Acta Scientific Medical Sciences (ISSN: 2582-0931)

Case Report Volume 4 Issue 5

Liddle’s Syndrome Associated with Acromegaly due to Enhanced Renal and Extrarenal ENaC Channel Activity: The First Case Report that Explained this Rare Association

Juna Musa1*, Jovan Basho2, Florian Toti3, Suela Mumajesi4, Mohammed Badi5, Adi Abduli6, Loran Rakovica7 and Ali Guy8

1Postdoctoral Research Fellow, Department of Surgery, Mayo Clinic, Minnesota, USA
2Department of Gastro-Hepatology, University of Hospital Center Mother Teresa, Tirana, Albania
3Department of Endocrinology, University of Hospital Center Mother Teresa, Tirana, Albania
4Department of Nephrology and Dialysis, University of Hospital Center Mother Teresa, Tirana, Albania
5Postdoctoral Research Fellow, Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA
6Department of Emergency Care, University of Hospital Center Mother Teresa, Tirana, Albania
7Faculty of Medicine, University of Prishtina, Kosovo
8Department of Physical Medicine and Rehabilitation, School of Medicine - NYU Medical Center, New York, USA

*Corresponding Author: Juna Musa, Postdoctoral Research Fellow, Department of Surgery, Mayo Clinic, Minnesota, USA.

Received: April 12, 2020; Published: April 27, 2020

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Abstract

  Liddle’s syndrome is a rare genetic autosomal dominant disease affecting the activity of the epithelial sodium channels (ENaC) or the amiloride-sensitive sodium channels, which leads the kidneys to excrete potassium but retain too much sodium and water causing early, frequent and severe, high blood pressure associated with low plasma renin, metabolic alkalosis and normal to low levels of aldosterone [1,2]. Disease-associated mutations either activate the channel directly or abrogate aldosterone-inhibited retrieval of ENaC subunits from the plasma membrane [3]. The end result of these mutations is increased expression of activated ENaC channels at the plasma membrane of principal cells which manifests as severe early onset hypertension with hypokalemia unresponsive to spironolactone [4]. We observed an isolated case of a Liddle’s syndrome in a 23-year-old man who presented with signs of acromegaly. The patient initially presented to the emergency room with palpitations, weakness of the extremities and a three-year history of low potassium levels and uncontrolled hypertension. Six months later he was admitted again to the hospital with signs of hypokalemia, including palpitations, fatigue and weakness. Upon further evaluation, he was found to have low renin and aldosterone levels. Physical examination revealed mild diastolic hypertension, acromegalic features, weight gain, excessive sweating, widening of both hands and feet [5]. Laboratory results revealed increased levels of GH and IGF-1-a. After oral administration of oral glucose levels of IGF-1 remained elevated. MR imaging of the brain revealed a 1.3 x 1.2 x 0.7 cm pituitary adenoma. A diagnosis of acromegaly and Liddle syndrome was made. Coexisting acromegaly and Liddle syndrome are reported together only in rare cases and it can be explained due to enhanced renal and extrarenal ENaC activity.

Keywords: Liddle’s Syndrome; Epithelial Sodium Channels (ENaC); Acromegaly

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References

  1. Biff F Palmer., et al. “Liddle’s Syndrome”. The American Journal of Medicine 104 (1998): 301-309.
  2. Botero-Velez M., et al. “Liddle's syndrome revisited: disorder of sodium reabsorption in the distal tubule”. The New England Journal of Medicine 330 (1994): 178-181.
  3. Snyder PM., et al. “Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel”. Cell 83 (1995): 969-978.
  4. Jameson, Fauci., et al. “Harrison’s Principle of Internal Medicine 20th edition”.
  5. Peter Kamenicky., et al. “Body Fluid Expansion in Acromegaly Is Related to Enhanced Epithelial Sodium Channel (ENaC) Activity”. Journal of Clinical Endocrinology and Metabolism 7 (2011): 2127-2135.
  6. Zennaro MC., et al. “Inherited forms of mineralocorticoid hypertension”. Best Practice and Research Clinical Endocrinology and Metabolism 29 (2015): 633-645.
  7. Yibo Wang., et al. “A novel epithelial sodium channel γ-subunit de novo frameshift mutation leads to Liddle syndrome”. Clinical Endocrinology 67 (2007): 801-804.
  8. Marko Bertog., et al. “Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle’s syndrome”. The Journal of Physiology 2 (2008): 459-475.
  9. Sawathiparnich P., et al. “A novel mutation in the ß-subunit of the epithelial sodium channel gene (SCNN1B) in a Thai family with Liddle's syndrome”. Journal of Pediatric Endocrinology and Metabolism 22 (2009): 85-89.
  10. Hansson JH., et al. “A de novo missense mutation of the ß subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity”. Proceedings of the National Academy of Sciences of the United States of America 92 (1995): 11495-11499.
  11. Wang Y., et al. “A novel epithelial sodium channel γ-subunit de novo frameshift mutation leads to Liddle syndrome”. Journal of Clinical Endocrinology 67 (2007): 801-804.
  12. Kamide K., et al. “Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives”. Hypertension Research 5 (2004): 333-338.
  13. Alexander Staruschenko., et al. “Acute Regulation of the Epithelial Na Channel by Phosphatidylinositide 3-OH Kinase Signaling in Native Collecting Duct Principal Cells”. Journal of the American Society of Nephrology 18 (2007): 1652-1661.
  14. E Gonzalez-Rodriguez., et al. “IGF-1 vs insulin: Respective roles in modulating sodium transport via the PI-3 kinase/Sgk1 pathway in a cortical collecting duct cell line”. Kidney International 71 (2007): 116-125.
  15. Martina Tetti., et al. “Liddle Syndrome: Review of the Literature and Description of a New Case”. International Journal of Molecular Sciences 3 (2018): 812.
  16. Mulatero P., et al. “Diagnosis and treatment of low-renin hypertension”. Journal of Clinical Endocrinology 67 (2007): 324-334.
  17. Yamashita Y., et al. “Two sporadic cases of Liddle's syndrome caused by de novo ENaC mutations”. American Journal of Kidney Diseases 37 (2001): 499-504.
  18. Peter Kamenicky., et al. “Epithelial Sodium Channel Is a Key Mediator of Growth Hormone-Induced Sodium Retention in Acromegaly”. Endocrinology 7 (2008): 3294-3305.
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Citation

Citation: Juna Musa., et al. “Liddle’s Syndrome Associated with Acromegaly due to Enhanced Renal and Extrarenal ENaC Channel Activity: The First Case Report that Explained this Rare Association". Acta Scientific Medical Sciences 4.5 (2020): 79-83.



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