Hormone resistance in children: what primary care physicians need to know

Main Article Content

Kotb Metwalley
Hekma Saad Farghaly


hormone resistance, Laron syndrome, pseudohypoparathyroidism, insulin resistance, thyroid hormone resistance


Hormone resistance is defined as a reduced or absence of  target tissues responsiveness to a hormone, where the presentation is related to either a relative lack or excess of hormones. Various disorders of hormone resistance were encountered including, Laron syndrome, nephrogenic diabetes insipidus, thyroid hormone resistance syndrome, pseudohypoparathyroidism, insulin resistance, familial glucocorticoid deficiency, pseudohypoaldosteronism, X linked hypophosphatemic rickets  and androgen insensitivity syndrome. The article gives a summary that presents, in concentrated form, what the primary care physicians need to know about recognition,  clinical presentation, diagnosis, and management  of various hormone resistance in children.


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1.Melmed, Shlomo, Kenneth S. Polonsky, P. Reed Larsen, Henry M. Kronenberg. Williams Textbook of Endocrinology E-Book. Elsevier Health Sciences, 2015.
2.Jameson JL. Hormone resistance syndromes. Springer Science & Business Media; 1999.
3.Achermann JC, Jameson JL. Human disorders caused by nuclear receptor gene mutations. Pure Appl. Chem. 2003;75:1785-96.
4.Laron Z. Lessons from 50 years of study of Laron syndrome. Endocr Pract. 2015;21:1395-402.
5. Laron Z. Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958–2003. J Clin Endocrinol Metab. 2004;89:1031-44.
6.Laron Z, Klinger B. Body fat in Laron syndrome patients: effect of insulin-like growth factor I treatment. Horm Res. 1993;40:16-22.
7.Janecka A, Kołodziej-Rzepa M, Biesaga B. Clinical and molecular features of Laron syndrome, a genetic disorder protecting from cancer. In Vivo. 2016;30:375-81.
8.Laron Z, Kauli R, Lapkina L, Werner H. IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome. Mutat Res Rev Mutat Res.;772:123-133.
9.Laron Z, Klinger B. Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance). Eur J Endocrinol. 1998;138:176-80.
10.Refardt J. Diagnosis and differential diagnosis of diabetes insipidus: Update. Best Pract Res Clin Endocrinol Metab. 2020;34:101398.
11. Atmis B, Bayazit AK, Melek E, Bisgin A, Anarat A. From infancy to adulthood: challenges in congenital nephrogenic diabetes insipidus. J Pediatr Endocrinol Metab. 2020 ;33:1019-25.
12.Refardt J, Winzeler B, Christ-Crain M. Diabetes Insipidus: An Update. Endocrinol Metab Clin North Am. 2020;49:517-531
13.Weiner A, Vuguin P. Diabetes Insipidus. Pediatr Rev. 2020;41:96-99.
14.Mortensen LA, Bistrup C, Jensen BL, Hinrichs GR. A mini-review of pharmacological strategies used to ameliorate polyuria associated with X-linked nephrogenic diabetes insipidus. Am J Physiol Renal Physiol. 2020 ;319:F746-F753.
15.Zucchi R. Thyroid hormone analogues: An update. Thyroid. 2020;30:1099-105.
16.Tylki-Szymańska A, Acuna-Hidalgo R, Krajewska-Walasek M, et al. Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor α gene (THRA). J Med Genet. 2015;52:312-6.
17. Brent GA. Mechanisms of thyroid hormone action.  J Clin Invest. 2012;122:3035-43.
18 .Agrawal NK, Goyal R, Rastogi A, Naik D, Singh SK. Thyroid hormone resistance. Thyroid hormone resistance. Postgrad Med J. 2008;84:473-7.
19..Deng F, Yang ZY, Zhang YP, Wang YL, Hu JY, Zhang F. TSH adenoma and syndrome of resistance to thyroid hormones—Two cases report of syndrome of inappropriate secretion of thyrotropin. Brain Behav. 2021 ;10:e02081.
20-Germain-Lee EL. Management of pseudohypoparathyroidism. Curr Opin Pediatr. 2019;31:537-549. 
21-Mantovani G, Bastepe M, Monk D, et al. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement.  Nat Rev Endocrinol. 2018;14:476-500.
22-Linglart A, Levine MA, Jüppner H. Pseudohypoparathyroidism. Endocrinol Metab Clin North Am. 2018;47:865-888
23.Goto M, Yamamoto Y, Ishii M, et al. Sporadic pseudohypoparathyroidism type‐1b with asymptomatic hypocalcemia.  Pediatr Int. 2016;58:1229-1231.
