

An MRI with intravenous contrast is usually required to confirm the presence of a pituitary lesion in patients with acromegaly.

<p>False</p> Signup and view all the answers

Ketoconazole requires a dose adjustment in patients with renal impairment.

<p>False</p> Signup and view all the answers

Copeptin levels are decreased in patients with CKD.

<p>False</p> Signup and view all the answers

Measurement of AVP is less exacting than measurement of copeptin.

<p>False</p> Signup and view all the answers

Lanreotide depot requires dose adjustment in patients with normal renal function.

<p>False</p> Signup and view all the answers

Pasireotide is a somatostatin analogue used to treat acromegaly in CKD.

<p>False</p> Signup and view all the answers

Cabergoline is used to target GH receptors in pituitary tumors.

<p>False</p> Signup and view all the answers

The increase in copeptin in CKD is similar to that of AVP.

<p>False</p> Signup and view all the answers

Neurophysin II is a product of proteolytic cleavage of AVP.

<p>False</p> Signup and view all the answers

The peptide content in secretory vesicles accounts for the faint signal observed on the T1-weighted MRI of the neurohypophysis.

<p>False</p> Signup and view all the answers

In patients with CKD, the diagnosis of acromegaly is facilitated by the typical decrease in growth hormone after an oral glucose load.

<p>False</p> Signup and view all the answers

Arginine vasopressin levels are decreased in patients with renal impairment due to increased clearance.

<p>False</p> Signup and view all the answers

Diabetes insipidus can be diagnosed early in patients with advanced kidney disease.

<p>False</p> Signup and view all the answers

Hypothalamic dopamine stimulates the secretion of prolactin.

<p>False</p> Signup and view all the answers

Prolactin levels are typically decreased in patients with chronic kidney disease (CKD).

<p>False</p> Signup and view all the answers

Surgery is the first-line treatment for acromegaly in patients with CKD.

<p>True</p> Signup and view all the answers

PRL levels follow a circadian rhythm with higher levels during the daytime and lower levels during sleep.

<p>False</p> Signup and view all the answers

The diagnosis of the syndrome of inappropriate antidiuretic hormone is similar in patients with advanced kidney disease as in normal subjects.

<p>False</p> Signup and view all the answers

What is the effect of V2R activation in vascular endothelial cells?

<p>Release of coagulation factor VIII and von Willebrand factor</p> Signup and view all the answers

What is the primary site of action for V1a receptors?

<p>Smooth muscles of arterioles</p> Signup and view all the answers

What is the reason for increased AVP levels in patients on HD?

<p>Decreased metabolic clearance rate</p> Signup and view all the answers

Which receptor is responsible for the stimulatory effect of AVP on ACTH secretion?

<p>V1b receptors</p> Signup and view all the answers

What is the site of arginine vasopressin synthesis?

<p>Supraoptic and paraventricular nuclei of the hypothalamus</p> Signup and view all the answers

What is the primary metabolic pathway for pasireotide LAR?

<p>Hepatic metabolism</p> Signup and view all the answers

What is the recommended dosage adjustment for octreotide in acromegalic patients with CKD?

<p>Not mentioned in the package insert</p> Signup and view all the answers

What is the function of V2Rs in the kidney?

<p>Regulation of water absorption from the glomerular filtrate</p> Signup and view all the answers

What is the primary mechanism of V2R activation by AVP?

<p>Insertion of aquaporin 2 molecules</p> Signup and view all the answers

What is co-secreted with AVP in equimolar amounts?

<p>Copeptin</p> Signup and view all the answers

Which somatostatin analogue does not require dose adjustment in patients with CKD?

<p>Pasireotide LAR</p> Signup and view all the answers

What is the effect of AVP on the kidney in patients with CKD?

<p>Increased absorption of water from the glomerular filtrate</p> Signup and view all the answers

What is the primary site of action for V2 receptors?

<p>Principal cells of the distal convoluted tubes and collecting ducts</p> Signup and view all the answers

What is the recommended dosage adjustment for oral octreotide in acromegalic patients with CKD?

<p>Start with a lower dose</p> Signup and view all the answers

What is a possible effect of ineffective deactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase 2 in patients with CKD?

<p>Hypertension</p> Signup and view all the answers

Which of the following medications has a shortened half-life in patients with CKD?

<p>Dexamethasone</p> Signup and view all the answers

What is a potential consequence of CKD on the metabolism of exogenous glucocorticoids?

<p>Prolonged half-life of hydrocortisone</p> Signup and view all the answers

Which of the following medications is used to treat nausea in patients with CKD?

<p>Chlorpromazine</p> Signup and view all the answers

Why may hyperkalemia occur in patients with advanced CKD?

<p>Due to CKD itself</p> Signup and view all the answers

What is a potential side effect of glucocorticoid therapy in patients with CKD?

<p>Hypertension</p> Signup and view all the answers

Which of the following medications is NOT used to treat gastrointestinal motility disorders in patients with CKD?

<p>Verapamil</p> Signup and view all the answers

What is a difference in the metabolism of exogenous steroids in CKD?

<p>Prolonged half-life of hydrocortisone and prednisolone, but shortened half-life of dexamethasone</p> Signup and view all the answers

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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Description

This quiz covers the diagnosis and treatment of Acromegaly in patients with Chronic Kidney Disease (CKD). It includes the signs and symptoms, hormone levels, and surgical treatment options.

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