Acromegaly resident survival guide: Difference between revisions

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* Physicians should not rely on the use of random [[GH]] levels to diagnose [[acromegaly]].  
* Physicians should not rely on the use of random [[GH]] levels to diagnose [[acromegaly]].  
* Preoperative medical therapy should not continue to improve biochemical control after surgery.
* Preoperative medical therapy should not continue to improve biochemical control after surgery.
* In a patient with parasellar disease making total surgical resection is not recommended, surgical debulking should be done to improve subsequent response to medical therapy. <ref name="pmid25356808">{{cite journal| author=Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A | display-authors=etal| title=Acromegaly: an endocrine society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2014 | volume= 99 | issue= 11 | pages= 3933-51 | pmid=25356808 | doi=10.1210/jc.2014-2700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25356808  }} </ref>
* In a patient with parasellar disease making total surgical resection is not recommended, surgical debulking should be done to improve subsequent response to medical therapy.
* Monitoring of [[GH]] and/or [[IGF-1]] levels during [[pregnancy]].<ref name="pmid25356808">{{cite journal| author=Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A | display-authors=etal| title=Acromegaly: an endocrine society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2014 | volume= 99 | issue= 11 | pages= 3933-51 | pmid=25356808 | doi=10.1210/jc.2014-2700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25356808  }} </ref>


==References==
==References==

Revision as of 08:49, 21 August 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Synonyms and keywords:Somatotroph adenoma; Growth hormone excess; Growth hormone secreting pituitary adenoma

Overview

Acromegaly is the clinical syndrome that results from excessive secretion of growth hormone (GH). Its annual incidence is six to eight per million people. The mean age at diagnosis is 40 to 45 years. The most common cause of acromegaly is a somatotroph (GH-secreting) adenoma of the anterior pituitary. Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated. There is no life-threatening cause of acromegaly. However, if left untreated, 30% of patients with acromegaly may progress to develop cardiovascular manifestations, pulmonary dysfunction, and cerebral complications. These comorbidities will increase the mortality rate.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated. There is no life-threatening cause of acromegaly. However, if left untreated, 30% of patients with acromegaly may progress to develop cardiovascular manifestations, pulmonary dysfunction, and cerebral complications. These comorbidities will increase the mortality rate. [1]

Common Causes

Diagnosis

The approach to diagnosis of Acromegaly is based on a step-wise testing strategy. Below is an algorithm summarising the identification and laboratory diagnosis of Acromegaly.[9]

 
 
 
 
 
 
 
 
 
 
 
 
Characterize the symptoms:

Headaches
❑ Enlargement of the hands (change in ring or glove size) and feet (change in shoe size)
Lethargy
Hyperhidrosis (excessive sweating)
Paraesthesia [10]
Fatigue
Jaw pain
❑ Body odor
Blood in the stool
Sleep apnea
Weight gain [11]

❑ In males:
Sexual dysfunction
Loss of libido
Gynecomastia [12]

❑ In females:
Amenorrhea
Galactorrhea [12]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient:

❑ HEENT

❑ Musculoskeletal exam:

❑ Neurological exam:

❑ Cardiovascular exam:

❑ Skin exam:

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure Insulin like growth factor-1 (IGF-1) levels
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal
 
Equivocal
 
Elevated
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Active acromegaly ruled out
 
Oral glucose tolerance test (OGTT) with growth hormone (GH) levels
 
Acromegaly confirmed in a patient with typical clinical manifestations
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Growth hormone (GH) suppressed
 
 
 
 
Inadequate suppression
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Active acromegaly ruled out
 
 
 
 
 
Order pituitary MRI
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal
 
Mass or empty sella
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest and abdominal CT, Growth hormone-releasing hormone (GHRH) measurement
 
GH-secreting pituitary adenoma
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Extra-pituitary acromegaly
 


This algorithm developed and modified according to Endocrine Society (ES): Clinical practice guideline on acromegaly.

Treatment

Shown below is an algorithm summarizing the treatment of Acromegaly according the the Endocrine Society (ES): Clinical practice guideline on acromegaly.