24..Al Jneibi F, Hen T, Rajah J, Nair R. Early diagnosis in familial glucocorticoid deficiency. Dermatoendocrinol. 2017 ;9:e1310787.
25.Metherell LA, Chapple JP, Cooray S, et al. Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Nat Genet. 2005;37:166-70. 
26. Rumie H, Metherell LA, Clark AJ, Beauloye V, Maes M. Clinical and biological phenotype of a patient with familial glucocorticoid deficiency type 2 caused by a mutation of melanocortin 2 receptor accessory protein. Eur J Endocrinol. 2007;157:539-42.
27.Metwalley KA, Farghaly HS. Familial glucocorticoid deficiency presenting with generalized hyperpigmentation in an Egyptian child: a case report.  J Med Case Rep. 2012;6:110.
28.Chung TT, Chan LF, Metherell LA, Clark AJ. Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2. Clin Endocrinol (Oxf). 2010;72:589-94.
29.Amin N, Alvi NS, Barth JH, et al . Pseudohypoaldosteronism type 1: clinical features and management in infancy. Endocrinol Diabetes Metab Case Rep. 2013;2013:130010.
30.Riepe FG. Pseudohypoaldosteronism. Endocr Dev. 2013;24:86-95.
31.Semmekrot B, Monnens L, Theelen BG, Rascher W, Gabreels F, Willems J. The syndrome of hypertension and hyperkalaemia with normal glomerular function (Gordon's syndrome). Pediatr Nephrol. 1987;1:473-8
32.GKIzIs IG, CholIDou KG, PaPaDoPoulos DP. A case report of Gordon’s syndrome in a 20-year-old male with free medical family history. Hellenic J Cardiol. 2013;54:64-8.
33..Tagi VM, Giannini C, Chiarelli F. Insulin resistance in children.  Front Endocrinol (Lausanne). 2019;10:342.
34.Galli-Tsinopoulou A, Karamouzis M, Nousia-Arvanitakis S. Insulin resistance and hyperinsulinemia in prepubertal obese children. J Pediatr Endocrinol Metab. 2003 ;16:555-60.
35.Rung J, Cauchi S, Albrechtsen A, et al . Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet. 2009;41:1110-5. 
36.Levy-Marchal C, Arslanian S, Cutfield W, et al. Insulin resistance in children: Consensus, perspective, and future directions. J Clin Endocrinol Metabol.  2010; 95:5189–98
37. Juárez-López C, Klünder-Klünder M, Medina-Bravo P, Madrigal-Azcárate A, Mass-Díaz E, Flores-Huerta S. Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents. BMC Public Health.  2010; 10:318.
38..Raimann A, Mindler GT, Kocijan R, et al . Multidisciplinary patient care in X‐linked hypophosphatemic rickets: one challenge, many perspectives. Wien Med Wochenschr. 2020;170 :116-123.
39..Zheng B, Wang C, Chen Q, et al. Functional Characterization of PHEX Gene Variants in Children With X‐Linked Hypophosphatemic Rickets Shows No Evidence of Genotype–Phenotype Correlation. J Bone Miner Res. 2020;35:1718-1725
40.Chesher D, Oddy M, Darbar U, et al. Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J Inherit Metab Dis. 2018;41:865-876.
41.Emma F, Cappa M, Antoniazzi F, et al. X-linked hypophosphatemic rickets: an Italian experts’ opinion survey.  Ital J Pediatr. 2019 ;45:1-7.
42.Rothenbuhler A, Fadel N, Debza Y, et al. High Incidence of Cranial Synostosis and Chiari I Malformation in Children With X‐Linked Hypophosphatemic Rickets (XLHR). J Bone Miner Res. 2019;34:490-496.
43..Makitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E. Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets.  Clin Endocrinol Metab. 2003;88:3591-7
44.Schindeler A, Biggin A, Munns CF. Clinical evidence for the benefits of burosumab therapy for X-linked hypophosphatemia (XLH) and other conditions in adults and children. Front Endocrinol (Lausanne). 2020;11:338.
45.Liu Q, Yin X, Li P. Clinical, hormonal and genetic characteristics of androgen insensitivity syndrome in 39 Chinese patients. Reprod Biol Endocrinol. 2020;18:34. 
46.Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J. Androgen insensitivity syndrome.  Lancet. 2012 ;380:1419-28.
47.Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Androgen insensitivity syndrome. Best Pract Res Clin Endocrinol Metab. 2015;29:569-80.
48.Oakes MB, Eyvazzadeh AD, Quint E, Smith YR. Complete androgen insensitivity syndrome-a review.  J Pediatr Adolesc Gynecol. 2008;21:305-10.