Hillel J. Gitelman

Biographical Timeline

• 1932 – Born December 23, in Rochester, New York, son of Jacob Gitelman (judge and lawyer) and Belle Gitelman (artist and concert pianist).
• 1949 – Graduated from Monroe High School, Rochester NY. Awarded scholarship to Princeton University.
• 1954 – Graduated AB, Princeton University.
• 1958 – Graduated MD, University of Rochester Medical School.
• 1960 – Completed internal medicine residency at Duke University. Commenced research fellowship at the National Institutes of Health (NIH).
• 1962 – Nephrology fellowship at University of North Carolina School of Medicine, Chapel Hill.
• 1966 – Described a novel familial kidney disorder involving hypokalaemia and hypomagnesaemia in two sisters, later known as Gitelman syndrome.
• 1970s–1990s – Continued research in nephrology and bone metabolism, including studies on aluminium-related bone disease and calcium-magnesium-phosphate homeostasis.
• 1990s – Gene responsible for Gitelman syndrome (SLC12A3) cloned by his group at the time of his retirement.
• 1995 – Retired after a 30-year career at UNC, Chapel Hill.
• 2015 – Died January 12, aged 82 at Carolina Meadows, Chapel Hill, NC, from complications of Parkinson’s disease.

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Medical Eponyms

Gitelman Syndrome (1969)

Gitelman syndrome is an autosomal recessive renal tubulopathy characterised by hypokalaemia, hypomagnesaemia, hypocalciuria, and metabolic alkalosis, with normal or low blood pressure. It affects the distal convoluted tubule, mimicking the action of thiazide diuretics. First described by Hillel Gitelman in 1966 and genetically defined in the 1990s, it is now recognised as one of the most common inherited salt-wasting disorders.

1966 – Original description by Gitelman HJ, Graham JB, and Welt LG. published as A familial disorder characterized by hypokalemia and hypomagnesemia. Gitelman’s team documented clinical and biochemical features distinguishing the disorder from Bartter syndrome. Their patients had low urinary calcium and no juxtaglomerular hyperplasia, setting the stage for recognition of a distinct renal salt-handling defect.

The syndrome presented in two sisters revealed consistent electrolyte abnormalities — notably hypokalaemia and hypomagnesaemia — without significant renal sodium wasting or hypertension.

Gitelman, 1966

Molecular Genetics and Diagnostic Criteria

In the mid-1990s, Gitelman syndrome was linked to mutations in the SLC12A3 gene encoding the thiazide-sensitive Na⁺-Cl⁻ cotransporter (NCC) in the distal convoluted tubule. This clarified its pathophysiology and confirmed it as a discrete entity from Bartter syndrome, which involves NKCC2 or ROMK mutations in the loop of Henle.

Diagnosis:

• Persistent hypokalaemia and hypomagnesaemia
• Hypocalciuria (vs. hypercalciuria in Bartter)
• Normal or low blood pressure
• No response to spironolactone
• Genetic confirmation of SLC12A3 mutations

Management:

• Consideration of amiloride, spironolactone or NSAIDs in select cases
• Lifelong potassium and magnesium supplementation; amiloride, spironolactone, and NSAIDs may assist in some cases.
• Cardiac monitoring is advised in symptomatic patients.
• Pharmacological chaperones (e.g., 4-phenylbutyrate) are being explored to stabilise mutant NCC protein trafficking.

Summary

Comparative Context:

Feature	Bartter Syndrome	Gitelman Syndrome	Liddle Syndrome
Defect location	Thick Ascending Limb of Loop of Henle	Distal Convoluted Tubule	Collecting Duct (ENaC channel)
Transporter affected	NKCC2 (Na⁺-K⁺-2Cl⁻ cotransporter)	Na⁺-Cl⁻ cotransporter (SLC12A3)	Epithelial Na⁺ Channel (ENaC; SCNN1B/SCNN1G)
Pathophysiologic mimic	Loop diuretics (lose Ca²⁺)	Thiazide diuretics (preserve Ca²⁺)	Aldosterone excess (but low aldosterone)
Serum potassium (K⁺)	↓ Hypokalaemia	↓ Hypokalaemia	↓ Hypokalaemia
Serum bicarbonate (HCO₃⁻)	↑ Metabolic alkalosis	↑ Metabolic alkalosis	↑ Metabolic alkalosis
Serum magnesium (Mg²⁺)	Normal or mildly ↓	↓ Hypomagnesemia	Normal
Urinary calcium	↑ Hypercalciuria	↓ Hypocalciuria	Normal
Blood pressure	Normal or low	Normal or low	↑ Hypertension
Renin	↑ Elevated	↑ Elevated	↓ Suppressed
Aldosterone	↑ Elevated	↑ Elevated	↓ Suppressed
Age of onset	Neonatal/Childhood	Childhood/Adolescence	Childhood/Adolescence
Response to treatment	NSAIDs (↓ prostaglandins), K⁺, spironolactone	Mg²⁺ and K⁺ supplementation, ± NSAIDs	Amiloride or triamterene (ENaC inhibitors)

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Major Publications

• Gitelman HJ, Graham JB, Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Physicians. 1966;79:221-35. [Gitelman syndrome]
• Gitelman HJ, Kukolj S, Welt LG. The influence of the parathyroid glands on the hypercalcemia of experimental magnesium depletion in the rat. J Clin Invest. 1968 Jan;47(1):118-26. 
• Gitelman HJ, Graham JB, Welt LG. A familial disorder characterized by hypokalemia and hypomagnesemia. Ann N Y Acad Sci. 1969 Aug 15;162(2):856-64.
• Bello VA, Gitelman HJ. High fluoride exposure in hemodialysis patients. Am J Kidney Dis. 1990 Apr;15(4):320-4.

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References

Eponymous terms

• Cruz DN, Shaer AJ, Bia MJ, Lifton RP, Simon DB; Yale Gitelman’s and Bartter’s Syndrome Collaborative Study Group. Gitelman’s syndrome revisited: an evaluation of symptoms and health-related quality of life. Kidney Int. 2001 Feb;59(2):710-7. 
• Unwin RJ, Capasso G. Bartter’s and Gitelman’s syndromes: their relationship to the actions of loop and thiazide diuretics. Curr Opin Pharmacol. 2006 Apr;6(2):208-13.
• Knoers NV, Levtchenko EN. Gitelman syndrome. Orphanet J Rare Dis. 2008 Jul 30;3:22.
• Graziani G, Fedeli C, Moroni L, Cosmai L, Badalamenti S, Ponticelli C. Gitelman syndrome: pathophysiological and clinical aspects. QJM. 2010 Oct;103(10):741-8.