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Transphenoidal surgery
❑ Complete resection
❑ Tumors that are unresectable, a surgical debulking procedure may be performed followed by medical therapy
 
Yes
 
Patient is not a surgical candidate
❑ Patient preference
❑ High risk due to medical comorbidities
❑ Unresectable tumors
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Are the following criteria met postoperatively?
❑ Morning serum GH the day after surgery <1ng/ml
❑ 12 weeks postoperative:
  • Normal serum IGF-1 (for age and gender)
  • No evidence of residual tumor on pituitary MRI
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Remission
❑ Monitor with annual IGF-1
 
Is there residual tumor that appears resectable and readily accessible (eg, not invading the cavernous sinus)?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform MRI for clinical or biochemical evidence of recurrence
 
Medical therapy

Somatostatin analogs:

  • Preferred regimen (1): Octreotide 50 mcg q8hr subcutaneous as initial dose and 100 mcg q8hr as effective dose.
  • Preferred regimen (2): Lanreotide 90 mg q4week for 3 months every 4 weeks subcutaneous.
  • Preferred regimen (3): Pasireotide 40 mg q4wk intramuscular.

Dopamine agonists:

  • Preferred regimen (1): Cabergoline 0.25 mg 2x/week orally.
  • Preferred regimen (2): Bromocriptine 1.25-2.5 mg qDay orally.

GH receptor antagonist:

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Failure of medical therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Radiation therapy
❑ Stereotactic radiotherapy is most common method
 
 
 
 
 


This algorithm developed and modified according to Endocrine Society (ES): Clinical practice guideline on acromegaly.

Do's

Don'ts

  • Physicians should not rely on the use of random GH levels to diagnose acromegaly.
  • Preoperative medical therapy should not continue to improve biochemical control after surgery.
  • In a patient with parasellar disease making total surgical resection is not recommended, surgical debulking should be done to improve subsequent response to medical therapy.
  • Monitoring of GH and/or IGF-1 levels during pregnancy.[9]

References

  1. Melmed S (2009). "Acromegaly pathogenesis and treatment". J Clin Invest. 119 (11): 3189–202. doi:10.1172/JCI39375. PMC 2769196. PMID 19884662.
  2. Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L (1989). "GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours". Nature. 340 (6236): 692–6. doi:10.1038/340692a0. PMID 2549426.
  3. Vallar L, Spada A, Giannattasio G (1987). "Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas". Nature. 330 (6148): 566–8. doi:10.1038/330566a0. PMID 2825031.
  4. Hayward BE, Barlier A, Korbonits M, Grossman AB, Jacquet P, Enjalbert A; et al. (2001). "Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly". J Clin Invest. 107 (6): R31–6. doi:10.1172/JCI11887. PMC 208949. PMID 11254676.
  5. Melmed S, Ezrin C, Kovacs K, Goodman RS, Frohman LA (1985). "Acromegaly due to secretion of growth hormone by an ectopic pancreatic islet-cell tumor". N Engl J Med. 312 (1): 9–17. doi:10.1056/NEJM198501033120103. PMID 2981107.
  6. Altstadt TJ, Azzarelli B, Bevering C, Edmondson J, Nelson PB (2002). "Acromegaly caused by a growth hormone-releasing hormone-secreting carcinoid tumor: case report". Neurosurgery. 50 (6): 1356–9, discussion 1360. doi:10.1097/00006123-200206000-00029. PMID 12015856.
  7. Beuschlein F, Strasburger CJ, Siegerstetter V, Moradpour D, Lichter P, Bidlingmaier M; et al. (2000). "Acromegaly caused by secretion of growth hormone by a non-Hodgkin's lymphoma". N Engl J Med. 342 (25): 1871–6. doi:10.1056/NEJM200006223422504. PMID 10861322.
  8. "Correction to Lancet Infectious Diseases 2020; published online April 29. https://doi.org/10.1016/ S1473-3099(20)30064-5". Lancet Infect Dis. 20 (7): e148. 2020. doi:10.1016/S1473-3099(20)30370-4. PMID 32595044 Check |pmid= value (help). External link in |title= (help)
  9. 9.0 9.1 9.2 9.3 Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A; et al. (2014). "Acromegaly: an endocrine society clinical practice guideline". J Clin Endocrinol Metab. 99 (11): 3933–51. doi:10.1210/jc.2014-2700. PMID 25356808.
  10. 10.0 10.1 10.2 Molitch ME (1992). "Clinical manifestations of acromegaly". Endocrinol Metab Clin North Am. 21 (3): 597–614. PMID 1521514.
  11. 11.0 11.1 11.2 "Acromegaly: MedlinePlus Medical Encyclopedia".
  12. 12.0 12.1 Iuliano SL, Laws ER (2014). "Recognizing the clinical manifestations of acromegaly: case studies". J Am Assoc Nurse Pract. 26 (3): 136–42. doi:10.1002/2327-6924.12076. PMID 24170330.
  13. Ben-Shlomo A, Melmed S (2006). "Skin manifestations in acromegaly". Clin Dermatol. 24 (4): 256–9. doi:10.1016/j.clindermatol.2006.04.011. PMID 16828406.


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